Plastic and Aesthetic Regenerative Surgery and Fat Grafting: Clinical Application and Operative Techniques 3030774546, 9783030774547

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Plastic and Aesthetic Regenerative Surgery and Fat Grafting Clinical Application and Operative Techniques Amin Kalaaji Editor

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Plastic and Aesthetic Regenerative Surgery and Fat Grafting

Amin Kalaaji Editor

Plastic and Aesthetic Regenerative Surgery and Fat Grafting Clinical Application and Operative Techniques

Editor Amin Kalaaji Oslo Plastic Surgery Clinic Oslo, Norway

ISBN 978-3-030-77454-7    ISBN 978-3-030-77455-4 (eBook) https://doi.org/10.1007/978-3-030-77455-4 © Springer Nature Switzerland AG 2022 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Foreword 1

Fat grafting has not only been a disruptive force in Aesthetic and Reconstructive Surgery, of more significance is the primary role it has assumed in opening up the field of Regenerative Medicine. Though Regenerative Medicine may be in its infancy significant strides have already been made. Dr. Kalaaji is to be commended for bringing together, from all over the world, the thought leaders, and major contributors to the field, into these extensive volumes. Each author shares their expertise and unique views on this vast topic sharing what they have learned and nuances of techniques. With 242 international contributors, 13 sections and 117 chapters this work is timely providing the most comprehensive, most up-to-date and clinically relevant information on this rapidly expanding field. A field that already has had significant impact on such varied parts of our practices from facial rejuvenation, breast surgery, body contouring to the care of challenging wounds. The basic science and clinical applications are discussed in a clear fashion. All clinical applications of fat grafting and regenerative medicine ranging from facial aesthetic surgery, breast reconstruction, and body contouring are clearly detailed and demonstrated in the Surgical Technique chapters. With the vast amount of information included, here it will not only be an excellent primer for those who are just embarking on these treatments and techniques, but of equal value for those already familiar with them. For the novice, new basic information, for the expert, valuable practical information, surgical nuances, and tips to improve results and enhance safety. Foad Nahai Emory University, Plastic Surgery Atlanta, GA, USA

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Foreword 2

The use of fat grafts in different aesthetic and reconstructive procedures nowadays is state of the art. But looking back on history, it is just a revival of a technique described by the German surgeon Gustav Neuber in 1893 [1]. He was the first to perform a fat autograft in a human by the transplantation of a bloc of adipose tissue from the upper arm to the face. Sydney Coleman in 1992 pioneered the modern technique of autologous fat transfer by using a defined protocol. He called his technique for facial rejuvenation “Lipostructuring” [2]. Over the past two decades, it has become increasingly apparent that adipose tissue is not only a filler but has shown its regenerative potential. Patricia Zuk described the presence of adult mesenchymal stem cells in the adipose tissue, which were referred to as Adipose-Derived Stem Cells (ASCs) [3]. Since the discovery of the ASCs, the regenerative potential of adipose tissue has become an important area in Plastic Surgery. The regenerative effect of the fat grafts has been scientifically examined and mainly attributed to the Stromal Vascular Fraction (SVF) cells with the Adipose-Derived Stem Cells (ASCs), the angiogenic growth factors [4], and the proliferation of the keratinocytes [5]. The techniques of harvesting, processing as well as of injecting the fat grafts have been further developed. That way in addition to the macro-fat grafts introduced by Sydney Coleman [6], the milli-fat graft technique described by Stephen Cohen [7] and the micro-fat graft technology developed by Guy Magalon [8] were used for different indications. For regenerative indications, Patrick Tonnard [9] revolutionized the use of fat grafts by developing the nano-fat grafting technology. Norbert Pallua [10] with his lipoconcentrate optimized the use of emulsified fat grafts for regenerative indications by a mechanical technique getting a significant higher number of SVF cells, ASCs, and Endothelial Progenitor Cells (EPCs) when compared to the native fat and the nano-fat. SVF cells—especially ASCs and EPCs—and angiogenic growth factors contribute to both, the volume augmentation as well as the skin regeneration. For this reason, fat grafting became a major tool in Plastic and Aesthetic Surgery to improve the appearance of aged skin and scars as well as to correct facial and body contour defects. Since more than 25 years, when Sydney Coleman developed his defined “Lipostructuring” protocol [2], an immense number of experimental and clinical studies have been focusing on an increased retention and an optimized regenerative potential of the autologous fat grafts. Despite great advances in vii

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science and clinical use of adipose tissue, the saying of the Greek philosopher Socrates still applies to many fields of regenerative plastic surgery: “I know that I know nothing.” All the more important is the publication of this book that reflects the current standard of research and clinical use of adipose tissue. Fat grafting as a minimal-invasive procedure may replace many of the reconstructive and aesthetic procedures in the face and body. In this book, “Plastic and Aesthetic Regenerative Surgery and Fat Grafting: Clinical Application and Operative Techniques” edited by Amin Kalaaji and published by Springer in two volumes and in 13 sections and 117 chapters cover all clinical and scientific aspects of Regenerative Plastic Surgery and of fat grafting. The editor-in-chief invited renowned experts in fat grafting from five continents to write a chapter in the main field of their experience. A total of 242 authors and co-authors were involved to complete this book. The contributions of these international experts encompass the history, the current concepts and techniques and provide an outlook on the future of fat grafting as well as on the Regenerative Plastic Surgery. I am sure this book is going to become an integral part in the library of established colleagues as well as an important help for students, young plastic surgeons, and all colleagues from related specialties. Norbert Pallua Medical Faculty of the Rhenish-Westphalian Technical University Aachen Aachen Germany Private Clinic, Königsallee 88 Düsseldorf Germany

References   1. Neuber G. Fettransplantation. Chir Kongr Verhandl Deutsche Gesellschaft für Chir. 1893;22:66.  2. Coleman SR.  Long-term survival of fat transplants: controlled demonstrations. Aesthet Plast Surg. 1995;19:421–5.   3. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim AL, Lorenz HP, Hedrick MH.  Multilineage cells from human adipose tissue: implications for cellbased therapies. Tissue Eng. 2001;7(2):211–8.   4. Pallua N, Pulsfort AK, Suschek C, Wolter TP. Content of the growth factors bFGF, IGF-1, VEGF, and PDGF-BB in freshly harvested lipoaspirate after centrifugation and incubation. Plast Reconstr Surg. 2009;123(3):826–33.  5. Kim BS, Gaul C, Paul NE, Dewor M, Stromps JP, Hwang SS, Nourbakhsh M, Bernhagen J, Rennekampff HO, Pallua N. The effect of lipoaspirates on human keratinocytes. Aesthet Surg J. 2016;36(8):941–51.   6. Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997;24:347–67.   7. Cohen SR, Hewett S,  Ross L,  Delaunay F,  Goodacre A,  Ramos C,  Leong T,  Saad A. Regenerative cells for facial surgery: biofilling and biocontouring. Aesthet Surg J. 2017;37(Suppl 3):S16–32.   8. Nguyen PS, Desouches C, Gay AM, Hautier A., Magalon G. Development of microinjection as an innovative autologous fat graft technique: the use of adipose tissue as dermal filler. J Plast Reconstr Aesthet Surg. 2012;65(12):1692–9.   9. Tonnard P, Verpaele A, Peeters G, Hamdi M, Cornelissen M, Declercq H. Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013;132(4):1017–26. 10. Pallua N, Grasys J, Kim BS. Enhancement of progenitor cells by two-step centrifugation of emulsified lipoaspirates. Plast Reconstr Surg. 2018;142:99–109.

Foreword 2

Foreword 3

The rapid development and widespread use of regenerative surgery, particularly the adipose stem cell-based therapies, have opened up new horizons for plastic surgeons and allied specialists. Fat grafting is one of the most common procedures performed not only for cosmetic purposes but also to treat fibrosis in non-cosmetic applications, aiming at volumetric enhancement as well as rejuvenating and improving the tissue quality. Thanks to research, innovation, new instrumentation, and the ever-changing concepts of what regenerative surgery is all about, what we are doing now is not what we were doing 10 years ago. Plastic and Aesthetic Regenerative Surgery and Fat Grafting: Clinical Application and Operative Techniques edited by Dr. Amin Kalaaji is an extensive guide based on the most recent and up-to-date research findings in the field of regenerative surgery. This new book with 117 chapters describes comprehensively the current surgical techniques and its applications from top to toe. The two volumes guide the readers through the biology, anatomy, and surgical details of a field that is constantly evolving. The text is implemented with multiple videos illustrating the surgical techniques to achieve good outcomes in safety because a simple procedure is not necessarily a procedure that presents no complications. This book provides an invaluable resource for graduate students, plastic surgery trainees, recently specialized plastic surgeons and researchers who might face challenges in acquiring relevant and updated information in the field. I recommend this book not only to the youngest approaching this topic, but also to more experienced plastic surgeons who aim to update their knowledge and to surgeons from other specialties wishing to familiarize themselves with the current philosophies in the field of regenerative plastic surgery. I would like to express my sincere appreciation to the editor Dr. Amin Kalaaji for this great contribution to education. Aurora Almadori University College of London London, UK

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Preface

 Book for an “Almost New” Revolution—Created During A Extraordinary Times

 This is from an interview with the Editor in 1998  in Oslo University Hospital, Plastic Surgery Department in Oslo, Norway, when I was working as Chief of Plastic Surgery, treating a child with an acute burn injury. This picture illustrates that it is our responsibility as plastic surgeons to aid patients in reconstructive surgery. “Appreciate the tissue, your patients, and their specific need—and do no harm” should be our mantra in fat grafting and regenerative surgery

I ntroduction: How It All Began: A Recent E-mail and Long-­Time Goal In November 2018, I received an e-mail with the mysterious subject line: “Maybe you don’t know me, but I know you.” This sounds as if it has been taken out of a crime novel, and normally something like this would have ended up in my trash folder. But for some reason, I was intrigued and opened the e-mail. To my surprise, it was a publisher offering me the chance to write a book about one of my professional passions: fat grafting in modern plastic reconstructive and aesthetic surgery. I was fortunate to contribute new content to a rapidly growing subject with world-renowned colleagues—an opportunity that I might have missed and, luckily, did not.

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While I received that mysterious e-mail relatively recently, the origin of this text’s creation goes back much further. For many years, I have been dreaming about writing a book. This dream began when I completed my MD in Aleppo, Syria in the 1980s. However, the real, legitimate opportunity to write a book did not present itself until I fully concluded my clinical training, PhD, and jobs in Paris, Göteborg, and Oslo in the 1990s, 2000s, and 2010s, respectively. Nonetheless, I did contribute my knowledge to our plastic surgery field in the form of publications in medical journals on topics and concepts related to our specialty. The journey of getting the book approved was long and daunting. The publisher wanted a book proposal with additional references from colleagues and specialists, but I only had a vague idea whom I was going to name. I wanted someone who would be supportive and who knew how dear this specific topic was to me. When I received overwhelmingly kind and positive affirmations from my colleagues about publishing such a book, I was delighted. They inspired me to make this dream become a reality. Their good faith and confidence laid the foundation for this book and established a basis for me to get a head start on writing. At long last, 30 months later, this book has come into fruition with the help of my amazing collaborators at Springer Nature and my colleagues around the world, as we are facing an extraordinary time in our collective history with COVID-19.

An Established Method with a Long Way to Go Fat grafting has become a well-established method, with expanding indications in the fields of cosmetic and regenerative surgery, but there is room for development. Although I have performed thousands of fat grafting procedures from tip to toe, these experiences have given me a humbling fear and respect—as we still achieve unsatisfactory results in the form of complications or undesirable results. I remember a time when safety concerns about fat transfer prevented their implementation. Much time has passed since our work with fat first met fierce international criticism. However, with perseverance, patience, and genuinely hard work, the procedures gained the confidence, respect, and appreciation of my colleagues all over the world, and we have managed to break new ground in this field. The importance of fat grafting in modern plastic reconstructive and aesthetic surgery is, after three decades of development, a fact we no longer doubt. It now shares a prestigious place in history comparable with microsurgery and the improved understanding of the skin’s blood supply. The strongest advice I can give to young surgeons is: Enrich your everyday practice by learning and adapting fat grafting techniques. Do not use it only to improve results from conventional reconstructive and aesthetic procedures, but, more importantly, realize its use when you are faced with complex deformities (i.e., congenital, developmental, iatrogenic). With careful planning

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and a full understanding of how “simple” fat grafting is best used, we can solve many of our most complicated cases. This book features chapters that discuss fat grafting procedures for the face, breast, gluteal area, abdomen, back, upper, and lower extremities, intimate areas, and other regions of the body that patients seek to correct for a variety of reasons. It addresses traditional methods and the role that fat grafting can play in successfully dealing with complex deformities.

Present or Future Revolution? We cannot forget that fat grafting is (not-yet) revolutionary. I am sure it will be soon, but in light of the many controversies and misunderstandings that have occurred in the past, we will have to work even harder to establish a fresh foundation for the procedure and build on it, making it stronger and more prevalent in our specialty. As we do, we must continually ask ourselves: How much do we really know about fat and regenerative surgery? I recall a story from my Swedish father-in-law, Eric, who remembers being a young man in the 1950s in Göteborg buying fruits at the market at 6:00 a.m. When asking the seller whether there were a lot of vitamins still in the fruits, the seller, who was a simple man, hid his uncertainty and impishly said: “Do not worry! All of them (meaning, the vitamins) are washed out very well. I washed it by myself.” Seventy years later, do we know more than this simple man? Probably not. This anecdote reminds me how very much we still do not know about fat, and how important it is to be transparent with ourselves about this. So many contradictory opinions and certainly no agreedupon methods exist about how to prepare and process the fat. Are we washing out the “vitamins”—that is, stem cells and growth factors—from the fat while we process it? This is just one example of the kinds of questions we need to ask ourselves. Or another: Do we harm the fat during centrifugation, or by using smaller cannulas, or during long exposure to air? I still remember when I first started doing breast augmentation with fat in the 2000s and called some of my colleagues and friends around the world, informing them with great joy: “It is now my breast case [number 2 or 5, for example] that I operated on today.” At that time, I thought surgeons, myself included, knew everything there was to know about augmentation with fat. Now, many years later, and after personally performing thousands of fat grafting procedures, I know we are not there yet; there is much more to learn. However, in that uncertainty is the exciting thought: What if in fat lies hidden treasure? This may be the story of fat: It has properties that have been there the whole time, and only now can we experience the joy of discovering all of its potential. We must remain realistic, however, and not become “fat fanatics.” We should not overestimate the potential of fat and assume that it will solve all of our problems. The goal of the fat revolution and this book is to increase the indications of fat while knowing its limits.

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 hat to Expect as You Read This Book: Content W and Intentions It has become crucial to me that this book is an exercise in inclusion. I was given the choice between deciding to be a single author or an editor of a larger, multi-authored book. It was not difficult to choose the latter. My principles when accepting this great challenge as the editor were to represent five continents—with as many countries as possible, as many female colleagues as possible, and as many voices of experience as possible, and to introduce young, very promising new authors who are not very well-known yet. I have had the privilege of hosting and organizing various high-quality international meetings across the globe. In addition, I am invited regularly as international faculty to teach worldwide. These opportunities enabled me to get to know some of the most experienced surgeons, from different continents, who authored highly valuable chapters. This text represents a wonderful collaboration between many leaders in our specialty, offering different perspectives and possibilities for innovations. While we initially intended to restrict ourselves to 50 chapters, the high response rate of 95% of the potential contributors led us to dream of a bigger goal: two books comprised of 117 chapters written by 242 authors from 5 continents and 31 countries. I chose not to write many chapters myself, intentionally leaving space for other colleagues, and settled with my contribution of nine chapters in addition to my role as Chief Editor. Then there was the title. I wanted an inclusive title to reflect the aim of the book: the real clinical applications and techniques of fat grafting, and its integration with traditional plastic, aesthetic, and reconstructive surgical procedures— such as breast reconstruction, wound healing, scar treatment, and the use of stem cells. With this in mind, the table of contents has been thoughtfully classified. As part of our writing process, a systematic review of the literature was performed, with no stone left unturned and every term in our specialty’s rich language searched for—terms like “fat grafting,” “lipofilling,” “Coleman technique,” “autologous fat transfer,” “structural fat grafting,” “regenerative surgery,” and “regenerative medicine”—just to name a few examples. Because of the variable depth of knowledge between authors and the overlapping content between chapters, there might be some repetition, but we see this as valuable because the information is presented from different angles and perspectives. The most important topics have their own detailed chapters. In total, we have 13 sections that fully cover the topic of fat grafting, as explained in the following overview:

 ook Title: Plastic and Aesthetic Regenerative Surgery B and Fat Grafting: Clinical Application and Operative Techniques I. Introduction: 7 chapters II. Stem Cells and Clinical Application: 5 chapters III. Operative Techniques for Fat Grafting: 12 chapters

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IV. Regenerative Surgery: Reconstructive Areas of Application: 18 chapters V. Regenerative Surgery: Aesthetic Areas of Application, Hair: 2 chapters VI. Regenerative Surgery: Aesthetic Areas of Application, Skin: 4 chapters VII. Regenerative Surgery: Aesthetic and Reconstructive Areas of Application, Face: 14 chapters VIII. Breast Augmentation and Mastopexy with Fat: 12 chapters IX. Breast Reconstruction with Fat: 12 chapters X. Gluteal Augmentation with Fat, Brazilian Butt Lift, and Related Body Contouring: 10 chapters XI. Genital Rejuvenation: 11 chapters XII. Upper Extremities: 5 chapters XIII. Lower Extremities: 5 chapters In addition to these chapters, there is “front matter” and “back matter”: Prefaces, acknowledgment, table of contents, contributors list, index, and “about the editor.” These 117 chapters (2 volumes, 13 sections and about 1800 pages), 1625 educational figures and 131 educational Video files proudly represent the knowledge and expertise of 242 authors (including 72 female colleagues) from more than 31 countries, 81 cities, and 5 continents. All sections were consistently structured, covering surgical anatomy, safety, complications, and limitations. Furthermore, for almost every chapter, there are multiple figures, tables, and video clips available. These are invaluable to further illustrate the techniques mentioned in the related chapters and to greatly enhance the educational experience for easy reference to some of the most salient knowledge. The contributors’ efforts to integrate multimedia content to keep abreast with today's technology requirements is helpful and greatly appreciated.

A “COVID-19 Book” and “WhatsApp Book”? If I were to give this book an alternative title, I would call it the “WhatsApp book” (no commercial interest). This technology, as well as other social media, tremendously shortened the time we, authors and other collaborators, used to communicate with one another across the globe. While everyday e-mail correspondence is like sending information in a fast car, it was like a high-speed rocket using WhatsApp. It enabled us to set up a chapter project in a matter of days or sometimes even hours; within minutes, decisions were made, and problems were solved at once. The journey of developing this book has been incredible. It is satisfying to see so many people collaborating together to create such an amazing book, especially during these extraordinary times while facing the COVID-19 pandemic. We continuously adapted to worldwide lockdowns and employed today’s technological advances, enabling us to work together, which other-

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wise might have seemed impossible. COVID-19 has slowed down the process, as many colleagues had plenty of other challenges to face. We had to remain patient during this time to ensure that the book’s value would not be affected when it was published because many of the chapters are time sensitive. Despite the negative impact of the pandemic, it has had positive consequences—the most obvious of which was more time available. I can say with certainty that this is the case for myself, as I was not travelling my average of two times a month as an international faculty invitee. In addition to gifting me with more time to spend with my family, the lockdown provided me with more time to devote to this book. Therefore, despite the pandemic’s negative consequences on our everyday and work lives, it supplied those of us working on this project with a good balance to overcome time and priority challenges. This permitted us to further focus on the quality of each chapter, which will hopefully be evident as you read this book.

Final Thoughts: This Is Only the Beginning! This book represents a much-needed reference to the present-day clinical application of fat grafting and regenerative surgery. It can be considered an informative contribution to a field that is constantly changing and developing, and it will hopefully be used to help us all become better surgeons. We are all looking forward to a future with promising new approaches like maximum fat take, hetero fat grafting, and cryopreserved fat grafting—procedures that show us that there is still room for improvement and that there is a lot of potential going forward. Thank you to each and every one of you who made the best out of the given resources and worked in a professional, efficient, and friendly way. These challenging times have taken a toll on all of us, but something positive has resulted: We have managed to produce a masterpiece. Oslo, Norway June 2021

Amin Kalaaji

Acknowledgments

First and foremost, I would like to thank my amazing life partner, Jenny, as well as my lovely daughters, Aida and Mai Lea. You have all been incredibly supportive, and I will always be grateful for your never-ending love, encouragement, patience, and energy. I am eternally grateful to my beloved parents and their continuous support and belief in me. I cannot thank my mother, Mofeda, enough, who sadly passed away while I was presenting at the ISAPS meeting in Miami in 2018. I lost a big pillar of strength in my life and she is dearly missed. A special tribute also goes out to my father, A. Jawad, who is now 93 years old. His constant interest in science and ceaseless support of me and my career in this field has always motivated me to achieve more. Considering that we were a family of 9 born in Aleppo, Syria, with a modest economic status, he still insisted that we all pursue higher education; words cannot describe how grateful I am to him. Moreover, I would like to sincerely express my appreciation to Mrs. Daniela Heller, Editor Medicine Books Continental Europe and the UK in Springer Nature, for first “discovering” me and inviting me to write this book without any further intermediation. She trusted my ability to pursue this project, and I highly value her great willingness to expand and be flexible with all the new ideas that came up as we have been developing this project. We originally started with a small idea and ended up with the development of two textbooks. Therefore, I want to thank her for her ability, availability, and positivity. Also, many thanks to my Project Coordinator Ms. Hema (Hemalatha) Gunasekaran for her enormous help during the preparation of this endeavor. A big “thank you” goes to Dr. Nobert Pallua from Germany for supporting me when this book was still a “secret idea,” which I was unwilling to share with most people because I did not yet believe it would truly happen. I still remember our Japanese dinner in Dubai in December 2018: your encouragement and belief in me meant a lot and motivated me to pursue this project. In addition, thank you for your valuable contribution to an important chapter, as well as your co-authorship of the preface of this book. Thank you, Dr. Foad Nahai from the USA, ever so much for being such an inspiring role-model. Since I was a young newcomer, I have admired Dr. Nahai’s work on the classification of muscle flaps with Dr. Stephen Mathes in 1981, thus making this legendary plastic surgeon my personal idol. He inspired me not only with his clinical and research approach, but also with his work ethic and contribution to the field of plastic surgery through numerous xvii

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publications and textbooks. I feel very honored to have him participating in an important chapter of this book, as well as his co-authoring of the preface. A third thanks goes to my third preface co-author Dr. Aurora Almadori from UK/Italy, who represents the youth and the future of our profession with basic research. Still early in her professional years, Aurora has contributed as author of three chapters and co-author of the preface of this book. Her important work on this project coincided with another, important project—finalizing her PhD on Regenerative Medicine with the use of fat grafting to treat fibrotic conditions and scarring in London, United Kingdom. I wish to express my sincere gratitude to all contributors and authors of this endeavor for their wonderful efforts. We ended up with 117 chapters, 1625 educational figures, and 131 video clips proudly submitted by 242 authors (of these, 72 are female colleagues) from more than 31 countries, 81 cities, and 5 continents. It is only due to the limit of space on this page that I am unable to write down all your names individually and thank each one of you personally. Nevertheless, your contribution is greatly appreciated as you continued to show outstanding dedication and commitment during this exciting but eventful and challenging period for all of us. I am fully aware that it has been tough at times, and my apologies for any difficulties you faced while doing the revisions—this was a tremendous amount of work for both you as authors and me as editor-in-chief. It has been a rewarding experience, and we collaborated to create an outstanding result: We now have an excellent, informative book that contributes significantly to these relevant topics. Apart from the book’s formal contributors, I also received a lot of valuable support from noncontributors, colleagues, and friends. They engaged in helpful discussions with me and offered encouragement when I first had the idea for this project but was still uncertain whether I could conduct it. Thanks to my dear colleagues, Lars Haasted and Anadi Begic, for following and encouraging me all the way. I even received inspiration from a colleague whom I did not personally know well, Bryan Mandelson. He took the time to write me and express his admiration about this enterprise. In doing so, Bryan, you helped me to find more motivation to continue writing this book. Thank you all very much. It has been my honor to serve as President of the Norwegian Society of Aesthetic Plastic Surgery (NSAPS) for the past 2 years. This position provided me with a lot of responsibility but also enabled me to gain the extra confidence needed to undertake this endeavor. I greatly appreciate the support from all my Norwegian colleagues and members who put their trust in me. A big thanks goes to Professor Hans Holmström, my former chief and professor from Gothenburg, Sweden, who first introduced me to a plastic surgery department and opened further possibilities for me. Additionally, many thanks to my former supervisor, Jan Lilja, who granted me the Doctor of Philosophy on bone grafting in cleft lip and palate in 1999 in Gothenburg. That was the main foundation for my research career, leading up to the accomplishment of creating this book. Furthermore, I would like to express my gratitude to my patients, who believed in me and trusted me to perform different and new procedures on

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them. I am truly grateful for these opportunities and to receive their valuable feedback. Last but not least, I am very grateful for all my staff members and collaborators at my clinic Oslo Plastikkirurgi Clinic in Norway for their continuous support. None of this would have been possible without your assistance and support. Special thanks to Vanja Jönsson, Stine Dreyer, Jakob Schnegg, Anne Holseth, Othilia Torske, Melanie Baumgartner, and Jannika Brinkmann: You contributed so much to the success of this work. Finally, I want to pay a tribute to Violette Skorobac Ašanin and Bryant A. Toth, dear colleagues and excellent chapter writers in this book from Beograd, Serbia and USA. Violette passed away unexpectedly on June 13, 2020, and Bryant on October 3, 2021 while we were in development of the book. Rest in peace, Violette and Bryant, and thank you. Amin Kalaaji, MD, PhD Oslo, Norway June 2021

Contents

Part I Introductory Part 1 The Era of Regenerative Surgery ������������������������������������������������    3 Ryan S. Burke and Foad Nahai 2 Evolving of Concepts in Fat Grafting and Regenerative Surgery��������������������������������������������������������������������   11 Riccardo F. Mazzola 3 Regenerative Surgery: Definitions and Background������������������   27 Stefania de Fazio and Elena Lucattelli 4 Current Status of Regenerative Plastic Surgery ������������������������   37 Joseph M. Firriolo and Lee L. Q. Pu 5 Adipose Tissue Transplantation: Autologous Versus Cryopreserved (Frozen) Versus Heterologous. Present and Future of Fat Transfer������������������������������������������������������������   47 Fabiana Zanata, Fabio Xerfan Nahas, Tomas Fortoul, Jeffrey M. Gimble, and Lydia Masako Ferreira 6 Fluid Balance, Electrolytes, and Anesthetic Options in Regenerative Surgery and Fat Grafting��������������������������������������   57 Lyly Nguyen, Vincent Riccelli, and K. Kye Higdon 7 Comparison Between Fat and Fillers ������������������������������������������   69 Gianluca Campiglio and Nebojša Srdanović Part II Stem Cells and Clinical Path 8 Features and Biological Properties of Different Adipose Tissue Based Products. Milli-, Micro-, Emulsified (Nano-) Fat, SVF, and AD-Multipotent Mesenchymal Stem Cells����������   91 Viacheslav S. Vasilyev, Anna A. Borovikova, Sergey A. Vasilyev, Natalia I. Khramtsova, Sergey A. Plaksin, Roman A. Kamyshinsky, Mikhail Y. Presnyakov, and Ilya I. Eremin

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9 Regenerative Technologies and Adipose-Derived Stem Cells (ADSCs): Regulatory, Ethical, and Technical Updates��������������  109 Michele L. Zocchi, Andrea Pagani, and Franco Bassetto 10 Stem Cell Research, Concepts, and Emerging Technologies ����  123 Angelo Trivisonno 11 Stem Cells and Their Clinical Applications ��������������������������������  131 Shima Jamshidi, Naghmeh Naderi, and Afshin Mosahebi 12 Fat Grafting, Tissue Banking, and Adipose Stem Cell Therapies: European Regulatory Status in 2021����������������  139 Kai-Uwe Schlaudraff Part III Operative Techniques for Fat Grafting 13 Aesthetic Lipofilling: Trends, Patient Needs and Assessment������������������������������������������������������������������������������  151 De Fazio Domenico, Gentile Pietro, and Campiglio Gianluca 14 Novel Strategies to Improve Graft Survival and Retention ������  165 Valerio Cervelli and Gabriele Storti 15 Injectable Tissue Replacement and Regeneration: A New Standardized Fat Grafting Technique ����������������������������  183 Steven R. Cohen and Sierra Hewett 16 Fat Processing Methods����������������������������������������������������������������  197 Alexandra Condé-Green and Alvaro Luiz Cansanção 17 Impact of Age, Gender, Body Mass Index, Harvesting Site, Suction Pressure, Smoking, Diabetes, Systemic Lupus and Other Diseases on the Regenerative Properties of the Grafted Adipose Tissue ������������  207 Ahmed A. Noreldin, Lobna Y. Ghanem, Hussein Saber Abulhassan, Aly Hussein Abulhassan, and Dina T. Ghorra 18 New Strategies in Regenerative Medicine: The Bio-active Composite Grafts ��������������������������������������������������������������������������  221 Michele L. Zocchi and Andrea Pagani 19 New Perspective in Regenerative Surgery: The Acellular Adipose Matrix������������������������������������������������������  237 Michele L. Zocchi, Nguyen Thi Ngoc My, Carlotta Scarpa, Andrea Pagani, Tran Le Bao Ha, and Franco Bassetto 20 Classification of Safe Autologous Fat Grafting: Quantity and Location Site���������������������������������������������������������������������������  251 Meredith Montgomery, Carter Boyd, Pallavi Archana Kumbla, William Blake Swicord, and Sherry Collawn

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21 Complications in Regenerative and Fat Transfer Surgery: Pathophysiology and Management with Technical Tips to Reduce Risk ����������������������������������������������������������������������  263 Nora F. Nugent, Anne Marie Kennedy, Riccardo F. Mazzola, and Foued Hamza 22 Fat Grafting and Fat Embolism. How to Prevent, Diagnose, and Treat ����������������������������������������������������������������������  277 Katarina Andjelkov and Nikola Music 23 Potentials and Limitations of the Use of Platelet-Rich Plasma (PRP) in Combination with Lipofilling. An Evidence-­Based Approach������������������������������������������������������  285 Joris A. van Dongen, Hieronymus P. Stevens, and Berend van der Lei 24 The Role of Nurses and Surgical Assistants in Fat Grafting Procedures: Planning, Preparation, and Implementation ��������  301 Cathrine Nordahl, Lena Løvfold, Lena Torske, and Amin Kalaaji Part IV Regenerative Surgery: Reconstructive Areas of Application 25 Fat Grafting as an Ancillary Treatment for Burns and Other Complex Wounds and Their Sequelae����������������������  317 Nelson Sarto Piccolo, Mônica Sarto Piccolo, Nelson de Paula Piccolo, Paulo de Paula Piccolo, and Roberta Piccolo Lobo 26 Cellular Optimized Nanofat for Microneedling and as a Unique Nanofat Biocrème������������������������������������������������������  339 Steven R. Cohen and Sierra Hewett 27 Treatment of Radiation-Induced Rectovaginal Fistula: Safety and Efficacy of Fat Grafting and Stromal Vascular Fraction Injections ��������������������������������������������������������  351 Viacheslav S. Vasilyev, Zhanna I. Triushkova, Andrey V. Vazhenin, Anna B. Semenova, Evgenyi A. Lomakin, Georgyi P. Dimov, Ilya I. Eremin, Igor S. Vasilyev, and Andrey A. Pulin 28 Post-burn and Keloid Scar Treatment with Adipose-Derived Stem Cells (ADSC) ������������������������������������������  367 Gianluca Campiglio, Francesco Klinger, Fabio Caviggioli, Luca Maione, Andrea Battistini, Valeriano Vinci, and Marco Klinger 29 Fat Grafting as Plastic Surgeons’ Best Friend: Solving Complex Reconstruction Problems with Simple Regenerative Solutions������������������������������������������������������������������  377 Fazel Fatah

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30 Scar Modulations and Maturation in Post-burn Scar Contractures and Skin Grafts Using Autologous Fat Injections Grafts����������������������������������������������������������������������  405 Ashok Gupta and Amita Hiremath 31 Treatment of Chronic Wounds with Fat Grafting and Adipose-­­Derived Stromal Vascular Fraction������������������������  417 Viacheslav S. Vasilyev, Nicolay B. Shismentsev, Sergey A. Vasilyev, and Yuri S. Vasilyev 32 Treatment of Scleroderma with Fat Grafting, PRP, and ­Adipose-­­Derived Stem Cells ����������������������������������������  431 Aurora Almadori and Peter E. M. Butler 33 Treatment of Fibrotic Radiotherapy Damages in Head and Neck with Fat Grafting������������������������������������������������  447 Aurora Almadori, Nicholas Kalavrezos, and Peter E. M. Butler 34 Vampire Scar: Outpatient Quality Improvement of Scar Regeneration with a Composite Approach with Needling and PRP������������������������������������������������������������������������������������������  459 Daniele Bollero and Anna Fogli 35 Complex Regional Pain Syndrome and Steroid Atrophy Scar Retraction Treatment with Adipose Grafting��������������������  471 William Blake Swicord, Carter Boyd, Jeremy Bosworth, Felicia R. Hataway, and Sherry Collawn 36 Acute Burns Management: The Current Role of Regenerative Surgery and its Challenges��������������������������������  479 Annarita Agovino, Matteo d’Alessio, Kwang Lee, Vlad Bloanca, Zorin Crainiceanu, and Roberto d’Alessio 37 Regenerative Surgery Choices in Burns Sequelae Management ������������������������������������������������������������������  495 Annarita Agovino, Kwang Lee, Matteo d’Alessio, Zorin Crainiceanu, and Roberto d’Alessio 38 The Role of Adipose Tissue Graft on Nerve Regeneration from the Perspective of the Adipose-Derived Stem Cell������������  513 Vlad Bloanca, Zorin Crainiceanu, Tiberiu Bratu, Annarita Agovino, and Anca Maria Cimpean 39 Physical Therapies to Improve Fat Grafting and Regenerative Surgery Results in Wound Healing ����������������������  525 Claudio Ligresti and Erind Ruka 40 Fat and Stromal Cells for Acute Burn Treatment����������������������  543 Sophie Brosset, Mona Alkhotani, Fabien Boucher, Hristo Shipkov, Céline Auxenfans, and Ali A. Mojallal 41 Combined Fat, PRP, and Laser for Skin and Soft Tissues Regeneration. Clinical Applications��������������������������������  559 Dana Mihaela Jianu, Ioana Ghiurco, and Stefan Jianu

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42 Regenerative Surgery and Acellular Dermal Matrix as Reconstructive Surgical Options in Plastic Surgery. Theoretical and Practical Basis����������������������������������������������������  579 Carlos Rodrigo Jorrat, Hugo Alberto Drago, Alejandro Jorge Beltrami, Lucas Sebastian Zurlo, Silvia Bossi, and Flavio Mateo Sturla Part V Regenerative Surgery: Aesthetic Areas of Application, Hair 43 Hair Regrowth with Micrografts Enriched with Human Follicle Mesenchymal Stem Cells and Platelet-Rich Plasma ����  595 Pietro Gentile 44 The Efficacy of Platelet-Rich Plasma for Hair Loss: A Proven Therapy��������������������������������������������������������������������������  603 Vinod K. Chopra, Rana Shalhoub, and George J. Bitar Part VI Regenerative Surgery: Aesthetic Areas of Application, Skin 45 The Process of Aging, State-of-the-­Art: Evidence Behind Regenerative Surgery��������������������������������������������������������������������  615 Lina Triana 46 Wrinkles, Etiology, Causes, Treatment, and Prevention������������  623 Fabián E. Cortiñas and Abel Chajchir 47 Skin and Structural Aging in Patients of African Ethnicity. Features, Management and the Role of Regenerative Surgery����������������������������������������������������������������  641 Izolda Heydenrych, Eva Siolo, Ncoza C. Dlova, and A. Luiz Eduardo Avelar 48 The Use of Fat Grafting to Improve Skin Quality����������������������  657 Angelo Trivisonno Part VII Regenerative Surgery Aesthetic and Reconstructive Areas of Application, Face 49 Surgical Anatomy in Regenerative Surgery of Face, Scalp, and Neck������������������������������������������������������������������������������  669 Amani Landoulsi Helal and Sarah Houimli Charfeddine 50 Facial Fat Grafting During Facelift Surgery������������������������������  685 Timothy Marten and Dino Elyassnia 51 Properly Diluted Fat (P.D.F.): A Safer Approach to Periocular Fat Grafting������������������������������������������������������������  743 Mario Pelle-Ceravolo and Matteo Angelini 52 Improved Facial Rejuvenation and Scar Regeneration by the Autologous Stem Cell-Rich Lipoconcentrate������������������������������  761 Norbert Pallua, Mauro Vasella, and Bong-Sung Kim

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53 Aesthetic Chin Augmentation With Fat: Is There Still a Need for Chin Implants?����������������������������������������������������  773 Amin Kalaaji and Vanja Jönsson 54 Microfat Graft in Facial Rejuvenation����������������������������������������  787 Gianluca Campiglio and Alfredo Colapietra 55 Transgender Facial Aesthetics and Regenerative Techniques���  799 Ashkan Afshari, Lyly Nguyen, and Julian S. Winocour 56 Posttraumatic Contour Deformities Reconstruction and Scar Treatment with Microstructural and Nanofat Grafting in the Face ����������������������������������������������������������������������  813 Gergely Pataki, Tamás Varga, Artúr Kalatovics, and Sarolta Magyar 57 Nanofat Grafting in Facial Rejuvenation: An Innovative Technique��������������������������������������������������������������  837 Sophie Menkes 58 Parry-Romberg Syndrome Treatment with Microstructural Fat Grafting of the Face������������������������������������  851 Gergely Pataki, Artúr Kalatovics, and Zoltán Lóderer 59 Correction of Secondary Craniosynostosis Deformities with Autologous Fat ����������������������������������������������������������������������  885 Karima Ismail and Bryant A. Toth 60 The Regenerative Approach For The Management of Severe Dysphonia ��������������������������������������������������������������������������  895 Giovanna Cantarella and Riccardo F. Mazzola 61 The Safe Treatment of Mild Velopharyngeal Insufficiency (VPI) with Autologous Fat Grafting����������������������  905 Riccardo F. Mazzola, Giovanna Cantarella, and Isabella C. Mazzola 62 Degenerative Retinopathy Treatment with ADSC: Our Experience������������������������������������������������������������������������������  917 Paolo G. Limoli, Gianluca Campiglio, and Celeste S. Limoli Part VIII Breast Augmentation and Mastopexi with Fat 63 Aesthetic Breast Augmentation Using Autologous Fat Grafting: Indications, Patient Assessment, and Comparison Between Different Processing Methods in 204 Cases ����������������  937 Amin Kalaaji, Vanja Jönsson, and Melanie Baumgartner 64 New Trends in Breast Augmentation with Fat Grafting: Implant Conversion with Fat and Hybrid Implant-Fat Breast Augmentation/Revision������������������������������������������������������  957 Amin Kalaaji and Vanja Jönsson

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65 Implant Conversion with Fat Grafting����������������������������������������  973 Klaus Ueberreiter and Parshanak Azdasht 66 Composite Breast Augmentation with Implants and Fat Grafting����������������������������������������������������������������������������  985 Obaid Chaudhry and Daniel Del Vecchio 67 Correction of Severe Congenital Breast Asymmetry in Poland Syndrome and Other Breast Asymmetries with Autologous Microstructural Fat Transfer and the Combination of Other Techniques�������������������������������������������������������������������������������������� 1001 Gergely Pataki, Máté Jancsó, and Artúr Kalatovics 68 Autologous Fat Grafting for Breast Augmentation in Asian Women���������������������������������������������������������������������������������� 1023 Kim Siea Lee and Kasey Kisu Sung 69 Treatment of Tuberous Breast by Fat Grafting�������������������������� 1039 Klaus Ueberreiter and Parshanak Azdasht 70 Stromal Enriched Lipograft for Breast Augmentation�������������� 1051 Aris Sterodimas 71 Mastopexy with Auto-­Augmentation and Fat Grafting�������������� 1067 M. Bradley Calobrace and Chet Mays 72 Breast Augmentation with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling (PALLL) Technique ���������������������������������������������������������������������� 1085 Nicolas M. Abboud and Marwan H. Abboud 73 Improving Breast Footprint and Shape Using Anchor Threads in Fat Grafting Breast Augmentation �������������������������� 1107 Giuseppe Visconti, Alessandro Bianchi, and Marzia Salgarello 74 Inverted Nipple Correction with Central Tunnel Technique and Fat Grafting���������������������������������������������������������������������������� 1119 Amin Kalaaji, Vanja Jönsson, and Jakob Schnegg Part IX Breast Reconstruction with Fat 75 Breast Reconstruction with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling (PALLL) Technique ���������������������������������������������������������������������� 1133 Nicolas M. Abboud and Marwan H. Abboud 76 Fat Grafting for Breast Reconstruction�������������������������������������� 1159 Alfred Fitoussi 77 The Prepectoral, Hybrid Breast Reconstruction: The Synergy of Lipofilling and Breast Implants������������������������ 1181 Filip B. J. L. Stillaert

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78 Breast Reconstruction with Inferior Flap and Fat Transfer as Curative Treatment for BIA-ALCL������������������ 1191 Ruth Maria Graf, Maria Cecilia Closs Ono, and Dayane Raquel de Paula 79 Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction: The Role of “Conservative Hybrid Regeneration Approach (HRA)”������������ 1205 Giovanni Dal Pra, Luigi Gliosci, Andrea Conversi, Rossella Campa, Maristella Guerra, Pietro Cavalcanti, and Roberto Valeriani 80 Stem Cell-Enriched Fat Injection in Aesthetic, Reconstructive Breast Surgery ���������������������������������������������������� 1227 K. Tunc Tiryaki and M. Mustafa Aydınol 81 Enhancing Flap Breast Reconstruction with the Percutaneous Purse-­String Suture and Fat Grafting ���������������� 1241 Moustapha Hamdi and Lisa Ramaut 82 Lipomodeling for Breast-­Conservative Treatment Sequelae������������������������������������������������������������������������������������������ 1253 Emmanuel Delay and Richard Vaucher 83 Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction ���������������������������� 1265 Delay Emmanuel and Frobert Paul 84 Revision Surgery with Fat Grafting After Implant and Flap Breast Reconstruction���������������������������������������������������������� 1277 Ara A. Salibian, Jordan D. Frey, and Nolan S. Karp 85 Safety of Autologous Fat Transplantation in Oncological Postmastectomy Breast Reconstruction: A Prospective Study ���������������������������������������������������������������������� 1285 Fabio Santanelli di Pompeo, Benedetto Longo, and Michail Sorotos 86 Oncologic Safety of Fat Graft to the Breast�������������������������������� 1295 Jordan D. Frey, Ara A. Salibian, and Nolan S. Karp Part X Gluteal Augmentation with Fat, Brazilian Butt Lift (BBL) and Related Body Contouring 87 Gluteal Augmentation with Fat: Patient Assessment, Operative Technique, and Safety Guidelines������������������������������ 1307 Amin Kalaaji, Vanja Jönsson, and Trond Hugo Haukebøe 88 Artnatomy for Advanced Body Contouring and Aesthetic Balance Between Breast and Body ���������������������������������������������� 1327 Alfredo Hoyos, Mauricio Pérez, and Ivan Mogollon

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89 Gluteal Augmentation with Fat and Threads Using Power-Assisted Liposuction, Loops and Lipofilling (PALLL) Technique ���������������������������������������������������������������������� 1349 Nicolas M. Abboud and Marwan H. Abboud 90 Expansion Vibration Lipofilling (EVL) Technique in Gluteal Augmentation and Waist Feminization���������������������� 1363 Alexander Aslani, Daniel Del Vecchio, Laura Wulff, and Miguel G. Bravo 91 Gluteal Augmentation: Avoidance of Intramuscular Injection Using Precise Superficial Fat Graft Technique ���������� 1373 Ricardo Luis Rodriguez, Richard Anthony D’Amico, and Joseph Peter Rubin 92 Gluteal Augmentation Assisted by Stromal Enriched Lipograft ���������������������������������������������������������������������������������������� 1385 Aris Sterodimas 93 Circumferential Lipoabdominoplasty Combined with Fat Grafting the Hips and Buttocks������������������������������������ 1399 Paul M. Phillips and Sadri O. Sozer 94 MWL and Post Bariatric Surgery Patients: The Role of Fat Grafting and Regenerative Surgery������������������ 1407 Gudjon Leifur Gunnarsson and Jørn Bo Thomsen 95 High-Definition Abdominal Sculpting with Fat Grafting Highlights���������������������������������������������������������������������������������������� 1425 Douglas S. Steinbrech and Eduardo Gonzalez 96 Safety for Advanced Body Contouring: The Darkest Hour�������������������������������������������������������������������������� 1435 Alfredo Hoyos, Mauricio Pérez, and Ivan Mogollon Part XI Genital Rejuvenation 97 Surgical Anatomy of Female Genital Area to Achieve Safety in Fat Grafting����������������������������������������������������� 1445 Massimiliano Brambilla 98 Vulvovaginal Rejuvenation by Fat and Stromal Cells���������������� 1457 Fabien Boucher, Hristo Shipkov, Sophie Brosset, and Ali A. Mojallal 99 Quality of Life and Rejuvenation Techniques in Female Intimate Cosmetic Genital Surgery���������������������������������������������� 1465 Amin Kalaaji and Vanja Jönsson 100 Fat Graft for the Treatment of Vulvar and Vaginal Laxity�������� 1481 Massimiliano Brambilla

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101 Fat Grafting as a Regenerative Measure for Vulvar Atrophy and Vaginal Laxity���������������������������������������������������������� 1493 Nelson Sarto Piccolo, Mônica Sarto Piccolo, Nelson de Paula Piccolo, Paulo de Paula Piccolo, and Roberta Piccolo Lobo 102 Microfat and Nanofat Grafting in Genital Rejuvenation���������� 1511 Sophie Menkes, Mounia SidAhmed-Mezi, Jean Paul Meningaud, Laurent Benadiba, Guy Magalon, and Barbara Hersant 103 Fat Grafting and Adipose Stem Cells to Treat Vulvar Scarring and Fibrosis Post Female Genital Mutilation (FGM)�������������������������������������������������������������������������� 1521 Aurora Almadori, Marzia Salgarello, and Peter E. M. Butler 104 Male Genital Regenerative Surgery �������������������������������������������� 1535 Bjørn J. Tvedt 105 Penile Enlargement by Fat Grafting�������������������������������������������� 1549 Fabien Boucher, Hristo Shipkov, Sophie Brosset, and Ali A. Mojallal 106 The Treatment of Genital Vulvar and Penile Lichen Sclerosus with Autologous Fat Grafting�������������������������������������� 1559 Aurora Almadori, Francesco D’Andrea, and Peter E. M. Butler 107 Fat Grafting to Treat Vulvo-Vaginal Stenosis������������������������������ 1571 Massimiliano Brambilla Part XII Upper Extremity 108 Microfat Grafting in Dupuytren’s Contracture: From Hypodermis Reconstruction and Scar Optimization to Recurrence Prevention�������������������������������������������������������������� 1583 Elias T. Sawaya, Viken Vahan Yerganyan, Julie Bastien, and Jean-Maxime Alet 109 Management of Dupuytren’s Disease: The Role of Regenerative Surgery. Overview������������������������������ 1597 Petr Polák and Ondřej Měšťák 110 Hands Function and Esthetic with Regenerative Surgery �������� 1607 Guy Magalon, Jeremy Magalon, Charlotte Jaloux, and Régis Legré 111 Hand Rejuvenation by Minimally Invasive Injection of Stromal Enriched Lipograft ���������������������������������������������������� 1613 Aris Sterodimas

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112 Emulsified Fat Grafting to the Atrophic Post-traumatic Digital Pulp: A Promising Reconstruction Procedure���������������� 1623 Benjamin Sommier, Viken Vahan Yerganyan, Jean-Maxime Alet, and Elias T. Sawaya Part XIII Lower Extremity 113 Fat Grafting in the Surgical Treatment of Pressure Sores and as a Preventive Measure Against Recurrences���������� 1635 Nelson Sarto Piccolo, Mônica Sarto Piccolo, Nelson de Paula Piccolo, Paulo de Paula Piccolo, and Roberta Piccolo Lobo 114 Fat Grafting for Pedal Fat Pad Atrophy�������������������������������������� 1655 Natoli Farber, Beth Gusenoff, and Jeffrey Gusenoff 115 Leg Augmentation with Autologous Fat Tissue �������������������������� 1663 Violeta Skorobac Asanin 116 Composite Calf Augmentation Combining Fat and Implants���������������������������������������������������������������������������������� 1675 Katarina Andjelkov 117 Osteoarthritis of the Knee: Comparison Between Intra-­articular Injection of Adipose-­Derived Stromal Vascular Fraction and Nanofat���������������������������������������������������� 1683 Ivan Aleksandrovich Smyshlyaev, Sergey Ilsuverovich Gilfanov, Elena Viktorovna Batuchtina, Igor Popov, Viacheslav Sergeevich Vasilyev, Andrey Alexeevich Pulin, and Ilya Igorevich Eremin Index�������������������������������������������������������������������������������������������������������� 1701

List of Videos

Video 15.1  ITR2 Harvest and Processing Video 15.2  ITR2 Technique Video 20.1  Infiltration tumescent abdomen site of harvest Video 20.2  Fat washed with normal saline Video 20.3  Washed fat emulsified Video 20.4  Fat graft upper lip Video 20.5  Fat grafting buttocks ultrasound assisted Video 20.6  Injection site of morphea scleroderma right arm Video 21.1 Animation showing the pathophysiology of fat embolism secondary to gluteal fat grafting including pulmonary and cerebral embolism Video 23.1  PRP-enriched lipofilling Video 26.1 Cellular Optimized Nanofat for Microneedling and as a Unique Nanofat Biocrème_1 Video 26.2 Cellular Optimized Nanofat for Microneedling and as a Unique Nanofat Biocrème_2 Video 26.3 Cellular Optimized Nanofat for Microneedling and as a Unique Nanofat Biocrème_3 Video 26.4 Cellular Optimized Nanofat for Microneedling and as a Unique Nanofat Biocrème_4 Video 27.1 Enzymatic stromal vascular fraction isolation from lipoaspirate Video 27.2 Fat graft preparation and technique for stromal vascular fraction and lipograft injection Video 29.1 Harvesting of fat with 10 cc syringe with a syringe vacuum of less than 1 cc throughout Video 29.2 Taking large volume of fat graft using a closed system fat collector that allows the fat to float and remove the liquid by suction through a filter. There is no need to centrifuge this fat Video 29.3 In vitro demonstration of the correct way of depositing small separate particle of fat as you pull the cannula back as opposed to slowly depositing thick columns of fat. It is a good method of training with left over fat in theatre Video 29.4 Grafting fat after autologous tissue breast reconstruction to further enhance shape and volume. Notice that a 10 cc of fat requires 35–45 passes to deposit the whole volume Video 29.5 Grafting of fat in the buttock in the subcutaneous level with 10 cc syringe and 2 mm cannula xxxiii

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Video 30.1 Fat graft manual harvest A: showing the technique of 1.2 mm super Luer lock cannula mounted on 10 cc syringe and creating a negative suction and with gentle to and fro movements, aspirating yellow fat grafts from abdomen Video 30.2 Fat graft manual separation A; showing the technique of removal of the bottom layer contains amounts of tumescent fluid and blood, using 24 G needle and 1 cc syringe. Also shows filling of the syringes with fat graft Video 30.3 Fat graft injection breast: showing techniques of fat injections during withdrawal of the needle and at multiple plains Video 30.4 Fat graft injection breast: showing excellent results in terms of softness, pliability and smoothness of texture Video 30.5 Fat graft injection forehead: showing techniques of fat grafts in heavily scarred forehead using small cannula and injecting while withdrawing Video 30.6 Fat graft injection results 2 years: showing excellent results in terms of softness, pliability and smoothness of texture following autologous fat grafts Video 31.1 Centrifuged microfat processing and injection technique Video 31.2 Nanofat processing and injection technique Video 34.1  PRP preparation Video 34.2  Acne Scar Video 34.3  Patient Fig 8 - Surgical Scar protocol Video 35.1  CRPS Final Video 37.1  Clinical Case Video 37.2  SVF Video 39.1  Lipofilling in vasculitic ulcer Video 39.2  Lipofilling scar Video 41.1  AdipoLaser rejuvenation movie Video 43.1  The mechanical and controlled injection of HF-MSCs Video 44.1 PRP injection technique to the scalp showing needle entering scalp at a 45-degree angle at a depth of approximately 2.0–2.5 mm Video 44.2 PRP injection technique to the scalp Video 46.1  Fat preparation and transfer Video 46.2  Skin aging process Video 49.1  Surgical anatomy in regenerative surgery of Face, Scalp, Neck Video 51.1 Preparation of the properly diluted fat (PDF). After centrifugation, the oil is removed, and the bottommost 1 mL of reddish fluid (which is thought to contain a high concentration of stromal vascular factors) is aspirated from the syringe. The remaining serum and hematic fluid are discarded, and 7 mL of centrifuged fat is recombined with 1 mL of the reddish infranatant fluid. Subsequently, 2 mL of saline is added, thereby yielding a 70% solution of centrifuged fat Video 51.2 Tunnelization and fat injection. Multiple tunnels are created by means of an empty 1.2-mm cannula inserted as a vertical vector into a plane beneath the orbicularis. Additional tunnels

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then are made as horizontal vectors in the same plane. Injected fat then is distributed smoothly into the prepared channels Video 51.3 Injecting PDF into the lower eyelid. Due to the previously created tunnels and the dilution the almost liquid fat can be injected rapidly without recurring to a high number of passes Video 51.4 72-year-old woman 3 months after upper minimal blepharoplasty and fat grafting on upper and lower lids. Visible fat nodules on lower lid bilaterally were removed through direct transcutaneous approach Video 53.1 Preparation for the harvesting, processing, and grafting of 32 mL in the chin area in a 46-year-old man Video 55.1 Facial fat grafting technique Video 57.1 This video displays nanofat grafting Video 58.1  SUPPLEMENT Animation preop PAT 1 Video 58.2  SUPPLEMENT Animation preop PAT Compare_face Video 58.3  Supplement Patient 4 -B55A4293 Video 60.1 This video was recorded during direct microlaryngoscopy under general anesthesia in a young man undergoing a fat injection procedure for severe dysphonia due to iatrogenic paralysis of the right vocal fold. The lesion of the laryngeal recurrent nerve occurred during previous thyroidectomy. The paralyzed fold is markedly hypotrophic, as long-­standing denervation has caused a progressive loss of muscular bulk. Multiple injections are performed in the paralyzed fold that regains volume at the end of the procedure. A mild overcorrection is achieved Video 60.2 This is the preoperative videolaryngoscopy of a 45-year-old woman affected by left vocal fold paralysis. The paralyzed vocal fold is flaccid and hypotrophic. The voice is very breathy because during phonation the vocal folds do not adduct adequately and there is air escape Video 60.3 This videolaryngoscopic recording demonstrates the result obtained 6 months after the procedure of vocal fold fat grafting; phonatory closure of the vocal folds is achieved and the voice sound is normal Audio 60.4 This is a typical example of breathy voice while reading a text in a woman affected by unilateral vocal fold paralysis Audio 60.5 The patient—6 months after vocal fold fat injection—is reading the same text as in the audiofile No.1; she has achieved a normal voice Video 61.1 The velopharyngeal sphincter. (a) Complete closure of the velopharyngeal sphincter during phonation. The velum is pushed against the posterior pharyngeal wall by the elevation of the levator veli palatini muscle. On phonation the air passes through the mouth and not through the nose. (b) Incomplete closure of the velopharyngeal sphincter. A gap remains between the oro- and nasopharynx. On phonation the air passes through the oral and the nasal cavity, the so-called velopharyngeal incompetence (VPI). [1] Palatopharyngeus; [2]

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levator veli palatini; [3] musculus uvulae; [4] constrictor pharyngeus superior Video 61.2 Fat harvesting from the abdomen. It is important to pinch the abdominal skin to avoid entering the abdomen with the cannula Video 61.3 The video shows the placement of fat in the posterior pharyngeal wall using a bent blunt cannula Video 61.4a Sequela of cleft palate. (a) Preoperative nasendoscopic view of a patient with VPI Video 61.4b Sequela of cleft palate. (b) result at one year, following 3 ml of fat injected in the posterior pharyngeal wall and 9 ml in the palate Video 61.5a (a, b) Sequela of cleft palate, previously operated on with velopharyngeal flap elsewhere. (a) Preoperative nasendoscopic view of the patient with moderate VPI Video 61.5b (a, b) Sequela of cleft palate, previously operated on with velopharyngeal flap elsewhere. (b) result at 1 year, following 1.5 ml of fat injected in the posterior pharyngeal wall Video 62.1 LRRT Sintesi Video 63.1 Machine centrifugation and preoperative planning, with the expected amount of fat and donor sites. The centrifugation is for 3 min at 3000 rpm/1200 g-force Video 63.2 Manual centrifugation and preoperative planning with the expected amount of fat and donor sites. This is a closed system. The centrifugation is for 10 min with 15 g-force. There is the capacity to centrifuge four 60 mL syringes for 3 min, which results in 240 mL of centrifuged fat Video 63.3 Female, 36 years old, with rippling after multiple implant removal and insertion subglandularly. Needed delayed hybrid revision to treat rippling. Fat was processed with MicroAire with decanting in two sessions. Video is showing the second session. Right side: 150 mL; left side: 205 mL, and the lower pole was also grafted on the left side due to asymmetry. The fat should be grafted perpendicular to the rippling lines after peroperative expansion with a multihole 3 mm cannula vibrating without suction Video 63.4 Female, 38 years old, with hypotrophy together with slight asymmetry. Grafting technique using 20 mL syringe and 2.7 mm cannula. Retrograde grafting with constant cannula tip feeling in different layers Video 64.1 Simultaneous implant conversion with fat in a 35-year-old with MicroAire and decanting. Five years earlier, the patient had mastopexy augmentation with submuscular implant size of 275. The implant was removed, and 325 mL fat grafting was injected. Note the depression in the left vertical scar, which obliged us to make a lower entry incision) Video 64.2 Simultaneous implant conversion with fat: 26-year-old woman who had a submuscular implant. 260/280 mL,

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implant conversion with capsular contracture grade 3. A conversion with fat grafting, 150 mL before removing the implant and 85 mL after removing the implant Video 64.3 Simultaneous hybrid augmentation in a 29-year-old woman: 200-size round implants inserted subfascial with 125 mL fat graft was grafted around the implant per side between the fascia and the skin using MicroAire and decanting Video 64.4 Delayed hybrid revision. Status after 350 mL submuscular implant insertion 1 year earlier in a 27-year-old woman; request to soften the edges as the implant. Two sessions of decanted fat were performed. Right: 150/175 mL and left: 150/175 mL. At the same time, an augmentation of gluteal area with fat was performed Video 64.5 Mastopexy augmentation with posterior flap as auto-prosthesis and fat grafting, in 57-year-old woman, to augment the upper pole and cleavage areas. The fat was grafted (175 mL per side) through separate lateral and medial entry sites Video 66.1 A 1:1 composite breast augmentation is accomplished with 200 cc implants and 200 cc of fat Video 66.2 Markings and explanation for a 1:1 composite breast augmentation technique Video 67.1 (Operation on Patient 1) Closed intraoperative tissue dilatation with liporestructuring and shifting (tissue “manipulation”) is also a recipient-site restructuring before lipofilling (MOV 60796 kb) Video 67.2 (Operation on Patient 1) Microstructural autologous fat tissue transplantation (lipofilling) of the hypoplastic (aplastic) breast tissue (two stages) Video 67.3 Operative technique of Poland syndrome correction with autologous fat grafting by manual liposuction, decantation, and manual lipofilling. In some cases, manual centrifugation or decantation alone can be used, too. When deciding for this we may prefer to decant the fat material without any filtering or transfer to centrifuge. This method is leaving the 20 mL syringes in a vertically standing position for 12 min, then draining the bottom layer (blood and tumescent fluid), and then transferring the fat from the syringes to 2.5 ml LuerLock syringes through a Luer-Lock transfer hub or “T” adapter. In our case 135 ccs of microstructural fat was used to reconstruct the aplastic breast in the adolescent with diagnosed Poland syndrome Video 68.1 It is a brief video clip on fat harvesting with low-vacuum manual syringes after tumescent infiltration and fat grafting using axillary approaches into the sub-glandular layer of the breasts. After centrifugation to eliminate blood and fibrotic materials, the graft should be distributed evenly in all the layers of the breast except the glandular tissues Video 68.2 A short video on cell-enriched fat graft to the breasts

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Video 69.1 Pentagram—Part I Video 69.2 Pentagram—Part II Video 70.1 Preparation of Stromal Enriched Lipograft Video 70.2 Performing the SEL for breast augmentation. T blunt tip of the injection cannula of 1.9 mm is tilted and inserted through a 2 mm wound cut. A multilevel, multi-tunnel, and multipoint percutaneous injection of SEL is done in the breast. Fat droplets are delivered, while the cannula is withdrawn. In a fan-shaped manner, numerous fat parcels can be consistently micro-transplanted. The injection cannula is then advanced to the entire subcutaneous and glandular plane of the breast and 220 ml of SEL is injected in each breast Video 71.1 Fat grafting using a 20 cc syringe and 2 mm cannula to inject fat through the surgical incision into the soft tissue of the breast Video 71.2  Fat harvesting with a 4 mm Mercedes cannula using traditional suction-assisted lipectomy into a sterile graduated cylinder Video 71.3 Utilization of the Del Vecchio spinner to centrifuge the fat to allow separation from the lipoaspirate Video 72.1 Markings & surgical technique—Breast augmentation using PALLL Video 73.1 High definition Video 74.1  Technique for central tunnel and fat grafting. Upper left: Drawing the inversion line. Second upper left: Local anesthesia. Third upper left: Making lifting suture of 3–0 PDS. Upper right: Central tunneling with 14 G. Lower left: Applying the suspension device. Second left, lower: Tightening the thread around the pin of the suspension device and checking the capillary filling. Third lower right: Preparing the donor site. Lower right: Grafting after decanting, with 1 mL syringe Video 74.2  Central tunnel technique. Fat grafting in a severe (third degree) nipple inversion Video 75.1 Breast reconstruction with fat and threads using PowerAssisted Liposuction, Loops and Lipofilling (PALLL) technique Video 76.1  Better definition of infra-mammary fold with the introduction of a suture passer in the lower pole of the breast. To get a better definition of the infra-mammary fold, we put a thread lift Video 77.1  Fat Grafting Video 77.2  Intraoperative view on the injected fat. The previous mastectomy scar was opened with a clear view on the injected fat that is viable. A thick layer of subcutaneous tissue was restored with fat grafting and will provide nice covering of the implant. In this case we revised the mastectomy scar because it was enlarged and distorted after the initial mastectomy. It shows the importance of not opening the mastectomy scar in secondary cases to insert the expander. Not reopening

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this scar at the beginning of the procedure allows us to augment the tissues beneath the scar Video 78.1 Graf Mastopexy Video 79.1 Prepectoral breast reconstruction with T loop mesh Video 80.1 Stem Cell Enriched Fat Injection In Aesthetic, Reconstructive Breast Surgery Video 81.1 PPSS and fat grafting Video 84.1 Fat Grafting Video 85.1 AFT Video 87.1 Operative techniques with a 4 mm MicroAire cannula for harvesting and for grafting with a syringe and a 4 mL cannula Video 87.2 Operative techniques with a 4 mm MicroAire cannula for harvesting and for grafting with a syringe and a 4 mL cannula Video 87.3 Operative techniques with power-assisted gluteal augmentation; expansion vibration lipofilling (EVL) technique in gluteal augmentation (Abboud and Del Vecchio) [16, 21] Video 87.4 Operative techniques with power-assisted gluteal augmentation; expansion vibration lipofilling (EVL) technique in gluteal augmentation (Abboud and Del Vecchio) [16, 21] Video 89.1 Preoperative markings Video 89.2 Surgical technique Video 90.1 Infiltración grasa 720 Video 90.2 Método Video 91.1 Focal defect correction Video 91.2 No migration Video 91.3 Gluteal fat grafting Video 92.1 Mixing of the SVF containing ADSCs Video 92.2 Gluteal SEL Video 93.1 Fat straining silent Video 93.2 Fat grafting silent Video 94.1 Syringe Assisted Lipo-Transfer (SALT) method is based on a set of principles used to harvest and graft fat, rather than to rely on equipment. In its most basic form SALT requires only a harvesting cannula and a syringe in order to harvest and transplant fat Video 94.2 Tissue rearrangement, mastoplasty with the use of autologous tissue is the mainstay of our current treatment of female breast reconstruction after MWL. Visualized here on a 32-year-old woman with moderate MWL breast deformity and hypoplasia, augmented with bilateral LICAP flaps and AFG Video 98.1 Fat and vulvovaginal Videos 99.1 and  99.2 Technical details of rejuvenation of the vaginal canal. Film 1: left: 1 mL syringe with 0.7 mm cannula grafting from lateral entry point. Film 2: right: Starting from lateral vaginal wall. Right: Grafting the introitus to get more volume to the aperture and contribute to tightening of the introitus

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Video 102.1 Gyneco 3 min sous titres copy Video 104.1 Secondary girth enhancement Video 105.1 Fat and penile Video 108.1 Superposition of both superficial and deep anatomical planes involved in DD surgery Video 108.2 Microfat grafting in Dupuytren’s contracture Video 108.3 The syringe of fat_Part 1 Video 108.4 The syringe of fat_Part 2 Video 108.5 The syringe of fat_Part 3 Video 109.1 Technique of the PALF procedure step-by-step Video 110.1 Coleman technique Video 111.1 lipoaspirate Video 111.2 SEL using the Nanocube device Video 111.3 Hand Rejuvenation by minimally invasive injection of Stromal Enriched Lipograft Video 112.1 Pulp Video 116.1 Composite calf augmentation: fat grafting in subcutaneous plane after calf implant surgery; staged procedure Video 117.1 Injection—the Injection of SVF or Nanofat into the knee joint is performed through a standard lateral suprapatellar access. Puncture of the knee joint is performed in a clean dressing room, in aseptic conditions Video 117.2  Liposuction—liposuction is performed in the operating room under local or General anesthesia under aseptic conditions through paraumbilical access Video 117.3  Transportation—syringes with lipoaspirate are Packed in a sterile bag and then placed in a shipping container. The accompanying documentation is sent along with the syringes. It indicates gender, age, blood type, medical history number, volume of lipoaspirate, and donor area. After that, the container is sent to the laboratory for SVF isolation Video 117.4  Preparation of Nanofat—to obtain the Nanofat product, adipose tissue was taken in the same way in a volume of 20 mL. In the operation room, the syringe with the collected product was connected to a syringe of the same volume through a specially designed connector. By moving the product 60 times from one syringe to another, large fatty grafts were mechanically ground to an emulsion state. The resulting emulsion was cleaned of large components through a sterile filter with a pore size of 15 μm (Fig. 117.1). The final Nanofat product is an emulsion with particle sizes of less than 0.2 mm (adipose tissue fragments and cell elements) that passes through a needle with a minimum diameter of 0.25 mm

List of Videos

About the Editor

Amin  Kalaaji, MD, PhD  is the Medical Director and consultant plastic surgeon at Oslo Plastic Surgery Clinic in Oslo, Norway, a position he has held for the past 20 years. Dr. Kalaaji was also the president of the Norwegian Society of Aesthetic Plastic Surgery (NSAPS) from 2018 to 2020. For 20 years, Dr. Kalaaji’s focus has been on aesthetic plastic surgery, including the use of fat grafting for various indications on the body—which is the subject of this text, Plastic and Aesthetic Regenerative Surgery and Fat Grafting: Clinical Application and Operative Techniques. Dr. Kalaaji earned his medical degree from Aleppo, Syria, and completed his surgical training in Paris, France, and Gothenburg, Sweden, where he also completed his PhD in bone grafting of the cleft lip and palate. For 10 years, Dr. Kalaaji was a consultant plastic surgeon/vice chief and chief at the plastic surgery department at Telemark Central Hospital and Oslo University Hospital in Norway. Dr. Kalaaji has published many peerreviewed scientific papers and has given more than 300 lectures, courses, and conference presentations in plastic and aesthetic surgery worldwide—for organizations such as the American Society for Aesthetic Plastic Surgery (ASAPS), the International Society of Aesthetic Plastic Surgery (ISAPS), the International Society of Plastic Regenerative Surgeons (ISPRES), and the International Master Course on Aging Science (IMCAS) in addition to speaking at many national and international meetings worldwide. He curxli

About the Editor

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rently serves on the editorial boards for the Aesthetic Surgery Journal, the Journal of Plastic Surgery and Hand Surgery, and the Acta Chirurgiae Plasticae. Dr. Kalaaji is also an active member and a board member of the Norwegian Society of Aesthetic Plastic Surgeons, and a former board member of the Norwegian Society of Plastic Surgeons. He is also an active member of the Swedish Society of Plastic Surgeons; the Nordic Society of Plastic Surgeons; and ASAPS, including its international and education/program committees, ISAPS and ISPRES. In 2015, 2017, and 2019, Dr. Kalaaji served as chairman of the 1st, 2nd, and 3rd Norwegian American Aesthetic Meetings (NAAM 1, 2, 3) held in Oslo, Norway. In July 2017, he was elected as the national secretary for ISAPS in Norway for a term of 4 years, in addition to being on the member committee from 2018 through 2020. In October 2018, after a unanimous vote, Dr. Kalaaji became a member of the executive board of directors of ISPRES.  A month later, he was elected president of NSAPS—a position he held until the end of 2020. In 2020, Dr. Kalaaji also became the chairman of the membership committee of ISPRES and a member of the safety committee of ISAPS—a position he will hold until 2022. This book—with its 117 chapters, approximately 1625 educational figures, and 131 video clips—proudly represents the knowledge and expertise of 242 authors from 31 countries, 81 cities, and 5 continents.

Oslo Plastic Surgery Clinic (Oslo Plastikkirurgi Clinic), Oslo, Norway

Contributors

Marwan  H.  Abboud Plastic and Reconstructive Surgery Department, Centre Hospitalier Universitaire de Tivoli, La Louvière, BelgiumUniversité Libre de Bruxelles (ULB), Brussels, Belgium Nicolas M. Abboud  Plastic and Reconstructive Surgery Department, Centre Hospitalier Universitaire de Tivoli, La Louvière, BelgiumUniversité Libre de Bruxelles (ULB), Brussels, Belgium Nicholas  Kalavrezos  Charles Wolfson Center for Reconstructive Surgery, Royal Free Hospital, London, UK Head and Neck Centre, University College London Hospital, London, UK Aly Hussein Abulhassan  Plastic and Reconstructive Surgery Unit, Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt Hussein  Saber  Abulhassan Plastic and Reconstructive Surgery Unit, Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt Ashkan  Afshari Department of Plastic and Reconstructive Surgery, Vanderbilt University Medical Center, Nashville, TN, USA Annarita  Agovino  Plastic Reconstructive Surgery Department and Burns Unit, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Department of Plastic Surgery, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Hugo  Alberto  Drago  Burns Unit, Department Plastic and Reconstructive Surgery, Burns Hospital, Sanatorio Güemes, Ciudad Autónoma de Buenos Aires, Argentina Jean-Maxime Alet  Institut Aquitain de la Main, Pessac, France Mona  Alkhotani Pierre Colson Burn Center, Edouard Herriot Hospital, Lyon, France

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Contributors

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Aurora Almadori  Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, UK Department of Plastic Surgery, Royal Free NHS Foundation Trust Hospital, London, UK Charles Wolfson Center for Reconstructive Surgery, Royal Free Hospital, London, UK Department of Plastic Surgery, Policlinic Hospital Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy Department of Plastic and Reconstructive Surgery, Royal Free London NHS Foundation Trust Hospital, London, UK Katarina Andjelkov  Faculty of Medicine, University of Belgrade, Belgrade, Serbia BelPrime Clinic, Belgrade, Serbia Matteo  Angelini University of Padua, Italian Association of Aesthetic Plastic Surgeons, Rome, Italy Violeta Skorobac Asanin  Hospital Diona, Belgrade, Serbia Alexander Aslani  Cirumed Clinic, Marbella, Spain Céline  Auxenfans Banque de Tissus et de Cellules, Edouard Herriot Hospital, Lyon, France A. Luiz Eduardo Avelar  Department of Anthropology and Plastic Surgery, Dermatology, Sao Paulo, Brazil M. Mustafa Aydınol, Teşvikiye Mahallesi Fulya, Nişantaşı Hospital, Şişli, Turkey Parshanak  Azdasht  Park-Klinik Birkenwerder, Germany Park-Klinik, Birkenwerder, Germany

Birkenwerder,

Plastic

Surgery,

Tran Le Bao Ha  Tissue Engineering and Biomedical Materials Department, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam Franco Bassetto  Institute of Plastic and Reconstructive Surgery, University of Padua, Padua, Italy Institute of Plastic and Reconstructive Surgery of the University of Padua, Padua, Italy Julie Bastien  Institut Aquitain de la Main, Pessac, France Andrea  Battistini Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy Elena  V.  Batuchtina Central Clinical Hospital of the Presidential Administration, Moscow, Russia Melanie Baumgartner  Oslo Plastikkirurgi Clinic, Oslo, Norway

Contributors

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Alejandro  Jorge  Beltrami  Burns Unit, Department Plastic and Reconstructive Surgery, Burns Hospital, Sanatorio Güemes, Ciudad Autónoma de Buenos Aires, Argentina Laurent Benadiba,  Geneva, Switzerland Alessandro Bianchi  Dipartimento Scienze Salute della Donna, del Bambino e di Sanità Pubblica, UOC Chirurgia Plastica, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy George J. Bitar  Bitar Cosmetic Surgery Institute, Fairfax, VA, USA Vlad Bloanca  Plastic Reconstructive Surgery Department and Burns Unit, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Department of Plastic Surgery, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Daniele Bollero  Burn Unit, Department of Plastic Surgery, CTO Hospital, Turin, Italy Anna  A.  Borovikova Topclinic of Aesthetic Medicine, Moscow, Russian Federation Silvia  Bossi Burns Unit, Department Plastic and Reconstructive Surgery, Burns Hospital, Sanatorio Güemes, Ciudad Autónoma de Buenos Aires, Argentina Jeremy Bosworth  UAB Division of Plastic Surgery, Birmingham, AL, USA Fabien Boucher  Department of Plastic and Reconstructive Surgery, CroixRousse Hospital, Lyon, France Carter Boyd  UAB School of Medicine, Birmingham, AL, USA Massimiliano  Brambilla Plastic Surgery Service, Department for the Health of Women, Children and Newborn, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy University of Milan, Milan, Italy Tiberiu Bratu  Department of Plastic Surgery, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Miguel G. Bravo  Cirumed Clinic, Marbella, Spain Sophie Brosset  Pierre Colson Burn Center, Edouard Herriot Hospital, Lyon, France Ryan  S.  Burke Plastic and Reconstructive Surgery, Emory University, Atlanta, GA, USA Peter E. M. Butler  Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, UK Department of Plastic Surgery, Royal Free NHS Foundation Trust Hospital, London, UK Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, UK

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M.  Bradley  Calobrace Private Practice, CaloAesthetics Plastic Surgery Center, Louisville, KY, USA Clinical Faculty, Division of Plastic Surgery, University of Louisville, Louisville, KY, USA Clinical Faculty, Division of Plastic Surgery, University of Kentucky, Lexington, KY, USA Rossella Campa  General Surgery Unit, Ospedale Santo Spirito – Asl Roma1, Rome, Italy Gianluca  Campiglio  Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy Campiglio Plastic Surgery Center, Milan, Italy Alvaro  Luiz  Cansanção Plastic Surgery, Universidade Iguacu, Rio de Janeiro, Rio de Janeiro, RJ, Brazil Giovanna  Cantarella Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy Otolaryngology Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy Pietro Cavalcanti  Plastic Surgery Unit, Ospedale Santo Spirito - Ospedale San Filippo Neri - ASL Roma 1, Rome, Italy Fabio  Caviggioli Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy Abel Chajchir  Instituto Medico Quirurgico Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina Sarah  Houimli  Charfeddine University Tunis el Manar, Faculty of Medicine, Tunis, Tunisia Universite Pierre et Marie Curie Paris VI, Paris, France Head of Depatment of Plastic, Reconstructive and Aesthetic Surgery, in Trauma and Burns Center, Ben Arous, Tunisia Obaid Chaudhry,  Private Practice, Beverly Hills, CA, USA Manhattan Eye, Ear, and Throat Hospital, New York City, NY, USA Vinod K. Chopra  Chantilly Cosmetic Surgery, Chantilly, VA, USA Anca  Maria  Cimpean Department of Histology, Angiogenesis Research Center, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania Steven R. Cohen  FACES+ Plastic Surgery, Skin and Laser Center, La Jolla, CA, USA Plastic Surgery, University of California, San Diego, CA, USA

Contributors

Contributors

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Alfredo Colapietra  Plastic Surgeon in Private Practice, Milan, Italy Sherry Collawn  UAB Division of Plastic Surgery, Board Certified American Board of Plastic Surgery, Birmingham, AL, USA UAB Division of Plastic Surgery, Birmingham, AL, USA Alexandra Condé-Green  ACG Plastic Surgery, Boca Raton, FL, USA Andrea  Conversi Plastic Surgery Unit, Azienda Ospedaliera Policlinico Umberto I, Rome, Italy Fabián  E.  Cortiñas Instituto Medico Quirurgico Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina Zorin Crainiceanu  Plastic Reconstructive Surgery Department and Burns Unit, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Department of Plastic Surgery, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Matteo d’Alessio  Plastic Reconstructive Surgery Department, University of Naples “Luigi Vanvitelli”, Naples, Italy Roberto  d’Alessio  Plastic Reconstructive Surgery Department and Burns Unit, “A. Cardarelli” National Hospital, Naples, Italy Plastic Reconstructive Surgery Department, University of Naples “Luigi Vanvitelli”, Naples, Italy Giovanni Dal Pra  Plastic Surgery Unit, Ospedale Santo Spirito - Ospedale San Filippo Neri - ASL Roma 1, Rome, Italy Richard  Anthony  D’Amico  Englewood Medical Center, Englewood, NJ, USA Francesco  D’Andrea  Department of Plastic Reconstructive and Aesthetic Surgery, University Federico II, Naples, Italy Stefania de Fazio  International Liaison SICPRE, Rome, Italy Emmanuel Delay  Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Lyon, France Daniel Del Vecchio,  Private Practice, Beverly Hills, CA, USA Manhattan Eye, Ear, and Throat Hospital, New York City, NY, USA Massachusetts General Hospital, Boston, MA, USA Back Bay Plastic Surgery, Boston, MA, USA Dayane Raquel de Paula  Division of Plastic and Reconstructive Surgery, Hospital de Clínicas, Federal University of Paraná, Paraná, Brazil Pietà Medical Center, Paraná, Brazil Nelson  de Paula  Piccolo Department of Plastic Surgery, Pronto Socorro para Queimaduras, Goiânia, Goiás, Brazil

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Paulo de Paula Piccolo  Department of Plastic Surgery, Pronto Socorro para Queimaduras, Goiânia, Goiás, Brazil Georgyi P. Dimov  South Ural State Madical University, Chelyabinsk, Russia Fabio Santanelli di Pompeo  Department of Plastic Surgery, University of Rome, Rome, Italy Ncoza C. Dlova  Department of Dermatology, University of KwaZulu-Natal, Nelson R Mandela School of Medicine, Durban, South Africa De  Fazio  Domenico Plastic and Reconstructive Surgery Unit, IRCCS Galeazzi Orthopedic Hospital Institute, Milan, Italy Dino Elyassnia  Marten Clinic of Plastic Surgery, San Francisco, CA, USA Delay Emmanuel  Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Cancer Institute, Lyon, France Ilya  I.  Eremin  National Research Center “Kurchatov Institute”, Moscow, Russia Natoli Farber  University of Pittsburgh, Pittsburgh, PA, USA Fazel Fatah  The Westbourne Centre, Birmingham, UK Lydia Masako Ferreira  Plastic Surgery Division, Universidade Federal de Sao Paulo UNIFESP, Sao Paulo, Brazil Joseph  M.  Firriolo Division of Plastic and Reconstructive Surgery, University of California Davis, Sacramento, CA, USA Alfred Fitoussi  Breast Center Paris, Paris, France Anna Fogli  Dr. Anna Fogli Aesthetics, Turin, Italy Tomas  Fortoul Plastic Surgery, Centro Medico Docente La Trinidad, Caracas, Venezuela Jordan  D.  Frey Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA Gabriele Storti   Plastic and Reconstructive Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, Rome, Italy Pietro  Gentile Surgical Science Department, Plastic and Reconstructive Surgery Unit, University of Rome “Tor Vergata”, Rome, Italy Lobna  Y.  Ghanem Department of Clinical Pathology, Theodore Bilharz Research Institute, Cairo, Egypt Ioana Ghiurco  Emergency University Hospital Elias, Bucharest, Romania Dina  T.  Ghorra Plastic and Reconstructive Surgery Unit, Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt Campiglio Gianluca  Campiglio Plastic Surgery Center, Milan, Italy Sergey Ilsuverovich Gilfanov  Central Clinical Hospital of the Presidential Administration, Moscow, Russia

Contributors

Contributors

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Jeffrey  M.  Gimble Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, USA Luigi Gliosci  Plastic Surgery Unit, Ospedale Santo Spirito - Ospedale San Filippo Neri - ASL Roma 1, Rome, Italy Eduardo  Gonzalez Hansjorg Wyss Department of Plastic Surgery, NYU School of Medicine, New York, NY, USA Ruth Maria Graf  Division of Plastic and Reconstructive Surgery, Hospital de Clínicas, Federal University of Paraná, Paraná, Brazil Pietà Medical Center, Paraná, Brazil Maristella Guerra  Plastic Surgery Unit, Ospedale Santo Spirito - Ospedale San Filippo Neri - ASL Roma 1, Rome, Italy Gudjon  Leifur  Gunnarsson Department of Plastic Surgery, Sørlandet Hospital, Arendal, Norway Ashok  Gupta Division of Plastic and Reconstructive Surgery, Bombay Hospital Institute of Medical Sciences, Mumbai, India Beth Gusenoff  University of Pittsburgh, Pittsburgh, PA, USA Jeffrey Gusenoff  University of Pittsburgh, Pittsburgh, PA, USA Moustapha  Hamdi Plastic Surgery Department, Brussels University Hospital—Vrije Universiteit Brussel (VUB), Brussels, Belgium Foued Hamza  The London Welbeck Hospital, London, UK Felicia R. Hataway  UAB School of Medicine, Birmingham, AL, USA Trond Hugo Haukebøe  Oslo Plastic Surgery Clinic, Oslo, Norway Amani  Landoulsi  Helal  University Tunis el Manar, Faculty of Medicine, Tunis, Tunisia Universite Pierre et Marie Curie Paris VI, Paris, France Department of Plastic, reconstructive and cosmetic Surgery, Oriana Hospital Pulman Hotel Sharjah, Dr Kayle Aesthetic Clinic, Valiant Clinic and Hospital Dubai, Dubai, UAE Barbara Hersant  Department of Maxillofacial and Plastic & Reconstructive Surgery, Henri Mondor Hospital, Créteil, France Sierra  Hewett  FACES+ Plastic Surgery, Skin and Laser Center, La Jolla, CA, USA Plastic Surgery, University of California, San Diego, CA, USA Izolda Heydenrych  Cape Town Cosmetic Dermatology Centre, Milnerton, South Africa Division of Dermatology, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa K.  Kye  Higdon Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

l

Amita Hiremath  Division of Plastic and Reconstructive Surgery, Bombay Hospital Institute of Medical Sciences, Mumbai, India Alfredo Hoyos  Total Definer Research Group, Bogota, Colombia Dhara Clinic, Bogota, Colombia Karima  Ismail  Dept. of Plastic Surgery, Cairo University (Kasr Al-Ainy Hospitals), Cairo, Cairo Governorate, Egypt Charlotte Jaloux  Hand Reconstructive Surgery, Timone Hospital, Marseille, France Shima Jamshidi  Royal Free Hospital NHS Trust, London, UK Máté Jancsó  Action for Defenceless People Foundation, Budapest, Hungary Premium Plastic Surgery, Budapest, Hungary Department for Plastic Surgery and Burns, Hungarian Defence Forces Medical Centre, Budapest, Hungary Dana Mihaela Jianu  ProEstetica Clinic, Bucharest, Romania Stefan Jianu  Emergency University Hospital Elias, Bucharest, Romania Vanja  Jönsson Oslo Plastikkirurgi Clinic (Plastic Surgery Clinic), Oslo, Norway University of Oslo, Working at Oslo Plastic Surgery Clinic, Oslo, Norway Oslo Plastikkirurgi Clinic, Oslo, Norway Oslo Plastic Surgery Clinic (Oslo Plastikkirurgi Clinic), Oslo, Norway Carlos Rodrigo Jorrat  Burns Unit, Department Plastic and Reconstructive Surgery, Burns Hospital, Sanatorio Güemes, Ciudad Autónoma de Buenos Aires, Argentina Amin Kalaaji  Oslo Plastikkirurgi Clinic (Oslo Plastic Surgery Clinic), Oslo, Norway Artúr  Kalatovics Action for Defenceless People Foundation, Budapest, Hungary Premium Plastic Surgery, Budapest, Hungary Roman A. Kamyshinsky  National Research Center “Kurchatov Institute”, Moscow, Russian Federation Nolan  S.  Karp Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA Anne Marie Kennedy  Queen Victoria Hospital, East Grinstead, UK Natalia  I.  Khramtsova Perm State Medical University, Perm, Russian Federation Bong-Sung  Kim Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland Francesco  Klinger Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy

Contributors

Contributors

li

Marco Klinger  Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy Rashmi Kshirsagar  Technical Development, Cambridge, MA, USA Pallavi Archana Kumbla  UAB Division of Plastic Surgery, Birmingham, AL, USA Kim  Siea  Lee  Plastic and Aesthetic Surgeon, The M Clinic, Penang and Kuala Lumpur, Malaysia Kwang  Lee Plastic Reconstructive Surgery Department and Burns Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK Régis  Legré Hand Reconstructive Surgery, Timone Hospital, Marseille, France Claudio  Ligresti  Department of Plastic Surgery, Italian Academy Wound Care (IAWC)—University of Asti, Asti, Italy Maria Pia Hospital, Turin, Italy Istituto Clinico Ligure di Alta Specialità, Rapallo, Italy University of Trieste, Trieste, Italy University of Pavia, Pavia, Italy Celeste S. Limoli  Low Vision Research Center, Milan, Italy Paolo G. Limoli  Low Vision Research Center, Milan, Italy Roberta Piccolo Lobo  Department of Plastic Surgery, Pronto Socorro para Queimaduras, Goiânia, Goiás, Brazil Zoltán  Lóderer Department of General, Vascular and Plastic Surgery, Markusovszky University Teaching Hospital, Szombathely, Hungary Evgenyi  A.  Lomakin  South Ural State Madical University, Chelyabinsk, Russia Benedetto  Longo Division of Plastic and Reconstructive Surgery, Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy Lena Løvfold  Oslo Plastikkirurgi Clinic, Oslo, Norway Elena  Lucattelli Plastic and Reconstructive Microsurgery, Careggi University Hospital, Florence, Italy Guy  Magalon  Plastic Surgery Department, Assistance Publique Hôpitaux de Marseille (APHM), Aix Marseille University, Marseille, France Jeremy  Magalon Culture and Cell Therapy Laboratory, INSERM CBT 1409, AP-HM, Aix Marseille University, Conception Hospital, Marseille, France Sarolta Magyar  Premium Plastic Surgery, Budapest, Hungary Department of Ophthalmology, St. Imre University Teaching Hospital, Budapest, Hungary

lii

Luca  Maione  Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy Timothy Marten  Marten Clinic of Plastic Surgery, San Francisco, CA, USA Chet  Mays Private Practice, CaloAesthetics Plastic Surgery Center, Louisville, KY, USA Isabella C. Mazzola,  Private Practice, Milan, Italy Riccardo  F.  Mazzola Department of Clinical Sciences and Community Health, University of Milan, Policonico Hospital, Milan, Italy G. Sanvenero Rosselli Foundation for Plastic Surgery, Milan, Italy Plastic Surgery, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda, Policlinic Hospital, Milan, Italy Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy Otolaryngology Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Jean  Paul  Meningaud Department of Maxillofacial and Plastic & Reconstructive Surgery, Henri Mondor Hospital, Créteil, France Sophie Menkes  Nescens clinique de Genolier, Genolier, Switzerland Geneva, Switzerland Ondřej Měšťák  Department of Plastic Surgery, First Faculty of Medicine, Charles University and Na Bulovce Hospital, Prague, Czech Republic Ivan Mogollon  Total Definer Research Group, Bogota, Colombia Ali A. Mojallal  Department of Plastic and Reconstructive Surgery, CroixRousse Hospital, Lyon, France Pierre Colson Burn Center, Edouard Herriot Hospital, Lyon, France Department of Plastic Surgery, Croix-Rousse Hospital, Hospices Civils de Lyon, University of Lyon, Lyon, France Meredith  Montgomery UAB School of Medicine, Birmingham, AL, USA Afshin Mosahebi  Royal Free Hospital NHS Trust, London, UK University College London, London, UK Nikola Music  “Colic” Hospital, Belgrade, Serbia Naghmeh Naderi  Royal Free Hospital NHS Trust, London, UK Foad Nahai  Plastic Surgery, Emory University, Atlanta, GA, USA Fabio Xerfan Nahas  Plastic Surgery Division, Universidade Federal de Sao Paulo UNIFESP, Sao Paulo, Brazil

Contributors

Contributors

liii

Nguyen  Thi  Ngoc  My Tissue Engineering and Biomedical Materials Department, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam Lyly Nguyen  Department of Plastic and Reconstructive Surgery, Vanderbilt University Medical Center, Nashville, TN, USA Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA Cathrine Nordahl  Oslo Plastikkirurgi Clinic, Oslo, Norway Ahmed  A.  Noreldin Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt Nora F. Nugent  Purity Bridge Clinic, Tunbridge Wells, UK Maria Cecilia Closs Ono  Division of Plastic and Reconstructive Surgery, Hospital de Clínicas, Federal University of Paraná, Paraná, Brazil Pietà Medical Center, Paraná, Brazil Andrea Pagani  Institute of Plastic and Reconstructive Surgery, University of Padua, Padua, Italy Norbert  Pallua Aesthetic Elite International—Private Clinic, Düsseldorf, Germany Gergely  Pataki Department of Pediatric Surgery and Traumatology, St. John’s Hospital and North Buda Unified Hospitals, Budapest, Hungary Action for Defenceless People Foundation, Budapest, Hungary Premium Plastic Surgery, Budapest, Hungary Department of Pediatric Surgery and Traumatology, Action for Defenceless People Foundation, Budapest, Hungary Rohan Patil  Bioprocess Development, Sanofi, Framingham, MA, USA Frobert Paul  Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Cancer Institute, Lyon, France Mario Pelle-Ceravolo  University of Padua, Italian Association of Aesthetic Plastic Surgeons, Rome, Italy Mauricio Pérez  Total Definer Research Group, Bogota, Colombia Dallas, TX, USA Paul M. Phillips  El Paso Cosmetic Surgery, El Paso, TX, USA Mônica Sarto Piccolo  Department of Plastic Surgery, Pronto Socorro para Queimaduras, Goiânia, Goiás, Brazil Nelson Sarto Piccolo  Department of Plastic Surgery, Pronto Socorro para Queimaduras, Goiânia, Goiás, Brazil Gentile  Pietro Plastic and Reconstructive Surgery, University of “Tor Vergata”, Rome, Italy

liv

Sergey A. Plaksin  Perm State Medical University, Perm, Russian Federation Petr  Polák Department of Plastic Surgery, Hospital České Budějovice, České Budějovice, Czech Republic Igor Popov  Municipal Clinical Hospital No. 2, Chelyabinsk, Russia Mikhail  Y.  Presnyakov National Research Center “Kurchatov Institute”, Moscow, Russian Federation Lee L. Q. Pu  Division of Plastic Surgery, University of California at Davis, Sacramento, CA, USA Andrey A. Pulin  National Medical Surgical Center named after N.I. Pirogov, Moscow, Russia Pirogov National Medical and Surgical Center, Moscow, Russia Lisa Ramaut  Plastic Surgery Department, Brussels University Hospital— Vrije Universiteit Brussel (VUB), Brussels, Belgium Vincent Riccelli  Vanderbilt University Medical School, Nashville, TN, USA Ricardo Luis Rodriguez  Cosmeticsurg.net, Baltimore, MD, USA Joseph Peter Rubin  Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Erind Ruka  Department of Plastic Surgery, Italian Academy Wound Care (IAWC)—University of Asti, Asti, Italy Department of Plastic Surgery, Mauriziano Hospital of Turin, Turin, Italy Thomas Ryll  VP Technical Operations, ImmunoGen, Inc., Waltham, MA, USA Marzia  Salgarello Department of Plastic Surgery, Policlinic Hospital Agostino Gemelli, Catholic University of Sacred Heart, Rome, Italy Dipartimento Scienze Salute della Donna, del Bambino e di Sanità Pubblica, UOC Chirurgia Plastica, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy Ara  A.  Salibian Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA Elias T. Sawaya  Institut Aquitain de la main, Pessac, France Carlotta Scarpa  Institute of Plastic and Reconstructive Surgery, University of Padua, Padua, Italy Kai-Uwe Schlaudraff  Concept-Clinic, Geneva, Switzerland Jakob  Schnegg Oslo Plastic Surgery Clinic (Oslo Plastikkirurgi Clinic), Oslo, Norway Anna  B.  Semenova Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine, Chelyabinsk, Russia Rana Shalhoub  Bitar Cosmetic Surgery Institute, Fairfax, VA, USA

Contributors

Contributors

lv

Hristo Shipkov  Department of Plastic and Reconstructive Surgery, CroixRousse Hospital, Lyon, France Nicolay  B.  Shismentsev Purulent Surgery Department, Chelyabinsk Railway Clinical Hospital, Chelyabinsk, Russia Mounia  SidAhmed-Mezi Department of Maxillofacial and Plastic & Reconstructive Surgery, Henri Mondor Hospital, Créteil, France Eva Siolo  Aesthetic Wellness Practice, Sandton, Johannesburg, South Africa Ivan  Aleksandrovich  Smyshlyaev Central Clinical Hospital of the Presidential Administration, Moscow, Russia Benjamin Sommier  Institut Aquitain de la main, Pessac, France Michail  Sorotos  Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, PhD School of Translational Medicine of Development and Active Ageing, University of Salerno, Salerno, Italy Sadri O. Sozer  El Paso Cosmetic Surgery, El Paso, TX, USA Nebojša Srdanović  Private Practice, Belgrade, Serbia Douglas S. Steinbrech  Gotham Plastic Surgery, New York, NY, USA Hansjorg Wyss Department of Plastic Surgery, NYU School of Medicine, New York, NY, USA Aris  Sterodimas Department of Plastic and Reconstructive Surgery, Metropolitan General Hospital, Athens, Greece Hieronymus P. Stevens  Velthuis Kliniek, Rotterdam, the Netherlands Filip B. J. L. Stillaert  Department of Plastic and Reconstructive Surgery, University Hospital Ghent, Ghent, Belgium Flavio  Mateo  Sturla Burns Unit, Department Plastic and Reconstructive Surgery, Burns Hospital, Sanatorio Güemes, Ciudad Autónoma de Buenos Aires, Argentina Kasey  Kisu  Sung  Cosmetic Fat Surgeon, Lilac BLC Clinic, Seoul, South Korea William Blake Swicord  UAB School of Medicine, Birmingham, AL, USA Jørn  Bo  Thomsen Department of Plastic Surgery, Odense University Hospital, Odense, Denmark K. Tunc Tiryaki  Cadogan Clinic, Istanbul, Turkey Lena Torske  Oslo Plastikkirurgi Clinic, Oslo, Norway Bryant A. Toth  Craniofacial Program, UCSF Benioff Children’s Hospital, Oakland, CA, USA Lina  Triana Department of Plastic Surgery, Clinica Corpus y Rostrum, Cali, Colombia

lvi

Zhanna  I.  Triushkova Coloproctology Department, City Hospital #8, Chelyabinsk, Russia Angelo Trivisonno  Clinica Assunzione di Maria Santissima, Rome, Italy Bjørn J. Tvedt  Akademikliniken Oslo, Oslo, Norway Klaus Ueberreiter  Park-Klinik Birkenwerder, Plastic Surgery, Birkenwerder, Germany Roberto  Valeriani  Specializing in Plastic Surgery, Università Sapienza  – Asl Roma 1, Rome, Italy Valerio Cervelli  Plastic and Reconstructive Surgery, Department of Surgical Sciences, University of Rome “Tor Vergata”, Rome, Italy Berend van der Lei  Department of Plastic Surgery, University of Groningen and University Medical Center of Groningen, Groningen, the Netherlands Bergman Clinics, Heerenveen, the Netherlands Joris  A.  van Dongen Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, the Netherlands Department of Plastic Surgery, University of Groningen and University Medical Center of Groningen, Groningen, the Netherlands Tamás  Varga South Pest Central Hospital —National Institute for Hematology and Infectious Diseases, Department of Plastic Surgery, Budapest, Hungary Mauro Vasella  Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland Igor  S.  Vasilyev Department of Plastic Surgery and Cosmetology, South Ural State Medical University, Chelyabinsk, Russia Sergey  A.  Vasilyev Plastic Surgery and Cosmetology, South Ural State Medical University, Chelyabinsk, Russia Viacheslav S. Vasilyev  Plastic Surgery and Cosmetology, South Ural State Medical University, Chelyabinsk, Russia Yuri S. Vasilyev  Plastic Surgery and Cosmetology, South Ural State Medical University, Chelyabinsk, Russia Richard  Vaucher  Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Lyon, France Andrey  V.  Vazhenin  Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine, Chelyabinsk, Russia Valeriano Vinci  Plastic Surgery Post-Graduate School, University of Milan, Milan, Italy Giuseppe Visconti  Dipartimento Scienze Salute della Donna, del Bambino e di Sanità Pubblica, UOC Chirurgia Plastica, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy

Contributors

Contributors

lvii

Jason Walther  Bioprocess Development, Sanofi, Framingham, MA, USA Julian  S.  Winocour Department of Plastic and Reconstructive Surgery, Vanderbilt University Medical Center, Nashville, TN, USA Laura Wulff  Cirumed Clinic, Marbella, Spain Viken Vahan Yerganyan  Institut Aquitain de la Main, Pessac, France Fabiana  Zanata Plastic Surgery Division, Universidade Federal de Sao Paulo UNIFESP, Sao Paulo, Brazil Michele L. Zocchi  Institute of Plastic and Reconstructive Surgery, University of Padua, Padua, Italy C.S.M. Institute for Regenerative Surgery, Turin, Italy Tissue Engineering and Biomedical Materials Department, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam Lucas Sebastian Zurlo  Burns Unit, Department Plastic and Reconstructive Surgery, Burns Hospital, Sanatorio Güemes, Ciudad Autónoma de Buenos Aires, Argentina

Part I Introductory Part

1

The Era of Regenerative Surgery Ryan S. Burke and Foad Nahai

Key Messages • Adipose Derived Stem Cells (ADSCs) are a subtype of mesenchymal stem cells that retain the ability to differentiate into fat, bone, and cartilage but effects of growth factors may stimulate all cellular subtypes. • Autologous Fat Grafting (AFG) is not synonymous with Adipose Derived Stem Cell therapy, while AFG is largely utilized for contour irregularities, ADSCs are utilized to stimulate growth or regeneration of surrounding tissues. • ADSCs can be applied for growth stimulation across multiple cell types, with early studies showing their ability to influence growth unrestricted to cells of mesenchymal origin. • As we move into the era of regenerative surgery, ADSCs are just a single stem cell subtype currently being evaluated to assist in tissue growth and regeneration. Further research will continue to advance the field of knowledge and utilization of this cell population.

R. S. Burke (*) Plastic and Reconstructive Surgery, Emory University, Atlanta, GA, USA F. Nahai Plastic Surgery, Emory University, Atlanta, GA, USA

1.1

Introduction

Regenerative surgery is the science of replacing, engineering, or regenerating human cells/tissues/ organs to restore or establish normal form and function. It is often referred synonymously as the utilization of adipose derived stem cells for grafting to improve volume enhancement and or replacement as well as the possibility of tissue regeneration. This in itself is the only one aspect of regenerative medicine and surgery, which can also be extrapolated to any tissue of the body, including nerve regeneration through the application of autologous transfers as well as nerve conduits or allografts, skin via decellularized matrices, tissue expansion, and bone via allotransplants. Advances in both technology and technique have allowed not just the transfer of tissue, but the creation of new tissue which has seeded an entire new focus of research and advancement. Since the mid-1990s, autologous fat grafting has continued to rapidly expand in diversity of application to spawn an entire new focus of regenerative medicine. Not since the advent of microsurgical techniques and adaptation of muscle flaps have a concept been as influential across the broad spectrum of plastic and reconstructive surgery. Autologous fat grafting has not only found applications in all aspects of plastic surgery (craniofacial, extremity, wound management, breast, and cosmetic) but has spanned

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_1

3

R. S. Burke and F. Nahai

4

multiple surgical and medical subspecialties with its broad applications to other cell lines such as nerve, muscle, and bone. While initially used for volumization, fat grafting has been shown to promote local cell growth, broadening its applications to all tissues of the body, and thus captivating multiple medical and surgical specialties in attempt to find more efficient solutions to problems and obeying the time old mantra of “Replacing like with like.”

1.2

The History of Fat Grafting

Although we have entered an era where fat grafting is common in many aesthetic and reconstructive procedures for some degree of volumization, it is not a new concept. Fat grafting can be traced back to its first known utilization by the German Plastic Surgeon, Gustav Neuber in 1893 [1]. He transferred fat from the arm to the orbital region to correct several depressed scars. At this time he noted that graft volume appeared to be the limiting factor, stating only small grafts were viable when transferred. In the Early 1900s a German Surgeon Eugene Hollander was the first to introduce the concept of fat injections for soft tissue defects. He noted there was a high resorption rate during simple fat transfer, and to remedy the problem he mixed the patient’s fat with a more solid fat of a ram. He subsequently heated the solution to a liquid and reinjected with a syringe resulting in a satisfactory correction of a defect. This technique was published in 1912, but pictorial results date back to 1901 [2]. Concurrently, in 1910, a German Maxillofacial surgeon Erich Lexer was utilizing fat to correct lipoatrophy of the face for aesthetic purposes to correct rhytides and hollowness of the periorbita [3]. In 1919, Brunning was the first to introduce syringes for the harvesting of fat, eliminating donor site incisions from direct harvest [4]. In 1926, a United States cosmetic surgeon Charles C. Miller began transferring fat for correction of contour irregularities and wrinkles, as was done in Germany, but while short term results were satisfactory, there was a significant amount of resorption lead-

ing to suboptimal long term results. He attempted to standardize a method of blunt cannulas for fat placement [5]. Like many devices/methods in plastic surgery the idea was largely abandoned until improved methods of fat harvest, such as liposuction and standardization of technique were developed. The modern era of fat grafting began in 1975 when the advent of liposuction, blunt cannulas for the harvest of adipose tissue. Arpad and Giorgio Fischer were the first to describe this method, but without an anesthetic it was poorly tolerated by patients. In 1977 Fournier and Ilyouz introduced modern liposuction with blunt cannulas. Argentinean Abel Charjchir emphasized a stepwise process in an attempt to decrease resorption of implanted fat. This concept centered around cautious manipulation of the adipocyte to ensure survival, rinsing the lipoaspirate in saline to remove unwanted debris, and reinjection into a well-vascularized donor site. This was further built on by Sydney Coleman, in the 1990s by further isolating adipocytes with centrifuge (3000 rmp) and emphasizing that technique in fat placement would further optimize adipocyte survival with small aliquots in narrow tunnels which he termed “Lipostructure.” Early fat grafting was predominantly utilized for contour deformities including Rhomberg disease, post-burn scars, and hemifacial microsomia. Coleman’s contributions were significant and credit is due to him for single handedly re-introducing fat grafting and researching the science behind it. Many today, deservedly, consider him the father of modern day fat grafting [6–8]. The history of fat grafting has not always been a positive one. Early adaptors of this technique, as innovators often are, were criticized. Theoretical risks marred early fat grafting due to its potential side effects of fat necrosis and oil cysts. These calcifications were initially thought to potentially obscure the early detection of breast cancers, leading to the American Society of Plastic Surgeons to denounce its utilization in 1987. Since that time, multiple institutions/surgeons have proven safe early detection of breast cancer in patients with autologous fat grafting.

1  The Era of Regenerative Surgery

1.3

 asic Science of Adipose B Derived Stem Cells

In the early 2000s Bill Futrell and a team of surgeons/researchers from Pittsburgh discovered that adipose tissue is the largest source of adipose derived stem cells, which is at the heart of our current understanding of fat grafting and its regenerative powers [9]. This solidified that fat is not just made of adult adipocytes but also a source of mesenchymal stem cells. The concept of fat regeneration rests on the current theory of Adipose Derived Stem Cells or ADSC’s. Stem cells are capable of self-renewal while also possessing multilineage differentiation potential. With each differentiation, the cell becomes more restricted in its differentiation potential. Fetal stem cells are termed pluripotent stem cells as they have the ability to differentiate into all three germ layers, once differentiated beyond this point, termed multipotent, adult stem cells are largely limited to one of the three germ layers. Additionally, these stem cells retain their property to self-renew, but unlike pluripotent cells, they have a limited life span. Mesenchymal stem cells are of mesoderm origin and have the ability to differentiate into cartilage, bone, and fat. Further differentiation of a mesenchymal stem cell results in a pre-adipocyte later termed an adipose derived stem cell. As its name suggests, these are differentiated mesenchymal stem cells that are precursors for adult stem cells and reside within the adipose tissue, distinct from those derived from bone marrow as they express different surface molecules. ADSCs are capable of self-renewal although with a defined life span also have the ability to differentiate into an adult adipocyte. Adult adipocytes function as a lipid synthesizing and storage cell while also marking the end of the differentiation cycle. Further research has revealed that although ADSCs are largely considered synonymously with pre-­ adipocytes, they still possess the ability to differentiate into different cell subpopulations of mesenchymal origin and even endodermal and ectodermal with appropriate external molecular stimulation further suggesting that this is not a simple linear relationship [10, 11].

5

Isolation of ADSCs has been well described by Gamble et al. through the careful temperature control and enzymatic degradation of the surrounding stroma with a high yield of ADSC in what is termed the stromal vascular fraction (SVF). ADSC can be further extracted from the SVF with various adhesion cell techniques that are beyond the scope of this chapter. The process is time intensive and thus not suitable in an operating room setting. Many proprietary systems are currently available that attempt to offer a streamlined isolation to ADSCs, but their efficacy beyond standard liposuction techniques is still being elucidated. Once isolated ADSCs appear to have both angiogenic and soft tissue modeling properties via local signal molecules such as chemokines, cytokines, and growth factors. It is this ability of ADSCs that allow them to accomplish more than simple increased volume after injection, they stimulate local growth of surrounding and implanted cells while also promoting an angiogenic environment better suited for further grafting if needed.

1.4

Volume Enhancement

Applications of both adult adipocytes and ADSC in volume enhancement have long been an enticing option given its ability to provide a natural appearance while also avoiding prosthetic implants. Adult adipocytes are frequently injected to provide volume in the face, hand, and breast in aesthetic surgery to restore youthful appearance, or camouflage rippling of breast implants. Unfortunately, previously stated, resorption, fat necrosis, oil cysts, and occasionally pain have often been limitations which have largely been overcome with proper techniques as advocated by Coleman. Meticulous placement of fat in small aliquots provides a more permanent solution compared to hyaluronic acid fillers for lip augmentation, malar fat pad projection, and dorsal hand contour. Additionally, volume replacement can be used to ameliorate pathologic processes such as hemifacial microsomia, Parry Romberg disease, and secondary temporal wast-

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ing. Although under recent scrutiny for safety efficacy, larger volume fat grafting has been utilized to improve contour of the buttock and avoidance of prosthetic devices. In the same right large volume fat grafting has been used for breast augmentation, termed liposculpting. Fat grafting has long been part of both breast augmentation and reconstruction. For breast augmentation, larger volume fat grafting has been used in an attempt to create a more natural appearing and feeling breast while avoiding breast implants that can lead to complications such as capsular contracture and in rare instances BIA-ALCL ­ [12]. Drawbacks are well described with long term data lacking. Large volume fat transfer which would be required to offer significant volume as would be provided by a breast implant often leads to variable levels of graft failure. This leads to fat necrosis manifesting as lumpiness, pain, tenderness, erythema, and contour irregularities. Various devices have recently been introduced to assist with improving the recipient site, largely by enlarging proposed tunnel to create space and ultimately improve graft vascularity, but long term data is lacking and graft reabsorption continues to be an issue [13]. In breast reconstruction, autologous fat grafting is often utilized to mask rippling, or smooth and augment the contour of the superior pole. With increasing placement of breast implants in the pre-pectoral plane for immediate reconstruction, autologous fat has been as an adjunct to improve results. The major concern with ADSCs and AFG in the breast following cancer treatment is that of tumor recurrence. ADSCs are recognized to produce various growth factors which promote neoangiogenesis, cell proliferation, migration, and renewal that in theory could be tumorigenic. Although isolated adhesion molecules and chemokines associated with ADSC have been linked to tumorigenesis it is unproven if a transplanted ADSC is tumorigenic. Contrarily Wakako et  al. demonstrated that ADSCs when directly placed into contact of tumor cells in a murine model did not support tumor growth, in fact there was evidence of tumor suppression [14].

1.5

Skin Rejuvenation

Injection of ADSC allows for increased collagen synthesis and angiogenesis while also decreasing melanogenesis and oxidative stress. Adipose derived stem cells accomplish this by the release of local agents such as vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor beta (TGF-B). These local agents signal local cells, such as fibroblasts, to increase production of collagen while also preventing apoptosis. VEGF allows for local stimulation of blood vessel growth inducing localized angiogenesis. While fat grafting has often been applied to improve volume, ADSCs can improve overall skin quality. This is often completed in the form of nano-fat grafting which differs from standard Coleman processing of the lipoaspirate. The lipoaspirate is transferred between two lure lock syringes to improve fluidity of the aspirate. The filtrate is then passed through a nylon cloth which leads to removal/lysis of adult adipocytes while maintaining ADSCs and SVFs. The result is an effluent that can be placed just beneath the skin in the subdermal plane which is rich in both ADSCs and growth factors. This can be used to improve appearance of fine rhytides, sun damaged skin, scars, or dark lower eyelids [15].

1.6

Wound Healing

Much in the same way adipose derived stem cells are applied for skin rejuvenation, the same principles can be applied to promote wound healing. Paracrine effects of ADSCs are angiogenic, anti-­ apoptotic particularly of pro-inflammatory cells, and promote collagen synthesis to assist with expedited wound healing. Additionally, they have been shown to influence keratinocyte in a similar manner resulting in increased proliferation and migration resulting in a thickened epidermis as well as lateral expansion. These properties have led to expanded research on utilization of ADSCs

1  The Era of Regenerative Surgery

in wound healing matrices in an attempt to promote wound closure, particularly those of diabetic foot ulcers [11].

1.7

Alopecia

Although in its early stages of clinical application, recent studies have shown promise with improvement of alopecia after injection of ADSCs into the scalp. A study of 27 patients by Shin et al. with mild alopecia showed improvement in both hair density and thickness of hair shafts 12  weeks after injection. Furthermore a study by Anderi et al. analyzed 20 patients treated with ADSCs SVF and were found to have increased hair growth, diameter and decreased hair removed with a pull test. The proposed mechanism is likely through paracrine recruitment of dormant hair follicles while also upregulating active hair follicles. Given the relatively large amount of available ADSCs this would provide an attractive alternative to grafting, which is labor intensive and limited by donor site availability [16].

1.8

Radiodermatitis

Radiodermatitis is a result of healthy soft tissue damage as a bystander in treatment of malignancy with radiation. Given that skin has a high proliferative nature and its superficial location it is often subject to significant damage. Radiodermatitis is often described in terms of acute or chronic. Acute being soon after treatment, and results in discoloration and sometimes desquamation or ulceration. The chronic phase is marked by fibrosis, scarring, and retraction which can often lead to restricted movement typically 4–12 months after radiation treatment. Although other treatment modalities have been attempted, such as topical steroids, moisturizers, antioxidants, massage and physical therapy with varying levels of improvement. Recently autologous fat grafting has been utilized in an attempt to reverse radiation induced fibrosis. In 2007 a study com-

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pleted by Rigotti et al. demonstrated 20 patients treated with autologous fat grafting to affected areas had symptomatic relief as well as visual improvement of the affected skin. Additionally microscopic analysis of treated areas demonstrated improved vascularity as well as decreased fibrosis. It is theorized that ADSCs release certain growth factors to improve vascularity and decrease cell apoptosis. Additionally ADSCs may directly differentiate into endothelium to help with angiogenesis. Unfortunately there are some drawbacks of autologous fat grafting to radiation induced injury. This recipient tissue is often poorly vascularized and thus is not an ideal environment for cell grafting. This leads to higher rate of graft failure and reabsorption and ultimately will require multiple sessions to adequately treat [17].

1.9

Arthritis

Recent studies have begun to evaluate autologous fat grafting’s efficacy for treating arthritis, particularly of the hand first carpometacarpal joint. As the joint space is relatively avascular, theories proposed largely focus on the fat itself providing a cushion when it undergoes cell death and subsequent fibrosis. Other theories include proposed mechanism of ADSC differentiation into cartilage for joint regeneration or antiinflammatory properties of ADSCs resulting in symptomatic relief. A study of 99 patients completed by Haas et al. showed 61% of patients had major improvement of pain scores at 6  months compared to 27% that felt no difference. Koh et  al. examined ADSC injection to the knee in joints affected by OA in 18 patients resulted in decreased pain and increased ROM.  Of more interest treated patient pain scores appeared to improve with time and cartilage defects appeared to improve suggesting more than just a cushioning affect. Further investigation into MSC differentiation into cartilage for joint remodeling is currently under way, but clinical symptomatic improvement appears to have been achieved without significant morbidity [18].

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1.10 Dupuytren’s Disease Dupuytren’s disease is a fibroproliferative disorder that causes a progression of palmar nodules that may eventually organize into fibrous cords that limit flexion of the affected digit. Treatment alogarithms range from simple collagenase injections or needle aponeurotomies to invasive fasciectomies to restore function of the affect digit. Given the ability of adipose derived stem cells to promote neoangiogenesis and effectively regulate inflammation of their surrounding environment, interest has been garnered in their application to fibrotic disease states such as Dupuytren’s disease. The underlying cell population responsible for flexion contraction of Dupuytren’s disease are myofibroblasts. Stimulated myofibroblasts synthesize collagen and involved extracellular matrix while also causing localized contraction, identical to their function in wound healing. In a study completed by Verhoekx et al., myofibroblasts were cultured with harvested adipose derived stem cells. When myofibroblasts were subsequently evaluated they were found to contain less expression of alpha-­ smooth muscle actin (responsible protein for cell contraction), while also decreasing their proliferation. Application of adipose derived stem cells in conjunction with needle aponeurotomy may release the pathologic contracture while also preventing recurrence [19].

1.11 B  one, Cartilage, and Nerve Regeneration As previously mentioned, ADSCs are or mesenchymal origin and possess the ability to differentiate into cells or mesenchymal origin such as bone, cartilage, and fat. Additionally, growth factors secreted by ADSCs can affect other cell populations not from mesenchymal origin. Examples of such are seen in recent studies that have shown impregnating osteoconductive scaffolding such as allograft with ADSCs promoting bone healing. ADSCs can also be utilized to differentiate into chondrocytes as shown in murine model by [20]. Creation of functional adult car-

tilage could be applied to ear reconstruction, joint resurfacing, and cartilage grafting for nasal reconstruction. Lastly, ADSCs have had promising results in assistance with nerve regeneration. ADSCs [21] have been impregnated within nerve conduits that have shown improved results. If nerve conduits can be utilized to bridge greater nerve gaps, donor sites may be spared. Further research will be required, as well as clinical applications investigation.

1.12 Conclusion Adipose derived stem cells research has ushered in a new era of regenerative medicine. Given their relatively abundant and ease of harvest compared to bone marrow, they offer an expansive source of autologous tissue. Although there have been various methods of collection and processing, applications of adipose derived stem cells seem to be rising rapidly. Further research will be required to determine.

References 1. Neuber GA. Fettransplantation. Chir Kongr Verhandl Deutsche Gesellschaft für Chir. 1893. p. 22. 2. Hollander E, Veriag von Velt JM.  Cosmetic surgery. In: Josheph M, editor. Handbuch der Kosmetik. Germany: Leipzig, Veit & Co.; 1912. p. 690–1. 3. Lexer E.  Freie fett transplantation. Dtsch Med Wochenschr. 1910;36:640. 4. Brunning P. Contribution à l’étude des greffes adipeuses. Bull Mem Acad R Med Belg. 1919. 5. Miller C. Cannula implants and review of implantation techniques in esthetic surgery. Am J Opthalmol. 1926;9(11):855. 6. Coleman SR.  Long-term survival of fat transplant: controlled demonstrations. Aesthet Plast Surg. 1995;19:421–5. 7. Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997;24:347–67. 8. Mazzola R. The fascinating history of fat grafting. J Craniofac Surg. 2013;24(4):1069–71. 9. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-­ based therapies. Tissue Eng. 2001;7:211–28. 10. De Ugarte DA, Alfonso Z, Zuk PA, et al. Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunol Lett. 2003;89(2–3):267–70.

1  The Era of Regenerative Surgery 11. Glass GE, Ferretti P.  Adipose-derived stem cells in aesthetic surgery. Aesthet Surg J. 2019;39(4):423–38. 12. de Boer M, van Leeuwen FE, Hauptmann M, et  al. Breast implants and the risk of anaplastic large-cell lymphoma in the breast. JAMA Oncol. 2018;4(3):335–41. 13. Tonnard P. Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013;132:1017–26. 14. Wakako T.  An animal model of local breast cancer recurrence in the setting of autologous fat grafting for breast reconstruction. Stem Cells Transl Med. 2018;7(1):125–1324. 15. Park BS, Jang KA, Sung JH, et  al. Adipose derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatol Surg. ­ 2008;34(10):1323–6. 16. Shin H, Ryu HH, Kwon O, Park BS, Jo SJ. Clinical use of conditioned media of adipose tissue-derived

9 stem cells in female pattern hair loss: a retrospective case series study. Int J Dermatol. 2015;54(6):730–5. 17. Borrelli MR. Radiation-induced skin fibrosis: pathogenesis, current treatment options, and emerging therapeutics. Ann Plast Surg. 2019;83(1):S59–64. 18. Haas E.  One-year outcomes of intraarticular fat transplantation for thumb carpometacarpal osteoarthritis. Plastic and Reconstructive Surgery. 2020;145(1):151–159. 19. Verhoekx J.  Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren’s disease. Plast Reconstr Surg J. 2013;132(5):1139–48. 20. Erickson GR.  Chondrogenic potential of adipose tissue-derived stromal cells in  vitro and in  vivo. Biochem Biophys Res Commun. 2002;290(2):763–9. 21. Sowa Y. Adipose-derived stem cells promote peripheral nerve regeneration in  vivo without differentiation into Schwann-like lineage. Plast Reconstr Surg. 2016;137(2):318e–30e.

2

Evolving of Concepts in Fat Grafting and Regenerative Surgery Riccardo F. Mazzola

Key Messages • The first report of fat grafting in plastic surgery literature was published in 1893 by Gustav Neuber (1850–1932). • In 1910, the German surgeon Eugene Holländer (1867–1932), instead of transplanting fat parcels en bloc, proposed an innovative procedure, that is injecting fat to the face, for correcting facial atrophy and to the breast, for improving postmastectomy sequelae. • Erich Lexer (1867–1937), a German orthopedist, extensively used fat grafting in numerous clinical situations. His results were published in a two volume tract Die freie Transplantationen (Free Transplantations), issued in 1919. • Treatment of the facially disfigured soldiers from World War I with fat grafting was pioneered by the French surgeon Hippolyte Morestin (1869–1919) and by the British Otolaryngologist Harold D.  Gillies (1882– 1960) in 1915 and 1920, respectively. • Johannes Ertl (1880–1951) first introduced the concept of regenerative surgery in his book Regeneration and its application in Surgery, published in 1939. For him, regeneration means restoration of function and the regenR. F. Mazzola (*) Plastic Surgery, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda, Policlinic Hospital, Milan, Italy e-mail: [email protected]

•

• •

•

erative potential applies to the following tissues: periosteum, dura, mucosa, and fat. In the 1980s, Yves-Gerard Illouz had the idea of reshaping the silhouette of Parisian ladies by means of the aspiration’s technique. Liposuction became one of the most popular aesthetic procedures. In the 1990s, Sydney Coleman systematized the details of fat injection procedure. Zuk PA et al. in 2001 demonstrated that adipose tissue is the greatest source of adipose-­ derived stem cells (ADSCs), capable of differentiating into other types of tissues. In 2009, after more than 20 years of endless discussions, the ASPS approved fat grafting to the breast, suspending the existing moratorium. Since then, fat injection to the breast for augmentation, reconstruction, or reshaping is a worldwide accepted procedure.

2.1

Introduction

The first report on fat grafting in the medical literature is usually attributed to the German surgeon Gustav Neuber (1850–1932), who, in 1893, harvested some parcels of adipose tissue from the arm and transferred them to the orbital region to correct sunken, adherent scars sequelae from osteomyelitis [1]. Two years later, another German, Vincenz Czerny (1842–1916), removed a lipoma from the buttocks of a patient

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_2

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and transplanted it to her left breast to correct a deformity resulted from the excision of a fibrocystic mastitis [1]. Since then fat grafting was extensively used in clinical practice for different applications. Reconstructive surgeons of the period empirically noted that fat had amazing healing properties and regenerative potential. This is the reason why fat was placed into open wounds en bloc or in parcels not only to improve the scar’s sequelae, but also to facilitate wound healing.

2.2

 he Experience of World T War 1

2.2.1 Fat Transplantation in the Facially Disfigured Soldiers from World War 1 (WW1) One of the most challenging applications of the newly developed fat grafting technique was the treatment of the facially disfigured soldiers from WW1. Hippolyte Morestin (1869–1919), surgeon in chief at Val-de-Grace Military Hospital in Paris (Fig. 2.1) greatly favored fat grafting as an adjuvant procedure for the management of disfiguring facial wounds. His technique was as follows [2]. Accurate hemostasis of the empty space to be filled in by fat, en bloc harvesting of the adipose tissue from the buttocks, its transplantation into the prepared cavity, until it appeared completely or almost completely depleted. Morestin believed that the adipose graft, could survive, although with great difficulty, partly replaced by connective tissue. “Adipose tissue—he affirmed—is an excellent way to fill in either dead spaces or bony cavities, and to improve soft tissues contour depressions.” “We have to keep in mind—he used to say—that the main indication for fat transplantation is a cosmetic improvement.” Harold D.  Gillies (1882–1960). Hippolyte Morestin greatly influenced the British-New Zealand Otolaryngologist Harold D.  Gillies, who visited him in 1915, when Gillies was based

Fig. 2.1  Hippolyte Morestin (1869–1919). Courtesy of the Fondazione G. Sanvenero Rosselli, Milan

at the British General Hospital of Rouen on behalf of the Red Cross. In 1917, upon his return home, Gillies created a unit for management of face and jaw injuries for British and Allied wounded in WW1 at Queen’s Hospital in Sidcup, which soon became the reference center in Europe. He developed several new reconstructive procedures and largely used fat transplantation. “Fat graft owing to fat necrosis,—he wrote—often undergoes a partial absorption, which is carried to greater lengths if the products of this disintegration become infected; but even in this latter unfortunate event not all the fat comes away and eventually there is left sufficient substance to aid very materially in any future work on the part.” For Gillies, the main indications of fat grafting were cheek with large depressed scars, zygoma and forehead. In a young officer, who received a gunshot wound on the left cheek, he employed the technique of fat

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery

flaps rolled in towards the depression. The skin was drawn over the fatty prominence and accurately sutured. The final result was very pleasing considering the dramatic initial open wound (Fig.  2.2a–c). His vast experience was summarized in his book, “Plastic Surgery of the Face,” issued in 1920 [3] (Fig. 2.3). Erich Lexer (1867–1937) (Fig. 2.4) was a talented orthopedist and skillful maxillofacial surgeon, head of the Surgical Clinic in Freiburg (Germany). He advocated the use of autologous fat grafting to correct depressed scars of the forehead and face, breast’s asymmetries, orbital cavity for anophthalmia, micrognathia, sequela of temporomandibular ankylosis, contour deformity in hemifacial macrosomia, finger contractures for Dupuytren’s disease. In a facially disfigured soldier from WW1 with an anophthalmic orbital cavity, he used fat in combination with local flaps and cartilage graft to create a socket, so as to accommodate a prosthesis, achieving an amazing result (Fig. 2.5a, b). In his two volume treatise Die freien Transplantationen (Free Transplantations) (Fig. 2.6) published in 1919 [4], he devoted more than 300 pages to fat grafting, of which he was a strong supporter, describing in detail the harvesting technique of fat from the lateral thigh and its application in a wide variety of clinical cases. On the contrary to Morestin and Gillies, who considered fat grafting a typical aesthetic procedure, Lexer recognized the regenerative potential of the transplanted fat. His theories were confirmed by the experimental works of his co-­ worker Eduard Rehn (1880–1972) [5] who demonstrated that fat, transplanted in the new hosting site, receives enough vascularization from the surrounding tissues, and this allows its survival. In a 5  months period fat regenerates, forming a structure very similar to the original one. Gustavo Sanvenero Rosselli (1897–1974) Gustavo Sanvenero Rosselli (Fig. 2.7) was trained in France at the International Otorinolaringological and Facio-Maxillary Clinic in Paris, having Fernand Lemaître (France) and Eastman Sheehan (USA) as Course Directors. In 1928, upon his

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return to Italy, he established himself in Milan and was appointed head of the Padiglione Mutilati del Viso (Pavilion for Facial Cripples) one of the leading Centers in Italy for postwar facial reconstruction. He treated numerous casualties from WW1 using flaps and fat grafting with amazing outcomes (Fig. 2.8a, b). Sanvenero Rosselli is rightly considered the founder of Plastic Surgery in Italy. Johannes von Ertl and the Regenerative surgery concept  Johannes Ertl (1880–1951) began work at the Reserve Hospital n. 6, one of the leading centers for the treatment of war facial injuries, located in Budapest, Hungary. He was then appointed surgeon-in-chief, and took care of the immediate repair of the wounds and of the step by step reconstructive procedures with many revolutionary operations. His vast experience was summarized in a book issued in 1918, Die Chirurgie der Gesichts- und Kieferdefekte (Surgery of the defects of the Face and Jaw) [6], where the dramatic cases of facial injuries were shown and their surgical management scholarly discussed. But J.  Ertl deserves recognition for having introduced the concept of regenerative surgery more than 80 years ago. The basic principles of biological regenerative surgery were published in a book issued in 1939, Regeneration, ihre Anwendung in der Chirurgie (Regeneration and its Application in Surgery) [7] (Fig. 2.9). Many of his contemporaries did not understand his innovative ideas, therefore he was often misinterpreted. According to him, the essence of regeneration in man was restoration of function. Surgeons recognized that human tissues like periosteum, dura, mucosa, epithelium, and fat retain their original regenerative potential. From this comes the Regenerative Surgery concept. Regeneration occurs either by reconstruction or by transplantation of tissues. Fat transplantation was widely used by Ertl for the treatment of WW1 facial injuries. He identified three different clinical situations: (a) the transplanted fat dies and becomes fluid; (b) the transplanted fat partially necrotizes and

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a

b

c

Fig. 2.2 (a–c) Facial open wound (a); use of fat flaps rolled into the wound to facilitate its closure (b); Final result (c) (from: Gillies HD., 1920) [3]

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery

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Fig. 2.3  Gillies’s Book Plastic Surgery of the Face, 1920 [3]

becomes connective tissue; (c) the transplanted fat regenerates forming a tissue very similar to the original structure. He based his theories on Rehn’s experiments [5].

To avoid fat necrosis he noticed that it was essential to transplant minimal amount of tissue. On the contrary, big amount of tissue will inevitably result in death of the graft.

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Adipocytes maintain their regenerative capacity, despite their rupture. They could regain their biological characteristics, so that the transplanted fat could not evolve into scar tissue, after closure of the primary defect. Regrettably, his landmark work in facial reconstruction and in the field of regenerative surgery achieved little recognition and Ertl’s work is rarely mentioned in the medical literature.

2.3

Fig. 2.4 Erich Lexer (1867–1937). Courtesy of the Fondazione G. Sanvenero Rosselli, Milan

a

 ugene Holländer and His E Revolutionary Idea of Fat Injection

Eugene Holländer (1867–1932), a professor of surgery in Berlin, instead of transplanting fat parcels en bloc, proposed the use of a fluid mixture of human and ram fat, injecting it into those areas of the face requiring improvement. He used ram fat because it was considered a harder type of fat by him, less prone to resorption. Here follows the verbatim translation of his procedure [8]:

b

Fig. 2.5 (a, b) Eye socket reconstruction using skin flap, cartilage, and fat graft. Before (a) and after (b) (from: Lexer E., 1919) [4]

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery

Fig. 2.6  Lexer’s Book Die freien Transplantationen (Free Transplantations), 1919 [4]

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Fig. 2.7 Gustavo Sanvenero Rosselli (1897–1974). Courtesy of the Fondazione G. Sanvenero Rosselli, Milan

a

“A method which gives favorable cosmetic results for correcting severe facial atrophy, consists of filling in the canine fossa with fat and also the areas below and above the malar bone, where the most significant signs of atrophy are noticeable (Fig. 2.10). Until now I used sterile human fat as filler. Fat was surgically harvested from healthy patients. It was then injected like saline, but it had the disadvantage of resorbing almost completely. Thus it was necessary to mix it with harder type of fat, and eventually I used a blend of ram and human fat, which at room temperature is creamy, whereas, if heated moderately, becomes fluid. If one adds more ram fat the reaction, which consists of a painful rash for 2–3 days, is more severe under certain circumstances. It is highly important to perform the injection of the mixture at blood temperature, otherwise it becomes painful. These principles apply for managing limited depressions. Also in case of facial atrophy secondary to facial palsy I achieved good cosmetic results. However, should the skin be adherent to the depth of the

b

Fig. 2.8 (a, b) Fat grafting to the face to improve a sequela from WW1 (from: Sanvenero Rosselli G., 1935)

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery

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Fig. 2.9  Ertl’s Book Regeneration, ihre Anwendung in der Chirurgie (Regeneration and its Application in Surgery), 1939 [7]

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a

b

Fig. 2.10  Treatment of facial atrophy by fat injection. (a) Preoperative view of a patient; (b) postoperative view of the same patient after fat injection (from Holländer E., 1912) [8]

a

b

Fig. 2.11  First case reported in the medical literature of fat injection into the breast. (a) Preoperative view of a patient; (b) postoperative view of the same patient after fat injection (from Holländer E., 1912) [8]

depression, as occurs in traumas or bony diseases, one should begin first from the mouth, or from the nose, possibly also from the eyebrow or from the skin of the skull to release the scar between the bone and the skin and then treat the inner layer. Use of liquid fat for cosmetic purposes is preferable to the transplantation of fat parcels (according to Lexer). However, if an invasive operation is already envisaged, like resection of maxillary bone or another aggressive procedure, then the latter option should be chosen with advantage.”

Regarding breast’s deformities, Holländer wrote [8]: “Defects of the breast, as they occur after operations for massive tumor excision, or for total mastectomy, leave the patient in a miserable condition. Czerny successfully transplanted a lipoma to replace the missing breast [1]. Personally, on several occasions, following mastectomy, I tried to solve the problem with fat injection” (Fig. 2.11). Fat injection was seldom reported in the European literature of the period. Despite this,

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery

Fig. 2.12  The syringe used by Charles C.  Miller for injecting fat (from Miller CC., 1926) [9]

Holländer occupies an important place in the history of plastic surgery, because he published the first paper on fat injection into the face and breast. On the other side of the ocean, in 1926, Charles C. Miller (1880–1950) from Chicago, considered a “blatant quack” by some and the “father of modern cosmetic surgery” by others, issued Cannula implants and review of implantation techniques in Esthetic Surgery [9], a textbook in which, besides the use of peculiar subcutaneous filler injections of rubber, celluloid and gutta percha to correct nasolabial folds, crow’s feet, and saddle noses, he reported on injections of fat for the first time in the U.S. literature. He harvested fat from the abdomen, inserted tiny parcels in a powerful screw piston syringe and injected them subcutaneously into the depressed areas requiring correction (Fig. 2.12).

2.4

The Decline of Fat Grafting

Because of the tendency of fatty tissue to resorb, to form cysts and to be almost completely replaced by fibrous tissue, with unpredictable results, in the 1930s fat grafting and fat injection fell from favor especially in the field of facial aesthetics. Over time it became a rather neglected technique.

2.5

 he First Scientific Studies T on Fat Graft Survival

In the 1950s, Lyndon A. Peer (1898–1977) studied the behavior of human fat grafting, the loss in weight and volume of large and small parcels of

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fat, the gross and microscopic appearance of adipose grafts at 1  year after transplantation [10]. He concluded that adipose grafts lose approximately 45% of their weight and volume at 1 year, because adipocytes rupture and die, but the survived cells form the fat graft that remains. Microscopic studies showed that early revascularization was essential for adipocytes to survive, as fat cells do not tolerate ischemia. On the contrary, breakdown of cells might occur and solid, fibrotic oil cysts form in areas that had not been sufficiently revascularized as a result of necrosis. This may explain why fat graft results are so unpredictable.

2.6

 he Advent of Liposuction T and the Resurrection of Fat Injection Technique

In the 1980s, Pierre Fournier [11] and Yves-­ Gerard Illouz [12] both from Paris, independently conceived the idea of reshaping the silhouette of wealthy Parisian ladies by removing deposits of fat from undesired zones of the body, by means of the aspiration’s technique. Fournier used the less traumatic syringe, whereas Illouz employed a suction pump with moderate vacuum. He modified the classical vacuum-­assisted cannula, normally adopted for pregnancy’s interruption, with a similar device, having a blunt, round tip, and lateral holes. A back-and-forth movement was necessary for aspiration. Aware of the great impact of the new procedure, Illouz popularized it through France and introduced it in the USA, where it became the most popular operation. To correct the unpleasant contour irregularities and depressions resulting from an aggressive suctioning, Illouz and Fournier reinjected the lipoaspirate, using a syringe. However, although they claimed to have obtained the solution of the problem, they were fairly disappointed, in noting a complete or almost complete resorption within a short period of time. Resorption rate was Illouz’s main concern. He recommended that although fat re-injection failed to achieve the desired results and was partially successful only, the procedure should be encour-

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aged. He understood the importance of fostering research in this particular field and postulated that to prevent resorption “it will be necessary to prepare the fat by means of more sophisticated laboratory techniques, in order to obtain pure isolated fat cells, ready for graft-culture.” As we shall see, it took several years to systematize fat injection procedure and to reduce the resorption rate.

2.7

The Systematization of the Fat Injection Procedure

Finally, within a few years of attempts, the successful outcome arrived. In 1989, Chajchir and Benzaquen first reported 86% of positive results in all the areas treated with fat injection for cosmetic and reconstructive purposes over a 4-year period [13]. Their recommendations were as follows:

3. Placement: Deposition of minimal amount of adipocytes, using a 20–22 G cannula, in tunnels in a retrograde way, to facilitate the close contact of the grafted material with the surrounding tissues and enhance their vascularization. Structural fat grafting was used for modifying contour deformities as well as to restore fullness, improve postburn scars, correct breast or facial asymmetries. It represented a great achievement in aesthetic and reconstructive surgery for obtaining a volumizing effect, with a minimally invasive procedure.

2.8

 he Adipose Derived Stem T Cells: A Crucial Discovery

At the beginning of the new millennium the Pittsburgh team of plastic surgeons and researchers, coordinated by Bill Futrell, M.D., made a 1. No local anesthesia to avoid modifications in crucial discovery. They demonstrated that adithe anatomic structure of the tissues. pose tissue is the greatest source of adult mesen 2. Delicate manipulation during aspiration and chymal stem cells, the so-called adipose-derived injection to avoid rupture of the adipocytes. stem cells (ADSCs), capable of differentiating 3. No rinsing of the graft in saline. into other types of tissues, such as bone, muscle, 4. Good quality adipose tissue only should be cartilage, nerve, blood vessels [15]. They identiused. fied the stromal vascular fraction (SVF) in the 5. Placement of the injected material under three lipoaspirate, a collection of ADSCs, endothelial different layers: skin, fascia, and muscle. progenitor cells, growth factors, T cells, B cells, mast cells adipose tissue macrophages, with And then came Sydney Coleman! In the repair and regenerative potential. They were 1990s, he systematized the procedure, re-­ obtained from the lipoaspirate, once the fluid and emphasizing the importance of the most atrau- adipose portion has been removed and processed. matic technique for fat harvesting and placement The ability to become other tissues, allowed the to preserve the fragile adipocytes, significantly transplanted fat to produce more capillaries or reducing the resorption rate [14]. He considered blood vessels and to create new blood supply. the following points, the key for a favorable This could explain the role of structural fat graftoutcome: ing in accelerating the healing process and in replacing damaged or missing cells. 1. Harvesting: use of a 18 G blunt cannula, conIn addition to the traditional concept that fat nected to a 10 mL luer-lock syringe, to mini- plays an important role as filler for correcting mize the damage to the adipocytes; body contour, it represents a high energy 2. Processing: centrifugation of the lipoaspirate ­reservoir, for its ability to bind large amount of for 3 min at 3.000 rpm for removing the aque- fluids. Fat has insulating characteristics and ous and oily components, so as to avoid an maintains thermoregulation at the same time, inflammatory response; hence it is typically involved in preserving

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery

homeostasis, but it is also an organ with healing potential in tissue regeneration. When it is transplanted to another part of the body, these healing properties appear more evident. Fat is an ideal material in reconstructive surgery, making difficult wound closure possible, improving the retraction of scars and reducing postmastectomy pain syndrome.

2.9

 at Grafting to the Breast. F A Long-Lasting Controversy

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published in Plastic and Reconstructive Surgery [16]. Here the quotation of some salient points from this paper: “Fat grafting to the breast could potentially interfere with breast cancer detection; however, no evidence was found that strongly suggests this interference…. Radiological studies suggest that imaging technologies (ultrasound, mammography and MRI) can identify the grafted fat tissue, microcalcifications and suspicious lesions; biopsies may be performed, if needed, for additional clarification.” Since then, plastic surgeons worldwide are injecting fat into the breast for augmentation, reconstruction, or reshaping.

Fat injection to the breast was first reported by Holländer in 1912 (Fig.  2.11) [8]. However, it was in the 1980s that surgeons started to inject autologous adipocytes into the breast mainly for 2.10 The Regenerative Medicine cosmetic purposes. In 1987, the ad-Hoc-­ and Surgery Committee on New procedures of the American Society of Plastic Surgeons (ASPS) strongly Rigotti et al. 2007 [17] obtained a complete restiadvised against the use of this procedure for tutio ad  integrum of the irradiated areas in 20 breast augmentation. A position paper was issued patients following injection of fat. Their report “deploring the use of autologous fat injection into demonstrated for the first time in a large series of the breast.” “Much of the injected fat will not sur- clinical cases the therapeutic and regenerative vive and the known physiologic response to effects of the ADSCs for the management of irranecrosis of this tissue is scarring and calcifica- diated tissue, through a process of replacement. tion. As a result, detection of early breast carci- The first International Panel Fat injection, noma through xerography and mammography expanding opportunities organized by the will become difficult and the presence of disease European Association of Plastic Surgeons may go undiscovered.” The ASPS position paper (EURAPS) in 2006 under the Presidency of created a worldwide moratorium on fat injection Riccardo F. Mazzola, confirmed the clinical value to the breast, which was banned, impairing clini- of structural fat grafting and its regenerative cal application of this particular procedure. It potential. From that panel evolved the book Fat took more than 20 years and an endless series of Injection from Filling to Regeneration, edited by discussions at major international meetings to Sydney R.  Coleman and Riccardo F.  Mazzola, convince oncologists, radiologists, and surgeons issued in 2009 [18]. that cancer related calcifications and those benign Numerous ongoing clinical trials in regeneraresulting from fat necrosis considerably differ for tive medicine and surgery using ADRCs and SVF radiological images and for location and cannot are currently progressing all over the world. be mistaken. Finally, to coordinate research, biology, cliniIn 2007, the ASPS was persuaded to establish cal applications of the regenerative potential of a task force to scientifically reevaluate fat grafting the SVF, standardization of the techniques, to the breast. Finally, in 2008 the ASPS, the Plastic safety, and regulation, two scientific Societies Surgery Educational Foundation (PSEF), and the were founded: IFATS (International Federation American Society of Aesthetic Plastic Surgery for Adipose Therapeutics and Science) estab(ASAPS) approved the task force report, which lished in 2002 and ISPRES (International Society led to withdrawal of the moratorium. In 2009, of Plastic and Regenerative Surgery) established results of the task force position statement were in 2011.

R. F. Mazzola

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2.11 Current Procedures and Future Perspectives Advanced researches have demonstrated that the SVF can be isolated mechanically or by enzymatic digestion obtaining several millions of cells, containing between 3 and 5% of stem cells to be utilized in cell-based therapies. At present, one of the disadvantages of using the SVF is the insufficient cell dose, if high amount of cell numbers are needed, resulting in lack of efficacy. In a near future it will be possible to enrich adipose tissue with SVF, improving either the trophism or the angiogenic effect of tissues, and as a consequence the regenerative potential of fat. New methods for processing and placement of the harvested fat have been described, including centrifugation at different force and duration, decantation, and washing. However, with the raising importance attributed to the SVF, it has been demonstrated that adipocytes may be ruptured, without reducing the benefits of fat transfer. It is essential that the SVF is included in the transfer. Recently, in selected cases, injections of emulsified fat or nanofat have been proposed by some surgeons to facilitate adipocytes’ placement [19]. The best method to be used is still one of the most controversial topics in fat grafting. Finally, in addition to the traditional knowledge of the healing properties of fat, Rigotti et al. [20] have shown that fat has an anti-aging capacity. The elastosis present in the facial skin, typical sign of aging, significantly diminished after treating selected areas with fat and multipotent SVF, obtaining a skin rejuvenation effect, smoothing the wrinkles at the same time. Is this a preliminary sign of the mythical Fountain of Youth?

2.12 Conclusions As we have seen in this fat grafting evolution of concepts, plastic surgeons continuously refined their techniques over the years for the improvement of this procedure. Originally fat grafting was used for obtaining a volumizing effect. During WW1, its clinical

application expanded for treating dramatic facial wounds. In the 1980s, the advent of liposuction changed the method of fat transfer in the body. Use of the syringe became the solution of choice. But plastic surgeons had to fight against a severe problem: resorption of the injected lipoaspirate. To contrast it, Chajchir and Benzaquen [13] and Coleman [14] issued technical recommendations for fat harvesting, processing, and placement, obtaining a considerable improvement of the resorption rate. The discovery, made in the 2000s by the researchers of the group of Pittsburgh [15] that adipose tissue is the greatest source of adult mesenchymal stem cells, the so-called adipose-­ derived stem cells (ADSCs), capable of differentiating into other types of tissues, and of the SVF, opened the road to the cell-based therapies. In 2007, Rigotti et al. [17] first demonstrated that the ability to heal difficult wounds was the result of the regenerative potential of the ADSCs included in the fat. It became apparent that fat is an organ with healing potential in tissue regeneration. To conclude, fat grafting revolutionized traditional plastic surgery. The minimally invasive nature of the procedure, the multiple clinical applications, positively changed our cosmetic and reconstructive outcomes.

References 1. Mazzola RF. The evolution of fat grafting: from soft tissue augmentation to regenerative medicine. In: Coleman SR, Mazzola RF, Pu LLQ, editors. Fat injection from filling to regeneration. New York: Thieme; 2018. 2. Morestin H. Quelque cas de greffes graisseuses appliquées à la chirurgie réparatrice. Bull Mém Soc Chir (Paris). 1915;41:1631. 3. Gillies HD.  Plastic surgery of the face. London: Frowde, Hodder, Stoughton; 1920. 4. Lexer E.  Die freien Transplantationen. Stuttgart: Enke; 1919. 5. Rehn E. Die freie Fetttransplantation. Arch klin Chir. 1912;98:1. 6. Ertl J. Die Chirurgie der Gesichts- und Kieferdefekte. Berlin: Urban & Schwarzenberg; 1918. 7. Ertl J. Regeneration, ihre Anwendung in der Chirurgie. Leipzig: Barth; 1939. 8. Holländer E.  Die kosmetische Chirurgie. In: Joseph M, editor. Handbuch der Kosmetik. Leipzig: von Veit; 1912.

2  Evolving of Concepts in Fat Grafting and Regenerative Surgery 9. Miller CC.  Cannula implants and review of implantation techniques in Esthetic Surgery. Chicago: Oak Press; 1926. 10. Peer LA.  Transplantation of tissues. Baltimore: Williams & Wilkins; 1955. 11. Fournier PF.  Microlipoextraction et microlipoinjection. Rev Chir Esthét Lang. 1985;10:36. 12. Illouz YG.  Remodelage chirurgical de la silhouette par lipolyse-aspiration, ou lipectomie selective. Ann Chir Plast Esthét. 1984;29:162. 13. Chajchir A, Benzaquen I.  Fat grafting injection for soft tissue augmentation. Plast Reconstr Surg. 1989;84:921. 14. Coleman SR.  Long term survival of fat transplants: controlled demonstration. Aesthet Plast Surg. 1995;19:421. 15. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-­ based therapies. Tissue Eng. 2001;7:211.

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16. Gutowski KA.  ASPS Fat Graft Task Force. Current applications and safety of autologous fat grafts: a report of the ASPS fat graft task force. Plast Reconstr Surg. 2009;124:272. 17. Rigotti G, Marchi A, Galié M, et  al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adiposederived adult stem cells. Plast Reconstr Surg. 2007;119:1409. 18. Coleman SR, Mazzola RF, editors. Fat injection from filling to regeneration. St. Louis: Quality Medical Publishing; 2009. 19. Tonnard P, Verpaele A, Peeters G, et al. Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013;132:1017. 20. Charles-de Sà L, Gontijo-de-Amorim NF, Maeda Takiya C, et al. Antiaging treatment of the facial skin by fat graft and adipose-derived stem cells. Plast Reconstr Surg. 2015;135:999.

3

Regenerative Surgery: Definitions and Background Stefania de Fazio and Elena Lucattelli

Key Messages • Regenerative surgery is a relatively new branch of plastic surgery which takes advantage of engineering human cells, tissues, or organs to replace, restore, or establish their normal functions. • Stem cells are undifferentiated cells which derive from various tissue sources, and each of them has different potentials for the cells to differentiate, being instrumental in repair following injury to the organ. • Adult Stem Cells (ASCs) derive from an adult tissue, and include mesenchymal stem cells (MSCs) and stem cells derived from placental tissue, such as human amnion epithelial cells. Adipose tissue (AT) is a very rich source of MSCs, is easier to extract than bone marrow (BM), and the stem cell population found in AT was determined to be an order of magnitude more prolific than BM cells. • Autologous adipose derived stem cells (ADSCs) were reported to be effective in the regeneration of several tissues, such as bone, cartilage, and soft tissues. • The stromal vascular fraction (SVF) contains extracellular matrix, MSCs precursors, pericytes, a significant pool of specific and unspeS. de Fazio (*) International Liaison SICPRE, Rome, Italy E. Lucattelli Plastic and Reconstructive Microsurgery, Careggi University Hospital, Florence, Italy

cific growth factors, bioactive proteins, hormones, exosomes, and other microvesicles. The human AT SVF is a great source of undifferentiated MSCs, similar but more abundant than the BM. • The adipose secretomes generate adipokines and cytokines leading to both local and systemic effects. ADSCs-conditioned media, a direct product of the secretome, has been demonstrated to exert endocrine and paracrine effects. • ADSCs-derived exosomes play a crucial role in improving wound healing and skin quality after radiotherapy, and in treating several conditions such as lymphoedema or neurological diseases. • New important perspectives in the field of regenerative surgery promote tissue regeneration and/or tissue transplantation from the use of stem cells, scaffolds, and local release of GFs and pharmacologically active molecules.

3.1

Definition of Regenerative Surgery

Regenerative surgery is a relatively new branch of medicine which treats injuries and diseases by harnessing the body’s own regenerative capabilities, rather than relying exclusively on invasive surgical procedures or drugs. Regenerative surgery takes advantage of engineering human cells,

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_3

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Fig. 3.1  Several different types of tissue would benefit from engineering-based repair or regeneration, like musculoskeletal tissues, bone, cartilage, soft tissues like sub-­ cutaneous fat and skin. PromoCell (2019) Using

mesenchymal stem cells in regenerative medicine. https:// www.promocell.com/blog/using-­m esenchymal-­s tem-­ cells-­in-­regenerative-­medicine/. Accessed 25 Nov 2019

tissues, or organs to replace, restore, or establish their normal functions. The term “regenerative surgery” includes not only therapies and devices which use stem cells, but also those which employ progenitor cells and other cellular products such as platelet-rich plasma (PRP) [1]. Several different types of tissue would benefit from engineering-based repair or regeneration, like musculoskeletal tissues, bone, cartilage, soft tissues like sub-cutaneous fat and skin. Regardless of the complexity of the targeted tissue, bioengineering strategies generally involve the combined application of biomaterials, cells, and biologically active factors to promote new tissue formation (Fig. 3.1). Both PRP and progenitor cells are widely used in the clinical setting, while stem cells are still in the early clinical trial stages. PRP is used to treat degenerative joint disease and orthopedic injuries. Moreover, progenitor cells have been used for many decades in the form of bone marrow (BM) transplants. Stem cells can also be added onto scaffolds, such as purified adipose tissue (AT) or biomaterials, which stimulate the long-­ term cell retention and subsequent colonization. These techniques could be useful to treat hard tissue defects, such as bone or cartilage injuries, or soft-tissue defects, like scars and burn injuries, or to regenerate other damaged tissues. Additionally, the use of autologous growth factors (GFs) derived from blood platelets can be an effective

support in tissue regeneration for their ability to stimulate cell proliferation, differentiation, and neoangiogenesis, thus helping the wound healing process.

3.2

Stem Cell Types

Stem cells are undifferentiated cells which can be found at all stages of life, embryonic, fetal, and adult. They give rise to differentiated cells that are building parts of tissues and organs [2]. Stem cells derive from various tissue sources, and each of them has different potentials for the cells to differentiate, being instrumental in repair following injury to the organ. Stem cells can differ between each other; their main characteristics are as follows: • Self-renewal: the ability to extensively proliferate; • Clonality: they usually arise from a single cell; • Potency: the ability to differentiate into different cell types. The human body develops from the zygote and the blastocyst from which Embryonic Stem Cells (ESCs) are derived into the germ layers, the endoderm, the mesoderm, and the ectoderm. Specific organs arise from each germ layer. Some

3  Regenerative Surgery: Definitions and Background

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of the progenitor cells that have contributed to the formation of such organ do not terminally differentiate but remain as tissue stem cells and can be found in BM, bone, blood, muscle, liver, brain, AT, skin, and gastrointestinal tract [2]. The tissue stem cells may be dormant within tissue but would proliferate under circumstances of injury and repair. In some organs, such as BM, liver, lung, and gut, stem cells regularly proliferate to supplement cells during normal turnover or injury, while in other organs, like pancreas, heart, or nervous system, they proliferate only to replace damaged cells following injury.

Oligopotent Cells  Oligopotent stem cells can self-renew for two or more lineages within a specific tissue. Hematopoietic stem cells are one example of this group, since they can differentiate into both myeloid and lymphoid lineages.

3.2.1 S  tem Cells Classification Based on Differentiation Potential According to their differentiation potential, stem cells can be grouped into the following five categories [3]. Totipotent Cells  Totipotent (or omnipotent) cells are the most undifferentiated cells, to be found in the early development. A zygote and the cells derived from the first two divisions belong to this group, as they differentiate into both embryonic and extra-embryonic tissues, forming the embryo and the placenta. Pluripotent Cells  Pluripotent cells can differentiate into cells which arise from the three germ layers (ectoderm, endoderm, mesoderm) from which all the tissues develop. ESCs belong to this group. Induced pluripotent stem cells (iPSCs), which are generated by reprogramming somatic cells, share similar characteristics with ESCs and can be included as well [4]. Multipotent Cells  Multipotent cells are found in almost all tissues and differentiate into cells from a single germ layer. The best known are the mesenchymal stem cells (MSCs). They can be derived from different tissues, including AT, BM, bone, umbilical cord blood, and peripheral blood. MSCs can differentiate into mesoderm-derived tissues (Fig. 3.2).

Unipotent Cells  Unipotent stem cells are able to self-renew and differentiate into only one specific cell type, forming a single lineage. Muscle stem cells, for example, give rise to mature muscle cells and to no other cells.

3.2.2 S  tem Cells Classification Based on Origin The ability to differentiate varies between stem cells depending on their origin: subsequently, they can be grouped into the following four broad categories: ESCs, fetal and adult stem cells, and iPSCs [2]. Generally speaking, ESCs and iPSCs are pluripotent, while adult stem cells (ASCs) are oligopotent or unipotent. Embryonic Stem Cells (ESCs)  ESCs are derived from the inner cell mass of the blastocyst, a stage of the pre-implantation embryo, 5–6 days after fertilization. They can differentiate into the three germ layers or maintain an undifferentiated state for a prolonged period in culture. The inner cell mass of the blastocyst will form the embryo, whereas the outer cell mass will form the placenta and is called trophoblast. ESCs that have been separated from the outer layer and cultured in an undifferentiated state with no genetic abnormalities are propagated as an ESC line. Unfortunately, because of ethical and religious issues they have been wrapped in controversy since the beginning. Actually, ESCs are mostly used mainly for research and to understand how regenerative cells work. Adult Stem Cells (ASCs) or Somatic Stem Cells (SCCs)  ASCs derive from an adult tissue, and include MSCs and stem cells derived from placental tissue, such as human amnion epithelial cells. ASCs have been shown to have an anti-­

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Fig. 3.2  Mesenchymal stem cells (MSCs) are multipotent cells which can differentiate into all mesoderm-derived tissues. PromoCell (2019) Using mesenchymal stem cells

in regenerative medicine. https://www.promocell.com/ blog/using-­m esenchymal-­s tem-­c ells-­i n-­r egenerative-­ medicine/. Accessed 25 Nov 2019

inflammatory and augment repair potential in animal models of injury. They cannot differentiate into every type of cell like ESCs, but they can create tissues such as bone or cartilage quite readily. They have the advantage of being autologous cells so they do not raise issues of rejection or ethical controversies [5].

currently investigating new methods to generate safe iPSCs without genomic manipulation [6].

Induced Pluripotent Stem Cells (iPSCs)  IPSCs do not come from embryos, but from adult cells. Their genetic code is reprogrammed so they become “pluripotent,” meaning that they can differentiate, or become any other type of cell [4]. Retroviral vectors, used to introduce the reprogramming factors into adult cells, and oncogenes like c-myc limit the use of iPSCs in clinical studies since they can cause cancer. Researchers are

3.2.3 Types of ASCs ASCs can be isolated from tissues of the three germ layers (e.g., BM, AT, umbilical cord blood, peripheral blood, dental pump) as well as of the placenta. Several studies have shown that transplantation of ASCs can restore damaged organs in vivo. Other studies have demonstrated that cultured ASCs secrete various molecular mediators with anti-apoptotic, immunomodulatory, angiogenic, and chemoattractant properties that promote repair [7]. The two most familiar sources of ASCs are BM and AT. (Fig. 3.3).

3  Regenerative Surgery: Definitions and Background

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Systemic infusion (e.g., graft versus host disease) Local injection (e.g., myocardial infarct)

MSC harvested from bone marrow or adipose tissue

+/– addition of phenotypemodulating factors

Implantation of engineered tissue (e.g., bone defects)

Fig. 3.3  Several studies have shown that adult stem cells (ASCs) can restore damaged organs in  vivo and secrete various molecular mediators with anti-apoptotic, immunomodulatory, angiogenic, and chemoattractant proper-

ties that promote repair. The two most familiar sources of ASCs are bone marrow and adipose tissue. © 2018 Ross E. B. Fitzsimmons et al. licensed under CC-BY 4.0

Bone Marrow Mesenchymal Stem Cells (BM-MSCs)  The earliest recognized form of ASCs in our body was that in the BM. BM-MSCs could be employed to help bone healing and to replace different blood cell types. Moreover, they could be used to restore BM after radiotherapy or chemotherapy. Unfortunately, BM-MSCs are hard to extract and not abundant: in order to be able to treat a patient, these cells must be taken to a lab and expanded in culture. Therapies using culture expanded BM-MSCs are not yet commercially available.

3.2.4 A  utologous vs. Allogeneic Cells

Adipose Derived Stem Cells (ADSCs)  AT is a very rich source of MSCs, and has remarkable advantages over BM. Not only is adipose fat easier to extract than BM, but the stem cell population found in AT was determined to be an order of magnitude more prolific than BM cells [8]. Most procedures using autologous ADSCs do not require that cells are expanded offsite in a lab, so most adipose-based therapies can be performed in the same operative session, which is advantageous, since BM cells are typically culture expanded for days in a lab before they can be reinjected back into a patient.

Stem cells used in regenerative surgery are largely divided into two classes: Autologous  Stem cells come from the patient’s own body, exclusively for its own use. Autologous treatments can be performed in the same operative session and the procedure uses the patient’s own cells, extracted from a tissue and then reinjected back into the same body. It is a one-to-one therapy. Allogeneic  Stem cells derive from another person (a donor). Before these cells can be put into another human they must undergo extensive testing for diseases, and the cells are usually culture expanded in laboratories to get higher cell counts. Allogeneic therapies are under strict Food and Drug Administration (FDA) guidelines as these stem cells will eventually scale up to mass production, be put in a bottle, and distributed to millions of patients. Several clinical trials are currently being carried out in order to study autologous and

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allogenic therapies for a wide range of diseases (cardiac, neurologic, autoimmune, orthopedic, etc.). The use of allogeneic versus autologous cells represents an unsettled issue in ASCs clinical applications. Studies in  vitro and in  vivo with MSCs showed similar efficacy of the two cell sources in suppressing immune response and stimulating tissue regeneration, and no serious adverse events were reported in clinical trials with allogeneic MSCs [9, 10]. Although allogeneic transplants usually need constant immunosuppression to prevent grafted cells rejection, the above-cited trials reported successful results with allogeneic MSCs for the treatment of several conditions. However, allogeneic MSCs are prone to cytotoxic lysis under inflammatory conditions in vitro, and induce the production of complement-­ activating antibodies in  vivo. Moreover, in  vivo studies showed that MSCs survival following transplantation is limited [11]. Therefore, persistent engraftment of transplanted cells does not seem to be a prerequisite for their therapeutic efficacy, suggesting that the observed clinical benefits result from a time-limited effect.

3.3

Adipose Tissue as a Regenerative Therapy

Nowadays, the role of the adipose tissue is widely accepted. It is acknowledged to be acting not only as an energetic deposit but also as a real and well-organized organ rich in MSCs precursors. These cells can differentiate and self-replicate to repair damaged tissue and organs via a paracrine activity, utilizing a variety of known and yet unspecified proteins and peptides. To obtain a strong regenerative effect, the harvested AT needs to undergo a specific engineering approach able to separate, extract, and concentrate the stromal vascular fraction (SVF) containing extracellular matrix (ECM), MSCs precursors, pericytes (assumed to be MSCs), a significant pool of specific and unspecific GFs, bioactive proteins, hormones, exosomes, and other microvesicles. The SVF of human AT is a

great source of undifferentiated multipotent MSCs, similar but more abundant than the BM; moreover it has a great potential of spontaneous differentiation into the adipogenic, chondrogenic, and osteogenic lineages [8]. The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) has proposed a minimum set of four criteria to define human MSCs, which the ADSCs meet for the majority: 1. MSCs are plastic adherent when maintained under standard culture conditions; 2. MSCs have the capability to differentiate in  vitro in osteoblasts, adipocytes, chondroblasts; 3. MSCs express CD73, CD90, and CD105; 4. MSCs lack expression of the hematopoietic lineage markers c-kit, CD14, CD11b, CD34, CD19, CD79, and human leukocyte antigen-DR. SVF manual extraction was performed as follows: liposuction aspirate was washed three times with phosphate-buffered saline (PBS) and suspended in an equal volume of PBS and 0.1% collagenase type I prewarmed at 37  °C.  Then, AT was placed in a shaking water bath at 37 °C with continuous agitation for 60 min and centrifuged at 600  g for 10  min at room temperature. The supernatant, containing mature adipocytes, was discarded. Then, the SVF pellet was resuspended in erythrocyte lysis buffer (155  mM NH4Cl, 10 mM KHCO3, and 0.1 mM ethylendiaminetetraacetic acid—EDTA) and incubated for 5 min at room temperature. After centrifugation at 600 g for 5  min, the pellet was resuspended in few microliters of growth medium and passed through a 100-μm Falcon trainer, then cells were counted using a hemocytometer. Cell viability by trypan blue exclusion was consistently more than 98%, and approximately 250,000 nucleated cells per milliliter of AT were obtained. For automatic SVF extraction, enzymatic digestion can either be used or not. The first approach was mostly adopted until 2014 and consisted in the introduction of AT into the

3  Regenerative Surgery: Definitions and Background

c­ell-­ processing device; removal of red blood cells and debris along with enzymatical digestion with collagenase type I followed. The released cells were then transferred into the centrifuge processing vessels, afterwards they were concentrated by short centrifugation and wash cycles. The cycles were repeated until the entire volume of input cell suspension was processed and cell population localized into the output chamber. The cells were washed one final time and then suspended for use in 5  mL of Ringer’s lactate solution. An aliquote of this SVF solution was incubated in erythrocyte lysis buffer, and after centrifugation at 600 g for 5 min, cell population was counted using hemocytometer. Cell viability by trypan blue exclusion was consistently more than 98%, and approximately 50,000 nucleated cells per mL of AT were obtained. In the second case, it is possible to isolate SVF by mechanical filtration of the fat, using the Platelet-Rich Lipotransfert: the AT is subjected to automatic filtration and centrifugation cycles at 1100 g for 10 min, after which 40 mL of the suspension is extracted from the bag. The suspension is further filtered through a 120-μm filter, obtaining about 20 mL of SVF suspension. The latter is centrifuged at 600 g for 10 min and then pellet is resuspended in erythrocyte lysis buffer and incubated for 5  min at room temperature. After centrifugation at 600 g for 5 min, the pellet is resuspended in few microliters of growth medium and cell population is counted using hemocytometer. Cell viability by trypan blue exclusion is usually consistently more than 98%, and about 65,000 nucleated cells per milliliter of AT are obtained [1].

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conditioned media, a direct product of the ADSC secretome, has been demonstrated in several studies to exert endocrine and paracrine effects. For instance, ADSC-conditioned media generated under proinflammatory stimuli improve wound healing rates in rodent models by means of the attraction of monocytes to sites of tissue damage and inflammation. Tissue regeneration through ECM remodeling, keratinocyte migration, an increase in capillary density has also been seen with the application of ADSC-secreted cytokines. Interestingly, the dimensional configuration of ADSCs used to generate conditioned media modifies the ADSC secretome, and subsequently the intensity of media induces endocrine and paracrine effects. Three-dimensional (3D) scaffold-­ free spheroid preparations of ADSCs generate media that exerts more powerful effects of wound healing rates than media generated by ADSCs grown in two-dimensional monolayers, perhaps because of reported synergistic effects that can occur between ECM and GFs [12].

3.3.2 Regulatory Overview

The current status of regulatory guidelines of regenerative technologies is fairly standard in most developed countries and, more or less, pattered on the American guidelines: exceptions are actually represented by Malaysia, Japan, Vietnam, Cambodia, Thailand, Germany, Switzerland, San Marino, and others. In the USA, cellular therapies are currently regulated by the FDA, the Office of Cellular, Tissue, and Gene Therapies (OCTGT) within the FDA Center for Biologies Evaluation and Research (CBER) [13]. 3.3.1 The Secretome The Section 361 of the Public Health Service (PHS) Act was intended to be an inspectional tool The ability of ADSCs to modify their environ- to assist FDA investigators in distinguishing ment is not restricted to direct differentiation into between the human cells, tissues, and cellulartarget tissue cells. A secretome is the compilation and tissue-based products, commonly known as of secretory organelles and their secreted protein 361 products, that are regulated by the Center for products. In particular, the adipose secretome Devices and Radiological Health (CDRH) as generates adipokines and cytokines leading to simple medical devices and those that are reguboth local and systemic effects. ADSCs-­ lated by the Center for Biologics Evaluation and

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Research (CBER) as drugs and biological products, commonly known as 351 products. In the present paper, a precise dividing line has been drawn between the limits of minimal-­ grade manipulation (MGM) and high-grade manipulation (HGM). MGM techniques include decantation, filtration, centrifugation, mechanical disruption, enzymatic digestion, and few others; these, however, are applied only when the tissue is harvested, treated, and re-implanted during the same surgical session and inside the same operating room. Some common HGM techniques are characterization, expansion, cultivation, and all the other complementary laboratory techniques routinely used for cell manipulation, as well as the above-listed MGM techniques whenever used outside the operating room (OR) or in a subsequent session. The use of all these cell derivatives is not allowed in private practice and outside strict protocols approved of and supervised by ethic committees. AT derivatives for clinical applications need to fulfill specific requirements, as outlined by the current good manufacturing practice (cGMP) for research purposes. Moreover, the employment of certified and validated instruments and components is required.

S. de Fazio and E. Lucattelli

3.4.1 Bioengineered Scaffolds for Tissue Regeneration

Tissue engineering focuses on developing functional surrogates for damaged tissues and organs. Cells in the natural microenvironment are surrounded by ECM, a complex 3D structure composed of fibrous molecules, which forms the physiological scaffold supporting cells. Therefore, it is important that biomaterials used for bioengineering scaffolds can provide a 3D structure to support tissue growth. The ideal scaffold should be made from a biodegradable nontoxic material, capable of resorbing as a function of time to create space for new tissues. It should also be highly porous to allow the diffusion of nutrients, oxygen, waste products, and the interaction between the cells and the surrounding microenvironment. Advances in biomaterial have led to the development of tailored scaffolds in order to provide appropriate structural support and, in some cases, biological and mechanical cues to promote tissue regeneration in vivo [14]. In addition, biomaterials for scaffolds can be modified to present biologically active signals, including cell-adhesion peptides and GFs, favoring cell attachment and tissue formation. Naturally derived polymeric materials, includ3.4 Clinical Application in Plastic ing polypeptides and polysaccharides, such as and Aesthetic Surgery collagen and hyaluronic acid, have been widely explored in the development of tissue-engineered An expansive toolbox of biomaterial and cell-­ scaffolds for soft-tissue repair; although they are based technologies stands ready to contribute to enzymatically degradable, the kinetics of degrathe production of tissue engineering solutions to dation may not be easily controlled or predicted. meet clinical needs. A common challenge Moreover, naturally derived polymers usually encountered in the development of tissue engi- present weak mechanical strength. neering technologies is the need to repair tissue Synthetic polymers present several key advandefects or to regenerate organs that have intricate tages relative to naturally derived polymers. They 3D structures. Furthermore, it is challenging to can be reproducibly manufactured with a wide integrate the regenerating tissue with surround- range of mechanical properties and degradation ing tissues and to maintain cell viability in large kinetics to enable the production of scaffolds constructs. New important perspectives in the with properties tailored for a particular applicafield of regenerative surgery promote tissue tion [15]. regeneration and/or tissue transplantation from Materials derived from the native ECM have the use of stem cells, scaffolds, and local release also been studied as scaffolds. Acellular tissue of GFs and pharmacologically active molecules. matrices have been shown to support the ingrowth

3  Regenerative Surgery: Definitions and Background

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of tissues in several applications, without inducing a severe immune response. Indeed, ­ given the natural origin of the matrices, they degrade slowly after implantation and are replaced or remodeled by the ECM derived from host cells.

The past decade has witnessed a growth in rational management of chronic wounds and some new approaches in wound dressings. Various “biological active” therapeutic attempts, mainly the delivery of local growth factors to enhance clinical management of chronic wounds, have been attempted with limited success so far [16]. Nowadays, in Europe there is a trend to use the GFs contained in PRP for the treatment of patients affected by lower limb ulcers and chronic wounds [17]. Recently, promising results have been shown in the treatment of the alopecia or hair loss [18].

3.4.2 Platelet-Rich Plasma and Growth Factors PRP is a concentration of platelets in a small volume of plasma that contains GFs including platelet-­ derived growth factor (PDGF), basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), insulin-like growth factor-­1 (IGF-1), and transforming growth factor-β (TGF-β), released after platelet activation [1]. It is possible to identify four main types of PRP preparation depending on cell content and fibrin architecture:

3.4.3 The Use of SVF/ADSCs

Autologous ADSCs were reported to be effective in the regeneration of several tissues, such as bone, cartilage, and soft tissues [1]. Although the biomolecular mechanism of cellular therapy is unknown, this therapeutic approach may play a pivotal role in the treatment of intractable ulcers, 1. Pure PRP or leukocyte-poor PRP prepara- as well as in chronic wounds [19]. tions: no leukocytes and low-density fibrin The injection of free fat together with autolonetwork after activation; gous SVF/ADSCs, isolated from a portion of 2. Leukocyte and PRP products: they contain liposuction aspirates, represents an alternative leukocytes and present a low-density fibrin strategy to soft-tissue augmentation surgery, network after activation; including also breast augmentation or reconstruc 3. Pure PRP fibrin or leukocyte-poor platelet-­ tion, increasing the long-term maintenance of fat rich fibrin preparations: no leukocytes and graft volume. In fact, SVF/ADSCs enrichment high-density fibrin network; was proven to induce the secretion of different 4. Leukocyte and platelet-rich fibrin or second cytokines and GFs encouraging angiogenesis and generation PRP products: they include leuko- fat graft revascularization, as well as pericytes cytes and present a high-density fibrin and endothelial cells, contained in the SVF, that network. directly contribute to neoangiogenesis [20]. However, it is still unclear whether grafted Briefly, the process of preparing PRP consists ADSCs increase the risk of the novo cancer of four phases: blood collection, centrifugation development or recurrence in patients treated for for platelet concentration, induction of gelation breast reconstruction after post-cancer surgery. (if the PRP is to be used in gel form), and activaFinally, recent studies showed that treatment tion. Current systems for the preparation of plate- with PRP and SVF/ADSCs increased survival of let concentrations routinely report the use of grafted adipose tissue. In particular, the comvarious centrifugation rates. After centrifugation, bined use of PRP and SVF/ADSCs in fat grafting the buffy coat layer, consisting of platelets and was reported to be effective in the treatment of white blood cells, was sequestered in a small or facial rejuvenation, scars on the face, soft-tissue large volume of plasma. defects, and breast reconstruction [1, 21].

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3.5

Conclusions

stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99(10):3838–43. The complexity of many tissues targeted for tis- 11. Schu S, Nosov M, O’Flynn L, Shaw G, Treacy O, Barry F, et al. Immunogenicity of allogeneic mesenchymal sue engineering therapies, coupled with constem cells. J Cell Mol Med. 2012;16(9):2094–103. founding factors associated with the clinical 12. Praveen Kumar L, Kandoi S, Misra R, Vijayalakshmi context, adds up to many barriers to product S, Rajagopal K, Verma RS.  The mesenchymal stem development and translation. Indeed, the field of cell secretome: a new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine tissue engineering will continue to focus on Growth Factor Rev. 2019;46:1–9. repairing complex tissues, taking into account 13. Zocchi ML, Vindigni V, Pagani A, Pirro O, Conti other tissue components such as the lymphatics. G, Sbarbati A, et al. Regulatory, ethical, and techniMoreover, we will need to better understand the cal considerations on regenerative technologies and adipose-derived mesenchymal stem cells. Eur J Plast in  vivo fate of various components of tissue-­ Surg. 2019;42(6):531–48. engineered products, including transplanted cells 14. Morissette Martin P, Shridhar A, Yu C, Brown C, and the biomaterial-based scaffold, before wideFlynn LE.  Decellularized adipose tissue scaffolds spread translation is possible. for soft tissue regeneration and adipose-derived stem/stromal cell delivery. Methods Mol Biol. 2018;1773:53–71. 15. Janoušková O.  Synthetic polymer scaffolds for soft References tissue engineering. Physiol Res. 2018;67(Suppl 2):S335–48. 1. Gentile P, Scioli MG, Bielli A, Orlandi A, Cervelli 16. Barrientos S, Brem H, Stojadinovic O, Tomic-­ V.  Concise review: the use of adipose-derived Canic M.  Clinical application of growth factors and stromal vascular fraction cells and platelet rich cytokines in wound healing. Wound Repair Regen. plasma in regenerative plastic surgery. Stem Cells. 2014;22(5):569–78. 2017;35(1):117–34. 17. Tian J, Cheng L-H-H, Cui X, Lei X-X, Tang J-B, 2. Ilic D, Polak JM. Stem cells in regenerative medicine: Cheng B.  Application of standardized platelet-rich introduction. Br Med Bull. 2011;98:117–26. plasma in elderly patients with complex wounds. 3. Smith A.  A glossary for stem-cell biology. Nature. Wound Repair Regen. 2019;27(3):268–76. 2006;441(7097):1060. 18. Gentile P, Garcovich S.  Advances in regenerative 4. Takahashi K, Yamanaka S.  Induction of pluripotent stem cell therapy in androgenic alopecia and hair loss: stem cells from mouse embryonic and adult fibroblast Wnt pathway, growth-factor, and mesenchymal stem cultures by defined factors. Cell. 2006;126(4):663–76. cell signaling impact analysis on cell growth and hair 5. McCormick JB, Huso HA. Stem cells and ethics: curfollicle development. Cells. 2019;8(5):466. rent issues. J Cardiovasc Transl Res. 2010;3(2):122–7. 19. Shukla L, Yuan Y, Shayan R, Greening DW, Karnezis 6. Trounson A, DeWitt ND.  Pluripotent stem cells T.  Fat therapeutics: the clinical capacity of adipose-­ progressing to the clinic. Nat Rev Mol Cell Biol. derived stem cells and exosomes for human dis2016;17(3):194–200. ease and tissue regeneration. Front Pharmacol. 7. da Silva Meirelles L, Nardi NB. Methodology, biol2020;11:158. ogy and clinical applications of mesenchymal stem 20. Gentile P, Orlandi A, Scioli MG, Di Pasquali C, cells. Front Biosci (Landmark Ed). 2009;14:4281–98. Bocchini I, Curcio CB, et al. A comparative transla 8. Sharath SS, Ramu J, Nair SV, Iyer S, Mony U, tional study: the combined use of enhanced stromal Rangasamy J. Human adipose tissue derivatives as a vascular fraction and platelet-rich plasma improves potent native biomaterial for tissue regenerative therafat grafting maintenance in breast reconstruction. pies. Tissue Eng Regen Med. 2020;17(2):123–40. Stem Cells Transl Med. 2012;1(4):341–51. 9. Comoli P, Ginevri F, Maccario R, Avanzini MA, 21. Rigotti G, Charles-de-Sá L, Gontijo-de-Amorim NF, Marconi M, Groff A, et  al. Human mesenchymal Takiya CM, Amable PR, Borojevic R, et al. Expanded stem cells inhibit antibody production induced stem cells, stromal-vascular fraction, and platelet-­ in vitro by allostimulation. Nephrol Dial Transplant. rich plasma enriched fat: comparing results of differ2008;23(4):1196–202. ent facial rejuvenation approaches in a clinical trial. 10. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Aesthet Surg J. 2016;36(3):261–70. Longoni PD, Matteucci P, et al. Human bone marrow

4

Current Status of Regenerative Plastic Surgery Joseph M. Firriolo and Lee L. Q. Pu

Key Messages • Fat grafting is more than a filler. Fat grafting demonstrates remarkable regenerative capacity. • The regenerative properties of fat grafting have been attributed to adipose-derived stem cells (ADSCs) and preadipocytes in the stromal vascular fraction (SVF) of adipose tissue. • Fat grafting has shown great potential to ameliorate the effects of scarring, fibrosis, and atrophy in a variety of clinical conditions. • Neuropathic pain may benefit from treatment by fat grafting due to a combination of mechanical and regenerative effects. • Fat grafting exhibits angiogenic and immunomodulatory properties in the context of autoimmune disease. • The broad clinical applications of regenerative fat grafting have the potential to improve quality of life through a combination of functional and aesthetic improvement. J. M. Firriolo Division of Plastic and Reconstructive Surgery, University of California Davis, Sacramento, CA, USA e-mail: [email protected] L. L. Q. Pu (*) Division of Plastic Surgery, University of California at Davis, Sacramento, CA, USA e-mail: [email protected]

4.1

Introduction

Recent developments have improved the reliability of autologous fat grafting and made it a powerful and efficacious addition to the contemporary plastic surgeon’s armamentarium. Historically, fat grafting has been considered an ideal filler: it is autologous, biocompatible, and naturally integrates into host tissue. Furthermore, it is potentially permanent and can be removed if indicated [1]. As such, fat transfer has been used since the late nineteenth century to address soft tissue contour deformities in the face and breasts [2]. However, fat grafting is much more than a filler, having demonstrated remarkable regenerative capacity, largely secondary to the action of adipose-derived stem cells (ADSCs) and preadipocytes in the stromal vascular fraction (SVF) of adipose tissue. Based on several initial studies, the use of fat grafting has expanded well beyond its properties as a filler. Today, tissue regeneration by means of fat grafting is a burgeoning field with a myriad of applications. This chapter will summarize the various clinical studies (level IV evidence and above), published in reputable, peer-reviewed journals that have successfully harnessed the regenerative properties of autologous fat grafting.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_4

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4.2

Initial Studies

In 2006, Coleman produced a three-patient case series, which highlighted the effect that fat grafting has on overlying skin and surrounding tissues [1]. All three patients underwent facial contouring with fat grating for acne scarring, radiation-­ induced changes, and periorbital rejuvenation, respectively. The patients experienced volume restoration, enhanced skin quality (notably improved softness, thickness, pliability, and the recovery of hair follicles), and favorable scar remodeling. Interestingly, patients experienced structural improvement in both bony and soft tissue deficiencies. The transplanted fat did not feel like isolated collections of fat, instead it integrated and blended with the recipient tissue such that fat injected near bone felt like bone and fat placed in muscle felt like muscle. Coleman’s findings were consolidated the following year by Rigotti and colleagues, who used fat grafting to treat 20 patients with side effects of radiotherapy tissue damage that had resulted in severe symptoms or irreversible function damage [3]. Investigators noted dramatic improvement in symptomatology in most patients, including remission of skin necrosis, as well as amelioration of fibrosis, atrophy, and skin retraction. Investigators also performed ultrastructural analysis of the radiodamaged subcutaneous tissue, both before and after fat grafting. At baseline, they noted microangiopathy, namely fibrosis and reduction of the capillary bed of affected tissue. Following fat transplant, they observed angiogenesis and improved hydration. While this study reinforced the clinical benefits of fat grafting, it also demonstrated the possible utility of this technique that may be extended to other forms of microangiopathies. These promising findings inspired surgeons to use fat grafting to address scarring and fibrosis in a variety of other clinical contexts. For instance, Klinger and colleagues applied fat grafting to the treatment of burn scars, noting clinical improvements in skin texture and thickness, as well as histological improvements, including new collagen deposition, local neovascularization, and dermal hyperplasia [4]. Additionally, Hovius

reported success in the treatment of Dupuytren’s contracture with percutaneous aponeurotomy (to release cord from the dermis), followed by interposition fat grafting [5]. This effectively restored subcutaneous fat over the affected area and prevented contracture recurrence.

4.3

Neuropathic Pain

Neuropathic pain has long been burdensome for patient and physician alike. The mainstay treatment for many forms of neuropathic pain is pharmacological (including antidepressants, antiepileptics, topical anesthetics, and opioids). Long periods of polypharmacy are associated with drug side effects and decreased quality of life. As such, there is interest in non-­ pharmacological interventions for neuropathic pain. The etiology of neuropathic pain is thought to be a combination of nerve entrapment, chronic inflammation, and neuroma formation. Pertinent to the plastic surgeon is the mechanisms by which the treatment of breast cancer may lead to neuropathic pain. Postmastectomy pain syndrome is a well-established phenomenon secondary to peripheral nerve injury during breast cancer extirpation. However, adjuvant therapy may further contribute to neuropathic pain in these patients [6]. Chemotherapy agents may induce musculoskeletal pain and arthralgia; radiation therapy may lead to fibrosis and associated nerve compression, as well as upregulation of pro-inflammatory cytokines with the propensity to induce peripheral nerve sensitization. In this context, autologous fat grafting for patients with postmastectomy pain syndrome—through mechanical, immunomodulatory, and regenerative mechanisms—has demonstrated clinically significant improvements pertaining to patient-­ reported pain and decreased neuropharmacological regimens [6]. Likewise, patients treated with fat grafting for neuropathic pain secondary to severe burns have experienced pain reduction, resolution of Tinel’s sign, and decrease reliance on analgesic drugs. One mechanism of neuropathic pain relief by means of fat grafting is hypothesized to be

4  Current Status of Regenerative Plastic Surgery

mechanical. Fat grafting procedures provide release of fibrotic tissues in conjunction with a cushioning affect around nerve endings and neuromas. The regenerative properties of fat grafting further potentiate these actions. Fat grafts contain adipose-derived stem cells, cytokines, growth factors, and other cellular components that serve to not only regenerate the dermis and subcutaneous tissue, but also remodel scars and fibrotic tissue, further relieving entrapped nerves and optimizing the nerve microenvironment. Furthermore, the adipose-derived stem cells and mesenchymal stem cells in autologous fat ­transfers can reduce T cell activation with downstream anti-inflammatory and analgesic effects [6].

4.4

Migraine Headaches

Migraine headaches are often successfully managed with lifestyle modification medical management. However, approximately one-third of patients with migraine headaches do not have complete elimination of headaches with standard therapy [7]. For cases where medical therapy has failed and for where there is an identifiable trigger site, surgical decompression of nerves has become an increasingly common practice among plastic surgeons, with impressive results. Neurectomy is often considered for patients for whom surgical decompression fails, however this comes at the expense of numbness. Fat grafting now presents an alternative; recent research suggests that for those with recalcitrant migraine headache, with persistent symptoms after surgical decompression, fat grafting may provide symptomatic relief. In a recent study by Guyuron and colleagues, most patients treated with fat grafting experienced a 50% or greater decrease in the frequency, intensity, and/or duration of migraine headaches [7]. It is possible that fat grafting provides further surgical decompression of nerves, by breaking up scar/fascia and providing cushioning around peripheral nerves. From a regenerative perspective, it has been proposed that the stem cell content in fat grafts may assist in trigeminal nerve axon repair, myelin regenera-

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tion, and a reduction in scar burden for nerve branches, thereby providing migraine relief.

4.5

Scarring, Fibrosis, and Difficult Wounds

As evident by previously mentioned reports, autologous fat grafting offers many benefits in the setting of scarring and fibrosis. This occurs through a combination of fibrotic tissue release, regeneration of normal dermis and subcutaneous tissue, and architectural remodeling of scar itself. A prospective study by Pallua and colleagues demonstrated improvements in facial scars following autologous fat grafting [8]. All subjects included in the study experienced subjective scar improvement with relation to color, stiffness, irregularity, pigmentation, and pliability. Laser Doppler spectrometry also revealed significant improvements in skin microcirculation following fat grafting in these patients. Others have applied fat grafting to burn scars. Byrne and colleagues employed fat grafting to secondary burn reconstruction of the hand, noting improvements in hand function and aesthetics [9]. Patients experienced significant gains in hand movement, greater satisfaction, and an improved ability to complete their activities of daily living. Again, authors credited fat grafting for releasing tethered skin from underlying tissues as well as its downstream regenerative effects. Piccolo and colleagues also investigated fat grafting to treat scars caused by burns and trauma; they also studied the healing of other difficult wounds with the application of fat grafting, including venous ulcers, diabetic ulcers, and open fractures of the tibia [10]. As seen in other studies, the treatment of scars resulted in reduced hypertrophy and fibrosis, decreased scar thickness, and improved scar malleability. The great majority (95%) of patients with chronic venous/ diabetic ulcers experience resolution of their wounds. The authors also infer that fat grafting may favor bone formation aiding in bone fractures and segmental bone loss.

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4.6

Radiation Wounds

As shown by the clinical studies by Coleman [1] and Rigotti [3], many radiation-induced changes are amenable to fat grafting. Irradiated skin and soft tissues show numerous histopathological changes; importantly, there is altered blood vessel morphology and a decreased density of microvasculature that together result in ischemic injury, fibrosis, and necrosis. In a case series by Phulphin, 11 patients were treated with autologous fat transfer for aesthetic and functional deficits following radiotherapy for head and neck cancer [11]. On a histologic level, following fat grafting, biopsied tissue exhibited a higher density microvascular network, an absence of necrotic areas, and improved fibrosis. For 10 of the 11 patients, this translated to marked aesthetic and functional gains. Skin became softer, more supple, and pliable, which served to improve neck mobility and mouth opening. Treated patients also experienced a decrease in perilaryngeal fibrosis, increased tongue volume, and the reappearance of more viscous saliva, resulting in superior breathing, phonation, and swallowing outcomes.

4.7

Hair Restoration

Coleman’s 2006 clinical study [1] featured a 23-year-old man who had undergone rhabdomyosarcoma excision and radiation therapy of his left masseter, with subsequent alopecia of his overlying facial hair. Following autologous fat grafting there were significant improvements in facial contour and skin quality. Interestingly, at 7 months follow-up the patient’s beard had also shown signs of regeneration, with a notable increase of facial hair density where there had been radiation-induced alopecia. Since then, adipose-derived mesenchymal stem cells have emerged as a new therapeutic option for hair loss. Epstein and Epstein [12] have described the use of fat grafting for both scarring and nonscarring alopecia. They started by pretreating scalp scars with fat grafting to induce angiogenesis in preparation for hair transplantation. These investigators then had success

applying fat grafting to androgenic alopecia, presenting three main mechanisms by which fat grafting may promote follicular regeneration: (1) anti-inflammatory action (preventing the advancement of perifollicular fibrosis and infiltrates); (2) anti-androgenic effect; and (3) neovascularization.

4.8

Alternative to Flap Reconstruction

Fat grafting represents a new rung on the reconstructive ladder, presenting a regenerative alternative to flap reconstruction. Khouri and colleagues presented a technique whereby “Rigottomies” (i.e., percutaneous aponeurotomy to make small cuts and nicks) were made into scars and fascia to release fibers and allow for the stretch and expansion of tissue [13]. These effectively turned tissue into a three-dimensional scaffold, whereby micro-openings serve as a recipient to fat grafting. Importantly, the technique relied on the judicious creation of Rigottomies to avoid merging small cuts into large slits, as this would form large cavities where fat grafts would be prone to pool and fail. They treated 31 patients with this technique as an alternative for flap reconstruction for the following indications: wounds that could not be closed primarily, contour defects that required megavolume fat grafts, radiation scars, and congenital constriction bands. Most patients required two fat grafting procedures. In all cases, tension was relieved without flap undermining. Authors report that the regenerated tissue had nearly normal texture and grossly preserved sensation. Using this technique, surgeons were able to regenerate tissue in situ, inducing the proliferation of “like” tissue, turning scarred and fibrotic tissue into a regenerative matrix.

4.9

Cleft Lip and Palate

Fat grafting may also prove to be a valuable regenerative adjunct in the treatment of cleft lip and palate, especially since infant fat produces

4  Current Status of Regenerative Plastic Surgery

more biologically robust adipose-derived stem cells than adult fat [14]. Investigators have compared the aesthetics outcomes of infants undergoing primary unilateral cleft lip repair with and without immediate fat grafting [14]. Blinded reviewers reviewed postoperative photographs, with results indicating that immediate fat grafting may improve lip contour, scarring, and overall appearance in primary cleft lip repair. In the context of cleft palate, fat grafting has been used in mild to moderate cases of velopharyngeal insufficiency (VPI) [15]. In this application, fat is injected into pharyngeal walls (within the fibers of the superior constrictor muscle) and into the soft palate (particularly in the midline and the nasal aspect of the uvula). This fat transfer improves contact between the velum and posterior pharyngeal wall to ultimately restore a competent velopharyngeal sphincter. In cases where children have had previous cleft palate operations, fat grafts can serve to soften scar contractures, which may further length or enhance mobility of the palate.

4.10 Autoimmune Disease The vascular, skin, and soft tissue manifestations of autoimmune disease may also benefit from the regenerative properties of fat grafting. For instance, Bank and colleagues applied fat grafting to the hands for the management of Raynaud phenomenon [16]. Fat was injected into the dorsal and volar surfaces of the hand, including all webspaces. Patients reported reduced pain, fewer cold attacks, decreased duration of cold attacks, improved skin and soft tissue texture, and a decrease in ulceration. Furthermore, 13 patients had their hand perfusion assessed with laser speckled imaging; five of these patients showed improved perfusion counts. Again, adipose-­ derived stem cells are believed to play an important role. It is hypothesized that fat grafting may stimulate growth factors (e.g., vascular endothelial growth factor) and subsequently induce angiogenesis and improvements in perfusion. Similarly, Magalon and colleagues applied fat grafting to address the facial and hand manifesta-

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tions of scleroderma [17]. Like Banks, they observed alleviation of vascular manifestations in the hands, particularly in relation to the severity of Raynaud phenomenon, digital ulcers, and hand pain. They also noted decreased finger circumference in treated hands, which was likely a consequence of improved finger skin edema. When injected into the face, fat grafting did result in some improvement in mouth opening, xerostomia, and skin quality. Lichen sclerosis is often classified as an autoimmune disease. It is a clinical condition characterized by white crinkled or thickened patches of skin, atrophy, scarring, and hypopigmentation. Healing these lesions requires tissue regeneration. Boero and colleagues conducted a study that included 36 women with vulval lichen sclerosis with symptoms refractory to topical corticosteroid therapy [18]. Nearly all patients experience better vulvar tropism of the skin and mucosa, increased volume of the labia majora and minora, and complete disappearance of scratching lesions. Most patients also experienced improved caliber and elasticity of the vaginal introitus, reduced clitoral burying, and remission of white lesions. The success of fat grafting in autoimmune disease not only reinforces its aforementioned regenerative properties, but also demonstrates the angiogenic and immunomodulatory properties of adipose-derived stem cells that have the potential to be applied more broadly to tissue repair.

4.11 Discussion Autologous fat grafting has long afforded plastic surgeons the ability to fill and contour with native biological tissue, for both reconstructive and aesthetic indications. However, in recent decades fat grafting has established itself as a new rung on the reconstructive ladder, largely due to its ability to regenerate and remodel. Ultimately thus far— despite the diverse clinical applications—the regenerative properties of fat grating have, for the most part, been harnessed to address a rather limited, recurring range of pathophysiological mechanisms, i.e., mostly volume loss, scarring/

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fibrosis, and ischemia. In the senior author’s practice, fat grafting has become an alternative approach for treatment of various conditions such as fibrotic conditions or depressed scars (Figs. 4.1 and 4.2). A list of the broad indications as summarized by the authors for regenerative fat grafting appears in Table  4.1. Impressively these indications lend transplanted fat to a vast suite of established and emerging clinical applications; the applications discussed in this chapter are summarized in Table 4.2. Moving forward, the use of fat grafting in plastic surgery is likely to have an increasing regenerative focus as evident by recent innovations, which include nanofat grating and stromal vascular fraction (SVF) gel. Nanofat represents a mechanically emulsified and liquified form of harvested fat. According to

a recent study by Tonnard and colleagues [19], nanofat contains no viable adipocytes, but does have a large number of good quality adipose-­ derived stem cells. Without adipocytes, nanofat has essentially no volumetric function, but does appear to retain the regenerative potential of transplanted fat when used by investigators to correct superficial rhytids, scars, and dark lower eyelids. It is hypothesized that the stem cells in nanofat stimulate collagen and elastin synthesis/ remodeling, thereby improving skin elasticity. Furthermore, it has been proposed that the fragmented adipocyte content of nanofat may release cytokines and attract macrophages that induce growth factors. SVF gel is produced by centrifugation and intersyringe shifting of harvested fat. It is rich in cellular content, namely adipose-derived stem

a

b

c

d

Fig. 4.1 (a) A 37-year-old woman had a sizable depressed facial scar and two noticeable facial scars following her previous facial trauma; (b) She underwent conventional fat grafting (8 cc fat) to the depressed facial scar and nano-

fat grafting (0.3  cc nanofat) to that two facial scars; (c) The result right after fat grafting on the OR table; and (d) The result at 18 month follow-up

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43

a

b

c

d

Fig. 4.2 (a) A 53-year-old woman developed a scar contracture over her right dorsal foot from her previous skin cancer resection. (b) She underwent conventional fat grafting (8 cc fat) to the fibrotic area of her right foot after

percutaneous scar release. (c) The result at 6 months follow-­up; and (d) The result at 6 month showing improved range of motion on her foot dorsal flexion

Table 4.1  The broad indications for regenerative fat grafting

also has utility as a dermal filler. Cai and colleagues [20] used SVF gel for the treatment of horizontal neck lines, noting improvement ­secondary to both dermal filling and the stimulation of collagen synthesis (likely secondary to the effects of adipose-derived stem cells).

Indications •  Tissue filling, contouring, and augmentation •  Remodeling scar tissue and fibrosis •  Ischemic injury •  Cushioning and protection of sensitive or important structures •  Vasculopathy, namely microangiopathy and vasospasm •  Nerve injury •  Localized symptoms of autoimmune disease •  Tissue aging and atrophy

cells, vascular endothelial cells, and condensed adipose tissue extracellular matrix fibers. This contrasts with nanofat, which contains negligible extracellular matrix content. For this reason, SVF possesses not only regenerative potential, but

4.12 Current Challenges of Regenerative Plastic Surgery Currently, the major drawbacks of regenerative fat grafting are: (1) the unpredictability of results and (2) the fact that the precise underlying mechanisms of regeneration remain largely unknown. In its early years, conventional fat grafting (i.e.,

J. M. Firriolo and L. L. Q. Pu

44 Table 4.2  Current clinical applications of regenerative fat grafting Clinical applications •  Neuropathic pain  –  Postmastectomy pain syndrome  –  Neuropathic pain in severe burns •  Migraine headaches •  Scarring, fibrosis, and difficult wounds  –  Dupuytren’s contracture  –  Facial scars  –  Burn scars  –  Venous and diabetic ulcers  –  Open fractures of the tibia •  Radiation-induced changes in skin and soft tissue • Reconstruction  –  Provision of “like” tissue as an alternative to flap reconstruction •  Cleft lip and palate  –  Lip contouring and scarring  –  Velopharyngeal insufficiency •  Autoimmune disease  –  Raynaud phenomenon  –  Hand manifestations of scleroderma  –  Vulva lichen sclerosis

for the purpose of filling) was plagued by issues of unpredictable graft take and long-term absorption although the reliability of fat grafting has greatly improved, both these outcomes remain variable and technique dependent. Likewise, regenerative fat grafting is still in its infancy; the clinical evidence for this field is limited to small cohort studies and case series, and optimal techniques, fat grafting volumes, and specific ­ indications are yet to be determined for each clinical application. While fat grafting can be credited for its effects on tissue quality, perfusion, and cellular repair, further research is required to characterize these regenerative mechanisms, to both advance the field of regenerative medicine/ surgery and ensure safety as the clinical applications broaden.

4.13 Conclusion Fat grafting is an exciting field of study in contemporary plastic surgery. Its indications continue to increase, largely due to the regenerative properties of transplanted fat. Fat grafting has the potential to serve as a regenerative option for difficult clinical problems that cannot be effectively

treated at the present time. It may present a less invasive avenue for clinical issues that today necessitate conventional surgical techniques. However, more well-controlled clinical studies are ultimately required to confirm its efficacy and safety.

References 1. Coleman SR.  Structural fat grafting: more than a permanent filler. Plast Reconstr Surg. 2006;118(3 Suppl):108–20. 2. Neuber F.  Fettransplantation. Chir Kongr Verhandl Dtsch Gesellsch Chir. 1893;22:66. 3. Rigotti G, Marchi A, Galiè M, Baroni G, Benati D, Krampera M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg. 2007;119(5):1409–22. 4. Klinger M, Marazzi M, Vigo D, Torre M. Fat injection for cases of severe burn outcomes: a new perspective of scar remodeling and reduction. Aesthet Plast Surg. 2008;32(3):465–9. 5. Hovius SER, Kan HJ, Smit X, Selles RW, Cardoso E, Khouri RK. Extensive percutaneous aponeurotomy and lipografting: a new treatment for Dupuytren disease. Plast Reconstr Surg. 2011;128(1):221–8. 6. Caviggioli F, Maione L, Forcellini D, Klinger F, Klinger M.  Autologous fat graft in postmastectomy pain syndrome. Plast Reconstr Surg. 2011;128(2):349–52. 7. Guyuron B, Pourtaheri N.  Therapeutic role of fat injection in the treatment of recalcitrant migraine headaches. Plast Reconstr Surg. 2019;143(3):877–85. 8. Pallua N, Baroncini A, Alharbi Z, Stromps JP. Improvement of facial scar appearance and microcirculation by autologous lipofilling. J Plast Reconstr Aesthet Surg [Internet]. 2014;67(8):1033–7. https:// doi.org/10.1016/j.bjps.2014.04.030. 9. Byrne M, O’Donnell M, Fitzgerald L, Shelley OP.  Early experience with fat grafting as an adjunct for secondary burn reconstruction in the hand: technique, hand function assessment and aesthetic outcomes. Burns [Internet]. 2016;42(2):356–65. https:// doi.org/10.1016/j.burns.2015.06.017. 10. Piccolo NS, Piccolo MS, Piccolo MTS.  Fat grafting for treatment of burns, burn scars, and other difficult wounds. Clin Plast Surg. 2015;42(2):263–83. 11. Phulpin B, Gangloff P, Tran N, Bravetti P, Merlin JL, Dolivet G.  Rehabilitation of irradiated head and neck tissues by autologous fat transplantation. Plast Reconstr Surg. 2009;123(4):1187–97. 12. Epstein GK, Epstein JS.  Mesenchymal stem cells and stromal vascular fraction for hair loss: current status. Facial Plast Surg Clin North Am [Inter-

4  Current Status of Regenerative Plastic Surgery net]. 2018;26(4):503–11. https://doi.org/10.1016/j. fsc.2018.06.010. 13. Khouri RK, Smit JM, Cardoso E, Pallua N, Lantieri L, Mathijssen IMJ, et  al. Percutaneous aponeurotomy and lipofilling: a regenerative alternative to flap reconstruction? Plast Reconstr Surg. 2013;132(5):1280–90. 14. Zellner EG, Pfaff MJ, Steinbacher DM.  Fat grafting in primary cleft lip repair. Plast Reconstr Surg. 2015;135(5):1449–53. 15. Mazzola RF, Cantarella G, Mazzola IC. Regenerative approach to velopharyngeal incompetence with fat grafting. Clin Plast Surg. 2015;42(3):365–74. 16. Bank J, Fuller SM, Henry GI, Zachary LS. Fat grafting to the hand in patients with Raynaud phenomenon: a novel therapeutic modality. Plast Reconstr Surg. 2014;133(5):1109–18.

45 17. Magalon G, Daumas A, Sautereau N, Magalon J, Sabatier F, Granel B. Regenerative approach to scleroderma with fat grafting. Clin Plast Surg [Internet]. 2015;42(3):353–64. https://doi.org/10.1016/j. cps.2015.03.009. 18. Boero V, Brambilla M, Sipio E, Liverani CA, Di Martino M, Agnoli B, et al. Vulvar lichen sclerosus: a new regenerative approach through fat grafting. Gynecol Oncol [Internet]. 2015;139(3):471–5. https:// doi.org/10.1016/j.ygyno.2015.10.014. 19. Tonnard P, Verpaele A, Peeters G, Hamdi M, Cornelissen M, Declercq H.  Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013;132(4):1017–26. 20. Cai J, Wang J, Hu W, Lu F. Mechanical micronization of lipoaspirates for the treatment of horizontal neck lines. Plast Reconstr Surg. 2020;145(2):345–53.

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Adipose Tissue Transplantation: Autologous Versus Cryopreserved (Frozen) Versus Heterologous. Present and Future of Fat Transfer Fabiana Zanata, Fabio Xerfan Nahas, Tomas Fortoul, Jeffrey M. Gimble, and Lydia Masako Ferreira Key Messages • Adipose tissue is an important source of volume and functional tissue as source of adipose-­ derived stem cells; • Harvest of adipose tissue is considered less invasive; • Adipose tissue still imposes some challenges bringing interest to other sources of fat; • Cryopreserved and heterologous tissue can be a source of adipose tissue for reconstructive purposes, regenerative medicine, and tissue engineering; • Experimental studies set proof of principles for the use of these alternative sources of adipose tissue;

F. Zanata (*) · F. X. Nahas · L. M. Ferreira Plastic Surgery Division, Universidade Federal de Sao Paulo UNIFESP, Sao Paulo, Brazil T. Fortoul Plastic Surgery, Centro Medico Docente La Trinidad, Caracas, Venezuela J. M. Gimble Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, USA e-mail: [email protected]

• Safety and well described protocols are subject to extensive investigation before current clinical application; • Alternative materials are under development and might overcome the needs for additional sources of tissue.

5.1

Introduction

Adipose tissue transplantation is the use of adipose tissue to replace or increase volume for aesthetic or reconstructive purposes in congenital or acquired shape deficiencies. In addition to its structural and volumetric properties, adipose tissue is now recognized based on its endocrine, immune, and metabolic properties. The increased knowledge regarding adipose tissue functional properties stimulates the search for alternatives techniques to improve results regarding volume and/or function for aesthetic or reconstructive purposes using adipose tissue transplantation in Plastic and Aesthetic Regenerative Surgery. Innovative ideas like cryopreservation of adipose tissue from lipoaspirates or lipectomies and also heterologous use of adipose tissue using tissue donors are alternatives that might increase the availability of fat for the multiple clinical uses described and also for regenerative medicine and tissue engineering [1] (Table 5.1).

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_5

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48 Table 5.1  Commonly used terms—adipose tissue transplantation Adipose tissue Fat pad Lipoaspirate

Tissue transplantation Tissue transfer Tissue grafting

5.1.1 History of Fat Transfer, Innovations, and Need for Alternative Sources of Adipose Tissue

Use Autologous Heterologous

Tissue preservation Fresh Cryopreserved

opening a new perspective of autologous fat transfer in regenerative medicine with the potential to heal and recover tissues or organs (angiogenesis, peripheral nerve regeneration, enhancement of dermal thickness and elasticity, reversal of fibroFat transfer was initially described with the use sis secondary to radiation therapy, scarring) with a of small lipomas to fill facial contour. Later, auto-­ direct use or through the reprograming of adiposetransplanted lipoma for breast asymmetry correc- derived stem cell (ASCs) with external chemicals tion after tumor excision. Other similar techniques and growth factors [1]. Optimized techniques to improve the viability and new procedures were described including the resection of abdominal fat tissue blocks trans- of fat cells and the subsequent outcomes of transferred with or without decorticated dermis, rota- planted tissue have resulted from a better undertion of fat flaps, and the transfer of autologous fat standing of the adipose tissue function beyond its into the subcutaneous tissue for correction of historically recognized role in generating struccontour deformities. Over time, these clinicians tural volume, increasing the interest regarding gained further insight into transplanted autolo- the possible use of tissue cryopreservation and gous fat procedures with respect complications heterologous options when immediate autolorelating to volume loss due to reabsorption, indu- gous tissue harvesting is not available or possible [1] (Table 5.2). ration, and deformities [2]. Progressive innovators advanced liposuction techniques by introducing specifically designed and dedicated instruments such as blunt cannu- 5.1.2 Techniques for Fat Harvesting, Processing, and Transfer— las, suction pumps with controllable negative Standard Processing suction, solutions yielding enhanced aspirates, Techniques That Should and improved mechanical, ultrasound, and laser Be Used for Cryopreserved handpieces (Fischer and Fischer, Fournier, Illouz, and Heterologous Tissue Klein, Scuderi and Zocchi) [2]. With these instruments and reagents, liposuction gained increased attention from the plastic and general surgical Various methods to harvest and process fat have community, making fat a more widely harvested been designed to improve the take of the graft and, thus, available tissue. The number of scien- and reduce oil cysts and other side effects. These tific studies related to liposuction and fat tissue include decanting, centrifugation, washing, and increased exponentially following the identifica- stromal vascular cell enrichment. Experimental tion and characterization of adipose-derived studies have not demonstrated any difference stem/stromal cells. While adipocytes account for between fat graft quality with dry liposuction most of the adipose tissue’s volume, the majority harvesting as compared to the tumescent/wet of the total cell content consists of adipose-­ technique. Furthermore, compared to decanted or derived stem/stromal cells, fibroblasts, endothe- centrifuged tissue, power/ultrasound assisted lial cells, and pericytes in an extracellular matrix. liposuction in combination with cotton gauze Adipose tissue serves not just as a passive rolling and washing yields a higher number of energy store and source of padding for surround- adipose-derived stem/stromal cells (ASC) and ing tissues, but as a biologically active tissue, maintains superior fat cell viability [3].

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Table 5.2  Advantages and disadvantages of unusual adipose tissue for fat graft Type of adipose tissue Advantages

Disadvantages

Fresh adipose tissue • Relatively noninvasive tissue harvesting with liposuction

•  Harvesting time •  Morbidity of harvesting surgical procedure •  Limited repetitions due to donor site restrictions

Cryopreserved fat transfer •  Alternative source of tissue: non-available donor site; risk for the harvest •  Immediately available •  Autologous use •  Can be repeated •  Tissue viability reduced •  Cryoprotective agent •  Storage space

The enrichment of the adipose tissue with stromal vascular fraction cells obtained from processed tissue has been reported to enhance clinical outcomes. Clinical trials are underway to reinforce these findings [4]. Meanwhile, until a definitive study verifies an optimal approach, each surgeon should decide the technique on a case by case basis. For example, since dry liposuction can only be performed under general or regional anesthesia and is limited by the amount of bleeding, it is indicated for cases requiring smaller volumes of fat transfer. For larger volumes, tumescent liposuction under general anesthesia should be considered. There is a general consensus that gentle techniques harvesting fat with small cannulas followed by injecting via microtunneling into different anatomical layers or planes can result in between 30 and 70% retention of the grafted fat volume [4]. Due to the risk of blood-borne pathogens, personnel should employ universal precautions whenever working with primary human tissue. Each institution should establish standard operating procedures to avoid contamination and the human tissue should meet quality control criteria outlined by the authorities, including tests confirming that the tissue is free of bacterial, endotoxin, mycoplasma, or viral contaminants and has not been altered significantly (i.e., that it has been “minimally manipulated”) [4]. As per U.S.  Food and Drug Administration Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products,

Heterologous fat transfer •  Alternative source of tissue: non-available donor site; risk for the harvest •  Tissue bank

•  Immunological reaction •  Ethical aspects •  Blood-borne pathogens screen needed

adipose tissue homologous transplantation is considered minimal manipulation of tissue. This is defined for structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement of a recipient’s tissues with a “product” that performs the same basic function in the recipient as in the donor. There are increased safety and effectiveness concerns for tissues that are intended for a non-homologous use, since there is less basis on which to predict the product’s behavior. Whenever immediate harvest is not possible, or in the presence of limitation for repeated harvesting, lack of volume of tissue available, cryopreserved or heterologous sources could be options for treatment and follow the same principles of tissue processing [5]. For heterologous use, current FDA regulations determine criteria to prepare, validate, and follow written procedures to prevent infectious disease contamination during tissue processing that may be caused by a variety of infectious disease agents (virus, bacteria, fungi, and transmissible spongiform encephalopathy (TSE)associated prions). Preparation, preservation for storage, and/or removal from storage to assure the quality and/or sterility of human tissue are key factors for cryopreserved tissue and heterologous use [5]. Basic criteria to maintain quality and preserve safety of cryopreserved or heterologous transplanted tissues include screening for contamina-

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Harvest of Adipose tissue: Liposcution Dermolipectomy Donor

Adipose Tissue Processing: Sterile manipulation Transfer tissue to tubes Washing and/or centrifuging Antibiotic/antifungic Cryopreservation and thawing

Implantation: Injection or Placement

Fig. 5.1  Standard processing techniques for adipose tissue: tissue harvesting; tissue processing; tissue injection

tion, identification of viability of the cells present in the tissue, precise and objective follow up and measure of outcomes, assessment and treatment of complications are important for any tissue transplantation and should be kept in mind for cryopreserved and heterologous use [5] (Fig. 5.1).

5.1.3 Experimental Studies Providing Proof of Principles for Cryopreservation and Heterologous Use of Fat Although the technique of fat transfer has gained significant popularity in recent decades, adipose tissue viability and graft retention remain unpredictable. This variability in outcomes has required the introduction of additional procedures. Experimental studies have now lent support to the functional properties of adipose tissue, resulting in a better understanding of its mechanism(s) of action and the codification of a minimum criteria for result assessment [6]. Different processing methods have been developed to preserve viability, minimize contaminants in the transferred tissue, reduce false volume and pro-inflammatory material, and preserve adipose-derived mesenchymal stem cells [1]. Cell yield and viability can be assessed

after processing the fat harvested by microscopic and flow cytometric assays [7]. Additionally, screening for bacterial contaminants should be performed before reinjecting the fat to the recipient [1]. The use of controlled protocols with well-­ defined cryopreservation solutions, storage temperature, thawing method and injection showed that although some cell viability is lost with tissue adipose tissue cryopreservation, it still preserves some degree of viable cell yield, intact cell surface markers, and proliferations and differentiation capabilities of the adipose-derived stem cells giving proof of principle data [1]. The majority of animal models use heterologous fat transfers or xenografts as opposed to syngeneic or autologous fat. These studies have resulted in new insights relating to tissue encapsulation and the contribution of neovascularization to the survival of the transferred tissue by proving the maintenance of cell yield and viability, the identity of the cells with expression of surface markers, the presence of adipose cells in a well vascularized niche allowing receptor adipose cells to repopulate the grafted tissue [1]. In addition, the heterologous adipose-derived stem cells in experimental models show the possibility of the use of heterologous cells that, with the culture passages, lose identification of the donor

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FAT FG

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CAT FG

Fig. 5.2  Experimental studies set the basis for the safe and standardized use of cryopreserved or heterologous fat transfer. This figure shows the aspects of Fresh Human Adipose Tissue and Cryopreserved Human Adipose

Tissue injected in mice as Heterologous Fat Grafts 9 weeks after implantation in mice showing viable tissue. The harvested tissue was viable with a pseudocapsular formation for both groups

maintaining the functional characteristics allowing favorable results [8]. These findings provide the basis for the clinical use of transplanted tissue and the long-term engraftment of viable cells within the transplant or through the repopulation and migration into the transplanted scaffold by the host’s innate stromal/stem cells [1] (Fig. 5.2).

repeatedly as needed with no risk of allergic reaction or rejection. Autologous fat transfer has been used for facial rejuvenation, facial contour abnormalities secondary to trauma, oncologic resection, involutional disorders, congenital anomalies, breast augmentation, and reconstruction and augmentation of upper and lower limbs. In addition, fat grafting has been shown to improve soft tissue damage caused by radiation therapy and to accelerate the recovery of chronic wounds [4, 6, 10–12]. Limiting factors to the use of fat transfer include partial resorption, necrosis, unsatisfactory end shape, volume loss, and unwanted increased volume due to patient weight gain. Due to these limitations, there remains a need to uncover the better options for fat harvesting and transference bringing tissue cryopreservation and heterologous fat transfer as options to overcome and improve results. The context of FDA Current Good Tissue Practice Guidance for Industry regarding tissues

5.2

Aesthetic, Reconstructive, and Functional Clinical Uses of Autologous Fat Transfer

The use of soft tissue fillers to address volume and contour anomalies has gained increased popularity in the USA for aesthetic and reconstructive surgery. According to statistics from the American Society for Plastic Surgeons, in 2018, more than 70,000 fat transfer were performed in the USA [9]. Autologous fat is, in many ways, an ideal filler: it is readily available, biocompatible, inexpensive, and can be harvested easily and

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establishes that the set of processing activities to be performed on Human Tissues or Tissue-Based Products taken together would be considered as subject to regulations under Title 21 Code of Federal Regulations, Part 1271. These would include processing of cell products such as red cell or plasma removal, cell selection, and cryopreservation for long-term storage. Under these directives, the heterologous use of adipocytes or any of it derivatives will require further testing and FDA approval [5].

5.3

 ryopreserved or Frozen Fat C Transfer: Is It Possible?

Cryopreservation of the harvested fat has the potential to reduce risks inherent to repetitive liposuction procedures, thereby making it safer to perform sequential graft procedures necessary to achieve the desired final volume or, alternatively, to develop a patient specific tissue bank. There are multiple clinical uses for cryopreserved tissue as blood, bone, corneas, eggs or embryos, ovarian tissue for in  vitro treatments [1]. Even though the protocols for cryopreservation of cells, embryos, sperm, ovarian tissue are normally vitrification (Fast Freezing technique), for fat tissue, the preferred technique so far is slow cooling cryopreservation technique in the presence of a Cryopreserving Protecting Agent, such as Dimethyl Sulfoxide (DMSO), to prevent or reduce cytotoxicity, and without the direct contact with Liquid Nitrogen. Despite much progress, it remains difficult to effectively preserve with good viability and function many tissues and organs. The difficulties are even more severe for solid organs and vascularized composite allograft tissues, which currently are limited to hours of viability [1]. The remaining challenges for developing improved methods of biopreservation, approaches leveraged by inspiration in nature, nanotechnology, the thermodynamics of pressure, and several other key fields will improve tissue and organ transplantation, regenerative medicine, and drug discovery. Almost all of these novel approaches are conceived and designed to circumvent the

barriers that have delayed the long-anticipated goal of biobanking to alleviate the global shortage of organs for transplantation [1]. While multiple authors have described different methods for the storage of the fat, this body of literature lacks a consensus metric(s) for assessing outcomes in a quantitative manner. Experimental protocols described earlier in this chapter should be taken in mind to create more thorough clinical reports regarding the use of cryopreserved adipose tissue including implementation of nontoxic cryopreservation agents, controlled-rate slow freezing, temperature of preservation, length of time for preservation, screening for blood-borne pathogens, definition of cell viability, and volume retention for proper control of outcomes [1]. A limited number of case reports have described the use of cryopreserved fat grafts in a clinical setting [1]. One case report described the complication of a periorbital lipogranuloma following the injection of cryopreserved autologous fat into the patient’s forehead. Of note, this study was not supported by a description of any previous data supporting the clinical use of cryopreserved adipose tissue for fat grafting. Furthermore, the report contained no details of the method used for the tissue cryopreservation, no discussion of whether the relationship between the clinical complication and the transplant of the cryopreserved tissue was causal or correlative, and the authors were uncertain if the granulomas occurred at the site of the cryopreserved tissue injection, leading them to postulate that tissue migration may have occurred [13]. A second clinical report evaluated a tissue “cocktail” containing dermis, fascia, and fat obtained from excised scar tissue, tissue from abdominoplasty, or tissue from reduction mammoplasty. This “cocktail” was used either as a fresh graft or after storage in liquid nitrogen at −196  °C without any cryoprotective agent (CPA) followed by thawing by sequential transfer to refrigerators at −80 °C, then −15 °C and finally at room temperature for an hour prior to injection. The “cocktail” was used in repeated autologous injections after 3 or 6  months in a

5  Adipose Tissue Transplantation: Autologous Versus Cryopreserved (Frozen) Versus Heterologous…

total of 5199 cryopreserved fat or tissue cocktail in intervals of 1–12 months in 2439 patients in a 10 years clinical experience; however, no reference was made to the amount of cryopreserved tissue transplanted or the number of sessions. Satisfactory clinical outcomes were based solely on subjective doctor and patient opinions as well as pre-operative and post-operative photographs. No objective analyses of outcomes, tissue composition, viability, or volume were presented [14]. In a third clinical report, Ohashi described a detailed protocol for cryopreserved adipose tissue clinical use in combination with fresh adipose tissue. Lipoaspirate was harvested using the Coleman’s technique and cryopreserved in 5 mL vials with CPA containing DMSO and trehalose for variable amounts of time in liquid nitrogen (196 °C). After thawing in a water bath, he performed fat transfer over 1–7 sessions for face rejuvenation in 173 patients. While the initial session was routinely performed using fresh lipoaspirate, all subsequent sessions relied on cryopreserved tissue. The fat tissue was preserved for all the patients. Then the author used cryopreserved autologous adipose tissue in small amounts for 240 applications. The volume injected ranged from 0.2–24.0  mL in different areas of the face. No complications were reported with the use of cryopreserved fat such as infection or fat necrosis, for all patients. The treatment outcomes were assessed subjectively by the patients and a peer Plastic Surgeon. The study concluded that the results were consistently good with no adverse effects; however, neither objective quantification nor long-term follow up observation were employed, thereby limiting the conclusions of the study [15]. Absence of details concerning adipose tissue cryopreservation methods and of tissue characterization pre- and post-implantation makes it difficult to analyze the impact of the adipose tissue cryopreservation on outcomes and any associated complications. Since no adipose tissue cryopreservation method has been universally accepted in the literature, it is imperative that future clinical studies incorporate a detailed study design. Specifically, the design needs to

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standardize the following procedures and metrics: the harvesting method, volume assessment, initial processing, in  vitro and in  vivo viability studies characterizing the fresh tissue prior to cryopreservation, the composition of the cryoprotective agent cocktail, the method used to freeze the samples, the storage temperature, the length of the cryopreservation (short- or long-­ term), the thawing method, the dilution of the cryopreservation agent, in vitro viability studies after cryopreservation and in  vivo use of the cryopreserved tissue. Only when all of these parameters are validated and independently reproduced by independent laboratories will it be possible to assess the safety and efficacy of transplanted cryopreserved adipose tissue. This clinical translation should be carried out in accordance with evidence based medical practices using randomized controlled study designs with blinded controls whenever possible [1].

5.4

 eterologous Fat Transfer: Is H It Safe?

As cryopreservation, a tissue bank with a ready to use product is the ideal solution for reconstruction and regenerative surgery but always focusing in patient safety. Innumerous heterologous flaps have been described as reconstructive options for severely ill patients. It has to be kept in mind that the use of heterologous tissue comes with legal and ethical aspects regarding the need for immunosuppression [16]. The goal of plastic surgery to replace with similar tissue is best achieved with composite tissue allotransplantation to reconstruct absent, damaged, or nonfunctional portions of the body. In the context of non-life-threatening deformities, it is still an experimental reconstructive procedure. Current surgical technique has allowed optimal outcomes in patients with massive facial and/or upper extremity defects. Recent advances in transplant immunology are driving a paradigm shift, from one of immunosuppression to one of immunoregulation. The result ultimately will likely benefit not only CTA but also all of transplant medicine by reducing morbidity from

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the antirejection regimens. Ethical arguments are still made both for and against the use of potentially life-threatening immunosuppressive regimens in situations of non-life-saving transplantation [16]. The patient selection criteria for this type of procedure and their mandatory ethical justification for clinical trials are as follows: unamenable to conventional reconstruction, capacity to understand and especially uncertainty, functional deficits, patient has realistic functional/physical goals, good coping skill, compliant patient after the procedure [16]. There are a limited number of studies in the literature regarding clinical heterologous fat transfer and the unsatisfactory outcomes highlight the need for investigation to create evidence to provide patient safety. Haik, J, et  al. reported a case of a cadaver fresh-frozen fat graft of an undefined area and volume and cryopreserved for an unknown period of time before implantation. The patient had received the tissue as a breast prosthesis by another surgeon and was seen 8 years afterwards. The authors commented that this technique had been widely used in former Soviet Union. The patient reported satisfaction with the result for the first 5 years until firmness, deformation and pain developed, ultimately requiring removal of the tissue. The macroscopic aspect of the extracted tissue appeared as fat tissue with partial fat necrosis, the presence of a silicone capsule was excluded and confirmed a fibrous fat tissue was identified on microscopic examination. A sample of removed tissue was sent for DNA characterization against a patient blood sample, confirming the heterologous origin of the tissue [17]. In a commentary letter, Shakhov analyzed the previous case report and stated that there were no other case reports describing the utilization of cadaver tissue as heterologous graft. He elaborated that the heterologous fat tissue allotransplant had suffered a chronic rejection by the recipient’s host immune system leading to encapsulation of the “foreign body” with the maintenance of residual viable tissue within the core of the mass [17].

Another case report used adipose tissue from one identical twin to another in order to treat lipodystrophy in the other HIV+ twin following anti-retroviral drug therapy for 18 years. A stable result was observed after 14 months of the transplant. The transplanted area was assessed by ultrasonographic measurement of dermal and subcutaneous thickness and visual analog scale score from before to 14 months after transplantation improved. The result might be related to the sympathetic nervous system denervation related to the HIV anti-retroviral medication may have protected the graft from lipolysis that would otherwise have been induced by humoral factors and autonomic neural regulation [18]. While heterologous fat grafting might increase access to adipose tissue for those patients where the desired volume is not available or there are contraindications for the harvesting procedure, its use contradicts the initial principles supporting autologous fat transfer; namely safety, reduced or absent risk for allergic reactions or rejection. Indeed, the ethical aspect of this clinical procedure can be challenged on the basis of potential risk of infection, rejection, need for immunosuppressant medication, and/or unpredictable donor–recipient anatomical compatibility. The recognition of decellularized adipose tissue as a scaffold allowing repopulation of the implanted material with receptor cells might be a more feasible use for heterologous graft as an “off-the-shelf” product available for broader clinical use without the need of immunosuppressant drugs and reduced risks of transmission of diseases [19].

5.5

Discussion

While adipose tissue transplantation is an important tool in Plastic Surgery, there remains a need to standardize procedures as well as to conduct thorough studies optimizing tissue cryopreservation and heterologous use of fat to provide consistent and safe outcomes regarding volume and functional properties. So far, there is no proof of

5  Adipose Tissue Transplantation: Autologous Versus Cryopreserved (Frozen) Versus Heterologous…

concept and body of investigation enough to compare these promising techniques with the traditional fresh autologous fat transfer. It is unlikely that allogeneic adipose tissue will be used routinely as an alternative source to autologous adipose tissue for fat grafting due to the immune substantial barriers and evidence to suggest that it will lead to morbidities (cysts, necrosis, calcification) [18]. Also, cryopreserved tissue would impose manipulation and storage that might increase clinical practice costs [1]. The goals may eventually be promoted by Regenerative Medicine and Tissue Engineering advancements and are the Future Challenges in Fat Transplantation. By incorporating the principles of cellular and molecular biology, material science, and bioengineering, these emerging disciplines may eventually advance Plastic Surgery’s objective to exploit the healing and regenerative properties of cryopreserved and heterologous adipose tissue in a processed form of “off the shelf” product-like scaffolds that might be even combined with Stromal Vascular Fraction cells, Adipose-derived stem cells, or exosomes to heal and restore function.

5.6

Future Challenges

Alternative materials that are under development and might overcome the needs for additional sources of tissue. Adipose-derived exosomes can potentially substitute adipose-derived cells as source of paracrine factors that will promote angiogenesis and adipogenesis [20]. Decellularized adipose tissue derived hydrogels and scaffolds are being developed as biomaterials that can augment or substitute autologous adipose tissue with respect to soft tissue reconstruction. When implanted alone or in combination with cells or exosomes, they can provide a foundation for the growth of new adipose depots in  vivo, particularly after host derived cells are recruited into the new microenvironment [20].

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These types of products, alone or in combination with autologous lipoaspirate grafts, will provide a basis for cosmetic and reconstructive repair of soft tissue defects. It is likely that they will improve implant volume retention and inherent cell viability by improving vascularity of the implant, recruiting host cells locally and accelerating the remodeling and differentiation processes within the grafted tissue.

5.7

Conclusion

Tissue cryopreservation and heterologous tissue are considered alternative sources of adipose tissue for transplantation in cases where harvesting is not possible, or the volume needed is not available, following strict protocols. There remains a need for continued research into alternative sources of freshly harvested autologous adipose tissue for purposes of cosmetic and reconstructive engraftment. In the near future, tissue cryopreservation presents an option in cases where tissue harvest can be conducted only on a single occasion. Under these circumstances, the excess tissue can be cryostored for future applications. In contrast, allogeneic adipose tissue presents substantial immune complications between donor and host that can lead to co-morbidities including cyst formation, calcification, necrosis, and rejection. In the longer term, the results of ongoing research suggest that additional materials will become available. These will include (a) adipose-derived exosomes which will incorporate the paracrine factors (adipokines, cytokines, and microRNAs) modulating stromal/stem cell function and differentiation and (b) adipose-­ derived decellularized extracellular matrix proteins which will mediate signal transduction across cell membranes to promote adipogenesis, angiogenesis, and vascularization required for long-term tissue growth and retention. Both the short- and long-term outcomes will require considerable research and development within both academia and industry to ensure the development of safe and effective therapies warranting regulatory approval.

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References 1. Zanata F, Bowles A, Frazier T, Curley JL, Bunnell BA, Wu X, et al. Effect of cryopreservation on human adipose tissue and isolated stromal vascular fraction cells: in  vitro and in  vivo analyses. Plast Reconstr Surg. 2018;141(2):232e–43e. 2. Glashofer M, Lawrence N.  Fat transplantation for treatment of the senescent face. Dermatol Ther. 2006;19(3):169–76. 3. Agostini T, Lazzeri D, Pini A, Marino G, Li Quattrini A, Bani D, et  al. Wet and dry techniques for structural fat graft harvesting: histomorphometric and cell viability assessments of lipoaspirated samples. Plast Reconstr Surg. 2012;130(2):331e–9e. 4. Rubin JP, Gurtner GC, Liu W, March KL, Seppanen-­ Kaijansinkko DR, Yaszemski MJ, et  al. Surgical therapies and tissue regeneration: at the intersection between innovation and regulation. Tissue Eng Part A. 2016;22(5–6):397–400. https://doi.org/10.1089/ ten.TEA.2016.0002. 5. Administration FaD.  Guidance for industry. Current Good Tissue Practice (CGTP) and additional requirements for manufacturers of human cells, tissues, and cellular and tissue-based products (HCT/Ps) December 2011. https://www.fda.gov/regulatory-­ information/search-­f da-­g uidance-­d ocuments/ current-­g ood-­t issue-­p ractice-­c gtp-­a nd-­a dditional-­ requirements-­m anufacturers-­h uman-­c ells-­t issues-­ and. 6. Gimble JM, Katz AJ, Bunnell BA.  Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100(9):1249–60. 7. Gaiba S, Franca LP, Franca JP, Ferreira LM. Characterization of human adipose-derived stem cells. Acta Cir Bras. 2012;27(7):471–6. 8. Freitas AL, Oliveira e Silva M, Matsumoto PM, Han SW, Ferreira LM.  Experimental model of obtaining tissue adipose, mesenchymal stem cells isolation and distribution in surgery flaps in rats. Acta Cir Bras. 2014;29(Suppl 2):29–33.

F. Zanata et al. 9. Surgery. ASfAP.  Cosmetic surgery national data bank: statistics 2018. http://www.surgery.org/media/ statistics. 10. Coleman SR.  Structural fat grafts: the ideal filler? Clin Plast Surg. 2001;28(1):111–9. 11. Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/ stromal cells. Aesthet Plast Surg. 2008;32(1):48–55; discussion 6–7. 12. Tholpady SS, Llull R, Ogle RC, Rubin JP, Futrell JW, Katz AJ. Adipose tissue: stem cells and beyond. Clin Plast Surg. 2006;33(1):55–62, vi. 13. Heo JH, Shin J, Choi GS, Byun JW. Periocular lipogranuloma after cryopreserved fat injection into the forehead. Dermatol Surg. 2019;45(12):1723–5. 14. Erol OO, Agaoglu G. Facial rejuvenation with staged injections of cryopreserved fat and tissue cocktail: clinical outcomes in the past 10 years. Aesthet Surg J. 2013;33:639–53. 15. Ohashi M.  Fat grafting for facial rejuvenation with cryopreserved fat grafts. Clin Plast Surg. 2020;47(1):63–71. 16. Siemionow M.  The decade of face transplant outcomes. J Mater Sci Mater Med. 2017;28(5):64. 17. Shakhov AA. Fat transplantation and breast augmentation. Aesthet Plast Surg. 2002;26(4):323–5. 18. Guaraldi G, Squillace N, De Fazio D, Prestileo T, Palella F.  Heterologous fat transplantation for the treatment of HIV-related facial lipoatrophy. Ann Intern Med. 2009;150(1):61–3. 19. Thomas-Porch C, Li J, Zanata F, Martin EC, Pashos N, Genemaras K, et al. Comparative proteomic analyses of human adipose extracellular matrices decellularized using alternative procedures. J Biomed Mater Res A. 2018;106(9):2481–93. 20. Casado-Díaz A, Quesada-Gómez JM, Dorado G. Extracellular vesicles derived from mesenchymal stem cells (MSC) in regenerative medicine: applications in skin wound healing. Front Bioeng Biotechnol. 2020;8:146.

6

Fluid Balance, Electrolytes, and Anesthetic Options in Regenerative Surgery and Fat Grafting Lyly Nguyen, Vincent Riccelli, and K. Kye Higdon

Key Messages • Liposuction can be performed safely as outpatient surgery in a variety of surgical settings with a relatively low complication rate. However, severe complications, both medical and surgical, are possible, and can be avoided with good clinical decision-making and discretion. • A thorough history and physical, with a medication reconciliation including all herbal and over-the-counter supplements, is essential for optimizing both surgical outcomes and safety. • The choice of anesthesia method is determined by a variety of factors, including surgeon preference, operative setting, amount of lipoaspirate, patient positioning, and length of procedure. For large-volume liposuction, general endotracheal anesthesia is recommended under the care of a certified anesthesia provider. • Large-volume liposuction, while generally safe, has the potential to cause significant hemodynamic and metabolic shifts. If misL. Nguyen · K. K. Higdon (*) Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA e-mail: [email protected]; [email protected] V. Riccelli Vanderbilt University Medical School, Nashville, TN, USA e-mail: [email protected]; [email protected]

managed, or improperly monitored, these can cause complications as severe as kidney injury, pulmonary injury, and death. • Careful consideration should be given to both the volume of wetting solution, and the dose of local anesthetic given in liposuction. To minimize risk of hemodynamic complications, evidence-based recommendations for wetting solution include use of the superwet technique and administering 0.25 mL of intravenous crystalloid per 1 mL of aspirate >5 L. • In the hands of certified plastic surgeons, autologous fat grafting is a powerful technique in both reconstructive and aesthetic surgery that can have substantial benefits for patients in the hands of certified plastic surgeons.

6.1

Introduction

Autologous fat grafting has become a common technique for treating volume and contour abnormalities in aesthetic and reconstructive surgery. A recent survey showed that approximately 80% of plastic surgeons have used fat grafting in their practice, and, in 2018, over 258,000 liposuction cases were performed [1]. While autologous fat grafting has substantial benefits in regenerative surgical techniques, the liposuction procedures for fat harvest, as well as grafting procedures themselves can cause significant shifts in fluid

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_6

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and electrolyte balance. Patient safety is a paramount consideration in these cases. In order to safely perform this widely used procedure, surgeons should be familiar with safety guidelines, as well as management strategies, for fluid and electrolyte balance in liposuction and fat grafting.

discontinue the use of non-steroidal anti-­ inflammatory drugs (NSAIDs), aspirin products, and fish oil 3 weeks prior to surgery due to risk of bleeding. If there is a medical indication for continuation of these medications, then there should be a discussion with an appropriate specialist or primary care physician before discontinuation. Any hormone therapy (i.e., oral contraceptives and estrogens) should be 6.2 Preoperative Considerations held 4 weeks before the procedure. Smoking is a known independent risk factor Liposuction and fat grafting have been proven for complications, and the benefit of cessation of to be safely performed as outpatient surgery in all forms of nicotine for 4 weeks preoperatively is a hospital, ambulatory surgery center, or office-­ supported by level 1 evidence [1]. Patients with based surgery center. In consultation, a careful diabetes mellitus are strongly predisposed to history and physical should be performed. infection, and have increased risk of perioperaMedicine reconciliation should also review any tive death, but tight glycemic control, with hemonon-essential medicines like vitamins, miner- globin A1c less than 6.5 has been shown to als, and herbal supplements, especially those significantly reduce these risks. All patients not regulated by the Food and Drug should be assessed for the risk of deep venous Administration (FDA), which may affect bleed- thromboembolism (DVT) and prophylaxis should ing. These types of medications and supple- be guided by the Caprini risk assessment model ments should be documented during the [3]. preoperative consultation, and in many cases Physical examination should carefully inspect should be stopped prior to surgery [2] for abdominal hernias, as the most common site (Table 6.1). Antidepressants including selective of visceral perforation in liposuction is the small serotonin reuptake inhibitors (SSRIs) should be intestine. Skin quality and visceral fat compostopped 2  weeks prior to liposuction with nent, as well as rectus diastasis should also be tumescent anesthesia as they compete with documented [3]. Table 6.2 describes recommenlidocaine for liver metabolism, and increase the dations for preoperative physical exam and prerisk of toxicity [3]. Some surgeons advocate to cautions during liposuction to decrease the rare

Table 6.1  Herbal supplements with increased risk of bleeding Coumarin-containing Horse chestnut bark Sweet clover plant Sweet vernal grass leaves Sweet-scented bedstraw plant Tonka bean seeds Vanilla leaf leaves Woodruff plant

Plants inhibiting platelet function Bromelain Cayenne fruit Chinese skullcap root Danshen root Garlic Ginger Ginkgo biloba Onion Turmeric root Vitamin E

Table 6.2  Recommendations to avoid perforation of abdominal viscera Preoperative physical exam Abdominal scarring/ irregularities from previous abdominal surgeries +/− previous liposuction Umbilical, ventral, inguinal hernias, diastasis recti

Abdominal protuberance Intra-abdominal fat proportion Extra-abdominal fat proportion Abdominal wall weakness

During liposuction Orientation of cannula should tangential and not be directed towards the viscera Use of the non-­ dominant hand should always feel for the tip of any cannula

6  Fluid Balance, Electrolytes, and Anesthetic Options in Regenerative Surgery and Fat Grafting

but serious risk of abdominal perforation of viscera [4]. If a large-volume liposuction is planned, a preoperative complete blood count (CBC) to check hemoglobin and hematocrit, and a baseline basic metabolic panel (BMP) should be obtained as significant fluid shifts can occur. All patients should additionally get intravenous antibiotics, which may be guided by surgeon and institutional preference. A warming device should be used over areas not being suctioned, and wetting solution should be warmed to prevent hypothermia.

6.3

Anesthetic Options

Anesthesia choice is dependent on multiple factors (i.e., surgeon preference, anesthesia preference, expected amount of lipoaspirate, patient position, length of the procedure, and patient overall health). American Society of Anesthesiologist Physical Classification (ASA) should be determined prior to performing these

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procedures as this can influence the type of anesthesia administered. Patients can safely undergo various forms of anesthesia without one form being superior than the other. However, it is recommended to avoid epidural and spinal anesthesia for concern of hypotension and volume overload issues in an office-based setting [5]. Different forms of anesthesia types are outlined in Table 6.3 [6]. Patients undergoing autologous fat grafting can receive a preoperative anxiolytic such as midazolam, which is useful for diminishing anxiety and counteracting the hemodynamic changes of epinephrine. Clonidine (2–5 μg/kg) can also be used as an anxiolytic, and additionally is an antisialagogue. In small-volume liposuction, local anesthesia can be sufficient. This can be performed with or without mild sedation. General endotracheal anesthesia (GETA) is recommended for large-­volume liposuction (>4  L) or complex cases. These cases should be performed under a certified anesthesia provider in licensed centers. Laryngeal mask airway is generally

Table 6.3  Anesthetic options in liposuction Anesthesia type General Endotracheal Anesthesia (GETA)

Advantages Appropriate for large-­ volume liposuction Multiple areas can be treated Paralytics can be used if needed Full control of airway

Monitored Anesthesia Care (MAC) or Total Intravenous Anesthesia (TIVA)

Appropriate for small-­ volume liposuction Protection of airway reflexes without intubation Patient can respond to verbal commands Shorter recovery time Decreased operative times Less postoperative nausea and vomiting

Lumbar epidural anesthesia Local anesthesia/tumescent only

Appropriate for small-­ volume liposuction Quick recovery time No postoperative nausea or vomiting

Disadvantages Longer recovery time Requires intubation Increased postoperative nausea and vomiting Increased risk of DVT Increased cost Increased variability in hemodynamics Cannot use paralytics if needed

Can cause significant hypotension— must be used in cardiac reserve Limited by maximal dosage of lidocaine (toxicity) Treatment of one body region at a time

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sufficient for airway control should the patient be in supine positioning or a short case. However, if the patient requires prone positioning, then the patient should be endotracheally intubated for airway control. This should be under the discretion of the operating physician and anesthesiologist to choose the best modality to ensure patient safety. Propofol is a good induction choice because it is antiemetic and because of its pharmacokinetic profile. Sedation can be achieved with midazolam (0.2–0.6  mg/kg IV) and analgesia with fentanyl (0.5–2  μg/kg bolus) or remifentanil (0.05–0.1  μg/kg/min infusion), with intermittent doses of propofol (250–500 μg/kg boluses). Additionally, ketamine in low doses (0.25– 0.5  mg/kg IV) along with midazolam in the intraoperative period decreases the consumption of opioids during the case and need for pain medications postoperatively. It is with caution to use lidocaine intravenous infusion as a method of analgesia and anesthesia due to concern of lidocaine toxicity. During the procedure, standard ASA monitoring can be used, with oxygen saturation, non-­ invasive blood pressure monitoring, end-tidal carbon dioxide, electrocardiogram, and temperature probe. While central venous pressure monitoring and invasive blood pressure monitoring have been suggested, this is rarely necessary, particularly in an outpatient setting. For large-­ volume liposuction (>5  L), urine output monitoring with a Foley catheter and overnight monitoring for observation are also recommended [7]. Early ambulation in the postoperative period is advised to minimize risk of deep venous thrombosis. It is important to note that hypothermia occurs commonly in liposuction cases. This defined as core body temperature less than 36.5 °C. A reduction in body temperature over 2.7 °C can have detrimental effects on coagulation, blood loss, wound infections, and can increase risk of cardiac events. Intraoperative hypothermia can be potentiated in body contouring when large surface areas of the patient

are exposed. This is compounded by the effects of anesthesia on autonomic regulation which restrict a patient’s ability to regulate their core body temperature. It is therefore encouraged for patients to undergo prewarming with forced air for at least 1 h (i.e., Bair Hugger) in the preoperative unit, as this maneuver has been shown to significantly decrease hypothermia [5]. In addition, use of warming devices, warmed wetting solutions, and increased room ambient temperature can help reduce heat loss during liposuction. All cases should be performed in an accredited facility, equipped to manage patients based on the complexity of the procedure and patient comorbidities. Specific to this, the American Society of Anesthesiology (ASA) recommends that individuals who have moderate to severe obstructive sleep apnea should have their procedure performed in a hospital setting with the capability of overnight observation or extended recovery to avoid post-procedure respiratory or cardiac events [8].

6.4

Wetting Solution

Wetting solution in liposuction was first proposed by Klein in 1987, and the most common solutions used in liposuction are those proposed by Klein and Hunstad [7, 9]. This solution is injected through the same incisions planned for liposuction and infiltrated with a blunt-tip injection cannula (7–9 mm). Wetting solution serves multiple purposes in liposuction, including volume replacement, hemostasis, hydrodissection, and pain control. In ultrasound-assisted liposuction, it also dissipates heat and enhances cavitation. Generally, wetting solution consists of a local anesthetic (typically lidocaine), epinephrine mixed in 1  L of balanced fluid (i.e., Lactated Ringer’s or Normal Saline), with or without sodium bicarbonate, which is typically used in awake patients [5]. Marcaine is avoided due to its potential cardiac toxicity and longer

6  Fluid Balance, Electrolytes, and Anesthetic Options in Regenerative Surgery and Fat Grafting Table 6.4  Common wetting solutions Klein’s solution 1000 mL normal saline 50 mL, 1% lidocaine 1 mL, 1:1000 epinephrine

Hunstad’s solution 1000 mL lactated ringers 50 mL, 1% lidocaine 1 mL, 1:1000 epinephrine

12.5 mL, 8.4% sodium bicarbonate

duration of action [8]. Common wetting solutions are seen in Table 6.4. The recommended maximal dose of lidocaine for local infiltration is 7  mg/kg. This recommendation from the Food and Drug Administration is based on an accepted limit for epidural anesthesia, which was determined in 1948 [10]. However, recent evidence suggests that the maximum dose in tumescent anesthesia is actually much higher. Systemic toxicity of lidocaine is seen at serum levels of 6 μg/mL, and symptoms include perioral numbness, lightheadedness, paresthesia, tinnitus, blurred vision, nystagmus, ataxia, slurred speech, and confusion. Intraoperative manifestations can include arrhythmias, and high doses of lidocaine can cause tremors, seizures, with eventual cardiac or respiratory arrest. Lidocaine is metabolized by the liver using the cytochrome P450 system, and drugs that are also metabolized by this system will compete with lidocaine and increase serum levels [5]. However, as lidocaine is infiltrated with dilute epinephrine, the local vasoconstriction provided by epinephrine reduces the systemic uptake of the drug from the interstitial space [10]. Additionally, a proportion of the wetting solution is removed with liposuction and sequestered by the surrounding fat [10]. These coupled with the relative avascularity of the subcutaneous fatty layer significantly reduces the amount of lidocaine in the wetting solution that makes it into the systemic circulation. There is no clinically significant difference between using normal saline and lactated Ringers as the solvent for tumescent anesthetic. Some

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authors note the burning sensation when injecting lidocaine in normal saline (a result of the acidity of lidocaine in non-buffered solution) and the added sodium load seen in normal saline and prefer using lactated Ringers as the solvent in their practice [5]. Since tumescent anesthetic infiltration in large-volume liposuction can be seen as analogous to a slow intravenous fluid infusion, a balanced electrolyte solution is, in theory, preferable. The electrolyte solution used may be guided by surgeon and facility preference. When tumescent anesthesia is administered with liposuction, peak serum lidocaine levels occur between 8 and 12  h after infiltration, simulating a steady lidocaine infusion during the case [10]. A study performed on human volunteers showed that without liposuction, the maximum safe dose for lidocaine infiltration was 35 mg/kg, however exceeded 45 mg/ kg when liposuction was used [10]. Currently, the American Society of Plastic Surgeons guidelines recommend 35 mg/kg as the maximum dose [1]. Although peak levels have been shown to be below the level of toxicity, there should be caution in using wetting solutions with lidocaine in patients with cardiac history or diminished cardiac reserve. Lipid emulsion injection or intralipid (20% 1.5  mL/kg) can reverse lidocaine toxicity by extracting the local anesthetic from plasma [1]. Propofol (20–50 mg) can halt seizure activity, and in the awake patient, rapid sequence intubation may be required, but treatment with intralipid to reverse cardiac toxicity should be the first priority [5]. There are four techniques described for the ratio of wetting solution infiltrated to fat aspirated: dry, wet, superwet, and tumescent (Table  6.5). Dry technique utilizes no infiltrated solution and is therefore the most traumatic, resulting in the most blood loss (20–40% of aspirated volume). This method has rare utility in current practice. Wet technique utilizes a standard 200–300 mL of solution per area, regardless of the amount of

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62 Table 6.5  Proportion of wetting solution Technique Dry

Definition No infiltration

Advantages Fastest

Wet

200–300 mL local anesthesia infiltrate per area, regardless of the amount of lipoaspirate to be removed 1:1 ratio of infiltrate to lipoaspirate

Less blood loss with more analgesia compared with dry technique

Superwet

Tumescent

2–3:1 ratio of infiltrate to lipoaspirate

Evidence-based approach for minimizing blood loss (1%) and maximizing analgesia, without using excess fluid Minimizes blood loss (1%) and maximizes analgesia

lipoaspirate. This method has a blood loss of 4–30% of the volume of aspirate and is not commonly performed. Superwet solution employs a 1:1 ratio of infiltrate to aspirate, while tumescent uses a 2:1 to 3:1 ratio of infiltrate to aspirate. Both of these most commonly performed techniques result in a blood loss of 1% of aspirated volume [1]. Although McKee et al. demonstrated that maximal vasoconstriction from the effects of epinephrine occurs at 25.9 min, it is safe to proceed after 7–10 min of infiltration [11]. The maximum recommended amount of tumescent solution infused is determined by the amount to be aspirated. Evidence-­based recommendations for liposuction suggest use of the superwet method as opposed to the tumescent method, as both confer an equivalent risk of blood loss, but tumescent anesthesia increases the risk of complications of hypervolemia [8].

6.5

Disadvantages Most traumatic, 20–40% of aspirated volume is blood 4–30% blood loss in lipoaspirate

Indications Rarely used in clinical practice

None

First-line technique recommended for both small and large-volume liposuction

Increased risk of fluid overload with higher volumes of infiltration

Still commonly used in both small and largevolume liposuction, but care should be taken to minimize infiltrate volumes to lower risk of fluid overload

Rarely used in clinical practice

Fluid Balance

Due to the need for wetting solutions, liposuction has the potential to cause significant hemodynamic changes through large-volume fluid shifts [12]. Fluid shifts can manifest as extremes of fluid status on either end of the spectrum: hypovolemia due to under-resuscitation or pulmonary edema and congestive heart failure due to over-­ resuscitation [11]. It is important for the surgeon and staff to record the amount of wetting solution and lipoaspirate of body area to ensure patient safety. It is also important for the anesthesia provider to be familiar with these types of procedures and provide supplemental fluids appropriately. Kenkel et al. performed a study on five female volunteers who underwent liposuction and monitored multiple hemodynamic parameters with a pulmonary artery catheter [12] (Table 6.6).

6  Fluid Balance, Electrolytes, and Anesthetic Options in Regenerative Surgery and Fat Grafting Table 6.6  Hemodynamic changes during liposuction Hemodynamic parameter Heart rate

Mean arterial pressure

Central venous pressure Stroke volume index

Systemic vascular resistance

Right ventricle stroke work index

Change with liposuction Immediate elevation in heart rate, peaking at 8 h postoperatively Immediate decrease after induction, followed by a second decrease 1–2 h after induction, steadily increasing postoperatively up to 24 h after surgery Slight elevation from preoperative level Immediate increase from preoperative value, sustained intraoperatively and postoperatively Decreased at induction, decrease intraoperatively lower than baseline, minimum at 24 h postoperatively Increased throughout the case and peaks 24 h postoperatively

Traditionally, liposuction volumes greater than 5  L (large-volume liposuction) were thought to confer greater risk of surgical complications [8]. As large-volume liposuction has the potential to cause significant alterations in hemodynamic parameters, the patient’s volume status must be monitored meticulously with such strategies as urinary catheterization, noninvasive hemodynamic monitoring, and constant communication with anesthesiologist, as appropriate [11]. Fluid management should be calculated with body weight dependent intravenous maintenance fluids, third space loss, volume of wetting solution infiltrated, and total volume of lipoaspirate. Body Mass Index (BMI) can increase complications in surgery. However, in a recent large study of complications and outcomes following liposuction, the overall rate of medical complications following liposuction, related to fluid and electrolyte balance was very low (0.1%) regardless of BMI. Increased BMI did not increase risk of medical complications, but did increase risk of

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surgical complications, namely seroma [13]. For this reason, BMI likely does not significantly impact the fluid balance, electrolyte balance, or anesthetic options in liposuction, but further research could provide conclusive evidence on this topic. Some authors have suggested that increasing operation time can predict increased fluid loss following liposuction, and this can affect metabolic profiles. However, evidence strongly supports the fact that the most significant shifts in both fluids and electrolytes happen several hours postoperatively, with peak urine output occurring at 6 h. The infiltration of tumescent anesthesia is thought to mimic a fluid bolus that the patient receives several hours postoperatively [14]. One study suggested that there are actually two peaks in urine output that can be expected in liposuction: one shortly after infiltration of tumescent anesthesia, followed by a decrease in urine output, and then a second peak in urine output postoperatively caused by the application of compressive garments following liposuction, which drives interstitial fluid into the intravascular space [14]. In large-volume liposuction, it is estimated that approximately 20% of wetting solution is aspirated. The patient can receive several liters of fluid in the form of tumescent anesthesia, which creates the potential for volume overload both intraoperatively and postoperatively if fluid balance is not astutely managed. This can cause damage to the lungs, kidneys, and heart. Therefore, patients undergoing high volume ­liposuction should receive a Foley catheter for monitoring. Based on concern for overhydration with the tumescent approach, multiple recommend use of the superwet infiltration technique. A commonly used fluid management strategy is based on the intraoperative fluid ratio in liposuction, which is equal to the sum of the intravenous fluid volume and the volume of local infiltrated, divided by the volume aspirated.

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Intraoperative fluid ratio =

Intravenous fluid volume + Infiltrate Aspirate

Rohrich et al. recommended the intraoperative fluid ratio of 1.8 in small-volume liposuction and 1.2  in large-volume liposuction [11]. Current evidence-based recommendations advocate that any aspirate under 5 L, the patient should receive maintenance fluid plus subcutaneous infiltrate. For aspirate over 5 L, patients should obtain maintenance fluid plus subcutaneous infiltrate plus 0.25  mL of intravenous crystalloid per 1  mL of aspirate >5  L [11]. These recommendations should serve as a general guideline for fluid management in liposuction cases, but readers are encouraged to exercise sound clinical judgment based on each patient’s individual needs [8].

6.6

Changes in Electrolytes

The shift of a large volume of fluid from the interstitium into the systemic circulation causes a significant alteration in the patient’s metabolic profile. Several studies have examined the effect of large-volume liposuction on electrolyte and plasma enzyme analyses (Table 6.7) [15]. Patients can undergo a slight decrease in sodium, usually noted postoperatively, which is likely due to patients receiving hypotonic intravenous fluid during surgery. This can be subsequently exacerbated by water consumption postoperatively. Recommendations for electrolyte sports drinks can mitigate this exacerbation. Potassium levels can decrease intraoperatively, and then normalize postoperatively. Hypokalemia secondary to elevated epinephrine levels and catecholamine stimulation can increase susceptibility to ventricular arrhythmias. Large-volume liposuction is therefore contraindicated in patients with significant cardiovascular disorders, which should be identified in the initial history and physical [11]. Carbon dioxide levels



have been noted to decrease on induction of general anesthesia, but these usually normalize 4 h postoperatively. In order to mitigate the risk of complications, the anesthesiologist should maintain normocarbia. Blood urea nitrogen levels can decrease postoperatively, which is likely due to hemodilution, and there is usually no significant accompanying change to chloride or creatinine. Aspartate aminotransferase and alanine aminotransferase both can substantially increase postoperatively, continuing up to 35 h postoperatively. This has been attributed to fat cellular damage during liposuction. Creatine kinase also has been demonstrated to increase postoperatively, peaking at 12 h and then normalizing, due to extrusion of the enzyme from adipocytes during liposuction. A thorough understanding of the complex effects that this procedure has on electrolyte biology and homeostasis cannot be underemphasized.

6.7

Fat Grafting

There is no current consensus in the literature regarding the maximum recommended amount of grafted fat. The amount of fat infiltrated should be tailored to restoring the volume or contour defect present, with the knowledge that 40–60% of the volume of grafted fat will be lost over time. Determination of lipoaspirate and the amount of infiltration of wetting solution needed are thus dependent on how much autologous fat one may need for fat grafting. Some common areas for fat grafting are the face, breast, and buttock regions. Facial fat grafting volumes depend on the anatomic zones of the face need that correction. Martin et al. describe fat grafting of the face in 20 anatomic regions. These regions require anywhere 0.5–9  cc per region and while uncommon, if all 20 zones

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Table 6.7  Electrolyte changes in liposuction Electrolyte or enzyme Change Sodium Slight ↓ Potassium Chloride Venous carbon dioxide Blood urea nitrogen Creatinine Albumin Total protein Aspartate aminotransferase Alanine transaminase Creatine kinase Calcium Hemoglobin

↓ then ↑ then normalize – ↓ then ↑ −/↓ – ↓ ↓ ↑

Explanation Hypotonic intravenous fluid administration, retained saline before surgery, patients drinking water postoperatively High dose epinephrine → catecholamine stimulation Respiratory alkalosis due likely to hyperventilation from general anesthesia and artificial ventilation Hemodilution Reduced preoperative intake, decreased synthesis, catabolism, redistribution, hemodilution Cellular damage during liposuction

↑ ↑, peaking at 12 h postoperatively, then ↓ ↓ –

Extruded from adipocytes during liposuction, may also signify trauma to underlying muscle Unknown

were anticipated to be grafted to their maximal extent, then one would require approximately 120  cc of total fat [16]. Fat grafting to the breasts or buttocks require more fat harvest. Obtaining adequate soft tissue coverage of an implant has been a persistent challenge in breast augmentation, particularly in thin patients with severe hypomastia. A paucity of breast tissue and subcutaneous fat can portend a poor cosmetic result despite excellent enhancement of volume and projection, due to the inability to hide the presence of the prosthesis under the patient’s native tissue. This mismatch between size and soft tissue coverage results in implant palpability, edge visibility, and often rippling which can be corrected and with autologous fat grafting. Based on a systematic review, the average amount of fat grafted in each breast is approximately 109–145 mL of fat per breast [17]. Buttock augmentation requires a significantly higher volume of fat, with typical augmentation averaging 300–400  mL per side but can range from 175  mL to about 1300  mL, depending on the patient’s desires and the amount of donor fat available [18].

Little is currently known about the effects on fluids and electrolytes with grafted fat. In an avascular fat graft, only the peripheral layer of adipocytes survives the hypoxia. The deeper layer is the regenerative zone where only adipose stem cells revascularize. Deep to the regenerative zone is the necrotic zone where there is no survival of cells. Techniques should be employed to allow the injected fat to be in direct contact with vascularized tissue to allow for the greatest survival. Revascularization of the fat transfer depends on a maximal 1.6 mm graft-to-recipient interface [19]. In the event that grafted fat does not become vascularized (i.e., fat necrosis), nodules formed by the innermost portion of the fat necrotizing zone can occur. Due to the intimate relationship of fat metabolism and inorganic phosphate, there is locally increased concentrations of phosphate which may provide an environment of calcium mineralization around the necrotic zone which can lead to calcification of the cyst wall. In small fat necrosis these effects may not be apparent as the necrotizing zone can be absorbed by the body in a short amount of time. The effect of inorganic phosphate is thought

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66 Table 6.8  Electrolyte changes in fat grafting Electrolyte or enzyme Calcium Phosphate

Change ↑ (localized) ↑ (localized)

Explanation Increased due to phosphate Increased with lipolysis

to be transient and no calcification would form. In contrary, in large fat necrosis, the necrotizing zone is large enough that the absorption of necrotic fat grafting could not be performed in a short enough amount of time and this could lead to calcium deposition in the cyst wall. Although these effects are hypothesized on the basis of pathologic calcification of other conditions such as breast cancer, trauma, and arteriosclerosis, the electrolyte disturbances would be localized with inconsequential effects systemically (Table 6.8); however does give insight to the possible causative factor behind fat necrosis [20].

6.8

Conclusion

Regenerative surgical effects from liposuction and fat grafting are powerful and can have substantial benefits to patients. These procedures have been proven to be very safe, especially in the hands of certified plastic surgeons and anesthesia providers, and when performed in accredited facilities. The complex interactions that preoperative medications, intraoperative events such as type of anesthetic used, wetting solution and volume required, fluid dynamics and electrolyte changes, must be understood to accomplish the goal of providing safe and effective care for our regenerative surgery and medicine patients.

References 1. Kling RE, Mehrara BJ, Pusic AL, Young VL, Hume KM, Crotty CA, et al. Trends in autologous fat grafting to the breast: a national survey of the American society of plastic surgeons. Plast Reconstr Surg. 2013;132(1):35–46. 2. Chang LK, Whitaker DC. The impact of herbal medicines on dermatologic surgery. Dermatol Surg [Internet].

2001;27(8):759–63. [Cited 2020 Mar 4]. http://doi. wiley.com/10.1046/j.1524-­4725.2001.01089.x. 3. Chia CT, Neinstein RM, Theodorou SJ.  Evidence-­ based medicine: liposuction. Plast Reconstr Surg. 2017;139(1):267e–74e. 4. Zakine G, Baruch J, Dardour JC, Flageul G. Perforation of viscera, a dramatic complication of liposuction: a review of 19 cases evaluated by experts in France between 2000 and 2012. Plast Reconstr Surg [Internet]. 2015;135:743–50. [Cited 2020 May 12]. Lippincott Williams and Wilkins. http://www. ncbi.nlm.nih.gov/pubmed/25719693. 5. Sood J, Sethi N, Jayaraman L. Liposuction: anaesthesia challenges. Indian J Anaesth. 2011;55(3):220. 6. Failey C, Aburto J, De La Portilla HG, Romero JF, Lapuerta L, Barrera A. Office-based outpatient plastic surgery utilizing total intravenous anesthesia. Aesthet Surg J. 2013;33(2):270–4. 7. Hunstad JP.  Tumescent and syringe liposculpture: a logical partnership. Aesthet Plast Surg [Internet]. 1995;19(4):321–33. [Cited 2020 Mar 4]. http://www. ncbi.nlm.nih.gov/pubmed/7484470. 8. Stephan PJ, Kenkel JM.  Updates and advances in liposuction. Aesthet Surg J. 2010;30(1):83–97. 9. Klein JA. Tumescent technique for local anesthesia improves safety in large-volume liposuction. Plast Reconstr Surg. 1993 Nov;92(6):1085–98; discussion 1099–100. PMID: 8234507. 10. Klein JA, Jeske DR.  Estimated maximal safe dosages of tumescent lidocaine. Anesth Analg. 2016;122(5):1350–9. 11. Tabbal GN, Ahmad J, Lista F, Rohrich RJ. Advances in liposuction: five key principles with emphasis on patient safety and outcomes. Plast Reconstr Surg [Internet]. 2013;1(8):e75. [Cited 2020 Mar 4]. http:// www.ncbi.nlm.nih.gov/pubmed/25289270. 12. Kenkel JM, Lipschitz AH, Luby M, Kallmeyer I, Sorokin E, Appelt E, et al. Hemodynamic physiology and thermoregulation in liposuction. Plast Reconstr Surg. 2004;114(2):503–13. 13. Chow I, Alghoul MS, Khavanin N, Hanwright PJ, Mayer KE, Hume KM, et al. Is there a safe lipoaspirate volume? A risk assessment model of liposuction volume as a function of body mass index. Plast Reconstr Surg. 2015;136(3):474–83. 14. Wang G, Cao WG, Zhao TL.  Fluid management in extensive liposuction A retrospective review of 83 consecutive patients. Medicine (United States) [Internet]. 2018;97:e12655. [Cited 2020 Mar 4]. Lippincott Williams and Wilkins. http://www.ncbi. nlm.nih.gov/pubmed/30313055. 15. Lipschitz AH, Kenkel JM, Luby M, Sorokin E, Rohrich RJ, Brown SA.  Electrolyte and plasma enzyme analyses during large-volume liposuction. Plast Reconstr Surg. 2004;114(3):766–75. 16. Marten T, Elyassnia D.  Facial fat grafting: why, where, how, and how much. Aesthet Plast Surg. 2018;42(5):1278–97. 17. Salibian AA, Frey JD, Bekisz JM, Choi M, Karp NS.  Fat grafting and breast augmentation: a sys-

6  Fluid Balance, Electrolytes, and Anesthetic Options in Regenerative Surgery and Fat Grafting tematic review of primary composite augmentation. Plast Reconstr Surg Glob Open. 2019;7(7): e2340. 18. Pane TA.  Experience with high-volume buttock fat transfer: a report of 137 cases. Aesthet Surg J. 2019;39(5):526–32. 19. Khouri RK, Khouri RK.  Current clinical applica tions of fat grafting. Plast Reconstr Surg [Internet].

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2017;140(3):466E–86E. [Cited 2020 Feb 7]. http:// www.ncbi.nlm.nih.gov/pubmed/28582333. 20. Li S, Luan J.  Recent advances on relationship between inorganic phosphate and pathologic calcification: is calcification after breast augmentation with fat grafting correlated with locally increased concentration of inorganic phosphate? Aesthet Plast Surg. 2019;43(1):243–52.

7

Comparison Between Fat and Fillers Gianluca Campiglio and Nebojša Srdanović

Key Messages • Traditionally, loosening of the soft tissues was the unique sign of aging process related to both face and body. Also, nowadays soft tissues deflation is considered a fundamental aspect of this process. • Deflation, especially in face, can be corrected using fat grafts or soft tissue fillers. • Soft tissue fillers can be obtained from biological or synthetic sources and can be temporary, semipermanent, or permanent. • Fat grafts and soft tissue fillers differ in properties and interactions with the injections site. • Selection of the best solution, fat or filler, as well as which type of filler to use is critical to obtain the best result for the patient. • In some cases fat grafts are better option thanks to greater amount of injectable material, regenerative properties, and long-lasting results. • In other cases fillers are preferable due to their simplicity and accuracy. • Both have drawbacks and potential complications that have to be considered as well.

G. Campiglio (*) Campiglio Plastic Surgery, Milan, Italy N. Srdanović Private Practice, Belgrade, Serbia

7.1

Introduction

One of the revolutionary new concepts introduced in facial rejuvenation is that fullness is the most important feature of youthfulness. This simple principle can be easily appreciated in many shapes in nature such as fruits or flowers. A luxuriant and full plum, for example, is much more attractive than a skinny one, or a lush flower is much more beautiful than a withered one. The same happens with the faces of our patients: aging in human face is evidenced not only by appearance of wrinkles and folds in a previously smooth cheek but also by its deflation with loss of volume. A fuller face seems not only younger but also healthier: indeed when we meet a friend that has lost weight the first impression is that he is not very well, while on the contrary, if he has gained some weight the first idea that comes into our mind is what a healthy period of his life he has been living. As a fuller face appears younger and healthier the same holds for the rest of the body and this is daily very well documented in movies, magazines, and other media. Nevertheless distribution of these volumes is also important for successful results: in face, for example, an increased projection of the cheekbones gives an inverted triangular shape to a face, resulting in nicer and younger appearance compared to a more squared shape usually seen in the elder patients. Similarly, in body, beauty is not related to a homogenous distribution of fat but to

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_7

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areas of increased volume such as buttocks and breasts surrounded by depressed zones. In conclusion we can state that volume preservation and restoration are primary goals in modern facial and body aesthetics. These achievements can be accomplished using implants, fat, or fillers. While implants require specific and invasive surgical acts, thus representing a category by themselves, fat grafts and soft tissue filler injections can be more easily compared to understand the advantages and disadvantages of each of the two techniques. Soft tissue fillers can be autologous tissues which are transferred (grafted) from one body region to another, or artificially (synthetically) made products introduced to a body via injection, for a purpose of regional filling. Autologous tissues are most often transferred via injection (like autologous fat transfer), but can also be transferred by other means (dermo-adipose grafts, cartilage, SMAS, fascia). If implants are not included in a group of artificially (synthetically) made products for purpose of filling, then their only mode of administration is via injection. Hence the popular term—injectables are frequently used for soft tissue fillers. The term dermal fillers, although very frequently used, are not completely precise. Depending of the type of filler, and the region of the body which should be treated, target tissue plane (layer) for the filler is only in some cases dermis (sometimes superficial dermis, sometimes deep dermis). In other cases target tissue can be subcutaneous fatty tissue, as well as submuscular (sub-SMAS) layer, or supraperiosteal layer [2, 14].

7.2

 oft Tissue Filler General S Classification

Soft tissue fillers can commonly be classified in two different, but overlapping ways. According to the origin of filler material, fillers can be: tissues of autologous origin or artificially (synthetically) made commercial products, which can be derived from organic sources (biological materials), or from nonorganic sources (synthetic materials). According to the longevity of filler in the body they can be defined as temporary, semi-permanent, or permanent [1–3, 7, 12, 14, 20].

Autologous materials are most commonly represented by fat grafts, which are the most commonly used autologous filler. Other autologous materials and fillers include: fascial grafts, lipodermal (dermo-adipose) grafts, dermal grafts, cultured fibroblasts, platelet-rich plasma (PRP), plateletrich fibrin matrix (PRFM), cartilage grafts, SMAS grafts, adipose-derived stem cells (ADSC)… The biggest advantage of using autologous materials is safety. Allergic reactions, immunogenicity, toxicity, carcinogenicity, and teratogenicity are of minimal concerns. On the other side, potential pitfalls could include concerns of infection, migration, and inflammatory reactions. Also, filler reabsorption and impermanence (limited longevity), technique dependence, and lack of reproducibility and reliability are potential downsides. Biologic Materials are represented by three major types of artificially made products of biologic origin—hyaluronic acid products, collagen, and acellular soft tissue (dermal) matrix. Advantages of this group include ready, off-the-­ shelf availability, and ease of use. Disadvantages include sensitization to foreign animal or human proteins, immunogenicity, and possible transmission of disease. Longevity is limited. Synthetic Materials are represented by two different subgroups: synthetic fillers with semipermanent longevity (e.g., Calcium hydroxyapatite and Polyl-lactic acid), and synthetic fillers with permanent longevity (e.g., Polytetrafluoroethylene (PTFE) and Polymethyl methacrylate). Advantages of synthetic materials include potential permanence, reduced concerns of disease transmission, and reduced sensitization to foreign animal or human proteins. Disadvantages can include potential for granuloma formation, acute and delayed infections, migration or displacement of material, and deformities that can result in complications necessitating removal of the material.

7.3

 istory and Evolution of Soft H Tissue Fillers (Table 7.1)

7.3.1 F  at Grafting: History and Evolution The first report of fat grafting was in 1893 by German surgeon Gustav Neuber when he trans-

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Table 7.1  History and evolution of soft tissue fillers Year 1893 1895

Fat grafting Gustav Neuber transplanted adipose tissue harvested from the arm to correct a depressed scar Vincenz Czerny transferred fist-sized lipoma from the buttock to the breast

1899 1909 1912 1926

Robert Gersuny described paraffin and petrolatum jelly injections for cosmetic purposes Eugene Hollander proposed use of fat injections through cannula to correct deformities Erich Lexer published a book dedicated to the technique and use of fat grafting Charles Miller described injections of transplanted fat for the correction of facial folds and wrinkles

1948

1950s

Liquid silicone (silicone oil with high viscosity) was designated as a physiologically inert substance. Its use as a filling material for cosmetic purposes began, and it lasted for the next three to four decades on a large scale Lyndon Peer studied gross and microscopic appearance of transplanted fat, discovering factors which led to fat cells death or survival

1960s 1974 1982

Gross and Kirk developed bovine collagen gel, which led to significant advancement in soft tissue fillers Fischer and Fischer developed liposuction technique to remove the fat from the outer thighs Fournier and Illouz further developed liposuction technique, using it in the whole body

1981

FDA approved Zyderm I, bovine collagen filler, the first soft tissue filler approved for soft tissue augmentation Balazs identified Hyaluronic aAcid (HA) as an appropriate facial filler because of its biocompatibility and lack of immunogenicity

1989

1987– 1990s

Sydney Coleman developed and later standardized the technique for fat grafting which became the gold standard

1999 2003

First HA filler being used in Europe (Restylane) FDA approved Cosmoderm and Cosmoplast, the first human-derived collagen fillers FDA approved Restylane, as the first HA filler for use in USA FDA approved poly-l-­lactic acid (PLLA, “Sculptra”), as a filler for HIV-related facial lipoatrophy FDA approved calcium hydroxyl apatite (“Radiesse”), as well as polymethyl methacrylate (PMMA, “Artefill”)

2004 2006 2007

Soft tissue fillers

Rigotti discovered the regenerative role of fat grafts—healing of irradiated tissues due to adipose-­derived stem cells

planted ­adipose tissue harvested from the arm to correct a depressed facial scar that had resulted from osteomyelitis. This was followed 2  years later by Vincenz Czerny, who transferred a fist-­ sized lipoma from the buttock to the breast. Since Neuber and Czerny there have been many reports

that have shown that fat, in pieces, can be transplanted and survive in various areas of the body. Looking for a solution to the problems caused by paraffin, in 1909 Eugene Holländer proposed the use of fat injected through a cannula to correct deformities. He noted considerable reabsorp-

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tion of the fat and therefore began mixing human fat with fat from a ram in an attempt to stabilize it. This resulted in a painful rash that lasted several days; however, a good cosmetic result was obtained. In 1912 Hollander published before-­ and-­after photographs of the use of injectable fat for correction of facial atrophy and breast scarring. Later, in 1919, Erich Lexer published a two-­ volume book dedicated to the technique of fat grafting. In this book, he presented a wide variety of conditions such as depressed scars, breast asymmetry, knee ankylosis, tendon adhesions, and micrognathia and the successful results after treatment with fat grafting. Charles Miller also described the injection of transplanted fat through cannulas for the correction of facial folds and wrinkles in his 1926 publication, Cannula Implants and Review of Implantation Technics in Esthetic Surgery. Despite some favorable results from these pioneers, fat grafting results in general were still unpredictable and it thus fell out of favor. It was not until the 1950s, when Lyndon Peer studied the gross and microscopic appearance of transplanted fat, that we began to understand and improve the predictability of fat grafting. He discovered that adipose grafts lose approximately 45% of their weight and volume at 1 year due to cell rupture and subsequent death. The fat cells that do not rupture, however, will survive and volume will be maintained. Improper handling of the fat prior to and during transplantation was also found to decrease the survival of the fat. Graft size also appeared to play a role in survival. A graft the size of a walnut was found to lose volume more rapidly than multiple smaller grafts of similar weight, likely due to the increased surface area of the smaller grafts. Revascularization, as seen microscopically, was noted by Peer to be essential for fat graft survival. With the advent of liposuction (in the 1974 and 1975 by Fischer and Fischer and in 1980s by Fournier and Illouz), there was a renewed interest in fat grafting. A byproduct of liposuction, the suctioned semiliquid fat could be reinjected through cannulas and needles. The ready availability of semiliquid fat after liposuction helped

G. Campiglio and N. Srdanović

to renew surgeons’ interest in grafting autologous fat through a cannula, and myriad techniques for grafting have been introduced since that time, with mixed results. Results, however, were only partially successful, and the thought at the time was that perhaps better preparation of the fat was essential for its survival. Illouz compared the longevity of grafted fat in the face to that of collagen. In the 1980s, many well-respected plastic surgeons denounced fat grafting based on negative results. However, as techniques changed, more positive results were obtained and surgeons began to realize that grafted fat could result in long-lasting contour changes. There was still great confusion as to what really worked until the 1990s when Coleman standardized the technique. The technique developed by Coleman began in 1987 and evolved over the next few years to become a standard for fat grafting. It emphasizes basic sound surgical techniques with the gentle handling of tissues to make fat grafting predictable and reliable. After initial success with grafting fat into iatrogenic liposuction deformities, Coleman began to place fat in the face for aesthetic reasons. These early efforts yielded long term structural changes that have demonstrated permanence. Since that time the technique has been refined, altered, and improved to ensure better integration and stability of the grafted fat and to provide an alternative method, outside of traditional surgical techniques, for altering facial contours and contributing to overall facial rejuvenation. It has also been used successfully for hand rejuvenation and for treating iatrogenic deformities resulting from liposuction. This technique, called Lipostructure, emphasizes gentle extraction of fat, centrifugation, and micro-particle injections in multiple tissue planes (Fig. 7.1). Rigotti et al. have used fat grafting in the irradiated breast and consistently showed an improvement or complete healing of the damaged tissues. As our understanding of fat and its constituent cells improves, so will our ability to positively affect other areas of medicine [2, 3, 5, 7, 9, 14, 20, 22].

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Fig. 7.1  Fat graft to mask a rippling due to a macro-textured implant. For this area fat graft is considered safer and more appropriate than hyaluronic acid as it can interfere with the oncological screening

7.3.2 C  ommercial Soft Tissue Fillers: History and Evolution In 1899, only 6 years after Neuber described fat grafting, the Austrian surgeon Robert Gersuny described Paraffin injections for cosmetic purposes, injected alone, with petroleum jelly, or with a combination of petroleum jelly and olive oil. He injected the material into the scrotum of a man to improve the appearance of the genitals after castration (to reconstruct a testicle). He later reported on the use of paraffin to correct facial contour deformities. Initially, the paraffin and petroleum jelly filled in soft tissue defects nicely, providing a soft, natural-appearing contour, and excellent aesthetic results, and therefore their use grew for the treatment of facial deformity. Paraffin was initially embraced as a safe, inexpensive, and effective way to rejuvenate the face. As experience increased, significant complica-

tions such as granulomatous inflammatory reactions (paraffinomas) and nodule formation in the location of the injection, embolization, and migration and product migration occurred and the popularity of paraffin and petroleum jelly as a fillers dwindled quickly and its use was soon inadvisable. Still, paraffin kept being used for over two decades before it was abandoned. The silicone in liquid form (silicone oil with high viscosity) was the first substance to be used on a large scale in clinical practice as filling material. The interest in this substance dates back to the late 1940s, after a toxicological study in 1948 called it a physiologically inert substance. Early flawed animal experiments suggested that injectable silicone was safe, and physicians relied heavily on this improper information. The first clinical applications started first in Europe and Asia in the late 1940s and the beginning of the 1950s (the first reports of the use of silicone date

74

from the end of World War II in Japan when numerous women had their breasts injected with non-medical grade silicone). Although James Barret Brown used silicone for soft tissue deficit in 1947, its widespread use in the USA started at the beginning of the 1960s and continued through the 1970s, even though the US Food and Drug Administration (FDA) had never authorized its use. Liquid silicone use was associated with multiple complications such as lump formation, ulceration, and extrusion, migration of the material, hepatic granulomas and hepatitis, and even death. The illicit injection of non-medical grade silicone continues to this day, even though the FDA took a more active role in criminalizing its use in the 1990s. Today, highly purified medical grade silicone oil (AdatoSil 5000, Silikone 1000) is FDA approved for the treatment of retinal detachment but not for cosmetic injections. These products can be used “off label” for soft tissue augmentation, but the safety data to back up such practices are unfortunately not available (Figs. 7.2 and 7.3). The early development of a bovine collagen gel in the 1960s by Gross and Kirk led to the significant advancement in soft tissue fillers in 1980s after the introduction of bovine collagen as the first “modern” filling agent for human Fig. 7.2  Foreign body granuloma following injection of liquid silicone. Macrophages surrounding particles of the silicone are clearly visible

G. Campiglio and N. Srdanović

use for the treatment of wrinkles, perioral lines, and certain scar types. In 1981, after the FDA approval of Zyderm I (INAMED Aesthetics, CA), an injectable bovine collagen filler was the first filler approved by the FDA for soft tissue augmentation. Zyderm II, a similar product with a higher concentration of collagen, was introduced in 1983 and Zyplast, a bovine collagen cross-linked with glutaraldehyde to increase longevity, received FDA approval in 1985. Bovine collagen soft tissue fillers soon became the gold standard against which all fillers were compared. However, with experience accumulating, its rapid resorption (characterized by a short duration of effect) and allergenic nature (required skin testing prior to injection) led to a series of efforts to develop a compound that would not cause allergic reactions and that would last longer. About 20 years later, a bioengineered humanderived collagen was developed to obviate the need for skin testing and reduce the incidence of hypersensitivity reactions. Cosmoderm and Cosmoplast received FDA approval in 2003. Human-derived collagen did not last any longer than bovine collagen. This lack of duration, particularly around areas of great animation, was collagen’s greatest disadvantage and was

7  Comparison Between Fat and Fillers

75

Today, plastic surgeons have in their armamentarium numerous safe fillers that can produce unprecedented aesthetic results, provided they are used in an educated/safe manner [1–3, 5, 12, 14, 16, 21].

7.4

 he Perspective of Soft T Tissue Fillers

Although there has been historical interest in the Fig. 7.3  Drainage of a cyst containing HA following use of injected material to modify the contour of injection for aesthetic purposes in the upper lip. This is a skin and underlying soft tissue, the effective and rare potential complication of the injection of HA that can safe tools to accomplish such a goal have become be easily solved using a big needle available only in recent decades. Up to 2010 fat grafts were used in 70% of no doubt responsible for its gradual decline in treatments as injectable filler, while soft tissue use and eventual disappearance from the mar- filler products were used in the remaining 30%. ket when newer, more durable products arrived After 2010, the use of soft tissue fillers increased, on the scene. making its use as an injectable of choice in 50% In 1989, Balazs identified Hyaluronic Acid of treatments. (HA) as an appropriate facial filler because of its The development of synthetic, biocompatible, biocompatibility and lack of immunogenicity. In temporary, and long-lasting fillers for soft tissue 1998, the first efficacy studies of non-animal-­ augmentation marked the new page in the history stabilized hyaluronic acid (Restylane, Q-Med, of facial rejuvenation. This trend is illustrated by Sweden) were performed. In 1999, the product recent data from the American Society of was purified further to reduce immunogenicity Aesthetic Plastic Surgery (ASAPS) and and hypersensitivity reactions. In 2003, after ASPS.  ASAPS data show that soft tissue filler 4 years of use in Europe, Restylane was approved treatments have increased by 35%, respectively, in the USA by the FDA as a first hyaluronic acid in the past 5  years. According to the American soft tissue filler. HA fillers rapidly replaced col- Society of Plastic Surgeons (ASPS) National lagen as the gold standard in cosmetic soft tissue Plastic Surgery Statistics, about 2.7 million soft augmentation. tissue filler procedures were performed in 2017 as The high demand and success of HA products well as in 2018. This is over a 300% increase led to an intense search for products that are simi- compared with the year 2000. The dramatic lar to HA, did not cause hypersensitivity reac- increase in the number of filler procedures pertions, but are longer lasting. This in turn led to a formed over the years is multifactorial. Firstly, it number of newer and longer-lasting products includes improved filler availability to surgeons, such as poly-l-lactic acid (PLLA: Sculptra, FDA non-surgeon physicians, physician extenders, as approval in 2004 for HIV-related facial lipoatro- well as certified medical and even non-medical phy; Sculptra Aesthetic, FDA approval in 2009), personnel, who perform filler procedures worldcalcium hydroxylapatite (Radiesse, FDA wide. Secondly, there is an increased understandapproval in 2006), polymethyl methacrylate ing of soft tissue and bone volume alterations (PMMA)/polyacrylamide products such as associated with the aging process. Thirdly, there Bellafill (previously Artefill, FDA approved in is an improved product quality and marketing [2, 2006). 12, 15, 20].

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7.5

Fat Grafts

Many clinical conditions in reconstructive surgery benefited of lipostructure. Fat grafts have been successfully used to improve the results of breast reconstruction, as the use of implant only, especially in thin patient, often did not produce satisfying results. Fat injections have been widely used also in Romberg disease, making in these cases the reshaping of the face easier and more tailored to the specific needs of each patient. Another common indication in reconstructive surgery has been the correction of retracted and depressed scars with very good results in terms of filling and softening of the fibrotic areas. In aesthetic surgery fat grafts offered an excellent solution for beautification or rejuvenation of the face

and of the body. Cheekbones or chin can be increased with fat injections, tear through deformity, facial folds and depressed temples can be filled and nice breasts and buttocks can be created using the own fat of the patients. There are many different techniques to perform fat graft in plastic surgery. The differences regards the site composition of the infiltrating solution, the caliber of the cannula and in particular of the hole along its wall, the number and shape of these holes, the use of centrifugation or decantation to separate fat cells from blood and the liquids used for the infiltration, the type and dimension of the cannula used to inject the fat. All these differences and the great variety of their combinations make it very difficult to compare the advantages of one technique over the others [1, 8, 9] (Figs. 7.4 and 7.5).

Fig. 7.4  Fat graft in the lower lid for rejuvenation. For this area both fat graft and HA can be used but in our opinion the former is better for its efficacy and reduced rate of complications

Fig. 7.5  Fat graft aimed to treat multiple depressions following atrophy in a female buttock. In this area for smaller defect fat graft or HA injections are good alternative but for larger area fat is safer and more efficacy

7  Comparison Between Fat and Fillers

7.6

Hyaluronic Acid Fillers

7.6.1 Natural Hyaluronic Acid Hyaluronic Acid (HA) is a naturally occurring linear polysaccharide that consists of regularly repeating non-sulfated disaccharide units of glucuronic acid and N-acetylglucosamine. Hyaluronic acid belongs to a larger class of molecules called glycosaminoglycans. Glycosaminoglycans are one of the essential components of ground substance, in which HA acts as a scaffold for protein fibers (collagen, elastic and reticular), which all together make the Extracellular Matrix (ECM) of connective tissues, contributing to cell proliferation and migration, as well as tissue repair. HA as a normal component of the ground substance in skin dermis is responsible for dermal hydration. It is quite hydrophilic, and the water that surrounds it is able to occupy a larger volume relative to its mass. It provides structural support to tissues by attracting up to 1000 times its weight in water. HA decreases with age, which results in reduced skin turgor, increased wrinkling, and a general deflation of tissues. In its natural state, HA is non-cross-linked, and has a half-life of approximately 24–48 h before it is broken down by hyaluronidase and free radicals into carbon dioxide and water. HA is identical in form in all mammalian species—there is no species specificity. Thus, there should be no concern for immunologic activity, allergenicity, and no need for a filler pre-injection skin test, giving HA a significant advantage over collagen fillers [1, 2, 5, 13, 16, 20, 21].

7.6.2 S  ynthetic Hyaluronic Acid Fillers HA fillers absorb water and expand after injection, making them able to retain 95% of volume with water. They act by increasing skin turgor, elasticity, and volume. The viscoelastic properties, stabilizing role, and protective action on cell membranes afforded by hyaluronic acid make it an ideal material with which to fill/lift skin depressions. It is recently reported (Wang et al.)

77

that, in addition to the physiochemical properties of HA, it may augment dermal filling by stretching fibroblasts and thereby stimulating de novo collagen formation. So besides increasing skin hydration, HA stimulates the synthesis of new connective tissue. Hyaluronic acid fillers are the most widely used because of their good safety profile, moderate duration of effect (up to 12–18 months), and lower potential for hypersensitivity reactions (0.6–0.8%). They are readily available and reliable to use. HA fillers are having added benefit of being reversible with hyaluronidase injection at the previous injected site. The distinct properties of various HA products should be considered when deciding on the appropriate filler for use [2, 12–14, 16, 20, 21].

7.6.3 Biophysical Characteristics of HA Fillers (Table 7.2) HA fillers have specific, modifiable characteristics that account for their biophysical properties. The important differences between currently available HA fillers include: the source of HA, concentration of HA in each syringe, agent used for cross-linking HA polymers, degree of modification and cross-linking, amount of free unmodified HA present, whether the product is monophasic (cohesive gel) or biphasic (particulate), and the elastic modulus (G’) of a gel [13, 20, 21].

7.6.3.1 The Source of Origin and Production HA fillers may be animal-based or non–animal-­ based. Animal-based HA fillers are from avian origin, derived from rooster combs, whereas non-­ animal-­ based (Non-Animal Stabilized Hyaluronic Acid—NASHA) are derived from bacterial fermentation of Streptococcus equinus. Animal-based HA fillers are no longer marketed in the USA [13, 14, 20, 21]. 7.6.3.2 Stabilization and Cross-Linking Stabilization of HA via cross-linking is essential for its utility as an injectable filler. Otherwise, it would degrade quickly, like a natural HA.  The

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78 Table 7.2  Biophysical characteristics of HA fillers

Origin Ease of obtaining

Ease of use Storage Mode of administration Injection technique and injection precision

Target tissue plane (layer) Patient preparation for the procedure

Procedure duration Post-procedure downtime

Predictability of the result

Reproducibility of the injection procedure Financial aspect

Tissue lifting and facial contouring effects Tissue volumization effect Regenerative potential Reversibility of effects Longevity of effects

Hypersensitive reactions Significant vascular compromise Dynamic (animation) deformities and filler migration Over-/under volumization complaints

General Fat transfer Autologous tissue Obtaining is possible only in surgical theaters Fat is obtained through a complex surgical procedure Storage is arguable Injection Lower precision due to technical need for multiplane, multi-pass fat distribution with blunt cannula

Subcutaneous tissue primarily +/− other tissue planes From none to various medical check-ups (depends on the amount of liposuction as well as the type of the primary surgical procedure) Generally longer than with HA fillers Depends on a size of a liposuction as well as primary surgery type Unpredictable (far more unpredictable than with HA fillers) Less reproducible than HA filler injections More affordable option for a patient (per mL of filler) Effects Weakly pronounced

HA soft tissue filler Synthetically made Obtaining a HA filler is possible to wide variety of medical personnel, as well as non-medical personnel Easy to use, available off-the-shelf in a pre-packed syringe form Easily stored Injection High precision can be achieved using specific techniques (e.g., MD codes) with full control of location point of injection, depth of injection, and amount of injection per point, using needle and/or cannula Various tissue planes (depending on the specific filler characteristics) None

Generally shorter than with fat transfers None

Predictable

More reproducible than fat injections More profitable option for doctor (per mL of filler) Highly pronounced (especially with HA fillers with high G’) Pronounced Minimal Yes, with hyaluronidase injection

Highly pronounced Significant No (could be partially reversed only via liposuction) Potentially permanent (only the portion of fat which survives the transfer) Side effects No Possible (more frequently than with HA fillers) More frequent with fat injections

Very rare, but possible Possible (less frequently than with fat transfer) Less frequent with HA filler injections

More frequent with fat injections than with HA fillers

Less frequent with HA filler injections than with fat transfer

Non-permanent (filler disappears in 6 months–2 years on average) (depending on the specific filler)

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synthetically made HA molecule is stabilized through cross-linking with hydroxyl groups— allowing them to resist digestion by hyaluronidase. Most dermal filler products will consist of HA cross-linked with a chemical such as 1,4-butanedioldiglycidyl ether (BDDE) (e.g., for Restylane, Belotero, and Juvéderm groups), divinyl sulfone (DVX) (e.g., for Hylaform), 1,2,7,8-diepoxyoctane (DEO) (e.g., for Puragen), and suspended in a physiological or phosphate-­ buffered solution. The product is then processed as a homogeneous gel or a suspension of particles in gel carriers. It is the degree and type of cross-­ linking that determines longevity of the various HA products on the market. A higher degree of cross-linking correlates clinically with longer duration of effect of the filler. Also, use of chemical compounds, which stabilize cross-links, or the incorporation of varying degrees of ­cross-­linking in a single product, may contribute to prolonged filler efficacy [13, 14, 20, 21].

7.6.3.3 Reversibility Cross-linked HA is the only filler that can be fully reversed via the use of intracutaneous hyaluronidase, a soluble protein enzyme that breaks down and hydrolyzes HA.  Reports demonstrate that injection with hyaluronidase works within 24–48 h to relieve patient discomfort due to product misplacement or unwanted adverse effects [1, 3, 13, 14, 20, 21]. 7.6.3.4 Viscoelasticity Viscoelasticity describes the property of HA filler that exhibit both viscous and elastic characteristics when undergoing shear deformation. Viscous modulus (loss modulus, G”) represents the inability to recover the original shape after shear deformation. Viscosity refers to the ability of the gel to resist shear forces. Factors affecting viscosity include size and molecular weight of the HA particles. Higher viscosity is associated with decreased spread of the filler within tissues but also with decreased ease of injection. Elastic modulus (storage modulus, G’, G prime) represents the ability to recover the original shape after shear deformation. In HA fillers G’ is a

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measure of HA firmness and refers to the ability of the gel to resist deformation when a force is applied. The G’ level is determined by bond strength which, in turn, dictates the degree that bonds between particles stretch with applied forces. The different HAs have varying degrees of hardness (G′), which also influence their suitability for a particular procedure. Clinically, variations in G’ manifest as differential ability to lift tissue, where higher G’ translates into greater tissue lift but also firmer feel, so the deeper should product be injected. Complex modulus (G*) represents the total ability of material to withstand deformation. It is defined as the sum of the elastic modulus (G’) and viscous modulus (G”) [15, 20, 21].

7.6.3.5 Cohesivity Represents the strength of the cross-linking adhesion forces that hold the individual HA units together. Cohesivity is determined by the concentration of HA and the degree of cross-linking. High cohesivity helps the filler maintain vertical projection [20, 21]. 7.6.3.6 Monophasic Versus Biphasic Products (Particulate Forms) HA fillers can be classified according to their particulate forms: either monophasic or biphasic gels. Monophasic products (such as the Juvéderm group, Teosyal group, and Belotero group) are viscoelastic gels that are not sliced or sized into particles during the manufacturing process. Monophasic gels consist of a single “phase” of HA.  They can be either monodensified, where HA is mixed and cross-linked in a single step (e.g., Juvéderm and Teosyal groups), or polydensified, where HA goes through two stages of cross-linking (e.g., Belotero group). Biphasic particulate gels (such as the Restylane group of products) are passed through screens during the manufacturing process, so that different products in a group have different number of particles per milliliter of product (e.g., Restylane Fine Lines has 200,000 particles per milliliter of product, Restylane has 100,000 particles, Perlane has 10,000, and Restylane Sub-Q is thicker with just 1000 particles

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per milliliter). Biphasic gels consist of two “phases” of HA, cross-linked HA of a specific size which is then suspended in non-­cross-­linked HA acting as a carrier. According to recent studies biphasic and monophasic monodensified HA fillers maintain a longer intradermal presence than monophasic polydensified fillers [21].

7.6.3.7 Classification of HA Fillers by Particles Size Hyaluronic acid derivatives are available in different particle sizes (small, medium, and large) for use in different sizes and depths of tissue defect. Combining different particle sizes allows tailoring of the therapy to treat a range of conditions, from deeper folds such as the nasolabial folds to finer lines. HA fillers with largest HA particles (e.g., Perlane, Juvéderm Ultra Plus (XC)/Voluma) should be injected into the deepest layer of the dermis, or in deeper tissue planes. HA fillers with midsized HA particles (e.g., Restylane, Juvéderm Ultra (XC, Belotero Balance) should be injected at the middle dermis level. HA fillers with smallest HA particles (e.g., Restylane Fine Lines) should be injected at the dermal epidermal junction [21]. 7.6.3.8 Resorption Duration HA filler’s time of resorption is variable, influenced by intrinsic and extrinsic factors. Unique to HA is its ability to follow isovolemic degradation, a process by which the remaining molecules of HA are able to bind an increasing amount of water thus maintaining volume until the majority of product is degraded. In general, fillers with the combination of larger particles and with more cross-linked connections that increase its molecular weight will prolong the filler persistence in tissue [21].

ticle sizes. Increased cross-linking, concentration, and particle size increase the viscosity and elasticity and the time necessary for degradation by native hyaluronidase. The more concentrated and/ or large-particle products will tend to absorb more water and thus cause more tissue swelling after injection. When treating the deep subdermal layers of the cheeks, it is important that the filler gives good volume and projection without spreading too easily through the tissues. Conversely, when injecting into superficial dermal layers, it is important that fillers can easily spread through the tight connective tissue in order to sit smoothly in the upper layers of the skin. Although more concentrated products with a higher degree of crosslinking have a longer duration of effect, they also increase reactivity in the body and thus the risk of inflammation and granuloma formation [21].

7.7

 at Grafts Versus Hyaluronic F Acid Fillers

The perfect soft tissue filler has yet to be created. The fillers in current use incorporate many, but not all, of the ideal characteristics. Each filler carries its own individual risk/benefit profile. Ideal soft tissue filler characteristics would be:

• Safe and nontoxic (minimal side effects or complications) • Non-allergenic (biocompatible) • Easy to use • Minimal downtime • Predictable action • Minimal product migration • Potentially reversible • Ages appropriately with the patient • Non-palpable • Readily available off-the-shelf 7.6.3.9 Some Clinical Tips Concerning • Easily obtained, stored, and used Biophysical Characteristics • Inexpensive for patient of HA Fillers Products with a higher concentration of cross-­ • Long-lasting linked HA or larger particle sizes are generally • Useful in multiple tissue planes indicated for deeper injection in the dermis and Although there are numerous groups of soft subcutaneous tissues to correct deep folds or for facial contouring and may have higher tissue resi- tissue fillers, as already mentioned, the HA filler dence times compared to products with lower and fat graft characteristics are closest to what a concentrations of cross-linked HA or smaller par- hypothetic ideal should have. So, we will focus

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on comparing advantages and disadvantages of these two fillers [1, 13].

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ness due to central retinal artery occlusion. Although there are theoretically more ­preconditions leading to this particular complication to happen with HA fillers (worldwide avail7.7.1 Safety Profile ability of filler to non-surgeons, non-doctors, and even non-medical personnel who performs this Both autologous fat grafts and HA fillers are con- treatment; fine tiny sharp needles prepacked with sidered very safe. However, both have their side fillers, which simply offer themselves to be used effects profile, so we will discuss the most fre- instead of searching for cannulas) compared with quent and the most significant of them. fat grafting (surgeons performing the procedure, larger caliber cannulas readily available for injection of fat around the eye) autologous fat (47.9%) 7.7.2 Hypersensitivity was the most common filler associated with this complication, followed by hyaluronic acid There are no hypersensitivity reactions to autolo- (23.5%). While this severe complication is diffigous tissue, and the fat grafts are not an exception. cult if at all possible to treat, in addition to other HA fillers, as previously explained in the text drugs, hyaluronidase is a significant weapon above, are in identical form in all mammalian spe- which could try to help alleviating this problem, cies—there is no species specificity, so there working not only if injected intra-arterially in should be no immunologic reactions to it. However, ophthalmic artery, but also para-arterially, as the recent data shows that, although rare, HA fillers enzyme dissolves natural HA around the blood can lead to hypersensitivity reactions, which can vessel, then crosses the artery wall, to finally disbe both antibody-mediated, or non-­ antibody-­ solve extrinsic HA in blood vessel itself [3, 5, 8, mediated, clinically manifested as edema or 9, 12, 17, 20, 21]. inflammatory nodules. Edema can develop usually with immunoglobulin E [IgE]) immune response • Conclusion: HA fillers led to blindness less frequently than fat grafting while having (type I hypersensitivity reaction) to an allergen. greater chances for potential rescue. Delayed hypersensitivity reactions are mediated by macrophages and T lymphocytes (type IV reaction). Mechanisms proposed for hypersensitivity associated with HA are immune stimulatory 7.7.4 Aesthetic Complaints effects of the HA either as an adjuvant, or directly via its structural composition (LMW-HA frag- 7.7.4.1 Insufficient Volume and Too Much Volume ments acting pro-­inflammatory), or as an antigen, or through its interaction with tissue resident mast It is one of the most common complaints in fat grafting that there is more or less volume than cells through the CD44 receptor [12, 19–21]. expected after the procedure. Because of fat • Conclusion: fat is better due to absence of absorption variability and unpredictability, there hypersensitivity reactions is no simple solution of this kind of problem. If there is too little of volume, there will be need to add additional fat, and since the use of frozen fat 7.7.3 Significant Vascular is not a good option, the patient should go on for Compromise another surgical procedure, with another liposuction, as well as preparation of recipient region for Both HA fillers and fat grafting can lead to vascu- the fat transfer, which both carry some level of lar complications ranging from local tissue invasiveness, leading to another procedure downnecrosis, blindness, and even stroke and death. time, and recovery period. If there is too much When discussing applications of fillers and fat in volume, things are not getting much simpler. Fat the face the most fearsome complication is blind- removal with liposuction of face is the most fre-

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quent option for solving the issue. This time there is no donor region to care about, but still, precisely locating the tissue plane where the excess fat is (and frequently it is in every plane), and performing a rescue liposuction from a region where multiple cannula passes from previous fat transfer already created fibrosis and scars will not be sweet and easy for any surgeon. On the other side, complaints of having too much or too little of volume with HA filler are pretty easy task to solve. Both hyaluronidase treatments and HA filler adding can be repeated whenever needed, in out-patient settings and a zero procedure downtime, [6, 9, 18, 21, 22]. • Conclusion: HA fillers are far easier solution when trying to avoid possible complaints of over or under volumization, then are fat grafts. If the fat grafting resulted in under volumization, HA fillers could be used to correct the volume instead of going through the second fat grafting procedure.

7.7.4.2 Dynamic (Animation) Deformities and Filler Migration When injecting a fat or HA filler into a dynamic region of the face (e.g., nasolabial folds, upper lateral cheek, lips, glabella) it is possible that with its animation filler could be moved from the desired position, or present itself in an undesired way. It would thus be helpful if these regions could be filled while patient awake, and able to animate during the procedure. While this is quite possible with HA filler injections, it is not always the case with fat grafting, where patients are frequently sedated or totally anesthetized. Also, the amount of fat which is grafted is frequently overcorrecting the region which it fills, so even when patient is fully awake and able to animate that region completely, overcorrection of it can mask the real picture [8, 18]. • Conclusion: HA fillers are more suitable for working in dynamic regions of the face than fat grafting, because they are almost always used in awake-patient settings, where there is better control of real-time animation behavior with each unit of volume injected.

7.7.5 Longevity Fat grafts could be potentially permanent, but only the fat graft partition which survives the transfer. The cutoff point when we can be sure about the results of a transfer could be 3  months postop. Until this moment, we can expect the decrease in the initial amount of fat filler, and on average about 50% of graft will be lost. On the other side, as the accepted fat ages with a patient, any significant weight loss of a patient would lead to a decrease in the amount of a fat graft. Also, there is a specificity of each region to which the fat is injected, where generally stable regions (example) allow longer graft acceptance (and survival), than the regions which are in constant motion (e.g., lips). HA fillers have variable longevity in a tissue depending on specific filler characteristics, as well as the mobility of the region which is injected. The amount of the filler injected will not have the downside of significant volume reduction in the first 3 months after injected. Even in very mobile region they could demonstrate acceptable persistence during time. However, even the longest lasting HA filler will disappear under best circumstances after 2 years, and most of the average lasting HA fillers frequently much earlier (after an average 6–12 months) [8, 17, 18, 21–23]. • Conclusion: Fat grafts have a slight advantage over HA fillers over longevity issue, but that advantage is not a clear-cut one.

7.7.6 Obtaining and Storage Obtaining of HA fillers is differently regulated in various countries. Generally, they are obtained by medical offices, centers or hospitals, or personally by surgeons, medical doctors, or even medical staff, depending on the specific country’s law. However, today, there is an increasing tendency worldwide for wide scale availability of HA fillers. In some countries every certified person (though not being a doctor, nor even a medical staff) can obtain and apply HA fillers. Storage of HA fillers is quite simple. They do not require any specific conditions, not even a fridge. If the filler is opened, and not used immediately in total, if antiseptic condi-

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tions are followed it can be safely reused again in same person (within some reasonable time). Obtaining a fat graft is a privilege of surgeons. Although plastic surgeons most frequently perform it, it is not entirely confined to plastic surgeons (ENT surgeons, dermato-surgeons, etc. also do it). But it is nowadays extremely rare that non-surgeon doctors perform this procedure, and hopefully nonexisting situation that it is performed by medical staff, or whether “certified” or uncertified nonmedical person. Although storage of fat by freezing is possible and it is often performed, the use of frozen fat exposes patients to the risk of severe infections, because it is composed of certain amount of dead tissue, and the results with frozen fat are variable, and most often the grafted material resorbs almost completely. The use of autologous banked fat should be strongly discouraged because of the significant potential for error [8, 9, 15]. • Conclusion: HA fillers have the advantage in both obtaining and storage of a filler. However, fat grafting is a privilege of surgeons, and plastic surgeons in specific. In the era when anti-aging medicine services are being available at every corner, it is great to have such a powerful anti-aging tool, which simply cannot be offered by everybody.

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7.7.8 Reproducibility of the Procedure HA fillers are available off-the-shelf and are easy to use. They offer a great reproducibility of results among different injectors, especially after various schemes with precise mapping of injection points are defined (e.g., “M.D. codes” by De Maio). Fat transfer procedure needs a whole process of preparations to be done properly. That process is quite specific from surgeon to surgeon, and it is not easily reproducible [10, 18]. • Conclusion: HA filler injection procedures are far more reproducible than the fat grafting procedure

7.7.9 Preparation for Procedure, Procedure Duration, and Post-­ procedure Downtime HA filler application is usually a short out-patient office procedure. Unless the planned volume to be injected is not abnormally high per treatment (e.g., more than 10 cc), there is no need for any pretest or medication to use before the procedure. There is no procedure downtime (Figs. 7.6 and 7.7).

7.7.7 Ease of Use HA fillers are off the shell products. Thus, their use cannot be more simple. The fillers are prepacked in appropriate syringes, with needles included. There is no need for operating room, they can be used in any type of office, and their use in beauty salons and even private apartments is getting bigger and bigger. Fat grafts are completely on the other side. To get a autologous fat graft, there needs to be the whole logistics, including hospital conditions, operating room, usually a scrub nurse, sometimes an anesthesiologist, specific instruments, and equipment for fat harvesting, fat processing, as well as fat injecting, as well as the procedure of liposuction of various size for collecting fat [2, 4, 6–9, 11, 22]. • Conclusion: fat grafts are far more complicated for use than HA fillers

Fig. 7.6 Hyaluronic acid injection for prolabium enhancement. For smaller defect, where precision is in the correction is fundamental, HA is preferable due to the use of small and sharp needle

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Fig. 7.7  Nose reshaping using 1 cc of HA (rinofill). As in the lip also in the nose HA is preferable to fat graft for the above-mentioned reasons (precision and safety)

Fat grafting can be a procedure of quite different durations, primarily depending on liposuction size. Small-volume liposuctions and transfers, usually done in  local anesthesia, do not require any specific pre-op preparation, and do not have any significant downtime. Medium-sized lipo-

suction requiring Intra Venous (IV) sedation might need for some pre-op blood tests and examinations, as well as at least couple of hours hospital stay. Large and very large liposuctions might require general anesthesia, implying various necessary pre-op examinations, as well as at

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least 1 day hospital stay. And, after the liposuction is over, it is only one part of the whole procedure, which should be followed with processing the fat, and injecting the fat, where each of these steps, properly done, takes its own time. In addition to facial recovery after filling procedure, which frequently takes longer with fat grafting than with an HA filler, fat grafting procedures have an additional disadvantage of having a donor region recovery to care about [6–9].

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• Conclusion: Fat grafts effects are far more unpredictable than those from HA fillers

7.7.11 Reversibility

One of the most important features about HA fillers is reversibility of their effects through the action of hyaluronidase. If there is too much of HA filler—hyaluronidase will help. If there is a complication of any kind, it will for sure be easier • Conclusion: HA fillers have the advantage of to solve it with this powerful “anti-dot-like” simpler preparation for the procedure, shorter weapon. procedure duration, as well as no post-­ Fat grafts, on the other hand, do not have that procedure downtime. kind of option. The only way to reverse its effect is to remove the fat, most frequently by a way of liposuction, or rarely by surgery. And if liposuc7.7.10 Predictability of Effects tion of fat transferred to the face should be performed, there are numerous difficulties on the When injected, effects of HA fillers are quite pre- way. Firstly, it is a difficult task to locate the exact dictable. The injected volume at the end of the layer where the fat is grafted, and from where it procedure should be more or less the same as the should be removed. Secondly, contrary to the volume which remains after 15 days when initial application of hyaluronidase, which can be done edema, swelling, and bruising subsides. After in multiple treatments, with multiple dose that period there is a stable filler volume, with increases and adjustments until the problem is gradual, very slow unnoticeable decrease in vol- solved, the removal of fat through liposuction is ume. So, there should not be overcorrection with best when done from a single treatment attempt. HA fillers. Every other attempt to remove the fat will be One of the main problems of fat grafting is its harder due to increased fibrosis and scaring in the unpredictability. And it remains an issue from the region, caused by previous liposuction [3, 13, 18, very beginning of the procedure until years after 20, 21]. the procedure. Firstly, the amount of fat h­ arvested, especially in skinny patients, can be smaller than • Conclusion: HA fillers have advantage over fat grafts because of easier, less invasive, expected. Secondly, the amount of fat which cheaper, more precise, and more complete remains after the processing is variable. Thirdly, way of reversing their effects by hyaluroniand most importantly, the amount (percentage) of dase, compared to reversing of fat graft effects. fat injected which will eventually survive is questionable. This issue puts a surgeon in position to always overcorrect with fat grafts, and after that wait for 3  months to be sure what is the stable 7.7.12 Plastic Surgeon’s Aspect result of the work. Finally, as the grafted fat which survived 3 months “ages with the patient,” Anti-aging medicine is getting more and more there is a chance that as the patient gets fatter popular every day. And with its worldwide growwith age (and this is for sure more frequent option ing popularity, the number of providers of anti-­ than is to get skinnier with age), she/he gets a aging services also grows rapidly. This is very unpleasant surprise of getting fatter in especially true for HA filler treatment providers. regions which were previously grafted, and with This significantly increases the competition. Fat which the patient was previously satisfied [6–9]. grafting is one of the tools which can make the

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need for lifting tissue and bone contouring, achieving better results with smaller volume, and greater precision and control of injection.

7.7.14 The Regenerative Potential Any trauma to the epidermis and dermis, which form a protective barrier against the environment, immediately initiates the tissue-repair cascade, in which inflammatory mediators induce fibroblasts to generate new collagen and elastin, ultimately Fig. 7.8  Intraoperative injection of fat for remodeling leading to re-epithelialization and re-modeling of and augmentation of the buttock. For buttock augmentation, when large amount of injectable material is needed the skin. Causing some trauma to the soft tissues of the face are inevitable events with injections of fat is preferable to HA both HA fillers and fat grafts, with the damage difference for plastic surgeons, making them still being usually greater with the fat grafting than “a little bit more important” than other non-­ with HA fillers, due to specificity of fat injection surgeon aesthetic providers, which (still!) cannot technique. offer fat grafting in their repertoire (Fig. 7.8). In addition to trauma-induced regeneration of tissue, HA fillers injections were also shown to • Conclusion: Fat grafting should be encour- have an additional positive effect on skin quality, aged and promoted as an anti-aging procedure promoting collagen synthesis by stimulating fibrowhich only plastic surgeons can perform. blasts by stretching them with dermal filling, and thereby stimulating de novo collagen formation. Fat grafts could have the most significant role 7.7.13 The Lifting and Contouring in reparative and regenerative medicine. Fatty tisEffect sue has been found to contain adipose-derived stem cells (ADSCs), mesenchymal stem cells Some face regions need simple volume augmen- (MSCs), endothelial cells and their progenitor cell tation, while some other regions (e.g., cheeks, lines, smooth muscle cells and smooth muscle chin) could benefit from strong lifting and con- progenitor cell lines, and numerous other stem touring effect of a filler. HA fillers with specific cells that are multipotent and could have the characteristics (high cohesivity, larger particles, potential in tissue regeneration. ADSCs have a large G’, higher level of cross linking), placed in number of functions and may be induced to difdepots (small boluses) on the periosteum at the ferentiate into many different cell types in culture, precisely defined injection spots (e.g., de Maio including ectodermal, mesodermal, and endoderMD Codes), are made for a prominent lifting and mal lineages. Additionally, ADSCs have been contouring effect. Fat, on the other side, should shown to induce blood vessel formation, mitigate not be placed in single tissue plane, neither fibrosis, and promote bone formation and wound should it be placed in a depot-sized bolus on any healing. It is believed that ADSCs within a fat single spot. Finally, grafted fat is soft, softer than graft may be a major contributor to the therapeutic a hard HA filler. So, it would be a mistake to try potential of the graft. They could help the survival to accentuate the bony shape with ever larger of the fat graft itself, as well as contributing to amount of fat; this would only lead to over-­ promote rejuvenation of surrounding tissues (e.g., volumized, shapeless face [10, 15, 18]. improving skin quality) [4, 6, 9]. • Conclusion: HA fillers (with specific characteristics) are better option than fat if there is

• Conclusion: Fat grafting is a clear-cut winner, a major tool in regenerative medicine, with its

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vast potential still not fully explored. Still, HA fillers are not simply just a filler. They also have their own small impact on tissue regeneration.

7.7.15 Practical Aspects Liposuction generally offers larger volume of filler then it is generally used with off-the-shelf synthetic products. Couple of details should be pointed out, however. Firstly, not all liposuctions necessarily yield large amount of fat. While smaller liposuctions give lesser amount of fat, they can be done in local anesthesia, which makes the procedure easier and cheaper. Bigger liposuctions can produce more fat, but that can push the procedure to be done under IV sedation, or general anesthesia, which makes the procedure harder for patient to recover from, as well as more expensive. Secondly, based on a rough approximation, if a surgeon plans for adding a 10 mL of volume with long term persistence, per side of the face, he/she should plan of filling with roughly 20 mL of purified fat per side of the face (accounting for average 50% graft acceptance over time). To achieve this 20 mL pure fat per side (40 mL pure fat for both sides) surgeon needs to aspirate anywhere from 100 to 150 mL up to 400 mL depending on the technique. While it is easy to obtain 400 mL of lipoaspirate from an obese patient from a single region, it can sometimes be hard to obtain even 100 mL easily from a skinny patient (and there are many of them) from a single region. This necessitates searching for fat in other body regions (more donor regions to recover), which leads to longer procedure, more local anesthesia, and possible need for systemic anesthesia. On the other side, it is not a frequent situation (at least in our experience) for patients to come for a 20 mL of HA filler per single treatment. And if they do, there is a question of safety, which does not exist with the same amount of autologous fat transfer. Thirdly, there is a question of reduced fat cells survival, if lidocaine is used as an anesthetic. Lidocaine will definitely not help fat in surviving, if not doing exactly the opposite. So, this fact could push towards the liposuction performed

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under IV sedation (although lidocaine is still needed in this case), if not even towards general anesthesia, for helping a better fat survival. So, at the end, there is a question of volume cutoff point. If it seems that for a goal of 20 mL volume in a whole face (for a long term graft persistence) fat transfer is the winning choice, what happens if we cut that volume to 10 mL (5 mL by side, on a long term)? If we cut it to 2.5 mL per side, the clear winning choice is HA filler. There is also a question of a proper patient candidate for a fat transfer procedure. And unfortunately for skinny patients, it seems they are not the good ones. Regarding the financial aspect in general, a total amount of about 100  cc of lipoaspirate are required to obtain about 10  cc of purified fat, which is usually enough to treat most of the cases. Considering the pricing of maintaining/renting an operative room and the anesthesiologist fee, 1 cc of centrifuged fat has finally a cost very similar to 1 cc of HA filler or, in other words, with the standard cost of a fat grafting procedure to harvest 10–15 cc of fat, a total of 10–15 syringes of 1 cc HA fillers can be bought. Of course, when the amount of harvested fat increases, the cost of each cc of centrifuged fat decreases significantly, while the cost per syringe of an HA filler remains more or less the same independently of the number of syringes used for the patient [6, 8]. • Conclusion: For smaller treatments the cost of the injected material be it fat or filler is similar, but for bigger procedures fat is much cheaper option. This gives doctor a possibility to offer the same treatment at a more convenient price or with his revenue being higher.

7.8

Conclusion

Both HA fillers and fat grafts are excellent choices for facial rejuvenation procedures. The choice between them is available only to surgeons, while the rest of aesthetic providers which are non-surgeons (and they are in increasing majority) can only count on HA fillers, making them far more commonly used option worldwide.

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When discussing surgeon’s choice, decisions should be made from patient to patient, having in mind the balance between patient’s desires and her/his body-fat reserves (obese or skinny), financial capabilities, advantages, and possible risks of each method. Fat grafting could be a method of choice for a surgeon if the patient is undergoing general anesthesia for some other procedure, and large amount of filler is needed in the face or in the body (e.g., buttocks, breast). If that particular procedure is liposuction, it is the best possible situation. HA fillers could be an option if there are localized small volume-deficient regions, when there is need for bone contouring, when the patient does not want to have any downtime after the procedure, or when the patient simply does not have enough fat for a transfer. HA filler injections are easier to perform, have more predictable and reproducible effects, fewer disadvantages, more easily solvable complications, and are more profitable for a doctor. Disclosure  The authors have no commercial agreements with any company involved in the production or marketing of soft tissue fillers or of devices for fat harvest and/or processing.

References 1. Beck DO, Obaid SI, Burns JL Jr. Nonoperative facial rejuvenation. In: Janis JE, editor. Essentials of plastic surgery. 2nd ed. QMP: CRC Press; 2014. 2. Born TM, Airan L, Motakis D, Nahai F.  Soft tissue fillers in aesthetic facial surgery. In: Nahai F, Nahai F, editors. The art of aesthetic surgery principles & techniques. 2nd ed. CRC Press; 2010. 3. Born TM, Airan LE, Suissa D. Injectables and resurfacing techniques: soft-tissue fillers. In: Neligan PC, editor. Plastic surgery. Vol. 2: aesthetic surgery. 4th ed. Elsevier; 2018. 4. Calabrese C, Tiryaki T, Findikli N, Tiryaki D. Aesthetic regenerative surgery. In: Scuderi N, Toth BA, editors. International textbook of aesthetic surgery. Springer; 2016. 5. Carruthers J, Carruthers A. Non operative facial rejuvenation. In: Farhadieh RD, Bulstrode NW, Cugno S, editors. Plastic and reconstructive surgery approaches and techniques. Wiley-Blackwell; 2015. 6. Chang EI. Fat grafting. In: Chung KC, editor. Grabb and Smith’s plastic surgery. 8th ed. Wolters Kluwer; 2019.

G. Campiglio and N. Srdanović 7. Coleman SR. Structural fat grafting: basics and clinical applications in the hand, face, and nose. In: Nahai F, editor. The art of aesthetic surgery principles & techniques—aesthetic facial surgery. 2nd ed. CRC Press; 2010. 8. Coleman SR, Mazzola RF.  Fat grafting for facial rejuvenation. In: Cohen M, Thaller S, editors. The unfavorable result in plastic surgery: avoidance and treatment. 4th ed. Thieme; 2018. 9. Coleman SR, Saboeiro AP. Structural fat grafting. In: Neligan PC, editor. Plastic surgery. Vol. 2: aesthetic surgery. 4th ed. Elsevier; 2018. 10. de Maio M.  Unlocking the code to facial revitalization: a step-by-step approach to using injectables with the MD codes. Allergan Medical Institute; 2015. 11. Desai U, Ellenbogen R.  Structural fat grafting to the face. In: Tran TA, Panthaki ZJ, et  al., editors. Operative dictations in plastic and reconstructive surgery. Springer; 2017. 12. Funt DK.  Dermal fillers and neurotoxins. In: Cohen M, Thaller S, editors. The unfavorable result in plastic surgery: avoidance and treatment. 4th ed. Thieme; 2018. 13. Ghavami A, Graivier M. Soft tissue fillers. In: Janis J, editor. Essentials of aesthetic surgery. Thieme; 2018. 14. Greco M, Vitagliano T, Ciriaco AG. Filler. In: Scuderi N, Toth BA, editors. International textbook of aesthetic surgery. Springer; 2016. 15. Gutowski KA. Discussion on Funt DK—dermal fillers and neurotoxins. In: Cohen M, Thaller S, editors. The unfavorable result in plastic surgery: avoidance and treatment. 4th ed. Thieme; 2018. 16. Kinney BM, Rowe DJ, Stepnick D.  Non-surgical facial rejuvenation with fillers. In: Guyuron B, editor. Aesthetic plastic surgery video atlas. Elsevier Saunders; 2012. 17. Lambros V. Filler injection into the upper periorbital area. In: Chung KC, editor. Operative techniques in plastic surgery. Wolters Kluwer; 2019. 18. Mowlds DS, Lambros V. Discussion on Coleman SR, Mazzola RF—fat grafting for facial rejuvenation. In: Cohen M, Thaller S, editors. The unfavorable result in plastic surgery: avoidance and treatment. 4th ed. Thieme; 2018. 19. Nugent AG, Nestor MS, McGee CS.  Dermal fillers. In: Tran TA, Panthaki ZJ, et al., editors. Operative dictations in plastic and reconstructive surgery. Springer; 2017. 20. Pestana IA, Marks MW.  Dermal and soft tissue fillers. In: Chung KC, editor. Grabb and Smith’s plastic surgery. 8th ed. Wolters Kluwer; 2019. 21. Prendergast PM. Facial fillers. In: Shiffman MA, Di Giuseppe A, editors. Cosmetic surgery: art and techniques. Springer; 2013. 22. Shiffman MA.  Fat transfer to the face. In: Shiffman MA, Di Giuseppe A, editors. Cosmetic surgery: art and techniques. Springer; 2013. 23. Sinno S, Stuzin JM. Fat grafting at the time of facelifting. In: Chung KC, editor. Operative techniques in plastic surgery. Wolters Kluwer; 2019.

Part II Stem Cells and Clinical Path

8

Features and Biological Properties of Different Adipose Tissue Based Products. Milli-, Micro-, Emulsified (Nano-) Fat, SVF, and AD-Multipotent Mesenchymal Stem Cells Viacheslav S. Vasilyev, Anna A. Borovikova, Sergey A. Vasilyev, Natalia I. Khramtsova, Sergey A. Plaksin, Roman A. Kamyshinsky, Mikhail Y. Presnyakov, and Ilya I. Eremin 8.1

Introduction

Since the reinvention of autologous fat transfer back in the 1980s [1, 2], the procedure has grown to be much more than simple “lipofilling”, and today we realize that there is no uniform “fat graft” (FG), as the lipoaspirate (LA) can be a source of a wide range of products, which differ by their physical characteristics, biological properties, and clinical applications. In this chapter we propose a classification of LA products based on the way fat tissue is harvested and processed.

V. S. Vasilyev (*) South Ural State Medical University, Chelyabinsk, Russia A. A. Borovikova Topclinic of Aesthetic Medicine, Moscow, Russian Federation S. A. Vasilyev Plastic Surgery and Cosmetology, South Ural State Medical University, Chelyabinsk, Russian Federation N. I. Khramtsova · S. A. Plaksin Perm State Medical University, Perm, Russian Federation R. A. Kamyshinsky · M. Y. Presnyakov · I. I. Eremin National Research Center “Kurchatov Institute”, Moscow, Russian Federation

We will also discuss cellular products that can be obtained from human fat. Various products obtained from human LA and the way they are related to each other are demonstrated in Fig. 8.1. Millifat and microfat  The first important variable that defines the LA product is the size of fat particles [3, 4]. Harvesting cannulas with big end-tip openings (generally larger than 1  mm) yield a product which we will further refer to as millifat. Cannulas with openings around 1  mm and smaller would produce microfat. Both products can be further processed in order to separate fat tissue from blood, tumescent fluid and oil from ruptured adipocytes. Microfat could be alternatively obtained by passing millifat through an appropriately sized filter-emulsifier. The classic fat grafting technique popularized by Coleman basically utilizes millifat [5], while microfat has emerged at the point when surgeons realized that the “classic” FG is suboptimal for use in certain clinical situations, like injection into delicate areas (eyelids) or thick tissues (wounds, scars). A thinner filling cannula and a more uniform product with smaller particles facilitating a smoother flow, as well as a more even distribution, were therefore sought [6, 7]. A

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Decellularized adipose tissue Millifat (> 1mm) Microfat (≤ 1mm)

Collagenase digestion

Emulsification

Processing (decantation, centrifugation, filtration, enrichment)

Stromal vascular fraction (eSVF, mSVF)

Emulsified fat (nanofat)

Fat graft

Adipose-derived stem cells

Cryopreserved fat

Fig. 8.1  Different products obtained from human LA and their interrelations

particle size of roughly 1 mm was found to meet these criteria. Histologically, both millifat and microfat present a well-preserved adipose tissue architecture with viable adipocytes [6, 8]. The difference is clinical: the main effects of millifat are volumetrical, while microfat is used more superficially for surface irregularities treatment and as a regenerative product. Detailed clinical uses of milliand microfat grafts are presented in Table 8.1. Emulsified fat (nanofat)  The concept of nanofat was introduced by Tonnard et al. in 2013. To obtain nanofat, a microfat graft is quickly shifted between two interconnected 10 cc syringes until a whitish liquid emulsion is obtained; it is further filtered and the effluent is collected as the resulting nanofat [8]. Alternative methods of obtaining nanofat include passing milli-/microfat through a series of emulsifiers and strainers with a diminishing hole size [3]. Nanofat is thus characterized by the least parcel size—400–600  μm or less. Emulsification completely destroys the normal adipose tissue structure leaving no viable adipocytes. The numbers of stromal vascular fraction (SVF) cells are

diminished, but their functionality seems to be preserved [8]. The liquid texture of nanofat allows to correct superficial irregularities without building up additional volume, and the pronounced regenerative properties render its wide use both for aesthetic and curative purposes (see Table 8.1). Centrifuged fat  Centrifugation effectively separates fat from nonviable components of the LA—the least dense oil fraction collects on the top and the blood-liquid fraction—at the bottom of the centrifuged syringe [9]. The middle fat layer displays a preserved native fat tissue architecture with a non-uniform distribution of both viable adipocytes and SVF cells [10]. The lower sublayer of centrifuged fat is characterized by a high concentration of SVF cells, presenting a ready-for-use enriched graft [11]. The putative mechanisms of better graft take when using the lower portion of centrifuged fat include stimulation of angiogenesis, preadipocyte differentiation, and decreased immune reactions at the site of injection. The main drawback for the wide use of centrifuged FGs in clinical practice is the relatively

8  Features and Biological Properties of Different Adipose Tissue Based Products. Milli-, Micro-…

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Table 8.1  Products obtained from human lipoaspirate (LA), their biological properties and clinical uses (MLF millifat, MCF microfat, EF emulsified fat/nanofat, CF centrifuged fat, SVF stromal vascular fraction, ASCs adipose-derived stem cells, CRF cryopreserved fat) Main features

Product type MLF MCF EF

CF

SVF ASCs CRF Method of preparation

MLF MCF EF

CF SVF ASCs CRF Biological properties

MLF MCF EF CF

SVF

ASCs

CRF

Description Tissue particle size 1–3 mm Injectability: 18 gauge Tissue particle size 38.5 °C) 3. Jaundice 4. Renal changes 5. Retinal changes 6. Drop in hemoglobin 7. New onset thrombocytopenia

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8. Elevated ESR 9. Fat macroglobulinemia Two major criteria or one major criteria and four minor criteria suggest a diagnosis of FES. Unfortunately, sometimes a diagnosis cannot be achieved based on these criteria and as a result it requires the use of other procedures—like some non-specific lab tests. In these patients the level of lipase, free fatty acids, and phospholipase A2 can be elevated. A CT will show diffuse vascular congestion and pulmonary edema, as well as pneumonitis. Patients will demonstrate hypoxemia while on room air on arterial blood gas. Fat globules can be identified in blood, urine, and sputum. Fat inclusions can be found in bronchoalveolar lavage. Although this is not a frequent diagnostic procedure when it comes to FES, it is slightly more specific than the rest. Also, an ECG and EHO of the heart can be useful. Shiva Prakash et al. found that elevated levels of IL-6 around the 12th hour after trauma is a strong indicator that FES will develop in these patients [13]. As said earlier, according to Cárdenas-­ Camarena’s newly acquired terms, FES fits MIFE.  So, the previously mentioned diagnostic procedures cannot be applied to MAFE.  The diagnosis of MAFE must be achieved based on the super acute clinical manifestation (momentarily after the fat particles enter the bloodstream or a few hours after). The clinical presentation of MAFE begins with deteriorated cardiopulmonary function, hypoxemia, hypocapnia, bradycardia, generalized anxiety, and respiratory effort. If possible, a transoesophageal ultrasound of the heart will confirm the diagnosis. Unfortunately, the diagnosis is usually confirmed on the coroner’s table [8].

22.6 Treatment and Therapy Treatment of a fat embolism, whether it is a micro or macro embolism, is always done in an intensive care unit. The treatment of MIFE is actually the same as treating FES which is well

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known in literature. The basics in treating FES are fluid restoration and cardiovascular and respiratory support. Half of the patients will need to be intubated and put on mechanical ventilation with positive pressure. The infusion of albumins has multiple benefits—they stabilize the intravascular volume and bound FFA thus reducing inflammation. Although useful, the infusion must be strictly controlled, as they can accumulate in the lungs and worsen respiratory function [8]. Dextran, corticosteroids, and heparin, according to some authors, can have a positive effect by reducing platelet aggregation and preventing thrombocytopenia. The use of ciclesonide, which is a corticosteroid that is inhaled, is a safe and efficient method in the prevention of severe hypoxia after posttraumatic FES.  It was noticed that alcohol reduces the activity of the serum lipase and that alcoholics are less affected by FES.  A bolus of 5% alcohol could be useful in the treatment of FES or in its prevention, but this method has not been accepted [14]. As previously stated, MAFE is very similar to a massive pulmonary embolism. Treatment consists of respiratory and cardiovascular support. Blood pressure is regulated with dobutamine and respiratory support means the intubation of the patient with positive airway pressure [15]. In literature some additional or alternative methods are also mentioned, such as administration of high doses of rosuvastatin and n-acetylcysteine which could eventually reduce respiratory symptoms of a fat embolism [16]. When the condition already occurred, treatment is supportive and usually insufficient. According to literature, 99% of these cases are fatal. In these cases, prevention is the only treatment [8]. Durán et  al. did a study that included 15 case reports and came to a conclusion that 100% of MIFE confirmed patients survived with adequate treatment, where as 100% of MAFE confirmed patients died. The authors suggested that this proves the existence of two different entities [1]. A recently published case report showed that MAFE can be survived. This patient survived the event due to early detection, aggressive management, and proper transfer to an intensive care unit [17].

K. Andjelkov and N. Music

22.7 Prevention of MIFE and MAFE The aesthetic surgery education and research foundation (ASERF) formed a Task Force of 11 surgeons, pathologists, and statisticians to study the risks of both fatal and nonfatal PFEs from gluteal fat grafting as well as any potential variables affecting these risks [7]. Their recommendations for preventing FES after gluteal fat grafting are as follows: 1. Avoid injecting into the deep muscle. 2. Use ≥4.1  mm diameter single hole injection cannula. 3. Avoid downward angulation of the cannula. 4. Position patient and place incisions to create a path that will avoid deep muscle injections. 5. Maintain constant 3-dimensional awareness of the cannula tip. 6. Only inject when cannula is in motion. 7. Consider pulmonary fat embolism in unstable intra- and postoperative patients. 8. Review gluteal vascular anatomy. 9. Include the risk of fat embolism and surgical alternatives in the informed consent process. Bayter-Marin et al. explained and emphasized the importance of differentiating MIFE and MAFE in their paper [18]. They also gave recommendations on how to prevent both events: 1. It is advisable not to lipoinject the upper fraction obtained during liposuction because it contains the greatest amount of free fatty acids, and this could be a factor that favors the appearance of microscopic fat embolism. 2. Adequate hydration of any patient undergoing liposuction is essential; this facilitates elimination of fatty acids from the blood. 3. Lipoinjection must be reduced in highly vascularized areas, such as muscles. This decreases the risk of introducing large amounts of fat into the bloodstream. 4. To prevent injuring the gluteal vessels, deep intramuscular injections in the gluteal region, especially in the medial portion adjacent to the piriformis muscle, should be avoided.

22  Fat Grafting and Fat Embolism. How to Prevent, Diagnose, and Treat

5. In case of a sudden deterioration of the general state of the patient, the surgical procedure should be suspended, and the possibility of having fat in the bloodstream should be considered. 6. The use of methylprednisolone or ciclesonide before surgery should be considered as a preventive measure. The last few years, the injecting of fat intramuscularly has become very controversial. As already mentioned, injecting fat in deep muscle tissue of the gluteal region can cause serious consequences and threaten the life of a patient. Surgeons are advised to avoid injecting in these regions. New studies show that the only the subcutaneous space is safe in the gluteal region [19]. It is important to note that the previous recommendations refer to the gluteal region. It could be expected that the injection of fat intramuscularly in other regions could lead to similar problems. But studies show that the intramuscular injection of fat in the pectoral and latissimus dorsi muscle is safe and is frequently used in breast reconstruction and aesthetic augmentation [20]. There are a small number of papers in literature concerning FES after lipofilling in deep muscle tissue in other regions, so caution is advised.

22.8 Conclusion Fat embolization in its two forms, MIFE and MAFE, is acknowledged as one of the most severe complications of fat grafting. Both forms of fat embolization occur as a result of fat particles entering the blood stream, but their clinical presentations, prevention, treatment, and prognoses are completely different. A quick diagnosis and immediate treatment drastically increase the chances of a positive outcome. To maximize the prevention of a fat embolism, the selection of an eligible patient, the selection of a safe region, correct performing of the procedure, and excellent knowledge of anatomy is of great importance.

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References 1. Durán H, Cárdenas-Camarena L, Bayter-Marin JE, Ramos-Gallardo G, Robles-Cervantes JA. Microscopic and macroscopic fat embolism: solving the puzzle with case reports. Plast Reconstr Surg. 2018;142(4):569e–77e. 2. Gauss H. The pathology of fat embolism. Arch Surg. 1924;9:593–605. 3. Neuber F.  Fettransplantation. Bericht über die Verhandlungen der Deutschen Gesellschaft für Chirurgie Zbl Chir. 1893;22:66. 4. Coleman SR. The technique of periorbital lipoinfiltration. Oper Tech Plast Reconstr Surg. 1994;1:20–6. 5. Gutowski KA, ASPS Fat Graft Task Force. Current applications and safety of autologous fat grafts: a report of the ASPS fat graft task force. Plast Reconstr Surg. 2009;124(1):272–80. 6. Cansancao AL, Condé-Green A, Gouvea Rosique R, Junqueira Rosique M, Cervantes A. “Brazilian Butt Lift” performed by board-certified Brazilian plastic surgeons: reports of an expert opinion survey. Plast Reconstr Surg. 2019;144(3):601–9. 7. Mofid MM, Teitelbaum S, Suissa D, et  al. Report on mortality from gluteal fat grafting: recommendations from the ASERF task force. Aesthet Surg J. 2017;37:796–806. 8. Cárdenas-Camarena L, Durán H, Robles-Cervantes JA, et  al. Critical differences between microscopic (MIFE) and macroscopic (MAFE) fat embolism during liposuction and gluteal lipoinjection. Plast Reconstr Surg. 2018;141:880–90. 9. Mentz HA. Fat emboli syndromes following liposuction. Aesthet Plast Surg. 2008;32(5):737–8. 10. Sito G, Manzoni V, Sommariva R.  Vascular complications after facial filler injection: a literature review and meta-analysis. J Clin Aesthet Dermatol. 2019;12(6):E65–72. 11. Beleznay K, Carruthers JDA, Humphrey S, Jones D.  Avoiding and treating blindness from fillers: a review of the world literature. Dermatol Surg. 2015;41(10):1097–117. 12. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br. 1974;56B:408–16. 13. Prakash S, Sen RK, Tripathy SK, Sen IM, Sharma RR, Sharma S. Role of interleukin-6 as an early marker of fat embolism syndrome: a clinical study. Clin Orthop Relat Res. 2013;471:2340–6. 14. Mellor A, Soni N.  Fat embolism. Anaesthesia. 2001;56:145–54. 15. Eriksson EA, Pellegrini DC, Vanderkolk WE, Minshall CT, Fakhry SM, Cohle SD.  Incidence of pulmonary fat embolism at autopsy: an undiagnosed epidemic. J Trauma. 2011;71(2):312–5. 16. Whalen LD, Khot SP, Standage SW. High-dose rosuvastatin treatment for multifocal stroke in trauma-­ induced cerebral fat embolism syndrome: a case report. Pediatr Neurol. 2014;51(3):410–3.

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17. Peña W, Cárdenas-Camarena L, Bayter-Marin JE, 1 9. Wall S Jr, Delvecchio D, Teitelbaum S, Villanueva NL, Dayan E, Durand P, Sanniec K, Rohrich McCormick M, Durán H, Ramos-Gallardo G, Robles-­ RJ.  Subcutaneous migration: a dynamic anatomiCervantes JA, Macias AA. Macro fat embolism after cal study of gluteal fat grafting. Plast Reconstr Surg. gluteal augmentation with fat: first survival case 2019;143(5):1343–51. report. Aesthet Surg J. 2019;39(9):NP380–3. 18. Bayter-Marin JE, Cárdenas-Camarena L, Aguirre-­ 20. Santanelli di Pompeo F, Laporta R, Sorotos M, et al. Latissimus dorsi flap for total autologous immediate Serrano H, Durán H, Ramos-Gallardo G, Robles-­ breast reconstruction without implants. Plast Reconstr Cervantes JA.  Understanding fatal fat embolism in Surg. 2014;134:871–9. gluteal lipoinjection: a review of the medical records and autopsy reports of 16 patients. Plast Reconstr Surg. 2018;142(5):1198–208.

Potentials and Limitations of the Use of Platelet-Rich Plasma (PRP) in Combination with Lipofilling. An Evidence-­Based Approach

23

Joris A. van Dongen, Hieronymus P. Stevens, and Berend van der Lei

Key Messages • The addition of platelet-rich plasma to lipofilling does not increase skin rejuvenation. • TCA peeling might be used as a trauma trigger to induce regeneration by platelet-rich plasma enriched lipofilling. • Platelet-rich plasma enriched lipofilling might be effective to augment dermal wound healing and decrease postoperative recovery time.

Supplementary Information  The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_23) contains supplementary material, which is available to authorized users. J. A. van Dongen (*) Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, the Netherlands Department of Plastic Surgery, University of Groningen and University Medical Center of Groningen, Groningen, the Netherlands H. P. Stevens Velthuis Kliniek, Rotterdam, the Netherlands B. van der Lei Department of Plastic Surgery, University of Groningen and University Medical Center of Groningen, Groningen, the Netherlands Bergman Clinics, Heerenveen, the Netherlands e-mail: [email protected]

• Scientific evidence of platelet-rich plasma as additive to lipofilling to regenerate skin fibrosis is lacking. • Platelet-rich plasma enriched stromal vascular fraction seems promising as a treatment of alopecia androgenetic although well-designed prospective randomized trials are lacking. • Well-designed prospective randomized trials are necessary to further develop the field of regenerative medicine in plastic surgery. • Growth factors released by platelets influence behavior of adipose derived stromal cells. • Autologous lipofilling can be used as treatment in four different ways: (non)-processed lipofilling, cellular stromal vascular fraction, tissue stromal vascular fraction, or adipose derived stromal cells.

23.1 Introduction Lipofilling, the transplantation of adipose tissue, has been used to restore volume loss due to aging and congenital or traumatic defects for decades. Later on, the number of clinical indications for using lipofilling expanded towards a more regenerative based approach, e.g., to remodel dermal fibrosis or to improve dermal wound healing [1]. The regenerative capacity of adipose tissue can be mainly ascribed to the stromal vascular fraction

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(SVF). SVF of adipose tissue contains all nonMeanwhile, new strategies to improve the adipocyte cell types, e.g., adipose derived stromal regenerative capacity of lipofilling were develcells (ASCs), fibroblasts, immune cells, endothe- oped such as platelet-rich plasma (PRP). PRP is lial cells as well as extracellular matrix (ECM). defined as a portion of plasma of autologous One of the most important cell types are ASCs, blood having a concentration of platelets above which reside in the SVF as precursor cells attached baseline which can be concentrated in different to vessels as pericytes and periadventitial cells. In amounts by several commercially available 2001, Zuk et  al. were the first to enzymatically devices [4]. As an isolated treatment, PRP has isolate SVF from adipose tissue and were able to been tested for multiple clinical indications such expand the number of ASCs in culture [2]. ASCs as wound healing or alopecia androgenetic showwere shown to be capable to differentiate into ing some beneficial effect. Platelets synthesize multiple cell lineages such as ectodermal, endo- large numbers of growth factors with regeneradermal, and mesenchymal cells. Upon culture, tive capacities, e.g., vascular endothelial growth ASCs secrete a plethora of growth factors, cyto- factor (VEGF), platelet derived growth factor kines as well as proteins, which are immunomod- (PDGF), transforming growth factor-β (TGF-β), ulative and are able to stimulate angiogenesis and and epidermal growth factor (EGF). These facremodeling the extracellular matrix. Hence, ASCs tors stimulate angiogenesis as well as proliferaare believed to be the key player in the regenera- tion and differentiation, e.g., adipogenesis of tive capacity of SVF from adipose tissue. ASCs and therefore might have a synergistic To increase the regenerative capacity of lipo- effect when combined with ASCs present in fat filling, ASCs were enzymatically isolated and grafts. For instance, VEGF is present in a high added to fat used for lipofilling (e.g., the so-called amount in fat graft as well as platelets and plays lipograft). The first enzymatic isolation proce- an important role in wound healing by stimulatdure was developed by Zuk et al. and required a ing endothelial proliferation and migration. specialized culture laboratory (good manufactur- PDGF stimulates proliferation and migration of ing practice facilities), which was expensive and ASCs and plays an important role in hair follicuvery unpractical for clinical use [2]. In the years lar stem cell activity and induction of the anagen following, numerous intra-operative enzymatic phase during the hair cycle in vivo. isolation devices have been developed. The vast Due to the variety of growth factors in platemajority of these intra-operative enzymatic isola- lets influencing ASCs in different ways, the comtion devices use collagenase to enzymatically bination of lipofilling with PRP might be even breakdown all adipocytes and cell–cell connec- more effective as a treatment for multiple clinical tions including extracellular matrix resulting in a indications, e.g., skin rejuvenation, dermal single cell suspension of SVF cells (cellular SVF wound healing, dermal fibrosis, or alopecia (cSVF)). However, these intra-operative enzy- androgenetic. Thus, the aim of this chapter is to matic isolation procedures are still time-­ discuss the current available clinical evidence of consuming and expensive [3]. Moreover, the the addition of PRP to lipofilling for the aforeclinical use of enzymes became forbidden by leg- mentioned clinical indications. islation in many countries. Therefore, other so-­ called intra-operative non-enzymatic or mechanical isolation procedures were subse- 23.2 Platelet-Rich Plasma quently developed for clinical use. Mechanical Enriched Lipofilling for Skin isolation procedures only use shear-stress to disRejuvenation rupt adipocytes while maintaining all cell–cell connections including extracellular matrix result- In 2006, Coleman discovered that lipofilling was ing in a tissue-like SVF (tSVF). These mechani- more than a permanent filler. Coleman described cal isolation procedures are less expensive and that the skin above the transplanted adipose tisless time-consuming as compared to enzymatic sue improved by showing a decreased pore size isolation procedures [3]. and less scarring caused by acne. In the years fol-

23  Potentials and Limitations of the Use of Platelet-Rich Plasma (PRP) in Combination with Lipofilling…

lowing, multiple studies described that lipofilling could rejuvenate aged skin [5]. To stimulate skin rejuvenation by lipofilling, PRP was added to lipofilling to function as a biological catalyst for ASCs. Gennai et  al. stated that PRP-enriched micro-superficial enhanced fluid fat injection, a form of autologous lipofilling, rejuvenated facial skin in 65 patients (Tables 23.1 and 23.2) [6]. Results were analyzed by subjective clinical assessment of photographs of patients up to till six months post-surgery by the senior author. This study, however, lacks all objective measurement outcomes necessary to analyze effects of skin rejuvenation, statistics and preoperative results. Besides, PRP-enriched lipofilling as single treatment was only used in seven patients. Ozer and Colak treated 14 patients with facial lipofilling mixed with PRP and showed a significant increase in the FACE-Q modules of satisfaction with skin when preoperative scores were compared to postoperative scores with a minimum of 9 months of follow-up [7]. Rigotti et al. was one of the first to show that the addition of PRP to lipofilling histologically changes treated facial skin [8]. This study compared preoperative skin biopsies with 3  months postoperative skin biopsies in 13 patients. PRP-enriched lipofilling resulted in a less organized elastic fiber network with more dissociated elastic fibers with a smaller diameter and smoother surface in the reticular dermis. Furthermore, PRP-enriched lipofilling also improved vasculature and increased inflammation in the postoperative skin biopsies. Although this study showed interesting histological changes of the skin after treatment of PRP-­ enriched lipofilling, no clinical results were mentioned nor described (Tables 23.1 and 23.2) [8]. Therefore, it remains unclear whether these histological changes are significant enough to lead to visible skin changes and/or improvement. Moreover, all the aforementioned studies did not use a control group. The lack of a control group implicates getting insufficient reliable results because a placebo effect cannot be excluded. It is also well-known that fine needling can induce skin changes, another reason definitely to include a control group.

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To date, only one well-designed prospective randomized double-blinded placebo-controlled clinical trial has been published studying the addition of PRP to facial lipofilling to rejuvenate aged skin (Tables 23.1 and 23.2) [9]. This study treated 25 patients divided into two treatment groups: saline enriched lipofilling versus PRP-­ enriched lipofilling. Patients were followed for 12 months and results were analyzed using a validated cutometer to measure skin elasticity. Skin elasticity in both groups did not improve when preoperative skin was compared with postoperative skin nor did the addition of PRP result in an improved skin elasticity postoperative [9]. However, when a regression analysis was performed of skin elasticity as a function of age, a negative correlation was seen preoperative in both intervention groups. After treatment of lipofilling or PRP-enriched lipofilling, the correlation reverses, especially in the PRP-enriched lipofilling group. Although the results were not significant, this could be an indication of some skin rejuvenation. Furthermore, the recovery time expressed as the number of days it took to return to work was significantly lower when patients underwent PRP-enriched facial lipofilling in comparison with saline enriched facial lipofilling [9]. These results indicate that the addition of PRP accelerates the recovery of damaged tissue that is caused during the intervention. The addition of PRP therefore might be more beneficial in case of restoring damaged tissue, e.g., fibrosis or wound healing, instead of rejuvenation of relatively healthy skin. To date, the evidence of PRP-­ enriched lipofilling as a treatment for skin rejuvenation is thus lacking although postoperative recovery time is significantly reduced.

23.3 Platelet-Rich Plasma Enriched Lipofilling for Wound Healing Chronic non-healing dermal wounds are a large socioeconomical burden worldwide. In 2018, the prevalence of chronic wounds of mixed etiologies, i.e., venous ulcers, diabetic ulcers, arterial

Prospective, controlled, blinded, randomized

Intervention: Lipofilling + PRP Control: Lipofilling + NaCl

Patients with aging facial skin (n = 25)

Skin elasticity measured with the cutometer up to 12 months postoperative

Histological analysis 3 months postoperative

Intervention: Lipofilling + PRP

Patients with aging skin in preauricular region (n = 13).

Reticular dermis showed a decrease in elastic fibers with reduced diameter and smoother. Increase of mononuclear cell infiltration around vessels. No statistics used No significant difference in skin elasticity between both groups and within each group when preoperative is compared to postoperative

*** Satisfaction with skin improved from 33.7 ± 18.1 to 88.0 ± 20.3

Results No preoperative results. No statistics used

No complications reported

Not mentioned

No complications reported

Complications No complications reported

PRP platelet-rich plasma, M-SEFFI micro-superficial enhanced fluid fat injection, SEFFI superficial enhanced fluid fat injection, MIVEL minimal incision vertical endoscopic lift, MAFT micro-autologous fat transplantation *** p  0.05) differences in the 3-month versus 12-month post-operative period comparisons are detected. Bleeding, infection, and asymmetry might occur. In our cases, the most common complication was hematoma at the recipient site when we used blunt cannulas in very hypoplastic tissues, the incidence decreased markedly with the use of tissue friendly cannulas with special finishing. We had no cases of infection. Hypaesthesia occurred in liposuction, but it disappears after a few months. Hemosiderin pigmentation (pigmentation of the superficial dermis) was seen in two cases that had bruises and remained between 6 and 9 months. In these cases, we used a gel with heparin that enhanced resolution. 58.4.4.8 T  echnical Aspects, Take Rate, and Overcorrection The necessity for secondary optimizing or complementary fat-graft sessions affects a large per-

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centage of the cases (in our series 6 out of 19) depending on patient factors (i.e., patient age), individual indication criteria, and adopted surgical techniques. There is no consensus on the ideal timing for complementary fat-graft sessions. It is difficult to assess the new final contours in the frame of the surgical outcome during the first 3 months, as the extent of tissue edema and inflammation cover actual anatomy and may act as confounding factors. Most volume resorption will be apparent at the 3–4-month postprocedure evaluation, at which time subsequent lipoinjections may be performed if there are no external signs of residual post-operative inflammation. Overcorrection of facial asymmetry in initial procedures is often recommended to compensate for post-operative volume loss and limit the number of successive injections [22]. It is expected that multiple sessions will be needed for larger defects. We have adopted overcorrection as a method to compensate for anticipated fat graft loss at PRS to resolve facial asymmetry in pediatric and adult patients, believing that overcorrection is useful. In the craniofacial fat grafting literature, overcorrection of up to 30% has been reported. Restriction to the volume required to achieve symmetry of each facial unit during the surgery is difficult as no one can predict the final take rate and exact volume necessary for the compartments. On the other hand, long-lasting primary overcorrection is hardly possible. The volume increase is limited by a patient’s tight skin envelope. Placing extensive, large fat-graft volumes to a recipient area is restricted. Patients with PRS deformities require higher fat volumes for each specific compartment like for example at facial aesthetic rejuvenation because they are so underdeveloped or atrophic. The scarred and/or atrophic soft tissue in PRS may impose a greater resistance to expansion in contrast to other patients. The fat grafting and its final take rate in PRS patients independent

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from age are less predictable, and supplementary fat grafting is more applicable to patients diagnosed with PRS. According to our experience, the take rate is decreased in those patients who underwent previous bone surgical intervention at the site receiving fat grafting, and/or those who have frontal/ temporal contour deformities. Recent studies suggest that the addition of platelet-rich plasma to the graft maximizes long-term outcomes and reduces graft resorption [23]. In the future, concurrent adipose-derived stem cell-rich transplants may enhance better retention. According to the observation of the authors, platelet-rich plasma (PRP) or injectable platelet-rich-fibrinogen (iPRF) to the graft may maximize long-term outcomes. Case 1. PRS Patient Treated with Two Sessions of Autologous Fat Grafting We describe a 26-year-old male patient who required significant soft-tissue augmentation utilizing microstructural fat grafting by Dr. Pataki, assisted by Dr. Kalatovics. The onset of PRS was at the age of 6. Progression type was a slowly progressing manifestation. The patient was affected from the frontal/temporal areas to the

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chin in all regions. It was first treated as scleroderma with local agents like creams with Vitamin E or colchicine at the age of 10. At the age of 16, the diagnosis of scleroderma en coup de sabre was set. At the age of 22, treatment with steroids and methotrexate with considering cyclophosphamide was suggested. Lipofilling, CAD_CAM frontal bone implant, and rhinoplasty were considered. The patient had no extracutaneous disease manifestations except ocular symptoms: enophthalmos, iris stromal atrophy, and atrophy/ hypoplasia of frontal bone and sinus and double curvature of nervus opticus in the orbita. He had no autoantibodies, no inflammation components, moderate cardiolipin IgG, and RF elevation. The patient had significant psychosocial problems as the facial asymmetry had caused shame in his daily interactions. Our patient was treated with 170 cc of microstructural fat from the waist and abdomen and thighs. Planned regrafting was carried at 4 months with 110 cc of fat. 2-year follow-up photos are presented. Rhinoplasty is planned as the next procedure. [Video animation of the change of the softtissue contour in Patient 1, before and after surgery (Animation.mpg/Animationpostop.mpg)]

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Fig. 58.9  Photos of Patient 1, before surgery: non-animated right lateral and frontal; second row: animated right lateral and frontal

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Fig. 58.10  Photos of Patient 1 before the treatment with marking (superior, frontal, right lateral and right oblique views)

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Fig. 58.11  Photos of Patient 1 before surgery. (a) frontal, (b) inferior frontal, (c) right oblique, (d) left oblique, (e) right lateral, (f) left lateral aspects

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Fig. 58.12  Photos of Patient 1, 5 days after surgery: frontal, right lateral views. Note the extensive swelling of the grafted areas of the face. Adhesive skin strips cover the entry points and support the lower lid and brow

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Fig. 58.13  Photos during the facial fat grafting surgery of Patient 1. Bimanual maneuvers (Inserting the cannula, elevating of the tissues, supporting the tissues and head). (a) Lipofilling of the forehead from a lateral temporal hairline entry point with protecting and leading the tip of the cannula with the left hand. (b) Close up: Lipofilling of the right forehead and brow from a lateral temporal hairline entry point with protecting and leading the tip of the cannula with left hand. (c) Lipofilling of the temporal region from a frontotemporal hairline entry point with protecting the tip of the cannula with left hand. (d) Lipofilling of the temporal region from a superciliar entry point with protecting the tip of the cannula with left hand). Photos of patient 1 after surgery: frontal, left

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oblique, right oblique, left lateral, right lateral views. (e) Lipofilling of the brow from a lateral entry point with protecting and leading the tip of the cannula with left hand. (f) Lipofilling of the cheek from a lower paranasolabial entry point with protecting the tip of the cannula with left hand. (g) Lipofilling of the cheek from a preauricular entry point with protecting the tip of the cannula with left hand. (h) Lipofilling of the cheek from a temporal entry point with protecting the tip of the cannula with left hand. (i) After Lipofilling of the right face taping with skin-friendly Omnistrips™. (j) inferior frontal view of the patient at postop 2 years. (k, l) Maneuver showing pinch test with volumetrized right midface and cheek

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Fig. 58.13 (continued)

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Fig. 58.14  Two years after surgery: frontal, superior frontal, inferior frontal, left oblique, right oblique, left lateral, and right lateral views

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Fig. 58.15 (a) 3D reconstruction models enable better analyzing and comparison. The models are based on the pre-operative and post-operative CT Imaging showing

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soft-tissue contour changes before and after surgery (frontal, right affected side, and superior aspect)

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Fig. 58.15 (continued) (b) 3D reconstruction models based on the pre-operative and post-operative CT Imaging showing soft-tissue contour changes before and

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after surgery (superior oblique aspects, and frontal and non- affected side aspects)

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Fig. 58.15 (continued) (c) 3D reconstruction models based on the pre-operative CT Imaging showing soft-tissue contour deficiency before surgery with the underlying skull (frontal, affected and non-affected side)

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Fig. 58.15 (continued) (d) 3D reconstruction models based on the post-operative CT Imaging showing soft-tissue contour changes after the fat grafting surgery (frontal, right affected side and non-affected side)

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Case 2 treated with 80 cc of microstructural fat from the 24 years old female patient with left-sided Parry-­ abdomen. Romberg syndrome before and 20 months after No regrafting was indicated. the operation by Dr. Pataki. Our patient was

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Fig. 58.16  Pre-operative status of a female patient (24 y) with left-sided PRS. Oblique views (a) and (b) and frontal view (c); note the left buccal inclination on picture (c)

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Fig. 58.17  20 months post-lipofilling follow-up of a female patient (24 y) with left-sided PRS. Oblique views (a) and (b) and frontal view (c); note the regained left buccal contour on picture (c)

58  Parry-Romberg Syndrome Treatment with Microstructural Fat Grafting of the Face

Case 3 4 months and 2.5 y preop-postop photo comparison of a 7-year-old female with Romberg’s hemifacial atrophy treated with microstructural fat grafting by Dr. Pataki, assisted by Dr. Kalatovics,

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for increasing volume and improving contours (pre-op., after 4 months, and after 2.5 years). Result: visible volume and midfacial and lateral contour change left (arrow).

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Fig. 58.18  Superior aspect. (a) Pre-operative status (b) 4 months post-op., with regained contour

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Fig. 58.19  Affected side view. (a) Pre-operative status (b) 4 months post-op. (c) 2.5 years post-op. with visible moderate contour improvement

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Fig. 58.20  Frontal angle. (a) Pre-operative status (b) 4 months post-op. (c) 2.5 years post-op. with visible moderate contour improvement

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Fig. 58.21  Inferior aspect. (a) Pre-operative status (b) 4 months post-op. (c) 2.5 years post-op., with visible moderate contour improvement

Case 4 Our 21-year-old female patient was diagnosed when she was 5 years old with progressive hemifacial atrophy (PHA) causing severe facial asymmetry. Physical examination showed extensive alopecia, localized hyperpigmentation, and severe atrophy of the skin and the underlying subcutaneous tissues on the left side of the face between the zygomatic arch, the body of the mandible affecting the left submental region, the nasolabial fold, and ear. The mimic muscles were not involved. Radiologic investigation showed bone involvement of the body of the mandible; however, relatively stable occlusion was observed. The main complaint of the patient was

severe facial asymmetry that constantly influenced her social interactions. Soft-tissue reconstruction was performed with a profunda artery perforator (PAP) flap to cover defect and tissue loss by Dr. Lóderer. At the same time, orthodontic treatment was started for the preparation of a further bimaxillary osteotomy. Concomitant optimizing autologous lipotransfer was performed at 1-year postop submental and mandibular and at 2 years postop hemifacial to refine the results achieved and to cover the remaining facial contour deformity. In our patient, no complications were experienced during the recovery period. At the 5 y follow-­ up (2.5 y from the last lipofilling), the

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patient showed outstanding quality and quantity of the facial skin with improved facial appearance, better symmetry, and good aesthetic out-

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come. This was well perceived by the patient, thus the main complaint has been managed successfully [18].

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Fig. 58.22  Patient 4. Pre-op. status and intraoperative demonstration of the free PAP-flap

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Fig. 58.23  Patient 4. Post-operative status at 1.5 years, 6 months after concomitant submental and mandibular optimizing autologous lipotransfer

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58.5 Conclusion

Fig. 58.24  Two years post-op. status of the affected side of the face with markings before secondary optimizing hemifacial lipofilling (frontal, temporal, mandibular, mental, submental, and cervical) to optimize the results achieved and cover the remaining facial contour deformity

Fat grafting is a safe and minimally invasive method for the treatment of facial contour deformities in PRS, and by shaping contours and adding volume, it can contribute to a significant improvement in the quality of life of the patients. This kind of reconstructive facial fat grafting is technically similar to fat grafting for facial rejuvenation purposes; however, it requires a unilateral, slightly different and more cautious approach for the reasons discussed in this chapter. Further well-executed randomized clinical trials or large comparative cohorts are necessary to define the real role of each fat-grafting technique in managing PRS-related hemifacial contour deformities. Finding predictors of facial fat-graft retention should be considered in these future studies. From a clinical perspective, plastic surgeons should consider the published outcomes to enhance pre-operative evaluation and surgical planning and to set realistic expectations for the patient and family when deciding on the operation (or series of operations) and obtaining informed consent.

Fig. 58.25  At the 5 y follow-up (2.5 y from the second lipofilling), the patient showed outstanding quality and quantity of the facial skin with improved facial appearance, better symmetry, and good aesthetic outcome.

884 Acknowledgments to Prof. Dr. József Piffkó and Dr. Huba Bajusz in the management of Patient 4. Special thanks to Alexandra Valéria Sándor for the general research support, writing assistance, translation, language editing, and proofreading. 3D animation video by courtesy of Dr. Kálmán Czeibert. Thanks to my assistant Dr. Botond Mihalovits for the photo selections.

References 1. Buonaccorsi S, Leonardi A, Cavelli E, et  al. Parry-Romberg syndrome. J Craniofac Surg. 2005;16(6):1132–5. 2. Tolkachjov SN, Patel NG, Tollefson MM. Progressive hemifacial atrophy: a review. Orphanet J Rare Dis. 2015;10:39. 3. Wong M, Phillips CD, Hagiwara M, Shatzkes DR.  Parry Romberg syndrome: 7 cases and literature review. Am J Neuroradiol. 2015;36(7):1355–61. https://doi.org/10.3174/ajnr.a4297. 4. Schultz KP, Dong E, Truong TA, Maricevich RS. Parry Romberg syndrome. Clin Plast Surg. 2019;46(2):231– 7. https://doi.org/10.1016/j.cps.2018.11.007. 5. Madasamy R, Jayanandan M, Adhavan UR, et  al. Parry Romberg syndrome: a case report and discussion. J Oral Maxillofac Pathol. 2012;16:406–10. 6. Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg syndrome: a ­retrospective review of 54 patients. J Am Acad of Dermatol. 2007;56:257–63. 7. Yamaguchi K, Lonic D, Ko EW, Lo LJ. An integrated surgical protocol for adult patients with hemifacial microsomia: methods and outcome. PLoS One. 2017;12:e0177223. 8. Romberg H. Trophoneuronsen. Klinische Ergebnisse 1846:75Y81 9. Xu M, Yang L, Jin X, Xu J, Lu J, Zhang C, Tian T, Teng L.  Female predominance and effect of sex on Parry-Romberg syndrome. J Craniofac Surg. 2013;24(4):1195–200. https://doi.org/10.1097/ SCS.0b013e318299759e. Review 10. Shah JR, Juhasz C, Kupsky WJ, et  al. Rasmussen encephalitis associated with Parry-Romberg syndrome. Neurology. 2003;61:395–7.

G. Pataki et al. 11. Stone J.  Parry-Romberg syndrome: a global sur vey of 205 patients using the internet. Neurology. 2003;61:674–6. 12. Przybilski R, Lemperle G.  Potential for operative correction in progressive facial hemiatrophy. Z Plast Chir. 1979;3(4):216–25. [Article in German] 13. Agostini T, Spinelli G, Marino G, Perello R. Esthetic restoration in progressive hemifacial atrophy (Romberg disease): structural fat grafting versus local/free flaps. J Craniofac Surg. 2014;25:783–7. 14. Berenguer B, Gallo H, Rodríguez Urcelay P, Marín Guztke M, González Meli B, Enríquez de Salamanca J.  Free fat flap for the treatment of Parry-Romberg disease in children. Cir Pediatr. 2005;18(1):49–51. [Article in Spanish] 15. Longobardi G, Pellini E, Diana G, Finocchi V. Rhytidectomy associated with autologous fat transplantation in Parry-Romberg syndrome. J Craniofac Surg. 2011;22:1031–4. 16. Sinno S, Wilson S, Brownstone N, Levine SM.  Current thoughts on fat grafting: using the evidence to determine fact or fiction. Plast Reconstr Surg. 2016;137:818–24. 17. Lu SM, Bartlett SP.  On facial asymmetry and self-­ perception. Plast Reconstr Surg. 2014;133: 873e–81e. 18. Loderer Z, Janovszky A, Lazar P, Piffko J.  Surgical management of progressive hemifacial atrophy with de-epithelialized profunda artery perforator flap: a case report. J Oral Maxillofac Surg. 2017;75:596–602. 19. Xie Y, Li Q, Zheng D. Correction of hemifacial atrophy with autologous fat transplantation. Ann Plast Surg. 2007;59:645–53. 20. Delay E.  Lipomodeling of the reconstructed breast. In: Spear SE, editor. Surgery of the breast: principles and art. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2006. p. 930–46. 21. Mojallal A, Auxenfans C, Lequeux C, Braye F, Damour O.  Influence of negative pressure when harvesting adipose tissue on cell yield of the stromal-vascular fraction. Biomed Mater Eng. 2008;18(4-5):193–7. 22. Blitstein MK, Vecchione MJ, Tung GA.  Parry-­ Romberg syndrome. Appl Radiol. 2011;40:34–6. 23. Modarressi A.  Platelet Rich Plasma (PRP) improves fat grafting outcomes. World J Plast Surg. 2013;2(1):6–13.

Correction of Secondary Craniosynostosis Deformities with Autologous Fat

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Karima Ismail and Bryant A. Toth

Key Messages • Lipofilling is a safe, effective way for correcting secondary deformities due to craniosynostosis. • Most secondary craniosynostosis surgery is done extracranially to improve facial appearance. • The secondary deformity depends on the suture involved. • Procedure can be done as an outpatient procedure with minimal morbidity. • All patients with craniosynostosis newly diagnosed are told about a possible secondary procedure involving fat.

59.1 Introduction Craniosynostosis is a condition in which premature closure of one or more of cranial sutures occurs resulting in potential intracranial pressure, The editor in chief wants to pay a tribute to Bryant A. Toth, dear colleague and an excellent chapter writer who passed away unexpectedly on October 3, 2021 while we were in development of the book. Rest in peace and thank you. K. Ismail Dept. of Plastic Surgery, Cairo University (Kasr Al-Ainy Hospitals), Cairo, Cairo Governorate, Egypt e-mail: [email protected] B. A. Toth (*) Craniofacial Program, UCSF Benioff Children’s Hospital, Oakland, CA, USA

along with abnormal brain and skull growth [1]. The incidence of craniosynostosis is 1:2500 live births [2]. Premature suture fusion may lead to a decrease in intracranial volume and potentially restrict brain growth (cephalocranial disproportion) [3]. Traditional management consists of craniectomy with removal of the involved suture and correction of the resultant deformity. Normally, we operate on these children between 4 and 12 months of age [1, 3]. Careful follow-up of these children reveals bones that have been moved during the correction of the craniofacial deformity do not always grow normally. Additional surgery for these secondary craniosynostosis deformities is therefore not uncommon. When elevated intracranial pressure is present or if the deformity is severe, a secondary intracranial procedure becomes necessary. However, most secondary craniosynostosis surgery is done extracranially to improve facial appearance in an effort to remove stigmata of fused sutures and restricted cranial growth. Extracranial options vary from, extracranial remodeling through coronal incision (sanding of the cranium), use of methyl methacrylate, or other alloplastic tissue substitutes (i.e., hydroxyapatite, bone pastes, Norion) or surgical osteotomy of the deformity done subcranially. We have found that autologous fat transfer to correct the deformity has turned out to be the best and most reliable way to deal with these deformities with a significant lower surgical morbidity.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_59

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59.2 T  he Secondary Deformity Depends on the Suture Involved With growth, resultant craniofacial deformities secondary to craniosynostosis are predictable depending on the suture involved. Without knowing the specific suture involved an experienced craniofacial surgeon can easily identify the ­original deformity purely through the secondary deformity. Below are examples of the typical secondary deformity that one sees in craniosynostosis.

59.2.1 Metopic Suture Synostosis or Trigonocephaly • • • •

Forehead is flat and frequently irregular. Supraorbital bar is recessed. Bilateral frontal and temporal hollowing. Persistent hypotelorbitism.

Fig. 59.1  Secondary metopic deformity

59.2.2 Unicoronal Suture Synostosis or Plagiocephaly 59.2.2.1 Secondary Unicoronal Deformity • Supraorbital bar recession on affected side can persist or increase with age • Forehead irregularity • Temporal hollowing on affected side

59.2.3 Sagittal Suture Synostosis or Scaphocephaly 59.2.3.1 Secondary Sagittal Deformity • Forehead is flattened and can be irregular • Left temporal hollowing • Right temporal hollowing Fig. 59.2  Secondary unicoronal deformity

59  Correction of Secondary Craniosynostosis Deformities with Autologous Fat

Fig. 59.3  Secondary sagittal deformity

Fig. 59.4  Secondary bicoronal deformity

59.2.4 Bicoronal Suture Synostosis or Brachycephaly 59.2.4.1 S  econdary Bicoronal Suture Deformity • Supraorbital bar recession • Forehead flattening and irregularity • Lateral frontal and temporal hollowing • Midface hypoplasia • Proptosis

59.2.5 Syndromic Bicoronal Suture Synostosis or Severe Brachycephaly 59.2.5.1 Secondary Syndromic Bicoronal Suture Synostosis • Magnification of the nonsyndromic form • Severe midface hypoplasia • Greater bifrontal flattering • Greater bifrontal temporal hollowing • Greater forehead irregularity

Fig. 59.5  Bicoronal suture synostosis

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59.3 Autologous Fat for Reconstructive Surgery Recently, autologous fat grafting for maxillofacial and craniofacial deformities has been reported. There are new horizons in application of structured fat grafting in complex reconstructive surgery. It can be applied in any area that lacks soft tissue resulting from tumor resection, trauma, congenital deformities, and clefts. Structural fat grafting is now commonly used in reconstructive surgery where previously it had been used exclusively in aesthetic surgery [4].

59.4 Correction of Secondary Craniosynostosis Deformities with Fat Over the past 35 years, we have treated in excess of 1000 patients with craniosynostosis. Beginning in 2010, we began to treat secondary deformities with autologous fat. Between 2010 and 2017 a total of 50 consecutive patients have been carefully followed who underwent correction of their secondary craniosynostosis deformity with autologous fat reconstruction. All surgery in this series of patients was done by the senior author. The breakdown of the deformities treated is as follows: • 15 secondary metopic deformities • 15 secondary syndromic deformities • 9 bicoronal deformities • 4 sagittal deformities • 7 unicoronal deformities

bicoronal

A total of 125 areas were treated with autologous fat in this series. The average age of the patient was 10 years 6 months old, varying from 4 years to 21 years old. The donor site was abdomen (60%) and upper buttock (40%). As a rule, we utilized the abdomen whenever possible, but if there was inadequate donor tissue available fat was harvested from the upper buttock. The average amount of fat transferred was 28.8 cc with a

range of 12 to 78 cc. Follow-up ranged from 3 months to 7 years.

59.5 The Surgical Procedure All procedures were performed under a general anesthetic as an outpatient unless fat was placed into the midface and concerns were raised over possible airway compromise. In that instance, patients were kept overnight for observation. Pre-surgically contour abnormalities of the face and forehead are carefully marked out in the waiting area. Photographs are then taken. In our experience, contour abnormalities are better visualized when the camera’s flash is not utilized. Observation: Irregular cranial contour Irregularities are best picked up without a flash Following the induction of general anesthesia, the abdomen or buttock (depending on the donor site) is carefully prepped with Betadine solution. Approximately 100 mL of tumescent solution (normal saline with 1:250,000 epinephrine) is infiltrated into the donor site. Through concealed 2–3  mm incisions appropriate fat amounts are harvested. By Coleman technique, harvesting cannula 3 mm diameter, blunt tip, and connected to 10 cc Luer-Lock syringe [5]. Donor sites are then closed with interrupted 5-0 rapid catgut suture, Steri-Strips applied, and a sterile dressing is placed on top. The fat which was harvested is then placed into 10 cc syringes and spun in a centrifuge for 3  min. After the separation of the supernatant fluid from oil, the fat is transferred into 1 cc tuberculin syringes. Attention is next focused to the recipient area. The entirety of the face is prepped with a soap solution (PCMX) and draped sterilely. The eyes are protected with Tegaderm or Steri-Strips to avoid any prep solution irritating the conjunctiva. Two to four small incisions are then made in concealed areas. In general, incisions are made in the brow and in the hairline. Small Coleman needles are then used and attached to the 1 cc tuberculin syringes. Initially, the passing of the cannula can

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Fig. 59.6  Irregular cranial contour is best photographed without the use of a flash

Fig. 59.7  Harvested fat is then centrifuged for 3 min

be met with resistance due to past scarring, but shortly passage becomes much easier. Slowly, the cannula is passed into the depressed area allowing us to precisely place fat in desired positions. We do not actively attempt overcorrect the ­forehead. We certainly try and make sure that when we are done the forehead and other areas

addressed are symmetric. No dressing is placed on the forehead. Patient’s discharge instructions are to keep the head in upright position (elevate head when sleeping), and are restricted from wearing anything (i.e., baseball cap, headband) that can result in placing pressure on the areas that have been addressed.

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Fig. 59.8  The SUPERNATANT fluid is allowed to flow out of the lower end of the syringe and fat is transferred to 1 cc syringes

Loose Areolar Tissue Musculoaponeurotic Layer Subcutaneous Layer

Fig. 59.9  Application of the fat starts deep from the loose areolar tissue just above the fixed periosteum and moves superficial towards the subcutaneous layer. The injection is volumetric and don’t get to the skin dermis

59.6 Results

59.6.1 METOPIC

Following are examples of secondary craniosynostosis deformities treated with autologous fat transfer. A minimum follow-up of one year is present in all patients in order to demonstrate the permanence of the fat.

• • • • •

14 cc to right temporal 9cc to left temporal 1cc to right supraorbital 1cc to left supraorbital 25 cc of total autologous fat

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59.6.2 Unicoronal • • • • •

8 cc to right temple 6 cc to right frontal 8 cc to supraorbital bar 5 cc to left temple 26 cc total autologous fat

59.6.3 Bicoronal • • • •

Fig. 59.10  Secondary metopic preoperative autologous fat grafting: location and amounts

40 cc to the forehead 11 cc to right orbit and temporal region 11 cc to left orbit and temporal region 62 cc total fat injected

In this series of 50 consecutive patients, there were two complications. One patient suffered from the overgrowth of fat on the affected side. The second complication was a small recipient site infection which resolved with antibiotics. No patient had long-term donor site problems from

Fig. 59.11  Metopic Suture SYNOSTOSIS preoperative (left); postoperative (right)

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Fig. 59.12  Secondary unicoronal deformity - autologous fat grafting planned location and amounts

Fig. 59.14  Secondary bicoronal deformity - autologous fat grafting locations and amounts

Fig. 59.13  Secondary right Coronal Synostosis. Preoperative (left); postoperative (right)

the procedure. The amounts of fat removed were small in proportion to the donor site. There are very few limits. Initially, all the patients were kept in the hospital overnight but now we feel as though it is safe, and they are sent home the evening of surgery.

59.7 Conclusions Autologous fat transfer to the face is an excellent technique for correction of secondary craniofacial deformities when open cranial surgery is not indicated. The need for autologous fat transfer as

59  Correction of Secondary Craniosynostosis Deformities with Autologous Fat

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Fig. 59.15  Secondary Bicoronal Deformity. Preoperative (left); postoperative (right)

Table 59.1  Injection site according to suture involved Suture involved Metopic Suture Synostosis

Unicoronal Synostosis

Sagittal Suture Synostosis

Bicoronal Suture Synostosis

Deformity Forehead flattening Supraorbital bar recessed Bilateral frontal and temporal hollowing Forehead irregularity Subraorbital bar recession on affected side Temporal hollowing on affected side Forehead flatten Bilateral temporal hollowing Forehead flattening Supraorbital bar recession Lateral frontal and temporal hollowing Midface hypoplasia

Site of fat Injection Supraorbital injection Temporal injection

Supraorbital injection Temporal injection Frontal injection

Forehead injection Temporal injection Forehead injection Orbital injection Temporal injection Midface injection

a planned secondary procedure in the future is frequently discussed at the time of the original procedure because certain deformities are predictable with growth and age. It has become our procedure of choice for craniofacial correction when intracranial pressure is absent.

References 1. Derderian CA, Bartlett SP.  Craniosynostosis syndromes. In: Thorne C, editor. Grabb and Smith’s plastic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. 2. Knoll B, Persing JA. Craniosynostosis. In: Bentz ML, Bauer BS, Zuker RM, editors. Pediatric plastic surgery. 2nd ed. St. Louis: Quality Medical Publishing; 2008. 3. Derderian C, Seaward J.  Syndromic cranisynostosis. Semin Plast Surg. 2012;26:64–75. 4. Clauser LC, et al. Structural fat grafting: facial volumetric restoration in complex reconstructive surgery. J Craniofac Surg. 2011;22:1695–701. 5. Coleman SR. Structural fat grafting. St. Louis: Quality Medical Publishing; 2004.

The Regenerative Approach For The Management of Severe Dysphonia

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Giovanna Cantarella and Riccardo F. Mazzola

Key Message (1) • Severe chronic dysphonia is a fatiguing and disabling condition. A vocal fold anatomical defect causes not only a voice alteration but also respiratory fatigue, due to the effort required to sustain the voice production. The dysphonic patient experiences global fatigue and dizziness due to respiratory alkalosis caused by hyperventilation. • Fat injection into the vocal folds fulfils the following main goals: • To volumize the vocal fold, in case of a soft tissue defect • To medialize the defective paralyzed vocal fold, and to compensate its muscular hypotrophy due to denervation

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_60) contains supplementary material, which is available to authorized users. G. Cantarella (*) · R. F. Mazzola Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy Otolaryngology Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy e-mail: [email protected]; [email protected]

• To improve the viscoelastic properties of the vocal fold tissue and to enhance its vibratory capability • Fat injection reduces the respiratory space between the vocal folds. Therefore, care must be taken to avoid respiratory obstruction. Overcorrection should be performed cautiously for vocal fold paralysis especially if the vocal folds’ mucosa is edematous. • A thourough preoperative assessment is mandatory: the decision about fat injection treatment is taken on the basis of the anatomic condition, of the perceptual features of the voice, and of the phonatory fatigue perceived by the patient. • Videolaryngoscopy is the most important objective assessment of vocal fold anatomy and function. • A stroboscopic light allows to analyze the vocal fold vibratory cycle. • High definition videolaryngoscopy allows to visualize or to suspect subtle malformations of the vocal fold microstructure. • Narrow band imaging enhances the view of scarred areas of the vocal folds, as areas without visible vessels.

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60.1 Introduction An impairment of voice quality is defined dysphonia, term deriving from the ancient Greek (Dys= alteration; phonia= phonation). Dysphonia may be due to several anatomical and dysfunctional disorders. In this chapter, we will focus on the clinical conditions causing an impairment of vocal fold approximation during voice production and to those causing stiffness of the vibrating structure of the vocal fold, induced by a soft tissue defect and/or by the alteration of the sophisticated micro-architecture of the vocal fold. A gap in closure determines an air escape with turbulent noise resulting in a breathy voice. It can be caused by a motility impairment, such as a paralysis or paresis of the recurrent laryngeal nerve or by a soft tissue defect of the vocal fold itself from congenital or acquired conditions. The majority of laryngeal paralyses are iatrogenic, mainly sequelae of thyroidectomy or other neck or thoracic surgery, but may also be idiopathic, or more rarely a consequence of neck trauma [1]. A vocal fold tissue defect may be provoked by previous endolaryngeal surgery for benign or malignant lesions or may result from congenital malformations. Less frequently, vocal fold scarring is caused by open neck trauma, and may occur in case of laryngeal fracture. If vocal fold closure is inadequate, also the sphincteric function of the larynx during swallowing can be impaired and aspiration of food occasionally occurs, particularly of liquids. A regenerative approach could be the ideal solution to correct a defective closure of the vocal folds. Dysphonia due to unilateral vocal fold paralysis has been approached in the last decades by several techniques of vocal fold medialization. Moving the paralyzed fold towards the midline to compensate for a defective closure may be achieved by open neck thyroplasty or by injection laryngoplasty [2]. Vocal fold scarring is a more challenging condition because it causes rigidity of the vibrating structure of the vocal fold; hence, medialization can reduce the air leakage without solving the cause of dysphonia. Few experimental and clinical studies have approached the problem of regenerating the vocal

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fold vibrating structure; the use of cultured stem cells and growth factors has been advocated [3, 4]. Nevertheless, isolation and in vitro culture of stem cells is expensive and requires a complex procedure; therefore at present, it is unfeasible in the clinical practice. Several recent trials have demonstrated the regenerative potential of fat grafting. Fat grafting to the vocal folds has first been described in the 1990s by Mikaelian et  al. [5] and Brandenburg et al. [6] who harvested the adipose tissue from the abdomen and transferred it to the recipient site by injection. The rationale of fat injection is to volumize the hypoplastic vocal fold and to achieve its medialization, so as to reduce the air escape, responsible for severe dysphonia. It is a promising mean to obtain also an improvement of the vocal fold pliability if scarred tissue is present. Alternatively, to obtain this goal, implants and/or biomaterials have been proposed, like silicone, teflon, hydroxyapatite, hyaluronic acid, etc. However, foreign body reaction has been reported, causing stiffness of the vocal fold and impairing the function of its gliding tissue [7]. Since 2005, we have published our experience with injection of fat, purified according to the Coleman procedure, into the vocal folds, obtaining long-term favorable results in the treated cases [8–10]. In the present report, we describe the indications, technique, and results of this procedure.

60.2 Essential Surgical Anatomy The vocal folds are located within the larynx and are protected by the thyroid cartilage. They abduct during inspiration dilating the laryngeal airway and close during phonation, thanks to the activity of the intrinsic laryngeal adductor and tensor muscles. Vocal fold closure allows to achieve a rise of subglottal pressure up to a threshold that will elicit the folds’ vibration. The vocal fold microstructure is highly specialized to allow an elevate number of vibrations and collisions during the daily voice use. It is a multilayered structure including an inner layer formed by

60  The Regenerative Approach For The Management of Severe Dysphonia

the vocal muscles, and a lamina propria, composed of three layers: superficial (rich in elastin fibers and fluids, called Reinke’s space), intermediate, and deep (these last two, rich in collagen fibers, constitute the vocal ligament). The outermost layer is a stratified squamous epithelium. The superficial layer of the lamina propria is the gliding tissue that gives rise to the mucosal wave elicited by the expiratory airflow during phonation; therefore, its integrity is critical for an efficient sound production. Hence, re-establishment of the gliding tissue is mandatory for voice production.

60.3 Technique The procedure is performed in general anesthesia and under direct microlaryngoscopy, utilizing a rigid laryngoscope to expose the vocal folds (Fig. 60.1). Figure shows the site of injection in a schematic anatomical view of the larynx and of the vocal folds. Fat is harvested from the lower abdomen with a 2- or 3-mm blunt cannula connected with a 10ml Luer-lock syringe. On occasion, in skinny patients, fat can be obtained from the inner knee or inner thigh. The lipoaspirate is

Fig. 60.1  Schematic representation of direct suspension laryngoscopy utilized for vocal fold fat injection under general anesthesia. A laryngoscope is placed through the mouth to expose the vocal folds and is stabilized in place through a suspension system; injection is performed under microscopic vision

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purified according to Coleman [11] and injected into the defective vocal fold to achieve a volumizing effect and the medialization of the vocal fold. Figure 60.2 shows the microlaryngoscopic view under direct laryngoscopy in a typical case of unilateral vocal fold paralysis and the result at completion of the procedure. To obtain the nanofat emulsion, part of the lipoaspurate is emulsified by shifting it between two 10-cc syringes connected to each other by a Luer-lock three-way stop cock connector, according to Tonnard et  al. [12]. No filtration is performed in our practice [13]. Usually, 0.5-2.5  ml are placed into the fold using a lipoinjection handle (Medicon Instrumente, Tüttlingen, Germany) with a 21G, 22-cm-long bayonet needle. A smaller quantity, about 0.2-0.4  ml is injected in the contralateral side. Placement represents the critical step of the procedure. The multilayered technique is currently employed with multiple entry points, while the needle is withdrawn, according to the spaghetti-­like technique. Depth is strictly related to the type of pathology. In case of vocal fold paralysis, fat is injected deep into the atrophic vocal muscle and into the paraglottic space, first laterally to the vocal process of the arytenoid to achieve medialization, and then in the mid-third and anterior third of the paralyzed fold. In patients with soft tissue defects of the vocal fold, fat is placed primarily into the superficial layers. The Videoclip 60.1 shows how fat injection is performed in the right vocal fold under microscopic vision in a patient affected by hemilaryngeal paralysis consequent to recurrent laryngeal nerve lesion occurred during thyroidectomy. The paralyzed fold is markedly hypotrophic, but it regains volume at the end of the procedure. The nanofat emulsion has been recently added to our armamentarium for the treatment of patients affected by scarring of the superficial layers to soften the scar tissue, to release adherences, and to restore the gliding tissue. Amoxicillin and clavulanic acid or clarithromycin is administered twice daily for 6 days. The procedure requires one-day hospitalization to assess the breathing condition before discharge.

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a

b

Fig. 60.2 (a) Videomicrolarygoscopic view of the vocal folds in a 35-year-old male affected by idiopathic right laryngeal paralysis since 12 years; both vocal folds are

hypotrophic; the arrows indicate the sites of fat injection. (b) At the end of the procedure, 0.4 cc have been injected in the left vocal fold and 1.3 cc in the right one

60.4 Outcome Assessment

60.5 Patients and Results

In our practice, voice outcomes have been assessed by the following means [10]:

We have treated 148 patients from 2002 to 2016 as reported in our recent article [10] with the majority of procedures being performed in patients affected by unilateral vocal fold paralyses. The series is actually steadily growing with a current particular increase of patients affected by soft tissue defects and scarring of their vocal folds since we have gained more experience in these difficult conditions and have refined our technique of scar release and of the use of emulsified fat when appropriate [13]. Favorable functional long-term results have been achieved both in cases of paralyses and in soft tissue defects, as demonstrated by a significant improvement in the outcome measures [10].

• Videolaryngoscopy, to detect the site and severity of the glottic gap, to visualize vocal folds vibration abnormalities, to make the surgical planning, and to assess post-treatment changes. • The GRBAS scale, for perceptual voice evaluation scoring the grade of dysphonia (G), roughness (R), breathiness (B), asthenicity (A), and strain (S). • The maximum phonation time (MPT), measured when the subjects sustain phonation of the vowel /a/ at a comfortable pitch and loudness, three consecutive trials are run and the best run is considered. It allows to indirectly test a reduction of air leakage. • The voice handicap index questionnaire (VHI), as patient self-assessment of the impact of the voice disturbance on quality of life. • CT and MRI radiological studies of the larynx in selected cases, to demonstrate the long-­ term persistence of the injected fat in the treated vocal folds.

60.6 Clinical Cases We report here some case examples to demonstrate the positive impact of fat grafting on selected cases of severe dysphonia. The following four patients represent the typical main clinical conditions of glottic incompetence, encountered and treated in our clinical practice.

60  The Regenerative Approach For The Management of Severe Dysphonia

Case 1: Unilateral Laryngeal Paralysis Case 2: Soft Tissue Defect Due to Cordectomy for Glottic Carcinoma Case 3: Vocal Fold Scarring Following Excision of Benign Vocal Fold Lesions Case 4: Congenital Soft Tissue Defect The Videoclip 60.2 is the preoperative videolaryngoscopy performed in a 45-year-old woman affected by unilateral vocal fold paralysis. The voice is very breathy. The Videoclip 60.3 shows the result obtained 6 months after the procedure of fat grafting: the voice is normal.

The Audiofile 60.4 is another typical example of breathy voice in a lady affected by unilateral vocal fold paralysis; 6 months after microlaryngoscopy for vocal fold fat injection the voice sounds normal, as can be heard in the Audiofile 60.5.

60.7 Discussion Phonation is essential for verbal communication and social relationships; its impairment requires an effective treatment. The voice production can be severely impaired if the vocal folds do not adduct completely. Numerous procedures have been reported to correct glottic insufficiency. They

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c

d

Fig. 60.3 (a) 65-year-old female patient affected by left vocal fold paralysis, sequela of thyroidectomy. The photographs are from a video recording obtained by high definition videolaryngoscopy. In A (inspiratory phase) and B (phonation) before lipoinjection: the right paralytic fold is in intermediate position, severely hypotrophic, with a bowing concave profile; on phonation glottis incompe-

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tence is evident. The paralyzed fold was injected with fat at four points (approximately 0.4 cc at each site), whereas the contralateral normal vocal fold was injected in two points (0.2 cc at each site). In c-D 8 months after the procedure, a straight contour of the paralytic fold can be seen; on phonation (d) a much better glottic closure is achieved

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Fig. 60.4  60-year-old man with persistent dysphonia, smoking 20 cigarettes /day for about 40 years. In (a) the arrow indicates an exophytic squamous cell carcinoma at the anterior third of the left vocal fold. He underwent a transoral endoscopic CO2 laser left cordectomy for cancer excision which caused severe dysphonia (b) stabilized result of cordectomy (Type 3 cordectomy, with partial removal of the vocal muscle) at 10 months postoperatively. (c) Result at 6 months after a single fat injection that filled the soft tissue defect and re-established a straight contour

of the left vocal fold. Images in (b) and (c) are obtained from high definition flexible videolaryngoscopy, with narrowband blue light having a short wavelength that penetrates into the mucosa; the superficial vascular network is highlighted. Narrowband light is commonly used in the diagnosis and post-treatment follow-up of laryngeal carcinoma to emphasize pathological vascularization; in our experience, it also allows to detect the scarred areas, which typically appear whitish, as shown in b)

include the medialization of the vocal fold using an external laterocervical approach, known as thyroplasty [2]. It has the drawback of being a more invasive technique than vocal fold injection. Augmentation of the vocal folds by injection with either implants or biomaterials like polydimethylsiloxane, hydroxyapatite, hyaluronic acid, and micronized dermis has the advantage of being a possible office-based procedure if performed under local anesthesia [14]. However, local and systemic complications may occur, including foreign body reaction and extru-

sion, reduced tissue pliability, with potential permanent worsening of dysphonia [7]. Fat has proven to be an effective vital filler to achieve vocal fold augmentation by a minimally invasive procedure [5, 6, 8–10, 15]. It is an autologous material readily available at no costs. Fat has viscoelastic properties similar to those of the superficial layers of the vocal fold (lamina propria); thus, it is the ideal material for augmenting the vocal fold and restoring its gliding tissue [16]. It is now widely accepted that human adipose tissue is a source of stem cells for regenerative

60  The Regenerative Approach For The Management of Severe Dysphonia

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Fig. 60.5  43-year-old lady who has a rough breathy voice and is experiencing vocal fatigue in her job, which requires many daily hours spent on phone calls. She has previously undergone elsewhere a microlaryngoscopy with vocal fold nodules removal exiting in severe scarring on the vocal fold free margins. (a) demonstrates the microlaryngoscopic aspect of her vocal folds with visible whitish scar tissue on the margins of the vocal folds at the beginning of the surgical procedure. (b) Image taken at the end of the procedure. On the left side, release of the scar tissue from the deeper layers by a micro sickle knife

has been performed; microfat has been injected in the deeper layers, whereas nanofat injection has allowed to complete the release of the scar tissue on both sides. (c) shows the videolaryngoscoic appearance of her vocal folds at narrow band light, the scar is enhanced as avascular tissue on the free margin of the left vocal fold (preoperative endoscopy). In (d), the aspect of the vocal folds is shown 18 months after fat injection and scar release; pliability of the tissue is regained, the glottic closure is achieved during phonation and voice quality is significantly improved

purposes [17]. Adipose-derived stem cells (ASCs) have demonstrated a high potential of differentiating into mature adypocites and other tissue types, including chondrocytes, osteoblasts, and skeletal muscle. Numerous ongoing clinical trials all over the world are currently devoted to evaluate the regenerative potential of ASCs, for the treatment of various pathological conditions. Thus currently there is sufficient evidence to consider fat grafting as a regenerative procedure. A future clinical use of isolated and expanded adipose-derived mesenchymal stem cells and growth factors might be postulated for enhancing the results obtained so far, especially for the

treatment of severe glottic incompetence due to soft tissue defects of the vocal folds. Current studies are evaluating this possibility in clinical practice [3, 18]. Resorption is a possible drawback of the technique. In our series of patients, resorption was overcome by primary moderate overcorrection; a second or third procedure was performed in selected cases to compensate the resorption rate and to enhance the result obtained at the first procedure. Multiple fat injections were typically necessary in cases of extensive soft tissue defects consequent to previous ablative oncological surgery or to congenital severe malformations. In case

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Fig. 60.6  27-year-old girl, who has a very breathy and poor audible voice since infancy. She is diagnosed with a severe bilateral soft tissue defect of both vocal folds, more evident on the left side. The defect is known as sulcus vocalis. Microlaryngoscopy under general anesthesia allows to confirm the diagnosis (a) and to perform surgery. She underwent a knife cordotomy and dissection of the vocal fold mucosal cover, which was strictly adherent to the vocal muscle with the absence of the normal gliding tissue. Microfat injection was performed deeply in the

vocal muscle of both sides to re-establish volume, whereas nanofat was placed on the surface. (b) Shows the final aspect at the end of the surgical procedure. (c) Preoperative videolaryngoscopy showed the soft tissue defect with escavated vocal folds. In the months following surgery, she progressively regained sonority of her voice with a significant reduction of the perceived vocal fatigue. (d) demonstrates the improvement of the vocal folds contour at 12 months postoperatively

of multiple treatments, airway obstruction could be a possible sequela; therefore, care must be taken in the preoperative assessment. Neverthless, our pletismographic and spirometric studies of airway resistance and of airflow dynamics have not shown a deterioration of inspiratory and expiratory airflows after vocal fold fat injection [19] It has been recently shown that nanofat emulsion has the same content in ADSCs and growth factors as the lipoaspirate [12]. Therefore, nanofat keeps the regenerative potential of fat tissue and can be easily placed with small diameter needles (23-25 G) suitable for injection in vocal fold superficial scars. We utilized unfiltered nanofat and the results were promising in our first series of treated cases [13]

60.8 Conclusions In conclusion, tissue engineering techniques are promising tools to re-establish the volume and to regenerate the gliding tissue in vocal folds. Microfat parcels can provide a long-term volume augmentation, whereas the nanofat injection can be a potential adjunctive procedure to restore the pliability of a scarred vocal fold. The mini-invasive autologous fat handling, processing, and injecting in multiple layers is a straightforward procedure and has proved to be a reliable technique to achieve voice improvement in the treatment of glottic incompetence. Adipose tissue may act both as a filler and as a regenerative mean, thanks to the effect of growth factors and ADSCs.

60  The Regenerative Approach For The Management of Severe Dysphonia Conflict of Interest  The authors have nothing to disclose and have no conflict of interest.

References 1. Cantarella G, Dejonckere P, Galli A, Ciabatta A, Gaffuri M, Pignataro L, Torretta S.  A retrospective evaluation of the etiology of unilateral vocal fold paralysis over the last 25  years. Eur Arch Otorhinolaryngol. 2017;274:347–53. https://doi. org/10.1007/s00405-­016-­4225-­9. 2. Cantarella G, Mazzola RF.  Structural fat grafting of the vocal folds. In: Coleman SR, Mazzola RF, Pu LLQ, editors. Fat injection: From filling to regeneration. II Ed. New York, NY: Thieme Publishers; 2018. p. 637–49. https://doi.org/10.1055/b-­0038-­149516. 3. Valerie A, Vassiliki K, Irini M, et al. Adipose-derived mesenchymal stem cells in the regeneration of vocal folds: a study on a chronic vocal fold scar. Stem Cell Int. 2016;9010279 4. Hirano S, Mizuta M, Kaneko M, Tateya I, Kanemaru S, Ito J.  Regenerative phonosurgical treatments for vocal fold scar and sulcus with basic fibroblast growth factor. Laryngoscope. 2013 Nov;123(11):2749–55. https://doi.org/10.1002/lary.24092.1. 5. Mikaelian DO, Lowry LD, Sataloff RT. Lipoinjection for unilateral vocal cord paralysis. Laryngoscope. 1991;101:465–8. 6. Brandenburg JH, Kirkham W, Koschkee D. Vocal cord augmentation with autogenous fat. Laryngoscope. 1992;102:495–500. 7. DeFatta RA, Chowdhury FR, Sataloff RT.  Complications of injection laryngoplasty using calcium hydroxylapatite. J Voice. 2012;26:614–8. 8. Cantarella G, Mazzola RF, Domenichini E, et  al. Vocal fold augmentation by autologous fat injection with lipostructure procedure. Otolaryngol Head Neck Surg. 2005;132:239–43.

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9. Cantarella G, Baracca G, Forti S, Gaffuri M, Mazzola RF.  Outcomes of structural fat grafting for paralytic and non-paralytic dysphonia. Acta Otorhinolaryngol Ital. 2011;31(3):154–60. 10. Cantarella G, Mazzola RF, Gaffuri M, Iofrida E, Biondetti P, Forzenigo LV, Pignataro L, Torretta S. Structural fat grafting to improve outcomes of vocal folds' fat augmentation: long-term results. Otolaryngol Head Neck Surg. 2018 Jan;158(1):135–43. 11. Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997;24:347–67. 12. Tonnard P, Verpaele A, Peeters G, Hamdi M, Cornelissen M, Declercq H.  Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013;132(4):1017–26. 13. Cantarella G, Mazzola RF.  Management of vocal fold scars by concurrent nanofat and microfat grafting. J Craniofac Surg. 2019;30(3):692–5. https://doi. org/10.1097/SCS.0000000000005206. 14. Mallur PS, Rosen CA. Office-based laryngeal injections. Otolaryngol Clin North Am. 2013;46:85–100. 15. Benninger MS, Hanick AL, Nowacki AS.  Augmentation autologous adipose injections in the larynx. Ann Otol Rhinol Laryngol. 2016;125:25–30. 16. Chan RW, Titze IR.  Viscosities of implantable biomaterials in vocal fold augmentation surgery. Laryngoscope. 1998;108:725–31. 17. Montelatici E, Baluce B, Ragni E, et al. Defining the identity of human adipose-derived mesenchymal stem cells. Biochem Cell Biol. 2015;93:74–82. 18. Kim DW, Kim EJ, Kim EN, et al. Human adipose tissue derived extracellular matrix and methylcellulose hydrogels augments and regenerates the paralysed vocal folds. PLoS One. 2016;11:e0165265. 19. Cantarella G, Fasano V, Maraschi B, Mazzola RF, Sambataro G. Airway resistance and airflow dynamics after fat injection into vocal folds. Ann Otol Rhinol Laryngol. 2006;115(11):816–23.

The Safe Treatment of Mild Velopharyngeal Insufficiency (VPI) with Autologous Fat Grafting

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Riccardo F. Mazzola, Giovanna Cantarella, and Isabella C. Mazzola

Key Messages  • A team approach is crucial for a correct assessment of velopharyngeal insufficiency (VPI). VPI evaluation should be performed by the surgeon along with a phoniatrician, trained in clefts’ rehabilitation, and a speech therapist. • Video-assisted nasopharyngoscopy gives information about the size and location of the VP closure gap. • Video-assisted nasopharyngoscopy has been recognized superior to videofluoroscopy in identifying small closure gaps. • In case of mild VPI, velopharyngoplasties may represent an overtreatment. • Autologous fat grafting is a good solution for mild-to-moderate VPI treatment. • In patients affected by submucous cleft palate, after levator muscle suturing, fat injection can

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_61) contains supplementary material, which is available to authorized users. R. F. Mazzola (*) · G. Cantarella Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy e-mail: [email protected] I. C. Mazzola Private Practice, Milan, Italy

be performed concurrently to improve the results. • Fat injection should be performed in the posterior pharyngeal wall, in the soft palate, and in the posterior pillars. • Sharp needles in the posterior pharyngeal wall must not be used. The risk of cannulating a vessel or even the internal carotid artery which courses laterally causing embolism is high.

61.1 Introduction Velopharyngeal insufficiency (VPI) is defined as the incomplete closure of the passage between oro- and nasopharynx, named velopharyngeal port. On phonation the levator veli palatini muscle elevates the velum in an upward and backward direction, while the palatopharyngeus muscle and superior constrictor muscle approximate the pharyngeal wall toward the midline (Video 61.1). If for different causes, during phonation, the air instead of going through the oral cavity completely flows partly through the nose interfering with normal speech articulation and resonance, the ensuing resonance alteration is defined as hypernasality, and is often accompanied by other typical signs of VPI, like nasal turbulence and facial grimaces. VPI can be either congenital or acquired. Short palate, sequelae of cleft palate repair, and submucous clefts, usually associated with

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bifid uvulae, are classified as anomalies of congenital origin, whereas velar paralysis and ­neurological disorders are included among the acquired conditions. Reducing the passage between oro- and nasopharynx and controlling nasal air escape, without causing a respiratory obstruction, have been the main concerns of cleft surgeons over the years, beginning from the second half of the nineteenth century. Basically, operations to correct VPI fall into three main categories: (a) advancing the posterior pharyngeal wall by means of implants or autologous tissue inserted along the midline of the posterior pharynx; (b) diminishing the existing nasopharyngeal gap using mucosal or mio-­ mucosal flaps outlined in the pharynx, the so-­ called velopharyngoplasties; and (c) correcting the soft palate with different types of procedures like palate re-repair [1], double-opposing Z-plasty [2], or pushback [3]. Velopharyngoplasties include the superiorly based and the less used inferiorly based pharyngeal flap [4, 5], or the transposition of the posterior pharyngeal pillars, containing the palatopharyngeus muscle [6, 7]. Their typical indication is related to severe VPI. Relevant morbidity in the immediate postoperative period with pain and potential bleeding, or at long term, with snoring and obstructive sleep apnea syndrome (OSAS) represent their drawbacks. Finally, in the presence of moderate VPI they might be considered an overtreatment. Advancement of the posterior pharyngeal wall is an old method proposed since the beginning of the twentieth century [8]. Implants [9, 10] or autologous tissue, like fat [11], have been inserted over the years into the retropharyngeal space. The aim is to advance the posterior pharyngeal wall forward to meet the velum and to reduce the size of the nasopharyngeal port. Correct position of the implant is crucial. It should be located at the ideal point of contact between the velum and the pharynx. Extrusion or dislocation represents typical complications. Independently from etiology a sharp distinction should be made between severe and mild VPI.  This distinction, which also includes

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patients receiving inappropriate speech therapy, is of paramount importance in the decision-­ making regarding the most suitable type of operation for VPI correction. Patient selection constitutes the key point [12]. Preoperative analysis of VP closure is based on a team approach evaluation performed by the surgeon along with a phoniatrician, trained in clefts’ rehabilitation, and a speech therapist. It includes: –– Voice perceptual evaluation, with spontaneous speech, repetition of sentences, and lists of words specially prepared to assess different parameters, like resonance, air escape, turbulence, articulation defects, and potential dysphonia –– Aerodynamic assessment to establish the amount of nasal air escape –– Videofluoroscopic study of the VP port in multiple projections –– Video-assisted nasopharyngoscopy In our clinical practice, perceptual evaluation and video-assisted nasopharyngoscopy are considered the gold standard for patient selection. Perceptual assessment includes video recording of several speech samples using a professional microphone. The videos are evaluated by speech therapists with specific expertise in VP rehabilitation. A distinction should be made between VP incompetence and VP dysfunction. The latter problem is best treated conservatively by speech therapy, whereas the first one by surgery. Video-assisted nasopharyngoscopy is performed introducing a flexible endoscope through the nasal fossa up to the nasopharynx. It allows the visualization of the velopharyngeal sphincter during speech tasks and gives information about the size and location of the VP closure gap. Video-assisted nasopharyngoscopy has been recognized superior to videofluoroscopy in identifying small closure gaps for establishing the surgical planning [13]. It is well tolerated, also by small children, provided that a flexible microchip endoscope, with a diameter inferior to 3 mm, is utilized.

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Table 61.1  Decision-making for VPI treatment (based on video-assisted nasopharyngoscopy) Scale 0 1 2 3 4

Closure gap Complete closure Minimal gap Mucous bubbling Moderate gap with less than 25% of the port at rest Intermediate gap between 25% and 50% of the port at rest Severe gap with more than 50% of the port at rest

As related to the above mentioned considerations and depending on the nasopharyngeal gap closure, patients are rated according to a 5-point scale [12]. 0 = complete VP closure; 1 = inconstant gap demonstrated by mucus bubbling; 2 = gap involving less than 25% of the VP port at rest; 3 = gap involving 25–50% of the VP port; 4 = severe gap involving more than 50% of the VP port. Patients with gaps 1–3 (50% of the VP port) are considered candidates for VP fat injection, whereas patients showing a severe gap, rated as 4, are best treated with velopharyngoplasties. In fact, in the latter group, the swelling created in the posterior pharyngeal wall by fat injection is not sufficient to reduce the size of the port and to control nasal air escape (Table 61.1). Recently, autologous fat transplantation to the velum and pharynx has proven to be successful in the treatment of mild-to-moderate VPI [12, 14, 15]. This report examines techniques, advantages, and limits of this particular type of procedure.

61.2 Material and Surgical Technique The procedure is performed under general anesthesia with endotracheal intubation. The patient lies in supine position, with a roll placed behind the shoulders to extend the neck. The Dingman mouth gag, suspended on a horizontal stand, facilitates exposure and depresses the tongue. Fat harvesting and purification: Procurement of fat is usually from the abdomen. The area is infiltrated with 50 ml of saline and 10 ml of lidocaine with epinephrine. A two-hole cannula 130  mm long and 2 or 3  mm in diameter, con-

Type of procedure No indication for surgery Fat grafting of the posterior pharyngeal wall Fat grafting of the posterior pharyngeal wall and of the velum Fat grafting of the posterior pharyngeal wall and of the velum Velopharyngoplasties

nected to a 10 ml Luer-Lock syringe, is used. The entry point should be inconspicuous as much as possible. A mild negative pressure is maintained in the syringe to allow fat aspiration. In harvesting fat from the abdomen it is important to pinch the skin to avoid gut or internal organ perforation with the cannula (Video 61.2). This may occur in skinny patients or in the presence of abdominal hernia. In case of insufficient or lack of abdominal fat, alternative harvesting sites are represented by the inner thigh or inner knee. A total of 15–20  ml of lipoaspirate is needed for VPI treatment. Once the lipoaspirate is obtained, it should be refined to obtain the purest fat possible by eliminating aqueous and oily components along with other debris. The presence of blood, fatty acids, and other debris seems to stimulate inflammatory response, which induces fat reabsorption. We use centrifugation performed at 3000 rpm for 3 min, according to Coleman. The aqueous and oily components are removed and purified fat is now ready for grafting. Fat injection into the pharyngeal wall: To obtain a good visualization of the operative field, a Nélaton probe is inserted into each nostril and passed through the corresponding choana into the mouth, tying the two heads together. By this maneuver, the velum is gently retracted superiorly and the area of the posterior pharyngeal wall is clearly exposed (Fig. 61.1). The odontoid process should be identified. It is in this area that fat parcels are injected for improving the contact between the velum and the pharynx. Two stab incisions are carried out 5  mm laterally with respect to the midline of the pharyngeal wall, on both sides, usually with No. 18 G needle, rarely No. 11 blade. Through this cut, a 21-gauge,

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Fig. 61.1  A Nélaton probe, inserted into the nasal cavity, and passed through the mouth, is gently retracted to allow a good visualization of the posterior pharyngeal wall, where fat should be placed

Fig. 61.2  21G malleable cannula used to inject fat into the posterior pharyngeal wall and velum

60 mm long, disposable malleable microcannula, bent as needed, is inserted (Fig. 61.2). The entry point should remain small to minimize the risk of fat to ooze out. Fat placement represents the critical step of the procedure and must be performed with utmost care. In doing this, the assistance of a 70° Storz 4  mm rigid nasal endoscope connected with a video camera and a monitor is utilized to obtain a better visualization of the nasopharynx, to assess the position of the cannula, the injection site, and the amount of fat placed (Fig.  61.3). The cannula, plugged into a 3.0 ml Luer-Lock syringe, is advanced in a cephalad and oblique direction, reaching the axis, and it continues laterally toward the ipsilateral pharyngeal wall in the submucosal plane. The parcels of fatty tissue should be injected anterior to the prevertebral fascia within the fibers of the superior constrictor muscle, and not behind, in the loose space which exists immediately anterior to the bodies of the vertebrae. Injecting fat into this space potentially results in migration of the graft caudally, along the natural cleavage plane. The cadaveric dissection shows this important detail (Fig.  61.4). Numerous tunnels are

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made to maximize the contact between injected fat and recipient tissue. Fat parcels are released in multiple directions always on withdrawal, according to the “spaghetti-like” technique [16]. An average of 2 ml of fat is injected per side. The entry points are closed with a 5/0 absorbable suture. Usually, 5.0–7.0 ml of fat is injected into the pharynx. Decision about the amount of fat to be injected and the points of fat placement is related to the preoperative nasopharyngoscopy examination. A short video summarizes the procedure (Video 61.3). On occasion, a lipoinjection dosage handle (Medicon Instrumente, Tüttlingen, Germany) is used to facilitate fat placement, if an excessive resistance is encountered while injecting fat (Fig. 61.5). The tight space existing between the posterior bony wall of the pharynx and the overlying mucosal-muscular tissue may oppose the passage of fat into the tunnels created by the cannula itself. In this case, the 1 or 3  ml syringe, filled with the centrifuged adipose tissue, is positioned into the dosage handle. The greater pressure applied on the plunger helps to overcome the problem. No risk of overcorrection occurs, provided that fat is injected with multiple passes, in different directions, always on withdrawal, and introducing spaghetti-like columns of fat [16]. It is mandatory to employ blunt cannulas only, never sharp needles, to prevent the possibility of injecting fat into the vessels or injuring the internal carotid artery, which courses laterally. Fat injection into the soft palate: At completion of the management of the posterior pharyngeal wall, fat is injected into the velum and particularly along the midline, where the suture, often rigid and retracted, due to the previous cleft palate approximation is located, and on the nasal aspect of the uvula (Fig.  61.5), with the dual goal to soften the scars, frequently present here, or to create a bulging which improves the contact between the velum and the pharynx. Three stab incisions are made on the velum. The first one on nasal surface of the uvula and on the posterior pillars. A second one in the midline velar scar. Should the midline scar be particularly stiff, its release is carried out using an 18 G sharp needle with continuous clockwise and

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Fig. 61.3 The assistance of a 70° Storz 4 mm rigid nasal endoscope, connected with a video camera, is utilized to better visualize the nasopharynx and to evaluate the amount of fat placement

counterclockwise movements. Fat is placed in the plane between nasal and oral mucosa. The third stab incision is made at the level of the arch of the tonsillar fossa. An average of 2 ml of fat is injected. The same amount is placed in the contralateral side. In patients affected by submucous cleft palate, dissection of the separated heads of the levator muscle from the posterior nasal spine and palatal plate is performed. The two heads of the muscle are released and sutured together with 5/0 non-­reabsorbable stitches. Fat injection is carried out concurrently to improve the results [12]. A total of 4.0–5.0 ml is injected into the soft palate.

No special postoperative care is needed. Intraoperative antibiotics are administered in every case. We have treated so far 18 patients affected by VPI.  Table  61.2 summarizes the number of patients treated, procedures performed, the age of the patients, their diagnosis, the injection site, and amount of fat injected. Twenty-nine autologous fat grafting procedures were performed in 18 patients. The average age of the population included in the study was 18.8 years. Out of 18 patients, 9 underwent two procedures (50%), 8 had 1 fat grafting procedure, and only 1 had 3 fat grafting procedures. The fat was injected primar-

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ily in the posterior pharyngeal wall and also in the soft palate. The recorded volume of fat grafted averaged 4.0 (posterior pharyngeal wall) and 2.0 ml (palate) per patient. Overall results were favorable (Fig. 61.6a, b. Videos 61.4a, 61.4b and 61.5a, 61.5b). No complication occurred in our series. None of the patients experienced respiratory obstruction after surgery. Two patients showed a fat bulge in the posterior pharyngeal wall, as a result of a significant weight gain in the postoperative period [12] (Fig. 61.7).

61.3 Discussion

Fig. 61.4  Cadaveric dissection showing the injection sites of fat for VPI correction. a) Anterior to the prevertebral fascia within the fibers of the constrictor pharyngeus superior muscle; b) within the nasal aspect of the musculus uvulae Fig. 61.5 Lipoinjection dosage handle, used to facilitate fat placement

Management of mild VPI represents a challenge for the surgeon. It is crucial to select patients properly, and to choose the most effective procedure for restoring a competent velopharyngeal sphincter so as to improve voice resonance and correct nasal air escape. Velopharyngoplasties may represent an overtreatment. They can give rise to potential sequelae like respiratory obstruction, snoring, and OSAS.

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Table 61.2  Fat grafting in IVF: list of patients Name S.A.

Age 13y

Diagnosis Submucous cleft

Injection site Velum + pharynx

No. of procedures 2

C.A. S.V. W.A.

12y 39y 8y

Short palate Sequela of cleft palate Sequela of cleft palate

Velum + pharrynx Velum + pharynx Velum + pharynx

1 1 2

B.A.

48y

Sequela of cleft palate

Velum + pharynx

2

B.R.

5y

Short palate

Velum + pharynx

2

L.U.

8y

Sequela of cleft palate

Velum + pharynx

2

D.D.

21y

Velum + pharynx

2

B.E.

8y

Velum + pharynx

2

A.L. P.A. G.R.

25y 19y 9y

Short palate Submucous cleft Sequela of cleft palate Submucous cleft Sequela of cleft palate Sequela of cleft palate Di George syndrome

Velum + pharynx Velum + pharynx Velum + pharynx

1 1 2

V.A. M.A.

10y 45y

Sequela of cleft palate Sequela of cleft palate

Velum + pharynx Pharynx

1 2

L.O. P.I.

13y 40y

Sequela of cleft palate Sequela of cleft palate

Pharynx Velum + pharynx

1 3

D.E. M.N.

12y 12y

DiGeorge syndrome Sequela of cleft palate

Velum + pharynx Velum + pharynx

1 1

a

Amount injected 4.0 Phar+2.0 velum 2.5 Phar+2.5 velum 5.0 Phar+6.0 velum 3.0 Phar+2.0 velum 6.0 Phar+2.0 velum 7.0 Phar+4.0 velum 4.0 Phar+2.0 velum 6.0 Phar+2.5 velum 5.0 Phar+3.0 velum 4.0 Phar+2.5 velum 4.0 Phar+2.0 velum 7.0 Phar+4.0 velum 5.0 Phar+3.0 velum 8.0 Phar+5.0 velum 2.0 Phar+1.5 velum 3.0 Phar+5.0 velum 4.0 Phar+1.5 velum 4.0 Phar+1.5 velum 4.0 Phar+2.0 velum 4.0 Phar+2.0 velum 4.0 Phar+2.0 vel 1.5 Phar. 1.5 Phar. 1.5 Phar. 8.0 Phar+2.0 velum 7.0 Phar+4.0 velum 7.0 Phar+4.0 velum 6.0 Phar+3.5 velum 5.0 Phar+2.0 velum

b

Fig. 61.6 (a, b) Sequela of cleft palate. (a) The midline scar, secondary to cleft palate repair; (b) result at 1 year after releasing and softening the scar by fat injection

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Fig. 61.7  Lipoma after fat injection developed in the posterior pharyngeal wall in a patient following a significant weight gain. The patient was previously operated on with velopharyngoplasty elsewhere

Augmentation of the posterior pharyngeal wall, using biomaterials, is subjected to c­ omplications. Reabsorbable materials vanish within a few months, whereas permanent implants may migrate, extrude, or cause foreign body reactions [9, 10, 17]. The wait-and-see approach, with endless speech therapies, focused on improving oral articulation and “strengthening” the velar musculature is the most typical choice. These patients, with small or moderately sized central gap, are often considered not appropriate for major surgery. They become frustrated because the nasal air escape with hypernasality, nasal turbulence, and resonance alterations is seldom corrected by speech therapy. Reduction of the passage between oro- and nasopharynx using autologous fat grafting offers several advantages to the patient: morbidity is minimal, anatomy of the pharyngeal walls is not altered, and postoperative course is irrelevant. Having calculated the risk-to-benefit of the abovementioned procedure, fat grafting to correct mild VPI should be strongly supported provided that the indication for treatment is properly posed. The key point for surgical planning is the dynamic study of the velopharyngeal port (VP)

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movements during speech and the quantification of the closure gap, using flexible video-assisted nasoendoscopy and/or videofluoroscopy. Recent publications suggest that autologous fat possesses the regenerative potential mediated by the pluripotent stem cells present in its stromal vascular fraction (SVF), and this may account for an important role in neoangiogenesis and regeneration of the host tissue [18]. The goals of fat injection for VPI: Fat injection for the treatment of VPI fulfils a dual goal. It reduces the existing VP gap, controlling nasal air escape, and it softens the midline scar secondary to cleft palate repair (Fig.  61.6a, b). The scar should be released and fat is then injected between nasal and oral mucosa. Once the scar becomes more pliable, the velum improves its elevation, facilitating its midline approximation to the posterior pharyngeal wall. In patients affected by submucous cleft, the results obtained by the levator sling suturing are improved with concurrent fat injection carried out on the four walls of the VP port (Fig. 61.8a, b). A further advantage of fat injection is the possibility of maintaining the achieved results by repeating fat injections when facial growth takes place, if decompensation of velopharyngeal closure occurs. Overcorrection, or fat bolus, performed in an attempt to further reduce the VP gap, is not considered an appropriate procedure. On the contrary, it may cause oily cyst formation [16]. To maximize the contact between the grafted fat and the host tissue and to enhance the survival of the transplanted parcels it is essential to place minimal amount of fat according to the spaghetti-like technique [16]. It is well known that transplanted fat undergoes a certain degree of reabsorption rate, which varies from 20% to 80%, depending on numerous factors [19]. For this reason, it is essential that the repeatability of the procedure is indicated in the informed consent, emphasizing that more than one surgical session is necessary.

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b

Fig. 61.8 (a, b) Submucous cleft palate. (a) Before surgery, the two heads of the levator muscle appear separated from each other, with the typical bluish image along the

midline of the palate. (b) Result at one year following levator sling suturing and concurrent fat injection in the posterior pharyngeal wall (4 ml) and in the palate (5 ml)

61.4 S  afety Principles of Fat Grafting for Velopharyngeal Incompetence

Table 61.3  Summary of basic principles about safety

Fat injection is usually considered a safe operation, provided that some basic principles are respected (Table 61.3), particularly the following: Knowledge of head and neck anatomy: As a general rule, surgery requires clear knowledge of anatomy. In dealing with the head and neck area, this rule is even more evident. To avoid injuring, disrupting, or perforating these delicate structures, the surgeon should be familiar with the anatomy of the region and in particular with the course of the big vessels of the neck. Prevention of infection: The velum and the posterior pharyngeal wall are contaminated zones. Fat grafting is a sterile procedure and sterile technique should be performed at all times. When injecting fat, it may be safer to previously disinfect the recipient site with iodopovidone, and to observe a rigorous sterile technique during the harvesting and processing phases. Intraoperative antibiotics are recommended. No bolus: An excessive amount of injected fat in the recipient site (overcorrection) may increase the risk of adipose tissue necrosis, with subsequent formation of oil cysts, calcifications, and infections [16]. It is well known that oil cysts can occur after bolus-type fat grafting. The necrotic

How to implement safety Knowledge of head and neck anatomy Knowledge of the course of the neck vessels Prevention of infections

Prevention of oil cyst formation Use syringes of small size (1–3 ml) Never sharp needles

Clinical relevance To avoid injuring, disrupting, or perforating the delicate structures of the region To avoid perforating the wall of the neck arteries

Disinfection of the oral cavity with iodopovidone is essential. Observation of sterile techniques at all times Large volume of fat may induce fat necrosis and calcifications, with a permanent state of inflammation. Bolus placement should be avoided To better control the amount of fat placed with each pass and to avoid the risk of overcorrection To avoid the risk of perforating the wall of the big vessels of the neck (internal carotid a.), cannulating the lumen, and injecting fat into the arterial system, with dramatic consequences

tissue maintains a permanent state of inflammation. Resorption of oil cyst rarely occurs. Therefore, overcorrection should be avoided. Only a minimal amount of fat parcels, according to the spaghetti-like technique, should be placed in the recipient site [16].

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Never sharp needles. Blunt cannulas only: Embolism is one of the most dramatic complications after fat injection. Sharp needles can incidentally perforate the wall of one of the vessels of the lateral neck, in particular the internal carotid artery, and fat will inevitably be introduced into the lumen of the vessel resulting in devastating consequences. In performing fat grafting for ­correction of VPI, it is mandatory to use blunt cannulas only, never sharp needles, and to inject fat in the median zone of the posterior pharyngeal wall, anterior to the bodies of the vertebrae, not laterally. In 2010, a dramatic event occurred in a British Hospital, when small amounts of fat (0.2–0.3 ml), injected in the posterior and lateral pharyngeal walls for treating VPI in an 18-year-old girl, affected by a sequela of cleft palate, were accidentally introduced into the carotid artery. Instead of blunt cannula, the surgeon used a 14G needle connected to a 10  ml syringe. Sadly, immediately thereafter, the patient suffered a massive stroke, as a consequence of fat embolism. At three years the patient is still aphasic and hemiplegic on the right-hand side and her left eye is amaurotic [20]. How to avoid a similar tragedy? From this report, three important considerations emerge. First of all, good knowledge of anatomy is essential, in particular when dealing with areas as delicate as the neck, where damage to underlying structures such as nerves, muscles, and vessels is always possible. Secondly, use of small-size, 1 or 3 ml, Luer-Lock syringe is essential to remain especially safe. Control over the amount of fat placed with each pass becomes much easier. On the contrary, if a bigger syringe (10 ml) is utilized, this control rarely takes place and with the high pressure applied to the plunger, a large volume of fat may erroneously be released. Finally, sharp needles must not be used. They can accidentally perforate the wall of an artery, as it occurred in the abovementioned report, and cannulate the lumen. Even small amount of fat passing into the arterial system may result in devastating consequences, such as blindness and stroke.

61.5 Conclusions Mild velopharyngeal insufficiency (VPI) is best treated by fat injection in the posterior pharyngeal wall and in the soft palate, lateral and posterior pillars included. Fat grafting represents a minimally invasive procedure with respect to major surgery and minimizes the risk of complications. It has a regenerative potential over the involved tissues, improving functionality, pliability, and vascularity. Blunt cannulas must be used to avoid the risk of injecting fat into the vessels, which course in the posterior and lateral pharyngeal wall. Safety is essential.

References 1. Sommerlad BC, Mehendale FV, Birch MJ, Sell D, et al. Palate re-repair revisited. Cleft Palate Craniofac J. 2002;39:295–307. 2. Furlow LT Jr. Cleft palate repair by double opposing Z-plasty. Plast Reconstr Surg. 1986;78:724–38. 3. Dorrance GM, Bransfield JW.  Push-back operation for repair of cleft palate. Plast Reconstr Surg. 1946;1:145–69. 4. Sanvenero Rosselli G.  La divisione congenita del Labbro e del Palato. Roma: Pozzi; 1934. p. 262–4. 5. Rosenthal W.  Zur Frage der Gaumenplastik. Zbl f Chir. 1924;51:1621–7. 6. Hynes W. Pharyngoplasty by muscle transplantation. Br J Plast Surg. 1950;3:128–35. 7. Orticochea M.  Construction of a dynamic muscle sphincter in cleft palates. Plast Reconstr Surg. 1968;41:323–7. 8. Gersuny R. Über eine subkutane Prothese. Ztschr f Heilk. 1900;21:199–201. 9. Brauer RO. Retropharyngeal implantation of silicone gel pillows for velopharyngeal incompetence. Plast Reconstr Surg. 1973;51:254–62. 10. Sturim HS, Jacob CT Jr. Teflon pharyngoplasty. Plast Reconstr Surg. 1972;49:180–5. 11. von Gaza W. Über freie Fettgewebstransplantation in den retropharyngealen Raum bei Gaumenspalte. Arch klin Chir. 1926;142:590–9. 12. Mazzola RF, Cantarella G, Mazzola IC. The regenerative approach to velopharyngeal incompetence with fat grafting. Clin Plastic Surg. 2015;42:365–74. 13. Lam DJ, Starr JR, Perkins JA, Lewis CW, et  al. A comparison of nasendoscopy and multiview videofluoroscopy in assessing velopharyngeal insufficiency. Otolaryngol Head Neck Surg. 2006;134:394–402. 14. Cantarella G, Mazzola RF, Mantovani M, Baracca G, et  al. Treatment of velopharyngeal insufficiency by

61  The Safe Treatment of Mild Velopharyngeal Insufficiency (VPI) with Autologous Fat Grafting pharyngeal and velar fat injections. Otolaryngol Head Neck Surg. 2011;145:401–3. 15. Cantarella G, Mazzola RF, Mantovani M, Mazzola IC, et al. Fat injections for the treatment of velopharyngeal insufficiency. J Craniofac Surg. 2012;23:634–7. 16. Eto H, Kato H, Suga H, Aoi N, Doi K, et al. The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg. 2012;129:1081–92. 17. Brigger MT, Ashland JE, Hartnick CJ.  Injection pharyngoplasty with calcium hydroxylapatite for velopharyngeal insufficiency: patient selection and technique. Arch Otolaryngol Head Neck Surg. 2010;136:666–70.

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18. Kato H, Mineda K, Eto H, Doi K, et al. Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months. Plast Reconstr Surg. 2014;133:303e–13e. 19. Kølle SF, Fischer-Nielsen A, Mathiasen AB, et  al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. Lancet. 2013;382:1113–20. 20. Filip C, Matzen M, Aagenæs I, Aukner R, et  al. Autologous fat transplantation to the velopharynx for treating persistent velopharyngeal insufficiency of mild degree secondary to overt or submucous cleft palate. J Plast Reconstr Aesthet Surg. 2013;66:337–44.

Degenerative Retinopathy Treatment with ADSC: Our Experience

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Paolo G. Limoli, Gianluca Campiglio, and Celeste S. Limoli

Key Messages • The suprachoroidal implantation of autologous mesenchymal cells according to LRRT has demonstrated its therapeutic potential, positively influencing various functional parameters. • The direct contact of the autograft with the choroid improves the incretion of the bioactive factors (cytokines and exosomes) produced by the mesenchymal cells in the choroidal flow and therefore promotes the diffusion through the retinal tissue, finally exuding in the vitreous body. • It is reasonable to believe that the interaction between GFs and retinal cells may lead to an improvement of the functional parameters in the course of retinal atrophic diseases, in order to prevent and/or delay progression of the latter diseases and, in some cases, to induce neuroenhancement. • The functional parameters seem to improve most in subjects that have more residual cells, or in other words in subjects that have greater Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_62) contains supplementary material, which is available to authorized users. P. G. Limoli (*) · C. S. Limoli Low Vision Research Center, Milan, Italy e-mail: [email protected]; [email protected], [email protected] G. Campiglio Campiglio Plastic Surgery Center, Milan, Italy

biological thicknesses measurable with optical coherence tomography. • No complications were observed in visual function after adipose-derived MSCs were applied under a deep scleral flap in the suprachoroidal area.

62.1 Introduction Retinal degenerative diseases affecting retinal ganglion cells (RGCs), photoreceptors, and retinal pigment epithelium (RPE) are important causes of poor vision. They can be caused by the dysfunction of neural cells or supporting cells, such as the RPE. As the disease progresses, the irreversible death or dysfunction of retinal neurons (RGCs and photoreceptors or RPE cells) eventually leads to permanent visual impairment. There are many types of retinal degenerative diseases, including glaucoma, inherited retinal dystrophy as retinitis pigmentosa (RP) or Stargardt disease, age-related macular degeneration (AMD), degenerative myopia, and diabetic retinopathy (DR). This heterogeneous group of diseases is associated with various underlying molecular mechanisms and morphological changes, which cause damage to the intact circuit of the retina in terms of both function and structure. The etiology and genetic patterns of these conditions vary; however, the end result is vision loss.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_62

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The number of patients suffering from degenerative or genetic retinal pathologies is so high, the derived costs are so important, and the quality of life of these patients is so compromised that the therapeutic problem in the coming years will have to receive greater attention from the ophthalmologic world. According to estimates from the World Health Organization (WHO) Prevention of Blindness and Deafness Programme, in 2017 about 285 million people have been registered as visually impaired worldwide: 39 million was blind and 246 million had low vision (severe or moderate visual impairment): 65% of visually impaired and 82% of blind people were over 50 years of age, although this age group comprises only 20% of the world population. Top causes of visual impairment were refractive errors, cataracts, and glaucoma. Top causes of blindness were cataracts, glaucoma, and age-related macular degeneration. The International Federation on Ageing estimates, at present (2020), that every day the costs deriving from the serious impairment of the vision are close to the figure of 2800 billion dollars for direct costs and another 750 billion dollars for indirect costs worldwide. In each of these pathologies, regardless of its nature, a given sequence of molecular events gradually leads to the death of retinal cells. These mechanisms cover various biological aspects and can be summarized thus: neurotrophism, oxidation, vascular change, apoptosis, inflammation, or immunology [1, 2]. The sequence begins with oxidation, photo-­ oxidation, or photo-sensitivity. It follows the liberation of oxidizing substances (ROS:  reactive oxygen species)  in the cellular environment

which in turn provoke lipid peroxidation, oxidation of critical bonds in protein chains and rupture in those of DNA, and up-activation of endogenous nuclease that blocks the expression of the Bcl2 gene with potential cell apoptosis. In physiological conditions and in a healthy retina the cells possess an arsenal of substances with a protective action, including antioxidant systems and enzymes, which serve to balance oxidants and free radicals, minimizing damage. One of the most well-known mechanisms for blocking or procrastinating apoptotic processes is the activation of the Bcl2 gene, for example by means of growth factors, thus avoiding the fate of death, and this independently of the triggering cause. There are cells like Müller cells or RPE cells, capable of producing,  in hpyoxia  conditions, angiogenic and neurotrophic factors such as FGF and VEGF, in order to counterbalance the insult, provided that it is transient [3]. In the case of cellular disequilibrium, for example due to genetic or inflammatory reasons, or when a large part of the cells have undergone apoptosis and death processes by activating chronic parainflammatory components, disease and progression of neuroretinal alterations occur. On these mechanisms it is possible in our opinion to apply a therapy that is aimed at reducing the impact and progression of the disease. The therapeutic aim is to slow down or prevent the retinal cell death [4]. The table summarizes the main authors who have conducted comparable research over the past 10 years, using stem cells implanted at various levels in order to restore damaged functions in the retina.

Disease AMD (GA), RP, and ischemic retinopathy

Institution University of Sao Paulo, Brazil

Cell source Autologous BMHSC

Delivery Intravitreal injection

AMD (GA), RP, RVO, and DR

University of California, Davis, USA Erciyes University, Kayseri, Turkey

Autologous BMHSC

Intravitreal injection

Embryonic stem cells

Subretinal application

AMD, Stargardt

WHO identifier NCT01068561 NCT01560715 NCT01518127 NCT01518842 NCT01736059

Reference Siqueira et al., (2011)

NCT01345006 NCT01344993

Schwartz et al. (2015)

Park et al. (2012-2015)

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Disease RP

Institution Erciyes University, Kayseri, Turkey

Cell source Autologous ADMSC

Delivery Subretinal application

WHO identifier Reference Not registered Oner et al. (2016)

AMD (GA), RP, OA

Low Vision Research Centre, Milan, Italy Erciyes University, Kayseri, Turkey

Autologous ADMSC and PRP Heterologous UC-MSCs

Suprachoroidal application

Not registered

Limoli et al. (2016–2020)

Suprachoroidal application

Oner et al. (2018)

RP

Erciyes University, Kayseri, Turkey

Autologous PRP

Subtenon injection

Ministry of Health 56733164/203 Not registered

RP

Erciyes University, Kayseri, Turkey

Heterologous UC-MSCs

Suprachoroidal application

Ministry of Health 56733164/203

Oner et al. (2020)

AMD, Stargardt

62.2 Potential Cell Therapy in the Degenerative Retinopathy

Arslan et al. (2018)

systemic or local injection of stem/progenitor cells in the injured area to treat multiple chronic disorders. Cell therapy aims to restore the cell density as well as to preserve retinal cells through In the last few years, visual rehabilitation for the improvements of the intra- and extra-cellular patients with degenerative retinopathy and low conditions [5]. visual acuity has been developed in a multidisciStem cells are undifferentiated cells which plinary approach. It focuses on the skills and have the ability to self-renew and differentiate functional needs of these patients by giving them into mature cells. a much higher level of autonomy. They are highly proliferative, implying that an The most frequently used devices are lights unlimited number of mature cells can be genermade especially for improving contrast, magni- ated from a given stem cell source. On this basis, fying systems, photoselective filters, smart- cell replacement therapy has been evaluated in phones, and pads. Their aim is to maximize the recent years as a viable alternative for various residual visual function. pathologies. This therapy hypothesizes that new However, the progressive loss of photorecep- retinal cells could be generated from stem cells to tors contributes to reducing the performances replace the damaged cells in the diseased retina. gained with visual rehabilitation, and the psychoThis objective can be achieved by delivering logical impact of the deterioration of vision must embryonic stem cells (ESC), induced pluripotent not be underestimated. stem cells (iPSC), and mesenchymal stem cells New approaches for therapy in degenerative (MSCs) to precise target locations in the eye [6]. retinopathy include restoring defective genes, ESC, iPSC, and MSCs are capable of self-­ when the disease is caused by a genetic defect, renewal and display multipotency, that is, the and stem cell transplantation to replace or repair ability to differentiate into all cells derived from defective or dead cells, regardless of the cause any of the three germ layers. [5]. Stem cell-based therapy casts a new hope for Gene therapy holds much potential, but it is treatment of retinal degenerative diseases as a currently at the experimental stages of develop- replacement or regeneration strategy. However, ment and has obtained only marginal therapeutic ESC and iPCS have generated much controversy results in vivo. For this reason, the interest of sci- concerning especially ethical, immunological, entific community is also addressed to stem cell-­ and oncological issues. Instead, the use of MSCs based restoratory strategies consisting of the seems to be free of these concerns.

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We could therefore define cell therapy, or cell-­ mediated therapy, as any therapeutic modality based on the use of cellular grafts aiming not only at the functional reactivation (or neuroenhancement) of the impaired cells and the possible regeneration of some elements (such as receptors, mitochondrial components, connection fibers), but also at their integration with the aforementioned cells. Therefore, the core of the issue is that it may be easier to preserve or promote the survival and the function of diseased cells rather than to restore the lost functions after the cell’s disappearance following the onset of the pathology.

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In addition, stem cells, particularly mesenchymal stem cells (MSCs), are able to perform multiple functions, such as immunoregulation, anti-apoptosis of neurons, and  neurotrophic secretion, and the current view is that MSCs can exert neuroprotective and proregenerative effects, mainly by secreting multiple factors that act in a paracrine fashion. Many studies suggested that MSCs are able to maintain and regulate the microenvironment in different models of retinal degeneration [8]. Of all the MSC collection sites, adipose tissue is particularly interesting. Adipose tissue can be obtained using simple procedures such as liposuction performed under local anesthesia, and the num62.3 Mesenchymal Stem Cell: ber of MSCs in adipose tissue is relatively large. The isolated stem cells are easily grown in culture, Therapeutic Instruments and they preserve their properties over many pasin Degenerative Retinal sages. These advantages make adipose tissue an Diseases attractive alternative source of stem cells [9]. MSCs are characterized by the panel of positive ADSCs, like all MSCs, are multipotent and and negative cell surface markers proposed by can differentiate into various cell types, including the International Society for Cellular Therapy in osteocytes, adipocytes, vascular endothelial cells, 2006. The MSC population is defined as >95% cardiomyocytes, pancreatic β-cells, and positive for CD105, CD73, and CD90 and >95% hepatocytes. negative for CD45, CD34, CD14, or CD11b; An increasing number of studies also report CD79𝛼 or CD19; and HLA-DR [7]. that MSCs are capable of giving rise to neuron-­ MSCs have the capacity to migrate to sites of like cells. They are not only able to differentiate injury following their intravascular administra- into neurons for cell replacement therapy but tion. This process depends on molecules present they also show paracrine effects by modulating on the surface of MSCs and endothelial cells, the plasticity of damaged host tissues. These cells such as P-selectin and integrins. After adhering to are able to secrete neurotrophic and survival-­ the endothelium, MSCs are capable of crossing it promoting growth factors, restore synaptic transin a metalloprotease-dependent manner. mitter release, integrate into existing neural and MSCs can be obtained from different sources: synaptic networks, and re-establish functional umbilical cord blood, peripheral blood, bone connections [9]. marrow, and adipose tissue. The multipotent ADSCs produce bFGF, vascular endothelial nature of MSC has been demonstrated in appro- growth factor (VEGF), macrophage colony-­ priate culture conditions with lineage-specific stimulating factor (M-CSF), granulocyte-­ growth factors that direct the differentiation of macrophage colony-stimulating factor (GM-CSF), MSCs into specific cell types (adipocytes, chon- placental growth factor (PlGF), TGFβ, hepatocyte drocytes, and osteoblasts). growth factor (HGF), IGF-1, IL, angiogenin, ciliTherefore MSCs play a key role in organogen- ary neurotrophic factor (CNTF), and brainesis and remodeling as well as tissue repair. derived neurotrophic factor (BDNF). Experimental studies also reported that MSCs Another mesenchymal tissue typology, reprehave the potential to differentiate into retinal pro- sented by adipose tissue, just like bone marrow, genitor cells, photoreceptors, and retinal neural-­ contains a large population of stem cells within like cells. its stromal compartment. Stromal adipocytes or

62  Degenerative Retinopathy Treatment with ADSC: Our Experience

adipose stromal cells secrete a series of hormones, factors, and protein signals, called adipokines, which are associated with the role of the adipocyte in energy homeostasis. Fat cells produce basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-­like growth factor-1 (IGF-1), interleukin (IL), transforming growth factor-β (TGFβ), pigment-­epithelium-derived factor (PEDF), and adiponectin. Another structure  of mesenchymal origin is platelet, originated by the subdivision from the megakaryocytes. Platelets, normally known for their hemostatic action, also release substances that promote tissue repair, angiogenesis, and modulation of inflammation. Furthermore, they induce cell migration and adhesion at angiogenesis sites, as well as the differentiation of endothelial progenitors into mature endothelial cells. Platelets produce platelet-derived growth factor (PDGF), IGF-1, TGFβ, VEGF, bFGF, EGF,

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platelet-derived angiogenesis factor (PDAF), and thrombospondin (TSP).

62.4 W  hy Use Mesenchymal Stem Cells in the Degenerative Retinal Diseases? The rationale behind autologous grafting of mesenchymal cells lies in the exploitation of the stabilizing effect on the retina exerted by cytokines and growth factors released paracrinally by the grafted cells. The binding of growth factor to its own specific receptor of the target cell is the initial step that triggers an intracellular signaling transduction cascade, activating particular second messengers. The latter ones can activate specific intracellular biochemical pathways generally by a series of phosphorylation events, with the ultimate aim of regulating the enzyme activity or the gene expression (Fig. 62.1) [10].

Suprachoroidal Mesenchimal Cells Autograft by LRRT

Suprachoroidal Choriorential blood circulation

Fat cells (yellow) produce: bFGF, EGF, IGF-1, IL, TGFβ), PEDF, and adiponection. ADSCs (orange) produce: bFGF, VEGF, M-CSF, GMCSF, BDFN, PIGF, TGF-β, HGF, IGF-1, IL, and angiogenin. Platelets (red) produce: PDGF, IGF-1, TGF-β, VEGF, bFGF, EGF, PDAF, TSP.

Subretinal

IGF-1, BDNF, CNTF, FGF in MCs and PEDF, FGF, VEGF, TGF-β, CNTF in RPE

Epiretinal

Bax

Surviving of RGCs

Bcl-2 IL-1β and TNF-α in PG

Fig. 62.1  A possible neuroprotective effect given by the incretion of growth factors produced by mesenchymal cells implanted in the suprachoroidal space through LRRT. These factors can act both directly on retinal cells and indirectly, through the mediation of Müller cells

(MCs) and RPE, generating angiotrophic, neurotrophic, anti-inflammatory, and anti-apoptotic effects [11, 12]. Image courtesy of P. Limoli—Centro Studi Ipovisione di Milano.

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Notably, the activated transcription factors, entering the nucleus and interacting  directly or indirectly to DNA, regulate the genetic  expression with different mechanisms and promote an increased synthesis of proteins including enzymes and cytokines. These final products play a key role in cell survival, as assessed by the enhancement of the ERG-recorded electrical activity [12]. The significance of growth factors lies in their essential role of cell cycle regulation, since their presence triggers the cell transition from G0 or quiescent phase to G1 or growth phase, necessary to enter the cellular growth cycle. And besides, they are also important for stimulating a wide range of cellular processes, including mitosis, cell survival, migration, and cellular differentiation. Mesenchymal cell graft into the suprachoroidal space promotes a continuous paracrine incretion of GFs that can interfere positively with the evolution of retinal diseases in several ways. Therapeutic mechanisms are synopsized as follows: 1. Hemorheological activity 2. Anti-oxidative activity 3. Anti-inflammatory activity 4. Anti-apoptotic activity 5. Cytoprotective activity 6. Synergic activity with electrical stimulation (ES) It is worth noting that the boundaries among these categories are thoroughly blurred. The hemorheological activity contributes to restoring effective retinal perfusion [13]. The photoreceptor loss that occurs in retinal diseases has been identified as a cause of microvascular dysfunction due to the release of cellular waste products secondary to apoptosis. In this case as well, the ensuing altered perfusion may end up in a vicious circle leading to the final other photoreceptors loss. Several factors, such as VEGF, bFGF, angiogenin, PDAF, PlGF, PDGF, EGF, and TGF-β, have been shown to promote endothelial regeneration and therefore may contribute to the cho-

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riocapillaris reperfusion. Moreover, others, including TSP and PEDF, inhibit pathological neovascular processes. The anti-oxidative activity prevents oxygen-­ induced photoreceptor cell death in the posterior retina [14]. One of the underlying causes of photoreceptor deterioration, which may explain the evolution of retinal degeneration, is hyperoxia resulting in a more intense oxidation process and reactive oxygen species (ROS) formation. Excess generation of reactive oxygen species causes damage to membrane lipoproteins and cellular DNA, thus leading to apoptosis and photoreceptor death. The mechanism involved in hyperoxia can be enlightened by the excessive amount of oxygen in the choroid, similar to arterial oxygen level, that stems from the deterioration and death of photoreceptor, plus the light exposition of the foveal area as well as the concomitant lack of anti-oxidative enzymes, such as superoxide dismutase (SOD) that is normally located in the mitochondria of cone inner segments, glutathione peroxidase and catalase, that catalyze the decomposition of hydrogen peroxide into water molecules and oxygen. The bFGF concentration within the photoreceptors has been shown to increase in response to stress in order to promote the retinal cell survival and to prevent the oxygen-induced photoreceptor cell death. The anti-inflammatory activity can counteract the negative effects induced by microglial activation, which occurs as soon as the apoptotic processes induced by retinal degeneration begin [15]. In turn, apoptosis and death of photoreceptors are suggested by the ignition of an inflammatory microclimate that underpins the chronicity and the progression of a vast number of neurodegenerative diseases. Particularly, RPE performs a number of processes essential for retinal homeostasis and function and constitutes the frontline of retinal immune defense: RPE cells are capable to secrete a diversified panel of proinflammatory cytokines, e.g., IL-6, IL-8, MCP-1 (monocyte ­ chemoattractant

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protein-1), IFN-β (interferon-β), as well as antiAlternately, mesenchymal cell administration inflammatory factors, e.g., IL-11 and TGF-β. can interfere with apoptotic process involved in Intravitreal administration of MSC has retinal degeneration. The growth factors excreted shown to exert a remarkable effect on the host by grafted mesenchymal cells perform a variety of immune response by suppressing pro-inflam- functions; in particular they are able to facilitate the matory cytokine production, such as INF and Bcl-2 gene expression in order to avoid the unreTNF through IL-1RA (IL-1 receptor antago- lenting cell death, regardless of any root causes. nist) and PGE2R (prostaglandin E2 receptor) The cytoprotective activity of the GFs contribactivation. utes to neuroprotection by regulating photorecepThe MSC therapeutic effect has also been tor metabolic activity, extensively impaired in corroborated by the neurotrophic action of retinal diseases [17]. CNTF (ciliary neurotrophic factor) and BDNF Like bFGF, PEDF has been found to exert (brain-­derived neurotrophic factor): in the cul- neurotrophic activity, inducing overall survival of ture of retinal ganglion cells, maintained under photoreceptors. oxidative stress conditions, the secretion of There are currently significant data suggesting these factors by MSCs, attenuates the release of that certain factors such as EGF play an imporproinflammatory cytokines, e.g., TNF-alfa tant role in enhancing the neuroprotective action (tumoral necrosis factor-­ alfa) and IL-1 of Müller cells, stimulating their intracellular (interleukin-1). transcription and expression of bFGF. M-CSF, GM-CSF, and IL exert anti-­ VEGF released by PRP has been shown to inflammatory function and recruit macrophages stimulate the proliferation of ADSCs that hence by chemotaxis which contribute to removing promote the survival of grafted autologous fat intraretinal cell debris. and adipocytes. The anti-apoptotic activity is regulated by bFGF is known to promote directly the surcytokines that can inhibit (anti-apoptotic) or vival of photoreceptors by binding the target induce apoptosis (pro-apoptotic) through the receptors on their surface. block of inhibitory mediators [16]. The synergic activity with electrical stimulaBcl-2 family proteins are most notable for tion (ES) addresses four main aspects: native cell their regulation of apoptosis by interacting with survival, transplanted cell survival, transplanted caspases, a family of protease enzymes contain- cell integration, and functional synapse formaing cysteine (cysteine aspartate-specific prote- tion/axon regeneration [18]. ases or CASPases). In recent years, the synergy between cellular RPE cells and Müller cells produce a wide therapies and electrical stimulation has begun to heterogeneity of factors, i.e., fibroblast growth be considered as a possible treatment for degenfactors (FGF-1, FGF-2, and FGF-5), transform- erative pathologies. ing growth factor-β (TGF-β), insulin-like growth ES-treated rat retinas exhibited decreased factor 1 (IGF-1), ciliary neurotrophic factor apoptosis. (CNTF), platelet-derived growth factor (PDGF), Light-induced retinal degeneration models vascular endothelial growth factor (VEGF), cer- have also been proven to preserve retinal structain members of interleukin family, and pigment ture after ES stimulation, reduce photoreceptor epithelium-derived factor (PEDF). cell death, and preserve outer segment length. This multitude of above-described growth facConsequently, it can be assumed that ES treattors released into the retinal cytosol is able to ment may create a more balanced and less hostile produce an extensive trophic action on the adja- environment, modifying the secretion of the neucent structures. It follows that the progressive rotrophic factors. loss of RPE and Müller cells hinders the incretion ES conditions up-regulation of neurotrophic of such bioactive agents: their anti-apoptotic factors in Müller cells, normally involved in this action is therefore prevented. protection mechanism. Increased in  vivo

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expression of fibroblast growth factor beta (FGF- tors of chorioretinal cells, better the increase of 2), insulin growth factor-1 (IGF-1), and brain-­ the cellular activity, and, ultimately, the improvederived neurotrophic factor (BDNF) has been ment of visual performance (VP) [12]. observed after ES. The delivering of growth factors in a retina Furthermore, ES downregulates pro-­with very low cellularity, hardly results in detectinflammatory cytokines like tumor necrosis factor able neuroenhancement. (TNF)-alpha, interleukin-1 beta (IL-1β), and proIn order to achieve this purpose different apoptotic gene Bax. The release of neurotrophic approaches have been explored by inserting these factors from the postsynaptic membrane made cells into the sub-tenon’s space, in the intravitreal possible by neuromodulation, together with the or subretinal space. But it appears that implant enrichment of the same factors in the extracellular placement in the suprachoroidal space can satisfy environment operated by autologous grafts, deter- efficacy and safety. mines the formation of synapses at presynaptic In fact, the grafting under the tenon, although level, facilitating and strengthening neurotrans- having a therapeutic significance, does not allow mission. The synaptogenesis process could be the growth factors produced to reach in important ignited by either the mesenchymal cell grafts or quantities the neuroretinal tissues inside of the the pulsed neuromodulation that cause the rhyth- sclera. mic formation of action potentials. The intravitreal injections of cellular material have similar efficacy to subretinal and suprachoroidal implants, but it is necessary to 62.5 Surgical Techniques pierce the bulb and leave this material free in the eyeball. Even serious complications are possiof Implant of ADSCs ble such as infection, vitreoretinal tractions, and and Mesenchymal Cells bleeding. How can ADSCs and other types of mesenchyThe subretinal implant would appear to be the mal cells be implanted at an ocular level in order best for the possibility of potential modification to obtain a restoration effect of the residual cells of cell lines due to direct contact of ADSCs to during atrophic neuroretinal diseases? neuronal cells but their grafting is even more danIn order to evaluate the efficacy of cell-based gerous when the retina appears to be comprotreatments for retinal dystrophy, aimed at stabi- mised by atrophic diseases [19]. lizing and neuroenhancing the visual function, it The suprachoroidal graft maximizes the supis important to consider two key elements: surgi- ply of growth factors that flow directly to the chocal implantation techniques and different cell lin- roidal level and through the choroid to the entire eages on the one hand, and residual retinal cells retina without creating bulbar perforation. on the other, i.e., early treatment. In order to be able to place the growth factors The technique needs to be simple, completely produced by the mesenchymal cells in the retinal without risks, and painless as well as the exploited environment and benefit from their therapeutic cells should not cause further damage to either action, we explored the possibility to treat the the residual retinal cell or the person. dystrophic retina with sovra-choroidal implant of Residual retinal cell should be of a substantial the cell types of mesenchymal origin mentioned number to exert an effective therapeutic action above, particularly adipose stromal cells (ASCs), since cytokines and growth factors, released adipose-derived stem cells (ADSCs) contained in paracrinally by the administered cells, must bind the stromal-vascular fraction (SVF) of adipose to membrane receptors to trigger intracellular tissue, and platelets (PLT) recovered in the signal transduction pathway. Cell therapy require platelet-­rich plasma (PRP) (41–43). still alive retinal cells. To this end we used a surgical technique From the studies carried out so far it seems defined as Limoli retinal restoration technique that the larger the residual cell number the greater (LRRT), described in previous works (Fig. 62.2) the interaction between GF and membrane recep- [12, 20].

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Scleral Flap

ADSCs

PRP to PGL

Orbital Adipocytes

Growth Factors bFGF

VeGF

TGF

VeGF

bFGF

TSP

BDFN

TSP

IGF

GM-CSF

Choroid Sclera

Pigment Epithelium Photoreceptors

Apoptosis area

Fig. 62.2 The suprachoroidal autograft obtained by Limoli retinal restoration technique (LRRT) allows to place fat stromal cells, ADCSs, and platelets close to the choroid. The production of growth factors (GF), characteristic of these cells, is poured directly into the choroidal flow, helping to maintain retinal cell trophism.

The GFs, through the choroidal flow, have a direct action on the choroid, on the Müller cells, on the RPE cells with improvement of physiology of outer segments (OS), on the rods, and on the cones. Image courtesy of P.  Limoli—Centro Studi Ipovisione di Milano

Cell therapy with ADSCs, ACS, and PLT has been proven to have a notable impact on certain functional parameters after the interaction with residual cells. The direct contact of the autograft with the choroid enhances the incretion of the bioactive factors produced by mesenchymal cells into the choroidal flow and consequently it promotes a widespread dissemination thereof through the retinal tissue, finally exuding in vitreous body. The cell therapy would directly and indirectly increase choroidal perfusion as well as contribute to a greater trophism of photoreceptors through GF–receptor interactions and Müller cell and RPE-mediated stimulation. The interaction between retinal cells and growth factors is there-

fore believed to play a crucial role in leading to improvement in the outlook for degenerative retinopathy, to prevent and/or delay its progression,  creating the conditions for an appreciable neuroenhancement creating the conditions for an appreciable neuroenhancement. The objectives that can be achieved  by cell therapy, schematically are: • The restoration and neuroenhancement on residual cells (Fig. 62.3) • The partial reduction of scotoma (Fig. 62.4) • The improvement of reading performance by the stabilization of fixation obtained with neuroenhancement (Fig. 62.5) • The improvement of choroidal flow (Fig. 62.6)

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Fig. 62.3  The image shows the evolution  of an optic atrophy (lower left) due to a head injury that occurred 2 years earlier. The patient began a rehabilitation process using neurotrophic supplements and neuromodulation cycles. We observed the sensitivity recorded with microperimetry and visual performance at the beginning of this

path (top and left). After one year the functional aspect has definitely improved (T0) and a suprachoroidal implantation of autologous mesenchymal cells was performed. The month following the intervention (T30) a subtotal restoration of damaged visual functions occurred. Image courtesy of P. Limoli—Milan Studies Center

• The preservation of helpful areas such as the fovea (when it is still present) or preferential reading field (Fig. 62.7) • The slowdown of the retinal disease evolution (Fig. 62.8)

predictive factor of outcome for patients treated with cell therapy.

62.6 L  imoli Retinal Restoration Technique (LRRT): Technical In our study greater foveal or retinal thickness Aspects

is associated with a better prognosis. On the other hand, the lack of cells has proven to hinder the yearned interactions between growth factors and membrane receptors [12, 20]. For this reason, cell therapies must be proposed as soon as the disease begins to advance or, in the case of inherited retinal diseases, when the cells are still numerous. If the reduction  of visual performances is accepted by the patient and the pathology is stable, it is preferable to wait to propose a cellular surgery. Knowledge of the overall amount of retinal cells is of particular importance: the rehabilitator and surgeon should be aware of that as a precise

The gold standard in anesthesia during LRRT is topical anesthesia, reinforced by sub-tenon’s infiltration of anesthetic and sedation. Only in specific cases, general anesthesia is preferred (for more details see Table 62.1). Limoli Retinal Restoration Technique represents a variant of Pelaez’s intervention by which orbital autologous fat is transplanted in the subscleral space [1]. In our technique, called Limoli retinal restoration technique (LRRT), ADSCs in addition to adipose stromal cells and PRP are grafted between the choroid and sclera [12, 20].

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Fig. 62.4  The described case highlights the natural functional decline over the course of 18 months in a case of glaucoma (a–c), despite the support of neurotrophic supplements. An autologous suprachoroidal implant was performed and from the first month (d) an improvement in

visual performance has been observed, which has been accentuated after 4 (e) and 12 months (f). After 4 months the visual stimulus was resumed using neuromodulation techniques (FSN). Image courtesy of P.  Limoli—Centro Studi Ipovisione di Milano

Surgically grafted cells can produce many GFs with neurotrophic and angiotrophic properties in the surrounding tissue, choroid, and retina. In LRRT, the distance between grafted autologous cells and choroid is reduced by means of deep sclerectomy, and the contact area between the stalk and choroid is expanded to promote the paracrine autologous cell secretion into the choroidal flow. We perform proper disinfection of each eye before surgery. After exposing the choroid, we place on its surface a pedicle of adipose tissue coming from the orbital space. We graft the ADSCs, obtained by Coleman technique (Figure 62.1) from SVF of abdominal fat, in the suprachoroidal space. We infiltrate adipose pedicle with platelets derived from PRP gel obtained through the following steps (Fig. 62.2).

Let us see this technique in more details. Fat tissue is collected and purified from the abdominal subcutaneous layer of patients, according to the Lawrence and Coleman technique. We manually harvest 10 mL of fat tissue from the abdominal subcutaneous layer of each patient, using a 3 mm blunt cannula connected to a locking syringe, according to the Lawrence and Coleman technique. We separate pure SVF of fat tissue from blood, fat, oil, and liquid by centrifugation for 5 min at 1500 × g at 20 °C. The SVF is very rich of ADSCs [1]. Flow cytometry analyses were performed in order to identify the phenotypic characteristics of the population of cells within the graft, specifically ADSCs, platelets, and stromal cells. CytoFLEX platform (Beckman Coulter, USA) was used for this purpose. The data were

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Fig. 62.5  Patient suffering from degenerative myopia (top left retinography) struck 1 year earlier by CNV and treated with photodynamic therapy (PDT) and anti-­ VEGF the scarring can be seen in the OCT scan (top right). The patient was treated with a suprachoroidal implant of autologous mesenchymal cells (T0). After 1 (T30) and 12

months (360) we observed an increase in sensitivity outside the now atrophic areas. Functional restoration drove fixation which became more stable by improving the reading capacity from 18 pts (T0) to 10 pts (T360). Image courtesy of P. Limoli—Centro Studi Ipovisione di Milano

analyzed with KALUZA software (Beckman Coulter). We collect 8 mL of human peripheral blood with a 22 G needle and in a separate tube for PRP preparation. For platelet-rich plasma (PRP) preparation, we use a Regen-BCT tube (RegenKit; RegenLab, Le Mont-sur-Lausanne, CH). The collected blood is centrifuged for 5  min at 1500 x g at 20 °C in order to obtain platelet-rich plasma (PRP). The stimulus to platelet degranulation causes GF release in the adipose pedicle (42, 43). In LRRT, the ensuing changes result in better survival of the autologous fat graft, ADSC proliferation which favors increased choroidal perfusion, and a more comprehensive modulation of the action of those factors that are secreted only by fat.

We build the scleral pocket in order to expose the surface of choroidal space and to accommodate the graft obtained from orbital fat and ­saturate the residual volume of this pocket with a mixture of ADSCs from SVF and PRP, obtained as above described (for more details see Table 62.2). It is important to reduce the distance between the grafted autologous cells and choroid by deep sclerectomy to increase  into the choroidal flow paracrine secretion from the autologous cells. For the same purpose, it is important to expand the area of contact between the pedicle and choroid. No complications were observed in visual function after adipose-derived MSCs were applied under a deep scleral flap in the suprachoroidal area.

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Fig. 62.6  Patient suffering from dry age macular degeneration. A central island corresponding to the fovea surrounded by atrophic areas remains (in the upper left blue arrows). The sensitivity appears to be compromised by a paracentral scotoma but the survival of the fovea allows a good visual capacity (lower left). Four months after cell

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surgery we observed (in the upper right and center right) an increase in the thickness of the choroid. The improvement in choroidal circulation contributed to the stabilization of visual performance. Image courtesy of P. Limoli—Centro Studi Ipovisione di Milano

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Fig. 62.7  Another case of dry AMD with savings of the foveal area (top) at T0. 6 months after cell surgery, despite the progression of the scotoma within the paracentral atrophic areas, the fovea

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maintained its sensitivity and visual performance was preserved (T180). The ERG activity (bottom left) showed an increase (bottom right). Image courtesy of P.  Limoli— Centro Studi Ipovisione di Milano

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Fig. 62.8 Patient with degenerative retinopathy of Stargardt. A suprachoroidal graft of autologous mesenchymal cells was performed in 2014. He maintained

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visual performance unchanged after 5 years. Image courtesy of P. Limoli—Centro Studi Ipovisione di Milano

Table 62.1  LRRT: Anesthesiological preparation Obtain corneal and conjunctival anesthesia by applying topical local anesthetics instilled dropwise 15–20 min before the surgery with lidocaine at 4% and ropivacaine at 1%. Inject anesthesia by infiltration directly into subconjunctival and sub-tenon’s spaces. Use local infiltration both in the abdominal region, before the adipose tissue is extracted, and in the subconjunctival and sub-tenon’s spaces, 12 mm from the limbus. Adopt local anesthetic of carbocaine or marcaine mixed with 1200 IU epinephrine. Provide intraoperative sedation through the anesthetic, which can be performed properly by using fentanyl as a narcotic analgesic through bolus perfusion. The dosage is generally 0.025 mg of fentanyl with 1 mg of midazolam per bolus.

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Table 62.2  LRRT: Surgical phases After anchoring the sclera with 6-0 silk suture, near the inferior-temporal limbus, the globe was deviated to the supero-nasal quadrant. We open the subconjunctival and sub-tenon’s space at 11 mm from the inferior-temporal limbus, using 5.5" Westcott Tenotomy curved scissors. We insert the Limoli-Basile conjunctival retractor in this space to make a scleral surgical field. Using a crescent knife angled bevel up, we pre-cut into the sclera a 5 mm square flap per side, 8 mm from the limbus. The flap hinge is always radial and to the left of the surgeon. A deep scleral flap of about 5 × 5 mm is opened at the inferotemporal quadrant, maintaining the radial hinge. The sclerectomy has to be deep enough to allow viewing the color of the choroid. We create a gap by removing a little operculum in the distal part of the flap, in order to facilitate blood circulation in the subsequent suprachoroidal autograft. We extract with ophthalmological forceps the orbital fat from a gap above the inferior oblique muscle. We have to make sure that the extracted fat is sufficiently vascularized to allow it to survive after its implantation. Gently we place the autologous fat flap on the choroidal bed and we suture with choroidal 6/0 polyglactin fiber at the proximal edge of the door. We suture the scleral flap to avoid compression on the fat pedicle or on its nutrient vessels. We infiltrate the stroma of the fat pedicle with 1 mL of PRP gel (obtained by centrifugation of the blood material, separation of the component, and platelet degranulation using a 30 G angled (30°) cannula. We prepare the sides of the conjunctiva for the suture. Then, we remove the conjunctival retractor. We suture the conjunctiva, using 6/0 polyglactin fiber. Before closing, in the space between the flap, the choroid, and the suprachoroidal autograft, we leave a small flexible plastic tube in order to insert the autologous ADSCs. The remaining space between the autologous fat graft, choroid, and scleral flaps is filled with 0.5 cc of 1 × 106 ADSCs and 0.5 of PRP using a 25-gauge cannula. After saturating the residual space, we close the suture. After surgery, we administer 3 days of antibiotic therapy with 500 mg azithromycin. Also, we provide eye-drop therapy with an antibiotic and steroid combination, such as chloramphenicol and betamethasone, for about 15–20 days.

Case Study The technique of implantation of autologous mesenchymal cells at the suprachoroidal level, defined as LRRT, has been applied in our center from 2012 to today (2019) on 517 eyes of 338 patients, united by the impairment of visual function due to the progression of the atrophic neuroretinal disease by which they were affected. The goal was, as far as possible, to restore cell trophism through metabolic, anti-inflammatory, and hemodynamic stimuli. The most treatable pathologies seem, for our experience, to be the atrophic macular degenera-

tions (high myopia, Stargardt diseases, AMD), retinitis pigmentosa, glaucomatous, and non-­ glaucomatous optic atrophies. In the graphic the details of the pathologies treated are shown. Legend: HM without GON: High Myopia without Glaucomatous Optic Neuropathy; HM and GON: High Myopia with Glaucomatous Optic Neuropathy; GON: Glaucomatous Optic Neuropathy; AON: Atrophic Optic Neuropathy; CD: Cone Dystrophy; Dry AMD: Dry ­Age-­related Macular Disease; RP: Retinitis Pigmentosa; SD: Stargardt Disease; Mix: Miscellanea.

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LRRT-Treated Neuroretinal Diseases Low Vision Research Center of Milan Mix 18-3%

HM without GON 59-11% HM and GON 26-5% GON 22-4%

RP 124-24%

AON 45-9%

CD 23-4%

Dry AMD 152-29%

62.7 Conclusion In our clinical experience, the suprachoroidal implantation of autologous mesenchymal cells according to LRRT has demonstrated its therapeutic potential, positively influencing various functional parameters. The direct contact of the autograft with the choroid improves the incretion of bioactive factors (cytokines and exosomes) produced by mesenchymal cells in the choroidal flow and therefore promotes the diffusion through the retinal tissue, finally exuding in the vitreous body. We can obtain directly, through interaction between growth factors and membrane receptors, and indirectly, through interactions with Müller and RPE cells, the increase of chorioretinal microcirculation as well as a greater trophism of photoreceptors and ganglion cells. It is reasonable to believe that the interaction between GFs and retinal cells may lead to an

improvement of the functional parameters in the course of retinal atrophic diseases, in order to prevent and/or delay progression of the latter diseases and, in some cases, to induce neuroenhancement. The functional parameters seem to improve most in subjects that have more residual cells, or in other words in subjects that have greater biological thicknesses measurable with optical coherence tomography. In fact, the retinal thicknesses indirectly indicate the trophic conditions of the photoreceptors or residual ganglion cells and can be used as a prognostic criterion in predicting the therapeutic response of the LRRT cell transplantation. The message that attains is that the visual rehabilitator and the ophthalmic surgeon should be jointly aware of the cellularity of the retina in order to propose to the visually impaired patient a therapeutic-rehabilitative action, based on cell therapy.

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References 1. Punzo C, Wenjun X, Cepko Costance L.  Loss of daylight vision in retinal degeneration: are oxidative stress and metabolic dysregulation to blame? JBC Papers in Press; 2011. https://doi.org/10.1074/jbc. R111.304428. 2. Langmann T. Microglia activation in retinal degeneration. J Leukoc Biol. 2007;81:1345–51. 3. Yafai Y, Iandiev I, Lange J, Yang XM, Wiedemann P, Bringmann A, Eichler W.  Basic fibroblast growth factor contributes to a shift in the angioregulatory activity of retinal glial (Müller) cells. PLoS One. 2013;8(7):e68773. https://doi.org/10.1371/journal. pone.0068773. Print 2013 4. Guadagni V, Novelli E, Strettoi E.  Environmental enrichment reduces photoreceptor degeneration and retinal inflammation in a mouse model of retinitis pigmentosa. Invest Ophthalmol Visual Sci. 2015;56(7):4261. 5. Melissa K, Jones BL, Girman S, Wang S. Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases. Prog Retinal Eye Res. 2017;58:1–27. Published online 2017. https:// doi.org/10.1016/j.preteyeres.2017.01.004. 6. Ding SLS, Kumar S, Mok PL.  Cellular reparative mechanisms of mesenchymal stem cells for retinal diseases. Int J Mol Sci. 2017;18:1406. 7. Dominici M, Le Blanc K, Mueller I, et  al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4): 315–7. 8. Zarbin M. Cell-based therapy for degenerative retinal disease. Trends Mol Med. 2016;22:115–34. https:// doi.org/10.1016/j.molmed.2015.12.007. 9. Konno M, Hamabe A, Hasegawa S, Ogawa H, Fukusumi T, Nishikawa S, Ohta K, Kano Y, Ozaki M, Noguchi Y, Sakai D, Kudoh T, Kawamoto K, Eguchi H, Satoh T, Tanemura M, Nagano H, Doki Y, Mori M, Ishii H.  Adipose-derived mesenchymal stem cells and regenerative medicine. Dev Growth Differ. 2013;55:309–18. https://doi.org/10.1111/dgd.12049. 10. Wahlin KJ, Campochiaro PA, Zack DJ, Adler R.  Neurotrophic factors cause activation of intracellular signaling pathways in Muller cells and other

P. G. Limoli et al. cells of the inner retina, but not photoreceptors. Invest Ophthal Vis Sci. 2000;41:927–36. 11. Limoli PG, Vingolo EM, Morales MU, Nebbioso M, Limoli C.  Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration. Medicine. 2014;93(29):e355. https:// doi.org/10.1097/MD.0000000000000355. 12. Limoli PG, Vingolo EM, Limoli C, Scalinci SZ, Nebbioso M. Regenerative therapy by suprachoroidal cell autograft in dry age-related macular degeneration: preliminary in vivo report. J Vis Exp. 2018;132 https://doi.org/10.3791/56469. PMID: 29553543 13. Mammoto T, Jiang A, Jiang E, Mammoto A. Platelet rich plasma extract promotes angiogenesis through the angiopoietin 1-Tie2 pathway. Microvasc Res. 2013;89:15–24. https://doi.org/10.1016/j. mvr.2013.04.008. Epub 2013 May 6 14. Cui Y, Xu N, Xu W, Xu G. Mesenchymal stem cells attenuate hydrogen peroxide-induced oxidative stress and enhance neuroprotective effects in retinal ganglion cells. Vitr Cell Dev Biol Anim. 2016;53:328–35. 15. Zeng HY, Zhu XA, Zhang C, Yang LP, Wu LM, Tso MOM. Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice. Invest Ophthalmol Vis Sci. 2005;46(8):2992–9. 16. Ding SLS, Kumar S, Mok PL.  Cellular reparative mechanisms of mesenchymal stem cells for retinal diseases. Int J Mol Sci. 2017;18:1406. 17. Zack DJ.  Neurotrophic rescue of photoreceptors: are Müller cells the mediators of survival? Neuron. 2000;26:285–6. 18. Manthey AL, Liu W, Jiang ZX, Lee MHK, Ji J, So KF, Lai JSM, Lee VWH, Chiu K.  Using electrical stimulation to enhance the efficacy of cell transplantation therapies for neurodegenerative retinal diseases: concepts, challenges, and future perspectives. Cell Transplant. 2017;26(6):949–65. https://doi.org/10.37 27/096368917X694877. Epub 2017 Feb 3 19. Oner A, Sevim DG. Complications of stem cell based therapies in retinal diseases. Stem Cell Res Open Lib. 2017;1(1):1–7. 20. Limoli P.  The retinal cell-neuroregeneration. Principles, applications and perspectives. Limoli Retina Regeneration Tecnique [Italian]. FGE Reg. San Giovanni 40, Canelli (AT). Ed. 2014, 407–424.

Part VIII Breast Augmentation and Mastopexi with Fat

Aesthetic Breast Augmentation Using Autologous Fat Grafting: Indications, Patient Assessment, and Comparison Between Different Processing Methods in 204 Cases

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Amin Kalaaji, Vanja Jönsson, and Melanie Baumgartner

Abbreviations ADSCs AFT ASPS BA DFS rpm SVF TIVA

Adipose-derived stem cells Autologous fat transfer American Society of Plastic Surgeons Breast augmentation Disease-free survival Revolutions per minute Stromal vascular fraction Total intravenous anesthesia

•

• Key Messages • Autologous fat transfer is a good alternative for patients who refuse implants and for patients who wish to achieve an increase in breast volume within reasonable limits. • Traditional indications include breast asymmetry, tuberous breasts or other deformities, and breast reconstruction. New indications

•

•

•

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_63) contains supplementary material, which is available to authorized users.

• A. Kalaaji · V. Jönsson (*) · M. Baumgartner (*) Oslo Plastikkirurgi Clinic, Oslo, Norway e-mail: [email protected]

include implant conversion after complications and hybrid augmentation with a silicone implant to add volume and enhance contours. The eligibility criteria of the Oslo study included excessive fat, a realistic expectation of volume increase, no history or family history of breast cancer, preoperative radiographic evaluation through ultrasound or magnetic resonance imaging (MRI), and the wish for autologous material. Enhance the contour of the donor area, but do not hunt for fat! Fat grafting does neither interfere with breast cancer screening, nor does it have significant oncological potential. Fat grafting is an extremely safe procedure with a low complication rate (4%). Complications are rare and significantly correlated to the surgeon’s technique and proficiency level. The highest satisfaction rates and best outcomes were achieved in the decanting with vibration technique group. This method also was less time consuming. The processing method leading to the best result was the vibration technique using the PAL-650 Power-­ Assisted Liposuction from MicroAire®. Assessment of the patient is crucial and should include BMI evaluation and managing patient expectations.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_63

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• Tumescent anesthesia is administered and per-­ operative tissue expansion with the MicroAire vibration system is performed prior to fat grafting. • All procedures are performed under total intravenous anesthesia (TIVA) and local anesthesia.

63.1 Introduction Fat grafting has been widely used in the field of aesthetic and reconstructive surgery. Over the past few decades, different techniques have evolved, and existing techniques have been modified. Although much research has been performed, a standardized protocol leading to the best possible result has not been published yet. Various fat processing methods have been described and used over the past decade. According to the American Society of Plastic Surgeons (ASPS), breast augmentation is the most frequently performed procedure in cosmetic plastic surgery. The demand and the number of breast augmentation interventions have been steadily increasing in recent years and have doubled since the year 2000. According to the ASPS report of 2018, 25% of all cosmetic procedures were breast augmentations, followed closely by liposuction [1]. In 1895, the first autologous breast reconstruction was performed by Vincenz Czerny, using a fist-sized lumbar lipoma to replace fat tissue loss caused by mastitis [2]. With the advent of liposuction, introduced by Fournier and Illouz in 1980, fat grafting gained popularity [3]. The first plastic surgeon to perform liposuction in North America, Mel Bircoll, published the first article on autologous fat transplantation to the breast in 1987 [4]. Initially, autologous fat transfer (AFT) was mainly used in reconstructive surgery but has evolved to become a central element in cosmetic surgery. After a brief pause in its evolution due to the condemnation of the American Society of Plastic and Reconstructive Surgery (ASPRS), breast augmentation with fat has become a well-­ established and acceptable method, with

expanded indications due in no small part to the unwavering commitment of pioneers [5–12]. Autologous fat grafting is widely used in aesthetic surgery as well as reconstructive surgery, but fat processing itself is still challenging—and the effect of various processing methods on adipocyte survival is rather undetermined and still quite vaguely defined. As new indications continuously emerge, it is even more imperative to go one step further toward the implementation of a universal protocol, which will optimize fat cell survival and the overall outcome [13–23]. We at the Oslo Plastikkirurgi Clinic retrospectively evaluated breast augmentation indications, as well as their final results, through the perspective of the main available methods of processing fat. We aimed to define the processing method that leads to the most favorable outcome for the respective indications. After 11 years of research, we present our results after comparing four different methods.

63.2 Patients 63.2.1 Setting and Study Population A retrospective comparison of four different fat processing methods and an evaluation of treatment indications for aesthetic breast augmentation with fat were performed at the Plastic Surgery Clinic of Oslo (Oslo Plastikkirurgi Clinic). From 2009 to 2020, a total of 204 procedures were performed on 143 patients. All patients underwent breast enlargement using AFT. The mean age of patients was 36 years (range 18-63; most patients were between the ages of 26 and 35). Even though women over age 56 underwent breast augmentation, the proportion of younger patients was higher (for the exact age distribution, see Table  63.1). Out of 143 patients, 58 patients underwent two surgeries, and only 3 patients underwent a third intervention, for a total of 204 interventions in a span of 10 years. The first and second fat transfers were mainly bilateral (137 and 64, respectively), whereas two patients were augmented unilaterally: one patient unilaterally, in the third session. The third session was mainly to correct mild irregularities.

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Table 63.1  Age distribution Age No. of operations No. of patients

18–25 23 19

26–35 83 58

36–45 55 38

46–55 32 21

56+ 11 7

Total 204 143

Average agea 36 (18–63)

Of total number of patients undergoing an operation

a

Table 63.2  Indications for breast augmentation with fat Hypoplasia mammae Breast asymmetry Deformities like tuberous breast Complementary to mastopexy and breast reconstruction after cancer Simultaneously with other operations, such as abdominoplasty and gluteal augmentation Conversion breast implant replacement with fat Hybrid or composite/combined augmentation (implant enhancement to modify volume and/or shape) Tuberous breast

63.2.2 Indications and Eligibility Treatment indications were hypoplasia mammae, breast asymmetry, and deformities like tuberous breasts. Furthermore, fat grafting was performed complementary to mastopexy and breast reconstruction after cancer, as well as simultaneously with other operations, such as abdominoplasty and gluteal augmentation. The indication spectrum was recently extended to include conversions of breast implants with fat and hybrid (or composite/combined) augmentations (implant enhancement to modify volume and/or shape) (Table 63.2). Patients had to meet five eligibility criteria to become a candidate for surgery: (1) excessive fat; (2) a realistic expectation of volume increase; (3) no patient history or no family history of breast cancer; (4) radiographic evaluation through ultrasound or MRI; and (5) wish for an alternative to implants to avoid the use of foreign objects (Table 63.3).

63.3 Methods 63.3.1 Procedures According to the processing method being used, the total study population of 204 patients was

Table 63.3  Eligibility to become a candidate for breast augmentation with fat 1. No desire to use foreign objects such as implants and the wish for an alternative 2. No hunting for fat: patients should have the wish and the requirements to correct areas in the body (donor sites) 3. Realistic expectation of volume increase: max. 1–2 cup sizes per 1–2 sessions 4. Good understanding for the process of fat grafting and the at least 1-year duration to get the final results 5. Wish to combine implant with more natural augmentation in certain areas of the breast 6. No history or family history of breast cancer 7. Radiographic evaluation through ultrasound or MRI

grouped into four cohorts. A total of 27 patients received fat, centrifuged for 3  minutes at 3000 revolutions per minute (rpm) (Method 1); 45 patients received fat centrifuged for 16 minutes manually (Method 2); 20 patients received fat that was decanted for 10 minutes (Method 3); and 110 patients received fat that was decanted using the vibration technique of MicroAire technology (Method 4) (Fig. 63.1). One patient consented for BRAVA treatment, an external tissue expansion device that expands breast tissue in preparation for fat grafting (Method 5; for a more detailed description, see Tables 63.4, 63.5, and 63.6).

63.3.2 Preoperative Assessment The assessment included taking the patient’s medical history, BMI, ultrasound or MRI, and evaluation of the body’s fat deposits. The BMI should not surpass 30, and be preferably under 28, to ensure figure-forming results. With this method realistic expectations are important. A maximal enlargement of 1 to 2 cup sizes or about 200–250 mL fat graft per side can be obtained. Of course, we can perform more sessions to achieve a greater augmentation provided that there is existing fat to harvest. Fat

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a

b

c

d

e

f

g

h

Fig. 63.1  Characteristics of some processing methods per-operatively. (a) Machine centrifuge showing 10 mL syringes ready for centrifugation. (b) Manual centrifuge showing the centrifugation (15 G) of 4 syringes, 60 mL each, which resulted in 240 mL of fat ready within 3 min. (c) After manual centrifugation the grafting proceeds by using a 10 mL syringe. (d) Grafting, using a 20 mL syringe and a 2.7  mm cannula. (e/f) Per-operative view

showing MicroAire vibration system with 1 liter canister and the harvesting cannula in a closed system (for manual or decanting processing methods). (g) PAL MicroAire machine, showing the regulation of the vibrating power. (h) Per-operative expansion with vibrating cannula; 6 holes of 3 mm without suction

Table 63.4  Distribution of unilateral and bilateral breast augmentation. Note that the total number of breasts operated on is 399 breasts Side Bilateral Unilateral Total

1st session 137 6 143

2nd session 56 2 58

Table 63.5  Distribution according to indication

Hypotrophy/hypoplasia or wish to augment the volume Hypotrophy and asymmetry or wish to augment the volume Ptosis with wish to augment the volume Hybrid (combined, simultaneous, or delayed) Implant conversion Post-breast cancer reconstruction Tuberous breast Revision after implant Missing upper or lower pole Total

No. of patientsa 75 49 12 21 17 4 3 11 8 201

Some patients had more than one indication

a

grafting as part of a hybrid approach often delivers satisfactory results, as the need for fat is limited as in cases of rippling or augmentation of special areas. Obtaining good information throughout the procedure is essential, because the whole process takes at least 1 year. A draw-

3rd session 2 1 3

Total 195 9 204

Table 63.6  Distribution of all five processing methods used in three sessions

1st session 2nd session 3rd session Total

No. of operations by methodª 1 2 3 4 24 35 16* 67 3 10 3 41** 0 0 1 2 27 45 20 110

5 1 1 0 2

Total 143 58 3 204

*5 of them were manual centrifuge patients **7 of them were manual centrifuge patients ªMethods: 1: machine; 2: manual; 3: decanting or gravity separation; 4: decanting through vibration; 5: BRAVA

ing calculation sheath to register the grafted amount of fat in all 4 quadrants of the breast and sides per-operatively is usually conducted by the anesthesiologist assistant (Fig. 63.2).

63.3.3 Harvesting Fat was harvested from the abdomen thighs, buttocks, and inner knee regions with a 4  mm

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a

b

Fig. 63.2 (a/b) Patient assessment with marking of donor (abdomen and hips) and recipient area as well as incision sites with the grafting’s main directions. Preoperative evaluation of the amount of fat available and calculation of the distribution over different areas of the breast, taking into consideration existing asymmetries.

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c

Entry sites are marked with X. (c) A drawing calculation sheath to register the grafted amount of fat over all 4 quadrants of the breast and sides per-operatively

tion process. Being the only open-system technique among the four above mentioned, this Donor-site location 1st session 2nd session 3rd session method consists of a 3-minute centrifugation at Abdomen 102 39 3 3000 rpm with consecutive decanting of the botLower extremity 81 38 3 tom layer (blood and tumescent fraction) and Arm 6 2 0 Other 13 4 0 removal of oil (with a cotton pad) (Video Clip Total 202 83 6 63.1). *Abdomen with flanks Machine centrifugation is more time conNote: Many patients had more than one donor site suming than manual centrifugation but easier to perform. However, it should be noted that due multiperforated cannula, leading to a more aes- to its additional gravitational force acting on thetic result and additional body sculpting. No the harvested fat cells this technique could lead significant differences regarding cell viability to an increased damage to viable cells, resulting and volume retention of the abovementioned in a lower residual fat volume at the follow-up donor sites are described in current literature examination. Nevertheless, centrifugation in (Table 63.7). general is believed to be superior, due to the For the fat transfer, a blunt 3  mm cannula increased concentration of progenitor cells in was used, which reduced the risk of intravascu- the graft (g-force: 1200 relative centrifugal lar injection as well as maximized fatty tissue force). survival by injecting fat in small aliquots. All procedures were performed under TIVA plus 63.3.4.2 Manual Centrifugation tumescent anesthesia (1:1), which has been doc- With this method, fat is centrifuged manually umented to improve cell viability, reduce blood within a totally closed system. The force affectloss and pain, and ease the process of fat ing the harvested fat cells is much lower (g-force: harvesting. 15 rcf) and is therefore gentler than the machine centrifugation, which results in an increased survival of fat cells. Figure 63.1 shows a manual centrifuge spin63.3.4 The Four Fat Processing Methods (Figs. 63.3–63.8) ning 4 syringes containing 60 mL each, which results in 240 mL of centrifuged lipoaspirate ready within 3  minutes. The g-force used in 63.3.4.1 Machine Centrifugation First introduced by Coleman in 1987, this method this clip is 15 G, which much less reduces the is considered the gold standard for the centrifuga- fat cell viability (Video Clip 63.2). Table 63.7  Donor sites

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Fig. 63.3  Female, 28 years old with moderate hypotrophy; follow-up at 87 months. Treated over two sessions by mainly grafting the upper pole and cleavage area. Lipoaspirate was processed by machine centrifugation.

Right side: 164/110 mL, respectively; left side: 167/110 mL, respectively. There was no change in weight. Upper row: preoperative. Lower row: 87 months postoperative

Fig. 63.4 Female, 24 years old with post-reduction asymmetry. Revision with corrective augmentation; follow-up at 18 months. Lipoaspirate was processed by machine centrifugation. Right side: 320/200 mL, respec-

tively; left side: 245/50 mL, respectively. No change in weight. Upper row: preoperative. Lower row: 18 months postoperative

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a

b

Fig. 63.5 Female, 48 years old with post-­ reduction asymmetry and bilateral hypoplasia. Corrective AFT using decantation and MicroAire in three sessions. Right side: 190/130/320 mL, respectively; left side: 400/130/270 mL, respectively. (a) Preoperative photo documentation including preoperative planning (upper row); stable result after a 35-month follow-up; period succeeding AFT

(lower row); The preoperative planning in the first row shows the first sessions main aim of asymmetry correction of the left lateral breast. Patient examination ought to be performed with arms upraised. (b) Stable result at the 35 months (upper row) and the 42 months follow-up examination (lower row)

Our manual centrifugation group showed good results and good satisfaction rates. It is less time consuming than machine centrifugation, but the learning curve is higher.

discarding the top and bottom layers, the fat can be transferred. Decanting is less time consuming and allows the harvest of an almost unlimited amount of fat within 10 minutes. Decanting led to particularly good results in our study cohort. In two sessions, more than two-thirds of patients had over 70% residual volume, and less than one-third lost 30% to 50% of the transplanted fat.

63.3.4.3 Decanting This method is based on gravity separation and leads to a time-dependent fractionation of the lipoaspirate in a completely closed system. After

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Fig. 63.6 Female, 55 years old with revision after implant removal; follow-up at 72 months. AFT performed in two sessions using manual centrifugation as fat processing technique. Right side: 317/140 mL, respectively;

left side: 307/140 mL, respectively. No change in weight. Upper row: preoperative. Middle row: 3 years postoperative. Lower row: 6 years postoperative

63.3.4.4 Decanting with Vibration Technique (Using the PAL650 Power-Assisted Liposuction from MicroAire®) (Figs. 63.9–63.15) This is a power-assisted liposuction technique using MicroAire technology. It consists of a totally closed system and is used for suctioning as well as reinjecting the fat. Decanting using a vibration technique is easier and less time consuming for the surgeon. The post-

operative results were extremely satisfying. In more than 80% of cases, residual volume of over 70% was measured at the follow-up examination. Sixteen percent had a resorption rate of 30–50%, and only one patient lost more than 50% of the transferred fat. Most patients were satisfied with these results. Procedural variations that alter the effectiveness of the procedure may account for the unpredictable resorption rates observed. In contrast, the studies conducted demonstrated more favorable outcomes with centrifuga-

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Fig. 63.7  Female, 28 years old with hypotrophy and slight asymmetry; follow-up at 23 months. Lipoaspirate was processed by manual centrifugation in the first and decantation in

the second session. Right side: 245/225 mL, respectively; left side: 225/200 mL, respectively. No change in weight. Upper row: preoperative. Lower row: 23 months postoperative

Fig. 63.8  Female, 28 years old with hypotrophy; follow­up at 31 months. Lipoaspirate was processed by manual centrifugation in the first session and decantation in the

second. Right side: 190/130 mL, respectively; left side: 185/130 mL, respectively. No change in weight. Upper row: preoperative. Lower row: 31 months postoperative

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Fig. 63.9  Female, 27 years old with hypotrophy; follow­up at 8 months. Lipoaspirate was processed by decanting with vibration after applying BRAVA preoperatively in two sessions. Right side: 400/212 mL, respectively; left

side: 400/210 mL, respectively. Upper left: preoperative, including redness/mark from using BRAVA. Lower two to the left: donor site and preoperative view. The three to the right show the 1-year postoperative result

Fig. 63.10  Female, 23 years old with pronounced asymmetry; follow-up at 18 months. Treated with only one session. Lipoaspirate was processed using MicroAire and

decantation. Right side: 330 mL; left side: 0 mL. Upper row: preoperative. Lower row: 18 months postoperative

tion compared to gravity separation. Comparative studies investigating the effects of fat processing with centrifugation, washing, and filtration showed no significant difference in fat retention; however, filtration resulted in nodule formation, whereas centrifugation did not. BRAVA preoperative expansion was applied to one patient and will be discussed as applicable.

63.3.5 Grafting Technique With all methods used, fat was harvested from the abdomen, thighs, buttocks, or area around the knees and grafted in intersecting and parallel canals through small incisions. A 3-hole 4 mm harvesting cannula connected to the MicroAire PAL vibration system and a straight 3 mm grafting cannula connected to a 10 mL or 60 mL

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Fig. 63.11  Female, 46 years old with delayed conversion and revision after breast implant removal, with adherence to the lower medial corner on the right side. Rigottomy with fat graft after complicated breast implant. Lipoaspirate was processed with MicroAire and decant-

ing and grafted in two sessions. Right side and left side: 440/380 mL, respectively. Inverted nipple to the left side was corrected using our central tunnel technique. Upper row: preoperative. Middle row: 10 months postoperative. Lower row: 18 months postoperative

Fig. 63.12  Female, 36 years old with rippling after multiple implant removal and insertion subglandularly. Needed delayed hybrid revision to treat rippling. Lipoaspirate was processed with MicroAire and decant-

ing and grafted in two sessions. Right side: 150/120 mL; left side: 140/205 mL. Fat is grafted perpendicularly to the rippling lines after a per-operative expansion using a multiple-hole 3 mL cannula without suction

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Fig. 63.13 Grafting cannula. F B 8FAC-1225-LL straight 12GA × 25 cm, luer lock. It is the same as a straight or curved type 2.7 mm inner diameter cannula; with an appropriate length of either 15 or 25 cm. This type

of cannula with two opposing openings enables an even distribution without exerting pressure on the fat. (image credit: Black & Black Surgical)

Fig. 63.14  Female, 41 years old with hypotrophy and slight ptosis. Lipoaspirate was processed with MicroAire and decanting and grafted in two sessions (215 mL and

88mL per side). Upper row: preoperative. Lower row: 4 years postoperative

syringe were used. The grafting cannula (a straight 12 G x 25 cm, luer-lock cannula (F B 8FAC1225-LL)) features two opposite lying holes for fat injection, which allow for an equal fat distribution to the recipient side without exerting pressure (Fig. 63.13). It is the same as a straight or curved type 2.7  mm inner diameter cannula; with an appropriate length of either 15 or 25 cm. Prior to grafting, breast tissue expansion using a vibrating cannula without suction was performed for 5  min followed by tumescent

infiltration of approximately 50 mL per side (Fig. 63.1). The grafting was done slowly using a 10 mL, 20 mL, or 60 mL syringe with multiple parallel and crescent passes through two to four entry points at the lower pole—medially and laterally and sometimes up medially or laterally. Care was taken not to destroy connective septa tissue between the skin and gland, because this could endanger circulation and therefore the survival of the fat. Retrograde grafting, as when pulling back the syringe,

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Fig. 63.15  Female, 38 years old with hypotrophy and slight asymmetry. The lipoaspirate was processed with MicroAire and decanting, and grafted in two sessions. By using a 50 mL syringe and a 2.7  mm cannula, 300 mL (left) and 350 mL (right) were grafted in the first, and 240

could be performed—but primarily it was going forth and retrograde as much as staying in the same direction and same tunnel. Caution was taken against squired fat or blanching of the skin; if either was noted, then grafting was stopped. Also, oil or gel on the skin of the breast could be applied at the end of the procedure, along with applying the vibrating flat side of the MicroAire handle against the skin for several minutes to help expand the skin circulation and allow for more integration of the fat to the skin. Grafting was performed in all layers but not in the muscle, as is done in reconstruction cases. Special attention was given to the cleavage area, upper pole and lower pole, submammary fold, as well as subcutaneously, subglandularly, and around the gland. A drawing calculation sheath to register the grafted amount of fat is filled out by the assistant (Fig. 63.2, right).

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mL (each) were grafted during the second session. No alteration in weight during follow-up time. Upper row: preoperative. Lower row: 30 months postoperative. Considerable volume and symmetry improvement

63.3.6 Postoperative Care To prevent pressure on the medial side, patients were encouraged to wear a loose bra postoperatively. Patients were also strongly advised to keep their weight stable (i.e., do not gain or lose weight).

63.4 Results 63.4.1 Grafted Volume The average grafted fat in the first session was 216 mL (left) and 204 mL (right) in the machine group (1); 209 mL (left) and 235 mL (right) in the manual group (2); 279 mL (left) and 233 mL (right) in the decanting group (3); and 286 mL (left) and 277 mL (right) in the vibration technique group (4). The patient receiving pre- and

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950 Table 63.8  Grafted fat per side and session

Right 1st session Right 2nd session Left 1st session Left 2nd session

Average grafted fat per side (mL) by methodª 1 2 3 4 204 235 233 277 110 152 191 161 216 209 279 286 110 134 206 179

5 400 400 210 210

Total average 255 159 259 165

ªMethods: 1: machine; 2: manual; 3: decanting or gravity-separation; 4: decanting with vibration; 5: BRAVA Table 63.9  Average fat resorption per method after all sessions

Less than 30% 30–50% More than 50% Total number

Average resorption per methoda No. (%) ** 1 2 12 (44%) 24 (53.4%) 11 (41%) 11 (24.3%) 4 (15%) 10 (22.3%) 27 45

3 13 (65%) 6 (30%) 1 (5%) 20

4 80 (83%) 15 (16%) 1 (1%) 96

5 2 (100%)* 0 0 2

Total 131 43 16 190***

Only 1 patient No. (%): number of patients (percentage of all patients with this method) *** Included only the at-least 9-month follow-up ªMethods: 1: machine; 2: manual; 3: decanting or gravity separation; 4: decanting through vibration; 5: BRAVA *

**

postoperative BRAVA treatment was grafted with 400 mL per side. The average grafted fat in the second session was 110 mL (left) and 110 mL (right) in the machine group; 134 mL (left) and 152 mL (right) in the manual group; 206 mL (left) and 191 mL (right) in the decanting group; and 179 mL (left) and 161 mL (right) in the vibration technique group. The patient receiving BRAVA treatment was augmented with 210 mL on each side. Regarding the third session, the average grafted fat to the right breast was 188 mL and to the left breast was 191 mL (Table 63.8).

63.4.2 Resorption Rate and Residual Volume After the first session, 10 out of 24 patients in the machine group showed a ≤30% resorption rate. Another 10 patients showed a resorption rate of 30–50%, and only four patients had more than 50% of the transplanted fat resorbed. The manual group had ≤30% fat resorption in 43% of the patients, and 26% of patients lost half of their transplanted fat. In the third group—the decanting group—half of the patients were found to

have a residual volume of over 70%, and the other half lost 30–50% of the injected fat. In the fourth group—the vibration technique group— 74% of the patients had less than 30% fat resorption, 24% of patients lost 30–50%, and only one person lost more than half of the transplanted fat. In the second session, 50 out of 53 patients had more than 70% residual fat volume after the follow-up examination. Breast augmentation using BRAVA (n = 1) led to a residual fat volume of more than 70% after the first session as well as after the second session (for more details, see Tables 63.9–63.11). In one diabetes patient, the resorption was more than 80%.

63.4.3 Follow-Up Follow-up was done both clinically and by photographs (both preoperative and postoperative). The residual breast volume was evaluated after an average resorption time of 4 to 6 months. On examination, the volume should be stable without recent major postoperative breast changes (volume loss or ptosis). Despite an expected absorption rate of only 30% the surgeons were

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Table 63.10  Average fat resorption per method after the first session

30% 30–50% More than 50% Total number

Average resorption per methoda No. (%) ** 1 2 10 (42.1%) 15 (43%) 10 (41.6%) 11 (31%) 4 (16.6%) 9 (26%) 24 35

3 8 (50%) 8 (50%) 0 16

4 43 (74%) 14 (24%) 1 (2%) 58

5 1 (100%)* 0 0 1

Total** 77 43 14 134 ***

*Only 1 patient **No. (%): number of patients (percentage of all patients with this method) ***Included only the at-least 9-month follow-up ªMethods: 1: machine; 2: manual; 3: decanting or gravity separation; 4: decanting through vibration; 5: BRAVA Table 63.11  Average fat resorption per method after the second session*

30% 30–50% Over 50% Total

Average resorption per methoda No. (%)** 1 2 3 (100%) 8 (80%) 0 0 0 2 (20%) 3 10

3 3 (100%) 0 0 3

4 35 (97%) 1 (3%) 0 36

5 1 0 0 1

Total 50 1 2 53

*Included only the at-least 9-month follow-up **No. (%): number of patients (percentage of all patients with this method) ªMethods: 1: machine; 2: manual; 3: decanting or gravity separation; 4: decanting through vibration; 5: BRAVA

generous regarding a second session if there was enough fat to harvest. The patients and board-certified plastic surgeons involved in this study were asked to rate their satisfaction levels. The provided satisfaction questionnaire was completed based on a comparison between photographs taken preoperatively and 1 year postoperatively. The residual breast volume was evaluated after an average resorption time of 4 to 6 months; the desired outcome to look for during the evaluation was a stable volume, without major postoperative breast changes (e.g., volume loss or ptosis). The mean follow-up time in the machine group was 40 months (group 1; range: 27–68 months) compared to 22 months in the manual group (group 2; range: 12–30 months). The mean follow-up time in the decanting (group 3) and vibration technique (group 4) groups was shorter—with 17 and 12 months, respectively. The average follow-up time for all participants was 9.9 months. Eight patients did not show up for their follow-­up examination and one patient did not wish to undergo further treatment. Seven patients,

mainly from the manual and machine groups, received breast implants.

63.4.4 Complications The complication rate in our study was low (7%), and the actual complications were benign, easy to treat, or not requiring an intervention. The originally reported complications included oil cyst formation (ten patients reported), postoperative infection (only one patient), formation of seroma or hematoma (one patient developed a benign small lump), benign indurations, and fat necrosis (two patients reported; it was along the mastopexy scar line in one of the patients) (Table 63.12).

63.4.5 Patient Satisfaction Most patients were satisfied or very satisfied with their results. A fuller, natural feeling was obtained without taking on the risk of capsular formation and contractions. In addition to achieving a more

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Cyst 10

Infection 1

Small benign lump 1

Fat necrosis 2

Rate of complicationsa 7%

Complications of all 204 procedures b Some patients had more than one complication a

favorable breast volume and shape, a simultaneous reduction of unwanted body fat with body contour enhancement was achieved. However, not all patients were satisfied after the first intervention, and needed more than one procedure to obtain the desired volume. Most patients underwent one or two lipotransfers, and a few patients were treated three times. The decanting and vibration technique group had the best outcomes. Approximately 90% of patients in the previously mentioned groups were either “satisfied” or “very satisfied” with their results. Twelve percent of the decanting group and 4% of the vibration technique group were “somewhat satisfied,” and 0% and 2% of these respective groups were “dissatisfied.” The machine and manual groups had comparatively lower results, with half the machine group being “satisfied” or “very satisfied,” and the manual group having a 64% satisfaction rate.

63.5 Discussion Autologous fat grafting is commonly used in cosmetic and reconstructive surgery, and this modality addresses many limitations of techniques commonly used in breast surgery. However, the AFT result is strongly dependent on high-quality harvesting, processing, and injection techniques. Many different procedures have been described but none of them appears to be superior to another. As highlighted by many important publications throughout the years, there is no universal protocol regarding fat grafting and processing methods available—even though a substantial amount of research on fat grafting has been done in past decades [13–23]. Volume retention, which is dependent on the balance between regeneration and absorption of

adipose tissue, is still a challenge and is affected by many different factors. Graft size, procedure techniques, and graft microenvironment largely influence adipose tissue survival. Despite numerous studies, factors like centrifugation, local anesthetics, cannulas, per-operative expansion, and injected amount of fat still have an unclear effect on the result; that is why further research is necessary; multicenter studies and studies with longer follow-up times are needed to determine the optimal lipoaspirate processing technique. Although the request for more research is still urgent, after carefully weighing our results we have found that processing method 4 (decanting by vibration using MicroAire technology) leads to the best outcome and is therefore recommended. The favorable results of decanting and decanting by vibration might be related to a lesser gravitational force which results in an increased fat cell survival. The vibration method comes along with additional advantages for the surgeon. It is less time consuming, requires less physical effort, and leads to better results of the donor site. The distribution of suction power allows for an even extraction of fat and consequently to a better retraction of the skin above the treated areas. This method functions as a closed system which due to reduced air exposure may in its turn positively affect the viability and survival of the fat (Table 63.13). Compared to patients receiving breast reconstruction, it was quite difficult to convince patients to use BRAVA for aesthetic breast augmentation. However, our only patient who opted for this device showed excellent postoperative results, which align with the findings of Khouri and colleagues [12]. The indications for implementing fat grafting to the breast are expanding. Adherence to these instructions in order to enhance our techniques

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Table 63.13  Detailed characteristics description of processing methods, g-force, fat exposure, time, and evaluation of the results Machine group

G-forcea 1200

Fat exposure Open

Time consumed 72 mL in 3 min + preparation 240 mL in 3 min + preparation

Manual group

15

Totally closed system

Decanting or gravity separation

0

Totally closed system

10 min for unlimited amount

Decanting with vibrationb

0

Totally closed system + per-operative expansion

10 min for unlimited amount

Result evaluation Clinical follow-up + photo + patient satisfaction Clinical follow-up + photo + patient satisfaction + learning curve Clinical follow-up + photo + patient satisfaction + learning curve Clinical follow-up + photo + patient satisfaction + learning curve

Gravitational force equivalent with a g-force of 1 g equal to the conventional value of gravitational acceleration on Earth (about 9.8 m/s) b Using the PAL-650 Power-Assisted Liposuction from MicroAire a

for a maximum retention rate and more aesthetically appealing results is essential (Figs.  63.3– 63.12, 63.14, and 63.15; Video Clips 63.3 and 63.4).

63.5.1 Methods of Evaluation To evaluate the residual volume (rather than fat absorption), the surgeon needs to have the patient undergo preoperative and postoperative examinations and follow-up with imaging of the breast. Various methods of evaluation are in use, as the ideal method has not yet been found. We performed a postoperative clinical and photographic follow-up. It is important to keep in mind that an exclusive clinical follow-up is a subjective method that causes interpretational bias. To achieve a high follow-up rate, we offered a 1-year guarantee, including an additional fat graft free of charge to all our patients. This approach enabled us to attain reasonable numbers and results that are as reliable as possible. The satisfactory residual fat volume on MRI or more standardized photographic follow-up does not necessarily mean that patients are satisfied. It is not just about volume. We therefore need to evaluate the practicality of expensive radiological follow-ups. Many other variables— such as lifting effect, tightening of the skin around the areola, and cleavage marking cannot be shown with radiological imaging.

63.5.2 Oncological Safety For many years, AFT has been surrounded by much controversy regarding the carcinogenic potential of adipose-derived stem cells (ADSCs) and potential interference of AFT complications with breast cancer screening [24–31]. In 2002, Zuk and colleagues [24] published a paper describing the regenerative potential of ADSCs, mainly found in the stromal vascular fraction (SVF)—leading to a differentiation between standard AFT and stem cell-enhanced fat grafting. The resulting fear of possible oncological potential has been confirmed as ­ unreasonable in many clinical studies. In a single-center, case-control study of 137 patients in 2010, Rigotti and colleagues could not confirm a significant association between AFT and recurrence of breast cancer in postmastectomy patients [31]. In 2016, Kronowitz and colleagues [27] verified the safety of fat grafting in a singlecenter, matched case-control study of 1024 breasts. In 2020, Stumpf and colleagues [28] published a retrospective cohort study on the oncological safety of AFT and reported no significant difference in disease-free survival (DFS) rates between 320 patients undergoing breastconserving surgery with or without fat grafting. No major complications were reported in either of our study cohorts. These findings further support conclusions reported by the aforementioned authors.

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Modern radiological technology has shown the ability to discriminate between neoplastic and necrotic calcifications, which makes the concern of interference with breast cancer screening redundant. Ørholt and colleagues [32] report even lower numbers, with major and minor complication rates of 1.6% and 0.5%, respectively. A total of 16.4% of patients needed additional diagnostic imaging, and 3.2% of patients underwent a biopsy. It should be noted that only changes leading to further procedures should be considered complications; radiological changes were not automatically perceived as complications [32–34].

63.5.3 Strengths Our study cohort can be considered a representative sample of the Western population undergoing breast augmentation. It is rather difficult to have patients return to private clinic follow-ups, so they were offered a 1-year guarantee for free second and third grafts, in case of an unsatisfactory result. This approach ensured high follow-up rates and rendered our results as reliable as possible. Furthermore, all procedures were carried out in the same department, leading to uniform and comparable results. Every year, a steady number of patients are still returning for additional fat grafting to existing locations throughout the country.

63.5.4 Limitations The study recognizes a few limitations. Despite the high follow-up rate, differences in follow-up time among all groups might influence the evaluation of results and patient satisfaction rate. Follow-up and satisfaction rates, as evaluated by photographical, clinical, and patient assessments, have some limitations and are user dependent, which may be a source of errors in volume measurements. It is rather difficult to calculate gained rest volume using VECTRA® 3D volume imaging. MRI is considered to be the most precise measurement, but it is expensive, not easily accessible, and time consuming, and an objectively

measured volume does not necessarily guarantee a happy patient. In addition, measures like lifting effect, tightening of the skin around the areola, and cleavage marking cannot be shown by MRI or more standardized measurements. The patient treated with preoperative and postoperative BRAVA showed good and satisfactory results. However, in cases of a solely aesthetic augmentation, it was difficult to convince patients to apply it due to its bulkiness and therefore its lack of practicality in daily life. Finally, it must be remembered that the effect of factors such as local anesthesia, type of cannula, per-operative expansion, and amount of injected fat is still unclear.

63.5.5 Cost-Effectiveness An implant-based breast augmentation takes on average 45 minutes, compared to 120 minutes for fat augmentation (>165% increase). The costs vary from $3800 USD to $6000 USD (>57% increase), respectively. Even though AFT is more expensive and the actual intervention takes three times as long as a regular breast implant, AFT should be encouraged in a pricing policy to make it more accessible as a good alternative for patients who refuse implants, desire additional body contouring, or wish to have an increase in breast volume within reasonable limits.

63.6 Conclusion AFT is a patient- and physician-friendly option with high satisfaction rates and ever-increasing popularity. It has many beneficial characteristics, such as accessibility, simplicity to perform/being a minimally invasive approach, low cost, comparatively long-lasting and natural results (feeling and fullness), and a practically non-existing risk for immune reactions. Traditional indications include breast asymmetry, tuberous breasts and other deformities as well as breast reconstruction. New indications include implant conversion after complications and hybrid augmentation with a silicone implant to add volume and enhance contours. Eligibility criteria include excessive fat, a realistic

63  Aesthetic Breast Augmentation Using Autologous Fat Grafting: Indications, Patient Assessment…

expectation of volume increase, no history or family history of breast cancer, preoperative radiographic evaluation through ultrasound or MRI, and a desire for autologous material. Fat grafting does neither interfere with breast cancer screening, nor does it have significant oncological potential. Fat grafting is an extremely safe procedure with a low complication rate (4%). With its wide range of potential applications it has expanded beyond reconstructive indications. As a completely independent approach or by complementing traditional methods, fat grafting allows soft-tissue augmentation and volume replacement, contour enhancement, and deformity correction with the additional benefit of body contouring. The current findings indicate that processing by means of manual centrifugation and decantation using vibration (in our case MicroAire technology) leads to the most desirable results and is therefore recommended as the processing method of choice. However, broader multicenter studies to further validate our results seem to be required.

References 1. American Society of Plastic Surgeons. National Plastic Surgery Statistics. 2018. https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-­ surgery-­statistics-­full-­report-­2018.pdf. Accessed 3 Oct 2020. 2. Czerny V.  Plastischer Ersatz der Bustdruese durch ein Lipom. Verhandl Deutsch Gesellsch Chir. 1895;24:216–7. 3. Illouz YG.  L’avenir d la reutilization de la graisse apres liposuccion. Rev Chir Esthet Lang Franc. 1984;9:36. 4. Bircoll M.  Cosmetic breast augmentation utilizing autologous fat and liposuction techniques. Plast Reconstr Surg. 1987 Feb;79(2):267–71. https://doi. org/10.1097/00006534-­198702000-­00022. 5. Coleman SR, Saboeiro AP. Primary breast augmentation with fat grafting. Clin Plast Surg. 2015;42(3):301– 6. vii 6. Davis MJ, Perdanasari AT, Abu-Ghname A, Gonzalez SR, Chamata E, Rammos CK, Winocour SJ. Application of fat grafting in cosmetic breast surgery. Semin Plast Surg. 2020;34(1):24–9. 7. Delay E, Garson S, Tousson G, Sinna R.  Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J. 2009;29(5):360–76.

955

8. Ho Quoc C, Taupin T, Guérin N, Delay E. Volumetric evaluation of fat resorption after breast lipofilling. Ann Chir Plast Esthet. 2015;60(6):495–9. 9. Li F-C, Chen B, Cheng L. Breast augmentation with autologous fat injection: a report of 105 cases. Ann Plast Surg. 2014;73(Suppl 1):S37–42. 10. Munhoz AM, Marques Filho A, Ferrari O.  Single-­ stage augmentation mastopexy with composite reverse inferior muscle sling technique for autologous reinforcement of the inferior pole: technical refinements and outcomes. Aesthet Surg J. 2019;40(6):NP356–73. 11. Mizuno H, Hyakusoku H. Fat grafting to the breast and adipose-derived stem cells: recent scientific consensus and controversy. Aesthet Surg J. 2010;30(3):381–7. 12. Khouri RK, Rigotti G, Marchi A, Cardoso E, Rotemberg SC, Biggs TM. Aesthetic applications of Brava-assisted megavolume fat grafting to the breasts: a 9-year, 476-patient, multicenter experience. Plast Reconstr Surg. 2014;133(4):796–807. discussion: 808-9 13. Charles-de-Sá L, Gontijo de Amorim NF, Dantas D, Han JV, Amable P, Teixeira MVT, et  al. Influence of negative pressure on the viability of adipocytes and mesenchymal stem cell, considering the device method used to harvest fat tissue. Aesthet Surg J. 2015;35(3):334–44. 14. Kang D, Luan J.  Fat necrosis after autologous fat transfer (AFT) to breast: comparison of low-speed centrifugation with sedimentation. Aesthetic Plast Surg. 2018;42(6):1457–64. 15. Strong AL, Cederna PS, Rubin JP, Coleman SR, Levi B. The current state of fat grafting: a review of harvesting, processing, and injection techniques. Plast Reconstr Surg. 2015;136(4):897–912. 16. Wang C-L, Luan S-S, Panayi AC, Xin M-Q, Luan J. Methods used for evaluation of volume retention rate in autologous fat grafting for breast augmentation: a systematic review. Chin Med J. 2019;132(18):2223–8. 17. Xue EY, Narvaez L, Chu CK, Hanson SE. Fat processing techniques. Semin Plast Surg. 2020;34(1):11–6. 18. Salinas HM, Broelsch GF, Fernandes JR, McCormack MC, Meppelink AM, Randolph MA, et  al. Comparative analysis of processing methods in fat grafting. Plast Reconstr Surg. 2014;134(4):675–83. 19. Condé-Green A, Wu I, Graham I, Chae JJ, Drachenberg CB, Singh DP, et  al. Comparison of 3 techniques of fat grafting and cell-supplemented lipotransfer in athymic rats: a pilot study. Aesthet Surg J. 2013;33(5):713–21. 20. Ramon Y, Shoshani O, Peled IJ, Gilhar A, Carmi N, Fodor L, Risin Y, Ullmann Y.  Enhancing the take of injected adipose tissue by a simple method for concentrating fat cells. Plast Reconstr Surg. 2005;115(1):197–201. discussion 202-3 21. Smith P, Adams WP Jr, Lipschitz AH, Chau B, Sorokin E, Rohrich RJ, et al. Autologous human fat grafting: effect of harvesting and preparation techniques on adipocyte graft survival. Plast Reconstr Surg. 2006;117(6):1836–44.

956 22. Pu LL. Towards more rationalized approach to autologous fat grafting. J Plast Reconstr Aesthet Surg. 2012;65(4):413–9. 23. Herold C, Pflaum M, Utz P, Wilhelmi M, Rennekampff HO, Vogt PM. Viability of autologous fat grafts harvested with the Coleman technique and the tissue trans system (Shippert method): a comparative study. Handchir Mikrochir Plast Chir. 2011;43(6):361–7. 24. Zuk P, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–95. https://doi.org/10.1091/mbc. E02-­02-­0105. 25. Groen J-W, Negenborn VL, Twisk JWR, Ket JCF, Mullender MG, Smit JM. Autologous fat grafting in cosmetic breast augmentation: a systematic review on radiological safety, complications, volume retention, and patient/surgeon satisfaction. Aesthet Surg J. 2016;36(9):993–1007. 26. Krastev TK, Schop SJ, Hommes J, Piatkowski AA, Heuts EM, van der Hulst RRWJ.  Meta-analysis of the oncological safety of autologous fat transfer after breast cancer. Br J Surg. 2018;105(9):1082–97. 27. Kronowitz SJ, Mandujano CC, Liu J, Kuerer HM, Smith B, Garvey P, et  al. Lipofilling of the breast does not increase the risk of recurrence of breast cancer: a matched controlled study. Plast Reconstr Surg. 2016;137(2):385–93. 28. Stumpf CC, Zucatto ÂE, Cavalheiro JAC, de Melo MP, Cericato R, Damin APS, Biazús JV.  Oncologic

A. Kalaaji et al. safety of immediate autologous fat grafting for reconstruction in breast-conserving surgery. Breast ­ Cancer Res Treat. 2020; 29. Veber M, Tourasse C, Toussoun G, Moutran M, Mojallal A, Delay E.  Radiographic findings after breast augmentation by autologous fat transfer. Plast Reconstr Surg. 2011;127(3):1289–99. 30. Vyas KS, DeCoster RC, Burns JC, Rodgers LT, Shrout MA, Mercer JP, et  al. Autologous fat grafting does not increase risk of oncologic recurrence in the reconstructed breast. Ann Plast Surg. 2020;84(6S Suppl. 5):S405–10. 31. Rigotti G, Marchi A, Stringhini P, Baroni G, Galiè M, Molino AM, et  al. Determining the oncological risk of autologous lipoaspirate grafting for post-­ mastectomy breast reconstruction. Aesthetic Plast Surg. 2010;34(4):475–80. 32. Ørholt M, Larsen A, Hemmingsen MN, Mirian C, Zocchi ML, Vester-Glowinski PV, Herly M. Complications after breast augmentation with fat grafting: a systematic review. Plast Reconstr Surg. 2020;145(3):530e–7e. 33. Lin J-Y, Song P, Pu LLQ. Management of fat necrosis after autologous fat transplantation for breast augmentation. Plast Reconstr Surg. 2018;142(5):665e–73e. 34. Tan L-C, Li X-Y, Lu Y-G.  Nontuberculous mycobacteria infection after autologous fat grafting for cosmetic breast augmentation. Ann Plast Surg. 2020;85(4):358–62.

New Trends in Breast Augmentation with Fat Grafting: Implant Conversion with Fat and Hybrid Implant-Fat Breast Augmentation/Revision

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Amin Kalaaji and Vanja Jönsson

Abbreviations AFG Autologous fat grafting BIA-ALCL Breast implant-associated anaplastic large-cell lymphoma BII Breast implant illness TIVA Total intravenous anesthesia

•

Key Messages • The main advantage of adding fat to a breast implant in a hybrid approach breast augmentation procedure is that the fat can be placed in selective areas, including the cleavage and around the implant to “soften the edges,” enhancing contour to a silicone implant and creating a much more natural look. • Implant conversion with fat involves removing a previously placed breast implant for reasons such as breast implant-associated anaplastic large-cell lymphoma (ALCL), breast implant illness (BII), and capsular con-

•

•

• •

•

• Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_64) contains supplementary material, which is available to authorized users. A. Kalaaji (*) · V. Jönsson Oslo Plastikkirurgi Clinic, Oslo, Norway e-mail: [email protected]

tracture, and substituting in its place the patient’s own fat tissue. It is preferable to perform implant conversion simultaneously with removing the implant, because the skin has already expanded. Fat is grafted in two phases in the simultaneous conversion indication: one before removing the implant, and the other after removing the implant in the same session through separate incisions. The method includes decanting for 10 min in a canister after harvesting the fat with a vibration device, specifically the PAL-650 Power-­ Assisted Liposuction from MicroAire®. Because these indications are on the rise, our techniques should be ameliorated. Fat grafting is used more and more in post-­ implant revision cases compared to what was previously done (i.e., only changing the implants). The simultaneous hybrid approach is on the rise because the trend toward more natural results and more volume is increasing. The eligibility criteria for implant conversion with fat and hybrid implant-fat breast augmentation/revision include excessive fat, a realistic expectation of volume increase, no history or family history of breast cancer, preoperative radiographic evaluation through ultrasound or MRI, and wish for autologous material.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_64

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64.1 Introduction

64.2 Definitions

Autologous fat grafting (AFG) has become a cen- Implant conversion with fat grafting is the tral element in plastic surgery and has expanded removal of a previously placed breast implant well beyond its roots in reconstructive indica- and substituting in its place the patient’s own fat tions. Initially, AFG (also called autologous fat tissue. This can be performed as a simultaneous transfer, or AFT) was mainly used complemen- or delayed procedure. tary to mastopexy procedures and breast conA hybrid breast augmentation refers to a struction post-cancer, or after mastectomy or breast enlargement procedure using both implants breast-conserving surgery [1]. and your own fat. This can also be performed as However, over time, AFG has also evolved a simultaneous or delayed procedure. “Hybrid” into a procedure with aesthetic indications for procedures are also often referred to as “composconditions such as hypoplasia mamma, asymme- ite” or “combined”; hybrid refers to the dual-­ try, slight ptosis, and deformities such as tuber- technique approach of fat with implant and does ous breast. Fat grafting is often performed not refer to any specific implant type. simultaneously with other procedures, such as abdominoplasty and gluteal augmentation. Fat grafting now has the reputation of being a surgi- 64.3 Indications cal option with many beneficial characteristics: it is simple to perform and minimally invasive; it is 64.3.1 Implant Conversion with Fat Grafting (Table 64.1) an accessible, low-cost option for patients; and there is no risk of having immune reactions. In the world of modern plastic surgery, fat grafting As previously mentioned, conditions such as is a widely accepted, valuable method with a ALCL, BII, severe capsular contracture, as well wide range of potential applications, a favorable as just the changing attitudes about implants (“I long-term safety profile, and high patient and am done with them”; “They have done their job”) physician satisfaction rates [2–9]. and changing fashion have created a special need Now, largely due in part to emerging potential for some patients to move toward smaller and long-term implications of breast implants and more natural combined augmentation, if not changing tastes, AFG has made another jump in whole-cloth removal. its evolution. Specifically, breast implant-­ The main advantage of adding fat to a breast associated anaplastic large-cell lymphoma implant in a breast augmentation procedure is (ALCL), breast implant illness (BII), capsular that the fat can be placed in selected areas in the contracture, and modern demands for more natu- cleavage and around the implant to “soften the ral results are expanding the indication spectrum edges” and give a much more natural look. to include conversions (i.e., alloplastic breast Another advantage is that a smaller implant can implant replacement with fat) and hybrid (also be used when fat is being added. referred to as composite or combined) augmentation (i.e., implant enhancement to modify volume Table 64.1  Indications for implant conversion with fat and/or shape) [2, 9–19]. This demand to remove grafting existing implants and/or adding fat to the existing BIA-ALCL: Breast implant-associated anaplastic large-cell lymphoma implant will surely be intensifying in the coming BII: Breast implant illness years. Severe capsular contracture The related techniques described here are rela- Trends have changed toward smaller and more natural tively new, and we will describe the indications, implants types, and timing of augmentation together with Implants have “done their job” the recommended fat processing technique in Need to do lipomodeling to other parts of the body simultaneously these different indications.

64  New Trends in Breast Augmentation with Fat Grafting: Implant Conversion with Fat and Hybrid…

The conversion could be simultaneous or delayed. The surgeon must do lipomodeling to other parts of the body as well, either simultaneously or delayed.

64.3.2 Hybrid Breast Augmentation (Table 64.2) Hybrid breast augmentation is now considered a good alternative for women who want a substantial increase in breast volume but who do not have sufficient fat to achieve this result by fat transfer alone. Hybrid breast augmentation is especially suitable for women who have asymmetry, are thin, have a bony chest, and have a chest wall deformity such as an indented or prominent sternum, as well as for women who want the more natural look that fat transfer provides but desire more volume than can be achieved by fat alone. In addition, this procedure is indicated for the following cases: • There is an insufficient amount of fat to do breast augmentation only with fat grafting. • The patient desires to have more than just the “artificial form” of breast augmentation/foreign bodies as implants. Table 64.2  Indications for hybrid (combined or composite) breast/fat breast augmentation and revision Insufficient amount of fat to do only breast augmentation Patient’s desire to not have only the “artificial form” of breast augmentation/foreign bodies as implants Patient’s wish for more volume,; specifically, to increase the cleavage and upper pole areas, which are specific areas in which fat grafting achieves excellent results Patient’s wish to avoid the unnatural form of a breast implant Need to revise special areas, such as a revision after previous implant insertion (e.g., increasing the lower pole or the cleavage) Mild cases of capsular contractures that do not necessitate implant removal Rippling in thin patients or in too large implants Need to do lipomodeling to other parts of the body simultaneously Mastopexy augmentation with a posterior flap as auto-prosthesis and fat grafting

959

• The patient wishes to have more volume, specifically to increase the cleavage and upper pole areas, which are specific areas in which fat grafting achieves excellent results. • The patient wants to avoid the unnatural form of a breast implant. • There is a need to revise special areas, such as a revision after previous implant insertion (e.g., increasing the lower pole or the cleavage). • For mild cases of capsular contractures that do not necessitate implant removal, this procedure is appropriate. • For rippling in thin patients or for implants that are too large, this procedure is appropriate. • There is a need to do lipomodeling to other parts of the body, either simultaneously or delayed. The simultaneous hybrid approach is most often indicated as an augmentation procedure, whereas the delayed approach is primarily indicated in cases of correction/revision.

64.4 T  he Oslo Plastikkirurgi Clinic Study We retrospectively evaluated the indications and compared different fat processing methods for aesthetic breast augmentation. The Oslo Plastikkirurgi Clinic has performed 204 breast augmentations using autologous fat grafting to treat hypoplasia mammae, breast asymmetry, implant conversion with fat, h­ ybrid/ combined augmentation, or deformities such as tuberous breast [9]. Five eligibility criteria must be met by patients to become a candidate for surgery: (1) excessive fat to be removed or corrected; (2) a realistic expectation of volume increase; (3) no history or family history of breast cancer; (4) radiographic evaluation through ultrasound or MRI; and (5) desire for an alternative to implants to avoid the use of foreign objects in the implant conversion indication. The following guidelines and recommendations follow the process and procedures of the Oslo Plastikkirurgi Clinic. For a more detailed

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discussion, please see Part VIII in this book: Chap. 63 Aesthetic Breast Augmentation Using Autologous Fat Grafting: Indications, Patient Assessment, and Comparison Between Different Processing Methods in 204 Cases [9].

64.4.1 Patient Assessment The assessments include medical history, BMI, ultrasound or MRI, and clinical examination of the fat deposits of the body. Patient expectations are important to manage with any procedure involving fat grafting. We can achieve 1–2 cup sizes, or about 200–250 mL of fat per size for the bigger conversion cases. Of course, we can do more sessions to augment the results, provided that there is existing fat to harvest. For the hybrid approach, it is often satisfactory because the need for fat is not as huge as in conversion and it is limited to certain areas, as in rippling or augmentation of specific areas such as cleavage. Good information is required about the procedure because this is a process that takes at least 1 year. The BMI should preferably be under 30 to achieve figure-­forming results.

64.5 P  rocedure Options and Their Methods and Techniques (Figs. 64.1 and 64.2) 64.5.1 Implant Conversion with Fat Grafting As previously noted, conversions may be simultaneous or delayed depending on the individual case and assessments made therein. The methods and techniques of each are as follows.

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64.5.2 Simultaneous Implant Conversion with Fat Grafting (Videos 64.1 and 64.2) (Figs. 64.3 and 64.4) Liposuction is performed to harvest the fat cells from the patient’s donor areas. After tumescent liposuction to the breast and donor site as well as local anesthesia to the incision sites, a 3 mm multi-hole cannula is inserted with MicroAire PAL vibration to dissect the space between the skin and the capsule without any suction; this is done for approximately 5 min per site. This allows per-operative expansion to the recipient site and good hemostasis. Then, the fat is harvested with a 4  mm Mercedes-type 3-hole cannula with the MicroAire PAL machine and collected to a 500  mL or 1000 mL canister. This will be set to decant for at least 10  min, during which time the recipient incision sites are sutured. Once completed, the liquid is emptied, and the rest of the fat is collected with a 10 or 60 mL syringe connected to a 3  mm cannula and grafted into the previously expanded area. Saturation of the fat is reached when the fat is squirting from the site, there is blanching, or there is hardness of the skin when the grafting is stopped. Then, the submammary incision (or the previous implant incision) is reopened to remove the implant. If the capsule is thick and calcified, it should be removed in its entirety. The pocket is then irrigated with saline and hydrogen peroxide, and a circular incision from inside the pocket is made to facilitate healing and to prevent a sizable dead space. A drain is evaluated and inserted in case there is oozing, especially when removing a thick and calcified capsule. After removing the implant, eliminating the “pocket” it had formerly occupied, a new second

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Fig. 64.1  Technical operation aspects for conversion. Upper left: Pre-op planning. Upper middle and upper right: Closed system; MicroAire and canister preparation. Middle left: Per-operative expansion. Middle second left: Filling the 60, 20, or 10  cc syringe from the canister. Middle right: First phase of grafting before removing the

implant. Lower left: Implant and calcified capsule are removed. Lower middle: The plan of grafting (not deeper and not superficial). Lower right: A drawing calculation sheath to register the grafted amount of fat in the 4 quadrants of the breast and side per-operatively conducted by the anesthetist assistant, x is entry site

phase of grafting begins because more laxity of the skin and subcutaneous tissue emerges. The grafting is performed to correct the shape and augment the volume until blanching or squirting of the fat occurs. This reduces pressure within the breasts, thus allowing for the injection of additional fat. This fat is directed into the subcutaneous space. It is possible to add fat to the lower pole from the submammary incision, but it is advisable to do it from new, separate incisions medially and laterally. The submammary incision is closed at the end (Table 64.3). The key to a successful simultaneous implant conversion with fat process is to embrace and peroperatively expand the subcutaneous space above the capsule and to augment the space with fat before carefully detaching the implant capsules and

removing the breast implants. Furthermore, careful adding of fat after removing the implant can be performed because more space is available.

64.5.3 Delayed Implant Conversion with Fat Grafting (Figs. 64.5 and 64.6) For various reasons, patients may come back for fat grafting after they have removed the implants. Potential reasons why patients return for fat grafting are because they thought they will not need additional volume, or because they thought they wanted or could live with the smaller breast without implants. Also, some patients may simply not know about this solution until after implant

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Fig. 64.2  Technical operation’s aspects for simultaneous and delayed hybrid implant fat augmentation; post-­ implant enhancement, auto-prosthesis with fat, rippling, postmastectomy implant fat enhancement. Upper left: Pre-op planning. Upper second left: Closed system; MicroAire and canister preparation. Upper third left: Subfascial dissection for implant. Upper right: Per-­ operative packing av. subfascial pocket with gaze for hemostasis and expansion for 15 min. Middle left: Filling

the 60 cc, 20 cc, or 10 cc syringe from canister. Middle second left: Grafting after inserting the implant. Middle third left: After suturing. Middle right: The plan for delayed hybrid grafting. Lower left and second left: Mastopexy augmentation with auto-prosthesis and fat showing the posterior flap. Lower third left: Planning rippling and smoothing the implant edges with fat. Lower right: Rigottomy before grafting in post-mastectomy case

Fig. 64.3  Simultaneous implant conversion with fat; removal of 200 mL inserted implant 26 years earlier. The capsule was calcified and removed in total. Simultaneous

fat grafting of 250 mL fat per breast. Upper row: before surgery. Lower row: 10 months postoperatively

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Fig. 64.4  Simultaneous conversion of breast implant: 35-year-old woman with simultaneous conversion of breast implant of 220  mL after 12  years; insertion with thin capsule. Augmentation was performed as delayed conversion in two sessions with MicroAire and decanting

with 310/164 mL fat on the right side and 310/164 mL on the left side. Upper row: Preoperative. Lower row: 60 months post-op. Note the normal ptosis that the patient was seeking instead of capsular contracture

Table 64.3  Main steps, tips, and pitfalls for the simultaneous conversion technique.

implant—leaving an unpleasant form. In cases like these, the motto is “the sooner, the better.” The more time that has elapsed after the removal, the less favorable the conversion results will be, because the skin is shrinking and the whole subcutaneous and glandular space has reduced, which lessens the amount of fat possible to graft and makes blood circulation less favorable for subsequent surgery.

  1. Per-operative expansion   2. Grafting before removing the implant   3. Grafting after removing the implant   4. Use separate entry sites for fat grafting. Not through submammary incision   5. Do not overfill   6. Per-operative massage to the grafted skin at the end of the procedure   7. Close the submammary incision at the end after grafting to make sure that no fat is coming out this way   8. No-pressure bra   9. Keep the capsule if it is thin and remove it if it is calcified 10. Incise the capsule from inside to create healing areas to prevent dead spaces

removal with another surgeon, so they seek a consult (second opinion) after learning about it. In the cases of delayed conversions, some uneven skin retraction can occur, especially if there is a mild degree of ptosis after removing the

64.5.4 Hybrid Augmentation/ Revision with Fat Grafting (Figs. 64.2, 64.7, 64.8, 64.9, and 64.10) For revisions, the expectation is to have a smoother, less traumatic procedure than there was previously—when a revision of an implant almost always constitutes implant exchange and/or soft-tissue revision. Using fat is less traumatic, because we can isolate the areas where we can increase the volume with fat.

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Fig. 64.5 Delayed conversion of implant with fat; 33-year-old woman with breast implant illness (BII), implant was removed 2 months earlier. Augmentation was performed as delayed conversion in two sessions with

MicroAire and decanting with 300/270 mL of fat on the right side and 300/270  mL on the left side. Upper row: Preoperative with drawing; upper left showing the estimated grafted amount. Lower row: 7 months post-op

Fig. 64.6  Delayed implant conversion with fat; 32-year-­ old woman. Indication: Conversion delayed, with fat grafting in two sessions after decanting and MicroAire, right: 220/215  mL and left: 215/195  mL.  Middle row: 4  months after removal of the 200  mL implant, after 12  years with grade 3 capsular contracture. Note the

severe retraction of the skin. Lower row: 18 months postop. Although the result is not as optimal as it could be if the patient came for simultaneous conversion, the results yielded patient’s satisfaction. Note the bigger difference between the upper row with implants and the lower row after two sessions

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There is also the reality of conditions such as ALCL, BII, and severe capsular contracture, where the need for this option is a matter of the patient’s health. By choosing hybrid breast augmentation, the implant can easily be placed subfascially because we can support the cleavage and upper pole with fat. As a result, submuscular insertion will not be as necessary for patients who do not desire to undergo this approach; for example, with big implant volume and very thin patients, it is a limitation. As with conversions, hybrid procedures may be simultaneous or delayed depending on the individual case and assessments made therein. The methods and techniques of each procedure are as follows.

64.5.6 Delayed Hybrid Revision with Fat Grafting (Video 64.4) (Figs. 64.8 and 64.9)

64.5.5 Simultaneous Hybrid Augmentation with Fat Grafting (Video 64.3) (Figs. 64.7 and 64.10)

64.5.7 Timing: Why Should We Do it at the Same Time and Not Delay?

When a simultaneous hybrid treatment is performed, an implant is placed in the breast and AFG is performed and injected together with the implant. This requires a longer operation time but can give good results for women wanting more drastic results than what is achievable with fat grafting alone and helps soften the edges of the implant. The AFG volume in hybrid procedures can be estimated utilizing measurements based on implant volume/projection. This lowcost method can be applied to guide surgical decision-­making in patients who are candidates for hybrid procedures. The advantage with this method is the ability to revise or augment specific areas, such as the cleavage or the upper or lower poles.

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In delayed hybrid procedures, the fat is injected at a later session after the implant is already in place. One special challenge in the delayed option pertains to the appearance of rippling. Hybrid grafting is an especially good choice in cases where better results can be achieved with previous implants, sparing the need for a removal, exchange, or submuscular insertion. Another indication for a delayed hybrid procedure is to augment a certain area of the breast or to correct asymmetry. Mastopexy augmentation with a posterior flap as auto-prosthesis and fat grafting can also be performed as another indication (Video 64.5).

Timing is a critical factor in breast augmentation conversions. This is because we already have an expanded skin and subcutaneous tissues that are often well vascularized (Fig. 64.6). Once the implants are removed, the skin will go through a retraction process that can give unevenness and asymmetry between the sides. If we modulated the breast directly, the skin would depose gently above the augmented parts and will have a better chance to be filled and symmetrical. We have seen the limitation of the amount of tissue reduced and fat grafted with more resorption when the patient came after removing the implant. For the hybrid, it is preferable to do it simultaneously as well as because it goes into the planning about how much and where the fat and implant will build.

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Fig. 64.7 Simultaneous hybrid augmentation with implant of fat in a 36-year-old. Fat harvested with MicroAire and grafted in two sessions: right, 140/65 mL;

left, 140/65 mL. Upper row: pre-op with 210 mL implant; lower row: 9  months post-op with 275  mL implant exchange in addition to fat

Fig. 64.8  Delayed hybrid revision implant with fat in a 32-year-old. Treated for enhancing the lower pole and cleavage area and to soften the consistency of seconddegree capsular contracture in two sessions: 325/110 mL on the right and 325/110 mL on the left. Upper row:

Before operation. Upper left: Drawing before operation; note more volume in the planes to the lower pole. Upper 3 rights: pre-operative profiles. Lower row: lower left: 1-day post-op. Lower 3 rights: post-operative profiles: 36 months post-op

64.5.8 The Three Stages of Fat Grafting

monly performed in three stages: (1) harvesting of the adipose tissue from a suitable donor site; (2) processing of the lipoaspirate to eliminate cellular debris, acellular oil, and excess infiltrated solution; and (3) grafting of the purified adipose tissue.

Whether dealing with a conversion or hybrid augmentation/revision, standard fat grafting is com-

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Fig. 64.9  Delayed hybrid revision. Rippling with 350 ml submuscular implant; 1 year before complained about moderate rippling; request to soften the edges as the implant was too big. Two sessions with decanted fat were performed. Right: 150/175 mL and left: 150/175 mL. At

a

b

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the same time, an augmentation of the gluteal area with fat was performed. Upper row: Pre-op. Lower row, lower left: Per-op drawing. Lower three right: 8 months post-op. Note the enhancement of the cleavage area and the general effect on the whole breast

m.Pectorals Fat

Fascia

Fascia

m.Pectorals

Implant

Fig. 64.10  Drawings showing the placement of implant and fat in simultaneous hybrid breast implant fat augmentation. Note that the fat is grafted between fascia and skin

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64.5.9 The Technique of Harvesting and Processing and Grafting of Fat Both conversion and hybrid cases use decanting or gravity separation as methods of processing (vibration technique using MicroAire technology). This power-assisted technique leads to a time-dependent fractionation of the lipoaspirate in a completely closed system. After discarding the top and bottom layers, the fat can be transferred.

64.5.10 Harvesting and Anesthesia Fat is most commonly harvested from the abdomen, thigh, buttocks, and inner knee region with a 4  mm multiperforated cannula, leading to a more aesthetic result and additional body sculpting. No significant differences regarding cell viability and volume retention of the previously mentioned donor sites are described in the literature. For the fat transfer, a blunt 3 mm cannula is used, resulting in a reduced risk of intravascular injection, as well as maximized fatty tissue survival by injecting fat in small aliquots. All procedures at the clinic were performed under total intravenous anesthesia (TIVA) plus tumescent anesthesia, which has been described to improve cell viability, reduce blood loss and pain, and ease the process of fat removal. For a more detailed discussion, please refer to Part VIII in this book: Chap. 63 [9].

64.5.11 Postoperative Care To prevent pressure on the fat and breast, patients were encouraged to wear a loose bra postoperatively. Patients were also strongly advised to keep their weight stable (i.e., do not gain or lose a considerable amount of weight) to achieve the optimal results.

64.5.12 Follow-Up Clinical follow-up is needed and must include photographs both pre- and postoperatively. Surgeons should be generous with the second session, if there is enough fat to take (30% fat resorption is expected). We are under the impression that volume retention is superior in these indications compared with primary breast augmentation, because fat at the recipient site is well vascularized and there is often an expansion in the recipient site.

64.5.13 Resorption Rate and Residual Volume The residual breast volume is evaluated after an average resorption time of 4 to 6  months. On examination, the volume should be stable without recent major postoperative breast changes (e.g., volume loss or ptosis).

64.5.14 Complications Only minor complications (oil cysts and small fat necrosis) were reported in these patients. In a study reported from the Oslo Plastikkirurgi Clinic study on 204 patients [9] with different indications who received fat grafting to the breast, 10 patients developed minor complications that were of no further concern and treated easily. One patient developed a benign small lump, a complication well known for its frequent occurrence after AFG. Two patients developed a small fat necrosis, one of which occurred along the patient’s mastopexy scar line. Only one patient showed signs of infection after the fat transfer, leading to an extremely low complication rate of 4% [2, 20]. However, as we know, the effects of factors such as local anesthesia, type of cannula, perioperative expansion, and amount of injected fat are still unclear. Further study is needed to determine

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whether these complications occur and, if so, to what extent.

64.5.15 Patient Satisfaction Most patients were satisfied or very satisfied with their results. The positive reaction to the procedure can be explained by the natural feeling achieved and the improved fullness in the desired areas (e.g., upper pole, medially, asymmetric areas). These results were obtained without taking the risk of capsular formation and contractions. In addition to a more favorable breast volume and shape, a simultaneous reduction of unwanted body fat with body contour enhancement was achieved. For the hybrid revision patients, we were able to avoid implant removal while adjusting the form and volume by fat grafting. Patients who desired removal achieved their desired feeling of freedom while still retaining the desired and satisfactory volume. Follow-up and satisfaction rates, which were evaluated by photographical, clinical, and patient assessment, have some limitations. The effects of factors such as local anesthesia, type of cannula, perioperative expansion, and amount of injected fat are still unclear.

64.5.16 Is it Cost Effective? There is no other alternative for conversion for those who want to remove their implant and substitute it with fat. However, for hybrid implant fat augmentation, the cost is an issue for some patients. We should be aware to make sure that surgeons avoid pricing this procedure so high that patients will simply choose bigger implants. Price policy is an important factor in attracting patients and promoting new, useful, and desirable techniques such as fat grafting. Even though AFG is more expensive and the actual intervention takes more time than a regular breast implant procedure, AFG is a good alternative for patients who want their implants removed, desire additional body contouring, or wish for a reasonable increase in breast volume.

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64.5.17 Oncological Safety In a single-center, case-control study of 137 patients, Rigotti and colleagues [21] could not confirm a significant effect of AFG on the recurrence of breast cancer in postmastectomy patients. Kronowitz and colleagues [22] verified the safety of fat grafting in a single-center, matched-controlled study of 1024 breasts. In 2019, Stumpf and colleagues [23] published a retrospective cohort study on oncologic safety and AFG, and reported no significant difference in disease-free survival rates between 320 patients undergoing breast-conserving surgery with or without AFG. No major complications were reported in either of the Oslo clinic cohorts [9]. These findings further support the conclusions reported by the previously mentioned authors. Modern radiological technology has shown the ability to discriminate between neoplastic and necrotic calcifications, which makes the concern of interference with breast cancer screening redundant. Ørholt and colleagues [20] reported even lower numbers, with a major and minor complication rate of 1.6% and 0.5%, respectively. A total of 16.4% of the patients needed additional diagnostic imaging, and a biopsy was performed on 3.2% of them. Only the changes leading to further procedures should be considered as complications, rather than automatically considering all radiological changes as complications.

64.6 Conclusions We should expect a considerable rise in demand for these implant conversion and hybrid procedures. Although the “traditional” implant era will not disappear soon, because as many as 35 ­million women have had breast implant surgery (70 million implants), we should be aware about these new indications and developments and make our techniques more efficient. Fat grafting as a completely independent approach, or by complementing traditional methods, allows soft-­ tissue augmentation and volume replacement, contour enhancement, and deformity correction

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with an additional side benefit of body contouring. It is a safe option that enjoys high satisfaction rates from surgeons and patients. Patients in both groups obtained a natural feeling and better fullness. Because of ALCL, BII, capsular contracture, and general trends of our time to get lower and more natural feeling breasts, it looks like these indications will be increasing in the coming years as a reason to remove the implants. Our techniques should therefore be ameliorated. We must continue to pursue more evidence-based studies. More studies and longer follow-up studies are required. It is preferable to perform implant conversion simultaneously because the skin is already expanded. Decanting for 10 min in a canister is performed after harvesting the fat with a vibration device using the PAL-650 Power-Assisted Liposuction from MicroAire®. The harvesting cannula was 4 mm, and the grafting cannula was 3 mm. Acknowledgement The authors wish to thank Melanie Baumgartner, MD, for her contribution to this chapter in the beginning of the work. Authors have no disclosures.

References 1. American Society of Plastic Surgeons. National plastic surgery statistics. 2018. https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-­ surgery-­statistics-­full-­report-­2018.pdf. Accessed March 2020. 2. Sampaio Goes JC, Munhoz AM, Gemperli R.  The subfascial approach to primary and secondary breast augmentation with autologous fat grafting and form-­ stable implants. Clin Plast Surg. 2015;42(4):551–64. https://doi.org/10.1016/j.cps.2015.06.017. Epub 2015 Aug 11. PMID: 26408443 Review 3. Nava MB, Blondeel P, Botti G, Casabona F, Catanuto G, Clemens MW, De Fazio D, De Vita R, Grotting J, Hammond DC, Harris P, Montemurro P, Mendonça Munhoz A, Nahabedian M, Pompei S, Rancati A, Rigotti G, Salgarello M, Scaperrotta G, Spano A, Stan C, Rocco N. International expert panel consensus on fat grafting of the breast. Plast Reconstr Surg Glob Open. 2019;7(10):e2426. https://doi.org/10.1097/ GOX.0000000000002426. eCollection 2019 Oct. PMID: 31772879 Free PMC article 4. Coleman SR, Saboeiro AP. Primary breast augmentation with fat grafting. Clin Plast Surg. 2015;42(3):301–6. vii

A. Kalaaji and V. Jönsson 5. Delay E, Garson S, Tousson G, Sinna R.  Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J. 2009;29(5):360–76. 6. Ho Quoc C, Taupin T, Guérin N, Delay E. Volumetric evaluation of fat resorption after breast lipofilling. Ann Chir Plast Esthet. 2015;60(6):495–9. 7. Khouri RK, Rigotti G, Cardoso E, Khouri RK, Biggs TM.  Megavolume autologous fat transfer: part I.  Theory Principles Plast Reconstr Surg. 2014;133(3):550–7. 8. Davis MJ, Perdanasari AT, Abu-Ghname A, Gonzalez SR, Chamata E, Rammos CK, Winocour SJ.  Application of fat grafting in cosmetic breast surgery. Semin Plast Surg. 2020;34(1):24–9. https:// doi.org/10.1055/s-­0039-­1700958. Epub 2020 Feb 15.PMID: 32071576 Review 9. Kalaaji A, Jönsson V, Baum M. Aesthetic breast augmentation using autologous fat grafting: indications, patient assessment, and comparison between different processing methods in 204 cases. Plastic and aesthetic regenerative surgery and fat grafting: clinical application and operative techniques. Springer Nature; 2021. Section XIII. Chapter XX 10. Auclair E, Blondeel P, Del Vecchio DA.  Composite breast augmentation: soft tissue planning using implants and fat. Plast Reconstr Surg. 2013;132(3):558–68. https://doi.org/10.1097/ PRS.0b013e31829ad2fa. PMID: 23985632 11. Auclair E, Anavekar N. Combined use of implant and fat grafting for breast augmentation. Clin Plast Surg. 2015;42(3):307–314, vii. https://doi.org/10.1016/j. cps.2015.03.005. Epub 2015 Jun 5. PMID: 26116936 Review 12. Auclair E, Marchac A, Kerfant N.  Secondary composite breast augmentation: concept and outcomes, introduction to a layered approach. Aesthet Surg J. 2020;40(9):981–6. 13. Özalp B, Aydinol M. Breast augmentation combining fat injection and breast implants in patients with atrophied breasts. Ann Plat Surg. 2017;78(6):623–8. 14. Graf RM, Closs Ono MC, Pace D, Balbinot P, Pazio ALB, De Paula DR. Breast auto-augmentation (mastopexy and lipofilling): an option for quitting breast implants. Aesthet Plast Surg. 2019;43(5):1133–41. https://doi.org/10.1007/s00266-­019-­01387-­5. Epub 2019 May 7 15. Del Vecchio D.  SIEF—simultaneous implant exchange with fat: a new option in revision breast implant surgery. Plast Reconstr Surg. 2012;130(6):1187–96. https://doi.org/10.1097/ PRS.0b013e31826d9c3c. 16. Hammond DC.  Discussion: “SIEF”—Simultaneous implant exchange with fat: a new option in revision breast implant surgery. Plast Reconstr Surg. 2012;130(6):1197–8. https://doi.org/10.1097/ PRS.0b013e3182717386. PMID: 23190804 No abstract available 17. Salibian AA, Frey JD, Bekisz JM, Choi M, Karp NS.  Fat grafting and breast augmentation: a sys-

64  New Trends in Breast Augmentation with Fat Grafting: Implant Conversion with Fat and Hybrid… tematic review of primary composite augmentation. Plast Reconstr Surg Glob Open. 2019;7(7):e2340. eCollection. https://doi.org/10.1097/ GOX.0000000000002340. 18. Kerfant N, Henry AS, Hu W, Marchac A, Auclair E.  Subfascial primary breast augmentation with fat grafting: a review of 156 cases. Plast Reconstr Surg. 2017;139(5):1080e–5e. https://doi.org/10.1097/ PRS.0000000000003299. PMID: 28445355 19. Maione L, Caviggioli F, Vinci V, Lisa A, Barbera F, Siliprandi M, Battistini A, Klinger F, Klinger M.  Fat graft in composite breast augmentation with round implants: a new concept for breast reshaping. Aesthetic Plast Surg. 2018;42(6):1465–71. https:// doi.org/10.1007/s00266-­018-­1240-­9. Epub 2018 Sep 27.PMID: 30264274 20. Ørholt M, Larsen A, Hemmingsen MN, Mirian C, Zocchi ML, Vester-Glowinski PV, Herly

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M. Complications after breast augmentation with fat grafting: a systematic review. Plast Reconstr Surg. 2020;145(3):530e–7e. 21. Rigotti G, Marchi A, Stringhini P, Baroni G, Galiè M, Molino AM, et  al. Determining the oncological risk of autologous lipoaspirate grafting for post-­ mastectomy breast reconstruction. Aesthet Plast Surg. 2010;34(4):475–80. 22. Kronowitz SJ, Mandujano CC, Liu J, Kuerer HM, Smith B, Garvey P, et  al. Lipofilling of the breast does not increase the risk of recurrence of breast cancer: a matched controlled study. Plast Reconstr Surg. 2016;137(2):385–93. 23. Stumpf CC, Zucatto ÂE, Cavalheiro JAC, de Melo MP, Cericato R, APS D, Biazús JV. Oncologic safety of immediate autologous fat grafting for reconstruction in breast-conserving surgery. Breast Cancer Res Treat. 2020;

Implant Conversion with Fat Grafting

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Klaus Ueberreiter and Parshanak Azdasht

Key Messages  • The rich blood supply of the capsule provides optimum take rate criteria of this layer. • Fat grafting is limited to a maximum of 350 cc per side depending on the breast size. • Change of gloves is recommended immediately before fat injection. • The presence of postoperative seromas can be reduced by refraining from suturing the capsule. • The major amount of the fat to be transplanted is injected through the incision site and about 10% through a separate incision. • The possibility of fat grafting beneath the posterior capsule must be evaluated considering the thickness of the presenting tissue layer while keeping a safe distance to the thoracic cavity. • Injecting the fat after retraction of the implants is a reliable and safe method under digital and visual control. • The risk of accidental injury to the implant is higher when injecting the fact before retracting the implant. • About 90% of the patients undergoing implant conversion with fat grafting are satisfied with the result and do not ask for a second session of fat grafting.

K. Ueberreiter (*) · P. Azdasht Park-Klinik Birkenwerder, Plastic Surgery, Birkenwerder, Germany e-mail: [email protected]

65.1 Introduction There are plenty of reasons for an implant conversion with fat commonly starting from complaints directly or indirectly caused by the implants, e.g., capsular contracture, foreign body sensation, rupture, exchange due to material fatigue, or breast implant illness. There are different published studies showing an average outcome of capsular contracture in patients undergoing breast augmentation with implants of 10% within a period of first 10 years after implantation. In some of these cases at least a temporary removal of the implants must be considered. The recommendation is even higher proportional to the number of relapses in capsular fibrosis if, for instance, the patient decides to have a replacement of the implants. In patients with capsular fibrosis undergoing implant conversion with fat grafting you can expect an improvement by the removal of the foreign body itself and the improvement of the tissue quality on the other hand with numerous publications stating the positive effect of autologous fat on scar tissue. At least after the third relapse of capsular contracture the removal of implants is recommended for 6 months. In those cases a change from implants to fat is highly recommended. There are patients who had not been eligible for lipofilling at the time of silicone breast augmentation when the amount of available fat tissue

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seemed too low for grafting at that point of time. There is a wide variety of the individual range of fat distribution but a BMI below 18 has proven to be the lower limit at our clinic. Occasionally patients succeed in gaining enough weight in the meanwhile to finally undergo lipofilling procedure at all. A loss of weight after a lipofilling procedure or fluctuations in weight by 2–3  kg has shown no reduction of the breast volume later on. The following section deals with the removal of silicone implants and its replacement by autologous fat grafting.

65.2 Looking for the Ideal Patient… 65.2.1 Requirements

65.3 Operation Technique The surgery is usually done under general anesthesia and takes approximately 60–90  minutes after a period of learning. An inpatient admission for 1–2 days is recommendable. The patients are being marked preoperatively with the donor sites for fat grafting preferably the tummy/flank region or upper thighs for logistic reasons if there is no preference from the patient’s side. In our clinic we start by harvesting the fat. The procedure of lipotransfer follows the Berlin Autologous Lipotransfer Protocol (BEAULI) that gives a detailed and reproducible hands-on description of the single steps. You can find a short version in Fig. 65.4.

65.3.1 Removal of Implants

Like in all fat tissue transplantations the abstinence of nicotine is an obligate requirement for sufficient circulation and thus healing of the grafted fat. Despite the fact that there are publications that figured out no difference between the survival rate of smokers and nonsmokers we can clearly see a notable difference of the results in practice. Per se, smoking is not a contraindication for surgery but the patient has to be well aware of the fact that the risk of a reduced survival rate of fat grafts is high when discontinuing with smoking is not an option. The fat distribution of a patient with BMI 18 or less does not usually allow harvesting a sufficient amount of fat for transplantation to the breasts. The patient can try to gain weight before having surgery.

According to the standard procedure of removing the implants, the surgical approach corresponds in most cases with the skin incision of the former implant insertion. It is mainly done via an incision in the inframammary fold but occasionally through a periareolar incision. Using the axillary access is not recommended because of the lacking possibility to check on the capsule. The former scar is excised. The tissue layers are dissected carefully onto the capsule surface of the implant (Fig. 65.1). The capsule is incised and dilated so that the implant can be mobilized and removed easily without harming it. Referring to the increasing number of BIA-­ ALCL (breast implant-associated anaplastic large-cell lymphoma), there is no scientific evi-

a

b

© Dr. K. Ueberreiter 2021

Fig. 65.1 (a, b) Curette and cleansing of the capsule prepared (© Dr. K. Ueberreiter 2021)

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dence for taking a swab and tissue specimen and search for CD30-positive marked cells as a matter of routine so far. Nevertheless, we recommend diagnostics to rule out pathologic findings that can macroscopically be missed. Even many patients ask for the examination in order to eliminate their worries about any kind of pathology being present. Seromas or suspicious lesions need to be examined under the aspect of BIA-ALCL. After inspecting the implant for any damages especially around the seal region the empty implant cavity is being cleansed thoroughly by repetitive flushing and wiping and inspected for any suspicious lesions (Figs.  65.1 and 65.2). When dealing with a defective implant one has to make sure that no silicone particles remain inside the capsule. This can be a very challenging process. A digital examination of the cavity is additionally very helpful because in all reported BIA-ALCL cases the tumor presented as a palpable mass inside the capsule. A frequent change of sterile gloves is indicated especially after the cleansing process. Recommended change of gloves immediately before fat injection.

time. The latter would lead to discontinuing the intention of fat transfer within the same session. Around 90% of the total amount of fat being grafted is injected via the implant incision area. By this approach a good overview is granted in order to position the cannula and the grafting right on the anterior capsule for the reason of an excellent circulation condition the more accurately you can approach to the capsule without harming it. The remaining 10% are infiltrated through a separate prick incision close to the axillary line after closure of the skin focusing on the former implant incision area.

65.3.3 Step I For giving a good projection to the breast shape one should not miss to infiltrate the dorsal capsule an intramuscular layer especially in subglandular implants. After the removal of implants you can frequently observe an atrophic pectoral muscle. The more volume is infiltrated the easier it gets fanning the cannula for graft distribution. It is impressive that this layer can accept a minimum of 150 cc of fat grafting.

65.3.2 Fat Injection

65.3.4 Step II

You can potentially inject the fat before as well as after implant removal. We decided on extracting the implant first for the benefit of gaining better digital and visual control. This leads to a lower risk of accidentally damaging the implant and missing suspicious lesions inside the capsule in

The next step is grabbing the capsule at the site of the incised margin with a Kocher’s clamp and holding it under slight strain. The blunt infiltration cannula (1  mm diameter, 10  cm length) is inserted right above the capsule. The index finger can easily palpate the correct position of the cannula from the inside of the capsule so that the tun-

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Fig. 65.2 (a, b) Infiltration around the capsule under digital control (prepared © Dr. K. Ueberreiter 2021)

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nels that are created are within the same layer. The infiltration is done by performing even pressure on the syringe plunger while withdrawing the cannula tip (Fig.  65.2). Each tunnel is infiltrated with about 1 cc so that the amount of fat in a 10 cc syringe is distributed by ten to twenty fan-­ shaped movements. In order to reach to the outward boundaries of the quadrants it might be advisable to choose on other access points with the Kocher’s clamp. A leakage of fat usually originates from lesions of the capsule caused by penetrating it with the cannula tip. The fat consequently assembles within the capsular cavity where it remains within a poorly vascularized surrounding. As these fat chunks will lack in nutrition, they will not survive transplantation and finally turn into oily debris. Therefore, the insertion of a drain is to be considered, if the capsule is lacerated accidentally.

–– Constant water flow during harvesting. –– Collecting the fat and separating it from the liquid and oily debris using, e.g., LipoCollector. –– Filling of five 10 cc syringes facilitates counting of grafted volume. –– Infiltration with blunt cannula of 10 cm length allows augmentation via one laterocaudal prick incision. –– Infiltration of 1 cc per 10 cm “tunnel”. –– Maximum volume of fat transfer 300 cc per side. Postoperatively –– Compression garment of suctioned region for 4 weeks. –– Keeping the breasts warm with a spool of wide absorbent cotton, no cooling, no pressure (Fig. 65.4).

65.3.4.1 Step III The subcutaneous infiltration is done almost equivalent to the aesthetic augmentation described in previous sections with paying extra attention to not harming the capsule if preserved (Fig. 65.3).

BEAULI Protocol “Short”

Preoperatively –– Analgesic sedation or general anesthesia. –– Tumescence solution: 3 L N/S + 150 cc lidocaine 1% + 3 cc adrenaline 1:1000  +  37.5  cc sodium bicarbonate 8.4 mVal –– Preheating of the tumescence solution to body temperature. Surgery –– Infiltration and suctioning through prick incisions using 3.8  cc rapid harvesting cannula and minimum negative pressure of −500.

Fig. 65.3 Subcutaneous infiltration (prepared © Dr. K. Ueberreiter 2021)

The rich blood supply of the capsule provides optimum take rate criteria of this layer.

65.3.5 How Much Fat? The amount of transplanted fat should approximately correspond to the former size of the implant but not exceed 350  cc because of the increasing risk of having oily cysts. However, it is the upper limit, but how much fat can be grafted at all per layer is self-limiting anyways. Trying to overfill the layers will not increase the amount of

65  Implant Conversion with Fat Grafting Fig. 65.4 BEAULI protocol “short”

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BEAULI-Protocol ‘short’ preoperatively -

-

Analgesic sedation or general anesthesia Tumescence solution: 3 liters N/S + 150 cc lidocaine 1% + 3 cc adrenaline 1:1000 + 37.5 cc sodium bicarbonate 8.4 mVal Preheating of the tumescence solution to body temperature

surgery -

-

Infiltration and suctioning through prick incisions using 3.8 cc rapid harvesting cannula and minimum negative pressure of -500 Constant water flow during harvesting Collecting the fat and separating it from the liquid and oily debris using e.g. LipoCollector Filling offive 10 cc syringes facilitates counting of grafted volume Infiltration with blunt cannula of 10 cm length allows augmentation via onelaterocaudalprickincision infiltration of1ccper10cm“tunnel” maximum volumeof fattransfer300ccperside

postoperatively -

compression garment of suctioned region for 4 weeks keeping the breasts warm with a spool of wide absorbent cotton, no cooling, no pressure

fat that heals in but lead to complications: a higher reabsorption rate and oily cysts. Fat grafting is limited to a maximum of 350 cc per side depending on the breast size.

65.3.6 Closure When the infiltration is finished a Redon drain is recommendably placed. We observed postoperatively seromas in our patient population when suturing the capsule. Since we were leaving the capsule open we enabled fluids to drain to the subcutaneous layer with no more similar complications. If seromas occur in rare cases they should be punctured. At the same time the injection of a corticosteroid can avoid a reoccurrence. The subcutaneous layer and the skin are closed in a usual manner. Finally the area directly above the wound is filled up with fat from an additional prick incision that is commonly done at a lateral point close to the anterior axillary line. The prick incisions are closed with adhesive stripes (e.g., steristrings) and sterile plasters. The

breasts are wrapped by a cotton dressing. The patient is dressed up with the respective compression garment of the liposuctioned area before leaving operation theatre (Fig. 65.5). The presence of postoperative seromas can be reduced by refraining from suturing the capsule (Figs. 65.6 and 65.7).

65.4 Aftercare 65.4.1 Daily Activities Postoperatively the patient is obliged to avoid any compression to the breast for a period of 4 weeks. Cooling the breasts reduces the survival rate by a physically induced vasoconstriction so that the cells cannot connect to the vascular system or survive. Especially the first days after surgery are decisive. Having a similar effect on the vessels, nicotine must be avoided as well at least 2 weeks before and 2 weeks after surgery. There is no need to completely avoid doing sports besides training your pectoral muscles for 4 weeks.

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a

b

c

d

Fig. 65.5 (a–d) Capsular fibrosis after breast augmentation with silicone implants in a patient with a history of fibroadenoma laterally left and its resection at the age of 17 causing a lack in volume and asymmetry (a, c) and 8  months after implant conversion with fat grafting of

200  cc left and 230  cc right (b, d), respectively, in the clinical aspect and in the MRI. Patient was satisfied with the result and did not ask for a lipofilling of former fibroadenoma area laterally left

65.4.2 Wound Care

65.5 K  eeping or Removing the Capsule of the Implant?

Most patients develop a moderate hematoma and swelling which will increase within the first week and subside within a period of 6  weeks. If a Redon drain is employed it can be removed on the first postoperative day. The adhesive straps remain approximately 4 weeks on the prick incision scar. Meanwhile the patient is allowed to take a shower and continue with the usual hygiene. According to our experience the hermetically sealed wounds showed the best aesthetic results (Fig. 65.8).

In general there are two situations for when to decide on keeping or removing the capsule: when there is a suspicious lesion or a reasonable suspicion that there are silicone particles accumulating in the capsule. Silicone particles can be found in the capsule if there is any kind of defect of the implant. The capsule itself will then enclose silicone particles as well but is not an impermeable border to them. If silicone particles are found inside the capsule one can surely assume that

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a

c

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d

Fig. 65.6 (a–d) Capsular fibrosis after breast augmentation with silicone implants (right: 305 cc; left: 265 cc) in a patient with a history of capsular contracture (a, c), 6 months after implant conversion with fat grafting and a

second session of fat grafting (each lipofilling with right: 180 ml and left: 160 ml) (b, d), respectively, in the clinical aspect and in the MRI

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b

c

d

Fig. 65.7 (a–d) Capsular fibrosis on both sides after breast augmentation with silicone implants in a patient with BMI of 18 (a) preoperatively, (b) intraoperatively after removal of the implants and before fat grafting, (c)

intraoperatively after removal of the implants and after fat grafting of 180  cc, and (d) 1  year postoperatively after implant conversion

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a

b

c

d

e

f

g

h

Fig. 65.8 (a–h) Patient before (a, c) and after (b, d) breast augmentation with silicone implantsSame patient 8  years later presenting with capsular fibrosis with

implants still in place (e, g) and 6  months after implant conversion with fat grafting of 220 cc per side (f, h)

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they also penetrated the capsule into the rest of the body. If or to which extent they harm the body has not been found out so far. Regarding the fact that the capsule is a foreign body reaction to the implant it is expectable that it will continuously dissolve by itself during remodeling processes of the body. The excellent blood supply of the capsule meets the requirement for the optimal healing-in condition of the fat chunks. Removing this layer without any specific reason would be a waste of resources. The significantly larger wound surface even reduces the average volume which can be achieved significantly, firstly due to the additional tissue volume which is removed and secondly by the lower survival rate on the sore surface. At the end it is a decision that has to be made together with the well-educated patient. Occasionally macro-calcifications of various sizes ranging from one or several small spots to a complete calcification of the whole capsule, resembling the consistency of an eggshell, can be observed. They can partially be removed by means of a sharp curette. The rest remaining within the capsule has not shown any negative impact neither on our patients nor on the quality of imaging techniques, such as mammography. These kinds of macro-calcifications are located retroglandularly in contrast to malign micro-­calcifications within glandular tissue (Fig. 65.9).

Fig. 65.9  Pros and cons of a remaining implant capsule

65.6 Breast Implant-Associated Anaplastic Large-Cell Lymphoma (BIA-ALCL) Because of the uprising numbers of breast implant-associated anaplastic large-cell lymphomas it is more than necessary to mention a few points that a surgeon should pay attention to capsule while carrying out this procedure. All published cases showed seroma after insertion of the silicone implants. As much liquid as possible (50 cc recommended) should be collected and sent to pathology for the examination of positive CD30 marker. An additional specimen of capsular tissue can be added. The BIA-ALCL could be identified in the seroma of all published cases. So far we can assume that this is a sensitive method to rule out BIA-ALCL. The case studies claim that the BIA-ALCL was palpable while a seroma was present which is an important note to the pathologist as well. Therefore we do a manual and optical inspection of the capsule.

65.7 S  pecial Case Breast Implant Illness (BII) Within the last few years more and more patients with silicone implants have complained of a variety of symptoms. They are quite unspecific and comprise fatigue, paresthesia, headaches, dizziness, exanthema, depressions, nausea, or palpitations.

Pros and Cons of remaining implant capsule Pros -

maintenance of volume optimal layer of fat transfer lower bleeding rate minimal wound surface higher survival

Cons -

questionable silicone particles left inside the capsule tissue possible contamination extracting broken implants

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There is a big social media community that exchanges experiences and information on internet platforms. Within these groups the patients are urgently recommended to insist on the removal of the capsule surrounding the implant (“en bloc resection”) regardless of the implant being intact or not. Silicone particles do not specifically accumulate inside the capsule but are also spread in the surrounding tissue or lymphatic system. But if the patient is personally convinced of negative health impacts due to the remaining capsular tissue we respect it. In those cases an en bloc resection is paramount.

65.7.1 Biofilm There is a strong belief that the biofilm developing on the surface of the implant is co-­responsible for their symptoms. It is a fact that biofilm only colonizes foreign bodies because the germs establishing the biofilm are not opposable for the immune system. Contrary to the opinion on the internet platform, there is no biofilm detectable in the liquid and the capsule. In case we are dealing with a patient suffering from BII, the symptoms start subsiding after the explantation surgery irrespective of en bloc removal or a remaining capsule. Breast implant illness remains a diagnosis by exclusion after ruling out other primacies of the underlying symptoms.

65.8 Specific Complications 65.8.1 Postoperative Bleeding In patients with a preserved capsule during surgery secondary bleeding is negligible. The rate of postoperative bleeding in patients with en bloc resection is higher but still low. In less than 5% of the cases a revision surgery is indicated which usually reveals rather a diffuse bleeding from the pectoral muscle rather than a localized lesion of a bigger vessel.

65.8.2 Implant Damage While removing the implant, especially when incising the superior tissue layers over the implant, it is possible to injure the implant iatrogenically. In this case the cleansing of the cavity must be done with an extra care.

65.8.3 Perforation of Capsule During Infiltration The perforation of the capsule can occur during the infiltration process of fat grafting when the blunt cannula is pushed forward with too much of a force. In order to avoid this complication the surgeon should pull the cannula a little back when any resistance occurs and choose on a different direction of the cannula tip. Usually this might happen more often in the very beginning of the grafting because the more fat is injected already the easier the following injections will become considering the tissue resistance. If the perforation of the capsule could not be avoided, the insertion of a Redon drain 12–14 Ch ending in the capsule cavity is strongly recommended at the end of the surgery. On the one hand the perforation is sealed up by the negative pressure and fat that penetrated the cavity is suctioned out as it will otherwise not heal in but rather remain as oily debris.

65.8.4 Seromas In rare cases seromas can occur postoperatively. In our experience it is due to too tight closure of the capsule at the end of the operation so that fluid exudate will accumulate there. By leaving the capsule unstitched a possible accumulation can be avoided.If a seroma occurs despite this method, we recommend a puncture and an injection of crystalline corticosteroids to provocate the adhesion of the capsular layers. The aspirate fluid should be examined for pathological findings anyhow.

65  Implant Conversion with Fat Grafting

65.8.5 Form Changes Some patients might be concerned about skin laxity or lack in volume of the breasts. If the size of the former implant does not exceed 300 cc the amount of fat-grafted volume in one session after healing is almost replaced as the former implant serves similar to an expander as a spacer. This results in a high degree of satisfaction among the patients so that less than 10% wish to undergo a second lipoaugmentation [1–16]. The patient needs to be well instructed that after surgery the breast will have a more natural and more ptotic shape than with the implants. Also the exaggerated fullness in the upper quadrants which is mainly due to capsular fibrosis will completely subside by itself and reshape the breasts. In case there is a relevant ptosis the implant conversion with fat grafting can be combined with a mastopexy in the very same session. Depending on the technique and experience of the surgeon the ptosis can be reduced to some extent already during grafting (Fig. 65.10).

65.9 Outcome In patients undergoing primary breast augmentation with lipotransfer without an underlying anomaly, the take rate approximately equals 76% of the transferred volume. In patients undergoing implant conversion with fat grafting the take rate seems to be even higher. This might be due to the pre-dilatation of the tissue surrounding the implant. Less than 10% ask for a second session of fat grafting. Form changes -

more ptotic smaller less upper pole fullness

Fig. 65.10  Form changes

-

no hardness no pain natural movement

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In patients with suspicious lesions of the capsule reminding of BIA-ALCL one should refrain from lipotransfer within the same session of implant removal. The focus should be treating the BIA-ALCL first. The fat transfer can be taken into consideration after recovery. Apart from that, a direct fat transfer within the same session has the amenity of getting the treatment as well as reaching the desired result by having only one surgery. The tissue is still pre-dilated right after explantation which seems to have a positive effect on the take rate. Besides the economic aspect, patients suffer psychologically from the outcome of the aesthetic result, if the implants are solely being removed. The appearance corresponds in best case to the initial situation before implantation which actually leads to surgery at all. The number of implant conversions with fat grafting has been continuously increasing over the past years. From January 2019 to May 2020 thirty-three patients underwent surgery. Approximately half of them (58%) asked for an en bloc surgery because of a suspected breast implant illness either combined with or without fat grafting. In the other patients the capsule remained inside. Just a specimen of it was examined histopathologically. Both patient cohorts delivered good results considering overall patient satisfaction.

65.10 Conclusions Implant conversion with fat grafting is a safe and easy method after a period of learning. The collateral damages like dimples and bumps after liposuction during surgery are minor compared to those of silicone implants. In patients with capsular fibrosis undergoing implant conversion with fat grafting you can expect an improvement by the removal of the foreign body itself and the improvement of the tissue quality on the other hand with numerous publications stating the positive effect of autologous fat on scar tissue.

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References 1. Coroneos C, Selber J, Offodile A, Butler CE, Clemens M.  US FDA breast implant postapproval studies: long-term outcomes in 99,993 patients. Ann Surg. 2019;269(1):30–6. https://doi.org/10.1097/ SLA.0000000000002990, PMID: 30222598 Issn Print: 0003-4932 2. Stevens WG, Calobrace MB, Alizadeh K, Zeidler KR, Harrington JL, d'Incelli RC. Ten-year core study data for Sientra’s food and drug administration-approved round and shaped breast implants with cohesive silicone gel. Plast Reconstr Surg. 2018;141(4S Sientra Shaped and Round Cohesive Gel Implants):7S–19S. https://doi.org/10.1097/PRS.0000000000004350. 3. Headon H, Kasem A, Mokbel K. Capsular contracture after breast augmentation: an update for clinical practice. Arch Plast Surg. 2015;42(5):532–43. https://doi. org/10.5999/aps.2015.42.5.532. 4. Papadopoulos S, Vidovic G, Neid M, Abdallah A.  Using fat grafting to treat breast implant capsular contracture. Plast Reconstr Surg Glob Open. 2018;6(11):e1969. https://doi.org/10.1097/ GOX.0000000000001969. 5. Peters W, Pritzker K, Smith D, et  al. Capsular calcification associated with silicone breast implants: incidence, determinants, and characterization. Ann Plast Surg. 1998;41(4):348–60. https://doi. org/10.1097/00000637-­199810000-­00002. 6. Peters W, Smith D.  Calcification of breast implant capsules: incidence, diagnosis, and contributing factors. Ann Plast Surg. 1995;34(1):8–11. https://doi. org/10.1097/00000637-­199501000-­00002. 7. Bui JM, Perry T, Ren CD, Nofrey B, Teitelbaum S, Van Epps DE. Histological characterization of human breast implant capsules [published correction appears in Aesthetic Plast Surg. 2015 Jun;39(3):316-7]. Aesthet Plast Surg. 2015;39(3):306–15. https://doi. org/10.1007/s00266-­014-­0439-­7.

K. Ueberreiter and P. Azdasht 8. Brody GS, Deapen D, Taylor CR, et  al. Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases. Plast Reconstr Surg. 2015;135(3):695–705. 9. Graf RM, Closs Ono MC, Pace D, Balbinot P, Pazio ALB, de Paula DR.  Breast auto-augmentation (Mastopexy and Lipofilling): an option for quitting breast implants. Aesthet Plast Surg. 2019;43(5):1133– 41. https://doi.org/10.1007/s00266-­019-­01387-­5. 10. Ueberreiter K, von Finckenstein JG, Cromme F, et  al. BEAULI  – a new and easy method for large-­ volume fat grafts. Handchir Mikrochir Plast Chir. 2010;42(6):379–85. 11. Ueberreiter K, Tanzella U, Cromme F, Doll D, Krapohl BD.  One stage rescue procedure after capsular contracture of breast implants with autologous fat grafts collected by water assisted liposuction (‘BEAULI Method’). GMS Interdiscip Plast Reconstr Surg DGPW. 2013;2:Doc03. 12. Heine NP, Prantl L.  Brustrekonstruktion durch Eigenfettinjektion. Chir Praxis. 2014;78:77–90. 13. Kwiatkowska K, Krapohl BD, Tanzella U, Ueberreiter K.  Long-term clinical results and quality of life in patients undergoing autologous fat transplantation for breast augmentation using the BEAULI™ protocol. GMS Interdiscip Plast Reconstr Surg DGPW. 2019;8:Doc10. https://doi.org/10.3205/iprs000136. 14. Herold C, Ueberreiter K, Cromme F, Busche MN, Vogt PM. MRT-Volumetrie der Mamma zur Kontrolle der Fettresorptionsrate nach autologem Lipotransfer [the use of mamma MRI volumetry to evaluate the rate of fat survival after autologous lipotransfer]. Handchir Mikrochir Plast Chir. 2010;42(2):129–34. https://doi.org/10.1055/s-­0029-­1243204. 15. Benelli L.  Technique personnelle de plastie mam maire péri-aréolaire: le ‘round-block’. Cah Chir. 1991;77(1):15–25. 16. Coleman SR, Saboeiro AP. Fat grafting to the breast revisited: safety and efficacy. Plast Reconstr Surg. 2007;119(3):775–87.

Composite Breast Augmentation with Implants and Fat Grafting

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Obaid Chaudhry and Daniel Del Vecchio

Key Messages • The composite breast augmentation was first described in 2013 by Auclair, Blondeel, and Del Vecchio as a means to provide breast augmentation patients the natural look and feel of fat with the core volume projection of a breast implant. • The majority of breast augmentation patients are composite candidates. • The amount of fat or ratio is secondary to the aesthetics of the mound. Visual harmony is key in order to achieve the 45/55 ideal breast ratio. • Do not violate the breast footprint with oversized implants. Follow the high-five principles.

• The superior medial transition zone is the most important area to transfer fat in order to attenuate the cleavage gap. • Donor-site deformities will detract attention away from excellent breast results. Follow the principles of SAFELiposuction. • Additional rounds of fat transfer may be needed to augment the first round. It is important to discuss this with the patient preoperatively. • Follow the 14-point plan when performing the dissection and implant placement. • A subfascial approach provides a quicker, painless recovery without the concerns for an animation deformity. • Composite breast augmentation does not interfere with mammography.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_66) contains supplementary material, which is available to authorized users.

66.1 Introduction

O. Chaudhry (*) Private Practice, Beverly Hills, CA, USA Manhattan Eye, Ear, and Throat Hospital, New York City, NY, USA D. D. Vecchio Private Practice, Beverly Hills, CA, USA Manhattan Eye, Ear, and Throat Hospital, New York City, NY, USA Massachusetts General Hospital, Boston, MA, USA

Fat grafting to the breast has many indications, ranging from post-mastectomy cancer reconstruction to cosmetic augmentation. According to the American Society of Aesthetic Plastic Surgeons (ASAPS) Cosmetic Surgery National Data Bank statistics, fat grafting to the breast has increased 37% from 2015 to 2019, and this is only expected to rise [1]. The potential of core volume breast augmentation with fat gained popularity; however its lack of adoption among patients and surgeons was significant secondary

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to BRAVA pre-expansion requirements and restrictions of fat transfer to the recipient site in one session due to graft-to-capacity limitations [2–6]. As a result of the above limitations, the composite breast augmentation was developed. With a composite approach, the core volume projection is derived from the breast implant, and the natural look and feel of fat are added to obtain the best of both worlds [3, 7, 8]. When used alone, breast implants have affiliated with higher revision rates and complications. The assumption by most would be that device failure is the cause of disappointing results; however it is usually violation of the breast footprint with improper sizing, and absence of abundant breast tissue leading to unnatural visibility and palpability. Core volume augmentation of the breast with fat became a potential savior for these implant-associated complications. However, it was quickly noted that large-volume fat transfer has its own inherent limitations, which can be explained by the “mountains of sand” analogy. The core volume projection of fat is inadequate and provides a broad breast base. With this in mind, the combination of the two concepts became an apparent solution, with the core volume projection of a breast implant and the natural look and feel of fat providing the best of both worlds. This concept led to the birth of the composite breast augmentation, a new wave in the era of breast enhancement. Since the introduction of the technique by the senior author, it has gained significant interest for both aesthetic and reconstructive purposes. The goal of this chapter is to highlight the key points of the composite breast augmentation in relation to fat:implant ratios, and emphasize certain cases where the ratios are ideally utilized.

66.2 Historical Perspective Composite breast augmentation was first described in 2013 by Auclair, Del Vecchio, and Blondeel and was first published as a new breast

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augmentation technique in the Journal of Plastic and Reconstructive Surgery that same year [3]. Prior to that time, the three authors had been independently employing some combination of breast implants and fat in their cosmetic surgery practices. In Europe, Auclair and Blondeel combined textured anatomic implants placed in the subglandular or subfascial position, with smaller volumes of fat on the order of 90–150  mL.  In the United States, larger volumes of fat were used to cover similarly sized smooth round gel implants placed in the submuscular plane (Del Vecchio). Hybrid breast augmentation is a corporate-­ sponsored attempt at marketing and branding a company’s implants and associated fat grafting instrumentation into a version of the original operation—called the composite breast augmentation.

66.3 Categories of Fat Transfer to the Breast When referring to fat transfer to the breast, three categories exist, all with unique considerations. This consists of the composite breast augmentation, core volume fat transplantation with BRAVA pre-expansion, and simultaneous implant exchange with fat (SIEF) [3–6, 9, 10]. The most sought-after technique by patients desiring fat transfer to the breast is the composite breast augmentation (Fig. 66.1). Fat transfer alone for primary breast augmentation is a reliable technique for less than 1% of patients (Fig.  66.1). Similar to “mountains of sand,” fat is unable to provide significant core volume projection. As the volume of fat transfer increases, the base of the breast becomes wider without significant projection of the breast mound (even when used in conjunction with BRAVA pre-expansion) (Fig. 66.2). Nevertheless, core volume fat augmentation is feasible for a variety of breast patients (Figs. 66.3, 66.4, 66.5, 66.6, and 66.7) [3]. In addition, core volume augmentation targeted to the lower pole of the breast

66  Composite Breast Augmentation with Implants and Fat Grafting

Fig. 66.1  Graph showing the distribution of ideal candidates for composite breast augmentation versus core volume or prosthetic-based augmentation. As one can see from the graph, fat for core volume is uncommon.

Fig. 66.2  Fat for core volume is a reliable technique, but it is not robust. An analogy provided here compares fat to “mountains of sand.” A significant limitation of fat in isolation is that it is unable to provide adequate core volume projection. Fat alone will help develop a base, or foundation to the mound

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Implant-only augmentation is only suitable for a quarter of patients. The remaining majority are candidates for the composite breast augmentation

aids in achieving the Mallucci 45/55 ideal breast ratio (Fig. 66.8) [11]. In certain situations, soft-tissue failure may occur and breast deformities may be pronounced. For these issues, soft-tissue envelope m ­ odification over the prosthetic device, rather than a removal and replacement, will provide a solution for the breast deformity (Fig. 66.9). The use of breast implants alone will provide an adequate outcome for patients with an ideal soft-tissue envelope, which encompasses approximately 25% of all patients desiring breast augmentation. However, the majority of patients’ soft-tissue characteristics will require a composite technique in order to obtain the best outcome. Initially described in 2013, the composite breast augmentation encompasses the best qualities of both worlds: the core volume projection of a breast implant with the combined natural look and feel of autologous fat. This technique has been utilized by many surgeons for both reconstructive and aesthetic breast patients [3, 6–8, 10, 12–14]. This chapter focuses on the range of fat-­ to-­implant ratios ideal for a composite technique

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Fig. 66.3 and 66.4  Severe congenital asymmetries treated with fat transplantation only. Figures 66.3 and 66.4 are shown at 1 year and 6 months postoperatively, respectively

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Fig. 66.5  Severe constricted breast treated with 600 cc total fat. Postoperatively, the lower pole has been significantly expanded

Fig. 66.6  Pre- and postoperative mastopexy combined with 400 cc of fat transfer shown at 3 years postoperatively. To prevent long-term ptosis, one may avoid an implant and use fat only

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Fig. 66.7  Fat combined with a mastopexy shown at 1 year postoperatively. One must appreciate that a breast lift is more than just nipple repositioning, but also involves

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volume restoration. When fat is used in lieu of an implant, the complications affiliated with a mastopexy augmentation are not present

Fig. 66.8  The ideal 45/55 upper-to-lower pole aesthetics, as described by Patrick Mallucci, is achieved with core volume fat transplantation. Here, the lower pole has been expanded with fat

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Fig. 66.9  A significant lower pole abnormality is seen on the left breast. This is not due to implant malposition, and rather than removing the prosthesis, the soft tissue can be

altered over the implant to create a natural, aesthetically pleasing lower pole. This is one of the basic concepts of the composite breast augmentation procedure

and the thought process behind choosing the appropriate ratios.

those unable or unwilling to accept the p­ ossibility of a secondary round of fat graft for further volume and adjustment of the cleavage gap are not candidates for a composite breast augmentation.

66.4 Indications and Contraindications The typical composite patient has small breasts with inadequate tissue to cover the prosthetic device. If an implant is used alone, and one follows a tissue-based analytical approach as described by Tebbetts, the surgeon is faced with a dilemma of placing an implant that is too small or that violates the soft-tissue footprint of the breast in order to obtain a narrow cleavage gap [15]. In a composite technique, one maintains the native soft-tissue footprint, and the “high-five” principles are preserved. The composite technique prevents the above dilemma by placing smaller implants with a narrow diameter while using fat for the transitional areas and cleavage gap. Contraindications for a composite procedure are similar to those for liposuction. In addition, patients with a significant family or personal history of breast cancer, those with unreasonable expectations with respect to size and shape, and

66.5 Preoperative Planning and Analysis The vast majority of patients presenting for primary breast augmentation are suited for a composite technique (Fig. 66.1). The implant provides the core volume projection, whereas the fat delivers width and transition, especially in the cleavage gap, and equalizes any asymmetries. Thus, the breast implants and fat are symbiotic entities. The ideal patient is one with minimal soft tissue and a thin body frame. One may address the abrupt transitional areas with fat in order to produce the ideal 45/55 ratio without the need of an anatomic implant. Certain females with ideal soft tissue and breast characteristics are eligible for breast implants alone; however this cohort does not embody a majority of patients. Then there are those who desire an increase in breast size, but are not willing to place prosthetic devices, com-

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prising the “padded bra” cohort. These women desire larger breasts but do not want a breast augmentation with any foreign body. These are the patients that may desire core volume augmentation with fat. A vital part of the preoperative analysis includes quantifying the amount of fat required to produce an aesthetically pleasing result. The original composite breast augmentation paper by Auclair et al. provided a wide array of case scenarios utilized by a cohort of authors [3]. A common combination implemented by Auclair included a 300 cc implant with approximately 80–100 cc of fat placed in the upper inner quadrant to produce a soft, full cleavage gap. In contrast, Del Vecchio’s technique employed an implant and fat of equal volumes. Looking closely at these two techniques, one can visualize two ratios: a 1:3 fat-to-implant ratio and a 1:1 ratio, respectively. A third option includes a 2:1 fat:implant ratio, where the implant provides the necessary core volume augmentation, while the fat aids in the width and transition. In all scenarios, the fat and implant are codependent entities, and the volume maintenance of fat is

crucial for a successful outcome. Regardless of the ratio, the surgeon is able to provide the patient with the best of both worlds with these ratios: the core volume projection of an implant with the natural look and feel of fat (Fig. 66.10). Based on the above principles, one can appreciate that an endless number of implant-to-fat ratios are available to implement. The senior author prefers a 2:1 ratio and usually does not utilize anything below a 1:2 ratio. Nonetheless, wide spectrums of ratios are available with a tendency for fat survival and ideal aesthetics. Anything below or above a 1:3 or 2:1 ratio of fat to implant would be fat insufficient or excessive, respectively (Fig. 66.11a, b). As the surgeon prepares for each case, a dilemma arises: How much fat should one transfer to achieve the best aesthetic result and maintain the volume transferred? As shown in Fig. 66.11a, b, the wide range of fat-to-implant ratios ranges from 1:3 to 2:1, with implant- or fat-only techniques being at the far ends of the curve. Nonetheless, it must be emphasized that ratios are the derivatives, and the end result is guided by the aesthetics of the breast mound. It must be empha-

Fig. 66.10  Composite breast augmentation can also be used in secondary revision cases. Here is an example of insufficient soft-tissue coverage, rippling, and a large cleavage gap. A 1:1 fat-to-implant ratio was utilized with

a 6-month postoperative result showing substantial improvement. Notice the improved cleavage gap and absence of rippling postoperatively

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Fig. 66.11 (a and b) The range of fat-to-implant ratios is displayed. Although a broad spectrum of rations can be applied, the realistic limits for composite breast augmentation are 1:3–2:1. The extreme ends of the spectrum are fat transplantation only, where a range of fat excess ratios

occur, to implant only, which is in the territory of fat-­ insufficient volumes. One must recognize that the ratio is a derivative, whereas aesthetics drives the end result. The ratio should not define the surgical strategy by the plastic surgeon

sized that the ratio is not what guides the surgical plan. A simple comparison is that of filling gas in a car. The driver does not preemptively decide on the amount of gas needed to fill the tank of gas in the car. Instead, they will fill the gas tank until it is full, and the amount of gallons and cost at the end will be evaluated. The same notion is true for the composite approach: the aesthetics is the major factor when analyzing the end result, while the ratio is secondary. The key takeaway point is to keep the implant within the soft-tissue footprint, and add fat to accentuate the cleavage gap. Another consideration to assess within the composite scenario is dissection plane and fat placement. Three different scenarios to consider include type 1: subglandular or subfascial primary breast augmentation and fat overlay; type 2: submuscular primary breast augmentation with implants and fat; and type 3: revision breast augmentation using implants and fat (Fig.  66.12). The senior author favors a subfascial approach with fat overlay as this avoids animation deformities and lateral migration of the implant. In type 3 patients, BRAVA pre-expansion is recommended in order to considerably increase the third space of the recipient site.

The location of fat placement can vary depending on the location of the breast implant. In a submuscular placement of the implant, a higher volume of fat can be placed for a larger overlay. If the implant is in the subfascial or subglandular place, there is a smaller volume of total fat that may be used for footprint coverage. The volume of fat that is required can be estimated preoperatively based on tissue characteristics and for a widespread range of implant volumes. Assuming the geometry of an implant to be that of a sphere, one can calculate the amount of fat required based on a variety of radius measurements for a range of breast implant volumes (Fig. 66.13). One may be able to quantitatively measure the residual volume postoperatively if a preoperative and postoperative three-dimensional image is obtained, which is based on the following equation: (Total breast volume postoperative)  – (Total breast volume preoperative)– (Implant volume) = Retained volume. Percent volume maintenance = Retained volume / Total volume of grafted material.

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*The versatility of implant position and fat offers three primary composite breast augmentation approaches. Each approach differs by the capacity of the recipient site. In general, the deeper the implant plane, the larger the capacity of the third space of the breast.

Fig. 66.12  Three different approaches for composite breast augmentation based on implant location [3]. Auclair E, Blondeel P, Del Vecchio DA. Composite breast

augmentation: soft-tissue planning using implants and fat. Plast Reconstr Surg 2013; 132 (3):558–568. (Table 2, p 565)

Fig. 66.13  Spectrum of fat required for coverage of the prosthesis, with different thickness, centered on implant size. This does not take into account the amount of volume that decreases over time [3]. Auclair E, Blondeel P,

Del Vecchio DA.  Composite breast augmentation: soft-­ tissue planning using implants and fat. Plast Reconstr Surg 2013; 132 (3):558–568. (Figure 7, p 567)

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66.6 Operative Procedure

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reduce contour irregularities of the donor site, similar to a rake flattening and “equalizing” a Preoperative markings and technique are shown mound of sand. The fat is collected in a sterile canister, and is in Videos 66.1 and 66.2. A comprehensive history and physical examination must include vol- separated from the tumescent via a gravity techume, nipple height evaluation, level of the nique. No separate washing or centrifuging sysinframammary fold, and any asymmetries of the tem is utilized. After the fat taken from the donor chest wall. The implant sizes are selected based areas is performed, the abdomen and other sites on the Tebbetts/Adams’ “high-five” technique. are once again visualized and palpated to assess The surgeon must remember not to violate the any irregularities. These must be addressed intrabreast mound, as any disturbance of the footprint operatively with equalization or further liposucwill lead to complications of the implant and/or tion. After this is performed, the surgeon then proceeds to the breasts. breast itself. A 4  cm inframammary incision is placed General anesthesia is commonly adminiswithin each fold, and a subfascial dissection is tered; however local anesthesia cases may be perundertaken. The amount of dissection is based on formed with a subglandular or subfascial approach (breast augmentation under local anes- preoperative markings and breast implant shape thesia, or BALA). The tumescent solution is pre- and base diameter. This plane should be bloodpared based on the surgeon preference and type less secondary to the tumescent fluid infiltrated. of anesthesia; however the senior author prefers After both breasts are dissected, the fat is injected to use epinephrine alone in general anesthesia prior to placement of the prosthesis in order to cases. Since lidocaine does not offer any long-­ prevent any inadvertent implant penetration; term postoperative analgesic effect based on pre- however injection after implant placement can be vious studies, this eliminates any concerns for performed safely, especially with a submuscular implant. The fat is placed most commonly in the lidocaine toxicity [16]. Simultaneous separation tumescence (SST) is superomedial transition zones in the subcutaneutilized to infiltrate all donor sites based on the ous plane to enhance cleavage gap. The senior amount of fat that is needed [17–19]. This tech- author utilizes a roller pump to directly inject the nique offers a bloodless lipoaspirate with a much fat through a power-assisted device with a flared-­ quicker means of infiltrating relative to a stan- tip cannula instead of a syringe-based method, dard infiltration cannula. The tumescent should similar to an expansion vibration lipofilling be placed in the subglandular plane of the breasts technique. After the fat has been placed in the breasts, the as this will provide a bloodless dissection if this pockets are irrigated with triple-antibiotic soluapproach is utilized for implant placement. A high-definition approach to the donor site(s) tion. The implants are opened and placed in is favored if the patient is a candidate, as this triple-­antibiotic solution, and the 14-point plan is complements the aesthetic results of a composite implemented [20]. A “no-touch” technique is breast augmentation. The author prefers a employed and an implant funnel is utilized for suction-­assisted approach without any adjunctive this purpose. Generally, the implant size ranges ultrasound-based technology for collecting the from 200 to 300 cc; however this can vary based fat. Incisions are placed in the groin creases and on the soft-tissue characteristics of the breast. In in the supraumbilical region for access to the cases of asymmetry, the fat provides a means to breasts. Donor-site deformities will undermine masking the inherent differences of the breasts, any excellent results of the breasts, and thus care and thus similar sized implants are employed, must be taken to avoid these complications. One and implant sizers are not used. Once the implants such way is to utilize SAFELipo, as described by are placed in the breast pockets, the wounds are Wall [18, 19]. Equalization with a flared-tip can- closed with absorbable sutures in a layered fashnula off suction on the power-assisted device will ion, starting from the fascia and ending with the

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skin. Donor sites are dressed with compression garments, and the breasts are left without any garments or bras to avoid pressure on the fat grafts.

66.7 Postoperative Care Composite breast augmentation is a same-day surgery, and patients are discharged the same day. No compression or bra is worn for 3 weeks to maximize fat graft survival. Since the authors prefer a subglandular approach, patients ­generally have a faster recovery and may to return to exercise and heavy lifting after 7–10 days. No drains are placed in either the breasts or the donor site. Pain control postoperatively may be with either a

narcotics or NSAIDs. The pain in the breasts is insignificant as the implants do not violate the breast mound and a subglandular or subfascial dissection is performed. A compression garment is placed on the donor sites. Patient satisfaction is high, as the ideal characteristics of an implant-based approach and fat transfer are combined into one quick, pain-free surgery, which ultimately provides the best of both worlds.

66.8 Case Examples The following are case examples of different ratios (Figs. 66.14a, b, 66.15, 66.16, 66.17, and 66.18): b

Fig. 66.14 (a and b) A 1:2 composite ratio (fat to Rigottomy incisions aid in expanding the lower pole by implant) is shown with preoperative and immediate-on-­ releasing fibrous bands and allowing an increased graft-­ table results. Silicone gel implants placed were 375  cc, to-­capacity ratio with 210  cc of fat on the left and 275  cc on the right.

Fig. 66.15  A 1:1 composite ratio is presented, with preoperative, immediate-on-table, and 3-year postoperative results, respectively. The long-term results demonstrate significant preservation of the fat with improvement of the

cleavage gap. The natural look and feel of a breast with the core volume projection of an implant are obtained (the composite goal)

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Fig. 66.16  Pre- and postoperative results displaying a 2:1 fat-to-implant ratio. A 180 cc implant in the subfascial plane was utilized with 350 cc of fat

Fig. 66.17  Pre- and postoperative outcome of a revision breast surgery with a 1:1 composite breast augmentation. A 38-year-old, mother of two children, complained of an unnatural look with her 275 cc implants. She opted for a larger implant size, and thus 350 cc silicone implants with

350 cc of fat were placed. Despite an increase in size, a more natural look is obtained. The power of a composite technique allows for a larger breast mound without risking an unnatural result. Note the high-definition results of the donor site, which augment the overall outcome

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Fig. 66.18  A 1:1 ratio is shown with a small-framed patient. Here, 400 cc silicone gel implants in the subfascial space were placed with 400 cc of fat overlay. Note the

naturally enhanced transition zones and cleavage gap with the core volume projection of an implant

66.9 Risks, Complications, and Outcomes

At times, an additional round of fat transfer may be necessary in order to fill deficient areas as a result of fat atrophy. Commonly, these patients may be thin with minimal fat reserve, and obtaining fat from previously harvested donor sites may be significantly more challenging, and thus the extremities may be utilized. To avoid this, overgrafting the recipient site during the original operation is recommended; however one must keep in mind the graft-to-capacity ratio. The clinical endpoint should be the aesthetics, rather than the amount placed. The survival of the grafted fat is superior in the composite breast augmentation rather than an isolated fat transfer approach, which is due to the graft-to-capacity ratio [2, 3]. There are less volumetric stresses on the recipient site, which in turn favors a model environment in the composite breast augmentation. The volume of fat does not violate the concept of the graft-to-capacity ratio, and its survival is similar to a two-dimensional skin graft model [3]. The different yet complementary volumetric spacers of both fat and implants allow the surgeon to size and shape breast in a customized fashion that typically is addressed with either a mastopexy or a use of differential implant

Complications, though infrequent, are similar to any primary breast augmentation, and include hematoma, malposition of the implants, and capsular contracture. Implant malposition can be treated with external massage; however if there is no improvement then reoperation will be required. Capsular contracture will require a full capsulectomy and replacement of the implant. The best treatment for capsular contracture is prevention, which includes following the 14-point plan, practicing prospective hemostasis, and adhering to a no-touch technique. To our knowledge, there is no difference in capsular contracture rates in the literature between a standard breast augmentation and the composite breast augmentation. Common donor-site issues include seroma and contour irregularities. Seromas are drained with percutaneous needle aspiration, and small contour irregularities can be treated with aggressive massage. However, if these abnormalities remain greater than 6 months, reoperation may be required with an aggressive equalization technique.

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sizes. One can achieve core volume augmentation with an implant and overlay this with the natural fill of fat. Drawbacks of the composite procedure include a steep learning curve. Unlike implants, fat grafting in the breast is technique dependent, and rates of survival are likely to vary depending on the expertise level and technique utilized by the plastic surgeon. Another fear among the patients and surgeon is the development of benign calcifications, which may arise suspicion on routine imaging. Nonetheless, Cameron et al. had shown composite breast augmentation to be safe and not interfere with interpretation on mammography, and additional studies were not necessary in their average follow-up period of 29 months [7, 21]. Finally, although satisfaction rates are high among patients and surgeons, there have been no objective studies to quantify this claim, and thus this should be addressed in future studies.

66.10 Conclusion The composite breast augmentation is not just implants combined with fat. It represents an answer for patients desiring a natural look and feel of their breasts, but without compromising the core volume projection. The concept exemplifies, at the very least, three major ratio subsets of a 1:2, 1:1, and 2:1 fat-to-implant ratio, all of which seek to achieve different solutions for patients with distinct breast features. The concept will continue to evolve and gain popularity in the future as the demand for robust, yet natural results is desired by patients and surgeons alike. Indications and contraindications of composite breast augmentation Indications Contraindications Wide cleavage gap Personal history of breast cancer Minimal soft-tissue Unwilling to undergo multiple coverage rounds of fat transfer Minimal to no donor fat Desire for simultaneous liposculpture Desire for a natural Unreasonable expectations result with regard to size and shape

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References 1. The Aesthetic Society. Aesthetic Plastic Surgery National Data Bank Statistics, May 2020. 2019. https://www.surgery.org/sites/default/files/Aesthetic-­ Society_Stats2019Book_FINAL.pdf. Accessed 20 Aug 2020. 2. Del Vecchio DA, Del Vecchio SJ. The graft-to-capacity ratio: volumetric planning in large-volume fat transplantation. Plast Reconstr Surg. 2014;133(3):561–9. 3. Auclair E, Blondeel P, Del Vecchio DA.  Composite breast augmentation: soft-tissue planning using implants and fat. Plast Reconstr Surg. 2013;132(3):558–68. 4. Khouri RK, Rigotti G, Cardoso E, Khouri RK Jr, Biggs TM.  Megavolume autologous fat transfer: part I. theory and principles. Plast Reconstr Surg. 2014;133(3):550–7. 5. Khouri RK, Rigotti G, Cardoso E, Khouri RK Jr, Biggs TM.  Megavolume autologous fat transfer: part II. Practice and techniques. Plast Reconstr Surg. 2014;133(6):1369–77. 6. Del Vecchio DA, Bucky LP.  Breast augmentation using preexpansion and autologous fat transplantation: a clinical radiographic study. Plast Reconstr Surg. 2011;127(6):2441–50. 7. Auclair E, Anavekar N. Combined use of implant and fat grafting for breast augmentation. Clin Plast Surg. 2015;42(3):307–14. 8. Kerfant N, Henry AS, Hu W, Marchac A, Auclair E.  Subfascial primary breast augmentation with fat grafting: a review of 156 cases. Plast Reconstr Surg. 2017;139(5):1080e–5e. 9. Del Vecchio DA. “SIEF”—simultaneous implant exchange with fat: a new option in revision breast implant surgery. Plast Reconstr Surg. 2012;130(6):1187–96. 10. Katzel EB, Bucky LP. Fat grafting to the breast: clinical applications and outcomes for reconstructive surgery. Plast Reconstr Surg. 2017;140(5S Advances in Breast Reconstruction):69S–76S. 11. Mallucci P, Branford OA.  Shapes, proportions, and variations in breast aesthetic ideals: the definition of breast beauty, analysis, and surgical practice. Clin Plast Surg. 2015;42(4):451–64. 12. Bravo FG.  Parasternal infiltration composite breast augmentation. Plast Reconstr Surg. 2015;135(4):1010–8. 13. Maione L, Caviggioli F, Vinci V, Lisa A, Barbera F, Siliprandi M, Battistini A, Klinger F, Klinger M. Fat graft in composite breast augmentation with round implants: a new concept for breast reshaping. Aesthet Plast Surg. 2018;42(6):1465–71. 14. Kerfant N, Marchac A, Auclair E. Fat grafting in composite breast augmentation with round implants: a new concept for breast reshaping. Aesthet Plast Surg. 2018; Letter to the Editor 15. Tebbetts JB, Adams WP.  Five critical decisions in breast augmentation using five measurements in 5 minutes: the high five decision support process. Plast Reconstr Surg. 2005;116:2005–16.

1000 16. Danilla S, Fontbona M, de Valdés VD, Dagnino B, Sorolla JP, Israel G, Searle S, Norambuena H, Cabello R. Analgesic efficacy of lidocaine for suction-assisted lipectomy with tumescent technique under general anesthesia: a randomized, double-masked, controlled trial. Plast Reconstr Surg. 2013;132(2):327–32. 17. Del Vecchio D, Wall S Jr. Expansion vibration lipofilling: a new technique in large-volume fat transplantation. Plast Reconstr Surg. 2018;141(5):639e–49e. 18. Wall SW.  SAFE circumferential liposuction with abdominoplasty. Clin Plast Surg. 2010;37:485–501.

O. Chaudhry and D. D. Vecchio 19. Wall SH Jr, Lee MR.  Separation, aspiration, and fat equalization: SAFE liposuction concepts for comprehensive body contouring. Plast Reconstr Surg. 2016;138:1192–201. 20. Deva AK, Adams WP Jr, Vickery K. The role of bacterial biofilms in device-associated infection. Plast Reconstr Surg. 2013;132(5):1319–28. 21. Cameron JA, Auclair E, Nelson M, et al. Radiologic evaluation of women following cosmetic breast augmentation with silicone implants and fat grafting. Plast Reconstr Surg. 2014;134(4 Suppl 1):91–2.

Correction of Severe Congenital Breast Asymmetry in Poland Syndrome and Other Breast Asymmetries with Autologous Microstructural Fat Transfer and the Combination of Other Techniques

67

Gergely Pataki, Máté Jancsó, and Artúr Kalatovics

Key Messages • Breast asymmetry is not just an aesthetic issue. It impacts the psychological quality of life very often, and care providers should be aware of the psychological impairments associated with breast asymmetry and supply proper support. • Autologous lipofilling can be used for the correction of breast asymmetries and associated soft tissue defects of any severity. • Commencing of early reconstruction of asymmetries should be available in teen-age with the definitive recommendation of a psychologist or a psychiatrist. These genetic disorders Supplementary Information The online version contains supplementary material available at (https://doi. org/10.1007/978-­3-­030-­77455-­4_67).

G. Pataki (*) Department of Pediatric Surgery and Traumatology, St. John’s Hospital and North Buda Unified Hospitals, Budapest, Hungary

may affect psychical development, so the surgery should have been considered at a very age already. • In Poland syndrome, abnormalities ranging from unilateral hypoplasia to absence of the breast and pectoral muscle frequently occur in combination with distal hypoplasia of the upper limb and anomalies of the hand. • Since the severity of breast asymmetries (e.g., in Poland syndrome) varies from person to person, the treatment has to be tailor-made as well, based on the patient’s anatomy, age, and wishes. It should be considered that the fat survival rate is higher at a younger age. • In cases of constricted lower pole, tubular deformities, or intraoperative tissue separa-

Premium Plastic Surgery, Budapest, Hungary Department for Plastic Surgery and Burns, Hungarian Defence Forces Medical Centre, Budapest, Hungary

Action for Defenceless People Foundation, Budapest, Hungary

A. Kalatovics Action for Defenceless People Foundation, Budapest, Hungary

Premium Plastic Surgery, Budapest, Hungary e-mail: [email protected]

Premium Plastic Surgery, Budapest, Hungary

M. Jancsó Action for Defenceless People Foundation, Budapest, Hungary

Heim Pál Children’s Hospital, Budapest, Hungary

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_67

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tion, tissue modeling may be performed with special cannulas mounted on the PAL ­(power-­assisted liposuction device with reciprocating vibrating effect) machine. • The precise atraumatic technique at every step of the lipofilling procedure is important for short-, medium-, and long-term fat survival, thus achieving long-lasting results. • With the proper use of autologous fat transplantation and techniques combined the patients’ satisfaction index regarding the breast and their whole body may increase considerably.

67.1 Introduction This chapter aims to present the technique of autologous microstructural fat transfer we can apply in the correction of congenital and post-­ traumatic breast asymmetries. We did not include patients with asymmetries after surgical removal of breast tumors; however, many of the descriptions may be applied in this group as well. The chapter discusses breast asymmetries (e.g., Poland syndrome) in female patients; the reconstruction of the male 1a

2

chest in Poland syndrome and breast asymmetries is focusing mainly on the reconstruction of the pectoral muscle contours and volume, which can be attained with fat grafting as well and is the subject of another chapter. In this chapter, we would like to discuss the treatment of adult and adolescent patients with moderate-to-large congenital breast asymmetry by autologous fat transplantation and combined techniques. Since for breast reconstruction larger volumes are indicated, we suggest that the harvesting of the fat from the donor site is most effectively and atraumatically done by power-­ assisted liposuction with “multihole” cannulas. In cases of constricted lower pole or tubular deformities or intraoperative tissue separation, tissue modeling is performed with special cannulas mounted on the PAL machine (Video 67.1. Operation on Patient 1. Figs.  67.2, 67.3, 67.4, and 67.5). After sedimentation and centrifugation of the fat, it is transferred into the hypoplastic or aplastic breast area with by blunt, thin cannulas with a 3D multilayer technique from various regional entry points (Video 67.2. Operation on 3

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Fig. 67.1  Various morphological features in various ages of amazia complicated with Poland syndrome (complete and partial absence of PM muscles). (1a) 10-year-old girl with unilateral amazia with the absence of pectoral muscles and contralateral tubular developing breast in a clinical picture of Poland syndrome. (1b) Abnormalities of the hands (e.g., hypoplasia) are often associated. (2) 12-yearold adolescent female with right-sided unilateral amazia and partial absence of pectoralis and trapezius muscles

and normal-developing left breast due to Poland syndrome. (3) 14-year-old adolescent female with unilateral amazia, absence of pectoralis muscles, and contralateral tubularity and ptosis due to Poland syndrome. (3) 16-yearold adolescent female with unilateral amazia which refers to the absence of one mammary gland but the nipples remain present (the partial absence of the pectoralis muscle in the malformation defines Poland syndrome, too)

67  Correction of Severe Congenital Breast Asymmetry in Poland Syndrome and Other Breast…

Fig. 67.2  (Patient 1, first comparison) First row: 16-yearold adolescent female, 50 kg, complete unilateral (right) amazia (MRI proven no gland at all), with partial PM absence—contralateral tubular breast with hypertrophy and ptosis (in the frame of Poland syndrome). Second row: Post-operative photos after 1 year after the multi-

Fig. 67.3  (Patient 1) (1) Pre-operative external vacuuming with Brava®. (2) Pre-operative markings of liposuction areas and pattern of symmetrization mastopexy (left). (3) Liposuction from the thighs with PAL. (4, 5) With the use of PAL we performed intraoperative closed skin envelop and connective tissue dilatation (tissue “manipulation”) with special designed reciprocating vibrating cannula (mounted on PAL) (Also on Video 67.1). (6) Preparation: filtering of the fat. (7) Preparation: manual centrifugating and decanting of the fat. (8) Post-op vacuuming of the fat-grafted breast (Video of Fat grafting in Video 67.2 of Patient 1)

1

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staged external vacuuming (pre-operative and post-operative expansion) and two stages of lipofilling (505 cc and 450 cc, early regrafting) and closed intraoperative tissue dilatation (tissue “manipulation”) of the recipient site (restructuring before lipofilling) with PAL machine (also on Video 67.1 and 67.2 of Patient 1)

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Fig. 67.4 (Patient 1, second comparison) First row: 16-year-old adolescent female, complete unilateral (right) amazia (MRI proven no gland at all), with partial PM absence—contralateral tubular breast with hypertrophy and ptosis (in the frame of Poland syndrome). Second row: Post-operative photos 5 years after the beginning of

the multi-staged external vacuuming (Pre-operative and post-operative expansion) and three stages of lipofilling (505  cc, 450  cc, and 250  cc) and liporestructuring with immediate tissue expansion with PAL and contralateral mastopexy (the mastopexy overcorrected the position of the breast, to allow further descent)

Pre-operative 3D reconstruction 1

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Fig. 67.5  (Patient 1) 3D reconstructions based on the MRI scans pre-operative and 4 years later. MRI showing excellent take of transplanted fat tissue. (1) Virtual surface 3D reconstruction model of pre-op status. (2) Virtual surface 3D reconstruction model of status after three stages

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of operations. (3–6) The correlating MRI sections of the surface models with the visibility of the fat as white hyperintensity in contrast to normal glandular parenchyma contralateral (by courtesy of Dr. Kálmán Czeibert)

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Fig. 67.6  (Patient 2) 16-year-old young lady with unilateral glandular hypoplasia (in lower pole) with moderate tubular breast anatomy with high original submammary fold. Therapy: Autologous microstructural lipofilling

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Fig. 67.7  (Patient 2) The picture shows a hypoplastic lower pole with an undefined inframammary crease. The most difficult part of the operation is to create the neosubmammary fold and a natural shaped lower pole. (1 and 2) Represent pre-operative drawing around the undevel-

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(plan: megadose single-step therapy with 450 cc) and at 3 years refinement with 100 ccs. First row: Pre-operative pictures. Second row: Post-operative photos 5 years after

5

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oped lower pole from two sides. (3 and 4) Intraoperative photos of lipofilling of the lower pole. (5) Pre-operative photo. (6) Post-operative photo with normalized lower pole and lowered submammary fold. Arrows show the desired anatomical position of the fold

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Patient 1. Figs. 67.2, 67.3, 67.4, and 67.5). The viability and high survival rate of the fat are ensured by a tissue-friendly technique.

67.2 Breast Asymmetry The body structure of most animals, including humans, exhibits mirror symmetry, also called bilateral symmetry. Symmetry is always relative in life. Most mature women have some degree of breast asymmetry. Breast asymmetry is a common presenting complaint among adolescents. In developed countries with a sufficient network of plastic surgeons, patients usually turn to the plastic surgeon with at least a 25–30% difference, and a 30% difference between the two breasts is the limit where a symmetrization could be considered without hesitation. Asymmetry may be more pronounced between Tanner stages 2 and 4 when the breast is developing but often improves by Tanner stage 5 [1]. Despite this improvement, many adult women have some degree of breast asymmetry. Other authors believe that over half of the female population would be affected if screened for small deformities. In our clinic, we have observed a 30–40 percent of—usually mild or moderate—breast asymmetry. Breast asymmetry may also result from unilateral limitation of breast growth related to injury of the prepubertal breast (e.g.: trauma, infection, surgery) or abnormality of the rib cage (e.g.: scoliosis) [2].

67.3 Psychological Impacts Breast asymmetry is not just a “simple” aesthetic issue. It affects the psychological quality of life very often, and care providers should be aware of the psychological impairments associated with asymmetry and supply proper support [3]. Asymmetries may have excessive negative physical and psychological impacts during puberty and adulthood.

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67.4 E  arly Breast Developmental Abnormalities with Signs of Asymmetry Accessory breast tissue is present at the time of birth in 1 percent of the population (both males and females) [4]. The terminology for accessory breast tissue depends upon the type of tissue that is present. Polymastia refers to the presence of any accessory breast tissue. Polythelia refers to supernumerary (or accessory) nipples. In most cases, accessory breast tissue consists of a small areola and nipple. However, glandular tissue may also be present. The most common site for polymastia is the lower axilla [5]. Athelia refers to the absence of a nipple. Amastia refers to the absence of breast tissue. This is a rare condition that is thought to occur from the obliteration of the milk line during embryogenesis. When bilateral, it is often associated with other congenital anomalies. Unilateral amastia is one of the manifestations of Poland syndrome [9]. In the case of amastia usually smaller and craniomedially located nipple-areola complex is present. Amazia is the absence of breast tissue when a normal nipple-areola complex is present (Fig. 67.1).

67.5 Asymmetry of the Breasts during Primary and Secondary Breast Development Breast development staging is based upon standards established by Marshall and Tanner [8, 9]. Under the influence of steroid hormones during childhood growth and primary breast development, the breast buds enlarge, and glandular elements appear [10]. Infants of either sex often have transient and asymmetric breast tissue enlargement secondary to perinatal maternal estrogen stimulation; this enlargement may remain for several months before spontaneous regression occurs. Asymmetry of the breasts—that does not need

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Table 67.1  Morphological classification (based on the clinical picture) of congenital female breast asymmetries with unilateral and bilateral hypoplastic breast and combined malformations and suggested possible treatments with autologous microstructural lipofilling (Treatment plan at St. John’n Hospital, Budapest) Classification based on morphology and severity A-1: Mild to significant asymmetry with unilateral hypoplasia (Figs. 67.6 and 67.7) A-2: Mild to significant asymmetry with bilateral hypoplasia B: moderate (hypoplasia, contralateral normotrophy with or without tubularity) (Fig. 67.9)

C-1 severe (hypoplasia, contralateral hypertrophy with tubularity) (Fig. 67.8)

C-2 severe (hypoplasia, bilateral tubularity, contralateral hypertrophy) (Fig. 67.8) C-3: Very severe (aplasia) (Figs. 67.2, 67.3, 67.4, and 67.5)

Diagnosis Unilateral tubular or nontubular glandular hypoplasia without concurrent ptosis Asymmetrical bilateral tubular or nontubular hypoplasia without concurrent ptosis Moderate asymmetric bilateral glandular hypoplasia with contralateral tubular breast with ptosis or unilateral hypoplasia with contralateral normotrophic ptosis and tubularity Severe unilateral glandular hypoplasia with contralateral hypertrophic tubular breast with ptosis

Bilateral tubular breast with one-sided hypertrophy and ptosis and one-sided hypotrophy Complete (severe) unilateral amastia, contralateral tubular breast with hypertrophy and ptosis (e.g., Poland syndrome)

Alternative therapy with composite breast Suggested therapy involving augmentation (lipofilling autologous microstructural and cohesive silicone implant) lipofilling Not suggested Aut. Microstructural lipofilling (plan: Megadose lipofilling in single-step therapy or multi-staged lipofilling)

Alternative to these operative therapies Implants and regional muscle and perforator fasciocutaneous flaps

Suggested if smaller, different sized implants are acceptable (with lipofilling the gap between the different sizes may be lessened) Possible (implant and aut. Microstructural lipofilling to the hypotrophic side and correction of normotrophic tubular breast in the same sitting with implant, mastopexy and lipofilling (Singlestep therapy or multi-staged lipofilling))

Implants alone without lipofilling

Aut. Microstructural lipofilling and correction of tubular breast in the same sitting (plan: Megadose lipofilling single-step therapy or multi-staged lipofilling; tubular breast correction: Mastopexy or reduction mastopexy and internal tissue manipulation) Uni- or bilateral mastopexy and contralateral microstructural aut. Lipofilling

Possible

Implants, expanders, flaps with mastopexy

Possible

Implants, expander, flaps with mastopexy

Multi-staged external vacuuming multi-staged aut. Microstructural lipofilling, liporestructuring, intraoperative tissue expansion, and multi-staged correction of ptosis with reduction mastopexy

Possible

Flaps, expanders, implants, and mastopexy

Aut. Microstructural lipofilling (plan: Megadose lipofilling in single-step therapy or multi-staged lipofilling) Aut. Microstructural lipofilling and correction of tubular, ptotic breast in the same sitting (plan: Lipofilling with single-­step therapy or multi-staged lipofilling; tubular breast correction: Mastopexy and internal tissue manipulation)

Implants, flaps with mastopexy

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surgical therapy—may have other reasons during secondary breast development. Both males and females may experience the development of a firm and often tender-to-­touch unilateral or bilateral subareolar nodule sometime in early adolescence. This could be part of the developmental pattern of adolescent male gynecomastia or in girls, puberty-induced hormone-influenced mammary gland alterations and asymmetries.

67.6 Manifested Clinical Composition, Combination, and Setup of Asymmetries of the Breasts of Adolescents and Adults The most common asymmetries of the breasts consist of the combination of bilateral or unilateral hypoplasia, hypertrophy, ptosis, tuberous breasts, or amastia of various degrees. Amastia is discussed above. Hypoplasia is the underdevelopment of the breast. Unilateral hypoplasia may be accompanied by a normal, hypoplastic, or hyperplastic contralateral breast. A severe form of it is amazia which usually presents as a component of a development syndrome and can be diagnosed during infancy or at the beginning of puberty [11]. These anomalies are amenable to reconstructive procedures [1, 2]. The most severe of these deformities, amastia or severe unilateral hypoplasia, is associated with hypoplasia of the pectoral muscle in 90 percent of cases. However, the reverse does not apply; in women with pectoral muscle abnormalities, 92 percent have a normal breast [12]. In Poland syndrome, abnormalities ranging from unilateral hypoplasia to absence of the breast and pectoral muscle frequently occur in combination with distal hypoplasia of the upper limb and anomalies of the hand (syndactyly, brachydactyly, oligodactyly) [2, 13, 14]. These anomalies may result from diminished blood flow in the underdeveloped or obliterated subclavian artery during early fetal development [15]. Tuberous breast is common in breast asymmetries. The available surgical options vary depending on the anatomy of the hypoplastic breast tissue and the overdeveloped nipple and areola. Fat grafting as a single or part

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of a combined operation is a reliable technique that produces excellent results and high levels of patient satisfaction [16]. Juvenile breast hypertrophy (also called virginal breast hypertrophy and macromastia) refers to a spontaneous overgrowth of breast tissue. It is rare, and unilateral features may be part of the congenital asymmetry. The overgrowth may be unilateral or symmetric (more common) and begins around menarche. A combination of amastia or amazia and juvenile breast hypertrophy is the most severe and rarest form of asymmetries (Figs. 67.1, 67.2, 67.3, 67.4, and 67.5). Poland syndrome—named after Sir Alfred Poland (1822–1872), a nineteenth-century British surgeon—is a well-researched breast abnormality with asymmetries of the chest and breasts. It is also known as Poland sequence; it occurs in 1/10,000 to 1/100,000 live births and encompasses a constellation of abnormalities [8]. It is mainly characterized by partial (28 percent) or complete (72 percent) absence of the major and minor pectoral muscles, most commonly unilateral (93 percent) [8]. Associated anomalies may include aplasia or hypoplasia of other chest wall muscles, breast tissue, nipple, absence of the costal cartilages of ribs 2 to 4 or 3 to 5, high-­riding scapula (Sprengel’s deformity), and uncommonly digital abnormalities (e.g., brachydactyly, syndactyly) [3, 8, 9]. Abnormalities of the pectoralis major muscle and hands (e.g., hypoplasia, syndactyly) are often associated (Fig. 67.1).

67.7 Presentation and Evaluation of Chest and Breast in Asymmetry The chest examination begins with careful observation and inspection of the chest wall. Chest shape, width, height, protruding ribs, sternum width, pectoral muscles’ anatomy with origin and insertion variations, soft tissue coverage, and skin laxity are observed and described. The thoracal osseous and cartilaginous components (e.g., the width of the ribs and length of the sternum) have a determining effect on the breast and its symmetry development. An asymmetrical chest wall and consequent moderate-to-severe breast asymmetry

67  Correction of Severe Congenital Breast Asymmetry in Poland Syndrome and Other Breast…

may occur because of scoliosis or an underlying cardiac disease that creates a precordial bulge. We check the breasts from five different angles in a standing position and a lying position (sixth position), and observe them in slightly leaning forward and backward positions. The looseness of the presternal tissue may be checked by a pinch test; this feature is informative when grafting fat into the inner poles around the midline. The transverse diameter of the chest, base widths of the breasts, the position of the mammillae, nipple shape, color and size, nipple-jugulum distance, and nipple-submammary fold distance are measured. Nipple alignment and distance between nipples should be noted. This could be the very first sign in early detection of a child with possible Poland syndrome. The presence of accessory nipples and nipple discharge should be noted. NA complex dystopia should be evaluated for multistaged reconstruction. Accessory nipples along the milk line are common. Surrounding structures of the thorax, e.g., arm lengths and shoulders, should be examined. According to our observation, various degrees of pectus excavatum (funnel chest) or pectus carinatum (pigeon breast) are common in patients with severe breast asymmetries including Poland syndrome. In Poland syndrome besides syndactyly and ipsilateral absence of the sternal head of the pectoralis major muscle, we may find various types of asymmetrical chest wall with a frontal positional asymmetry of the nipple position (craniomedial dislocation). Unique anatomy should be highlighted via CT or MRI before planning operations which is more effective with the instruments of modern diagnostics. CT will give more information about the osseous structure anomalies whereas MRI of the soft tissues, e.g., the density of glandular tissue and fat distribution, is the most suitable (and quantifying form) for follow-ups after surgery. 3D modeling can be applied with both CT and MRI (e.g.: Fig. 67.5 (Patient 1)).

67.8 Diagnosis The severity of breast asymmetries including Poland syndrome is unique in every patient. Mild cases may not be diagnosed or reported, because

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patients do not realize that they have the condition until puberty when the visible asymmetrical growth begins. During the examination, the stage of breast development, pectoral muscles, and the latissimus dorsi should be noted. Ruling out other problems, e.g., Moebius syndrome, may be needed by performing more examinations. According to McGrath and Mukerji, in a series of 49 female patients with severe developmental breast asymmetry, Poland syndrome and isolated unilateral hypoplasia were the most frequent etiological factor (69%). If the asymmetry is due to Poland syndrome, additional deformities may be present including the absence of the sternal head of the pectoralis major muscle and hand deformities [17]. The Foucras classification (I-III) of Poland syndrome describes morphological aspects of severity from mild asymmetry to aplasia. For diagnosis of various congenital breast asymmetries, we use a more morphological classification (based on the clinical picture) of breast asymmetries with unilateral and bilateral hypoplastic breasts including and describing contralateral malformations (for the Treatment plan at St. John’s Hospital, Budapest, see Table 67.1).

67.9 Various Treatments and Scientific Evidence of the Treatment with Autologous Fat Grafting Since the severity of congenital and non-­congenital breast asymmetries (e.g., Poland syndrome) varies from person to person, the treatment has to be tailor-made as well, based on the patient’s anatomy, age, and wishes. Hand reconstructions, e.g., in the case of syndactyly, should be started as early as possible in the first year of life. Whether in children, adolescents, or adults rare severe chest wall deformities (e.g., absence of series of ribs) should be treated with priority. The surgical treatment may consist of breast augmentation and symmetrization with implants and/or fat grafting, and/or flap surgery (from latissimus dorsi). Given our results and reports of other plastic surgeons, free fat grafting should be considered as an alternative or adjunct to classic breast augmentation and reconstruction procedures [18]. The results of treating young

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patients with breast hypoplasia with lipofilling after being very encouraging for decades are now becoming standard. It is an alternative of choice for the correction of young women’s breast deformities if the avoidance of scarring is preferred [19]. It is a simple, fast, and effective treatment option with

few complications [20]. Besides the literature sources, we necessarily point out that autologous fat grafting is the method of the fifth pillar of plastic surgery: regenerative medicine; therefore any such surgery should be performed only by qualified plastic surgeons (Tables 67.2, 67.3, and 67.4).

Table 67.2  Scheme of treatment of the affected breast in Poland syndrome

Severity/ Treatment Severe hypoplasia

Moderate hypoplasia Normotrophia but dystopic NAC

Treatment of the affected breast with conservative methods Tissue expander and implant

Cohesive silicone implant Round block mastopexy

Treatment of the affected breast with aut. lipofilling methods Multi-staged external vacuuming, multi-staged aut. Microstructural lipofilling, liporestructuring, intraoperative tissue expansion

Single-staged aut. Microstructural lipofilling Aut. Microstructural lipofilling, intraoperative tissue modeling

Treatment of the affected ribs, ribcage, muscle Treatment of the affected contours, sternal breast with implant and defect with aut. lipofilling aut. lipofilling method Possible Composite breast (E. g.: augmentation and Treatment of restructuring the hypoplastic pectoralis major muscle defect and contour deformity with autologous fat) Composite breast – augmentation – Aut. Microstructural lipofilling, intraoperative tissue modeling, and round block mastopexy

Treatment of the hypoplastic pectoralis major muscle defect and contour deformity Table 67.3  Scheme of treatment of the unaffected, contralateral breast in Poland syndrome Hypotrophic

Treatment of the unaffected breast Cohesive silicone implant

Hypertrophic Ptotic

Reduction mammaplasty Mastopexy

Treatment of the unaffected breast with fat Single-staged aut. microstructural lipofilling Only scar treatment with fat Only scar treatment with fat

Table 67.4  Treatment of the hypoplastic pectoralis major muscle defect and contour deformity

Mild hypoplasia Severe hypoplasia

Treatment of the hypoplastic pectoralis major muscle defect and contour deformity with conventional method No. Only treatment of the breast suggested Latissimus dorsi flap

Treatment of the hypoplastic pectoralis major muscle defect and contour deformity with lipofilling No. Only treatment of the breast suggested Single- or multi-staged autologous microstructural lipofilling

Treatment of the hypoplastic pectoralis major muscle defect and contour deformity with composite methods No Flap or implant and single- or multi-staged autologous microstructural lipofilling

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67.10 Pre-operative Planning and Consenting Patients with Poland syndrome or severe breast asymmetry (or the parents if the patient is underage) are asked to sign a detailed informed c­ onsent on the goals of the surgery, operative technique, surgical risks, and potential complications when they are ready for the breast reconstruction with the use of fat transfer. The weight of the patient must be stable at the time of surgery. The areas on the breast or chest that are to be treated are evaluated and marked in a standing position. Our first choice for the donor area for liposuction is abdominal and lumbar fat because it is appreciated by patients and there is no need to change position during surgery. Our second choices are the frontal, outer, and inner parts of the thighs and knees, rarely the lower leg. Photographic documentation is made before and after the markings as well.

67.10.1  Photo and Video Documentation Photographic documentation is made from the body with a focus on the chest (all areas to be treated) before and after marking as well. Seven angles are suggested (frontal, superior frontal from 45 degrees to vertical plane, inferior frontal from 45 degrees to vertical plane (sometimes only in laying position feasible), left oblique, right oblique, left lateral, right lateral). The picture focus should be set on the affected breast contour deformity. The photo is oblong with a longer vertical extent where the captured anatomy should be from the mandibular line (chin) to the superior anterior iliac spines if possible. Taking frontal photographs with proper light is an important key to documenting the patient’s asymmetry, contour deformity, and its shadows even give us an impression of the approximate projection of the breasts. We suggest making one series of photos with flash (possibly ring flash) and one without flash with natural-light conditions. Besides native patient pre-op-post-op pictures photographic docu-

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mentation of markings is very important for future comparisons and evaluation of improvements. Additional markings (with photodocumentaries) can be made when pulling and pressing the affected breast (Video 67.3). Video documentation should continuously involve the angles used in the native photodocumentaries and ask the patient for dynamic alteration of the position of the affected chest region (e.g., the elevation of arms, or flexing muscles).

67.10.2  Anesthesia and Pre-operative Antibacterial Shower and Prophylactic Medication Most patients are operated on under general anesthesia in ITN; longer elastic tubes and intubation are preferred to laryngeal masks. We recommend a pre-operative antibacterial shower a few hours before surgery, usually in the hospital. Usual prophylactic LMWH (Low Molecular Weight Heparin) and antibiotic administration are done perioperatively in adults and adolescents as well.

67.10.3  Positioning of the Patient and Disinfection As these operations for the correction of breast asymmetries, e.g., Poland syndrome, are long or very long, preventive measures are taken by adequate cushioning to prevent decubitus ulcers. Usually, the fat deposits of the abdomen, flanks, and anterior thighs but also the hips, posterior thighs, or lower part of the buttocks can be reached in a supine position; therefore, the patients are positioned this way. The patient is positioned in a supine position; for disinfection of the chest and donor areas we use efficient alcohol-based broad-­spectrum disinfection (e.g., Kodan (from Schülke); 100 g solution contains the following active ingredients: 25  g ethanol (94% w/w), 35 g propan-1-ol) solution. Colored disinfectants are preferred; we see the borders of our working field better and they do not disturb the proper evaluation of the surfaces. Instead of

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small pieces of gauze, a larger sterile sponge is recommended for disinfecting the skin.

67.10.4  I ncisions, Entry Points, and Tumescent Infiltration Incisions are marked with crosses (where the longer line represents the direction of the incision) on the skin with a preferably sterile singleuse skin marker before the operation in a standing position before the disinfection and sterile singleuse marker after the disinfection of the patient in a lying position. In general anesthesia, local anesthetics (lidocaine, xylocaine, prilocaine, or procaine) with adrenaline is given in a very small amount, with a short needle (e.g., 27 gauge) mounted on a 2 ml Luer-Lock syringe before the incisions to the entry points to cause vasoconstriction and prevent disturbing skin bleeding when penetrating with the cannulas. Incisions are made in the skin following the marked “cross” near the marked fat deposits with the tip of a No. 15 blade or a larger needle (e.g., 18 gauge). The whole donor area is infiltrated with a modified Klein solution to reach tumescent infiltration. For more information, please see chapter “Parry-­ Romberg Syndrome Treatment with Microstructural Fat Grafting of the Face” by Pataki et al. For infiltration, 20–40  cm blunt-tip, multihole infiltration cannulas can be used (e.g., Tumescent Infiltrator SuperLuerLok 2.1  mm  ×  20  cm, Tulip Medical Systems, San Diego, CA, USA). After infiltration of a tumescent solution, 10–15 min is required to diffuse into the tissues (intercellular spaces), causing vasoconstriction to reduce the risk of hematoma and allowing the harvester cannula to glide smoothly gaining accurate-size viable micrografts.

as breast symmetrization during the first procedure (e.g. mastopexy) on the opposite, non-aplasia- or hypoplasia-­affected side. The aspiration cannula has a diameter of 2.1–4  mm, with an atraumatic blunt tip that can be passed through a 3  mm incision (3  mm incision elastically dilatates to even pass 4 mm multihole cannulas.) The blunt-tip cannula is easy to navigate through fat and connective tissue and remove fat while still maintaining the integrity of adjacent soft tissue structures minimizing collateral tissue laceration and more serious damage. The aspiration cannula should be a multihole or multiport cannula with lateral holes of 0.5–1 mm to enable microstructural tissue to be gained from the donor area.

67.11.1  Manual Aspiration There are two groups of cannulas: aggressive and less aggressive multihole or multiport harvesters. For normal tissues, we suggest a less aggressive multiport harvester with beveled micro ports. The fat cell bucket can sit inside the pre-sunken holes. The 12 or 20 port-configured harvesters allow gentle, yet very efficient harvesting.

67.11.2  L  ength, Hole (micro Port) Construction, Number of Holes

The length of the cannula is the surgeon’s choice. In manual liposuction, we usually use 20 cm long multihole cannulas (e.g., Sorensen Harvester SuperLuerLok 2.4  mm  ×  20  cm, Tulip Medical Systems, San Diego, CA, USA). Sorensen Harvester with 1 mm micro ports is used to harvest tissue that is compatible with 1.6–1.8-2.1 microinjectors: Alternatively, Miller Speed Harvester 2.1 mm × 15 cm or Carraway Harvester 2.4  mm x 15  cm (Tulip Medical Systems, San 67.11 Aspiration Diego, CA, USA) can be used, too. The number The precise atraumatic technique at every step of of lateral openings on multihole harvesting canthe procedure is important for short-, medium-, nulas is individually defined by each producer and long-term fat survival, thus achieving long-­ company. Usually, 20 holes are enough to build lasting results [22]. Timing of aspiration: Mostly up a constantly decreasing negative suction in the the first procedure of often, in the case of severe cannula to maintain a cell-friendly, atraumatic symmetry, the aspiration is done at the same time environment during the suction and transport of

67  Correction of Severe Congenital Breast Asymmetry in Poland Syndrome and Other Breast…

the fat and adjacent cells. For non-normal tissue, for harvesting through fibrous tissue, we recommend effective multiport harvesters with elevated sharp micro ports (spikes). The 12 or 20 port-­ configuration allows for efficient harvesting both on the forward and backward strokes (e.g.: Tonnard Harvester). Port configuration here goes by the length of the instrument: 15 cm or less has 12 ports, and 20 cm or more has 20 ports. As a special consideration, such a cannula (e.g.: Tonnard Harvester, 2.1  mm) could be defined as a tubular multiscalpel that works with easy suction or vacuum; the cutting edge of the holes facilitate the splitting and rolling of the tissue into micrografts that are presented at the holes. Suction can be aided by external compression of the fingers pushing the adipose tissue into the holes. According to our clinical observation, micrografts obtained with this method also have an excellent survival rate, sometimes surpassing those obtained with other less traumatic liposuction cannulas. The reason may be better activation of cells, through adequate trauma. Technical aspects: Cleaning of the reusable harvester cannulas and filler cannulas with high-­ pressure airbrush is mandatory for the best sterility and safety.

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ual techniques can reduce fat trauma but also the volume that is gained (yielded). Negative suction is applied to the syringe by semi-tensioning (to 50% of maximum depth) the pulley of the syringe with by hand (e.g., hypothenar) or using a special locking device like “Johnny Lock” from Tulip. Alternatively, central suction or suction from a negative suction device (suction-­ generating source or traditional pump suction functioning at −350 and −700 mmHg) could be applied as well. In this case, a special syringe is mounted to the suction cannula. It is mandatory to adjust the suction power of such instruments to low suction (350  mmHg) in case of performing lipotransfer [23].

67.12 Power-Assisted Liposuction

The vibrating cannula moved by a quiet electric source at modern power-assisted liposuction reciprocates at 2000–4000 cpm with a 2–3 mm stroke and is easy to use in young patients. The speed of cannula movement can be adjusted according to the plastic surgeon’s preference. Used non-aggressively, PAL is a gentle, less traumatic form of suction lipoplasty and has advantages in large-volume fat grafting. PAL results in inherent skin contraction following adipose aspiration. Mounting a spe67.11.3  Manual of Fat Aspiration cial multihole cannula with 1-1,9 mm side holes, the gained fat can be used for breast fat grafting. Aspiration is either done manually (below 150 Harvesting cannulas are well suited for producing ccs) or if a larger volume is needed machine-­ small, consistent lobules for fat grafting. assisted with PAL (power-assisted liposuction— The multihole harvesting cannulas to be used MicroAire Surgical Instruments, Charlottesville, with PAL (e.g., Harvesting cannula of Microaire, VA, USA). Manual aspiration is done using a 10 Graph 67.1) enable 360° of extraction, are nonagor 20  ml Luer-Lock syringe adapted on the gressive, are excellent for removing fat of low­contralateral Luer-Lock or Super Luer-Lock can- volume and high-­ volume aspirations, produce nula (e.g., Tulip) and is done with a medium-pace, small lobules for small-volume grafting, and are intermitting movements. To create negative pres- also ideal for fine sculpting of the recipient and sure, the plunger of the syringe is pulled back just donor areas (multi-­ use MicroAire harvesting a few millimeters to create enough vacuum to har- cannulas: Diameter 3.0 mm, length: 15, 22, and vest fat while avoiding the excessive pressure that 30 cm, port diameter: 1.9 mm). could rupture fat cells. The amount of harvested fat depends on the planned procedure. Before the harvesting process, we may create several pretunnels using the blunt cannula without negative aspiration. A 15–20-min waiting period is allowed Graph 67.1  Schematic drawing of a multihole harvestbefore the beginning of the fat harvest. Slow man- ing cannula of MicroAire® to be used with PAL

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With a special adapter, any manual harvesting cannula (e.g., from Tulip Medical Systems) can be used on top of a power-assisted liposuction machine. For more information please see Fig. 58.5, Sects. 58.4.2.4 and 58.4.2.5 “Liposuction Using PAL from the Waist Area” in the chapter “ParryRomberg Syndrome Treatment with Microstructural Fat Grafting of the Face” by Pataki et al.

67.14 Fat Preparation

The process of how the fat is being refined varies between individual surgeons; many centrifuge fat whereas others do not. The evidence that supports centrifuging of the fat is not strong, but despite the lack of evidence, most surgeons do centrifuge, hoping that the concentrated adipocytes have a better survival rate. After aspiration, before centrifuging we allow the fat to decant in bigger syringes (20–50 ml) or special containers 67.13 Volume of Aspiration (Lipofilter, MicroAire) for some minutes. Then we prepare the syringes for centrifugation: the One should be aware that the amount of aspirated syringes are capped and centrifuged in a set of fat has to be more than needed to compensate for 2-4-6 for 20 seconds to 2 min at 3000 rpm. This the loss during decantation and/or centrifugation gravitational force is advantageous for condensand the loss after transfer. For the correction of ing the fat to improve long-term viability and severe unilateral hypoplasia (in a severe asymme- concentrate growth factors. Machine centrifugatry) we need large-volume fat from 300 to even tion allows the formation of three phases in the 600 cc-s. This normally can be achieved with the syringe, the top layer containing oil from cellular help of PAL or similar motor-aided suction lysis, the bottom aqueous layer containing blood devices within 30 minutes to one hour, depending and infiltration solution, and the central layer on the patient’s tissues. Incisions are closed with containing purified fat, the useful part of the aspia thin 6/0 Prolene, or fast-resorbable synthetic rate. The central layer is transferred, and the othsuture or 5/0 Monocryl. ers are drained and discarded [18, 21]. This central layer has graded densities of the fat, and the highest density fat remains at the bottom of 67.13.1  Post-operative Care the 10  mL syringes. Studies have shown better of the Donor Site graft take for high-density fat compared with and Recipient Site low-density fat [5]. Therefore, when transferring fat from the 10 to 1  mL injection syringes, the To prevent hematoma and seroma, a liposuction injection syringes can be grouped into high dencompression garment is applied to the donor sity, intermediate density, and low density to area. Semi-sitting position and intermittent cool allow for more thoughtful placement. In many compresses are advised to decrease the amount cases, manual centrifugation or decantation alone of edema in the treated area; massage should be can be used, too (Video 67.3). When using volavoided for 10 days. Taping and a special light umes exceeding 100 ccs many prefer to decant compression bandage to the breasts can be the fat material without any filtering or transfer to applied, but usually not necessary. Massage and a centrifuge. This method is leaving the 10  mL touching should be avoided for 14 days. Broad-­ (or 20 mL) syringes in a vertically standing posispectrum antibiotics are given for 5  days, and tion for 10–20 minutes, then draining the bottom anti-inflammatory drugs are given for 7–14 days. layer (blood and tumescent fluid), and then transOxygen is given from a nasal conductor for ferring the fat from the syringes to 1 ml (or 2 ml) 24 hours to enhance take rate and neoangiogen- Luer-­Lock syringes through a Luer-Lock transfer esis. Adequate fluid volume management has to hub or “T” adapter (various available). Also, a be calculated to compensate for extravasation to larger volume Puregraft system (Cytori, USA) the interstitial wound surface. 24-hour intensive can be used for fat preparation. Some plastic surcare management can be indicated. geons use sterilized metal tea filtering devices

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be a problem for cannula movement. In this case, we apply more controlled power, bigger (thicker) injection cannulas, or slightly changed directions. We should avoid breaking the cannulas or causing pneumothorax by injury. One may be very quick and at the same time very precise with these movements; it depends on the learning curve. There is a long learning curve to reach harmony between tissue-friendly techniques and 67.15 Fat Transplantation speed, which is also necessary to transplant bigFat transfer is done directly with 2–5 ml syringes ger volumes. In the first sessions at Poland synspecifically adapted with a 1.6–1.8 or 2.1-mm-­ drome or severe breast asymmetry, we try to put diameter cannula. Larger syringes or cannulas do as much fat into the breast as possible but never oversaturate it. At the last expected session, we not perform better in the means of take rate. Multiple incisions can be made with an have to overcorrect the treated area because fat 18-gauge sharp needle or the tip of a No. 15 blade: resorption is to be expected. Saturation is when the skin is still elastic with an intact blood supply • 2–4 of them in the inframammary fold are and the injected fat is not leaving the incision made on the breast. points. Puncture wounds are treated with nano• 1–2 at the medial and lateral border of the are- fat, and then closed with 6/0 Prolene or Steriola in the mammilla level (if NAC is present). Strip. Once saturation is attained, there is no • 1 around the suspected anterior axillary line or benefit of further continuing transferring fat, as it edge of the serratus anterior muscle. leads to complications such as aseptic fat necro• Additional incisions can be made anywhere if sis. Another session could be planned at least necessary but preferably not in the upper three months later. medial quadrant of the breast. To reach this area by lipofilling longer injection cannulas are suggested. 67.15.1  Timing to Perform and saline for preparing fat for treating breast hypoplasia and asymmetry; this open technique, however, should be avoided because of sterility problems in the open air. The authors of this chapter in his practice have experienced good results with all techniques described above.

The principle of fat transfer into the breast or chest soft tissue in Poland syndrome is 3D architectural multilevel and multidirectional ­ sculpturing of the breast (Video 67.2). We never transplant fat in bolus, but it is like planting seeds in the soil. Fat grafting is done from a deep to a superficial plane to achieve a three-dimensional pattern. The cannula is positioned into the hole and pushed inside to create a tunnel in the external soft tissues of the chest wall site of the breast to be created. While the cannula is gently withdrawn, transfer from the syringe and the cannula is done under low-pressure leaving a fine cylinder of fat resembling a chain. With these movements, partial fasciotomies and rupture of constricted bands can be attained as well, contributing to the formation of a normal-looking breast after volumetrization. Constriction bands and internal breast fascia may

Lipofilling or to Start the Multi-staged Operations

According to most of the older recommendations, breast reconstruction in Poland syndrome and other breast asymmetries should be performed only after full breast development. The American Academy of Pediatrics Bright Futures guidelines suggest that the breasts be assessed for sexual maturity rating between the ages of 11 and 20 years; clinical breast examination becomes routine after the age of 20 years [6, 7]. Clinical breast examination allows the clinician to identify abnormalities or asymmetries that the adolescent may have been reluctant to mention. In appropriate patients with the desire for breast surgery, breast surgery should occur after full growth is attained. Especially in the case of severe breast asymmetries—on the other hand—with the recent development of the internet and mass media we may

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observe that often adolescents search for surgical solutions at an earlier age with or without their parents. The adolescent age is the most significant stage of the psychosexual development of a child and the formation of definitive body perception; therefore the first operation or the beginning of a series of operations is justified from earlier than the age of 18. According to our observation, if we wait until 18 or 21 years of age, the psychological damage to the adolescent can be irreversible. In very obvious cases, the fat grafting procedure can be started even at 14 years of age (with parental consent and a psychologist’s recommendation) for optimal results. In rare cases of obvious and verified Poland syndrome and visible maturation of the unilateral breast, supported by cooperative parents, with a help of a pediatric psychologist we may even perform the first sitting of fat grafting at the early age of 11–12 (Fig. 67.12 and Video 67.3). With this early progressive treatment, based on the autoexpansion effects of the transplanted fat with the weight gain during midterm adolescence, probably fewer stages of the series of operations will be needed. Anytime we start with the multistaged procedures, lipofilling can be repeated over multiple sessions to obtain a precise volume of soft tissue augmentation and a long-lasting and natural-­appearing aesthetic outcome. Post-traumatic especially postcombustional breast asymmetries should be treated with lipofilling if the scars are non-active and no other conventional method comes into consideration (Figs. 67.10 and 67.11).

67.15.2  Overcorrection and Multistaging, Secondary Optimizing Sittings, Regrafting, Early Regrafting: Special Considerations Overcorrection of hypoplasia in breast asymmetry in initial procedures is often recommended to compensate for post-operative volume loss and limit the number of successive injections. It is expected that multiple sessions will be needed for larger defects. The volume increase is often lim-

G. Pataki et al.

ited by a patient’s tight skin envelope. Placing extensive, large fat graft volumes into a recipient area is not possible. Patients with severe hypoplasia deformities would require higher fat volumes and often this can only be reached in many sittings. Most volume resorption will be apparent at the 3–4-month post-procedure evaluation, at which time subsequent autologous fat grafting may be performed if there are no external signs of residual post-operative inflammation. Early regrafting is suggested in adolescents and young adults. According to our experience, the hypoplastic underdeveloped breast soft tissue in congenital breast hypoplasia may impose a ­ greater resistance to expansion in contrast to other patients. If expansion is reached correctly, fat grafting and its final take rate in these patients depend on their age, meaning that we can expect better results in adolescents. Special considerations at severe post-­ traumatic breast asymmetries: • Post-traumatic breast asymmetries should be treated with lipofilling once the scars are mature (6–24  months) and no other conventional method comes into consideration (Fig. 67.10). • The symmetrization procedure requires on top of autologous lipofilling closed contracture release, rigottomies, and nanofat grafting (sometimes not only of the chest but also of shoulder regions). The special intraoperative scar release is carried out with special semi-­ blunt-­tip cannulas and performing it correctly requires a long learning curve (Fig. 67.11). • In postcombustional scars of the chest lipofilling into the scar for regeneration purposes may play a more important role than the volumetrizing effect of the fat. • Expanders, flaps, and skin transplants should be used combined with lipofilling. Special considerations in Poland syndrome or severe breast asymmetry: –– Pre-operative evaluation is very important, with quantifying volume differences between the two sides.

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–– Avoid fat grafting close to the midline; one devices (e.g., pre-expansion with BravaTM) may could cause pseudo-symmastia. be recommended for 2–3 months before the oper–– Infiltration of space between pectoralis minor ation and 4 weeks after (Figs. 67.2 and 67.3). The and major with fat if possible (in a non-Poland device delivers a biomechanical stimulation to type of asymmetry). the tissues which may result in a higher take rate –– Pectoralis major (if available) infiltration with and relaxing the skin envelop to enhance the autologous fat is recommended. operation technically. –– Multidirectional and multilevel three-­ Closed intraoperative tissue dilatation (tissue dimensional architectural patterns should be “manipulation”) is a recipient-site restructuring followed during fat transfer. method before lipofilling (Video 67.1, Patient 1). –– In a larger breast, contralateral breast subcutaneIt may be a good aid in tight skin envelops of ous tissues could be considered as a donor site. breast or very constricted lower poles (e.g., com–– Height of mammilla (correction of NAC dys- plete unilateral amastia or amazia) that could topia is one of the most difficult challenges of hardly be treated with other methods. reconstruction). The technique consists of releasing/separating –– Non-violation of the expected submammary constricted tissues (fibers) and preparation of the fold is recommended: in mega-volume graft- recipient site with special blunt PAL (MicroAire) ing, it is difficult to plan the fold. cannulas, mounted on a PAL handpiece using the –– Very thorough planning is necessary with con- reciprocating effect of PAL motors. This techsidering the growing adolescent with the nique is followed by harvesting fat with, e.g., growing chest with the stepwise reconstructed PAL technique with a multihole cannula, and breast. after preparation of the fat then injecting the con–– Weight gain will affect the transplanted fat centrated fat into hypoplastic tissue and contour and its volume in the breast. defects in the same setting. –– A multistage operation might be needed in Additional techniques used in conjunction severe cases. with lipofilling such as flaps (TAP, SIEA DIEP, –– Saturation is seen differently in severe hypo- LD, and gracilis) can be valuable. Medical tattooplasia (more tissue manipulation is needed to ing in cases of missing NAC, camouflaging scars, prolong saturation). or imitating submammary fold or cleavage may –– Before injection, tissue manipulation for intra- be of good additional use. Reduction with round operative dilatation of skin may be necessary. block, vertical or inverted “T”-type mastopexy is –– Pre-operative vacuuming of skin and tissues often an additional procedure of the contralateral may enhance take rate and enable larger side in breast asymmetries with severe unilateral volumes. hypoplasia or aplasia (Figs. 67.2 and 67.8). Last but not least in a frame of a composite breast reconstruction we may combine variously shaped and sized cohesive silicone gel mammary 67.15.3  Additional Techniques implants with autologous lipofilling to correct in Conjunction asymmetric breasts (Fig. 67.9). with the Treatment

of Poland Syndrome or Severe Breast Asymmetry: Suction Devices and Intraoperative Tissue Dilatation (Tissue “Manipulation”)

Multi-staged external vacuuming and pre-operative and/or post-operative expansion with suction

67.15.4  Limitations of Fat Grafting In patients with breast asymmetries grafted fat tissue always undergoes variable rates of post-­ procedure resorption but also significant volume changes (hypertrophies) may occur with extensive weight gain or loss. This may generate

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Fig. 67.8  (Patient 3) 17-year-old young lady with unilateral glandular hypoplasia—contralateral tubular breast with hypertrophy and ptosis. Therapy: Autologous microstructural lipofilling and contralateral mastopexy with

minimal reduction (single-­step therapy). First row: Preoperative pictures. Second row: Post-operative photos 5 years later (after horizontal scar correction)

Fig. 67.9  (Patient 4) 17-year-old female patient featuring unilateral glandular hypoplasia—contralateral tubular breast with normotrophy and ptosis. Operative solution: Combination of conventional options in plastic surgery and autologous (regenerative) method: right breast:

255 cc anatomical textured implant + autologous lipofilling with 990  cc fat; left breast: small round textured 135  cc implant  +  vertical mastopexy. First row: Preoperative pictures. Second row: Post-operative photos 3 years after the combined operation

unpredictable results in the hands of various plastic surgeons as cited widely in the literature. Fat necrosis, ecchymosis, edema, and hematoma can occur too. Patients should know the risks and

potential complications, and sign the appropriate informed consent of the procedure. The necessity for secondary optimizing or complementary or supplementary fat graft sessions affects a decent

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a

b

c

Fig. 67.10  (Patient 5) 16-year-old female patient featuring bilateral scar contractures of the chest and breasts after acquired trauma (deep chest/breast burn at age 5 (II.B)) (a) Pre-operative photo. (b) 1.5-Year post-operative results after symmetrization and closed contracture release, rigottomies, and autologous lipofill-

ing and nanofat grafting of the chest and shoulder regions (with maximum saturation). (c) 3  years post-op after another closed contracture release, rigottomies, and autologous lipofilling and nanofat grafting of the chest and shoulder regions (small corrections) 2  years post-op (4.5 years post-op from the first operation)

percentage of the cases depending on patient factors (i.e., age), individual indication criteria, and adopted surgical techniques. The ideal timing for complementary fat graft sessions varies.

congenital breast asymmetries that were observed from 1998 to 2021. We included only patients in whom lipofilling was fully or at least part of the surgical solution. The patients’ age varied from 11 to 51  years. All patients except one (with Turner Syndrome) were normal chromosomal females (XX). 13 patients had post-traumatic breast asymmetries, all due to burns. All patients were able to present themselves for follow-ups. Fat transfer alone was performed in 43 cases. We combined fat transfer with mastopexy in 62 cases, and with silicone implants in 27 cases. We observed an average of more than 80% fat survival rate, somewhat higher than the proportion mentioned in other studies (60–80%). MRI follow-up helps to assess the survival rate of fat, especially in Poland syndrome (See Fig. 67.5).

67.15.5  Results, Complications, and Complication Management In this chapter, we discussed the treatment of adult and adolescent patients with large congenital and trauma (II.B and III. degree chest burn) related breast asymmetry by autologous fat transplantation and combined techniques. We present the conclusions based on the cases of 144 adult and adolescent patients with moderate and severe

G. Pataki et al.

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a

b

c

d

Fig. 67.11  (Patient 5) Symmetrization and closed contracture release, rigottomies, autologous lipofilling, and nanofat grafting of the chest and shoulder regions (deep chest/breast burn reconstruction). (a, b) Lipofilling into

scars requires special semi-blunt-tip cannulas and a long learning curve. (c) 2  days post-operative status. (d) 14 days postop status

The satisfaction index of the patients (on a 1–10 scale) was increased on average from 2 to 7–9 regarding their breasts. Good aesthetic results and symmetry were achieved with the planned operations. Most of the time one surgical step was enough to achieve the final planned volume and shape of the breast. Cases of Poland syndrome and severe hypoplasias required more stages. Usually, we may not expect major postoperative donor-site or recipient-site complications. Complication rates were low both in frequency and severity; we did not observe infections which can be led back to the newly researched antibacterial effect of the fat tissue. Lumps and cysts occurred in about 5% of the cases; most of them needed only post-operative observation. Significant fat necrosis occurred in two cases where reoperation was necessary. The formation of calcified and noncalcified knots or

masses that was common at the beginning of our learning curve became rare in the last years (usually, the constricted underdeveloped lower poles can be affected). Imaging (ultrasound and MRI) can identify fatty tissue grafts as micro-calcifications or the presence of suspicious lesions, determining the need for a biopsy to clarify the diagnosis or the need for revision if required. Hypertrophic scarring—but only at the site of mastopexy—occurred in six of our cases at 1-year follow-up; two of them needed surgical treatment and the other four were treated conservatively. On the site of fat injections, we always observed minimal scarring. We observed limited cases of capsular contractures in our cases treated with the combination of implants and lipofilling (composite reconstruction), not more in comparison to our patients with only implants for breast hypoplasia and ptosis in the same years.

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Fig. 67.12  (Patient 6) 11-year-old girl with unilateral amazia with the absence of pectoral muscles and contralateral tubular developing breast in the clinical picture of a Poland syndrome. In rare cases of obvious and verified Poland ­syndrome and visible maturation of the unilateral breast, supported by cooperative parents, with the help of a pediatric psychologist we may even perform the first setting of fat

grafting at the early age of 11–12. With this early progressive treatment, based on autoexpansion effects of the transplanted fat with the weight gain during midterm adolescence, the breast gets formed “biologically” and probably fewer operations will be needed. First row: Pre-operative pictures. Second row: 2 weeks post-operative pictures. Third row: One year post-operative follow-up pictures

67.16 Conclusion

However longer follow-ups, more data sharing, and scientific debates would be necessary for autologous microstructural lipofilling for it to become even more internationally recognized and standardized in the treatment of congenital breast asymmetries. The adolescent age is the most significant stage of the psychosexual development of a child and the formation of definitive body perception; therefore the first operation or the beginning of a series of operations is usually justified from the age of 14. Early reconstruction of asymmetries should be available in teenage with the definitive recommendation of the psychologist or psychiatrist (moral, ethical, and legal reasons should be considered) (See: Fig. 67.12 (Patient 6)).

Based on the authors’ experience, autologous microstructural fat grafting alone is a useful method, even with a large amount of fat, an effective and safe technique for the correction of breast asymmetries of any severity. With refined and well-standardized techniques it is possible to reproducibly achieve a previously unachievable quality of reconstruction with very limited side effects (e.g., negligible residual scarring) in the treatment of breast asymmetries. In severe breast asymmetries and chest wall deformities, e.g., Poland syndrome, autologous fat grafting appears to be a major progressive advance that can revolutionize the treatment of these disorders.

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In consideration of many different types of breast asymmetry, we suggest that the treatment plan with autologous microstructural lipofilling and applied combinations of techniques must be individually set in each case and should follow anthropometric planning based on morphological classification. Acknowledgments  Thanks to my young colleagues Dr. Krisztina Baranyai, Dr. Dániel Maksa, Dr. András Petrovics and Dr. Botond Mihalovits for their support during the operations performed on patients with severe breast asymmetries and with the photo selection. Special thanks to Alexandra Valéria Sándor for the writing assistance and language editing. The 3D animation of the case with Poland syndrome (Fig. 67.5) is by courtesy of Dr. Kálmán Czeibert.

References 1. Chan W, Mathur B, Slade-Sharman D, Ramakrishnan V.  Developmental breast asymmetry. Breast J. 2011;17:391. 2. Bergofsky EH, Turino GM, Fishman AP.  Cardiorespiratory failure in kyphoscoliosis. Medicine (Baltimore). 1959;38:263. 3. Nuzzi LC, et al. Psychological impact of breast asymmetry on adolescents: a prospective cohort study. Plast Reconstr Surg. 2004;134(6):1116–23. https:// doi.org/10.1097/PRS.0000000000000736. 4. Ho TH, Wang CC. Poland syndrome in an 18-year-old man. CMAJ. 2019;191:E793. 5. Friedman JM, Kaplan HG, Hall JG.  The Jeune syndrome (asphyxiating thoracic dystrophy) in an adult. Am J Med. 1975;59:857. 6. Yerian LM, Brady L, Hart J. Hepatic manifestations of Jeune syndrome (asphyxiating thoracic dystrophy). Semin Liver Dis. 2003;23:195. 7. Conroy E, Eustace N, McCormack D.  Sternoplasty and rib distraction in neonatal Jeune syndrome. J Pediatr Orthop. 2010;30:527.

G. Pataki et al. 8. Yiyit N, Işıtmangil T, Öksüz S.  Clinical analysis of 113 patients with Poland syndrome. Ann Thorac Surg. 2015;99:999. 9. Urschel HC Jr. Poland syndrome. Semin Thorac Cardiovasc Surg. 2009;21:89. 10. Behazin N, Jones SB, Cohen RI, Loring SH.  Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity. J Appl Physiol (1985). 2010;108:212. 11. Poyner SE, Bradshaw WT. Jeune syndrome: considerations for management of asphyxiating thoracic dystrophy. Neonatal Netw. 2013;32:342. 12. Bergofsky EH. Respiratory failure in disorders of the thoracic cage. Am Rev Respir Dis. 1979;119:643. 13. Lisboa C, Moreno R, Fava M, et al. Inspiratory muscle function in patients with severe kyphoscoliosis. Am Rev Respir Dis. 1985;132:48. 14. Weber B, Smith JP, Briscoe WA, et  al. Pulmonary function in asymptomatic adolescents with idiopathic scoliosis. Am Rev Respir Dis. 1975;111:389. 15. Poullin P, Toussirot E, Schiano A, Serratrice G.  Complete and dissociated forms of Poland's syndrome (5 cases). Rev Rhum Mal Osteoartic. 1992;59(2):114–20. PMID 1604222 16. Ho Quoc 2015: Fat grafting to improve severe tuberous breast 17. Mary H. McGrath and Sanjay Mukerji: plastic surgery and the teenage patient. J Pediatr Adolesc Gynecol. 2000;13:105–18. 18. Coleman 2007: Fat grafting to the breast revisited: safety and efficacy 19. Derder 2014: The use of lipofilling to treat congenital hypoplastic breast anomalies. 20. Russe 2015: Autologous fat grafting in breast surgery: results of a retrospective study. 21. Lee 2018: Autologous fat grafts harvested and refined by the Coleman Technique/A Comparative Study. 22. Delay E.  Lipomodeling of the reconstructed breast. In: Spear SE, editor. Surgery of the breast: principles and art. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2006. p. 930–46. 23. Mojallal A, Auxenfans C, Lequeux C, Braye F, Damour O.  Influence of negative pressure when harvesting adipose tissue on cell yield of the stromal-vascular fraction. Biomed Mater Eng. 2008;18(4–5):193–7.

Autologous Fat Grafting for Breast Augmentation in Asian Women

68

Kim Siea Lee and Kasey Kisu Sung

Key Message  • In this group of Asian women with a lean body and small dense breasts, obtaining a significant increase in breast size using AFG is “challenging.” • The process of AFG to breasts begins with fat harvesting after tumescent solution infiltration. Fat is harvested using a small cannula with low suction pressure from many sites due to the usual scarcity of the donor fat. The harvested fat is processed with centrifugation to compact the volume of the graft to be injected. • The processed fat is injected evenly into all layers of the breasts except the glandular layer. • The usual volume injected is about 200 cc or less. The increase in breast size is usually about 1–1 1/2 cup size; however, it is often unpredictable. • To improve the result, injecting the optimum amount in separate sessions and the use of cell-enriched fat graft should be considered. Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_68) contains supplementary material, which is available to authorized users. K. S. Lee (*) Plastic and Aesthetic Surgeon, The M Clinic, Penang and Kuala Lumpur, Malaysia K. K. Sung Cosmetic Fat Surgeon, Lilac BLC Clinic, Seoul, South Korea

68.1 Introduction Having relatively smaller breasts, with otherwise almost perfect figures, Asian ladies might have a desperate desire to enhance the volume of their breasts. Although breast implant surgery can provide satisfactory results, a significant number of women are still asking for breast enlargement through fat grafting for the natural feel. The dislike for foreign bodies and the recent discovery of breast implant-associated anaplastic large-cell lymphoma (ALCL) also help to shift the trend towards autologous fat grafting (AFG). Asians, especially in the far east like China, generally have smaller body frames as compared to Caucasians. They have thin and generally balanced body lines due to their lean statures, and prominently slimmer curvatures, although their volumes of chests and hips are relatively poorly defined [1]. It seems that Asian women, in general, are leaner with less fat resources when compared to Caucasians with the same body mass index. Even with the popularity of mega-fat grafting for breasts and hips, it is almost impossible to get significant volume enhancement in this group of women with low body fat, a smaller volume of original breasts, and limited expandability of the breast and skin. The same is also true for women with these features in other parts of the world (Table 68.1). When an Asian woman desires to have fat graft surgery for breast augmentation and does

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_68

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K. S. Lee and K. K. Sung

1024 Table 68.1  Challenges faced in breast fat grafting surgery in the subgroup of Asian women with small breasts and thin body compared with Caucasian women in general Thin and lean Asian women The lack of fat resources Lean body The volume overload in the lesser breast spaces available Dense fibrotic breast tissues Increased risk of complications with a lower chance of graft survival Difficulty in achieving desired breast size in a single operation

Caucasian women in general Availability of more donor fat tissue More subcutaneous fat Larger breast, hence more tissue spaces available More fatty tissues and less fibrotic breasts Less risk of complications Possible to get better graft take in a single operation

not have the optimal amount of fat tissue, she will learn that the goal of the surgery is hard to achieve. Would putting on weight before surgery to gain more fat tissues be a valid recommendation? As it is well known, in adulthood, an increase in body fat only increases the size and not the number of fat cells. So, harvesting the same amount of fat tissues for breast augmentation would yield a lower number of fat cells, resulting in a decreased number of cells that could be moved and eventually may result in lesser volume enhancement. Moreover, when the weight returns to the previous level, naturally, the size of the adipocytes will be reduced, resulting in a decrease in the volume of the transplanted fat tissue. AFG to breasts requires a large amount of fat graft, and insufficient fat tissues for transplantation would result in inferior accomplishments. In this situation, breast augmentation using implants or hybrid with implants may be more favorable alternatives. It will be useful if the patient is aware if she has the necessary amount of fat for AFG breast augmentation at the time of consultation. There should be an evaluation of the amount of fat tissue available for the surgery other than BMI, which is not a perfect indication of body fat. BMI generally overestimates adiposity on those with leaner body mass like most lean Asian women. In other words, Asian women with

the same BMI as Caucasian women would have less adipose tissues available as donor fat. With this in mind, however, BMI is still useful as a guide. The skin-pinch test on the areas of localized fat accumulation is more helpful. Body composition analyzer may be an optimal alternative to check how much body fat they have before the surgery. By experience, if there is more than 12 kg of body fat, it indicates an adequate amount of body fat for fat graft surgery. This, however, requires further clinical studies. The fat tissues are soft, fragile, and vulnerable to pressure or hypoxia. They are not stronger than the skin overlying them and are not as resistant as implants are. Therefore, any attempts to put too much fat tissue into a limited space will lead to the fat tissues becoming overcrowded, increasing the tissue pressure inside, which may result in poor blood supply to the grafted tissues, and a compromised situation develops. Smaller breasted ladies will have more trouble getting breast augmentation with fat graft for the same reason. With basically limited expandability, the original breasts have limited volume, which puts a limit on the amount grafted. Much like we cannot put too many coins in a small purse [2]. As the patients expect bigger breasts after the surgery, the surgeon might try to place as much graft as possible exceeding the limit of what the local tissues can support; this may result in a higher incidence of complications. When too much fat tissue is grafted, there will be an increase in the need for blood and oxygen delivery for better “take” of the grafted materials [3], but this need is difficult to be met by the host tissues. Moreover, the pressure from swelling and bruising that follows the procedure could worsen the situation. Early complications such as embolism, oil cysts, fat necrosis, and resorption of grafted materials would increase [4]. So do long-term complications such as lumps, calcification, and loss of volume. There are several possible explanations for the process of “take” of grafted fat tissues like the cell survival theory, cell replacement theory, and marginal survival theory. No matter which theory we believe in, it is critical to get enough blood and oxygen supply for the grafted fat tissues so

68  Autologous Fat Grafting for Breast Augmentation in Asian Women

they could survive, and they are very dependent on the capacity and volume of the original breasts. The question will be how much volume of grafted fat would be optimal for low complications and maximum possible results for patients, which unfortunately is hard to be standardized. And there would be differences in personal preferences, chest sizes, desired breast volumes, and many other variables to be considered. There have been many ideas to control complications and offer better take of the graft by many surgeons. Increasing the contact surface with the host tissue by grafting uniformly, collecting and transplanting with low negative and positive pressures, removing unnecessary elements such as blood or fibrous tissues, and using centrifugation to reduce the volume of the graft are some of the methods used by many surgeons together with the Brava tissue expander, cell-enrichment graft with stem cells, and repeating the AFG in several sessions with optimal amounts [4]. However, despite all these measures, commonly reported graft survival rates are often unsatisfactory. If we could adopt ways to move the average graft survival to the higher range consistently, it would be an achievement. As many Asian breasts are dense, there should be preoperational examinations for suspicious breast cancer, especially for those with a family history of breast cancer or lumps. Imaging studies should be done when indicated. Follow-up studies and regular checkups after fat grafting of the breasts [5] should be advised. Findings like lumps and calcifications could emerge long after the surgery, even when there were no problems in the initial year.

68.2 Patients and Methods Both authors reviewed their own series done at different periods. Both authors were performing the procedures in different centers. As there were no pre-planned studies, data collection was done by tracing old records. The authors encountered difficulty in getting complete information from

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Table 68.2  Patient number and characteristics

Numbers Author 97 1 Author 136 2

Age (years) Average Range 35.42 28– 55 36.65 20– 65

Body mass index (BMI) Average Range 21.22 17.8– 28.8 21.62 16.5– 36.9

the medical records of all the patients. Author 1 reviewed a series of patients between January 2008 and December 2016. This review was presented in several conferences on fat grafting, but it was not published in a journal. A total of 97 patients underwent AFG for cosmetic breast augmentation. All the patients were of Asian origin. AFG to breasts was performed for various indications by the author 1; however, only cases for primary cosmetic breast augmentation were included in this review (total of 97 patients). Author 2 reviewed the series of 136 patients between January 2010 and December 2013 who consulted for primary cosmetic breast augmentation. Table 68.2 shows the characteristics of the patients. AFG to breasts involved the process of fat harvesting, processing, and injection. The process of AFG to breasts could be done under local anesthetics or general anesthetics. Table 68.3 summarizes the techniques used by the authors. As the recipient breasts could be small, dense, and fibrotic, the volumes that could be safely injected were small to minimize the risk of complications. To improve the graft retention, several refinements of the technique were made. One of the authors preferred to stage the procedure, and the other author favored the use of cell-enriched fat graft (see Table  68.4). The cell-enriched fat was prepared by collagenase digestion of the processed fat and isolation of the stromal vascular fraction (SVF). The SVF, which is rich in stem cells, was added to the processed fat to form the cell-enriched fat for the use in grafting. 56 cases of cell-enriched fat graft from Author 1 and 8 cases from Author 2 were included in the series (Figs. 68.1–68.7).

K. S. Lee and K. K. Sung

1026 Table 68.3  Summary of authors’ preferred fat grafting techniques

Infiltration Harvesting

Fat processing

Fat injection Plane of injection

Wet technique (volume of solution infiltrated approximately equal to the estimated volume of aspirate) using Klein solution 3 mm cannula Manual using syringes Low-pressure suction pump assisted (Lipokit) Body jet assisted Decantation Centrifugation with Coleman’s technique Centrifugation with a closed system (Medikan Lipokit system) Collagenase-assisted extraction of stromal vascular fraction for cell-­ enriched fat graft Manual using 2 mm cannula Special injector device from Lipokit All layers except the glandular layer

Table 68.4  Number of patients and the volume of fat injected to the breasts Number of patients with AFG done in single session Number of patients with AFG done in two sessions Average volume (cc) of fat injected in a single-session group Average volume(cc) of fat injected in two-­ session group Session 1 Session 2

Author 1 95

2

Author 2 81

55

Left 215

Right 226

Left 167

Right 170

Left

Right

Left

Right

145 135

155 140

181 167

181 168

68.3 Results In most cases, the volume of breasts stabilized at about 6–9  months. Most, if not all, patients obtained 1–1 1/2 cup size increase in volume with a few below or above this size increase. It must be clearly stated that the increase of cup size from A to B or from B to C is two cup size increase not one. The breasts appeared to be

fuller with less visible ribs and better cleavage. It must be noted that the increase in cup size is based on the visual reports of the patients and the doctors; very few surgeons have the luxury of doing proper volumetric assessment pre- and post-surgery. The exact percentage of graft survival is difficult to measure using simple methods at the moment. According to estimate, it would take 100 to 150 cc implant to achieve one cup size increase. Based on this, if 200  cc of fat grafted gave an increase of 1–1 1/2 cup size, the estimated percentage of graft take is about 50%. This estimation is, however, not able to withstand any scientific scrutiny. For AFG with a cell-enriched fat graft group, the impression was that there was generally better retention of graft; very few patients in this group had poor graft retention. However, the best results from this group were not significantly better than the best from the non-cell-enriched group. All these interpretations were not based on objective measurement of the pre- and post-surgery breast sizes using devices which are able to measure the exact volume of the breasts. The decision to do cell-enriched fat graft to improve graft retention was inspired by published papers in medical journals and the acquisition of medical devices like Lipokit and Celltibator. There was no detailed comparative study planned; hence the author was not able to provide good scientific data to show the efficacy of the technique. Some of the patients received second AFG surgery after at least 3 months from the first graft. In general, the second AFG improved the results of the first graft. However, it is again difficult to estimate the percentage of graft retention. The second séance, however, increased the cost of AFG overall. It is a useful strategy for a group of Asian women with very small breasts but who desire to have a bigger increase in breast size (Figs. 68.2, 68.3 and 68.4). The patient satisfaction level towards the procedure was difficult to evaluate as this was not a pre-planned study. Implications were made based on the medical records of the patients. Of the 97 patients in the series from Author 1, only 7 patients (7.2%) were disappointed with the results. Long-term satisfaction was again difficult

68  Autologous Fat Grafting for Breast Augmentation in Asian Women

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Fig. 68.1 Photos of a patient. Preoperative (left), 9 months postoperative (middle), and 6 years postoperative (right). 38-Year-old woman with AFG to her breasts; 200 cc was injected into each breast. Postoperative photographs show a cup size increase in volume representing an

average graft take, and there was no change in body weight during this period. 6 Years after the procedure, the patient had put on 5 kg of body weight, and the breast size had also increased in tandem

to establish as only 54% of the patients came back for review after a year. 3 patients in this group, which were part of the 7 patients mentioned before, were still not happy with the size increase but accepted it without further procedure. It is interesting to note that 3 of the 97 patients had decided to opt for breast implant surgery after the fat graft. Overall, more than 90% of patients were happy with results at least in the first year. Based on the patients’ medical record, Author 1 reported 3 cases of palpable lumps which required ultrasonography and simple needle

aspiration. All patients experienced bruises and swelling, which took 2–3 weeks to resolve. One patient had pus discharge from the nipple, which resolved with antibiotic treatment. Among 136 cases of author 2, there were 2 cases of infection; both of the cases required incision and drainage with antibiotic therapy. It is interesting to note that one of the cases did perform unnecessary massage as she misunderstood the postoperative instruction. There was 1 case of aseptic inflammation, 2 cases of lump that were too small to need any treatments.

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Fig. 68.2  Photos of a patient. Before (left) and 3 years 6  months later (right). The 57-year-old patient had fat grafting to her breasts, at first 230  cc of centrifuged fat was injected to eachbreast. During second fat grafting 5 months later, 190  cc of fat was injected to each breast.

K. S. Lee and K. K. Sung

Lastly, she received 230 cc of fat grafting for each breast 1 year and 2 months after the second fat grafting. In the beginning, she weighed 54.4 kg, 163 cm, BMI was 20.5. 3 years 6 months later, she weighed 57.4 kg, and BMI was 21.3

68  Autologous Fat Grafting for Breast Augmentation in Asian Women

Fig. 68.3  Before and 2 years after two times fat grafting surgeries without weight gain. The 38-year-old patient had 140 cc of fat injected into each breast at the first ses-

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sion and 220  cc for each side at the second fat grafting session 3 months later

Fig. 68.4  Photos of 42-year-old patient. Before (left), after (middle) first graft of 120 cc, (right) 15 months after first fat graft and a year after second fat graft of 140 cc to each breast. Noticed fuller volume and better cleavage

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Fig. 68.5  Pre- and 9 months post-surgery photos of a 30-year-old lady after 250 cc of AFG; she had about 1 cup size increase in her breasts

68  Autologous Fat Grafting for Breast Augmentation in Asian Women

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Fig. 68.6  Pre- and 1 year post-surgery photos of a 38-year-old lady after 250 cc of AFG with cell-enriched fat; she had more than 11/2 cup size increase in her breasts

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Fig. 68.7  Pre- and 13 months post-op photographs of a 48-year-old lady with 300  cc of cell-enriched fat graft injected to her breasts. She had good graft take, giving her a two-cup increase in size and a better shape. This case

K. S. Lee and K. K. Sung

illustrated the fact that larger breasts allowed a larger volume of the graft to be injected as more tissue spaces were available, resulting in better retention of the graft

68  Autologous Fat Grafting for Breast Augmentation in Asian Women

68.4 Discussion

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sites to make up for the volume required. It would be helpful to ask for the history of liposuction surgery before because it will be It will be useful to follow in detail the whole proharder to harvest the fat tissue from the areas cess of the surgery from consultation to long-­ already treated. term follow-up for the review of Asian breast fat 2. The volume, before and after: While it is grafting. At the initial consultation, surgeons common to increase by 1 cup size using should discuss with patients on various options in AFG to breasts in Asian women, surgeons breast augmentation surgery. The advantages and should set the patients’ expectations with disadvantages of both implants and fat grafting realistically achievable results. After delivshould be clearly explained, matching the ery, the skin of the breasts expands easier patients’ expectations with possible realistic than before, and the blood supply might also results. There are criteria to look for in the physibe increased even without breastfeeding. cal examination for fat grafting like the amount One may expect better results for those who of body fat, the size and expandability of breasts have a history of delivery with better spaces that would assist in clinical decisions on the available, easy expandability, and better option chosen, and the results that could be blood supply. Because of the limitation of achieved. spaces available to be grafted for most young nulliparous Asian ladies, it will be reason 1. Body Fat Resources: There should be optiable to go for repeated grafting sessions with mal or enough amounts of fat tissues to be the optimal volume of fat tissues to minigrafted for good outcome of breast augmenmize unnecessary complications and tation. When we consider the lean, thin body resorption. shapes of Asian women, it may be the first Implant surgery is well known to be able important determinant for AFG surgery. On to give a good projection of the breasts; howphysical examination, the surgeon should ever, it would not be easy with fat grafting. confirm if there is an optimal amount of fat The problem is compounded by the lack of by checking or pinching the body areas of adequate fat tissues for grafting. As a result, the accumulated fat tissues. History of delivinstead of trying to graft the whole breasts, ery is a useful information as there would be priority would be to inject more volume of fat more accumulations of body fat, unlike on upper medial areas of each breast; this will young nulliparous women who do not have give a good midline cleavage of the breasts much body fat. And the breasts of a post-­ which women prefer when they dress up. pregnancy woman have been expanded and Another difference between fat grafting allow more space for a larger volume of the and implant surgery will be the correction of graft to be injected. the asymmetry of the breasts. It will be hard People who have a lot of body fat will gain to correct the differences in the size or volweight easily with aging; the results of fat ume of each breast with a single session of grafting for breasts will also be favorable for fat grafting when the difference is signifithis group. On the contrary, those who do not cant, especially when the patient desires to put on weight or remain lean in most of their augment both sides. The grafting will expand lives would have difficulty keeping the volume the original capacities of each breast. So, the grafted and might need more grafting sessions. bigger breast will take more volume after The typical donor areas for fat tissues grafting even though the surgeon planned for would be the thighs, abdomen, waist, and more enhancement on the smaller side. One buttocks. There is no difference in the fat suggested solution is to graft the smaller harvested from various sites as demonstrated breast until it matches the other side before by K. Li et al. [6]. Anyway, there is no quesgrafting both sides or have a larger volume tion of which is the best donor site in thin grafted to the smaller breast. patients, as the fat will be harvested from all

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Most of the changes will be from cup size A to B, or from cup size B to C in Asian women; changes from F to G cup are uncommon. This increase in size is small, but when seen in the smaller chest sizes of Asian ladies, the improvement is significant. This coupled with the natural feel and touch of the fat-grafted breasts has attracted many Asian women to opt for AFG for breast enhancement. This is especially true for those who are happy just to have a pair of fuller breasts. 3. Expandability: When the skin is soft and easily expanded, there are more spaces available to be grafted. As Asian patients have, unfortunately, tight and dense skin, there is always a risk of compression by the fat tissues themselves when too much graft is packed into the limited spaces. Even in ladies with a bigger chest, although the volume of original breasts might be optimally big, the skin may not expand as one might expect. There is always a limitation in the volume of fat that can be grafted although one may harvest a generous amount of fat tissues. Trying, as the surgeon may, to place the fat tissues as even as possible to have good contact with the recipient breast tissues, there is a limit on how much fat tissues can be injected due to the limited spaces available. Injecting too much, especially in bolus, may result in complications like fat necrosis, cysts, and calcification. 4. Preoperative evaluation and preparations for the surgery: The breasts will be dense and fibrotic in many Asian patients; it is recommended to have imaging studies or screening studies for the appropriate age groups. Any family history of breast cancers and the history of any surgery or procedures on the breasts should be asked before the surgery. It will not be easy to harvest the optimal amount of fat tissues from a single circumscribed local area; the surgeon and the patient should be prepared to have fat harvested from multiple sites. At the time of preoperative drawing, the surgeon would decide on the areas of fat harvesting and points of skin incisions for both harvesting and grafting. Postoperative care should also be discussed. Photography of the donor and recipient sites of various angles should be taken for records.

K. S. Lee and K. K. Sung

BRAVA can be used to expand the skin and improve the vascularity of the breasts; this will help in the “take” of the graft [7]; however, it is not readily available in this part of the world, and the added cost could be prohibitive. 5. Fat harvesting: It will be helpful to infiltrate an optimal amount of tumescent solution for local anesthesia and to produce a tumescent effect on the donor areas. A small amount of the same solution is also infiltrated into the breasts to control unnecessary bleeding and pain. It is generally accepted that the concentration and the amount of local anesthetic used in the infiltration of the donor and recipient sites have minimal toxicity to the graft and hence minimal effect on the results [8]. Harvesting should be done in the least traumatic way with gentle strokes, and the fat tissues should be aspirated using low vacuum pressure [9]. Although a larger cannula is less traumatic and causes less damage to the fat cells [10], the graft may be too large to be grafted; hence a small-caliber cannula like 3 mm is still preferred. It is also important to ensure that the donor sites do not suffer complications like surface irregularity and flatness, hyperpigmentation, and other undesirable appearance. This is equally important in AFG. 6. Fat processing: The unnecessary, even harmful, blood or fibrotic materials should be cleaned out or removed before grafting. There might be arguments for and against centrifugation, and there are many who centrifuge the fat tissues to pack the fat tissues eliminating the unwanted solutions that occupy the spaces [11, 12]. Centrifugation compacts the cells and increases cell density. Logically, this is useful in Asian women with small dense breasts as surgeons can place only a small volume of fat graft. The addition of platelet-rich plasma (PRP), stromal vascular fraction (SVF), and adipose-derived stem cells (ADSC) seems to have improved the “take” [13]. The fact that stem cells produce angiogenesis is well known, and earlier and speedier angiogenesis essentially enables earlier revascularization of the graft leading to better graft retention. However, the increase in time and hence the cost of the materials would war-

68  Autologous Fat Grafting for Breast Augmentation in Asian Women

rant a significant consideration [14]. A simpler way is to micronize the fat [15]. Micronization of fat enables smaller globules of fat to be grafted yet it retains cell viability. Theoretically, this should improve cell survival, hence better graft “take.” However, commercially available devices at the moment are not efficient for large-volume fat processing as required in AFG for breast augmentation. The author has tried this technique in two of his cases. The initial result is promising; however it is more time consuming. It will need more studies to confirm its usefulness. It is also noted that a closed system for harvesting, processing, and injection improves the safety, efficiency, and graft retention [16]. The authors use a closed system for AFG to breasts. As mentioned earlier, cell-enriched fat graft also appears to be useful in obtaining more consistency in graft retention, moving the percentage of graft retention to the higher percentage of commonly reported graft survival rate [17]. The extraction of the stromal vascular fraction (SVF) is commonly done using collagenase, which is not available in some countries. However, recent advances in mechanical separation of stem cells from fat tissues seems to hold a lot of promises in SVF isolation without the need for collagenase. 7. Grafting technique: The surgeon may approach through submammary, periareolar, or axillary incisions for fat grafting, and the incisions are small and well hidden. Infiltration of tumescent solutions into the breasts will be helpful to control bleeding and pain during and after the grafting. It may be more comfortable to start from the deepest layer of the breasts to the more superficial layers when placing the fat inside the breasts. The fat deposition should be done with small aliquots as this will help to increase the contact surface with host tissues and increase the chances of blood and oxygen supply. Even distribution in a thin manner will be the best policy of grafting [4, 18]. It is not recommended to inject into the glandular tissues. Bolus injection should be avoided, as it may lead to complications like oil cysts, lumps, calcification, and infection. They lower the survival of the graft. The intentional filling of

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more graft on the upper medial portion of the breasts will make midline cleavage better and result in better patient satisfaction on the breast shape. This is especially important when the available graft is limited. There are many devices available to assist in fat injection, e.g., MAFT gun; the aim of these devices is usually to improve consistency in the delivery of the volume of fat injection, which in turn helps in giving better contact between grafted tissues and native tissues. From the authors’ experience, the optimum volume of the graft to be injected in a small A-cup breast is between 150 and 200 cc. It is more in a parous woman than in a nulliparous woman. This, however, is a rough clinical guide without proper medical references. 8. Postoperative care and recovery: Bruises and swelling are common. Many Asians believe that massage is helpful for better recovery from breast surgery. However, this practice is not proven medically. It might even be harmful if too much pressure is applied during the massage. The use of g­ entle compression on the first day around the whole chest together with the breasts will be helpful for the control of bruising and edema. After that, continuing with a supportive bra is recommended. Maximal swellings develop during the first 5 days and subside mostly in a month or two. The volume recovers slightly in the following 2 or 3 months. While there is no medical evidence to support this, patients are encouraged not to lose weight during the recovery period. Patients are also advised not to do vigorous exercises during this period, especially those involving the use of upper limbs like tennis or badminton. 9. Complications: Most of the initial edema, swelling, and bruising will usually subside in 2–3  weeks after the surgery. The rare severe complication in the early period will be an infection. Localized erythema, heat with tenderness, fever, and swelling with discharge will need significant care and treatment like debridement, drainage, culture, and antibiotics coverage. These usually happen in the first week post-surgery. Similar signs and symptoms after the sev-

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K. S. Lee and K. K. Sung

Fig. 68.8  The calcifications found on a mammogram (left) and ultrasound imaging (right) at 10 years after fat grafting into the breasts

enth day of the surgery may indicate inflammation from fat necrosis. Low-grade erythema, warmth, and tenderness with no growth on culture are the signs. One should also be aware of possible Mycobacterium infection at this stage. When the patient complains of a mass inside, one should evaluate the nature by imaging studies, and define the quality of the mass. When it is an oil cyst and big enough, it will be better to aspirate with a needle and apply compression to control it. If they are a mass like packed fat or small calcifications, mammotome surgery, if available or other surgical treatments, may be considered to remove them if they give troubles like pain or tenderness. They may appear months or even years after the surgery, and they need to be treated accordingly [19]. As known, there is no clear evidence of cancer developing on the grafted fat tissues [19]. Calcifications in

the breast tissues from the procedure are common (Fig. 68.8); however, this can be easily discriminated from the malignant calcification independent of the AFG procedure [20]. 1 0. Longer term progress: In most cases, the breasts assumed its final state after 9 months to a year. The nature of grafted fat tissues seems to resemble the quality of the original sites before they were transplanted, so it would follow the changes of the donor areas. As the patients gain or lose weight, the volume of the breasts also fluctuates in tandem (Fig. 68.1). Patients, when selected optimally for the procedure, can enjoy positive results. Repeating the AFG session will further enhance the results with minimal complications. Overall patient satisfaction from the procedure was high as long as patients were well informed and understood the limitation (Table 68.5).

68  Autologous Fat Grafting for Breast Augmentation in Asian Women Table 68.5  Characteristic of fat grafting to thin Asian women with small dense breasts and suggested ways to improve graft take Lack of donor resources Volume overload in small breasts

Unable to achieve the desired breast size and shape

– Harvest from all available donor areas – Centrifugation to reduce the volume of injection and to compact the cells – SVF cell-enriched fat graft to increase the number of cells per gram of fat tissue – Injecting only optimum amount – Inject evenly in small aliquots to ensure as much contact as possible between local tissue and graft – More than one session of fat grafting, each session with optimum volume – Focus more on enhancing the upper pole and midline cleavage

68.5 Conclusion The ultimate goal of AFG to breasts is to achieve patients’ desired breast size and shape. There is a limit on how much AFG to breasts could be achieved each time. Patients need to be counseled and realistic expectations informed. AFG to breasts for augmentation in Asian women overall is similar to that in other populations. However, a larger portion of Asian women are lean with small dense breasts and poor skin expandability, with precious little fat resources; therefore extra steps are taken to maximize the ultimate retention of the graft. The emphasis on placing more graft to the upper and medial portions of the breasts to create a better midline cleavage when dressing up is especially important when the availability of graft is limited. The volume in fat graft injected for each session is usually small, in the region of 100–200 ml, to minimize possible complications. If desired and when donor sites are available, repeated sessions would render a better result. Cell-enriched fat graft appears to help in improving graft retention, and this, however, needs further evaluation. In the situation where donor fat is scarce, it may serve as a useful adjunct to improve the results.

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With a better understanding of the AFG procedure and better techniques, the inherent problem of unpredictable graft retention could eventually be overcome. AFG to breasts for cosmetic augmentation gives high patient and doctor satisfaction with a low incidence of complications. Conflict of Interests None.

References 1. Lim LY, Ho PJ, Liu J, Chay WY, Tan M-H, Hartman M, Li J. Determinants of breast size in Asian women. Sci Rep. 2018;8:1201. 2. Suga H, Eto H, Aoi N, Kato H, Araki J, Doi K, Higashino T, Yoshimura K. Adipose tissue remodeling under ischemia: death of adipocytes and activation of stem/progenitor cells. Plas Reconstr Surg. 2010;126(6):1911–23. 3. Lee P.  Mechanisms of fat graft survival. Ann Plast Surg. 2016;77:S84–6. 4. Jorien Tuin A, Domerchie PN, Scherpes RH, Willemsen JCN, Dijkstra PU, Spijkervet FKL, Vissink A, Jansma J. What is the current optimal fat grafting processing technique? A systemic review. J Craniomaxillofac Surg. 2016;44:45–55. 5. HyunJin Yang MD, HeeYoung Lee MD. Autologous fat transfer to breasts. Chapter 15, Aesthetic Plastic Surgery Vol.3 Korean Society for. Aesthet Plast Surg. 2018;3:169–201. 6. Li K, Gao J, Zhang Z, et  al. Selection of donor site for fat grafting and cell isolation. Aesthetic Plast Surg. 2013;37(1):153–8. 7. Daniel A, Del Vecchio RK. Chapter: cosmetic breast augmentation with fat grafting. In: International textbook of aesthetic surgery; 2016. https://doi. org/10.1007/978-­3-­662-­46599-­8_12. 8. Shoshani O, Berger J, Foder L, et  al. The effect of lidocaine and adrenaline on the viability of injected adipose tissue - an experimental study in nude mice. J Drugs Dermatol. 2005;4:311–6. 9. Pu LL, Coleman SR, Cui X, Ferguson RE Jr, Vasconez HC.  Autologous fat graft harvested and refined by the Coleman technique: a comparative study. Plast Reconstr Surg. 2008;122:932–7. 10. Ozsoy Z, Kul Z, Bilir A. The role of cannula diameter in improved adipocyte viability A quantitative analysis. Aesthetic Surg J. 2006;26:287–9. 11. Ueberreiter K, von Finkenstein JG, Cromme F, Herold C, Tanzella U, Vogt PM.  BEAULI- a new and easy method for large-volume fat grafts. Handchirurgie-Microchirurgie-Plastische Chirurgie. 2010;42:379–85.

1038 12. Fontes T, Brandao I, Negrao R, Martins MJ, Monteiro R.  Autologous fat grafting: harvesting techniques. Ann Med Surg. 2018;36:212–8. 13. Landau MJ, et  al. Review: proposed methods to improve the survival of adipose tissue in autologous fat grafting. Plast Reconstr Surg Glob Open. 2018;6:e1870. https://doi.org/10.1097/ GOX0000000000001870. 14. Spear SL, et  al. The safety, effectiveness, and efficiency of autologous fat grafting in brest surgery. Plast Reconstr Surg Glob Open. 2016;4:e827. https:// doi.org/10.1097/GOX000000000000842. 15. Takanobu M, Wu S-H, et  al. Mechanical micronization of lipoaspirates: squeeze and emulsification technique. Plast Reconstr Surg. 2016; https://doi. org/10.1097/PRS0000000000002920. 16. Alexander RW, Harrell D. Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting. Clin Cosmet Investig

K. S. Lee and K. K. Sung Dermatol. 2013;6:91–102. https://doi.org/10.2147/ CCID.S40575. 17. Hakakian CS, Aronowitz JA.  A side by side trial of pluripotent cell enrichment in autologous fat grafting of the breasts. Plast Reconstr Surg. 2014; 134(4s-1 suppl):85–6. https://doi.org/10.1097/01.prs. 0000455432.20261.48. 18. Groen J-W. Effectiveness and safety of autologous fat transfer in various treatment protocols. Maastricht: Universitaire Pers Maastricht; 2017. 19. Yoshimura K, Coleman S. Complications of fat grafting how they occur and how to find, avoid, and treat them. Clin Plastic Surg. 2015;42:383–8. 20. Groen J-W, et al. Autologous fat grafting in cosmetic breast augmentation: a systemic review on radiological safety, complications, volume retention, and patient/ surgeon satisfaction. Aesthet Surg J. 2016;36(9):993– 1007. https://doi.org/10.1093/as/sjw105.

Treatment of Tuberous Breast by Fat Grafting

69

Klaus Ueberreiter and Parshanak Azdasht

Key Messages  • Lipedema fat seems to be not suitable for fat grafting because of lower take. • Consider two sessions for the relocation of the inframammary fold. • Areolar reduction can additionally be done within the second session of lipotransfer. • The pentagram technique is a less invasive and less scarring technique for moderately enlarged nipple-areola complexes. • Silicone implants have a higher risk of persisting inframammary fold and upward dislocation in tuberous breast patients but a combination of both techniques can be a good option in patients with low body fat ratio. • The fat injection focuses on the subdermal layer beneath the former inframammary fold to dilate and soften the tissue downwards to the future position. • Moderate rigottomies can be considered within the tense area of the lower quadrants while forming a lower inframammary fold.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_69) contains supplementary material, which is available to authorized users. K. Ueberreiter (*) · P. Azdasht (*) Park-Klinik, Birkenwerder, Germany e-mail: [email protected]

• The double-bubble deformity is the trickiest complication to deal with depending on the rigidity of the inframammary tissue to be dilated.

69.1 Introduction Autologous fat transfer to the breast is not limited to the volumization of the tissue but can complementarily be applied to reshape or reconstruct the breast in primary or secondary developed asymmetric conditions. This section deals with the congenital morphologic anomaly of the tuberous breast.

69.2 Definition The tuberous breast is a congenital anomaly of the breast which becomes evident after hormonal stimulation during puberty. It can occur unilaterally whereas bilateral deformities occur more often. It is characterized by a number of morphologic alterations. What all of them have in common is the structural dermal weakness of the nipple-areola complex paired with a very tight dermis surrounding it. This results in a herniation of the gland and often stretching and widening of the areola. A deficient diameter of the mammary base, hypoplastic breast tissue especially in the lower quadrants, and a short distance between the nipple and inframammary fold typically provide

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_69

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the morphologic presentation of the tuberous breast. The surgical correction of the tuberous breast was first described by Ribeiro and published in 1973. He introduced a method of mobilization of the subareolar tissue and folding of an inferiorly based flap by a periareolar approach [1]. Rees and Aston combined this technique with the utilization of silicone implants in 1976 [2]. There are numerous other techniques involving flaps but the correction by remodeling the gland and inserting a silicone implant is still the most common technique at the moment. Besides the fact that patients being treated with silicone implants have to face subsequent surgeries in case of, e.g., symptomatic capsular fibrosis and breast implant illness or for the mere exchange due to material fatigue, they possibly have to deal with a persistent high inframammary fold [3, 4]. Since the introduction of the autologous fat transfer by Coleman we have gained further insight to new approaches of minimal invasive surgical treatments [5].

69.3 Prevalence Generally both women and men can be affected even though the female part is predominant. The exact proportion of the general population being affected is still not determined. Occasionally the tuberous breast reveals first after augmentation because prior to surgery the amount of tissue being present is too minor to pass through into the areola complex. Therefore there is a higher undiagnosed rate.

69.4 Classification Tuberous breasts can be classified either by Grolleau or von Heimburg (Figs. 69.1 and 69.2). The following will refer to the Von-Heimburg Classification [6, 7]. The higher the grade of classification the higher the severity of deformation. The risk of an areolar prolapse also increases gradually. Half of the patients with grade III tuberous breast defor-

mity already additionally.

have

an

areolar

prolapse

69.5 Operation Technique The overall aim of treating the tuberous breast by surgery is to achieve a relocation of the inframammary fold as a base for reshaping the breast into its normal silhouette and additional growth. The surgery can be done under analgesic sedation and takes approximately 60 to 90 min. There is no need for hospitalization if there are no specific circumstances so that after a postoperative period observation the patient can leave the clinic on the same day. After 4 days most patients are able to go back for work.

69.5.1 Marking To gain a better overview during surgery all patients undergo preoperatively the same marking procedure of the breasts as well as the donor sites. The preoperative markings are done in a standing position. While choosing the donor sites for harvesting the fatty tissue, you should consider easily accessible areas with suitable fat tissue besides the overall fat distribution of the patient. According to our experience the upper thighs as well as the abdomen and flanks were more than adequate. Dealing with a patient with a low amount of subcutaneous fat tissue the risk of disproportionate asymmetries as well as dents or striae from the liposuction part is higher. So a gain of weight before having surgery should at least be recommended. There is cutoff line at our clinic with a BMI of 18 to be the lowest ratio for autologous lipotransfer. Considering the marking of breasts is to recreate the new position of the inframammary fold in a lower position and to put emphasis on the quadrants or areas that lack in volume. In case the breasts are affected bilaterally from tuberous breast deformity or the alignment to the unaffected side proves to be difficult it is possible to realign the new inframammary fold at an average

69  Treatment of Tuberous Breast by Fat Grafting Fig. 69.1 Tuberous breast classification by von Heimburg

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Von-Heimburg Classification Type I

Hypoplasia of the lower medial quadrant

Type II

Hypoplasia of the lower medial and lateral quadrant, sufficient skin in the subabareolar region

Type III Type IV

Hypoplasia of the lower medial and lateral quadrant, deficiency of skin in th subabareolarregion Severe breast constriction, minimal breast base

Fig. 69.2  Tuberous breast deformity: schemes and photographs of classification types (with kind permission of Dr. von Heimburg)

distance to the nipple of 10 cm depending on the targeted breast size.

69.5.2 Lipedema and Fat Grafting Patients presenting with tuberous breast and lipedema at the same time need to be examined more thoroughly for possible donor sites. Up to now, there are no published studies analyzing the outcome of lipotransfer from lipedema fat. A lower grade of differentiation of pre-adipocytes in lipedema fat is proven in  vitro compared to unaffected fat tissue [8, 9]. This might be an explanation for a lower take rate that we experienced in these patients. In mutual exchange with other colleagues, the opinions and results differ. The severity of lipedema grade might also affect the efficacy and complication rate of lipotransfer,

but we discontinued with fat grafting from lipedema fat of any stage in our clinic. In general the fat tissue of the tummy area is not regarded as lipedema fat and is indeed feasible for lipotransfer.

69.5.3 Fat Injection In our clinic, the harvesting and infiltration technique of the fatty tissue follows the Berlin autologous lipotransfer (BEAULI™) protocol. You can find a short version of it in Fig. 69.3 [10]. The first-step surgery broadens the breast barriers and recreates a new inframammary fold. The adipose tissue is injected directly subcutaneously according to the preoperative marking. The distribution of the fat graft for the treatment of the micromastia is carried out just equivalently to

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aesthetic breast enlargement subcutaneously and retro-glandularly. An average of 200-250 ml per side can be grafted. It is important to explain to the patient that right after infiltration the area of the old inframammary fold is still very rigid but after a period of approximately 6 weeks the old fold continuously disappears letting the skin expand itself. The fact that the weight of the transplanted fatty tissue cannot automatically lower the inframammary fold by itself makes this first-step surgery decisive. In a second session taking place after an interval of 3  months the inframammary fold is furFig. 69.3 BEAULI™ protocol “short”

therly filled up in order to stabilize its relocated position. Given the fact that enough tissue layers have been established from the prior surgery the lower quadrants are infiltrated in a deep and superficial layer which will provide the breast with a rounder arc and eventually a newly shaped contour (Figs. 69.4, 69.5, and 69.6). Consider two sessions for the relocation of the inframammary fold. The external tissue expansion device called the BRAVA system can additively be used for conditioning the tight tissue layers prior to lipotransfer [11, 12].

BEAULI™-Protocol ‘short’ preoperatively -

Analgesic sedation or general anesthesia

-

Tumescence solution: 3 liters N/S+ 150 cc lidocaine 1% + 3 cc adrenaline 1:1000 + 37.5 cc sodium bicarbonate 8.4 mVal

-

Preheating of the tumescence solution to body temperature

surgery -

Infiltration and suctioning through prick incisions using 3.8 cc rapid harvesting cannula and minimum negative pressure of -500

-

Constant water flow during harvesting Collecting the fat and separating it from the liquid and oily debris using e.g. LipoCollector

-

Filling of five 10 cc syringes facilitates counting of grafted volume

-

Infiltration with blunt cannula of 10 cm length allows augmentation via one laterocaudal prick incision

-

infiltration of 1 cc per 10 cm “tunnel”

-

maximum volume of fat transfer 300 cc per side

postoperatively -

compression garment of suctioned region for 4 weeks

-

keeping the breasts warm with a spool of wide absorbent cotton, no cooling, no pressure

69  Treatment of Tuberous Breast by Fat Grafting

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Fig. 69.4 Tuberous breast type II in a 33-year-old Taiwanese patient; front view: marking of the inframammary fold and donor site for lipotransfer (top left); (top

right) 17  days after the infiltration of 290  cc left and 300 cc right; (down left) 6 months postoperatively; (down right) 9 months postoperatively

69.5.3.1 Areolar Reduction There is a plenty of different ways of areolar reduction. In most cases patients with tuberous breast present with an enhanced areolar diameter. About one-fourth of the patients in type I and II, half of the patients in type III, and 75% of patients in type IV are affected. Especially the ratio to the mostly small breast bothers the patients in particular so the reduction of the nipple-areola complex will be required in most cases. The results are better, when the circular tension is minor due to the relaxing skin. Therefore it is carried out in a second-step surgery. Preoperatively we need to figure out if an open or closed areolar reduction is indicated (Fig. 69.6). Areolar reduction can be done within the second session of lipotransfer.

reduced by the closed technique without causing a strong protrusion of the areola. Normally a periareolar incision will be sufficient if the distance from the inferior margin of the areola to the submammary fold does not exceed 6 cm; otherwise an additional perpendicular skin removal is highly recommended to avoid a flat breast shape [13]. First the desired size of the new areola is marked (3.2–3.8  mm). The outer diameter is defined by the border of the pigmented areolar skin and will be drawn as a parallel line surrounding the inner marking. Then the excess skin is de-epithelialized and the dermis is cut at the outer marking into the fat layer. A mobilization of about 2 cm subdermally in the periphery is necessary to allow for a shrinkage of the skin. Regarding the tendency of a re-­ enlargement of the new nipple-areola complex we achieve best long-term sustainability using silk 2–0 for a tobacco-pouch suture in a deep dermal layer (Fig. 69.7). By this method the skin excess is definitely removed but due to the pigmentation of the areola

69.5.4 Open Areolar Reduction: Double-Layer Technique The indication for an open procedure is a relatively big skin excess which cannot be solely

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K. Ueberreiter and P. Azdasht

Fig. 69.5 Tuberous breast type IV in a 34-year-old Caucasian patient; front view (top left) and side view (down left); 8 months after second BEAULI after the infiltration of 270 cc left and right in each surgery, front view (top right) and side view (down right). During the first surgery an additional rigottomy of the left side was done and a pentagram reduction (see below) of the left areola during the second BEAULI.  The inframammary fold is

persisting, especially in the medial lower quadrant. Considering the original condition the patient was satisfied with the result and did not wish any further intervention. Otherwise a third intervention with transplanting only a small amount of around 30 cc of fat into the very superficial layer of the persisting inframammary fold followed by rigottomies would have been the proposed surgical treatment

even excellently sutured and healed wounds will be visible as a hypopigmented scar after a year or earlier. Nowadays, it is possible to camouflage periareolar scars by means of medical tattooing with good aesthetic results. Especially patients with a higher skin pigmentation who also have significantly higher risk of developing hyperpigmented, hypertrophic scars or keloids must be well educated prior to this surgery. There are interesting clinical approaches to treat these conditions by means of botulinum injections.

The pentagram technique is a less invasive and less scarring technique for moderately enlarged nipple-areola complexes.

69.5.5 Closed Areolar Reduction 69.5.5.1 Indication In patients with a small amount of skin excess you can choose this procedure. Sometimes the patient wishes to avoid visible scars anyhow or the risk of developing hypertrophic scars or

69  Treatment of Tuberous Breast by Fat Grafting

Fig. 69.6  Tuberous breast type III with areolar prolapse in a 24-year-old Caucasian patient: (upper row) preoperatively; (lower row) before surgery; 6  months postopera-

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tively after lipotransfer of 290 cc to the left and 300 cc the right breast without subcisions and periareolar skin removal during the second procedure

2-0 silk 3-0 vicryl

m 6c

x!

ma

2-0 silk

Fig. 69.7  Open areolar reduction: Diagram of the areola reduction; tobacco-pouch suture with 2–0 silk (prepared © Dr. K. Ueberreiter)

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keloids (especially considering patients with a darker pigmented skin) is high.

69.5.6 Technique You can either do this intervention during the second-step surgery of tubular breast treatment or as a separate independent surgery. When choosing the latter, it is possible to go for local anesthesia. We recommend the usage of a tetracaine/ lidocaine ointment approximately 30 min before giving the local anesthesia. We use 10  cc of a mixture of bupivacaine and adrenaline for local anesthesia for each side. Preoperatively the marking of a pentagram shape is done with the nipple in the middle and the peak aiming to the most cranial point of the areola (Fig. 69.8). All angles are located on the pigmented areolar ring. A prick incision with a scalpel no. 11 is done at each angle of the pentagram penetrating the dermis. Beginning with the entry point of the needle it is important to push it linearly forward towards the emerging point of the needle which is always located on the opposite site. The layer must not be too superficial to prevent a translucent thread. Due to the prick incisions it is very comfortable to pull the needle out respectively. The emerging point is now the next entering

Fig. 69.8  Pentagram of closed areolar reduction with a double-sided needle: The edges of the pentagram represent the anchoring points within the dermal layer of the areola. The point of origin can be chosen by the surgeon (prepared © Dr. K. Ueberreiter)

K. Ueberreiter and P. Azdasht

point of the needle anchoring the thread at one angle of the pentagram to the other. Continuing in the same manner one should finally end at the entry point of the thread. By evenly pulling the ends together it is possible to adjust the cockling of the areola. The more the diameter of the areola is reduced the more it will be protruding in lateral projection. To some extent the protrusion will even out after a period of 6 months resulting in a reduced areolar diameter. In order to prevent infections one should pay attention to the angle points that no thread is lurking out of the incision wounds. After tying up the ends of the thread, the knot will be buried in a deeper layer and cut off. At our clinic this technique if applicable showed very stable results considering relapses even after a period of 2 years.

69.5.7 Complications While performing the open areolar reduction only a superficial circular de-epithelialization of the area between the future areolar margins takes place. Consequently the deeper dermal layer is not being intersected. The risk of significantly harming the vessels to an extent of compromising circulation and resulting in tissue necrosis is very low because they are located within the deeper dermal layer. Similar applies to the nerves that run through the same layer. The closed areolar reduction technique respectively produces even less wounds. In any procedure an areolar relapse has hardly been an issue since using a silk 2.0 thread. In both techniques infections can occur in about 5% of the cases. They occur secondary after wound healing. In all of the cases the infection was originating from the area around the knot of the silk thread which moved outwards of the skin. Removal of the thread or parts of it needs to be evaluated depending on the severity of the infection. Around 80% subsided by a local antiseptic therapy with chloramphenicol ointment. The rest needed oral antibiotic therapy or revision surgery. Although very seldom, allergic or hypersensitive reactions towards the silk thread have been

69  Treatment of Tuberous Breast by Fat Grafting

observed in a few patients as well. In these cases, patients showed a delayed wound healing and a serous inflammation with repetitive negative smears for bacterial growth.

69.6 Necessity of Subcisions (“Rigottomies”) The subareolar region in tuberous breast is characteristically a very dense and rigid tissue. When it comes to fat grafting the blunt infiltration needle has to be placed with a higher effort into the correct layers overcoming the higher tissue resistance. Assuming that a dense tissue offers fewer surfaces for fat grafts than looser tissue, it is possible to use a method called “rigottomy,” named after its originator Rigotti [14, 15]. It is a method of increasing the infiltration surface for fat grafting in scar tissue by means of a hypodermic 18-gauge needle. Staggering the tissue in multiple layers and directions will loosen and extend the tissue. The fibrotic tissue of a scar is comparable in rigidity to the dense skin in the subareolar region of tuberous breast and is used as a minimal invasive alternative to flap surgeries with good results. While releasing the fibrotic fibers the surgeon has to find the transition point where the benefit turns into damaging the tissue, especially the vascular system to which the grafting process is dependent. Too many “rigottomies” within the tissue will lead to structural loss of the fibrous network while the interconnection of smaller cuts into larger ones might cause the formation of small reservoirs of fat grafts that fail to heal into the surrounding tissue. After applying one-sided additional “rigottomies” to type III and IV tuberous breast patients (e.g., Fig. 69.5) we could not find any significant improvement compared to the side treated solely with a BEAULI.  Showing already excellent results in most cases we have not found a necessary application so far in our clinic but it might be a good additional technique in some cases of stubbornly persisting inframammary folds. A common device for releasing constricted tissue is the Toledo dissector with a V-shaped tip. If rigottomies do not succeed nor deliver suffi-

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cient results, it is possible to implement this cannula while considering the side damages to the tissue carefully. Eventually there is no comparison between the utilization of cannulas and Toledo dissector. In this context the invasiveness of the reconstruction should be adapted to the tissue density and enhanced stepwise.

69.7 S  ilicone Implants or Fat Grafting? There are three correction points we have to address at the same time: firstly the hypoplasia, secondly the asymmetry, and thirdly, if present, the enlarged areola. Treating the hypoplasia can in general be done with implants or fat ad libitum but especially in type III and IV the risk of a double-bubble phenomenon is high, depending on the subareolar skin deficiency. It is possible to do additional procedures to correct this circumstance by using flap techniques or tissue expansion but not without forfeiting excessive visible scars. Especially when choosing fat grafting, the subcutaneous infiltration will contribute to sufficiently eliminate the former position of the inframammary fold. The patient has to be aware of the fact that probably two surgeries are needed, depending on the tuberous breast type and the rigidity of the skin. Type IV patients can expect an improvement but still visible second inframammary fold even with fat grafting. Additional surgeries can further improve the condition. When choosing silicone implants there is a higher risk of persisting inframammary fold and upward dislocation assuming that the rigid lower quadrants will remain fibrotic even after mobilization during implantation. Patients that are not suitable for fat grafting for reasons of low body fat ratio or low BMI or nicotine abuse can rather be considered for primary treatment of tuberous breast with silicone implants. With fat grafting the distribution of the infiltrated volume can individually be proportioned to the hypoplastic lower quadrants whereas implants do not offer this flexibility so far. Combining both procedures can be a reasonable approach by

K. Ueberreiter and P. Azdasht

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planning several surgical steps in advance: first relocating and stabilizing the inframammary fold with fat grafting and then inserting silicone implants. An additional top-up with fat often gives a more natural appearance to the silicone implants. Performing both procedures within one surgery will set an unfavorable condition of an increased tissue pressure and consequently reduces either the take rate or the total amount of fat being injected. The loosening effect of fat grafting is not present from the time of injection but takes a period of time. As this part is so deci-

sive for the tight tissue of the lower quadrants a multistep approach is rather recommended here. Silicone implants have a higher risk of persisting inframammary fold and upward dislocation in tuberous breast patients but a combination of both techniques can be a good option in patients with low body fat ratio. Under these circumstances usually a second session is hardly viable. If contrary to expectations the patient gains enough weight, it is possible to choose a further session of fat grafting after an interval of 3 months according to common fat grafting (Fig. 69.9).

Recommended Treatment of Tuberous Breasts with Fat Grafting after VonHeimburg Classification Condition Type

Hypoplasia of the lower medial quadrant

Type

Hypoplasia of the lower medial and lateral quadrant, sufficient skin in the subabareolar region

Type

Hypoplasia of the lower medial and lateral quadrant, deficiency of skin in the subabareolar region

Type IV

Severe breast constriction, minimal breast base

Types

Enlarged a reolar complex

I

II

III

I-IV

Treatment Fat grafting into hypoplastic area + Relocation of inframammary fold (approx. 2 surgeries at intervals of three months necessary)

Fat grafting into hypoplastic area + Relocation of inframammary fold (approx. 2 surgeries at intervals of three months necessary) Fat grafting into hypoplastic area + Relocation of inframammary fold (approx. 2 surgeries at intervals of three months necessary)

Fat grafting into hypoplastic area + Relocation of inframammary fold (approx. >2 surgeries at intervals of three months necessary)

Areolar reduction (open vs. closed) after correction of inframammary fold and volume deficiency

Fig. 69.9  Recommended treatment of tuberous breast with fat grafting after classification by Von-Heimburg

69  Treatment of Tuberous Breast by Fat Grafting

69.8 Outcome Almost 50% of women presenting to our clinic with micromastia and the wish for breast augmentation turn out to be patients with tuberous breast of different stages. Often not exactly knowing about this condition, the patients are commonly diagnosed first at surgical consultation. Frequently the women seek for symmetry and adjustment in the volume of circumscribed areas rather than an evenly distributed gain in volume. This challenging requirement demands a more individual approach than in classic breast augmentation. Determining the possible outcome and the number of surgeries supplies a realistic overview and expectation for the patient. On average, 230 cc per side was transplanted in each session so that most patients required two surgeries for correction. Although the patient is free to choose the number of fat grafting sessions, provided that the preconditions are given, more than 90% decide on a second step of fat grafting after the first surgery. Less than 10% undergo a third surgery or more. Two-thirds of tuberous breast patients require either unilateral or bilateral areolar reduction.

69.9 Conclusion The treatment of tuberous breast with autologous fat grafting takes place in two steps comprising the reconstruction of the inframammary fold followed by the volumization of the breast and its continuous shift further downwards. In conclusion the relocation of the mammary gland as applied in other techniques can totally be abandoned because the widening of the inframammary fold is uncomplicated. Additional interventions like “rigottomies” can be a helpful device and were applied in deformities of high degree. Compared to other methods than the autologous fat transfer the big advantage of this technique lies in the fact that extensive surgeries of

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the mammary gland are avoided especially considering the patient’s still young age whereas complications like persistent inframammary folds are only to be seen in grade IV. Above all, the patient with tuberous breast deformity must be identified within all patients presenting with hypoplasia of the breast. The treatment and outcome differ in these patients. The augmentation alone is not the adequate treatment and the results will be unsatisfactory when the former inframammary fold persists and a so-called double-­ bubble phenomenon occurs. The overall reliable results combined with the low effort and the low risks and complications make this procedure superior to the still widely spread treatment with silicone implants. Therefore tuberous breast deformities have exclusively been treated by autologous fat transfer at our clinic instead of using silicone implants ever since 2007 [16].

References 1. Ribeiro L, Canzi W, Buss A Jr, Accorsi A Jr. Tuberous breast: a new approach. Plast Reconstr Surg. 1998;101(1):42–50; discussion 51–2 2. Rees TD, Aston SJ.  The tuberous breast. Clin Plast Surg. 1976 Apr;3(2):339–47. 3. Ueberreiter K, Tanzella U, Cromme F, Doll D, Krapohl BD.  One stage rescue procedure after capsular contracture of breast implants with autologous fat grafts collected by water assisted liposuction (‘BEAULI Method’). GMS Interdiscip Plast Reconstr Surg DGPW. 2013;2:Doc03. 4. Papadopoulos S, Vidovic G, Neid M, Abdallah A.  Using fat grafting to treat breast implant capsular contracture. Plast Reconstr Surg Glob Open. 2018;6(11):e1969. https://doi.org/10.1097/ GOX.0000000000001969. 5. Coleman SR, Saboeiro AP. Fat grafting to the breast revisited: safety and efficacy. Plast Reconstr Surg. 2007;119(3):775–87. 6. Von Heimburg D, Exner K, Kruft S, Lemperle G. The tuberous breast deformity: classification and treatment. Br J Plast Surg. 1996;49(6):339–45. 7. Grolleau JL, Lanfrey E, Lavigne B, Chavoin JP, Costagliola M.  Breast base anomalies: treatment strategy for tuberous breasts, minor deformities, and asymmetry. Plast Reconstr Surg. 1999;104:2040–8. 8. Bauer AT, von Lukowicz D, Lossagk K, et al. Adipose stem cells from lipedema and control adipose tissue

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respond differently to adipogenic stimulation in vitro. 1 4. Rigotti G, Marchi A, Galiè M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transPlast Reconstr Surg. 2019;144(3):623–32. https://doi. plant: a healing process mediated by adipose-derived org/10.1097/PRS.0000000000005918. adult stem cells. Plast Reconstr Surg. 2007;119:1409– 9. Priglinger E, Wurzer C, Steffenhagen C, et  al. 22; discussion 1423. 17 The adipose tissue-derived stromal vascular fraction cells from lipedema patients: are they differ- 15. Rigotti G, Marchi A, Khouri RK. Minimally invasive autologous mastectomy incisionless reconstruction; ent? Cytotherapy. 2017;19(7):849–60. https://doi. external expansion fat grafting and percutaneous scar org/10.1016/j.jcyt.2017.03.073. release: a multicenter experience. Paper presented 10. Ueberreiter K, von Finckenstein JG, Cromme F, at: 88th Annual Meeting and Symposium of the et  al. BEAULI  – a new and easy method for large-­ American Association of Plastic Surgeons; March 24, volume fat grafts. Handchir Mikrochir Plast Chir. 2009; Rancho Mirage, Calif. 2010;42(6):379–85. 16. Ueberreiter K, Tanzella U.  Behandlung der tuber11. Khouri RK, Schlenz I, Murphy BJ, Baker ösen Brust mit freier Fettgewebstransplantation. 47. TJ. Nonsurgical breast enlargement using an external Jahrestagung der Deutschen Gesellschaft der Plastischen, soft-tissue expansion system. Plast Reconstr Surg. Rekonstruktiven und Ästhetischen Chirurgen 2000;105(7):2500–12.; discussion 2513-4. https://doi. (DGPRÄC), 21. Jahrestagung der Vereinigung der org/10.1097/00006534-­200006000-­00032. Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC). 12. Heine NP, Prantl L.  Brustrekonstruktion durch Kassel, 08.-10.09.2016. Düsseldorf: German Medical Eigenfettinjektion. Chir Praxis. 2014;78:77–90. ISSN Science GMS Publishing House; 2016. p. Doc177. 0009–4846 https://doi.org/10.3205/16dgpraec177, urn:nbn:de:0183-­ 13. Nahabedian MY.  Breast deformities and mastopexy. 16dgpraec1779 published September 27, 2016. Plast Reconstr Surg. 2011;127:91–102.

Stromal Enriched Lipograft for Breast Augmentation

70

Aris Sterodimas

Key Messages  • The current most practiced technique of breast augmentation is the silicone gel implant. • The main concerns of silicone implant insertion are capsular contracture, delayed-onset seroma, anaplastic large-cell lymphoma (ALCL), implant malposition, implant animation deformity, double bubble, rippling, and visibility of the implant. • The degree of reabsorption of the injected adipose tissue is unpredictable as has been reported by numerous studies when using the non-stromal enriched lipograft. • Autologous fat breast augmentation using the Stromal Enriched Lipograft (SEL) technique by a multilevel, multi-tunnel, and multipoint percutaneous injection can achieve the required aesthetic effect without the drawbacks of the non-stromal enriched lipograft. • SEL is a safe and acceptable method for aesthetic and reconstructive breast surgeries due

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_70) contains supplementary material, which is available to authorized users. A. Sterodimas (*) Department of Plastic & Reconstructive Surgery, Metropolitan General Hospital, Athens, Greece e-mail: [email protected]

to its high patient satisfaction and low complication rate and it is a valuable new tool in the repertoire of every plastic surgeon for breast augmentation.

70.1 Introduction Over the last 30 years there has been a constant interest in breast augmentation by the use of autologous fat transplantation for reconstructive and cosmetic purposes. A 1987 American Society of Plastic and Reconstructive Surgeons position paper predicted that fat grafting would compromise breast cancer detection and should therefore be prohibited [1]. Up to now, adipose tissue injection to the breast or mammary lipoaugmentation has been stuck by two limiting factors. Firstly, fat injection in and around the breast could result in cyst formation, indurations, and fat necrosis that could be mistaken as cancerous calcifications. Secondly, the degree of reabsorption of the injected non-stromal enriched lipograft is unpredictable. Fat grafting remains shrouded in the stigma of variable results experienced by most plastic surgeons when they first graft fat [2]. Despite the safety and efficacy of breast implants, they do not last forever with an average life span of 10–15  years. Over time, device failure will become more likely due to rupture and/or capsular contracture that usually requires removal or replacement.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_70

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In 2009, the American Society of Plastic Surgeons Task Force on Autologous Fat Grafting (AFG) determined that autologous fat grafting was a safe procedure with a relatively low rate of complications. In addition, they stated that artifacts could indeed be identified and distinguished from malignancy in early breast cancer screenings [3]. The aim of fat grafting is to create a breast with an aesthetic, natural appearance. Fat grafting actually consists of a multiplicity of individual steps from fat harvest to graft preparation and to fat injection. Although a number of techniques for fat grafting have been described, they all aim to augment the breast, camouflaging irregularities in its shape and texture and more closely approximating a natural breast contour. Fat grafting to the breast also provides the added benefit of being minimally invasive and removing unwanted fat from potential donor areas. As many as 30% of all breast augmentations and reconstructions now undergo fat grafting, and while complications including cyst formation, fat necrosis, or even infection are all possible, the procedure is generally well tolerated with high rates of patient satisfaction [4]. Our group has extensively published on the Stromal Enriched Lipograft (SEL™) [5–7]. In SEL, freshly isolated SVF is attached to the aspirated fat, with the fat tissue acting as a living bioscaffold before transplantation [8]. The results of a series of patients using this technique for breast augmentation and reconstruction are presented in this chapter.

70.2 Surgical Technique Marking of the abdominal area to be liposucted and the breast area to be fat grafted is made while the patient is in standing position. Preoperative sedation in the surgical suite is administered. Anesthesia consists of local anesthetic and intravenous sedation. After the injection of normal saline wetting solution containing 1:500,000 of adrenaline by a small-bore cannula and waiting for 15 min, a 20-cc syringe attached to a 3 mm blunt cannula is inserted through one small incision in the flanks and in the abdominal area [9].

A. Sterodimas

Fat is aspirated by using the syringe method. The fatty tissue aspirated is treated in the following manner. Firstly the 2/3 of the aspirated fat is used in order to isolate the SVF.  Digestion is done with 0.075% collagenase (Sigma, St. Louis, MO) in buffered saline and agitated for 30 min at 37 °C using the Automatic Cell Station produced by BSL, Seoul, Korea. Separation of the SVF containing ADSCs is then done by using centrifugation at 1200  ×  g for 15  min and washing the enzyme out. The SVF is derived from the centrifuged fat (Video 70.1). The remaining 1/3 of the aspirated fat is treated in the following way: with the syringe held vertically with the open end down, the fat and fluid are separated. Mixing of the SVF containing ADSCs and the purified fat is finally done (Fig. 70.1) and transferred into 10 ml syringes for application [10]. This whole procedure is done inside the operating theatre, by two tissue engineers, automatically in a closed system, and the time required is about 55 min. The adipose tissue graft enriched with SVF is inserted (Video 70.2). Breast tissue SEL injection is then performed. Firstly the blunt tip of the injection cannula of 1.9 mm is tilted and inserted through a 2  mm wound cut using a 22G needle. A multilevel, multi-tunnel, and multipoint percutaneous injection of SEL is done in the breast. Fat droplets are delivered, while the cannula is withdrawn. In a fan-shaped manner, numerous fat parcels can be consistently micro-transplanted. The injection cannula is then advanced to the entire subcutaneous and glandular plane of the breast and an average of 50–320  ml of SEL is injected in each breast. The five golden rules for successful fat grafting to the breast and how to avoid complications are shown in Fig. 70.2a, b. No pressure or molding of the transplanted fat is needed. A broad-spectrum antibiotic, an analgesic, and an anti-inflammatory medication are prescribed during the following 3 postoperative days. The study included 87 patients, all Caucasian females with a mean age of 27 years (18–65). The mean BMI was 25.3 (22–29). The indications for treatment were 72 females with hypomastia, 3 females with severe breast asymmetry, and 12 females requiring breast reconstruction. The BREAST-Q scale was used to

70  Stromal Enriched Lipograft for Breast Augmentation

STEM CELL-RICH FAT GRAFT

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STROMAL ENRICHED LIPOGRAFT READY FOR INJECTION CENTRIFUGATION

ADIPOSE DERIVED STEM CELLS CONCENTRATED

COLLAGENASE DIGESTION

SALINE PURIFICATION

Fig. 70.1  Schematic representation of the Stromal Enriched Lipograft

a

b

Multi tummel Fat Grafting Multi leve; Fat Grafting Retrograde ‘spaghetti’ like Fat Grafting SELTM Protocol for Fat Grafting Subcutaneous Fat Grafting

AVOID Excessive Fat Grafting > 250 ml / side AVOID Bolus Injection > 10 ml / tunnel AVOID Prograde Injection AVOID Uniplane Injection

Fig. 70.2  The five golden rules for successful fat grafting to the breast and how to avoid complications

evaluate the outcome. It has procedure-specific structure with scales that evaluate both satisfaction and quality of life after breast augmentation. The BREAST-Q Augmentation Module has four scales: satisfaction with breasts, psychosocial well-being, sexual well-being, and physical well-­ being. Scale items are summed and transformed on a scale from 0 (worst) to 100 (best) using the Q-score program (Table 70.1).

70.3 Results 70.3.1 Patient 1 A 37-year-old female was referred to our clinic after she had been operated for breast cancer on the left breast performing quadrantectomy. On examination the patient had a significant deformity with retraction of the nipple-areolar ­complex

A. Sterodimas

1054 Table 70.1  Demographics of the patients Mean age Gender Ethnicity BMI Pre-op Q score Post-op Q score Volume of injected fat per breast Indications for treatment

27 Years (18–65) 87 Females Caucasian 25.3 (22–29) 54 (48–62) 85 (78–98) 175 (50–320 ml) 72 Hypomastia 3 Severe asymmetry 12 Reconstructive

on the left breast (Fig. 70.3a–c). She underwent Stromal Enriched Lipograft to the left breast. The total volume of fat grafted was 79 ml. The patient is shown 12 months after the procedure with no complications and a satisfactory aesthetic result (Fig. 70.3d–f). The preoperative Q score was 54 and the postoperative 85.

70.3.2 Patient 2 A 23-year-old female with hypomastia was referred to our clinic. She expressed the desire to undergo the least invasive procedure in order to achieve an aesthetically accepted result (Fig.  70.4a–e). She used the Brava system for 2 months (Fig. 70.5a–e). She underwent Stromal Enriched Lipograft and the total volume of fat inserted was 170 ml in each breast. The patient is shown 12  months after the procedure (Fig.  70.6a–e). Twenty-four months after the first procedure the patient underwent another SEL procedure with 190  ml in each breast of SEL. The patient is shown 4 years after the last procedure with no complications and a very satisfactory aesthetic result (Fig.70.7a–e). The MRI scan shows the preoperative and postoperative breast lipofilling 18 months after the second procedure (Fig. 70.8a, b). The total amount of fat inserted was 360 ml in each breast using the SEL™ method. The preoperative Q score was 32 and the postoperative 92.

70.3.3 Patient 3 A 27-year-old female presented to our clinic requesting breast augmentation but she did not have enough fat to be used for the procedure (Fig. 70.9a–c). She underwent composite breast augmentation using a 190  ml silicone implant bilaterally in combination with 120 ml of SEL in each breast. The patient is shown 6 years after the procedure with no complications and a satisfactory aesthetic result (Fig.70.9d–f). The preoperative Q score was 46 and the postoperative 88.

70.3.4 Patient 4 A 41-year-old female patient presented to our clinic requesting removal of the silicone implants and replacement with fat grafting (Fig. 70.10a–c). She underwent simultaneous removal of the silicone implants and SEL of 260 ml in each breast. The patient is shown 2 years after the procedure with no complications and a very satisfactory aesthetic result (Fig. 70.10d–f). The digital mammogram shows the preoperative and postoperative breast images 24  months after the surgical procedure (Fig.  70.11a, b). The preoperative Q score was 62 and the postoperative 81.

70.3.5 Patient 5 A 29-year-old female patient presented to our department having been operated five times for her breast ptosis and her mild pectus excavatum (Fig.  70.12a–c). She underwent breast implant replacement and composite breast augmentation using a 215 ml silicone implant bilaterally in combination with 90 ml of SEL in each breast using the SEL technique. In the area of the chest 85 ml of SEL was inserted to correct the mild pectus excavatum. The patient is shown 3 years after the procedure with no complications and a very satisfactory aesthetic result (Fig. 70.12d–f). The preoperative Q score was 23 and the postoperative 95.

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Fig. 70.3 (a–c) Preoperative photos of a 37-year-old female patient presenting with a significant deformity with retraction of the nipple-areolar complex on the left breast after quadrantectomy. (d–f) Postoperative photos of

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Fig. 70.4 (a–e) Preoperative photos of a 23-year-old female patient presenting with a significant hypomastia

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Fig. 70.5 (a–e) Photos of a 23-year-old female patient after 2 months of BRAVA use

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Fig. 70.6 (a–e) Postoperative photos of a 23-year-old female after Stromal Enriched Lipograft to both breasts with a 170 ml of fat grafted to each breast after 1 year

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Fig. 70.7 (a–e) Postoperative photos of a 23-year-old female after Stromal Enriched Lipograft to both breasts with a 190 ml of fat grafted to each breast 4 years after the last procedure

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Fig. 70.8 (a, b) The MRI scans show the preoperative and postoperative breast lipofilling 18  months after the second procedure

70.4 Discussion In 2004, the research team led by the senior author Dr. Sterodimas described a method of supplementing the lipoaspirate used for fat grafting with the stromal vascular fraction found in adipose tissue. This process was named Stromal Enriched Lipograft [11]. The rationale behind this technique is that aspirated adipose tissue is poor in progenitor cells, growth factors, and cytokines, which are contributing factors to poor ­survival in vivo of the fat graft [6]. While certain aspiration sites were initially thought to produce better graft take, these theories have not been supported by recent studies [7]. In the SEL technique, the donor sites are chosen together with the patient and care is taken in order to avoid reharvesting fat from a previous lipoaspiration site and also not to create contour deformities. At our department, the preferred donor sites for fat grafting are the flanks, abdomen, and thighs based on the availability of subcutaneous adipose tissue and also the patient preference. Studies demonstrate that mature adipocytes can tolerate hypoxia for approximately 24  h at normal core body temperature due to the relatively active metabolic demand of their intracellular cytoplasm. In vivo, fat grafting involves placement of 1–4 mm diameter adipose tissue fragments, each consisting of thousands of individual cells, into a profoundly ischemic adipose tissue recipient site

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microenvironment. Ideally, the graft fragment is initially nourished by diffusion of oxygen and glucose from the surrounding tissue and quickly revascularized through microvascular inosculation and neovascularization. The nature of the recipient site plays a key factor in lipoaugmentation. A vascularized recipient site can enhance the viability of fat grafts and abate liponecrotic lesions. The non-stromal enriched lipograft requires an extensive revascularization from the recipient site resulting in a low fat retention; as revascularization is not achieved, resorption of fat will occur. This could lead to fat necrosis, dissolution, and absorption, easily leading to infection, pain and cyst formation, fibrosis or calcification, and breast deformation. Stromal vascular fraction (SVF) is a heterogeneous population of cells that results from the processing of adipose tissue and is composed mainly of pericytes and both adipose-derived and vascular endothelial progenitor cells plus a number of cytokines and growth factors. The most important element in successful engraftment is the presence of ADSCs. These cells are pluripotent mesenchymal stem cells that reside in large numbers in adipose tissue. These small stellate-­ shaped cells are identified by surface antigens such as CD134 and their ability to form colonies in vitro. It is estimated that one to three million of these small stellate-shaped cells typically reside in proximity to small vessels of adipose tissue. They are known to tolerate the conditions associated with harvest and graft injection more successfully than mature adipocytes, participate in the tissue response to these stresses, and direct adipose tissue regeneration. ADSCs are able to differentiate into new adipocytes, replacing a portion of the adipocytes, which succumb to apoptosis due to hypoxic or physical stress and have been shown to actively promote angiogenesis via growth factor secretion and through neovascular differentiation [7]. By promoting the development of new vasculature in the grafted tissue, ADSCs are able to speed the recovery from ischemia after transplantation and reduce the number of cells succumbing to hypoxic stress, thereby improving graft volume retention. In 2013, Kølle et  al. conducted a randomized

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Fig. 70.11 (a, b) The digital mammogram shows the preoperative and postoperative breast images 24 months after the surgical procedure

placebo-­controlled trial to investigate the effects of ADSC enhancement on graft survival in humans. Using cultured ADSCs, they reported significantly higher levels of volume retention compared to the non-stromal enriched lipografts. The ADSC-enhanced group retained 80.9% of the initial volume on average, compared with the non-stromal enriched lipograft group which only retained 16.3% on average [12]. Clinical studies have not demonstrated malignant transformation or an increase in cancer recurrence in patients receiving autologous fat grafting [13, 14]. The use of SEL can augment certain areas of the breast, for example in the midline to build cleavage, adding upper pole fullness, or under the intended nipple position to provide additional projection, that cannot be achieved by the insertion of silicone implant alone. SEL can effectively improve implant animation deformity, rippling, and visibility of the implant in décolletage. Autologous SEL around the implant could help in the prevention of postoperative implant displacement, especially reducing the risk of medial or inferior displacement. The injection of SEL around the implant could strengthen the soft-tissue support, hence making the transition between the skin and the implant more natural and soft. Introduction of non-biologic materials into the body always induces formation of a capsule, but in the breast this may be particularly severe. Double-bubble and bottoming-out deformities are usually grouped within the category of implant malposition complications after breast

augmentation. SEL grafting has been proved to be effective in these cases, thus avoiding surgical interventions. Non-stromal enriched lipograft has also been used for the treatment of such cases with success. The BREAST-Q helped facilitate an evidence-based approach to the management of patients undergoing breast augmentation in this series of patients. For some lean and slim patients, the single use of autologous fat transplantation for breast augmentation is almost difficult due to the lack of appropriate harvest site for high quality and quantity of fat graft. The combination of a silicone implant with SEL could eventually lead to very satisfactory results, complementing the problems in the single applications of each procedure since after the implantation of the silicone gel prosthesis, transplantation of small amount of autologous fat around the implant could improve the overall effect, hence eventually also ameliorating the feel of the breast, making it more natural. In cases of breast reconstruction after mastectomy, SEL has proved to achieve satisfactory results when it is used alone or in combination with a silicone implant [15]. Breast implant-associated-anaplastic large-cell lymphoma (BIA-ALCL) has recently emerged as a public concern and is associated with the use of textured-surface breast implants. BIAALCL is extremely rare with a reported incidence that ranges from 1:1000 to 30,000 patients [16]. In these cases the implant needs to be removed and capsulectomy needs to be performed. SEL can provide an alternative option for breast reconstruc-

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Fig. 70.12 (a–c) Preoperative photos of a 29-year-old female requesting correction of breast ptosis and of her mild pectus excavatum. (d–f) Postoperative photos of a 29-year-old female who underwent breast implant replacement and composite breast augmentation using a

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tion for these cases [17, 18]. The cost of the SEL technique is 35% higher as compared to the rest of the fat grafting procedures available in the market. This is due to the consumables needed for the SEL protocol. A limitation of the study is that it was not feasible to compare the SEL versus the non-stromal enriched lipograft in the breast although this has been done for the face fat grafting and the results have been published already proving the superiority of the SEL technique [7]. A recent article published by the senior author proves the superiority of the SEL when it is used in composite breast augmentation compared to breast augmentation using silicone implant as it achieves a higher patient satisfaction and aesthetic outcome. The retrograde microfat injection has been used by the author in the last 17 years with success, avoiding complications like oil cysts and fat necrosis.

70.5 Conclusion SEL is a safe and acceptable method for aesthetic and reconstructive breast surgeries due to its high patient satisfaction and low complication rate. Future research will hopefully refine our understanding of the effect of fat grafting on the local tissue microenvironment and provide clues toward its optimization. Large-scale, controlled studies are needed to advance our ability to tailor the SEL technique further.

References 1. ASPRS Ad-Hoc Committee on New Procedures. Report on autologous fat transplantation, September 30, 1987. 2. Illouz YG, Sterodimas A. Autologous fat transplantation to the breast: a personal technique with 25 years of experience. Aesthet Plast Surg. 2009;33(5):706–15. 3. Gutowski KA. ASPS fat graft task force current applications and safety of autologous fat grafts: a report of the ASPS fat graft task force. Plast Reconstr Surg. 2009;124(1):272–80. 4. Pereira LH, Sterodimas A. Autologous fat transplantation and delayed silicone implant insertion in a case of Mycobacterium avium breast infection. Aesthetic Plast Surg. 2010;34(1):1–4.

1065 5. Sterodimas A, de Faria J, Nicaretta B, Boriani F.  Autologous fat transplantation versus adipose-­ derived stem cell-enriched lipografts: a study. Aesthet Surg J. 2011;31(6):682–93. 6. Sterodimas A, De Faria J, Correa WE, Pitanguy I.  Tissue engineering in plastic surgery: an up-to-­ date review of the current literature. Ann Plast Surg. 2009;62(1):97–103. 7. Sterodimas A, de Faria J, Nicaretta B, Papadopoulos O, Papalambros E, Illouz YG. Cell-assisted lipotransfer. Aesthet Surg J. 2010;30(1):78–81. 8. Sterodimas A.  Stromal enriched lipograft for rhinoplasty refinement. Aesthet Surg J. 2013;33(4):612–4. 9. Pereira LH, Sterodimas A, Nicaretta B.  Liposuction of the trunk and thighs. In: Aly A, Nahas F, editors. The art of body contouring. Thieme; 2017. 10. Sterodimas A. The role of stem cells in body contouring. In: Theodorou S, Chia C, editors. Liposuction & emerging technologies in body contouring. Thieme; 2018. 11. Sterodimas A.  Tissue engineering with adipose derived stem cells (ADSCs) in plastic & reconstructive surgery: current and future applications. In: Di Giuseppe A, Shiffman MA, editors. New frontiers in plastic and cosmetic surgery. Jaypee; 2015. 12. Kølle SF, Fischer-Nielsen A, Mathiasen AB, Elberg JJ, Oliveri RS, Glovinski PV, Kastrup J, Kirchhoff M, Rasmussen BS, Talman ML, Thomsen C, Dickmeiss E, Drzewiecki KT.  Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-­ controlled trial. Lancet. 2013;382(9898):1113–20. 13. Kaoutzanis C, Xin M, Ballard TN, et  al. Outcomes of autologous fat grafting following breast reconstruction in post-mastectomy patients. Plast Reconstr Surg. 2014;134:86–7. 14. Cohen S, Sekigami Y, Schwartz T, Losken A, Margenthaler J, Chatterjee A. Lipofilling after breast conserving surgery: a comprehensive literature review investigating its oncologic safety. Gland Surg. 2019;8(5):569–80. 15. Sterodimas A.  Adipose stem cell engineering: clinical applications in plastic and reconstructive surgery. In: Illouz YG, Sterodimas A, editors. Adipose derived stem cells and regenerative medicine. Berlin: Springer; 2011. p. 165–80. 16. Clemens MW. Horwitz SM NCCN consensus guidelines for the diagnosis and management of breast implant-associated anaplastic large cell lymphoma. Aesthet Surg J. 2017;37(3):285–9. 17. Sterodimas A, Nicaretta B, Boriani F.  Modified round block mastopexy versus traditional round block mastopexy. Eur Rev Med Pharmacol Sci. 2015;19(3):350–6. 18. Sterodimas A.  Silicone implant versus silicone implant assisted by stromal enriched lipograft breast augmentation: a prospective comparative study. Medicines (Basel). 2020;7(5):E28.

Mastopexy with Auto-­Augmentation and Fat Grafting

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M. Bradley Calobrace and Chet Mays

Key Messages  • Drawings are performed preoperatively as a guide with intraoperative adjustments expected. • Ideal candidates for mastopexy with auto-­ augmentation have a high footprint, dense breast tissue, minor to moderate ptosis, adequate volume, and good-quality skin. • Superior pedicle is reserved for modest mastopexies, with NAC elevation limit of 5–6 cm. • Resecting all extra skin through an inverted-T technique provides the most accurate appearance of the breast at the end of the procedure. • Maintenance of upper pole volume is less reliable with a mastopexy alone. It can be Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_71) contains supplementary material, which is available to authorized users. M. B. Calobrace (*) Private Practice, CaloAesthetics Plastic Surgery Center, Louisville, KY, USA Clinical Faculty, Division of Plastic Surgery, University of Louisville, Louisville, KY, USA Clinical Faculty, Division of Plastic Surgery, University of Kentucky, Lexington, KY, USA e-mail: [email protected] C. Mays Private Practice, CaloAesthetics Plastic Surgery Center, Louisville, KY, USA

improved with auto-augmentation and fat grafting and optimized with a breast implant.

71.1 Introduction Understanding the underlying cause of the ptosis, whether it be developmental or acquired secondary to weight loss, hormonal changes, pregnancy, and/or aging, is critical in determining the appropriate surgical approach. In the initial assessment, it is important to determine the volume status of the breast, the extent of loss of upper pole volume, the quality of the breast tissue, and the patient’s goals for the procedure. The majority of mastopexy techniques focus on the elevation of the NAC and the lower pole of the breast through skin tightening and potentially parenchymal resection. These techniques, however, have traditionally failed to establish and maintain volume in the upper pole long term. Patients desiring upper pole volume with breast ptosis often require placement of an implant with the mastopexy to achieve the desired appearance. The addition of an implant to the procedure, an augmentation mastopexy, is by far the most popular and most successful method for achieving and maintaining upper pole volume post-mastopexy. However, there are many patients who will not accept the inclusion of breast implant but are dissatisfied with their breast shape and seek a masto-

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pexy for improvement. Also, breast volume may be adequate and additional volume would be unacceptable to the patient. There are a variety of mastopexy techniques described to address the ptotic breast, such as the circumareolar technique, circumvertical technique, and inverted-T scar technique [1–5]. However, there is much more variation in the techniques, including the vascular pedicle orientation, management of the parenchyma, and additional ancillary procedures to enhance the results. In an effort to optimize upper pole volume, various surgical techniques have been employed, including parenchymal suturing techniques, local flap transpositions, and use of a pectoralis sling for stabilization of the flap transfer [6–12]. In our experience, the utilization of a lower pole parenchymal transposition flap to auto-augment the upper pole has been an excellent alternative. Our approach most closely resembles that first described by Ribiero and more recently modified by Hammond [9, 12]. This is often combined with upper pole fat grafting to further enhance the outcome. The decision on the appropriate mastopexy approach is based on not only the physical findings but also patient expectations. In the preoperative evaluation, breast measurements, breast tissue density, quality of skin and breast parenchyma, NAC and breast ptosis, chest wall characteristics, and breast footprint all must be considered when planning for the procedure. The ideal candidate would be a patient with adequate volume, dense breast parenchyma, mild-to-­ moderate ptosis, good-quality skin, and a high breast footprint (Fig. 71.1). The upper pole flap transposition not only creates volume higher in the breast, but also unloads the volume from the lower pole of the breast, potentially contributing to a more successful outcome as compared to a traditional mastopexy. Perioperative decision-making is critical to a successful outcome in an auto-augmentation mastopexy surgery. In this chapter, we review our approach to decision-making with a focus on patient selection, review of mastopexy options, vascular anatomy of the transposition flap, and selection and planning of the mastopexy auto-­ augmentation procedure. The operative technique

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Fig. 71.1  Breast ptosis present with good breast characteristics for a mastopexy with auto-augmentation including adequate volume, a high breast footprint, and dense breast parenchyma with good skin quality

and postoperative care will be outlined in detail, providing a predictable approach that can produce the most successful outcomes, minimal complications, and very satisfied patients.

71.2 Preoperative Evaluation The evaluation should begin with a breast exam with breast measurements including the base width, sternal notch-to-nipple distance, and nipple-­to-fold distance (at rest and under maximal stretch). The assessment should also include evaluation of the level of ptosis, skin thickness and elasticity, quantity and distribution of subcutaneous fat, composition and firmness of the breast parenchyma, integrity of the Cooper’s ligaments, nature and position of the underlying musculature, and shape and slope of the underlying chest wall. All these aspects of the breast composition influence the shape of the breast and ultimately the outcome after the mastopexy (Table 71.1). One additional aspect in considering the mastopexy with auto-augmentation is the presence of an adequate amount of lower pole tissue to make the transposition possible and worthwhile. In patients with significant nipple descent but with short N-IMF distance, the vertical lower pole

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Table 71.1  Assessment of breast ptosis Relationship of the NAC to the IMF (Regnault’s degree of ptosis)  a. Grade 1: Nipple at the level of the inframammary fold, above the lower contour of the gland  b. Grade 2: Nipple below the level of the inframammary fold, above the lower contour of the gland  c. Grade 3: Nipple below the level of the inframammary fold, at the lower contour of the gland Amount of breast tissue overhanging the fold Location of the NAC on the breast mound Amount of vertical excess and horizontal excess Footprint of the breast on the chest wall: Low, medium, high Quantity and quality of breast parenchyma and skin

Fig. 71.2  The (a) superior or superomedial pedicles in the design of the mastopexy. The superior is most often used based only off the second branch but the superomedial can be used based off the second and third branches, but would be less common as the dermis attachment for the blood supply would limit the use of the inferior pole of tissue (as shown)

segment of tissue would be too short and inadequate to provide any benefit in the upper pole. Also, the footprint should be observed. Whereas this procedure can be performed on any footprint, based solely on the surgeon’s comfort and experiit is the high-breasted patient that benefits the ence in utilizing a vertical approach with a supemost. In these patients, the short upper thorax riorly based or superomedial blood supply requires only a small amount of tissue to produce (Fig. 71.2). As the flap utilizes the lower pole tisa significant improvement. In the low-breasted sue, once the pedicle requires the use of the infefootprint patient, the auto-augmentation does not rior flap tissue in the design, the auto-augmentation elevate the upper breast border significantly is not possible. The flap transposition to the upper enough and an implant would be more appropri- pole is just a variant of the vertical mastopexy, ate for correcting the upper pole. Most patients and individual experience will determine the are not on either of these extremes, but more in appropriateness of this approach. the grey zone, and judgment will be necessary. Likewise, assessing the firmness of the parenchyma is important, as patients with more firm, 71.2.1 Blood Supply dense breasts do better at holding the shape long term compared to more lax breast tissue such as a An understanding and thorough assessment of the vascular anatomy are critical to performing weightless patient. The mastopexy auto-augmentation is a cir- the procedure safely. The breast has a rich blood cumvertical or vertical type mastopexy and thus supply from multiple sources, including the interan assessment of the pedicle planned must be nal mammary artery perforators, lateral thoracic done. The most common pedicle for this tech- arteries, and thoracoacromial, anterolateral, and nique is a superior pedicle, but a superomedial anteromedial intercostal perforators. The supepedicle is occasionally used. In our experience, rior pedicle is supplied by the second branch of elevation of the NAC beyond 5–6 cm, depending the internal mammary artery (IMA) that emerges on the quality of the tissue, is less reliable with a deep from the second interspace and courses superior pedicle and an inferior based pedicle superficial across the medial upper breast to enter would be used and a mastopexy auto-­ the NAC slightly medial to the midline and augmentation would not be performed. This final approximately 1 cm deep. The superomedial pedjudgment as to the viability of this technique is icle includes also the third branch of the IMA that

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emerges from the third interspace and similarly courses superficially across the breast parenchyma to the medial aspect of the NAC.  The superficial position of these vessels in the upper pole allows the entire breast to be elevated off the muscle and chest wall in a subcutaneous plane for the planned flap transposition. The central pedicle is supplied by the fourth branch of the IMA that courses deeply across the medial breast to enter through Wuringer’s septum approximately 1–2  cm above the IMF and often just medial to the breast meridian. This is the blood supply to the auto-augmentation flap [13] (Fig. 71.3). An understanding of the location of the fourth branch supplying this lower transposition flap is critical to creating a mobile flap of tissue with a viable pedicle blood supply. Obviously, if a patient has had a breast augmentation in the past or the breast has in any way been elevated off the chest wall previously, the central pedicle would have been divided and the flap transposition would not be possible.

Fig. 71.3  Blood supply to the inferior dermoglandular flap with the fourth branch of the IMA seen within Wuringer’s septum

71.2.2 Fat Grafting In the mastopexy patient, whether an auto-­ augmentation is utilized or not, lipofilling can be very effective in improving the upper pole volume without the use of an implant. Fat can reliably improve breast fullness, coverage, and cleavage, but is limited in the ability to appreciably enhance core projection of the breast. It is best utilized for patients who want a modest increase in breast size and a natural appearance of the upper pole of the breast. Patients who want a high degree of fullness in the upper pole and a convex curvature of their cleavage are not good candidates for lipofilling alone and require breast implants to achieve a more satisfying result. One technique that has been useful is the composite breast augmentation utilizing a small implant for core projection and augmenting this with fat to achieve greater upper pole volume and cleavage. In the same way, when employing an auto-­ augmentation with the mastopexy, the transposed auto-augmentation flap can provide additional projection and roundness to the upper pole, while utilizing the fat grafting to blend additional volume into the upper pole and cleavage area. The combination appears to have additive benefit in improving upper pole volume without the use of an implant. When lipofilling is performed at the same time as the auto-augmentation breast lift technique, it is important to assess the quality and tightness of the breast flaps prior to the fat grafting. When doing a lift, the tissue and flaps may become tight creating limited space to place fat. If the fat grafting recipient site is too tight, the interstitial fluid pressure increases leading to impaired capillary blood flow, potential poor graft-to-recipient interface, decreased oxygen delivery to the grafted adipocytes, and central graft necrosis [14]. When the tissues are tight, we employ techniques that provide more purified fat with limited extra fluid and blood products. If the tissue is looser and accommodating, and requires additional volumes, fat harvesting and injection techniques with minimal preparation are often employed, as will be discussed.

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71.3 Patient Expectations One of the most critical elements of the perioperative planning is patient education and understanding the patient’s desired outcome and expectations with the operation. Patients requiring a mastopexy have more significant changes to the breast than those needing simply a breast augmentation, and often have increased laxity of the tissue, stria, and nipple; breast ptosis; and loss of parenchymal volume and/or firmness. Patients often are unaware of asymmetries, significant atrophy of the breasts, and differences in the chest wall that affect the final outcome. During the evaluation, it is important to determine what “look” the patient would desire, especially in terms of nipple position and volume in the upper pole. Limitations must be discussed as to the results achieved with a mastopexy as compared to a breast augmentation or even an augmentation mastopexy. A patient desiring a more natural look and not requiring extremely full upper poles is an ideal candidate for this procedure. Mastopexy and auto-augmentation with or without fat grafting have limitations and can produce only a somewhat fuller, naturally sloping upper pole at best. The procedure will not create the firm, full roundness that an implant can produce. These patients will also have scars on the breast, which at times can heal unpredictably, and a clear understanding of the location of the scars and anticipated outcome should be discussed.

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medially and laterally to mark the location of the vertical incisions. This vertical mastopexy is based on a superior pedicle blood supply and is not dependent on the final skin excision pattern. Decision on nipple placement is performed and is based on the location of the fold and expected location of the new lifted breast’s central mound position. This can be approximated by simulating the mastopexy and identifying the probable location of the NAC. The nipple position is usually at or within two centimeters of the reflected inframammary fold, referred to as Pitanguy’s point [15]. Placement of the areola is marked, starting approximately 2 centimeters above the nipple position and extending the curved drawing down to meet the medial and lateral vertical markings. This areolar opening marking should produce an areolar opening of approximately 42  mm. Approximately 6–7 cm below the bottom of the keyhole opening, a line is drawn marking the inferior extent of the vertical incision. Curved transverse lines are then drawn from these medial and lateral points extending down to the IMF.  Approximately 2–3  cm above the fold a U-shaped line connects the medial and lateral vertical markings to define the extent of skin resection (Fig. 71.4).

71.4 Preoperative Markings Appropriate preoperative markings guide the surgeon in providing symmetrical NAC placement and mastopexy design. The patient is sitting upright during the markings. A line is initially drawn along the midline of the breasts and bilaterally down the meridians. The inframammary folds are then drawn, noting any asymmetries to be addressed at surgery. The position of the IMF is then drawn on the anterior breast through the meridian incision. The breasts are then rotated

Fig. 71.4  Pre-op markings showing NAC position, anticipated auto-augmentation flap based on the second branch superior pedicle. Thick black horizontal line just above the NAC is the transposed IMF. On the patient’s left breast the horizontal line just above the IMF is the anticipated extent of the vertical incision

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Fig. 71.5 (a) Pre-op breast tailor-tacking. (b) Tailor-tacking on the patient’s left side vs. no tailor-tacking on the right side

71.5 Surgical Technique

Each breast is then placed under maximal stretch and the areolas are marked with a 42 mm cookie cutter (range 38–45  mm depending on 71.5.1 Mastopexy desired aesthetics) and incised with a 15-blade with Auto-Augmentation scalpel. Utilizing a 10-blade scalpel, the entire The patient is placed on the operating room table area within the marks is then de-epithelized and with the arms secured to the sides at 45 to 60 cauterized for hemostasis and dermal shrinkage degrees. Once the patient is prepped with (Fig. 71.7). The lateral and medial flaps are disChloraPrep and draped appropriately, all mark- sected straight down toward the chest wall. The ings are confirmed and retraced as necessary. The lateral and medial pillars are then developed symmetry of the drawings is also confirmed. If keeping them at least 2 cm thick. It is important any questions exist as to the accuracy of the to maintain good pillar volume to avoid leaving markings, tailor-tacking can be performed in the lower pole to deficient (Fig. 71.8). The central pedicle in the lower pole is then many cases to reconfirm the markings. Tailor-­ tacking is performed with a stapler and the patient developed as a flap to transposition into the upper is placed in the upright position to confirm pole. Care must be taken to ensure that the flap is design, symmetry, and NAC positioning. The large enough to be worthwhile and yet leaves tailor-tacking should be adjusted as much as nec- enough tissue in the lower pole to avoid having a essary to create the ideal breast shape (Fig. 71.5). hollow lower pole. Flaps of less than 4  cm in Once satisfied with the appearance, the patient is length are probably not worth transposing. Once placed in the supine position, the staples are the flap is designed, dissection and mobilization removed, and the superior pedicle is designed to of this flap are then performed. The medial and be positioned in the superior keyhole from the 8 lateral dissections of the flap have already o’clock to 4 o’clock position. When in doubt occurred in creating the medial and lateral pillars. about the mastopexy markings, it is advisable to The flap is then transected at the inframammary stay conservative and leave a little more skin on fold and the dissection is carried cephalad from the breast flaps. These can be adjusted during the the fold staying on the chest wall (Fig. 71.9). This final assessment and contouring prior to the clo- flap is dissected circumferentially, and then sure. The operative field is then injected with incrementally dissected to free its attachment to 50  cc per side of local anesthetic solution create a mobile flap still attached to the deep fourth branch of the IMA that courses through (Table 71.2) (Fig. 71.6).

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Table 71.2  Concentrations of Breast Analgesic Solution Injected Prior to Prepping the Patient. 25 ml of each of the components listed on the left-hand side of the table is combined to make a 100 ml solution. This is split so that 50 ml of the solution is injected into each breast using a 20-guage syringe and spinal needle Breast local anesthetic formula ½% lidocaine plain ½% lidocaine/1:200,000 epinephrine ½% bupivacaine/1:200,000 epinephrine Injectable saline ¼% lidocaine, 1/8% bupivacaine, 1:400,000 epinephrine

Fig. 71.6  Breast analgesic injection

Fig. 71.7  De-epithelialized central flap. Areas of blue marking indicated the island of tissue that will be transposed

Wuringer’s septum. This vessel is identified usually approximately 1–1.5 centimeters cephalad to the IMF (Fig.  71.3). Doppler confirmation can also be performed if desired to ensure that the vessel has not been injured. Once the flap has been dissected and released for mobilization, the

Volume 25 ml 25 ml 25 ml 25 mL Total 100 mL

Fig. 71.8  Dissection of medial and lateral breast pillars

remainder of the breast above the flap is elevated off the pectoralis fascia. The distal end of the flap is then cut to assess bleeding and insure adequate circulation (Fig. 71.10). The lower island flap is then transposed into the upper pole and sutured into place with approximately four 2–0 Vicryl sutures. This flap is positioned slightly medial to provide some improved cleavage in the upper pole (Fig. 71.11). Once the flap is positioned and stabilized, tailor-­ tacking is performed to confirm the shape of the breast. Tailor-tacking begins at the inferior areola (6 o’clock position) and proceeds inferiorly towards the IMF. The ideal inferior areola-to-fold distance varies based on the size of the breast but is usually 6–7 cm. Adjustments are made with the tailor-tacking to create the desired breast shape (Fig. 71.12). Once the desired vertical limb length is determined, this location represents the base of the new breast. Any remaining breast tissue or skin below this level must be addressed. As in any ver-

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Fig. 71.9  Dissection of the central mound flap

Fig. 71.11 (a) Flap elevation and transposition to the upper pole. (b) Transposition flap sutured to the pectoralis fascia to maintain upper pole projection

tical mastopexy approach, the skin flaps can be undermined and the breast tissue resected to allow the skin to redrape onto the abdomen and the fold of the breast. This can also be accomplished with liposuction under the redundant skin with skin redraping. This allows the fold to come up and keep the incision vertical only. Alternatively, a horizontal wedge of skin and breast tissue is excised. The markings for the wedge excisions are extended medially and laterally to create the inverted-T scar and the final tailor-tacking is performed (Fig. 71.13). Once the breast shape is confirmed, the final excision of tissue is performed in preparation for closure. The pockets are irrigated with bacitracin saline solution and hemostasis is insured. Deep parenchymal sutures of 2–0 Vicryl are then placed

M. B. Calobrace and C. Mays

Fig. 71.10 Distal flap cut to evaluate for adequate circulation

Fig. 71.12  Breast tailor-tacking

along the vertical incision bringing the medial and lateral pillars together at the midline (Fig. 71.14). All incisions are then closed with interrupted 3–0 PDS dermal sutures. The vertical and horizontal scars are closed with a 4–0 Monocryl running subcuticular suture. The areolas are then closed with a simple running 5–0 nylon suture (Fig. 71.15a). The patient is made to sit upright on the operating room to confirm for symmetry (Fig. 71.15b).

71.6 Fat Grafting Depending on the volume of fat to be transferred, the mastopexy markings should be slightly looser when planning fat grafting as part of the procedure. This ensures that the recipient site

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Fig. 71.13  Estimation of horizontal wedge needed based on the excess tissue after tailor-tacking

Fig. 71.14  Medial and lateral breast pillars brought together with 2–0 Vicryl suture

will have adequate capacity to receive the volume of fat grafted. Fat is collected through a variety of techniques for planned injection. The fat is generally harvested using power-assisted or traditional liposuction with a 4 or 5  mm Mercedes cannula (Fig. 71.16). The donor site is selected based on multiple factors but the most significant include the patient’s aesthetic desires, availability of adequate volume for grafting, and convenience of patient positioning during the case. When preparing fat for large-volume grafting, especially when the breast flaps are thick enough and loose enough to accommodate larger volumes, the fat is collected through either traditional or ­ power-­ assisted liposuction and then allowed to settle (Fig. 71.17). The fat is then usually rinsed with lactated Ringers, approximately with volume equal to the volume collected, and allowed to settle once again to allow the blood to separate from the fat (Fig. 71.18). If the aspirate is especially bloody, a second rinsing is often performed. With this larger volume fat grafting, no additional processing or centrifugation is performed. Small incision sites remote from the surgical incisions are often selected for placement of the fat grafting to insure maximal retention within the recipient site and improve fat survival. However, when surgical incisions are present that are remote from the fat grafting recipient area, puncture holes can be made in incision lines, and from this area, fat can be grafted into the subcu-

taneous plane and into the breast tissue (Fig. 71.19). Care must be taken to insure that the grafting recipient sites do not interfere with healing of the mastopexy incisions. The fat is then placed in one of the two ways. If lesser volumes of 200 cc or less are being injected total and the flaps are at all thin, the fat is placed into 20  cc syringes and, utilizing a 2  mm blunt needle, injected into the upper poles of the breast and medially to create improved cleavage. Approximately 60–100  cc of fat is injected per side. The fat is placed in the subcutaneous fat just under the skin (Fig. 71.20). Care should be taken to inject fat predominantly into the upper pole of the breast and to fill the upper lateral breast as much as the upper medial breast. This will allow volume distribution more evenly and avoid the lateral dip that can occur between the upper lateral breast border and the axilla (Fig. 71.21). If smaller volumes of fat are being placed, then fat is harvested in a similar manner and then placed into 60 cc syringes. The syringes are then placed on a Del Vecchio spinner and the fat is separated into a more concentrated version to allow more precise placement of the fat (Fig. 71.22a, b) This is especially helpful when the mastopexy flaps are thin or tight. The more concentrated, purer fat is then carefully injected subcutaneously just under the dermis with the 2 mm cannula (Figs. 71.23 and 71.24). For significant breast asymmetry in patients undergoing auto-augmentation breast lift,

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a

b

Fig. 71.15 (a) Final closure of the breast 5–0 nylon in the nipple-areolar complex and running 4–0 Monocryl subcuticular. (b) Final closure of the breast with the patient sitting upright on the operating room table

Fig. 71.16  Collection of fat into a graduated cylinder from the abdomen using suction-assisted lipectomy and a 5 mm Mercedes cannula

patients should be advised that two rounds of fat transfer will often be required to achieve symmetric results. The competitive forces of tightening and lifting with volume expansion often limit the volume increase achievable with one round of fat transfer. Patients should be advised that a

Fig. 71.17  Collected fat is allowed to separate via gravity in a graduated cylinder

f­ ollow-­up procedure can be done to provide additional volume to the smaller breast. The area is massaged to allow the fat to spread evenly over the area. Steri-strips are placed over

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Fig. 71.20  Fat grafting to the breast after final closure into the subcutaneous plane Fig. 71.18  The fat has been rinsed with lactated Ringers and allowed to separate via gravity. Notice the yellow healthy fat at the top of the cylinder and the lipoaspirate and debris at the bottom

Fig. 71.21  Patient sitting upright on the operating room table after the fat grafting to the breast

Fig. 71.19  Fat grafting into the breast tissue and subcutaneous plane using a 2 mm Coleman cannula and a 20 cc syringe

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a

b

Fig. 71.22 (a) Harvested fat placed into 60 cc syringes and then suspended from the Del Vecchio spinner. (b) Spinner is manually operated to centrifuge the fat for 2 min

Fig. 71.23  60  cc syringes after centrifuging with Del Vecchio spinner. The fat has been separated from the lipoaspirate to provide a more concentrated product for injection

the incision. Contour tape is then placed along the lateral breast border and inframammary fold. The breasts are wrapped with a xeroform gauze, Kerlix, and ace wrap.

71.7 Postoperative Care and Expected Outcomes The patients are instructed to leave all dressing on for 48 h. The wraps are then removed, and a sports bra is worn for the following 4  weeks.

Fig. 71.24  Fluid is decanted off and the fat is transferred to 20 cc syringes for grafting

Dressing changes with antibiotic ointment and gauze are used over incisions for 1 week. Patients can shower after 48 h. Nylons around the areolas are removed 7–8 days postoperatively. The subcuticular Monocryls are clipped on the ends as they exit the skin at 2 weeks. Scar management with silicone gel or silicone sheeting is initiated on all patients at 2  weeks. Patients can resume activities of daily living almost immediately. Exercise is usually allowed at 4 weeks with heavy lifting at 6 weeks. Patients are counseled that they can expect swelling and firmness to develop as her breasts

71  Mastopexy with Auto-Augmentation and Fat Grafting

heal. The breasts will continue to soften over time and the breast will relax over the first few months. The results are stable after 6 months, but scars can continue to improve over the first year and some additional relaxation of the breast with loss of upper pole volume can continue for even longer. Whereas inferior pedicle shape looks relatively normal shortly and potentially deteriorates over time, the superior pedicle vertical mastopexy technique may look slightly abnormally shaped initially but will then improve to a very pleasing shape long term.

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space developed for the mastopexy. Careful placement respecting the limitations of the recipient site can minimize any issues associated with fat migration. Occasionally, an oil cyst or area of fat necrosis may develop but is of minimal consequence. Respecting the blood supply to the nipple-­areolar complex and mastopexy skin flaps is critically important when performed simultaneously. Thus, judicial placement of fat into the soft-tissue planes and avoidance of overfilling of the breast beyond the capacity for the fat are important to maximize fat survival and minimize ischemic complications. Since there is a limitation to the amount of fat that can be placed and some resorption will occur, additional fat graft71.8 Complications ing sessions may be required to achieve greater There are very few significant complications in volumes in the breasts. Hematoma rarely occurs within the first 24 h, the early postoperative period. The only significant concern early is ischemia to the nipple-­ but a late hematoma at days 10–14 is also occaareolar complex or skin flaps. Ischemia may be sionally encountered as activity level increases due to the dissection of the pedicle, but often is and clots are being resorbed at the end of cautersecondary to excessive tension on the skin clo- ized vessels. A very small hematoma can be sure and underlying volume under the skin flaps. allowed to resolve on its own, but any substantial If recognized immediately, all sutures should be hematoma should be explored, evacuated of removed to evaluate for improved circulation, blood, and drained. Small amount of blood within improved color, good capillary refill, and pin- the pocket in a mastopexy without a breast prick bleeding. It is important to assure that the implant is generally less concerning as there is pedicle is free of tension and not twisted or com- not potential for capsular contracture. Seromas promised. Topical nitroglycerin or dimethyl sulf- are generally managed conservatively with serial oxide (DMSO) can be used to improved venous aspiration until resolved. outflow. If the closure is too tight due to volume present under the flaps, additional breast volume can be removed to reduce the closure tension. If 71.9 Secondary Procedures any doubt exists, the wound around the NAC can be left unattached and closed the following day in Late sequelae include poor scarring, recurrent the clinic. Although conversion to a free nipple ptosis, bottoming out, asymmetry, contour deforgraft could be done if there is inadequate pedicle mities, fat necrosis, and loss of upper pole volflow through all of the abovementioned efforts, ume. These may require revisionary procedures this is by far more common in a breast reduction to improve the final aesthetic outcome. Most proand should be extremely rare in a mastopexy cedures are delayed at least 6 months or greater procedure. to allow for soft-tissue remodeling and stabilizaFat grafting simultaneous with a mastopexy tion of the results. Scars are often the product of has proven to be very safe with minimal compli- excessive tension on the closure and postoperacations in our experience which has been sup- tive swelling and can often be improved with scar ported in recent publications [16, 17]. Potentially revisions when the environment for scar maturathe most common, especially when thin skin tion is more optimal. Lower pole stretch deformienvelopes are present, is for the fat to migrate out ties and recurrent ptosis are managed with a of the soft-tissue planes and into the dissected revision of the mastopexy with or without the

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addition of some additional support from a mesh or acellular dermal matrix. More commonly, the lower pole can become empty as the flap is transposed to the upper pole, leading to a flattened, empty lower pole contour (Fig. 71.25a). This can be avoided by ensuring that adequate pillar volume is present to fill the lower pole. The empty lower pole can be treated with revision of the mastopexy with or without fat grafting (Fig. 71.25b). Fat necrosis is often simply monitored if it is small and not deforming the shape of the breast. If it involves the transposed flap, it may present as firmness in the upper pole of the breast. If the area of fat necrosis impairs the

a

shape or softness of the breast or is interfering with cancer surveillance, excision of the involved area is appropriate. Loss of upper pole volume is the most common late finding after mastopexy and has been to some degree mitigated using transposition flap into the upper breast. This can be secondary to relaxation and loss of lower pole support or simply due to the lack of stable, firm volume in the breast envelope. The most effective management is tightening of the lower pole if needed and addition of a breast implant. Additional fat grafting can also be employed to provide volume and avoid the use of an implant.

b

Fig. 71.25 (a) Loss of lower pole volume after auto-augmentation leading to an empty flattened lower pole contour. (b) Improvement in lower pole volume after revisionary surgery to improve lower pole contour

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71.10 Conclusion

more stable and predictable results. The added advantage of this technique is that the volume With proper preoperative evaluation and employ- unloaded from the lower pole is transposed into ing accurate surgical techniques, excellent results the upper pole to provide additional projection and can be achieved with mastopexy with auto-­ volume. Fat grafting can further enhance the augmentation. The significant advantage of the results, adding volume to augment the upper pole superior pedicle technique in the appropriately and improve postoperative cleavage. This techselected patient is not the elimination of an infra- nique is simply a modification of a well-­established mammary scar, but rather the parenchymal shap- technique that can be easily mastered and provides ing and lower breast pole unloading that provides optimal results with high patient satisfaction.

Case Examples

Case 1  31-year-old female with breast ptosis and asymmetry who underwent bilateral full wise mastopexy with Ribeiro auto-augmentation transposition flaps to provide breast volume without the use of implants

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Case 2  20-year-old female with breast ptosis seeking a lift and volumization of her breast without the use of an implant. An inferior based Ribeiro flap for inverted-T

mastopexy with auto-augmentation was used to transpose lower pole volume into the upper pole

Case 3  19-year-old female with breast ptosis and asymmetry. A superior based auto-augmentation flap with an inverted-T mastopexy was used to restore symmetry and

provide shape and volume to the breast without the use of implants

71  Mastopexy with Auto-Augmentation and Fat Grafting

Case 4  42-year-old female with breast ptosis. Before and after photos of a superior based auto-­augmentation flap with an inverted-T mastopexy and Galaflex mesh soft-tis-

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sue support to provide shape and volume to the breast without the use of an implant

Case 5  45-year-old female with breast ptosis. Before and after photos of a superior based auto-­augmentation Ribeiro flap with an inverted-T mastopexy to provide shape and volume to the breast without the use of an implant

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References 1. Binelli L. A new periareolar mammoplasty: the “round block” technique. Aesth Plast Surg. 1990;14:93–100. 2. Lejour M.  Vertical mammoplasty for breast reduction and mastopexy. In: Spear SL, editor. Surgery of the breast: principles and art. Philadelphia, PA: Lippincott-Raven; 1998. p. 73. 3. Hall-Findlay EJ. Pedicles in vertical breast reduction and mastopexy. Clin Plast Surg. 2002;29:379–91. 4. Wise RJ. Treatment of breast hypertrophy. Clin Plast Surg. 1976;3:289–300. 5. Marchac D, Olarte G.  Reduction mammoplasty and correction of ptosis with a short inframammary scar. Plast Reconstr Surg. 1982;69:45–55. 6. Graf R, Biggs TIM. In search of better shape in mastopexy and reduction mammoplasty. Plast Reconstr Surg. 2002;110:309–17. 7. Lassus C.  A 30-year experience with vertical mammoplasty. Plast Reconstr Surg. 1996;97:373–80. 8. Hall-Findlay EJ.  Vertical breast reduction with a medial based pedicle. Aesth Surg J. 2002;22:185. 9. Ribeiro L.  A new technique for reduction mammoplasty. Plast Reconstr Surg. 1975;55:330–4. 10. Ribeiro L, Accorsi A, Buss A, et  al. Creation and evolution of 30 years of the inferior pedicle in

M. B. Calobrace and C. Mays reduction mammaplasties. Plast Reconstr Surg. 2002;110:960–70. 11. Rubin JP, Khachi G.  Mastopexy after massive weight loss: dermal suspension and selective auto-­ augmentation. Clin Plast Surg. 2008;35:123–9. 12. Hammond DC, O’Connor EA.  The lower island flap transposition (LIFT) technique for control of the upper pole in circumvertical mastopexy. Plast Reconstr Surg. 2014;134(4):655–60. 13. Hall-Findlay EJ.  Applied anatomy: key concepts for modern breast surgery. In: Hall-Findlay, editor. Aesthetic breast surgery: concepts and techniques. 14. Khouri RK, Rigotti G, Cardoso E, Khouri RK Jr, Biggs TM.  Megavolume autologous fat transfer: part I.  Theory and principles Plast Reconstr Surg. 2014;133(3):550–7. 15. Pitanguy I. Surgical treatment of breast hypertrophy. Br J Plast Surg. 1967;20(1):78–85. 16. Graf RM, Closs OMC, Pace D, et  al. Breast auto-­ augmentation (mastopexy and lipofilling): an option for quitting breast implants. Aesth Plast Surg. 2019;43(5):1133–41. 17. Walter J, Bourn L, Tessler O, et al. Single-staged mastopexy with autologous fat grafting: an alternative to augmentation mastopexy with implants. Aesthet Surg J. 2020;40(4):NP152–8.

Breast Augmentation with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling (PALLL) Technique

72

Nicolas M. Abboud and Marwan H. Abboud

Key Messages  • Preoperative markings are made to achieve a precise and symmetrical cartography of both breasts. • Extensive infiltration is performed for hydrodissection of the subcutaneous tissues. • Tunnelization of the breast, upper abdomen, and lateral thoracic region then detaches the skin from the matrix and the matrix from the deep plane, creating a gliding plane and facilitating the recruitment of perimammary tissue into the breast. • Deep undermining of the breast is utilized to free the tethering fibers and the attachments of the matrix to the pectoralis fascia. • Liposuction of the upper abdomen and axillary region is performed to release the skin tension. • Proper placement of the footprint loop, which recruits tissues from the upper abdomen and lateral thorax, redefines the breast footprint and increases the breast volume.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_72) contains supplementary material, which is available to authorized users.

N. M. Abboud (*) · M. H. Abboud Plastic and Reconstructive Surgery Department, Delta Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium e-mail: [email protected]

• Proper placement of the inframammary fold (IMF) loop provides better definition of the IMF, when judged necessary. • Fat grafting is used to increase the breast volume and projection.

72.1 Introduction Autologous fat grafting has proven to be reliable in breast surgery. It can be performed to correct breast asymmetries and deformities, but can also be used solely in breast augmentation for patients who desire bigger breasts. Many sessions are usually required to obtain optimal results, because large amounts of injected fat can be lost after each session. This loss is mainly due to an excessive tension in the recipient site and can also be influenced by vascular comorbidities such as diabetes and smoking [1–8]. Many well-known authors have studied the need for recipient-site preparation for the success of the fat grafting procedure, number of the fat grafting sessions, and fat graft retention [1, 9]. Khouri [1] introduced the use of a purse-string suture that recruits an epigastric crescent into the breast and better defines the breast. Other authors, such as Hamdi [10] and Visconti [11], also described the use of a thread passed subcutaneously to better define the IMF. More recently, the senior author reported his experience in breast remodeling utilizing threads for breast reconstruction, breast augmentation following implant

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removal, and breast reduction, and also the experience in extending the application of threads to body-contouring procedures [12–16]. This chapter introduces a single-stage scarless method of tri-composite breast augmentation using internal threads to recruit a vascularized adipocutaneous flap from the upper abdomen and lateral thorax to the breast. This technique remodels the breast’s matrix by expanding it, reducing the skin tension, and allowing better fat survival. The first loop is utilized to recruit adipocutaneous tissue from the upper abdomen and lateral thorax, whereas a second loop can be utilized to better define the IMF. The senior author presents his experience using the power-assisted liposuction and lipofilling (PALL) [17–20] technique associated to the use of loops (PALLL) in breast augmentation. This technique increases breast volume and projection, redefines the new footprint (and IMF if needed), and reduces the number of required sessions.

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The design of the loops is then marked. The first loop, the footprint loop, is marked in a circular pattern to match the skin surface to that of the contralateral breast (Figs.  72.1 and 72.2). The inner limit of the footprint is located 1 cm laterally to the midline, and the distance between the nipple and this point is named “x.” The footprint loop then continues superiorly following the breast footprint and extends laterally “x + 2” cm from the nipple, and inferiorly at “x-1” cm. The second loop, designed to better define the new IMF if necessary and to suspend it along the breast axis, is marked in a triangular pattern. Markings are also made for the zones in the upper abdomen and the lateral thorax. Tissues in these zones will be loosened to facilitate tissue advancement, and the zones of liposuction for fat harvesting are marked. Those measurements are then verified with the patient in the supine position.

72.2 Preoperative Evaluation and Markings A thorough clinical assessment is performed preoperatively, including history and examination. Patients who smoke are told to quit at least 4  weeks before the intervention. Each patient younger than 30 years old had a breast echography, whereas older patients (>30 years old) also required a mammography. The preoperative markings are essential for the optimal outcome of the surgery. It is important to verify that each breast quadrant has the same cutaneous surface, through the measure of the radius originating from the nipple to the breast footprint. Preoperative markings must be performed with the patient in the standing position. The lines marked include the midline, the anterior axillary line (defining the lateral limit of the breast), the horizontal interaxillary line joining the anterior axillary folds (defining the upper limit of the breast), and the horizontal line passing through the IMF (defining the inferior limit of the breast). The breast meridians are marked, and the breast is divided into eight pie-shaped sections (Fig. 72.1).

Fig. 72.1  We first mark the midline, the anterior axillary line, the interaxillary horizontal line, and the IMF.  The breast is divided into eight parts as in a pie (A- to H-axes). A ninth and tenth zone can also be drawn, representing, respectively, the areola and nipple. Both vertical and horizontal dimensions on both breasts must be equal. The footprint is drawn in a circular pattern with a dotted line

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72.3.2 Tunnelization and Liposuction Extensive tunnelization of the matrix is then performed using a cannula, liberating the skin from the matrix and the matrix from the fascia. This not only reduces the tensile force of the matrix but also facilitates the mobilization of a vascularized adipocutaneous flap from the upper abdomen and lateral thorax to the breast with the use of loops (Fig. 72.3). This detachment is enhanced by performing liposuction in the axilla, upper abdomen, and other donor sites. Following tunnelization, a Molt elevator is employed to release the deep attachments of the matrix to the pectoralis fascia along the newly positioned IMF, the native IMF (if intact), and the scar tissue. This step helps to erase the memory of the native IMF and reduces the tensile force of the matrix, allowing the flap to be advanced with minimal tension. Fig. 72.2  The native breast is shown in yellow, and the blue crescent located in the upper abdomen and lateral thorax shows the adipocutaneous flap which will further be recruited. The new footprint is drawn in a circular pattern with a dotted line. The G-axis corresponds to the distance from the nipple to a point located 1 cm laterally to the midline, named “x.” The C-axis measures “x + 2 cm” and the E-axis “x-1 cm.” These landmarks are essential for the markings of the footprint loop

72.3 Surgical Procedure 72.3.1 Preparation and Infiltration The patient is operated in a supine position with the arms abducted, under general anesthesia. An intravenous administration of 2 g of cefazolin is performed 30 min prior to the intervention. Using a power-assisted liposuction system, the plastic surgeon infiltrates the breast, the perimammary tissues, and the fat donor sites with a tumescent solution containing epinephrine 1:100,000 per liter of normal saline associated with 5  mL of Exacyl® (tranexamic acid) 0.5 g/5 mL [21]. This step is essential for optimal hydrodissection, for release of subcutaneous tethering fibers originating from scar tissue, and for internal expansion of the recipient site.

72.3.3 Placement of the Loops While the fat is being prepared in a closed system, following the PALL technique [17], the first loop, the footprint loop (Figs. 72.4 and 72.5), is passed using nonabsorbable sutures. This loop crosses the lower quadrants of the breast in a superficial subcutaneous plane; in the upper breast quadrants, the footprint loop is passed deeper, in a suprafascial plane. This maneuver is performed twice, and the knot is tied. This footprint loop will define the breast footprint and enhance the breast projection. In cases of an asymmetrical IMF, a second loop— the IMF loop (Figs. 72.6 and 72.7)—can be passed along the new IMF in a superficial subcutaneous plane; it then goes cephalad to reach the midpoint of the interaxillary axis, traveling in a deep subcutaneous plane. The thread is passed twice, and the knot is tied. This triangular loop aims to fix the IMF in its new position to achieve symmetry [12–14]. Contour deformities and remaining subcutaneous attachments are then released using a Varady extractor. Additional liposuction can be performed in the upper abdomen to reduce the tension on the loops and to more clearly delineate the transition between the abdomen and the breast.

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a

b

Fig. 72.3 (a–c) Tunnelization is an essential step to dissociate the matrix from the deep plane and the superficial plane, and expand the matrix itself. (a) It is performed in the upper abdomen, lateral thoracic region, and breast (b, c). (b) Superficial tunnelization is performed in a deep plane in the upper quadrants (light red) and in the lower

c

quadrants of the breast (dark red). Deep undermining is then performed using a Molt elevator, in order to detach all of the tethering fibers and the attachments of the matrix to the pectoralis fascia. This liberation will facilitate the advancement of the adipocutaneous flap into the breast

For the double loop, we currently utilize nonabsorbable sutures (Filapeau 2, Peters Surgical, Bobigny, France). In case of the nipple-areola complex (NAC) ptosis, this is followed by an elevation of the NAC using a number 0  V-Loc (Medtronic, Minneapolis, Minnesota, USA) absorbable suture. Skin detachment by tunnelization from the breast parenchyma is verified by passing the cannula over the area where the 0  V-Loc loop will be passed. The loop is then passed circumferentially around the areola to reduce the areola size and then cephalad along the breast axis, after which it is pulled up until the desired NAC elevation has been achieved. Herniated areolas can also be treated by passing the threads subcutaneously in a crisscross pattern. Please refer to Table  72.1 of the chapter “Breast Reconstruction Using Fat and Threads” explaining the different existing techniques using threads. Fig. 72.4  The footprint loop is shown in red dotted lines. It is marked in a circular pattern to achieve the same horizontal dimension of the breast footprint as the contralateral breast

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a

Fig. 72.5 (a, b) These figures show the tightening of the loop’s knot (red cross). The footprint loop will recruit skin and fat from the upper abdomen and the lateral thorax toward the breast in a centripetal pattern along the breast

b

axis (red arrows). It increases the matrix for fat injection and increases breast projection, but also defines the horizontal dimension breast footprint, the lateral and the inframammary folds

72.3.4 Lipofilling

Fig. 72.6  In cases of IMF malposition, an IMF loop is designed. This loop, shown in blue dotted lines, is drawn in a triangular pattern which apex is the midpoint of the interaxillary axis. The vertical dimension of the breast footprint is defined by it

With the use of the Lipomatic system, which is now disconnected from the suction, fat grafting is performed in a multiplanar fashion through a customized V-shaped three-hole cannula (3  mm diameter), enabling simultaneous vibration at the recipient site (Fig. 72.8). If the areola is located too medially, lipofilling should be performed in the medial pole of the breast to correct this deformity. As the final step, we use the handpiece of the power-assisted liposuction system to perform external vibration. Hacdil-S cleaning solution (Mölnlycke Health Care AB, Göteborg, Sweden) is applied on the breast. This then allows friction-­ less external vibration over the breast to promote further diffusion and equal distribution of the fat lobules. Please refer to the attached video of the preoperative markings and the surgical technique. Clinical cases are shown in Figs. 72.9, 72.10, 72.11, 72.12, and 72.13.

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a

Fig. 72.7 (a, b) These figures show the tightening of the loop’s knot (blue cross). The IMF loop will better define the inframammary fold, suspend it along the breast axis in

a

Fig. 72.8 (a, b) Fat injection is then performed in the residual breast matrix and in the advanced adipocutaneous flap from the upper abdomen and the lateral thorax. Lipofilling is performed superficially in a multidirectional multiplanar fashion, above the muscle. The final breast

b

order to obtain symmetry, as well as recruit tissue from the upper abdomen and increase the breast’s projection (blue arrows)

b

volume is composed of the crescent advanced from breast surroundings, the residual breast volume, and the injected fat. The horizontal and vertical dimensions of both breasts should be symmetrical

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a

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Fig. 72.9  This is the case of a 41-year-old female patient with bilateral stage 1 tuberous breasts. She underwent one session of PALLL with a volume of injected fat of 200 mL on the right breast and 150 mL on the left breast. Frontal view with arms in resting position (a–c), three-quarter left

profile (d–f), and left lateral profile views (g–i). Peroperative basal view before and after placing the loops and fat grafting (j–m). Photographs are taken preoperatively with (a, d, g) and without markings (b, e, h) and 18 months postoperatively (c, f, i)

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k

Fig. 72.9 (continued)

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m

The exclusion criteria included lean patients with minimal adipose storage, active smokers who refused quitting smoking prior to the intervention, and patients who desired a large breast volume.

72.4.2 Procedure Characteristics

Fig. 72.9 (continued)

72.4 Patient Characteristics, Postoperative Care, and Complications 72.4.1 Patient Characteristics A total of 193 patients (351 breasts) underwent breast augmentation utilizing PALLL.  Of these patients, 55 had symmetrical breasts with a small-to-moderate breast size (110 breasts), 21 patients had asymmetrical breasts (42 breasts), 33 had tuberous breasts (65 breasts), 23 had oncological breasts following radiotherapy/ lumpectomy (23 breasts), and 61 patients underwent implant removal (111 breasts). These patients were distributed into four groups. Patients with small- to moderate-sized symmetrical breasts and asymmetrical breasts were included in group 1, patients with tuberous breasts were in group 2, patients with oncological breasts were in group 3, and patients who underwent implant removal were in group 4. The mean age was 46 years old (range 17 to 73), the mean body mass index was 24 (range 21 to 31), and the mean follow-up was 26 months (range 9 to 51). Out of those 193 patients, 27 (14%) were former smokers and 17 (9%) had balanced diabetes. Forty-three patients (22%) had radiotherapy on their breast(s) (Table 72.1).

The mean procedure time was 54  min (range 42–76) for group 1, 76  min (range 61–83) for group 2, 59 min (range 52–77) for group 3, and 62 min (range 54–87) for group 4. The average fat grafting volume per breast was 175 cc (range 150–280 cc) for group 1, 168 cc (range 50–260 cc) for group 2, 113 cc (range 100–150 cc) for group 3, and 231 cc (range 50–345 cc) for group 4. The patients required, on average, one session for each group (Table 72.2).

72.4.3 Postoperative Treatment Access incisions are closed with nylon 6/0 sutures, and a compressive garment is applied before the patient recovers from anesthesia. A prophylactic dose of low-molecular-weight heparin is administered 8 h later; its continued use depends on the patient’s Caprini risk assessment [22]. Postoperative analgesia comprising 1000  mg paracetamol (acetaminophen) four times per day along with a nonsteroidal anti-­inflammatory drug (NSAID) such as ibuprofen (600 mg, three times per day, if necessary, with a proton pump inhibitor) is used for an average of 1  week. This is a 1-day surgery. Patients are advised to wear a loose sports bra for 2 months and to limit abduction of the shoulder for 1 month.

72.4.4 Complications The patient might experience mild-to-moderate postoperative pain for a few days and discomfort for 2–3  weeks. Other complications that were

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a

b

c

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Fig. 72.10  This is the case of a 23-year-old female patient with asymmetrical hypoplastic breasts, shown in the video. She underwent one session of PALLL for bilateral breast augmentation. The volume of injected fat was 110 mL for the right breast and 140 cc for the left breast. Frontal view with arms in resting position (a–d), three-

quarter left profile (e–h), and left lateral profile view (i–l). Frontal view with arms elevated (m–p), three-quarter left profile (q–t), and left lateral profile view (u–x). Photographs are taken preoperatively without (a, e, i, m, q, u) and with markings (b, f, j, n, r, v), 6 months (c, g, k, o, s, w), and 2 years postoperatively (d, h, l, p, t, x)

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g

h

i

j

k

l

Fig. 72.10 (continued)

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m

o

q

Fig. 72.10 (continued)

n

p

r

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s

t

u

v

w

x

Fig. 72.10 (continued)

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a

b

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Fig. 72.11  This is the case of a 42-year-old female patient with symmetrical hypoplastic breasts. She underwent one session of PALLL with a mean volume of injected fat of 250 mL per breast. Frontal view with arms

in resting position (a, b), three-quarter right profile (c, d), and right lateral view (e, f). Photographs are taken preoperatively (a, c, e) and 2 years postoperatively (b, d, f)

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Fig. 72.12  This is the case of a 66-year-old female patient operated for bilateral breast augmentation using implants 10 years ago (300 cc R, 360 cc L). She underwent implant removal and breast augmentation using one session of PALLL The volume of injected fat was 200 mL per breast.

Frontal view with arms in resting position (a–c), three-­ quarter left profile (d–f), and three-quarter right profile (g–i). Photographs are taken preoperatively (a, d, g), at 6 months (b, e, h), and 2 years (c, f, i) postoperatively. Per-operative views (j: preoperative, k: after implant removal and PALLL)

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g

h

i

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k

Fig. 72.12 (continued)

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Fig. 72.13  This is the case of a 31-year-old female patient with a stage 2 tuberous breast deformity on the right side. She underwent a left breast no-scar mastopexy and a bilateral breast augmentation using one session of PALLL with 160  mL of fat being grafted to the right breast and 80 mL to the left breast. Frontal view with arms in resting position (a–c), three-quarter right profile (d–f),

and right lateral profile view (g–i). Frontal view with arms elevated (j–l), three-quarter right profile (m–o), and lateral right profile (p–r). Photographs are taken preoperatively (a, d, g), at 6 months (b, e, h), and 2 years (c, f, i) postoperatively. Per-operative views (s, u: preoperative; t, v: after left breast mastopexy and bilateral PALLL)

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g

h

i

j

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l

Fig. 72.13 (continued)

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j

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l

m

n

o

Fig. 72.13 (continued)

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Fig. 72.13 (continued) Table 72.1  Patient demographics (N = 193 patients) Number of patients Number of breasts Mean age, y (range) Mean BMI, kg/m2 (range) Number of smokers (%) Number of diabetic patients (%) Number of irradiated patients (%)

193 351 46 (17–73) 24 (21–31) 27 (14%) 17 (9%) 43 (22%)

BMI body mass index

reported include ecchymosis and limitation of movement in the first 2 weeks post-surgery. Broken threads were assessed in five breasts (1.4%), requiring a secondary procedure to remove the threads and replace them if deemed necessary. Four breasts (1.1%) suffered from mild breast infection successfully treated by antibiotics, and three others (0.8%) presented thread extrusions (Table 72.3).

Table 72.2  Operative data per group (for bilateral breast augmentation) Group (number of patients) Mean procedure time, min (range) Mean injected volume per breast, mL (range) Mean number of sessions (range)

Group 1 (76) 54 (52–76)

Group 2 (33) 76 (61–83)

Group 3 (23) 59 (52–77)

Group 4 (61) 62 (54–87)

175 168 113 231 (150–280) (50–260) (100–150) (50–345)

1 (1)

1 (1–2)

1 (1)

1 (1–2)

72  Breast Augmentation with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling… 1105 Table 72.3 Complications Broken thread (%) Thread extrusion (%) Infection (%) Hematoma (%) Seroma (%) Skin necrosis (%) Thromboembolic events (%) Pneumothorax (%) Oil cyst (%)

5 (1.4) 3 (0.8) 4 (1.1) 0 0 0 0 0 12 (3.4)

None of the patients reported hematomas, seromas, skin necrosis, thromboembolic events, or pneumothorax. Position stability of the IMF was assessed at 12 months for each patient, showing eight (2%) cases of IMF relapse to its original position. In those breasts, the threads were either broken or extruded, and those patients required a touch-up procedure. Twelve breasts (3.4%) showed oil cysts at 12 months postoperatively on echography, but no suspicious lumps were noted. None of the patients encountered problems in the interpretation of their follow-up echography 12  months after the intervention.

72.4.5 Limitations This technique is not indicated for lean patients because the adipose tissue surrounding the breast is required to increase the breast volume. Moreover, small- to moderate-size breasts can exclusively be obtained utilizing the PALLL technique, leaving the use of implants essential for bigger breasts. In the meantime, contrary to implants, this procedure cannot achieve upper pole fullness.

72.5 Conclusion Autologous breast augmentation using the PALLL technique is a one-stage, safe, reliable, precise, fast, and minimally invasive procedure

that requires a small learning curve. This is a one-­ day surgery, with a low complication rate that only leaves a limited number of cysts in the breast because a lower volume of fat is injected. Through extensive detachment of the subcutaneous adherences in the breast, upper abdomen, and axillary region, and the use of internal threads, a vascularized adipocutaneous flap is recruited to the breast. This scarless approach better defines the breast footprint and IMF, and it avoids the need for multiple sessions of fat grafting.

References 1. Khouri RK Jr, Khouri RK.  Current clinical applications of fat grafting. Plast Reconstr Surg. 2017;140(3):466e–86e. 2. Hivernaud V, Lefourn B, Guicheux J, Weiss P, Festy F, Girard AC, Roche R. Autologous fat grafting in the breast: critical points and technique improvements. Aesthetic Plast Surg. 2015;39(4):547–61. 3. Coleman SR, Saboeiro AP.  Primary breast augmentation with fat grafting. Clin Plastic Surg. 2015;42(3):301–6. 4. Bayram Y, Sezgic M, Karakol P, Bozkurt M, Filinte GT.  The use of autologous fat grafts in breast surgery: a literature review. Arch Plast Surg. 2019;46(6):498–510. 5. Simonacci F, Bertozzi N, Grieco MP, Grignaffini E, Raposio E.  Procedure, applications, and outcomes of autologous fat grafting. Ann Med Surg. 2017;20:49–60. 6. Davis MJ, Perdanasari AT, Abu-Ghname A, Gonzalez SR, Chamata E, Rammos CK, Winocour SJ. Application of fat grafting in cosmetic breast surgery. Semin Plast Surg. 2020;34(1):24–9. 7. Voglimacci M, Garrido I, Mojallal A, Vaysse C, Bertheuil N, Michot A, Chavoin JP, Grolleau JL, Chaput B. Autologous fat grafting for cosmetic breast augmentation: a systematic review. Aesthet Surg J. 2015;35(4):378–93. 8. Groen JW, Negenborn VL, Twisk JW, Ket JC, Mullender MG, Smit JM. Autologous fat grafting in cosmetic breast augmentation: a systematic review on radiological safety, complications, volume retention, and patient/surgeon satisfaction. Aesthet Surg J. 2016;36(9):993–1007. 9. Del Vecchio DA, Bucky LP.  Breast augmentation using pre-expansion and autologous fat ­transplantation: a clinical radiographic study. Plast Reconstr Surg. 2011;127(6):2441–50. 10. Hamdi M, Anzarut A, Hendrickx B, et al. Percutaneous purse-string suture: an innovative percutaneous tech-

1106 nique for inframammary fold creation and improved breast projection in reconstructive surgery. Aesthet Surg J. 2018;38(12):1298–303. 11. Visconti G, Salgarello M.  Dual-anchor cog threads in fat grafting breast augmentation: a novel scarless method for defining breast footprint and enhancing shape. Plast Reconstr Surg. 2019;143(4):1039–49. 12. Abboud MH, Kapila AK, Bogaert S, Abboud NM.  Composite breast remodeling after implant removal by tissue recruitment and loops fixation with power-assisted liposuction and lipofilling (PALLL). Aesthet Surg J. 2021;41(7):770–82. 13. Abboud MH, El Hajj H, Kapila AK, Bogaert S, Abboud NM.  Scarless composite breast reconstruction utilizing an advancement skin flap, loops and lipofilling. Aesthet Surg J. 2021:sjab049. 14. Abboud NM, Hajj HE, Abboud MH.  A novel approach in breast reconstruction: The extended lateral thoracic flip-over flap combined with loops and lipofilling (ELT FOLL). J Plast Reconstr Aesthet Surg. 2021;74(5):974–80. https://doi.org/10.1016/j. bjps.2020.10.024. 15. Abboud MH, El Hajj HN, Abboud NM.  No-scar breast reduction utilizing power-assisted liposuction mammaplasty, loops, and lipofilling. Aesthet Surg J. 2021;41(5):550–62. https://doi.org/10.1093/asjsjaa165. Online ahead of print 16. Abboud M, Geeroms M, El Hajj H, Abboud N.  Improving the female silhouette and gluteal projection: an anatomy-based, safe, and harmonious

N. M. Abboud and M. H. Abboud approach through liposuction, suspension loops, and moderate lipofilling. Aesthet Surg J. 2021;41(4):474– 89. https://doi.org/10.1093/asj/sjaa157. Epub ahead of print 17. Abboud MH, Dibo SA, Abboud NM. Power-assisted liposuction and lipofilling: techniques and experience in large-volume fat grafting. Aesthet Surg J. 2020;40(2):180–90. 18. Abboud MH, Abboud NM, Dibo SA.  Brachioplasty by power-assisted liposuction and fat transfer: a novel approach that obviates skin excision. Aesthet Surg J. 2016;36(8):908–17. 19. Abboud MH, Dibo SA, Abboud NM. Power-assisted gluteal augmentation: a new technique for sculpting, harvesting, and transferring fat. Aesthet Surg J. 2015;35(8):987–94. 20. Abboud MH, Dibo SA.  Immediate large-volume grafting of autologous fat to the breast following implant removal. Aesthet Surg J. 2015;35(7):819–29. 21. Abboud NM, Kapila AK, Abboud S, Yaacoub E, Abboud MH. The combined effect of intravenous and topical tranexamic acid in liposuction: a randomized double-blinded controlled trial. Aesthet Surg J Open Forum. 2021;3(1):ojab002. https://doi.org/10.1093/ asjof/ojab002. 22. Cronin M, Dengler N, Krauss ES, Segal A, Wei N, Daly M, et al. Completion of the updated Caprini risk assessment model (2013 Version). Clin Appl Thromb Hemost. 2019;25:1076029619838052.

Improving Breast Footprint and Shape Using Anchor Threads in Fat Grafting Breast Augmentation

73

Giuseppe Visconti, Alessandro Bianchi, and Marzia Salgarello

Key Message  • Modern fat grafting breast augmentation should incorporate both volume enhancement and shape improvement. • Breast footprint, including the IMF, has an impact on the overall breast shape. • Breast fat grafting is a “closed” procedure; thus there is no direct control on the breast footprint. • By missing the management of footprint during fat grafting breast augmentation, there is an increased risk for asymmetric IMF, lateral breast pole fading with lateral thoracic tissues and bottoming out. • These complications are related to an unwanted weakening of breast ligamentous structures. • Dual-anchor cog thread technique represents a scarless surgical option in controlling the breast footprint after fat grafting in order to improve breast shape besides augmentation.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-3-030-77455-4_73) contains supplementary material, which is available to authorized users. G. Visconti (*) · A. Bianchi · M. Salgarello Dipartimento Scienze Salute della Donna, del Bambino e di Sanità Pubblica, UOC Chirurgia Plastica, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy e-mail: [email protected]

• The dual-anchor cog technique defines the new IMF, controls breast footprint and favours a redirection of interstitial pressure on the lower pole improving its convexity and enhancing the NAC-IMF length. • This technique enables improvement of breast shape and definition but it cannot recruit abdominal/lateral thoracic tissue in the breast.

73.1 Introduction Cosmetic breast augmentation with fat grafting is gaining increasing success and demand worldwide and nowadays it is considered an established scarless surgical alternative to augmentation with implant. Advances in basic science and refinements in surgical techniques allow to obtain consistent, natural and durable results with the adjunct benefit of donor-site liposculpture [1–3]. Besides hypoplastic breasts with normal shape, one of the most powerful indications of this procedure is the treatment of constricted and tuberous breasts as well as of breast asymmetries. In fact, fat grafting breast augmentation allows to reshape and augment the breast in a more controlled and tailored fashion than traditional implant approach. In the last decades, the scientific research on fat grafting has been mainly focused on the understanding and improvement of fat graft take in order to provide clear basic principles for

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p­ erforming the surgery with consistent and stable results, which nowadays is a reality. However, in cosmetic breast augmentation we should always consider two main outcomes, the volume enhancement and the breast shape. In fat grafting, breast reshaping is mainly dictated by a fine balance between interstitial pressure and tailored soft-tissue weakening/ expansion. Ancillary manoeuvres, such as 2D and 3D percutaneous aponeurotomies, combined with fat grafting allow to successfully expand constricted areas as well as to lower a high inframammary fold [4, 5]. Although these powerful manoeuvres allow to expand and enlarge successfully a breast, there is no fine control on final breast width, on position of the new inframammary fold and finally on boosting lower pole convexity as it happens with implant augmentation. The reason behind this main difference between implant augmentation and fat grafting augmentation resides in the surgical technique itself. Fat grafting breast augmentation is a “liquid,” closed augmentation where the surgeon disperses small fat gems to enlarge and augment the breast, with no direct control on breast boundaries. Implant augmentation is a “solid,” open procedure where the surgeon directly controls breast boundaries by pocket dissection as well as dictates final breast shape by “solid” fabric products (i.e. implant), which finally define total volume as well as volume distribution. Mallucci et  al. [6, 7] recently set four main parameters for the “ideal breast”: –– Upper-to-lower pole ratio of 45:55 –– Nipple-areola complex position pointing 0 to 10° upward –– Lower pole tight convexity –– Linear to gentle concave upper pole All these parameters can represent a reference for the cosmetic surgeons when shaping a breast, considering also patients’ preference and ethnical and fashion influences. Besides breast shape’s features, the breast boundaries represent the foundation on which a beautiful breast is defined.

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In fact, a beautiful breast has a foundation set by the following boundaries: –– Inframammary fold (IMF): well-defined indentation between the 5th and 6th ribs, extending from sternum to anterior axillary line; this separates the breast from the abdomen as well as it represents the pivot point for slight breast ptosis in the beautiful breast. –– Anterior axillary line: ideal reference line which separates the breast from the lateral thoracic area which should be flat to slight concave. –– Axillary fold horizontal line: the uppermost limit of the breast, where the gentle concavity or linear profile of the upper pole starts smoothly. –– Parasternum: the medialmost limit of the breast. Within these boundaries, the breast may have different shapes that can make it more or less attractive. Differently from shape, breast boundaries have well-defined anatomical structures which can be manipulated directly or indirectly to adjust, when needed, the ideal foundation on which breast volume and shape are enhanced.

73.2 S  urgical Anatomy Related to Breast Foundation I performed dedicated breast dissections to understand the anatomy related to breast foundation, with special reference to the IMF [8, 9]. The main anatomical fascial structure in defining the breast foundation is the superficial pectoralis fascia (SPF), which is a fascial coverage of pectoralis major (PM) muscle. The PM is wrapped by the pectoralis major fascia that anatomically represents a downward continuation of the superficial cervical fascia. In anatomy books, the relationship of this fascia with the surrounding anatomical structures is usually not described in depth. The pectoralis major fascia wraps the PM by splitting itself in the deep pectoralis fascia (DPF) and the SPF.

73  Improving Breast Footprint and Shape Using Anchor Threads in Fat Grafting Breast Augmentation

The DPF is located on the inner side of PM. Inferiorly it ends where PM ends and laterally it fuses itself with the SPF to define the pectoralis fascia laterally, or lateral pectoralis ­ fascia (LPF). The SPF is located on the outer side of PM, just below the deep layer of the superficial fascia (i.e. breast capsule). Many fibrous connections exist between the SPF and the deep layer of the superficial fascia (i.e. breast capsule), making a blunt dissection very difficult. These are: –– Numerous thin, fibrous bundles in the upper third of PM –– The presence of the Wuringer septum at the level of the fourth and fifth intercostal spaces –– A tight connective tissue connecting the inframammary fold (IMF) with SPF The SPF thickness varies with different sites of fascia. According to Jindle et al., SPF average thickness is 0.49, 0.60, 0.52 and 0.68 mm in the upper, lower, medial and lateral side. In our cadaver dissection experience, we found the SPF to be a thin and fragile but well-defined fascia with strict anatomical relationship with PM epimysium (Fig. 73.1), confirming Jindle findings. The cleavage between SPF and PM is anatomically not well delineated because of the strict relationship between SPF and PM epimysium. For this reason, few PM fibres have to be included in the fascia dissection. We found that the SPF shows a peculiar behaviour at the level of the IMF. At this point, the SPF has a fan-shaped structure with two main divergent directions: upper fibres that go superficially ending in the subcutaneous ligamentous structure (i.e. superior wing) and lower fibres going inferiorly, fusing with fifth rib periosteum and vanishing over rectus abdominis (RA) sheath (i.e. inferior wing) (Fig.  73.1). SPF is anatomically superficial to RA fascia and vanishes on it without having any continuity. Lateral to PM, the SPF fuses with the deep pectoralis fascia defining the axillary fascia (AF) that extends laterally to the lateral margin of latissimus dorsi muscle and enwraps it. This superficial fascia (i.e. AF), along with the intermediate clavi-coraco-pectoral fas-

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cia (enwrapping the pectoralis minor and subclavian muscle) and the deep serratus anterior fascia, is the structure that defines the lateral fascial confluence. The superiormost and medialmost boundaries of breast are defined by osseous structures such as the clavicle superiorly and the sternum medially.

73.3 I mplications in Breast Fat Grafting In breast fat grafting, the aim should be not only to augment the breast volume but also to sculpt the breast to provide an appealing shape on the augmented volume. The surgeon should be able to shape the breast in “closed” fashion, meaning not adding incisions. When augmenting a hypoplastic or constricted breast we need to add volume beyond that breast boundaries. In fact, we are overpassing the old boundaries to enlarge the breast as we do with implant breast augmentation. The main boundaries needed to be overpassed are the IMF and lateral breast area. By augmenting these areas, we are weakening breast foundation in a controlled fashion. However, these weakened areas will be interested by oedema accumulation which may further weaken them and may jeopardize the final breast foundation, creating a large but not projected breast. This is why breast fat grafting augmentation is compared to a mountain of sand: the more we augment, the more the base increases compared to projection. The main drawback in fat grafting breast augmentation is no control of breast boundaries. This is true not only during the surgery, but especially in the post-operative period when swelling takes place. Swelling has a peak phase in the first week post-operatively and then starts to subside in the following 8–10 weeks. Boundaries can be controlled post-operatively using external bandages or foams. However, these are not comfortable for the patient and they may cause skin irritation and breakdown, which may lead to their removal, thus losing their effectiveness.

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Fig. 73.1  Superficial pectoralis fascia dissection. We found a peculiar behaviour of the SPF at the level of the IMF. At this point the SPF has a fan-shaped structure with two main divergent directions: one that goes superficially ending on the skin, which is called superior wing (blue dotted line) at the level of the IMF, and the other one that

goes inferiorly, which is called inferior wing (green dotted line) vanishing on the rectus sheath. This structure plays a fundamental role in defining the IMF as, through this aponeurotic structure, the IMF is firmly attached to the chest wall [8]

I introduced a new scarless technique using anchor threads which allows to control b­ oundaries in the post-operative period, aiding in defining the breast shape and taking advantages of the post-operative swelling by driving expanding forces in the most dependent area, the lower pole [10] (Fig. 73.2). Notice that the tightening of the thread allowed plication of the inframammary fold superior wing toward the rib cage.

centrifuged for 15 s, and reinjected through 3 mm syringes using 14- and 16-G cannulas. The existing inframammary folds were lowered by a combination of blunt and sharp instruments weakening and filling the space with grafted fat. At the end of the procedure, a bolus of 2.5  cc of saline and adrenaline 1:500,000 is injected on top of the fifth rib touching the perichondrium medially and laterally. This manoeuvre serves to reduce bleeding and to expand soft tissue in order to catch more tissue with the Deschamps-like needle. Then, two 1–0 polydioxanone dual-anchor thread sutures were percutaneously looped down to muscular fascia/ perichondrium on the medialmost (parasternum) and lateralmost (mid-axillary line) new inframammary fold using dedicated Deschamps-like needles. The threads are 360° cog anchor threads with a smooth portion in the middle and opposite cog direction so that when they are folded, the cogs have the same direction.

73.4 Surgical Technique Preoperatively, the desired new position of inframammary fold is designed symmetrically on both sides from parasternum to mid-axillary lines to set the new inframammary fold and to control final breast width (Fig. 73.3). Fat grafting procedure was performed using microfat technique. The fat was harvested through a 1.8 mm cannula with three 1 mm slits,

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Fig. 73.2 Artist drawing of dual-anchor cog thread technique showing the anatomical level placement of threads before tightening. Notice that the cogs shown in the small framework are not opened. (Above, right) Close-up artist drawing of the anchor of the medial thread, which shows that the anchor passes through the subcutaneous tissue and the entire pectoralis major, up to the fifth-rib periosteum. (Below) Artist drawing of the dual-anchor cog thread technique after tightening

After looping, the threads were percutaneously passed along the designed new ­inframammary fold using 35  cm flexible 2  mm straight needles, exiting the skin along the centre of the IMF. Then the threads were tightened up to the desired effect. The surplus threads were cut at skin level (see Video 73.1, which shows the technique). A high-definition, symmetric new IMF was immediately achieved along with a high-defined, symmetric breast width. No post-operative external bandages were used.

73.5 Our Experience A high-definition new inframammary fold was achieved in all cases and the IMF new location remained stable at follow-up. In our experience, we applied successfully this procedure on 35 patients with an average age of 25  years and BMI of 25.71. Majority of our patients were affected by breast hypoplasia and rejected implant augmentation (51.5%). The other half of the patients were affected by major asymmetry (25.7%) (breast hypoplasia on the

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Fig. 73.3  Preoperative planning of unilateral fat grafting breast asymmetry to correct a case of left anterior thoracic hypoplasia with breast asymmetry. The left native IMF (marked in blue) is higher than contralateral. A lower IMF symmetric to the contralateral side has been marked in black. This will be defined intraoperatively by using anchor thread technique

one side and ptotic and hyperplastic breast on the other side) and 22.8% by tuberous breast. Based on patient features and desire, one or two sessions of fat grafting were performed to achieve the desired volume and contour. In patients affected by major asymmetry a contralateral reduction/pexy was also performed and for 90% of tuberous breast a periareolar mastopexy was needed to improve matching with the contralateral side (Table 73.1). No post-operative complications were experienced such as thread infection, extrusion or inflammation. The most interesting result, in our opinion, was not only the definition of the new IMF but also to observe dynamic changes of breast shape related to internal swelling force redriven by the threads (Figs. 73.4, 73.5, and 73.6). The threads act as a “cerclage” along the entire IMF (from midsternum to midlateral axillary line), which represents the most dependent area of the breast. This “cerclage” has two main positive effects in the healing phase: –– Define a nicely indented IMF by favouring scar formation between new IMF dermis and deeper tissue.

Age (average ± SD) 25 ± 4.20 BMI (average ± SD) 25.71 ± 2.48 Indications Patient with bilateral hypoplastic 18 (51.5%): 36 breasts (%): No. of breasts treated Patients with unilateral tuberous/ 8 (22.8%): 8 constricted breast (%): No. of breasts treated 9 (25.7%): 9 Patients with major asymmetry and unilateral hypoplastic breast (%): No. of breasts treated Number of sessions: Amount of grafted fat per session Bilateral hypoplastic breasts All cases 1: 241.5 ± 26.4 Tuberous/constricted breasts All cases 2: 210.4 ± 16.07 Four cases 1 and Major asymmetry: One hypoplastic breast five cases 2 250.16 ± 18.40

–– Create a block to the oedema, which cannot overpass the threads and thus is redriven upward on the lower pole. This creates a constant pressure on the entire lower pole during the healing phase which allows to expand the skin of the lower pole leading to an expanded and tight convex lower pole and an indirect lifting of the NAC due to the increase of NAC-­ IMF distance.

73.6 Discussion Three key elements are crucial to obtain natural and pleasant results in breast augmentation: high-­ defined inframammary fold, balanced breast width and lower pole convexity with NAC sitting at its apex. The three key defining elements are structurally related. Lower pole convexity is strictly dependent on a high-defined new inframammary fold and breast width. Failure in having a well-­ defined, nicely indented and firm inframammary fold corresponds to a flaring in breast width ­definition and loss of the tight convex lower pole curve. Breast enhancement with fat grafting means augmenting the breast by a diffuse injection of fat

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Fig. 73.4  Preoperative (left) picture of left-breast hypoplasia with constricted lower pole. Notice the short distance between NAC and IMF and NAC pointing downward as well as a straight lower pole. After fat grafting breast augmentation by lowering and defining the IMF using dual-anchor thread technique, the breast was augmented and the new IMF lowered and well defined. (Right) Notice

that the lower pole became tight convex, the NAC-IMF distance increased and the NAC is now pointing forward. This clearly demonstrates the favourable expansion of the lower pole with footprint preservation, NAC-IMF distance lengthening and NAC tilting upward

graft in all anatomic planes (i.e. from subpectoral to subdermis). Achievement of a pleasant breast shape and volume is dictated by a combination of volume distribution, weakening/reshaping of constricted areas with ancillary percutaneous aponeurotomies and fine balance of interstitial pressures. Management of the three key defining elements is not straightforward as in implant breast augmentation. In fact, although in breast augmentation with fat grafting it is technically simple to expand breast boundaries (lowering inframammary fold, increasing breast width) and to improve lower pole convexity, it is not technically possible to high-define these boundaries and consequently to have a tight convex lower pole. We found the dual-anchor thread technique a safe and reliable adjunct to fat grafting breast

augmentation to control footprint and enhance breast shape. We believe that the placement of dual-anchor cog thread played a key role in defining breast footprint, IMF and an improved breast shape very likely for two key effects: 1. Precisely defining breast footprint and IMF after the procedure. In fact, it allows stabilizing the IMF and lateral breast footprint tissue. 2. Redirection of post-operative oedema. The thread will prevent the 3–4-month post-­ operative oedema to push downward the IMF and lateral breast footprint, thus favouring its redirection toward the lower pole, just above the IMF. The result is natural expansion of the lower pole soft tissues with a corresponding

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Fig. 73.5  Preoperative (above) pictures of right tuberous breast and breast asymmetry. The patient underwent prior right-breast augmentation with fat grafting (two sessions 300 cc + 250 cc) and anchor thread placement to stabilize

the new lower IMF and obtain a new lower pole. Final result after bilateral mastopexy using vertical technique at 6-month follow-up (below)

dramatic improvement of breast shape (i.e. tight convex lower pole, well-indented and nicely defined IMF and lateral breast footprint). Once the oedema subsides, internal scars related to thread placement would have very likely stabilized the IMF and there is no more oedema to counteract. Thus, the presence of the thread, which has been resorbed, becomes useless.

Indications, advantages, limitations, and complications of our technique are reported in Table 73.2. The use of threads to improve breast footprint and shape is not novel. Both smooth and barbed sutures have been reported in literature for the demarcation of IMF and lateral breast footprint [11–13]. However, these procedures were opened and thus not comparable to FGBA, which is a closed surgery.

73  Improving Breast Footprint and Shape Using Anchor Threads in Fat Grafting Breast Augmentation

Fig. 73.6  Preoperative (left) picture of tuberous breast. Notice the short distance between NAC and IMF, constricted lower pole and NAC herniation. 14 months after fat grafting breast augmentation by lowering and defining the IMF using dual-anchor thread technique, the breast was augmented and the new IMF lowered and well

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defined. (Right) Notice that the lower pole became tight convex, NAC-IMF distance increased, and tuberosity and NAC herniation effect was corrected. This clearly demonstrates the favourable expansion of the lower pole with footprint preservation with NAC-IMF distance lengthening

Table 73.2  Indications, limitations, advantages, complications Indications Cosmetic breast augmentation

Limitations Tissue recruiting Not able to recruit lateral thoracic tissue/abdominal tissue in the breast mound

Major breast asymmetry

Breast malformations (i.e. tuberous breast) NAC nipple-areola complex, IMF inframammary fold

Advantages Scarless

Footprint control (i.e. IMF contolled lowering; avoid fading with lateral thoracic tissues) Cerclage effect → pexy effect (i.e. enhances lower pole convexity, increases NAC-IMF distance; NAC tilting upward)

Complications Dimpling Transient dimpling around the suture entry points NO thread-related complications experienced

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1116 Table 73.3  Comparison among the four techniques of breast fat grafting using threads Indication

RAFT (Khouri)a Cosmetic and reconstructive

PALL (Abboud)a Cosmetic and reconstructive Not absorbable (nylon)

PPSS (Hamdi)b Reconstructive

DAT (Visconti) Cosmetic

Absorbable (PDS)

Absorbable and barbed (PDO) Tissue imbrication (no knot) Half loop along the entire new IMF Define new IMF Increase IMF-NAC distance Improve lower pole convexity Indirect NAC scarless lifting

Suture material

Absorbable (PDS)

Biodynamic

Suspension (loop with single knot) + interrupted buried fixing stitches Looping around and beyond breast borders

Multiple suspension (loop with single knot) Looping around and beyond breast borders

Suspension (double loop with single knot) Looping within the breast borders

Recruiting in the breast extra tissue from abdomen and lateral thoracic area to enhance volume (flap + lipofilling) defining new breast footprint

Similar aim as for RAFT In reconstructive cases, also associated with flaps from lateral thoracic area

Increase breast projection and borders

Technique

Aim

RAFT reverse abdominoplasty and fat transfer, PALL power-assisted lipo Based on data shown in Meetings’ presentation b Hamdi M, Anzarut A, Hendrickx B, Ortiz S, Zeltzer A, Kappos EA. Percutaneous Purse-String Suture: An Innovative Percutaneous Technique for Inframammary Fold Creation and Improved Breast Projection in Reconstructive Surgery. Aesthet Surg J. 2018;38(12):1298–1303. https://doi.org/10.1093/asj/sjx190 a

Khouri has been the first author who introduced the use of percutaneous threads in breast fat grafting. He called his procedure RAFT (reverse abdominoplasty and fat transfer) which briefly consists of a percutaneous pursestring PDS smooth suture with the aim to recruit abdominal tissue into the breast and at the same time to improve breast shape and control footprint [11]. Similarly, Abboud et  al. also reported the advantages of using percutaneous threads to recruit local tissue in order to improve fat grafting breast augmentation results [12]. Dr. Khouri and Dr. Abboud techniques bring extra soft tissue (i.e. from lateral thoracic area and/or from upper abdomen) within the breast, providing an increased scaffold space for grafting the fat. Hamdi et al. have recently reported the percutaneous purse-string suture (PPSS) technique, which briefly consisted of a double-PDS purse-­ string suture without any tissue-recruiting aim,

but mainly for improving breast shape [13] (Table 73.3). ____________________. All those procedures are elegant adjunctive techniques to breast fat grafting in which smooth threads have been used, with the suture tensile strength downloaded on buried surgical knots, thus classifiable as suspension thread procedures. The use of dual-anchor cog threads is based on the principle of progressive tissue imbrication within each cog, and thus the tensile strength is progressively downloaded and finally locked by the anchor part of the thread into two deep firmer structures (i.e. pectoralis major muscle medially and serratus anterior fascia laterally). The aim of this procedure is not to recruit further tissue into the breast, rather to stabilize the new IMF and positively control and take advantage of the post-­ operative oedema to enhance breast shape. This procedure is knotless and it requires minimal stab incisions (no need to bury the knot) with no visible scar (1 mm).

73  Improving Breast Footprint and Shape Using Anchor Threads in Fat Grafting Breast Augmentation

73.7 Conclusion The dual-anchor thread suture technique is a new, effective, simple, reliable, safe and scarless method to control and high-define the new inframammary fold and breast width in fat grafting breast augmentation. By allowing an upward redirection of interstitial pressure on the lower pole rather than on the new inframammary fold, a further benefit is achieved due to an enhanced shaping effect on lower pole convexity. Disclosure  Authors do not have any interest to disclose.

References 1. Coleman SR, Saboeiro AP.  Primary breast augmentation with fat grafting. Clin Plast Surg. 2015;42(3):301–6. 2. Khouri RK, Khouri RK Jr, Rigotti G, Marchi A, Cardoso E, Rotemberg SC, Biggs TM.  Aesthetic applications of Brava-assisted megavolume fat grafting to the breasts: a 9-year, 476-patient, multicenter experience. Plast Reconstr Surg. 2014;133(4):796– 807. discussion 808-9 3. Voglimacci M, Garrido I, Mojallal A, Vaysse C, Bertheuil N, Michot A, Chavoin JP, Grolleau JL, Chaput B. Autologous fat grafting for cosmetic breast augmentation: a systematic review. Aesthet Surg J. 2015;35(4):378–93. 4. Khouri RK, Rigotti G, Cardoso E, Khouri RK Jr, Biggs TM.  Megavolume autologous fat transfer: part II. Practice and techniques. Plast Reconstr Surg. 2014;133(6):1369–77.

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5. Khouri RK, Smit JM, Cardoso E, Pallua N, Lantieri L, Mathijssen IM, Khouri RK Jr, Rigotti G. Percutaneous aponeurotomy and lipofilling: a regenerative alternative to flap reconstruction? Plast Reconstr Surg. 2013;132(5):1280–90. 6. Mallucci P, Branford OA.  Concepts in aesthetic breast dimensions: analysis of the ideal breast. J Plast Reconstr Aesthet Surg. 2012;65(1):8–16. 7. Mallucci P, Branford OA. Design for Natural Breast Augmentation: the ICE principle. Plast Reconstr Surg. 2016;137(6):1728–37. 8. Salgarello M, Visconti G, Barone-Adesi L.  One-­ stage immediate breast reconstruction with implants in conservative mastectomies, breast reconstruction  - current techniques, Marzia Salgarello, IntechOpen, 2012. https://doi.org/10.5772/39212. Retrieved from https://www.intechopen.com/books/ breast-­reconstruction-­current-­techniques/one-­stage-­ immediate-­breast-­reconstruction-­with-­implants-­in-­ conservative-­mastectomies 9. Salgarello M, Visconti G.  Staying out of double-­ bubble and bottoming-out deformities in dual-plane breast augmentation: anatomical and clinical study. Aesthet Plast Surg. 2017;41(5):999–1006. 10. Visconti G, Salgarello M.  Dual-anchor cog threads in fat grafting breast augmentation: a novel scarless method for defining breast footprint and enhancing shape. Plast Reconstr Surg. 2019;143(4):1039–49. 11. Khouri RK Jr, Khouri RK.  Current clinical applications of fat grafting. Plast Reconstr Surg. 2017;140(3):466e–86e. 12. Abboud MH, Dibo SA, Abboud NM. Power-assisted liposuction and lipofilling: techniques and experience in large-volume fat grafting. Aesthet Surg J. 2019. Epub ahead of print 13. Hamdi M, Anzarut A, Hendrickx B, Ortiz S, Zeltzer A, Kappos EA.  Percutaneous purse-string suture: an innovative percutaneous technique for inframammary fold creation and improved breast projection in reconstructive surgery. Aesthet Surg J. 2018;38(12):1298–303.

Inverted Nipple Correction with Central Tunnel Technique and Fat Grafting

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Amin Kalaaji, Vanja Jönsson, and Jakob Schnegg

Key Messages  • Inverted nipples are prevalent in 3–10% of the population and can often cause functional, psychological, and aesthetic problems. • Numerous corrective procedures exist, which are mostly characterized by a short follow-up period and small sample size of patients. • The goals of a corrective procedure for inverted nipples include restoring the aesthetic appearance of the nipple, minimizing ductal disruption, preserving the ability to breastfeed, and reducing recurrence rates. • Clinical examination is essential to determine the appropriate method to be used. • The implementation of fat grafting in the central tunnel technique results in diminished traumatic impact and minimal scarring, while at the same time providing more viable support for the corrected nipple. • Fat grafts could be taken from the abdomen with a multi-hole cannula and after decanting Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_74) contains supplementary material, which is available to authorized users. A. Kalaaji (*) · V. Jönsson · J. Schnegg Oslo Plastic Surgery Clinic (Oslo Plastikkirurgi Clinic), Oslo, Norway e-mail: [email protected]

could be grafted to the empty space beneath the elevated nipple with 1 mL to 3 mL of fat. • Our algorithm is based on three important aspects: (1) complete release of the internal structures; (2) providing support to the underlying tissue by filling the dead space with fat; and (3) postoperative suspension of the nipple to prevent reinversion. • Postoperative suspension is a key factor in the procedure and lasts for approximately 4 weeks.

74.1 Introduction Inverted nipples, which affect approximately 3–10% of women, are defined as nipples that do not extend past the areolar plane [1]. Consequences of this deformity include functional problems (e.g., in breastfeeding) and negative aesthetic perceptions, which may even induce psychosexual difficulties. Severe nipple inversion might also cause recurring inflammation and irritation, often triggered due to poor hygiene of the nipple-areola complex. Most commonly, inverted nipples are an inherited genetic trait seen from birth, but this condition can also be the result of recurrent ductal mastitis, breast surgery, macromastia, or ductal carcinoma [1–6].

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_74

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The universally accepted grading system to help determine the severity of inverted nipples was created by Han and Hong [7]:

74.2 Methods

• Grade 1: Intact soft tissue with little or no fibrosis and normal lactiferous ducts; the nipple can be pulled out easily and stays ­ projected. • Grade 2: The nipple can be pulled out manually but retracts when released. • Grade 3: The most severe form; the nipple is difficult to pull out manually.

All surgical procedures were performed by the main author, with the patient under moderate sedation and local anesthesia, or only local anesthesia. The surgical procedure was identical for each patient and involved three elements: (1) the treatment of the inverted lactiferous ducts; (2) the support (via filling) of the remaining dead space; and (3) the suspension to provide support to the nipples after the first two procedures are performed. After sterile washing and dressing, local anesthesia, consisting of 3  mL xylocaine (lidocaine HCl) and 1% adrenaline, was infiltrated into each nipple as a round block. The inverted nipple was maximally elevated with a hook and suspended by a 3–0 PDS thread/suture (Ethicon Inc., Somerville, NJ, USA) attached vertically to the inversion line from the 12 o’clock to the 6 o’clock position, 11 o’clock to 5 o’clock position, etc. The thread was inserted deeply to the nipple base, and across the full width of the nipple. The thread was then elevated and stabilized by a needle holder to pull the nipple out while the correction was completed.

Over time, various techniques have been developed to correct inverted nipples. More conversative approaches include continuous traction, aspiration/ suction, as well as piercing. Invasive surgical approaches include dermal glandular and dermoglandular flaps, internal sutures, stabbing incisions, endoscopic release of fibers, and interposition of artificial or autologous materials [8–20]. Postoperative adverse effects related to the previously mentioned interventions include lactation difficulties, dulled sensation, areolar deformity, and inversion recurrence. There is, unfortunately, no consensus as to the preferred treatment [8]. The ideal method should be safe and easy to perform, and should offer reliable results, while simultaneously being less time consuming. Additionally, it should allow for easy application of dressings, minimal visible scarring, and a low risk for recurrence and complications. Although there are numerous studies on inverted nipple repair, few have included a large patient sample size, and even fewer express data on the long-term postoperative outcomes [8]. Therefore, the authors present an attempt to create an algorithm for treating inverted nipples [8], which includes the implementation of well-­ established methods as well as a new, minimally invasive surgical technique. The results are described therein. The expressed goals were to treat inverted nipples while minimizing ductal (lactiferous) disruption, retaining the ability to breastfeed, supporting the corrected nipple with fat grafting to create a satisfactory aesthetic appearance of the nipples, and keeping recurrence rates low.

74.2.1 Surgical Techniques

74.2.2 Techniques that Treat Inverted Lactiferous Ducts Three unique surgical techniques were applied for the treatment of inverted lactiferous ducts. The optimal procedure for each patient was determined by their age, fertility status, and grade of nipple inversion (Fig. 74.1).

74.2.2.1 T  echnique 1: Central Tunnel Method After elevation of the nipple with a 3–0 PDS suture, a central tunnel was created using a 14- or 18-gauge cannula (hollow needle) ending at the base of the nipple, severing the main inversion line that is usually oblique from side to side, as from 2 o’clock to 8 o’clock, 4 o’clock to 10 o’clock, etc. (Figs. 74.2, 74.3, and 74.4). At this

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Fig. 74.1  Main release central tunnel with needle or knife and different kinds of support with flap and fat. Schematic illustrations of the technique. Upper left: Central tunnel with knife in lateral view (left); note that lactiferous ducts are mostly intact in the circle to the right. Upper middle: The tunnel seen from anterior showing the intact anterior lactiferous ducts. Upper right: Central tunnel made less traumatic with gauges 14–18. Middle left: Fat grafting syringe with 1 mL. Middle second left: Fat graft transferred after decanting with a 1 mL syringe. Middle right: At the end of the operation, Vaseline (petro-

leum jelly) is applied on the elevated nipple with gauze. Lower left: The other method for supporting the elevated nipple: dermal flap design and the thread lifting the nipple at the beginning of the operation (left). Lower second left: Raising the flaps with frontal view, thus preserving the lactiferous ducts. Lower third left: Flipping and suturing the flaps; the knot will be in the center of the nipple on the base of the tunnel. Lower right: Crestinu method with complete cutting of the ducts. This artwork was reproduced partially from Kalaaji A, et al. Aesthetic Surgery Journal 2020;40(5):NP238-NP250 [8]

Fig. 74.2  Third-degree inverted nipple in a 21-year-old girl, corrected with central tunnel release and fat grafting of 2 mL, 4 weeks after applying the suspension and performing central tunnel technique combined with fat grafting. Assessment and technique. Upper row: left and second left: Inversion lines; from 2 to 8 o’clock on the right and 4 to 10 o’clock on the left. Third upper left: Showing the suspension device before the procedure. Upper right: Donor site for fat harvesting. Central tunnel performed with 14 G needle at the base of the nipple from

side to side and parallel to the inversion line. Lower left: Elevating the nipple with hooks and 3–0 PDS. Lower second left: Creating the central tunnel with a 14 G needle. Lower third left: After putting on suspension device; note the pink color of the nipple indicating good capillary circulation. Lower right: 4 weeks postoperatively. Note the fine color of the nipple and its good size and form. The thread starts to loosen as the traction lessens; healing under the corrected nipple is completed, which makes recurrence less likely

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Fig. 74.3  Fat grafting and per-operative dressing. Upper left: Preparing the fat between 5  mL syringe and 1  mL syringe. Upper right: Grafting with 1  mL syringe from separate incision, approximately 12 o’clock. Lower left:

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Vaseline (petroleum jelly) jelly gauze to moisturize the nipple. Lower right: A simple dressing to keep the suspension device at 90 degrees toward the nipple to prevent twisting

Fig. 74.4  24-year-old girl. Third-degree nipple inversion, treated with central tunnel release and fat grafting 3 mL. 3 years of follow-up; ability to breastfeed. Upper row: Before surgery. Lower row: 3 years after surgery

74  Inverted Nipple Correction with Central Tunnel Technique and Fat Grafting

position, the fibers were incised, and the retraction of the nipple led to the severing of the most inverted area. The first attempts at this novel technique were performed with a knife, and then later, a less traumatic instrument replaced the knife: an 18- or 23-gauge needle. In severe cases of nipple inversion, a 14-gauge needle was used instead. As support was required from within and beneath the tunnel, the subsequent dead space was filled via fat grafting. The width of the tunnel was approximately 1  mm to 2  mm. This technique preserved most of the lactiferous ducts from above and below the tunnel (Video 74.1).

74.2.2.2 T  echnique 2: Central Tunnel Creation Via Lateral Partial Cut After elevation of the nipple, a small bilateral incision was made with a 2  mm, no. 11 blade. The contracted connective tissue was cut through a narrow tunnel beneath the inversion line— approximately 2 mm—while maintaining the lactiferous ducts that come forth from the inferior and superior (Fig. 74.1). 74.2.2.3 T  echnique 3: Severing the Lactiferous Ducts (The Crestinu Method) The total cut method as described by Crestinu [5] is performed on patients based on the criteria that the patients are not of childbearing age or did not want to have children. All lactiferous ducts are severed via a small incision of 2 mm around the 6 o’clock position. The connective tissue causing the nipple inversion is cut using a no. 11 blade or small scissors (Figs. 74.5, 74.6, and 74.7).

74.2.3 Techniques that Offer Support Under The Elevated Nipple A hollow space was created via the dissection of fibrous tissue ducts. In mild cases, this space was limited to the central tunnel. However, in more severe cases, this space was enlarged and extended from the subcutaneous space to the breast tissue after cutting the connective fibrous

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tissue associated with the inversion. A simple test called a pressure test was used to ascertain whether support was needed, and it was performed in conjunction with a preoperative clinical evaluation to decide which filling, if any, should be applied.

74.2.4 The Pressure Test The pressure test was developed to determine the breast tissue volume beneath the inverted nipple, mostly depending on the size of the breast and grade of inversion. When severing an acutely inverted (i.e., grade 3) nipple, a sizable dead space should be anticipated, regardless of the chosen technique, and it must be filled to maintain eversion. The test is performed by placing a finger on the nipple and gently pressing it vertically backward, so that the resistance, or emptiness, in the area behind the nipple can be evaluated. It is expected that severe mammary hypoplasia, serious ptotic breasts, and higher degrees of nipple inversion (grade 2 or 3) require support.

74.2.5 Three Techniques to Manage Support for the Elevated Nipple 74.2.5.1 Technique 1: No Filling This technique is appropriate for grade 1 inversions in which there is no need to support the under-nipple area mechanically. In cases where no filling is needed, the final stage of treatment (i.e., the application of the suspension device) is initiated. 74.2.5.2 T  echnique 2: Subdermal Triangular Flaps Two small 3 × 6 mm dermal flaps were placed at the edges of the inversion line of the nipple. After the flaps were marked, they were de-epithelized and positioned under the tunneled area to provide support to the elevated nipple. A suture of 4–0 Vicryl (Ethicon Inc., Somerville, NJ) was placed on the top of one flap and then threaded through

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Fig. 74.5 61-year-old woman. Third-degree nipple inversion presented for bilateral nipple repair; total cut, and second total cut with fat transplant. Upper row:

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Preoperative views. Lower row: Postoperative views after 12 months. Note that a second treatment with a 3 mL fat transplant was necessary to achieve satisfactory results

Fig. 74.6  46-year-old woman. Left-sided nipple inversion, presented for combined breast augmentation and unilateral nipple repair; total cut and fat grafting. Upper row: Preoperative views. Lower row: Postoperative views at 16 months

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Fig. 74.7  40-year-old woman. Right-sided grade 3 inversion presented for unilateral nipple repair: total cut and fat transplant. Upper row: Preoperative views. Lower row:

Postoperative views after 8 months. This figure was reproduced from Kalaaji A, et  al. Aesthetic Surgery Journal 2020;40 (5):NP238-NP250 [8]

to the other side, where it caught the top of the opposing flap and returned to the original side. The knot was made and precisely positioned in the center of the nipple just beneath the central tunnel (Fig. 74.1).

74.2.6 Postoperative Suspension

All nipples were suspended using a suspension device/stent, which was procured from the bottom of a 10 mL syringe and applied for 4 weeks postoperatively. The device was about 1 cm high, 74.2.5.3 Technique 3: Fat Grafting with dual-ended openings approximately 8  mm Application of the central tunnel technique for from the base, where it could be bridged with a the treatment of the lactiferous ducts was com- pin from each side. The nipple was then susbined with a less invasive method for maintaining pended to the pin with a 3–0 PDS suture, ensureversion: fat grafting in the tunnel and dead ing that circulation was not restricted. In cases of space. The colloquial “microfat” was harvested a wider nipple, a 20 mL syringe is recommended. from the abdomen by using a small multihole The suspension height may also be altered with cannula (0.8 mm) after tumescent infiltration of the usage of a 6, 8, or 10 mm side hole height. the affected area. A 10 mL syringe with a Luer-­ Circulation was checked while the knot was lock tip was used. The extracted fat was decanted tightened to avoid compromising the capillaries for 10  min, separated, transferred to a 1  mm and cutting off the circulation of blood. syringe, and then injected through a small inci- Depending on the patient’s desired amount of sion via a 0.7 mL cannula. nipple lift, the degree of eversion was ascertained The amount of grafted fat required for a suit- and both breasts were checked for symmetry. The able filling was approximately 1–4 mL, depend- PDS suture was then locked on the pin, bridging ing on the severity of the inverted nipple and the the holes on either side. There should at least be a amount of dead space to be filled (Fig. 74.2, 74.3, ten-time roll of the knot to prevent suture failure 74.4, 74.5, 74.6, and 74.7) (Video 74.2). during the 4-week-long postoperative period.

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Finally, JELONET paraffin gauze (Smith & Nephew, London, England) was applied under the base of the syringe and around the nipple.

74.2.7 Immediate Postoperative Follow-Up Before the patient was discharged, the nipple was checked for color and capillary filling. On day 1 postoperatively, it was necessary to recheck the nipple for color and capillary filling again. If the nipple was entirely blue or whitish, the suture was released or severed to ensure the circulation and vitality of the nipple. Additionally, patients received further education on the daily care of their wounds: disinfection using Hibiscrub antimicrobial skin cleanser (chlorhexidine gluconate solution; BCM Ltd., Beeston, Nottinghamshire, United Kingdom) and application of sterile petroleum jelly (Vaseline; Unilever, London, United Kingdom) to keep the wound area moisturized. Patients were also advised to place gauze under the device toward the skin to avoid friction and subsequent irritation. Direct postoperative photos of the nipple are shown in Figs.  74.2 and 74.3. If geographically convenient to the patient, the patient was encouraged to come in for postoperative follow-up visits during weeks 1, 2, and 4. After 4 weeks, the device would be removed by cutting the PDS suture, and a hollowed gauze turned toward the bra would be applied until the next biweekly follow-up. This measure was undertaken to reduce the recurrence of inversion due to undue pressure on the nipple. The healing process of the flap, tunnel, and dead space underneath took place as expected. If this ideal situation of biweekly, in-clinic follow-ups was not possible, a video call was scheduled at the same intervals and the patient could remove the device independently or with the help of medical assistants under our guidance and supervision. The authors followed the guiding principles from the Declaration of Helsinki.

74.2.8 Treatment Algorithm The authors have developed a unique treatment algorithm (Fig.  74.8) addressing all aspects of inverted nipple cases, including techniques to release the inverted lactiferous ducts, to support the underlying dead space, and to provide postoperative support via a novel suspension device. These three aspects must be taken into consideration and applied according to each patient. The patient’s age, the grade of inversion, and the pressure test to feel the underlying support define the method of choice for each patient (Fig. 74.1). For the release of lactiferous ducts, the central tunnel technique has been established, which has minimal traumatic effect on the ducts and focuses on their preservation.

74.3 Discussion A perfect method for the treatment of inverted nipples does not exist. We conducted a study on a total number of 161 inverted nipples at the Oslo Plastic Surgery Clinic [8]. As mentioned previously, our algorithm is based on three important aspects that must be addressed for successful treatment: (1) complete release of the internal structures preventing nipple eversion; (2) providing support to the underlying tissue by filling up empty spaces; and (3) suspension of the nipple postoperatively to prevent reinversion (Fig. 74.1). The algorithm suggests performing one of the three surgical techniques depending on the patient’s age and the severity of the inversion. The central tunnel or the partial cut technique are methods of choice for women of childbearing years or those who anticipate having children. The decision of which method to choose is determined by assessing the degree to which the tethering bands are pulling the nipple inward. Milder inversions might best be treated with the central tunnel technique, which spares the ducts and leaves no visible scarring. The partial cut technique, on the other hand, might be more suitable for cases in which a greater release of the fibrous structures is needed.

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Fig. 74.8  Treatment algorithm. Tool to help evaluate and treat different kinds of inverted nipples, as well as give an overview on possible treatment options. This figure was

reproduced from Kalaaji A, et  al. Aesthetic Surgery Journal 2020;40 (5):NP238-NP250 [8]

The total cut technique by Crestinu is only appropriate for patients who are not of childbearing age or who are unable or unwilling to have children. If this technique is suitable, it represents a promising method that should be considered, because it has a low recurrence rate. Depending on whether a defect is detected with the pressure test and its scope, it can be determined whether support of the nipple through fat grafting (which is better for smaller defects) or triangular flaps (recommended for more substantial defects) is needed. The option between fat grafting and flaps is available in all cases and must be decided on a case-by-case basis. Fat grafting represents a rather new technique that is less traumatic and offers the benefit of resulting in no visible scarring. The pressure test is conducted in parallel to the clinical evaluation and offers an easy method to determine if support is required or whether treatment is sufficient with only ductal release and suspension.

To further enhance the surgical result, postoperative suspension with a distraction device is recommended in all cases of nipple inversion correction. In cases of hypotrophy or hypertrophy of the breasts, mastopexy, or breast augmentation with implants, fat grafting may be performed to reinforce nipple support. This should be considered when support of the underlying tissue is required. Purse-string suture methods are not included in the algorithm due to the risk of ischemia from the burden on the blood supply that inevitably results [4]. In addition, sufficient correction of volume loss under the nipple after removal of the fibro-ductal tissue might not be possible. This is demonstrated in the postoperative nipple height reduction, which ranges from 10% to 50% for this technique. Although alternative suture techniques have been proposed, the ability to breastfeed cannot be preserved in most purse-string suture techniques due to destruction of lactiferous ducts, which further justifies omitting these methods from the algorithm.

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74.3.1 The Central Tunnel as the Optimal Technique to Address Lactiferous Ducts When treatment of the inverted nipple was initiated at our clinic in 2005, established techniques from that time period were used. However, the use of these methods revealed the limitations of the numerous flap designs, as well as the insufficient filling of the empty space beneath the nipple as a result of severing the ducts. In addition, the purse-string suture method did not present a suitable alternative at the time because of the high rate of complications due to the reduced blood supply to the nipple. Therefore, we realized that the challenge of successful nipple inversion repair involves achievement of proper support beneath the nipple to occupy the dead space; this is a greater challenge than avoiding severing of the tethering ducts. If the hollow space was not adequately filled, recurrence was likely, regardless of the deployed method for dissection of the fibrous tissue. Later, the concept of a postoperative suspension device was created, and it was used in all cases onward. Once the previously mentioned treatment principles were established, we focused on reducing trauma, decreasing procedure length, and importantly preserving nipple viability via the tunnel technique. Trauma was reduced to a greater extent by using the central tunnel method with a 14- or 18-gauge needle. Compared to the partial cut technique, this technique improved protection of the surrounding lactiferous ducts and eliminated visible scarring. In addition, better control was achieved when applying this method as opposed to using a blade or separating the tissue with scissors. Overall, the central tunnel technique represents a refinement in the treatment of inverted nipples. Furthermore, the diameter of the tunnel created with the central tunnel method is more precise and easier to work with than in blade use—because the central tunnel technique results in less damage to the peripheral lactiferous ducts. By choosing the central tunnel technique, only the fibrous bands (including possible functioning

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lactiferous ducts in the center that most commonly retract the nipple) are cut. It is estimated that approximately 80% (2 mm wide tunnel of an average nipple diameter of 12 mm) of the lactiferous ducts in the peripheral nipple area can consequently be preserved. We are convinced that even cases of grade 3 inversion still possess intact lactiferous ducts in the periphery of the nipple, and that these could be saved and lifted with this technique. When considering other possible reasons for the impairment of breastfeeding, e.g., hypotrophic mammae, preserving 11 to 15 of the 15 to 20 normally existing ducts is a worthy outcome. The central tunnel method achieves traction that lifts the nipple, thus creating a hollow space, which supports the expansion of other structures such as the lactiferous ducts external to the central tunnel. It is essential to note that the degree of the inversion, as well as the nipple diameter, dictates the size of the gauge to be used.

74.3.2 Underlying Tissue Support Schwager and colleagues [21] reported that the thickness of the dense connective tissue beneath the congenitally inverted nipples measured to be approximately 50% of the thickness seen in uninverted nipples. Research by Han and Hong [7] supported this finding by demonstrating that the subareolar tissue of inverted nipples is made up differently and varies depending on severity; more severely inverted nipples have atrophied lactiferous ducts with fibrosis, primarily in the center and underneath the nipple. This defect might warrant filling of the dead space [22–24]. Depending on the emptiness under the inverted nipple, as assessed by the pressure test, the dead space was then filled via fat grafting or subdermal triangular flaps. The subdermal triangular flaps were favored in cases with a stronger substantive defect beneath the nipple, and primarily used in a hybrid treatment plan combined with the partial cut technique. Fat grafting was predominantly applied in patients treated with the novel central tunnel method. Additionally, fat grafts were mainly used in cases with minor

74  Inverted Nipple Correction with Central Tunnel Technique and Fat Grafting

defects in which the implementation of fat was deemed adequate for support [8]. However, a relatively small number of cases with the central tunnel technique and the total cut technique by Crestinu required further support with fat or triangular flaps [8]. Moreover, the partial cut technique necessitated support with triangular flaps in approximately 70% of cases, which serves as a powerful evidence that this technique does not adequately elevate the nipple without further action. To sum up, it has thus far been established that the stronger the degree of nipple inversion, the greater the need for additional support.

74.3.2.1 The Pressure Test in Combination with the Clinical Evaluation Clinical evaluation is essential to assess the grade of inversion, breast volume, and ptosis. However, the pressure test offers the important evaluation of the underlying tissue to determine the need for support. It is an easy method that helps identify the amount of empty space between the nipple and the underlying breast tissue. Generally, severe mammary hypoplasia or severe ptotic breasts and severe nipple inversion (grades 2 and 3) often require support. Nevertheless, the pressure test is beneficial given the heterogeneity of these defects.

74.3.3 Patient Satisfaction and Postoperative Complications In a published study by Kalaaji and colleagues in 2019 [8], patient satisfaction regarding the aesthetic outcome was 93% after the second session, and satisfaction rates increased to 97% after the third session. The recurrence rate and postoperative complications were minor and reported in the same study.

74.3.4 Limitations and Final Recommendations Patient information such as bra size, body mass index, breast ptosis, and medical comorbidities

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could be essential to better classify and therefore offer the most suitable treatment to patients. Another recommendation is to conduct a prospective study and consider the potential differences between the pre- and postoperative quality of life. Getting to know whether patients were able to breastfeed postoperatively would have been valuable. More large-scale, multicenter studies are needed to further clarify the importance of ­duct-­sparing techniques for nipple inversion correction. Investigations regarding methods, meant to preserve nipple-areola complex integrity and breastfeeding function, are recommended.

74.4 Conclusion We present a suggested treatment algorithm that highlights three important goals of inverted nipple repair: (1) release of the structures that prevent nipple eversion; (2) supporting the tissue beneath the nipple after a dead space forms; and (3) postoperative suspension to preserve the integrity of the newly everted nipple. Clinical examination of the patient and severity grading are essential for deciding which treatment option to perform. The central tunnel technique and fat grafting to support the nipple are promising options, although longer followup is needed. Future research must be conducted to evaluate postoperative breastfeeding function and to study whether more extensive postoperative suspension can help achieve even better results and avoid recurrence.

Funding The authors received no financial support for the research, authorship, or publication of this chapter. Conflict of Interest  The authors declare no conflicts of interest.

References 1. Lee M.  Aesthetic and predictable correction of the inverted nipple. Aesthetic Surg J. 2003;23(5):353–6.

1130 2. Stevens WG, Fellows DR, Vath SD, Stoker DA.  An integrated approach to the repair of inverted nipples. Aesthet Surg J. 2004;24(3):211–5. 3. Chen SH-T, Gedebou T, Chen PH-H. The endoscope as an adjunct to correction of nipple inversion deformity. Plast Reconstr Surg. 2007;119(4):1178–82. 4. Peled IJ.  Purse-string suture for nipple projection. Plast Reconstr Surg. 1999;103(5):1480–2. 5. Crestinu J. The correction of inverted nipples without scars: 17 years’ experience, 452 operations. Aesthet Plast Surg. 2000;24(1):52–7. 6. Gould DJ, Nadeau MH, Macias LH, Stevens WG. Inverted nipple repair revisited: a 7-year experience. Aesthetic Surg J. 2015;35(2):156–64. 7. Han S, Hong YG.  The inverted nipple: its grading and surgical correction. Plast Reconstr Surg. 1999;104(2):389–95. 8. Kalaaji A, Dreyer S, Jönsson V, Schnegg J, Orejuela I, Maric I, Vadseth L. Central tunnel technique and fat grafting for surgical correction of inverted nipples and introduction of a treatment algorithm. Aesthet Surg J. 2020;40(5):NP238–50. 9. Li W, Wu Y, Deng Y, Zhang P, Ren GS. An adjustable-­ traction technique for correction of inverted nipples. Ann Plast Surg. 2016;76(1):29–33. 10. Mu D, Luan J, Mu L, Xin M. A minimally invasive gradual traction technique for inverted nipple correction. Aesthet Plast Surg. 2012;36(5):1151–4. 11. Chakrabarti K, Basu S. Management of flat or inverted nipples with simple rubber bands. Breastfeed Med. 2011;6(4):215–9. 12. Hyakusoku H, Chin T.  Usefulness of the nipple-­ suspension piercing device after correction of inverted nipples. Aesthet Plast Surg. 2006;30(4):396–8. 13. Long X, Zhao R. Nipple retractor to correct inverted nipples. Breast Care. 2011;6(6):463–5. 14. Kim DY, Jeong EC, Eo SR, Kim KS, Lee SY, Cho BH.  Correction of inverted nipple: an alternative

A. Kalaaji et al. method using two triangular areolar dermal flaps. Ann Plast Surg. 2003;51(6):636–40. 15. Dessena L, Dast S, Perez S, Mercut R, Herlin C, Sinna R. Inverted nipple treatment and Poliglecaprone spacer. Aesthet Plast Surg. 2018;42(4):958–63. 16. Jeong H-S, Lee H-K.  Correction of Inverted Nipple Using Subcutaneous Turn-Over Flaps to Create a Tent Suspension-Like Effect. Rubino C, ed. PLoS One. 2015;10(7):e0133588. 17. Wu HL, Huang X, Zheng SS.  A new procedure for correction of severe inverted nipple with two triangular areolar dermofibrous flaps. Aesthet Plast Surg. 2008;32(4):641–4. 18. Burm J, Kim Y.  Correction of inverted nipples by strong suspension with areola-based dermal flaps. Plast Reconstr Surg. 2007;120(6):1483–6. 19. Elsahy N.  Correction of inverted nipples by strong suspension with areola-based dermal flaps. Plast Reconstr Surg. 2009;123(3):1131. 20. Feng R, Li W, Yu B, Zhou Y. A modified inverted nipple correction technique that preserves breastfeeding. Aesthet Surg J. 2019;39(6):NP165–75. 21. Schwager R, Smith J, Gray G, Goulian DJ. Inversion of the human female nipple, with a simple method of treatment. Plast Reconstr Surg. 1974;54(5):564–9. 22. Kurihara K, Maezawa N, Yanagawa H, Imai T.  Surgical correction of the inverted nipple with a tendon graft: hammock procedure. Plast Reconstr Surg. 1990;86(5):999–1003. 23. Peeters G, Decloedt J, Nagels H, Cambier B. Treatment of the severe or recurrent inverted nipple by interposition of a resorbable polydioxanone sheet. J Plast Reconstr Aesthetic Surg. 2010;63(2):e175–6. 24. Yamada N, Kakibuchi M, Kitayoshi H, Kurokawa M, Hosokawa K, Hashimoto K. A method for correcting an inverted nipple with an artificial dermis. Aesthet Plast Surg. 2004;28(4):233–8.

Part IX Breast Reconstruction with Fat

Breast Reconstruction with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling (PALLL) Technique

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Nicolas M. Abboud and Marwan H. Abboud

Key Messages 

75.1 Introduction

• Extensive infiltration is used for hydrodissection of the subcutaneous tissues. • Tunnelization of the breast, upper abdomen, and lateral thoracic region then detaches the skin from the matrix and the matrix from the deep plane, facilitating the recruitment of perimammary tissue into the breast. • Deep undermining of the breast to liberate the tethering fibers and the attachments of the matrix to the pectoralis fascia. • Liposuction of the upper abdomen and axillary region releases the skin tension. • Placement of the footprint loop, which recruits tissues from the upper abdomen and lateral thorax, redefining the breast footprint. • Placement of the inframammary fold (IMF) loop, which better defines the new IMF. • Fat grafting is used to increase the breast volume and projection.

Breast reconstruction remains a major challenge for plastic surgeons. Autologous fat grafting has proven to be an efficient approach, but when large volumes of fat are injected in a recipient site under tension, the resorption rate is increased and extra sessions of grafting are required [1–5]. This chapter introduces a scarless method of composite breast reconstruction using tissue recruitment by internal threads (loops) and lipofilling. A key step is matrix dissociation using the principle of power-assisted liposuction and lipofilling (PALL), performed with infiltration, extensive tunnelization, and liposuction [6–9]. Loops are then used to recruit an adipocutaneous flap from the upper abdomen and lateral thorax, in order to reconstruct the breast footprint and the inframammary fold (IMF). In this way, the breast matrix is increased and tension in the recipient site is reduced, allowing the grafting of a larger amount of adipose tissue and facilitating fat survival. This combination of power-assisted liposuction, loops, and lipofilling (PALLL) [10–14] ensures an identical breast footprint, volume, shape, projection, and IMF.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_75) contains supplementary material, which is available to authorized users. N. M. Abboud (*) · M. H. Abboud Plastic and Reconstructive Surgery Department, Centre Hospitalier Universitaire de Tivoli, La Louvière, Université Libre de Bruxelles (U.L.B.), Bruxelles, Belgium e-mail: [email protected]

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_75

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75.2 Preoperative Evaluation and Markings This technique can be used after unilateral or bilateral total mastectomy, for patients who desire a small-to-moderate breast size. Key elements for success in recruiting enough tissue are an adequate amount of fat in the donor site and sufficient skin laxity of the lateral thorax and upper abdomen. Patients who smoke are asked to stop smoking 4 weeks prior to the surgery. All patients undergo preoperative breast examination, including ultrasonography and mammography. Preoperative markings (Fig.  75.1) are performed with the patient in standing position. Lines marked include the midline, the anterior axillary line (defining the lateral limit of the breast), the horizontal interaxillary line joining a

Fig. 75.1 (a, b) Frontal view (a) and three-quarter profile view (b) of the preoperative markings. These drawings include the midline axis, the anterior axillary line, the horizontal interaxillary line, and the inframammary fold (IMF). The breast is divided into eight pie-shaped parts;

the anterior axillary folds (defining the upper limit of the breast), and a horizontal line passing through the IMF (defining the inferior limit of the breast). The breast meridians are marked, and the breast is divided into eight pie-shaped sections. For unilateral procedures, a mirror image of the unaffected breast is drawn on the breast to be reconstructed. The design of the loops is then marked. The first loop, the footprint loop, is marked to match the skin surface to that of the contralateral breast. The vertical dimension of the non-operated breast is measured from the interaxillary line to the IMF, and this dimension is copied onto the breast being reconstructed, to define the new position of the IMF and the distance required to be advanced from the upper abdomen. The horizontal dimension of the non-operated breast is measured from the midline to the lateral limit; this is copied onto b

the areola and nipple can also be marked as additional zones. If the mastectomy has been unilateral, the dimensions of the unaffected breast are copied onto the breast being reconstructed. In any case, the dimensions of both breasts must be equal

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the reconstructed breast to define the lateral limit of the loop and the distance required to be advanced from the lateral thorax. The footprint loop is then marked in a circular pattern. The second loop, designed to better define the new IMF and suspend it along the breast axis, is marked in a triangular pattern. Markings are also used for the zones in the upper abdomen and the lateral thorax. Tissues in these zones will be loosened to facilitate tissue advancement, and the zones of liposuction for fat harvesting are marked. A video showing the preoperative markings is joined in the appendix (Video 75.1).

75.3 Surgical Procedure 75.3.1 Preparation and Infiltration The patient is placed in supine position with the arms abducted. Using a power-assisted liposuction system [15], the breast, the perimammary tissues, and the fat donor sites are infiltrated with a tumescent solution consisting of a solution containing epinephrine 1:100,000 per liter of normal saline associated with 5  mL of Exacyl® 0.5  g/5  mL.  This step is essential for optimal hydrodissection, for release of subcutaneous tethering fibers originating from scar tissue, and for internal expansion of the recipient site.

75.3.2 Tunnelization and Liposuction Extensive tunnelization of the matrix is then performed using a cannula, liberating the skin from the matrix and the matrix from the fascia, reducing its tensile force and facilitating the mobilization of a vascularized adipocutaneous flap from the upper abdomen and lateral thorax to the breast with the use of loops (Fig.  75.2). This detachment is enhanced through liposuction performed in the axilla, upper abdomen, and other donor sites. Following tunnelization, a Molt elevator is used in order to release the deep attachments of the matrix to the pectoralis fascia along the newly

positioned IMF, the native IMF (if intact), and the scar tissue. This step helps to erase the memory of the native IMF and reduces the tensile force of the matrix, allowing the flap to be advanced with minimal tension.

75.3.3 Placement of the Loops While the fat is being prepared in a closed system, following the PALL technique [6], the first loop, the footprint loop (Fig.  75.3), is passed using nonabsorbable sutures. This loop crosses the lower quadrants of the breast in a superficial subcutaneous plane; in the upper breast quadrants, it is deeper, in a suprafascial plane. This maneuver is performed twice, and the knot is tied. This loop will define the breast footprint and enhance the breast projection. The second loop, the IMF loop (Fig. 75.4), is passed along the new IMF in a superficial subcutaneous plane; it then goes cephalad to reach the midpoint of the interaxillary axis, traveling in a deep subcutaneous plane. The thread is passed twice and the knot is tied. This triangular loop aims to fix the IMF in its new position [12]. Contour deformities and remaining subcutaneous attachments are then released using a Varady extractor. Additional liposuction can be performed in the upper abdomen to reduce the tension on the loops and to more clearly mark the transition between the abdomen and the breast. Table 75.1 summarizes the different described techniques using threads in breast reconstruction and augmentation.

75.3.4 Lipofilling Fat injection (Fig. 75.5) is then performed in all breast quadrants, combining internal and external vibration, using the PALL technique [6]. A mean volume of 150 cc can be injected per session. If deformities remain, such as asymmetric footprints or IMFs, additional sessions of PALLL can be performed. Patients usually require two to three sessions in order to obtain optimal results.

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a

b

c

Fig. 75.2 (a–c) Tunnelization is first performed to dissociate the matrix from the deep plane and the superficial plane, and to expand the matrix. This is performed in the to-be-reconstructed breast, upper abdomen, and lateral thorax (a, b). (b) Deep tunnelization is performed in the upper quadrants of the new breast (red) and in a superficial plane in the lower quadrants (green). Undermining is

then performed using a Molt elevator (c). This step detaches the tethering fibers and the attachments of the matrix to the pectoralis fascia, enabling the flap to be advanced into the breast. The zone in yellow represents the breast’s initial footprint, whereas the blue crescent represents the to-be-recruited perimammary adipocutaneous surface

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a

b

c

Fig. 75.3 (a–c) The circular footprint loop ensures that the footprint of the breast being reconstructed matches the footprint of the contralateral breast (a, red dotted lines). When the knot is tied (b, red arrows), this loop will define the horizontal dimension of the breast footprint, as well as

the IMF. It also recruits skin and fat from the upper abdomen and the lateral thorax, bringing it toward the breast in a centripetal pattern, increasing the matrix for fat injection and improving breast projection (c)

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a

b

Fig. 75.4 (a, b) The IMF loop follows a triangular pattern, with its peak at the midpoint of the interaxillary axis (a). This loop defines the vertical dimension of the breast footprint, and it suspends the new IMF (b)

The threads are removed and placed again according to the defect. Additional lipofilling can also be performed if the desired volume has not been obtained. A video showing the surgical technique is joined in the appendix ( Video 75.1). Clinical cases are shown in Figs.  75.6, 75.7, and 75.8.

75.4 Patient Characteristics, Postoperative Care, and Complications 75.4.1 Patient Characteristics A total of 43 consecutive women (49 breasts) underwent breast reconstruction utilizing PALLL.  The

average age was 55 years (range 34–83 years), and the mean BMI was 28 (range 23–35). Eight of the 43 patients (18.6%) were former smokers, 5 were irradiated (11.6%), and 8 received chemotherapy (18.6%). The mean injected volume of fat was 156 mL per breast (range: 110–240 mL) during the first session, 187  mL during the second session (range: 150–250 mL), and 106 mL during the third session (range, 70–150  mL). Patients were monitored for an average of 28  months (range 12–48 months) (Table 75.2).

75.4.2 Postoperative Treatment Access incisions are closed with nylon 6/0 sutures, and a compressive garment is applied before the patient recovers from anesthesia. A

Suture design Percutaneous purse-string suture

Percutaneous purse-string suture

Khouri [1]

Hamdi [17]

First superficial pass under the deep dermis Second deep pass along the deep subcutaneous tissues along the lateral side of the breast and the IMF, deep to the pectoralis muscle along the superior pole of the breast

Suture passes In the subdermal tissue at the caudal end of the epigastric crescent. The suture was suspended to the clavicle at first, and then to the pectoralis muscle after the technique had been refined

Type of suture Absorbable (2.0 polydioxanone suture)

Absorbable (2.0 polydioxanone suture)

Suture passer Sharp needle

Lipofilling cannula

Table 75.1  Comparison between different loop techniques in breast surgery Suture effect Recruitment of an epigastric crescent into the breast as in a reverse abdominoplasty Definition of the IMF Increase in breast projection Tightening of the existing layer through breast footprint reduction Better IMF definition Increased breast projection

Indication Adjunct to flapsPrimary breast reconstruction with and without BRAVA Breast augmentation for tuberous breasts Adjunct to flaps Adjunct to lipofilling with and without BRAVA None

(continued)

Consideration prior to thread placement Liposuction beyond the-to-be-­ recruited area

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Abboud [12, 13]

Suture design Double loop: a circular footprint loop designed to define the breast footprint and enhance breast projection, and a triangular IMF loop designed to suspend and fixate the IMF in its new position

Table 75.1 (continued)

Suture passes The first loop spans the superficial subcutaneous tissues at the lower quadrants of the breasts (between 3 o’clock and 9 o’clock) and the deep subcutaneous tissues, in a suprafascial plane in the upper quadrants (between 9 o’clock and 3 o’clock) The second loop spans the superficial subcutaneous tissues along the newly positioned IMF and then cephalad to reach the midpoint of the interaxillary axis Each loop is passed twice The suture is anchored in the subcutaneous tissue of the upper inner quadrant

Suture passer Abboud 3 mm three-hole blunt cannula

Type of suture Nonabsorbable Filapeau 2250 cm

Suture effect Recruit skin and fat from the upper abdomen and lateral thorax Reconstruct the same skin surface, breast footprint, and IMF as the contralateral breast Increase breast volume and projection

Indication Main component in total breast reconstruction with lipofilling considered as an adjunct Adjunct to flap and lipofilling Main component in breast augmentation with lipofilling considered as an adjunct Main component in breast augmentation following implant removal with lipofilling considered as an adjunct Main component in tuberous breast deformity correction with lipofilling considered as an adjunct

Consideration prior to thread placement Extensive liposuction and tunnelization in the upper abdomen and lateral thorax beyond the loop markings Deep undermining using a Varady retractor along the scar tissue and the remnant of the native IMF This is performed in order to release the subcutaneous attachments, to expand the tissue to be advanced and facilitate its mobilization

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Visconti [18]

Dual-anchor cog threads: Percutaneous suture for IMF definition

Two threads are percutaneously looped down to pectoralis major muscle on the medialmost (parasternum) end and down to the serratus anterior fascia on the lateralmost (midaxillary line) end of the new inframammary fold. Both threads are passed along the subdermal layer of the marked new inframammary fold

Modified flexible Deschamps needles, after two 20-gauge needle entry ports had been made

U.S. Pharmacopeia 1 polydioxanone anchor cog threads

Definition and stabilization of the IMF and lateral breast footprint

Adjunct to fat grafting in breast augmentation

None

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prophylactic dose of low-molecular-weight heparin is administered 8 h later; its continued use depends on the patient’s Caprini risk sassessment [16]. Postoperative analgesia comprising 1000  mg paracetamol (acetaminophen) four times per day and an NSAID such as ibuprofen (600 mg, three times per day, if necessary, with a proton pump inhibitor) is used for an average of 1 week. This is a 1-day surgery. Patients are advised to wear a loose sport bra for 8  weeks and to limit abduction of the shoulder for 1  month. As an oncological follow-up, every patient should receive postoperative breast imaging annually. Breast sensitivity has shown to be improved (mostly in the lower quadrants) in the weeks following the procedure (Table 75.3).

75.4.3 Complications Fig. 75.5  Fat injection is performed in a multidirectional, multiplanar fashion in the residual breast matrix and in the adipocutaneous advanced flap recruited from the upper abdomen and the lateral thorax. The final breast volume comprises the advanced flap, the residual breast volume, and the injected fat

a

Fig. 75.6 (a–o) This 60-year-old female patient presented with a bilateral mastectomy with immediate left-­ breast reconstruction using an extended lateral thoracic flap. A delayed right-breast reconstruction and left-breast remodeling were performed with three sessions of PALLL. The volume of injected fat was 120 cc during the first session, 170 cc during the second session, and 60 cc during the third session in the right breast. In the left

A very low rate of hematomas, seromas, infection, extrusion of threads, or skin necrosis is observed when using this technique. Thromboembolic events and pneumothorax have

b

breast, 300 cc of fat was injected during the first session, 180  cc during the second session, and 50  cc during the third session. Frontal view with arms in resting position (a–d), three-quarter right profile (e–h), and lateral profile (i–l). Photographs were taken preoperatively (a, e, i), and at 6 months (b, f, j), 1 year (c, g, k), and 2 years postoperatively (d, h, l). Per-operative views (m: preoperative, n: after the first session, o: after the second session)

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d

e

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Fig. 75.6 (continued)

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h

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Fig. 75.6 (continued)

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m

o

Fig. 75.6 (continued)

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a'

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b'

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'

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Fig. 75.7 (a-z, za, zb, zc, a’–h’) This 40-year-old female patient presented with a right mastectomy with radiotherapy, and underwent a right-breast reconstruction with three sessions of PALLL. A volume of 100 cc of fat was injected during the first session, 200 cc was injected during the second session, and 90 cc was injected during the third session. One session of PALLL was performed in the left breast with 100 cc of injected fat. Frontal view with arms in resting position (a–e), three-quarter right profile

c'

(f–i), and lateral right profile (j–n). Frontal view with arms elevated (o–s), three-quarter right profile (t–x), and lateral right profile (y, z, za–zc). Photographs were taken preoperatively (a, b, f, j, k, o, p, t, u, y, z), and at 6 months (c, g, l, q, v, za), 1 year (d, h, m, r, w, zb), and 2 years postoperatively (e, i, n, s, x, zc). Per-operative views of the first session (a’, b’: before PALLL; c’, d’: after PALLL). Per-operative views of the third session (e’, f’: before PALLL; g’, h’: after PALLL)

75  Breast Reconstruction with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling… 1147

d

d'

e

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f

f'

Fig. 75.7 (continued)

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g

g'

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h'

i

j

Fig. 75.7 (continued)

75  Breast Reconstruction with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling… 1149

k

l

m

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o

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Fig. 75.7 (continued)

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r

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v

Fig. 75.7 (continued)

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x

y

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za

zb

zc

Fig. 75.7 (continued)

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a

a'

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b'

c

c'

Fig. 75.8 (a-z, za, zb, a’-d’) This 52-year-old female patient presented with a left mastectomy with radiotherapy, and underwent a left-breast reconstruction with three sessions of PALLL. A volume of 130 cc of fat was injected during the first session, 190  cc was injected during the second session, and 100 cc was injected during the third session. One session of PALLL was performed in the left breast with 100 cc of injected fat. Frontal view with arms

in resting position (a–f), three-quarter left profile (g–l), and lateral left profile (m–r). Frontal view with arms elevated (s–w) and three-quarter left profile (x–z, za, zb). Photographs were taken preoperatively (a, b, g, h, m, n, s, x), and at 6  months (c, i, o, t, y), 1  year (d, j, p, u, z), 2 years (e, k, q, v, za), and 3 years postoperatively (f, l, r, w, zb). Per-operative views of the first session (a’, b’: before PALLL; c’, d’: after PALLL)

75  Breast Reconstruction with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling… 1153

d

d'

e

f

g

h

Fig. 75.8 (continued)

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i

j

k

l

m

n

Fig. 75.8 (continued)

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o

p

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r

s

t

u

Fig. 75.8 (continued)

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v

w

x

y

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za

Fig. 75.8 (continued)

zb

75  Breast Reconstruction with Fat and Threads Using Power-Assisted Liposuction, Loops, and Lipofilling… 1157 Table 75.2  Patient demographics and operative data (N = 43 patients) Number of patients Number of breasts Mean age, y (range) Mean BMI, Kg/m2 (range) Number of smokers (%) Number of irradiated patients (%) Number of patients who received chemotherapy (%) Mean volume injected, mL (range) 1st session 2nd session 3rd session

43 49 55 (34–83) 28 (23–35) 8 (18.6%) 5 (11.6%) 8 (18.6%) 156 (110–240) 187 (150–250) 106 (70–150)

BMI body mass index Table 75.3  Breast sensation assessment pre- and post-PALLL comparing the breasts in patients who had mastectomy and those who did not

Zone 1 Zone 2 Zone 3 Zone 4 Zone 5 Zone 6 Zone 7 Zone 8 Zone 9 Zone 10 P-value

Preoperative average Postoperative average Mastectomy (n = 17) Mastectomy (n = 17) 3.2 2.4 (25% better) 3.2 2.1 (28% better) 3.3 1.8 (45% better) 3.9 2.0 (49% better) 3.9 2.1 (46% better) 4.0 2.2 (45% better) 3.9 2.9 (26% better) 3.5 2.7 (20% better) 3.5 4.2 (20% worse) 3.8 4.2 (11% worse) P = 0.006 (statistical difference)

Preoperative average Postoperative average Nonmastectomy (n = 11) Nonmastectomy (n = 11) 1.7 1.8 (6% worse) 1.7 1.8 (6% worse) 1.7 1.8 (6% worse) 1.7 2.3 (35% worse) 2.1 2.3 (10% worse) 2.3 2.3 (no change) 2.2 1.9 (14% better) 1.8 1.9 (6% worse) 2.3 3.1 (35% worse) 2.8 3.2 (14% worse) P = 0.8 (normal variability)

We notice that in breasts of patients who had PALLL following mastectomy, there is a significant rise in breast sensation as measured by Semmes-Weinstein monofilaments (P = 0.0006). Especially in the lower quadrant (zones 3 through 6), we can appreciate the most improvement, likely in part related to the recruitment of abdominal and axillary tissue. As a control, Semmes-Weinstein is also performed in breasts of patients who did not have mastectomy and who did not have loop-based tissue recruitment. In this group, we note normal variability in the results (P = 0.8)

never been reported, as the fat is injected in a sub- ized, adipocutaneous flap can be recruited to the cutaneous plane, parallel to the muscular plane. reconstructed breast. This approach avoids visiThe patient might experience mild-to-­ ble scarring and enables partial recovery of breast moderate postoperative pain for a few days. Also sensitivity. reported are ecchymosis and burning sensations in the first 2 weeks.

References

75.5 Conclusion Breast reconstruction using the PALLL technique is safe, reliable, and minimally invasive. Through extensive detachment of the subcutaneous adherences in the breast, upper abdomen, and axillary region, and the use of internal threads, a vascular-

1. Khouri RK Jr, Khouri RK.  Current clinical applications of fat grafting. Plast Reconstr Surg. 2017;140(3):466e–86e. 2. Hivernaud V, Lefourn B, Guicheux J, Weiss P, Festy F, Girard AC, Roche R. Autologous fat grafting in the breast: critical points and technique improvements. Aesthet Plast Surg. 2015;39(4):547–61. 3. Agha RA, Fowler AJ, Herlin C, Goodacre TE, Orgill DP.  Use of autologous fat grafting for breast

1158 r­econstruction: a systematic review with meta-analysis of oncological outcomes. J Plast Reconstr Aesthet Surg. 2015;68(2):143–61. 4. Bayram Y, Sezgic M, Karakol P, Bozkurt M, Filinte GT.  The use of autologous fat grafts in breast surgery: a literature review. Arch Plast Surg. 2019;46(6):498–510. 5. Groen JW, Negenborn VL, Twisk DJWR, Rizopoulos D, Ket JCF, Smit JM, Mullender MG.  Autologous fat grafting in onco-plastic breast reconstruction: a systematic review on oncological and radiological safety, complications, volume retention and patient/ surgeon satisfaction. J Plast Reconstr Aesthet Surg. 2016;69(6):742–64. 6. Abboud MH, Dibo SA, Abboud NM. Power-assisted liposuction and lipofilling: techniques and experience in large-volume fat grafting. Aesthet Surg J. 2020;40(2):180–90. 7. Abboud MH, Abboud NM, Dibo SA.  Brachioplasty by power-assisted liposuction and fat transfer: a novel approach that obviates skin excision. Aesthet Surg J. 2016;36(8):908–17. 8. Abboud MH, Dibo SA, Abboud NM. Power-assisted gluteal augmentation: a new technique for sculpting, harvesting, and transferring fat. Aesthet Surg J. 2015;35(8):987–94. 9. Abboud MH, Dibo SA.  Immediate large-volume grafting of autologous fat to the breast following implant removal. Aesthet Surg J. 2015;35(7):819–29. 10. Abboud MH, El Hajj HN, Abboud NM.  No-scar breast reduction utilizing power-assisted liposuction mammaplasty, loops, and lipofilling. Aesthet Surg J. 2020:sjaa165. https://doi.org/10.1093/asjsjaa165. Online ahead of print 11. Abboud M, Geeroms M, El Hajj H, Abboud N.  Improving the female silhouette and gluteal projection: an anatomy-based, safe, and harmonious

N. M. Abboud and M. H. Abboud approach through liposuction, suspension loops, and moderate lipofilling. Aesthet Surg J. 2020:sjaa157. https://doi.org/10.1093/asj/sjaa157. Epub ahead of print 12. Abboud MH, Kapila AK, Bogaert S, Abboud NM.  Composite breast remodeling after implant removal by tissue recruitment and loops fixation with power-assisted liposuction and lipofilling (PALLL). Aesthet Surg J. 2021;41(7):770–82. 13. Abboud MH, El Hajj H, Kapila AK, Bogaert S, Abboud NM.  Scarless composite breast reconstruction utilizing an advancement skin flap, loops and lipofilling. Aesthet Surg J. 2021:sjab049. 14. Abboud NM, Hajj HE, Abboud MH.  A novel approach in breast reconstruction: The extended lateral thoracic flip-over flap combined with loops and lipofilling (ELT FOLL). J Plast Reconstr Aesthet Surg. 2021;74(5):974–80. https://doi.org/10.1016/j. bjps.2020.10.024. 15. Abboud NM, Kapila AK, Abboud NH. The combined effect of intravenous and topical tranexamic acid in liposuction: a randomized double-blinded controlled trial. Aesthet Surg J Open Forum. 2020; 16. Cronin M, Dengler N, Krauss ES, Segal A, Wei N, Daly M, et al. Completion of the updated Caprini Risk Assessment Model (2013 Version). Clin Appl Thromb Hemost. 2019;25:1076029619838052. 17. Hamdi M, Anzarut A, Hendrickx B, et al. Percutaneous purse-string suture: an innovative percutaneous technique for inframammary fold creation and improved breast projection in reconstructive surgery. Aesthet Surg J. 2018;38(12):1298–303. 18. Visconti G, Salgarello M.  Dual-anchor cog threads in fat grafting breast augmentation: a novel scarless method for defining breast footprint and enhancing shape. Plast Reconstr Surg. 2019;143(4):1039–49.

Fat Grafting for Breast Reconstruction

76

Alfred Fitoussi

Key Messages • Fat grafting can prepare the skin for breast reconstruction with implant. • Fat grafting is the best solution for esthetic sequelae after radiotherapy. • Whole-breast reconstruction is possible only with fat grafting. • It is possible to transfer big volume of fat, between 200 and 500 cc, to reduce the number of surgeries. • It is necessary to wash the fat before transfer to get a better viability. • You must use one donor site totally at each surgery. • Fat transfer can be a good alternative technique to microsurgical flap for breast reconstruction with the same long-term results. • Complications are few and not very serious with fat grafting. • Multiple rigottomies are very important and necessary to get a good shape and volume for breast reconstruction with fat grafting.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_76) contains supplementary material, which is available to authorized users. A. Fitoussi (*) Breast Center Paris, Paris, France

Breast reconstruction is an integral part of breast carcinoma treatment. Indeed, fat grafting is used nowadays in essentially all breast reconstructions, and it often involves the use of flaps in order to enlarge the breast. In this chapter, we describe how fat is used in breast reconstruction, with or without an implant. Fat is used either before the implant to prepare the thoracic wall and to make it soft and more compliant or after the implant to cover it. Fat grafting alone (i.e., without a breast implant) can be used to generate a soft and well-­ shaped new breast using only a limited number (2–6) of injections. Fat is sometimes used to correct aesthetic sequelae after conservative treatment (ESACT). In this chapter, we provide examples of a variety of fat grafting applications.

76.1 F  at Grafting of the Thoracic Wall After a Mastectomy Before a Breast Implant Prosthetic breast reconstruction is the most common reconstruction technique in the world (more than 60% of breast reconstruction procedures) because it is simple, easy, and fast and does not result in additional scarring. Unfortunately, in some cases, this technique is not possible or very difficult and it entails a high risk of failure. Most often, this is due to the tro-

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_76

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phicity of the chest wall after various treatments. The skin is sometimes thin, irregular, rigid, or difficult to expand without risking the well-being of the patient. The risk of exposure of the prosthesis is then sufficiently high that a musculocutaneous flap—with or without a prosthesis—is the preferred option, sometimes even when not favored by the patient. The injection of fat in all planes, starting deep within at the ribs and then up to the skin at the surface, allows the compliance of this wall to be modified. It becomes thicker, more flexible, and better vascularized. It is then better able to accommodate tensioning when a retromuscular implant is introduced 2–4  months later. This preparation of the chest wall increases the number and indications of reconstruction by prosthesis. Many patients refuse any other reconstruction technique that causes back or ventral scars. They are often afraid of the sequelae at the areas of musculocutaneous flap removal. With this technique, many women will still be able to achieve a more straightforward and acceptable breast reconstruction in terms of sequelae.

76.1.1 The Operative Technique The sample does not differ from the other indications. A moderate volume (100–200  cc) is collected because the reinjection into these fine and sclerous tissues remains limited initially due to the risk of creating “ranges” of fat and thus cytosteatonecrosis. It may be preferable to perform a second injection of the preparation in order to limit local complications. The injection is carried out with a long (10– 20 cm in length) and thin (1.4–2 mm diameter) foam needle. The fat is deposited by retro-­tracing, like “spaghetti,” in all planes and in all directions. If a second injection is necessary, there should be a delay of 2–4 months between the two injections in order not to reintervene on an area in which fat is poorly integrated.

76.1.2 Indications Some patients are very embarrassed by very thin tissues (muscle and skin) that reveal very prominent ribs with hollows between each of them. Their request may only be to make the chest wall “flat” or slightly curved, which is easier to accept and even to fit (self-adhesive external prosthesis) (Fig. 76.1a, b). In most cases, a single injection is enough in preimplantation. This will make it easier to place the prosthesis on softer tissues. It is possible to perform a new injection after the placement of the implant to improve the result, which is increasingly the case during reconstruction of the nipple-areola complex (NAC) (Fig. 76.2a–f).

The transfer of fat to the chest wall after a mastectomy and/or radiotherapy facilitates secondary reconstruction by a prosthesis. Our aim is to make the technique reliable (fewer complications: exposure, too rigid implant, pain, …), as well as to increase the number of indications by making it possible on thin and rigid fabrics. This is a real “plus” for women who wish to avoid extra scars and the aftereffects of musculocutaneous flaps.

Some patients, after one or two injections and in light of the trophic and volumizing effect of fat, opt for exclusive breast reconstruction in three to four sessions.

76.2 F  at Grafting of “Resurfacing” After Reconstruction with an Implant Prosthetic breast reconstruction is the most widely used technique because of its simplicity, accounting for more than 60% of breast reconstructions in France and Europe. However, it has drawbacks, particularly in terms of the appear-

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Fig. 76.1 (a) Thoracic wall after mastectomy and pectoralis muscle removal. Impossible to use adhesive external prosthesis before fat grafting. (b) Good curve for the thoracic wall after fat grafting

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Fig. 76.2 (a) Mastectomy and radiotherapy make a very hard chest wall. (b) It became softer with two fat injections. (c) The implantation of the prosthesis became very

easy. (d) New fat grafting over the implant and nipple reconstruction. (e) Result 1 year after reconstruction without flap. (f) Stable result at 5 years. The tissue is very soft

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ance of the surface of the reconstruction, which is often irregular. It can also be too rigid and sometimes have a lower volume due to gradual retraction of the covering tissues. In order to improve these results, fat can be injected in the irregular areas, upper quadrants, subclavicular, cleavage, or even subaxillary tissue, which allows a more harmonious volume to be generated (Fig. 76.3a, b). This procedure is often difficult to perform due to the limited thickness of the “lipomodeler” tissues. There is always a degree of risk of perforation of the underlying implant. Moreover, great care must be taken during this procedure, and one should not hesitate to use an ultrasound system intraoperatively and, if p­ossible, change the implant in case of the slightest doubt at the end of the procedure (Fig. 76.4a, b). Fasciotomies (or “rigottomy”), often required to release adhesions and to create a thicker and more regular premuscular space, can also be deleterious to the implant. It is, therefore, necessary to undertake them with great care and in a very superficial manner (Fig. 76.5a–c). This minimally invasive surgery, which is often performed on an outpatient basis, reduces the number of reinterventions involving implant changes and a need for hospitalization in case of modification of the result (weight gain, periprosthetic retraction, localized defect, etc.). Other procedures can be performed at the same time: tattooing, liposuction of the inframammary groove, nipple reconstruction, implant replacement, etc. With this injection of fat in the superficial planes, the aesthetic result can be improved as well as the flexibility of the reconstructed breast and sometimes even the local pain. This technique is now an integral part of breast reconstruction, before, during, or after the reconstruction, regardless of the surgical technique. The transfer of fat between the implant and the skin significantly improves the results of prosthetic breast reconstructions. This often avoids having to change the implant completely by replacing the old implant with a thicker or softer pad.

A. Fitoussi

These procedures are usually performed on an outpatient basis and they minimize the length of hospitalization, work stoppages, periods without sports or bathing, etc. Implant changes are, therefore, less frequent and they provide better results over time.

A significant degree of caution is required, however, due to the risk of implant injury during fasciotomy (MRI should be performed in case of even the slightest doubt).

Some patients, after one or two injections and due to the trophic and volumizing effect of fat, opt for an exclusive breast reconstruction in three to four sessions after removal of the implant at their convenience.

76.3 Fat Grafting of Musculocutaneous Flaps Fat injection during a musculocutaneous flap or free flap reconstruction is often performed when there is a degree of asymmetry between the volume of the existing breast and that of the reconstructed breast. This procedure is easy to perform because the flap is often bulky and will readily accommodate a large amount of fat (200–400 cc if necessary) at several levels. Similarly, in immediate breast reconstruction, a musculocutaneous flap with a very small volume can be used that can be adjusted to the desired volume by performing two or three injections during the symmetrization and/or reconstruction of the nipple-areolar complex. In addition, this fat injection allows the musculocutaneous flap reconstruction techniques to be modified, particularly for dorsal flaps, which used to be very bulky, wide, and extended when

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Fig. 76.3 (a) Very bad result: implant reconstruction with very thin or tight skin. (b) New implant and two fat grafting. Great improvement of the result

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Fig. 76.4 (a) Very thin chest wall with a small implant and thin skin covered. (b) Better result with a new implant and two fat grafting

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Fig. 76.5 (a) Immediate breast reconstruction with implant and radiotherapy. The skin is retracted around the implant. (b) Better outcome with one fat grafting. (c) And with two fat grafting, the skin is softer

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harvested (Fig. 76.3 to be taken back in LMC Gd DO) with fatty areas very distant from the muscle and, therefore, poorly vascularized, often with an increased risk of cytosteatonecrosis (Fig.  76.6a, b). The samples are much more limited nowadays because “filling” of this musculocutaneous flap allows the desired volume to be restored in one or two sessions. This modification of the type of sampling allows better control of the risks of complications of these musculocutaneous flaps on the donor area (delayed healing, skin disunity, residual pain, backache, adhesions, etc.). Consequently, patients are more accepting of this otherwise often feared surgery, as it results in shorter scars, less severe sequelae, and a better esthetic result for the sampling area (Fig. 76.7a, b).

This area can even be the site of lipomodeling in case of a defect or pain to improve the esthetic result in the back and even the painful sequelae in this area. Muscle harvesting of long dorsal CML may also be more limited using the anterior branch of the pedicle. This technique allows smaller musculocutaneous flaps to be taken, with a 4 cm muscle band while leaving the rest of the muscle in place. Although this technique does not allow a very large flap to be obtained, it can later be “lipofilled.” This allows the desired volume to be achieved while retaining good function of the latissimus muscle by minimizing the dorsal deformity and the length of the scar. This lipomodeling in these flaps also allows the outline of these flaps to be redrawn.

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Fig. 76.6 (a) Breast reconstruction with autologous flap (latissimus dorsi). The upper pole is empty. (b) Good result after fat grafting in the flap

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Fig. 76.7 (a) Very small latissimus flap for breast reconstruction. (b) Better result after fat grafting

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Fig. 76.8 (a) Immediate left reconstruction with abdominal flap. (b) Result after fat grafting and symmetrization

The same technique can be used for abdominal flaps (TRAM, DIEP, etc.) or all other types of perforating flaps. They are often very useful in cases of flap pain with loss of volume by lipolysis or partial loss of the musculocutaneous flap (Fig. 76.8a, b). It should also be noted that a number of techniques for flap harvesting or new local flap techniques are emerging that are based on complementation by lipomodeling. These flaps can, therefore, be smaller and even local. Fasciocutaneous flaps of the region can be used (Holmstrom flap, see the chapter on local flaps), and these techniques can help limit the scarring and make this surgery less invasive. There continue to be further indications for lipomodeling and its use in breast reconstruction. Optimization of this technique will allow breasts to be reconstructed in their totality by iterative injections of fat, whether as immediate breast reconstruction or as secondary breast reconstruction without radiotherapy, or even after radiotherapy. A number of authors have even pointed out the positive effect of this technique when an area is injected with fat a few weeks before radiotherapy. Further testing of this technique may allow neoadjuvant fat to be used to limit the local sequelae of this treatment.

76.4 E  xclusive Fat Grafting in Immediate or Secondary Mammary Reconstruction 76.4.1 In Immediate Mammary Reconstruction (IMR) The injection of fat into a mastectomy site is thought to be very difficult due to substantial detachments and because it is hard to see where to inject the fat. However, the pectoral muscle and the retropectoral zone, as well as the superficial fascia, are highly vascularized areas and they can accommodate a relatively large amount of fat. The injection is carried out under visual control, directly into the muscle in several planes (from deep within to the surface), always crossing the “fat spaghetti” that is crossed in 2–4 or 6 axes. The area of the superior-internal neckline is the easiest to fill and will be the most visible to the patient postoperatively. Postoperative edema should be prevented, and the final result should be 30–50% lower. The most difficult infero-­ external area to fill will often be poorly projected postoperatively, and the patient must be made aware of this. This area will be easier to fill after healing of the planes, during the second or third lipo-

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modeling session. The volume injected in this first operative session, just after the mastectomy, must be limited, because of the risk of a “greasy lake” when the undertaking of this fat graft has not been adequately considered, thereby leading to complications such as oily cysts, cytosteatonecrosis, infection, liquefied fat flow, etc.

76.4.2 First Injection For this first session, concomitant with the mastectomy, the volumes are between 100 and 200  cc. The volume depends on the size of the patient, the pectoral muscle, and the quality of the surrounding tissues, and in some cases can exceed these values. This injection is done “open,” especially when intramuscular, because this is a very-well-vascularized area that is able to readily accommodate a sizeable amount of fatty tissue.

What will happen if there is a need for post-­ mastectomy radiotherapy? In our experience, lipomodeling helps to limit the radiation sequelae (fibrosis, retraction, and adhesions) that are normally common in this context, after which exclusive lipomodeling is resumed as for patients undergoing secondary breast reconstruction after radiotherapy, knowing that it will be somewhat longer and more difficult. This reconstruction by fat injection is gradual and it requires one or two more injections than for patients without radiotherapy, but there is no known contraindication to date to radiotherapy on this area of “lipofilling” (Fig. 76.9a–d). In immediate breast reconstruction, the reconstruction of the breast volume, its shape, its inframammary crease, its projection, etc. will often be easier to achieve because the skin left in place can readily assume its original shape (i.e., the way it was prior to the mastectomy) and this is all the more so in case of preservation of the nipple-­ areola complex (Fig. 76.10a, b).

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b

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Fig. 76.9 (a) Right-breast carcinoma with two tumors. Mastectomy and immediate reconstruction with fat grafting. (b) Result after one immediate fat grafting and radio-

therapy (45  gy). (c) Result after four fat grafting (face). (d) Good projection after exclusive fat grafting and radiotherapy (profile)

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Fig. 76.10 (a) Immediate reconstruction with exclusive fat grafting and NAC preservation. First operation with 240 cc of fat. (b) Very good result after four fat grafting without radiotherapy

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Fig. 76.11 (a) Immediate breast reconstruction with fat grafting and NAC conservation. Radiotherapy. (b) Result after four fat grafting

For the women who had radiotherapy few years before, we can keep NAC and correct esthetic sequelae to radiotherapy with more rigottomy and fat transfer (Fig. 76.11a, b).

76.4.3 Other Operating Sessions Depending on the volume to be achieved, three to six injections are required to restore the initial breast volume. In some cases, contralateral breast reduction can reduce the number of sessions. Clearly, each injection of 200–400  cc (on average) is easier at the end of the treatment because the larger mammary volume can more readily accommodate a large injected volume. In our series, the average injected volume was 270 cc.

76.4.4 The “Fasciotomies” or “Rigottomy” In order to reconstruct the breast volume, it is necessary to obtain ample flexibility and especially a good projection, which is most often blocked by multiple adhesions. Fasciotomies on these areas of sclerosis or fibrosis allow a more open space to be created that can better accommodate the injected fat and thus improve projection of the reconstructed breast. They are most often made with IV needles that are regularly changed so that they remain sharp, while some use dedicated instruments. This procedure is essential to release the tissues, facilitate the injection of fat, and provide the reconstructed volume with the desired shape.

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At the beginning of our experiment, we performed this type of reconstruction on patients selected for very small mammary volumes and, if possible, who were not scheduled to undergo radiotherapy. As the experiment progressed, much larger mammary volumes could be generated in IMR. While the number of injections is slightly higher, the main difference is that a much larger amount can be transferred with each injection (Fig. 76.12a–c and Fig. 76.13a–e).

76.4.5 In Secondary Breast Reconstruction Without Radiotherapy The operating times are the same as for the first reconstruction procedure. It is easier to inject nonirradiated tissue with fat. In order to improve adipocyte intake, a local aspirational system called “BRAVA” (developed by Dr. Khoury) is sometimes used. a

By applying aspiration for approximately 10 h at night for 15–20 days before the intervention, this system is thought to facilitate the operative procedure and the quality of the adipocyte graft “take” process (pictures). Those who use this procedure are of the opinion that it reduces the number of operating sessions by one or two injections, although this has not been scientifically proven (Fig. 76.14). Nevertheless, without this system, the injection is easier as the tissues are flexible or already injected. Three to six injections are usually needed to rebuild a breast. These injections are spaced 3–4  months apart for good adipocyte intake. On average, the volume injected per o­ perating session was 270 cc in our experiment, in three or four sessions, for a total injection of 800–1000 cc for an average breast of 270 g (Fig. 76.15a, b). We must emphasize the importance of fasciotomies, as they allow the reconstructed breast to be sculpted and to obtain the desired shape, volume, and projection. b

c

Fig. 76.12 (a) Breast carcinoma recurrence with sequelae of the treatment in the upper and external quadrant. (b) Result after mastectomy and immediate breast

reconstruction with three fat grafting time (face). (c) Profile view with a good projection and better shape in the upper quadrant

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a

b

c

d

e

Fig. 76.13 (a) Mastectomy for left-breast carcinoma in big breast with NAC preservation. (b) Result after 400 cc of fat grafting and mastectomy. (c) Result with three times

of fat grafting. (d) Result with four fat grafting and NAC complex reconstruction. (e) Result 7 years later and 10 kg more for this woman

76.4.6 Exclusive Breast Reconstruction with Fat Grafting of the Irradiated Area

Exclusive breast reconstruction with fat grafting on women with radiotherapy is usually possible, but the injections should be more numerous (one or two more for the same volume) and more progressive so as not to increase complications (abscess, cytosteatonecrosis, etc.), as they are sometimes difficult to treat in this sequela context (Fig. 76.17a–e). The BRAVA system is, therefore, used more often; the injection volumes are reduced, at least at the beginning of the reconstruction, and the

In this case, the issues have been irradiated. Their flexibility varies and they sometimes exhibit a considerable degree of sclerosis. This sclerosis and the skin defect need to be evaluated in order to determine the difficulties that may arise in such cases of reconstruction by repeated iterative fat injections (Fig. 76.16a–e).

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operating times are multiplied and especially the fasciotomies, possibly by a degree of spacing in the timing plus the injections.

Despite these difficulties, exclusive lipomodeling reconstruction is usually possible, provided that the patient is amenable to undergoing repeated injections that are 3 or 4 months apart. Between 4 and 6 sessions (1–2  years of treatment) are needed to rebuild the desired volume. A varying degree of reduction of the contralateral breast is often necessary in order to limit the number of injections needed to obtain symmetry of the reconstructed breast relative to the contralateral breast (Fig. 76.18a, b). The fasciotomies that separate the sclerosis that forms in the different planes are an even more essential element to obtain a satisfactory shape and flexibility for the reconstructed breast. This is the only procedure that can rebuild the breast and improve its volume, shape, and projection. Indeed, this section of the deep fibrous areas allows for more injections than other sites, thereby facilitating the generation of a shape and volume very similar to the contralateral breast.

76.4.7 Management of the Inframammary Fold (IMF)

Fig. 76.14  BRAVA system for better result with fat grafting

a

The submammary furrow often stands out visually in immediate breast reconstruction or after implant removal and lipomodeling. On the other hand, in secondary breast reconstruction and especially after a mastectomy, which is not very

b

Fig. 76.15 (a) Right mastectomy before exclusive reconstruction with fat grafting. (b) Result with three sessions of fat grafting in one-day surgery

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c

d

e

Fig. 76.16 (a) Left mastectomy with radiotherapy. (b) After the first fat grafting. (c) After two fat grafting. (d) After three fat grafting and nipple graft. (e) After four fat grafting with tattoo for NAC

economical in terms of skin, it is difficult to provide a good projection of segment 3. It is hard to obtain a good definition of the inframammary sulcus. It is, therefore, necessary to pay more attention locally in regard to this area. Several techniques can be used for this: 1. The submammary furrow can usually be defined progressively through iterative injec-

tions of this area, multiple fasciotomies, and possibly liposuction of the area below the submammary groove (Fig. 76.19a–c). 2. An abdominal advancement flap: It can be performed as a reconstruction by prosthesis, during the second or third session of lipomodeling, by an internal approach and fixation of the deep dermis to fascia or periosteum (Fig. 76.20a–c).

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c

d

f

Fig. 76.17 (a) Woman with left mastectomy and radiotherapy. (b) Result after two sessions of fat grafting. (c) After three fat grafting. Better projection of the breast. (d)

a

Result 2 years after exclusive fat grafting (face). (e) Four fat grafting. Reconstruction with tattoo and nipple graft (profile view)

b

Fig. 76.18 (a) Big deformation of the chest wall with mastectomy. (b) Result after four sessions of fat grafting and NAC tattoo

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Fig. 76.19 (a) Left mastectomy without radiotherapy. (b) Result with two fat grafting. (c) Result with three fat grafting, 4 years later

a

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Fig. 76.20 (a) Right mastectomy with a failure of breast reconstruction with latissimus flap (profile view). (b) Result after two fat grafting (profile view). (c) Result with four fat grafting and NAC reconstruction (profile view)

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3. It can also be achieved by a direct approach in the submammary groove and by fixing three or five separate points or two hemisites, as this avoids crossing back the injected areas (Fig. 76.21a–e). 4. Less invasive devices can also be used, passing a notched wire from the subclavicular area to the submammary furrow. After a major fasciot-

omy of the region under the inframammary furrow, as well as traction + fixation of this wire, a neo furrow under the mammary can be generated gradually (Fig. 76.22a–c and Video 76.1). But in 80% of the cases, we can create the IMF only with rigottomy and without any surgical procedure.

a

b

c

d

e

Fig. 76.21 (a) Right mastectomy with radiotherapy. (b) Result after two fat grafting (face). (c) Result after two fat grafting (profile view). (d) Result with four fat grafting

and fixation of inframammary fold with four stitches (face view). (e) Result of the reconstruction with fat grafting and fixation of the inframammary fold (profile view)

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Fig. 76.22 (a) Right mastectomy with radiotherapy. (b) Result after three fat grafting. (c) Result of the breast reconstruction after 2 years

76.4.8 Reconstruction of the Breast by Fat Grafting After Prosthesis Ablation (Conversion) Many patients are often embarrassed by the physical appearance of their reconstruction prosthesis. This tensioning of the tissues by the implant or by an expander is also often uncomfortable or even painful, especially if the mastectomy was very close to the dermis or when the irradiation has led to local sequelae involving fibrosis, sclerosis, and devascularization of the chest tissues. For a long time, the only solution to improve the local status (pain, heat, flexibility, vascularization, mobility, etc.) was either removal of the implant or use of a musculocutaneous flap, which is known to entail a number of adverse effects. For these reasons, patients remain very reluctant to undergo a new surgery that they consider to be burdensome and often a source of dreaded sequelae.

Iterative lipomodeling can provide a simple and very effective solution to these problems. In this case, the procedure proceeds as in the case of immediate breast reconstruction. During the first or second operating session, removal of the implant is concomitant with the first or second fat injection. This first injection involves a moderate volume, as for immediate breast reconstructions (100–200 cc), and is in the superficial and intramuscular planes (Fig. 76.23a–f). There is clearly a need to avoid the periprosthetic area. Most often, multiple capsulotomies or partial capsulectomies are necessary to avoid excessively rigid scarring that could prove problematic for the subsequent operative sessions, but also to reduce the risk of postoperative lymphocele. Thus, the subsequent injections may be more voluminous. This reconstruction typically requires three to four operation sessions to replace an implant of approximately 300  cc (Fig. 76.24a, b).

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a

b

c

d

e

f

Fig. 76.23 (a) Left-breast reconstruction with implant. (b) Result after removed implant and first fat grafting. (c) Result after three fat grafting. (d) Result after exclusive

a

reconstruction with four fat grafting. (e) Result after 2 years. (f) Result after 7 years

b

Fig. 76.24 (a) Right-breast reconstruction with implant and one fat grafting. (b) Result after removal of the implant and two more fat grafting operation

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a

b

c

d

Fig. 76.25 (a) Conservative treatment of the left breast with radiotherapy. (b) Better result with fat grafting and symmetrization. (c) ¾ before fat grafting. (d) ¾ after fat grafting

The results are often very satisfactory and the well-being of these patients who have suffered for years is immense. Consequently, requests for this type of procedure are becoming more and more common, especially since the result is definitive and will no longer require implant changes or iterative refinishing. In cases of bilateral prostheses (one for reconstruction and one for augmentation on the breast in place), because of an increase in the size of the contralateral breast, the two implants are removed to reduce the volume that needs to be rebuilt.

76.5 Treatment of Esthetic Sequelae After Conservative Treatment (ESACT) For more than 20 years, the esthetic sequelae due to conservative treatment of breast cancer and local radiotherapy have often been treated by the use of fat. This has allowed the positive effects of

this technique to be noted on the local trophicity, vascularization, and pigmentation as well as the flexibility, shape, and volume of reconstructed breasts that are often rigid and deformed as a result of local treatments. These sequelae are frequent and lead to deformation, defects, and often also associated pain. The injection of fat in these areas allows correction of the defects as well as improvement of the flexibility and pain of the treated breast. With very strong rigottomy, we can modify the very big sequelae (Fig. 76.25a–d). Sometimes, the problem is only with volume and with one or two injections, we can get the contralateral size (Fig. 76.26a, b).

76.6 Complications There are few complications with this technique. The first one is cytosteatonecrosis which can be broken with rigottomy and new fat injection.

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a

b

Fig. 76.26 (a) Asymmetry after breast carcinoma treated by lumpectomy and radiotherapy. (b) Good symmetry after one fat grafting in right breast

a

b

Fig. 76.27 (a) Complication after fat grafting with an abscess in the right breast. (b) Small deformity after evacuation of the abscess

The second one is abscess, when we inject too much in very sclerosis place. We get seven cases in 1000 injections and frequently it is a spontaneSummary table of fat grafting Number of cases FG before BIR 50 FG after BIR 250 FG for whole IBR 35 FG for whole DBR 60 FG for replace implant 35 totally FG for ESACT 100

ous cicatrization after draining the abscess (Fig.  76.27a, b). Pneumothorax is the third one with 5 cases for 1000 fat transfer.

Number of injections 1.5 1.3 3.15 3.3 3.0

Average volume/patient 240 175 297.40 287.30 279.30

Total volume injected 360.80 229 936.80 948.10 837.90

1.4

195

274

FG fat grafting; BIR breast implant reconstruction; IBR immediate breast reconstruction; DBR breast reconstruction; ESACT treatment of esthetic sequelae after conservative treatment

76  Fat Grafting for Breast Reconstruction

76.7 Conclusion

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MD, Rinker BD, Vasconez HC. Autologous fat grafting does not increase risk of oncologic recurrence in the reconstructed breast. Ann Plast Surg. 2020;84(6S As we can see in this presentation, “fat grafting” is Suppl 5):S405–10. today everywhere in breast surgery. You find fat 6. Stumpf CC, Zucatto ÂE, Cavalheiro JAC, de Melo MP, Cericato R, Damin APS, Biazús JV.  Oncologic grafting in all techniques of breast reconstruction, safety of immediate autologous fat grafting for reconbut also in ESACT, and also in oncology breast surstruction in breast-conserving surgery. Breast Cancer gery as tuberous breast, asymmetry, Poland synRes Treat. 2020;180(2):301–9. drome, augmentation surgery, and all the failing 7. Hoppe DL, Ueberreiter K, Surlemont Y, Peltoniemi H, Stabile M, Kauhanen S. Breast reconstruction de breast surgery (with or without implant); and this novo by water-jet assisted autologous fat grafting—a place will grow more and more in the next decade. retrospective study. Ger Med Sci. 2013;11:Doc17. 8. Spear SL, Pelletiere CV. Immediate breast reconstruction in two stages using textured, integrated-valve tissue expanders and breast implants. Plast Reconstr Bibliography Surg. 2004;113:2098. 9. Sommeling CE, Van Landuyt K, Depypere H, et  al. 1. Herly M, Ørholt M, Larsen A, Pipper CB, Bredgaard Composite breast reconstruction: implant-based R, Gramkow CS, Katz AJ, Drzewiecki KT, Vester-­ breast reconstruction with adjunctive lipofilling. J Glowinski PV. Efficacy of breast reconstruction with Plast Reconstr Aesthet Surg. 2017;70:1051. fat grafting: a systematic review and meta-analysis. J 10. Delay E, Garson S, Tousson G, et al. Fat injection to Plast Reconstr Aesthet Surg. 2018;71(12):1740–50. the breast: technique, results, and indications based 2. Cai L, Han XF, Wang BQ, Li FC. Application of autolon 880 procedures ever 10 years. Aesthet Surg J. ogous fat grafting in breast reconstruction. Zhonghua 2009;29:360. Wai Ke Za Zhi. 2017;55(9):696–701. https://doi. 11. Doi K, Ogata F, Eto H, et al. Differential contributions org/10.3760/cma.j.issn.0529-­5 815.2017.09.011. of graft-derived and host-derived cells in tissue regenChinese. eration/remodeling after fat grafting. Plast Reconstr 3. Kosowski TR, Rigotti G, Khouri RK.  Tissue-­ Surg. 2015;135:1607. engineered autologous breast regeneration with 12. Hamza A, Lohsiriwat V, Rietjens M.  Lipofilling in ® Brava -assisted fat grafting. Clin Plast Surg. breast cancer surgery. Gland Surg. 2013;2:7. 2015;42(3):325–37. 13. Howes B, Fosh B, Watson D, Yip JM, Eaton M, 4. Manconi A, De Lorenzi F, Chahuan B, Berrino Smallman A, Dean NR.  Autologous fat grafting for V, Berrino P, Zucca-Matthes G, Petit JY, Rietjens whole breast reconstruction. Plast Reconstr Surg. M. Total breast reconstruction with fat grafting after 2014;2(3):e124. internal expansion and expander removal. Ann Plast 14. Mestak O, Mestak J, Bohac M, Edriss A, Sukop Surg. 2017;78(4):392–6. A. Breast reconstruction after a bilateral mastectomy 5. Vyas KS, DeCoster RC, Burns JC, Rodgers LT, Shrout using the BRAVA expansion system and fat grafting. MA, Mercer JP, Coquillard C, Dugan AJ, Baratta Plast Reconstr Surg. 2013;1(8):e71.

The Prepectoral, Hybrid Breast Reconstruction: The Synergy of Lipofilling and Breast Implants

77

Filip B. J. L. Stillaert

Key Messages • Breast reconstruction with expansion and serial fat grafting creates a prepectoral autologous tissue unit. • The prepectoral implant provides additional volume and central core projection. • The hybrid technique is a valid alternative for autologous breast reconstruction and combines an implant with fat grafting. • The capsule around the expander creates a well-defined niche that is compliant and stretchable. • The niche in between the capsule and the skin is the recipient site for the fat grafts to build up the subcutaneous tissue layers. • The fat grafting sessions restore the subcutaneous tissue layers and establish the tissue coverage of the prepectoral implant. • The implant is inserted in the prepectoral plane and provides additional volume and central core projection. • The combination of a prepectoral implant and fat grafting results in a dynamic breast and

Supplementary Information The online version contains supplementary material available at (https://doi. org/10.1007/978-­3-­030-­77455-­4_77).

F. B. J. L. Stillaert (*) Department of Plastic and Reconstructive Surgery, University Hospital Ghent, Ghent, Belgium e-mail: [email protected]

bypasses the disadvantages of a retropectoral implant. • Overall the aesthetic outcome of the hybrid breast-reconstructive technique is very much appreciated by the patients. • The only drawback of this procedure is the serial fat grafting sessions to build up the subcutaneous tissue layers. • The interval in between two fat grafting sessions is 3 months.

77.1 Introduction Implant-based breast reconstructions (IBR) are still outnumbering autologous reconstructions by a ratio of 4:1 [1, 2]. An IBR involves fewer scars and no donor-site morbidity and the length of the procedure is far less compared to a microsurgical reconstruction [3, 4]. Nonetheless, we cannot ignore the long-term repercussion of an implant. After all, an autologous reconstruction is the all-­ embracing standard in breast reconstruction as it adheres to the replace-like-with-like principle. Tissue coverage is the worry in an IBR and without it the result will look and feel unnatural and fabricated. Submuscular or dual-plane techniques are examples of the struggle to achieve tissue coverage. Issues relevant with an IBR are exposure to infection, tissue atrophy, capsular contraction, animation deformity, implant displacement, and

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_77

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poor aesthetic results [3–8]. The outcome is very often a motionless, rigid breast with an aberrant shape. The breast mound can be reconstructed directly after the mastectomy or can be deferred to a later stage (two-stage procedure). Immediate, prepectoral, bioengineered concepts in breast reconstruction have been documented [9–11]. Acellular dermal matrices (ADM) have been applied to compensate for soft-tissue loss but the results are questionable [12–14]. The decision for a particular method to reconstruct the breast is mainly guided by the patient’s preference. Autologous means can be unavailable or are utterly not asked for by patients. A breast reconstruction implicates not only volume repair but also restoration of the breast footprint. The aesthetic side is managed by the surgeon’s competence and artistry but also affected by the leftover tissue quality as well as the implant’s properties. An implant alters the neighboring tissues and causes tissue atrophy and scarring. It will dictate the final outcome in the long term. The well-accepted lipofilling technique uses a liquified material (lipoaspirate) for tissue augmentation. The challenge with fat grafting in breast reconstruction is to develop a 3-­dimensional tissue substitute that resembles a breast. In general, fat grafting is used to reconstruct small volumes. Reconstructed, more voluminous breasts need more core projection and better stability. These two features can be managed with the addition of an implant. A hybrid breast reconstruction has subsequent advantages: (1) The establishment of a prepectoral tissue unit that equals the stage of mammary hypotrophy (as seen in breast augmentation patients), (2) optimal tissue “envelopment” of the implant, (3) more precise shaping of the breast envelope, and (4) a revival of skin quality with a natural perception. The final implant volume will also be lessened with diminished foreign material because part of the volume will be restored with injected fat.

F. B. J. L. Stillaert

77.2 Patients and Methods The hybrid approach for breast reconstruction is based on a thoughtful, personalized approach of the patient. It is selected in specific cases. Microsurgical tissue transfer is often not requested by patients or there is a lack of acceptable donor tissue. Patients should be motivated and informed that various fat grafting sessions are necessary and that the hybrid approach implicates several steps. Primary reconstructions with fat grafting are completed when no adjuvant treatment is involved. In case adjuvant chemotherapy or radiation therapy is planned it is advisable to postpone the reconstruction at least 6  months after completion of the adjuvant treatment protocol. In secondary reconstructions expander insertion is safe when the abovementioned 6-month delay has been respected. Obviously, smoking is a relative contraindication to perform the procedure as it has a deleterious impact on fat graft survival. Patients are advised to quit smoking at least 6 weeks before surgery. Between 2014 and 2017, 56 prepectoral hybrid breast reconstructions were performed in 33 patients with a mean age of 42 (range, 21–77  years old) with a mean follow-up of 24.1  months (range, 6–54  months). Indications were genetic predisposition with prophylactic mastectomy (36 breasts), primary reconstructions (7 breasts), secondary reconstructions (10 breasts), and a history of failed autologous reconstructions (3 breasts).

77.3 Surgical Technique (Fig. 77.1) 77.3.1 Step 1: Expander Insertion The expander’s role (CPX4 Contour Profile Tissue Expander, Mentor™) is to preserve the prepectoral pocket in primary cases and to expand the skin in secondary cases. The reconstruction focuses on the prepectoral space. Preoperative markings are made in an upright position and include the existing inframammary

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Fig. 77.1  The expander is introduced in the prepectoral pocket. Expansion is started approximately 2 weeks after. The expansion process generates a vascularized capsule and the vascular plexus in the outer layer of the capsule reaches its maximum at 8  weeks. At this time point the

first fat grafting is initiated and fat grafting sessions are repeated with an interval of 3 months. When an acceptable subcutaneous fat tissue layer is obtained an implant can be inserted to provide additional projection and volume

fold (IMF) in primary reconstructions, the hypothetical IMF in secondary reconstructions, and the limits of planned dissection or skin undermining which includes the footprint of the breast. In primary reconstructions skin flaps were consistently checked for thickness and skin via-

bility. On any occasion of doubt the pectoral muscle was mobilized and a submuscular pocket was chosen. Patients with a prophylactic mastectomy had the breast removed through an IMF incision. The final scar is well hidden in the IMF in those cases (Figs. 77.2 and 77.3).

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Fig. 77.2  A 32-year-old patient with genetic predisposition for breast cancer. Plan is to perform the mastectomy through an inframammary fold incision. She requested an immediate breast reconstruction with the hybrid approach

In secondary cases, the mastectomy scar was left untouched. The deflated expander is introduced through an imaginary IMF incision for a subcutaneous position (Figs.  77.4 and 77.5). Leaving the mastectomy scar intact preserves the entire skin envelope which is considered the recipient site for fat grafts. In secondary cases the expander is positioned slightly lower than the existing inframammary fold to create sufficient lower pole expansion (Fig. 77.6). The expanders are anchored to the pectoral muscle with suture tabs. This prevents shifting of the expander within the pocket and preserves the footprint during the expanding process. To counter excessive seroma accumulation a closed suction drain stays in place until drainage output is 1  cm) and perfusion of the flap: an adequate mastectomy and a “vital” flap are the basis for this technique. For this purpose, several investigations have been suggested, among which the preoperative evaluation of breast soft-tissue thickness by digital mammography and the intraoperative evaluation, after mastectomy, of skin flap perfusion by fluorescence with indocyanine green [11–19]. The contraindications, to prevent complications of this technique, in particular those due to the mastectomy skin flap necrosis (MSFN), which will be described in the next paragraph, are summarized in Table 79.4.

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction… Table 79.4  Limits of prepectoral reconstruction Poor tissue quality of breast/chest area: marked thinness, serious radiotherapy outcomes Poor skin flap perfusion following aggressive mastectomies Tumor-infiltrating muscular plane and/or skin (pT4) BMI >40 Immunocompromised patients Associated comorbidity factors (smoke, obesity, diabetes, cardiac diseases, dermal or connective tissue diseases, lymphatic diseases, neoadjuvant or adjuvant chemotherapy) can increase the risk of postoperative complications

In any case, apart from the preoperative evaluation of the patient’s characteristics and skin thickness with the techniques described, the most important parameter to prevent complications is a careful mastectomy technique that respects the thickness and vascularization of skin flaps. All types of prosthesis can be implanted: expanders, definitive, round or anatomical, and smooth or microtextured prostheses. Synthetic meshes or biological membranes can be used. Our “prepectoral DTI breast reconstruction” using “synthetic mesh TiLOOP” or “ADM SurgiMend” provides the following steps: The reconstructive procedure prolongs, except for skin-reducing mastectomy, the whole surgical time by no more than 15–20  min, since the skin wound must still be resutured independently of the reconstruction. We performed almost 350 consecutive “DTI prepectoral reconstructions,” as a standard technique in all patients, in the last 4 years, with an overall complication rate close to 25%, of which 12% included major complications due to mastectomy skin flap necrosis (MSFN).

79.5 Complications of Breast Reconstruction with Implants: The “Surgical Disasters” Complications in breast reconstruction are summarized in Table 79.5.

Table 79.5  Surgical reconstruction

steps

of

our

1211 prepectoral

Drawing and planning the incision lines carried out preoperatively by the reconstructive surgeon in accordance with the requirements of the breast surgeon (possibility of ipsilateral mastopexy associated) (Pictures 79.1 and 79.2) Mastectomy is performed by the breast surgeon (except in cases of skin-reducing mastectomy in which the reconstructive surgeon proceeds to de-epithelialization according to the Wise pattern and prepares in advance a NAC-bearing flap with a wide base and inferior pedicle before the mastectomy is performed) The reconstructive surgeon starts when the mastectomy is over; Video 79.1 Assessment and evaluation of the mastectomy skin flap, control of hemostasis Placement of suction drainage (19 Blake) in the subcutaneous pocket Selection of the implant using sizers Preparation of the breast implants wrapped with the TiLOOP mesh (we use a TiLOOP bra in prostheses below 300 cc, while a TiLOOP pocket, which ensures better coverage of the upper pole of the implants from 300 cc upwards) Immersion of the mesh/implant in antibiotic solution (two vials of gentamicin) Positioning the mesh/implant in the prepectoral pocket Fixation of the mesh/prosthesis to the medial margin of the pectoralis muscle fascia with 1–3 stitches (0 Prolene) Careful subcutaneous sutures in 3-0 Vicryl and skin with intradermal suture (3-0 Monosyn) In case of skin-reducing mastectomy, a similar prepectoral positioning of the mesh/implant is performed, with reassembly of the lateral flaps above it and the NAC-bearing inferior pedicle flap, with periareolar and inverted-T sutures, as in normal breast reduction with the Wise pattern Flat dressing and slight modeling compression at the upper poles Postoperative antibiotic coverage until drainages are removed

The postoperative complications for which we propose the treatment with our technique are all due to a vascular suffering with consequent “mastectomy skin flap necrosis” (MSFN) [12]. In fact, marginal suffering of the wound, of the NAC, or of thinned portion of skin even far from the surgical incision can determine a more or less extensive dehiscence, which, by becoming secondarily infected, triggers a mechanism of progressive tissue damage that extends the suffering dehiscence, with the final consequence of

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a

b

Picture 79.1  Preoperative drowing (NSM) - postoperative result. (a) Right nipple-sparing mastectomy (NSM), prepectoral reconstruction and minimal contralateral pexy, preoperative drawing. (b) Postoperative

a

b

c

Picture 79.2  Preoperative drowing (SRM) - postoperative result. (a) Left skin-reducing mastectomy (SRM), prepectoral reconstruction and contralateral reductive mammoplasty, preoperative drawing. (b) Preoperative drawing of the NAC-bearing flap; (c) postoperative

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction… Table 79.6  Complications of breast recontruction Early Complications Acute or subacute postoperative hematoma in the implant’s pocket Persistent postoperative seroma Red breast syndrome (associated only to biological membranes) Surgical wound dehiscence Surgical wound and/or pocket infection Mastectomy skin flap necrosis—MSFN (skin flap and/ or NAC suffering/necrosis and possible implant’s exposure/extrusion) Late Complications Rippling Clear feeling of implant contour under thin tissue at palpation Capsular contracture Dislocation and/or implant rotation Implant rupture Secondary wound and soft-tissue dehiscence or suffering during radiotherapy or adjuvant chemotherapy as their consequence Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL)

a more or less extensive exposure of the implant. In other cases it may happen that the vascular suffering of the flap is extended and deep immediately after the mastectomy, evolving into a necrotic full-thickness eschar, whose colliquation secondarily exposes the implant. In the effort of assessing the severity of MSFN, a scoring system called SKIN (skin ischemia and necrosis) has recently been described. This system is based on the depth and area of skin necrosis visible: a 4-point letter score (A–D) is given to assess depth (A  =  no evidence, D  =  full thickness) and a 4-point numeric score (1–4) is given to assess the surface area of breast skin (1  =  0%, 4  =  30%), which is also documented photographically [20]. In all these clinical pictures, especially when the skin suffering is extensive, with a wide exposure of the prosthesis, a discomforting scenario, also “visually frightening,” emerges from an objective and therapeutic clinical point, giving the immediate awareness of the total failure of the reconstruction. It is immediately necessary to remove the prosthesis, cover the defect temporarily or per-

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manently, and, last but not least, deal with the point of “what to tell to the patient.” This general situation of a disastrous clinical objectivity of the patient, associated with the professional frustration of the operator, can be effectively defined as “surgical disaster” (Picture 79.3). In these cases the removal of the implant was the only possible solution.

79.6 Management of Flap Complications and Surgical Disasters with Our Personal Technique of “Hybrid Regeneration Approach (HRA)” Completely demolishing a reconstruction in which the patient and the surgeons have intensely committed their techniques, hopes, and energies, giving up and declaring complete failure, is a truly frustrating experience for all the stakeholders. Being able to solve, through a conservative type of intervention, even a modest percentage of “surgical disasters.” preserving in this way at least partially the work done, seemed to us to have not only an undoubted clinical advantage, but also an important psychological impact on both the patient and the surgical team, together both committed to solve a problem without starting from scratch, but from a base already present and with the possibility of going through a much less traumatic path. With these premises, we have started to implement the conservative treatment, treating as a first step the simplest cases (Picture 79.4). Successively we extended the application of this technique also to more complex cases and after evaluating the comforting results obtained, we decided to keep using it by developing and perfecting the practice by formalizing it in a rescue protocol that we called “hybrid regeneration approach” (HRA) technique. We currently use this conservative technique as the “first-choice treatment” in all complications, large and small linked to skin flap suffering, including “surgical disasters.”

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a

b

c d

Picture 79.3  Examples of “surgical disasters” (a–d)

The first objective and premise of this technique are the preservation “at all costs” of the “prosthetic pocket,” even if very small in size, and of the residual skin above. This has the meaning of not completely giving up the previous reconstructive work done, to shore it up, strengthen it, restore it, and make it the starting point for the subsequent reconstruction. A conservative reconstruction, which proceeds step by step, with short and nontraumatic interventions during which the patient, previously devastated by the terrible complication, and who now instead sees her breast progressively improving and

acquires new confidence with each new step, is projected towards the final result. Let us move on to the exposure of our personal technique; in certain cases it may be ­sufficient to use only some of the steps described below. Step 1: Fundamental Step Pocket Rescue: Direct Suture and Small Round Implant (Pictures 79.5 and 79.6) Starting an empirical antibiotic therapy: gentamicin+ceftriaxone Necrosectomy and debridement of the suffering skin which is sent for definitive histological examination

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction… Removal of the implant Accurate pocket washing with saline solution and introduction of gentamicin 4 cc Placement of a small or even minimal volume (100 cc) round implant to preserve the pocket Placement of drainage (19 Blake) Direct suture of the surgical breach with horizontal U sutures: thick 1 or 0 Silk or Nylon Paraffine gauze dressing In some cases reinforcement of suture with application of dermal substitutes (Integra, Matriderm)

This operation allows to rescue the pocket, in an acceptable percentage of cases, thanks to the introduction of a small round maintenance prosthesis, without having to resort to reconstruction with flaps, through a simple, fast, nontraumatic

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intervention, under local anesthesia, saving part of the previous reconstruction. Step 2: Regeneration: Lipostructuring Alone, and/or Replacement of the Prosthesis (About 1–2 months After the Consolidation of the Wound) Infiltration of Klein’s solution in the abdominal, trochanteric, or knee region; after 7 min suction of the adipose tissue Centrifugation according to Coleman’s technique Lipostructuring in the breast in order to obtain the volumetric and regenerative effects: 50–100 cc of fat x section Possible replacement of implant with another of greater volume

a

b

c

d

Picture 79.4  Mild left MSFN. (a) Age 73, mild left MSFN with implant exposure (previously radiated breast); (b) direct suture; (c) lipostructuring; (d) postoperative

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Picture 79.5  Severe MSFN - direct vertical suture. (a) Age 58, full-thickness right MSFN after SRM with implant exposure; (b) direct suture

a

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Picture 79.6  Severe MSFN - direct horizontal suture. (a) Age 62, left MSFN with secondary total wound dehiscence, infection, and extended implant and mesh exposure; (b) direct suture

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction…

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Lipostructuring can be repeated several times, with intervals of at least 40  days until an adequate volumetric effect and an improvement in the quality of the tissue with the regenerative effect are achieved.

We included in the reports of Table 79.8 all the patients treated by HRA, for both DTI prepectoral and previously two-stage reconstruction complications.

Step 3: Final Reshaping: Implant Replacement + Contralateral Symmetrization (About 1–2 months Following the Last Lipostructuring)

79.7 Results

Optional reshaping with lipostructuring Replacement of implant with another one of greater volume after remodeling of the pocket (capsulotomies/ capsulectomies, inframammary fold lowering, NAC recentering) through access from the submammary fold Contralateral symmetrization

This last operation, which may require even more surgical steps, completes the breast “restoration” also with the optional contralateral symmetrization. The access to the pocket for the implant replacement and pocket remodeling should be carried out from the submammary sulcus, in order not to interfere with the old laboriously healed scars. The result, in favorable cases of “surgical disasters” treated with “hybrid regenerative approach (HRA),” is a “new breast” with a hybrid composition: a “central prosthetic core” of relative non-preponderant volume and a “surrounding noble new regenerative tissue around it” (Table 79.7).

Mastectomy skin flap necrosis (MSFN) is a common early complication of mastectomy, with reports in the literature ranging from 5 to 30%. Increasing DTI reconstructions using NSM or SSM techniques, which preserve large surfaces of skin flaps, may contribute to the higher rates reported. Excessive thinning of the flaps, with impairment of the vascular plexus located in the subdermis and subcutaneous adipose tissue, causes an insufficient blood supply to the skin flaps, with consequent MSFN. MSFN and consequent wound dehiscence and implant exposure can cause breast implant extrusion or infection, wound management problems, psychological morbidity for the patient, serious aesthetic consequences, and delay in beginning adjuvant chemotherapy. The management of severe MSFN has always been carried out through the demolition of the reconstruction with implants and the eventual reconstruction, immediate or delayed, with autologous tissue. It is reported that high rates of patient who are explanted decide to give up reconstruction permanently [11, 12, 20].

Table 79.7  General overview of HRA technique Step 1 Main procedure: pocket rescue Implant removal + debridement+ direct suture + small round implant/expander To save the pocket Local Anesthesia

Step 2 Regenerative procedures Lipostructuring Multiple sections (50–100 cc of fat x section) Local Anesthesia

Step 3 Final reshaping Implant change and/or contralateral symmetrization + optional additional lipostructuring

Table 79.8  Results of MSFN complications treated with HRA Severe MSFN Treated by Hybrid Regeneration Approach (HRA), number of patients Age 51 38–76

Success of the procedure Number of patients 28 (55%)

Failures Definitive explants; delayed lack of wound consolidation; very poor results 23 (45%)

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In our case history we have recorded an incidence of MSFN close to 25% of reconstructions and severe “surgical disasters” in about 12% of all reconstructions. It is important to note that in our hospital the mastectomy is performed by the breast surgeon and that the plastic surgeon begins the reconstruction, with the existing flaps, already at the end of mastectomy. We believe that the separation of duties is for the patient a greater guarantee of oncological radicality, even if at times it penalizes the vitality of the flaps. In our effort to apply “conservative hybrid regeneration approach” technique for the management of “surgical disasters” we have recorded an overall success rate of above 55%. The first cause of failure was represented by extensive, immediate, or early dehiscence/necrosis, within 7–30  days from the pocket rescue operation, which has burdened over 25% of all the cases, making definitive explanting almost always necessary. In the mildest complications (non-repeated dehiscence, persistent seromas, limited necrosis/suffering), we, once again, performed the conservative technique with good resolution percentages. The second cause of failure, in slightly less than 20% of all the cases, was the late, often repeated dehiscence/suffering, due to the persistence of inconsistent margins which could not be resected until healthy tissue was reached, if not at the cost of making the pocket completely useless, and in which we, regretfully, had to explant. These were the most frustrating cases, especially observed either in very thin or previously radiotreated patients (e.g., mastectomies for recurrences on previous quadrantectomies with radiotherapy) or during adjuvant chemotherapy or during or after postoperative radiotherapy. It can therefore be said that a repeated, even segmental, dehiscence represents a negative prognostic factor for the final result of the procedure. We did not notice any particular problem in patients undergoing neoadjuvant therapy, while we observed, as said, increased complications in patients undergoing adjuvant chemotherapy and obviously undergoing postoperative radiotherapy.

In selected explanted cases, we have performed several lipostructuring sessions, after about 2  months from the explantation, with the purpose of improving general tissue conditions, thickening soft tissues, and reducing adherences to achieve a better scrolling of the tissues over the chest wall on the site of the explantation. Very recently we have started to treat with a “conservative regenerative” technique also some cases of definitive explantation that have sufficient adipose tissue: with medium-small breasts it is possible to proceed with an entire adipose tissue reconstruction, while in larger breasts it is possible, after having recreated an adequate layer of soft tissue with regenerative techniques, to reintroduce a prepectoral prosthesis (Picture 79.7). Lastly, the eventual late capsular contracture, which is to be theoretically more frequent, given the increased pocket handling and the possible contamination that occurred while salvaging the latter, presents a less clinical impact than expected, since the implant is coated by a thick adipose tissue layer. In all cases it is possible, in such problematic instances, going from a capsular contracture to implant rupture, to reoperate with the usual surgical procedures, through an inframammary fold approach, as we are used to perform for the third reconstructive step of implant substitution. This is done making way through healthy, regenerated tissues, in complete safety, avoiding the old healed scars of the first step of the procedure.

79.8 Clinical Cases 79.8.1 Patient 1 (Picture 79.8a–f ) Age: 47 Surgery: Right mastectomy + expander Complication: Extended MSFN, expander exposure Hybrid conservative regeneration approach: Picture 79.8a–f right debridement + right direct suture + right implant replacement (twice) + right lipostructuring + contralateral breast reduction

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction…

a

b

c

d

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Picture 79.7  HRA in previous definitive implant explantation. (a) Age 52, previous left implant explant; (b) lipostructuring; (c) prepectoral left implant replantation and contralateral breast symmetrization (preoperative); (d) postoperative

79.8.2 Patient 2 (Picture 79.9a–f ) Age: 49 Surgery: Bilateral skin-reducing mastectomy + prepectoral DTI Complication: Extended left MSFN, implant exposure Hybrid conservative regeneration approach: Picture 79.9a–f left debridement + left direct suture + left implant replacement (twice) + bilateral lipostructuring (several) + contralateral implant change

79.8.3 Patient 3 (Picture 79.10a–f ) Age: 55aa—associated connective tissue disease Surgery: Bilateral mastectomy + implants Complication: Left breast MSFN, with secondary infection and abscess, implant exposure Hybrid conservative regeneration approach: Picture 79.10a–f left debridement + left direct suture + implant➔expander + bilateral breast implant replacement + bilateral lipostructuring

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a

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f

Picture 79.8  Patient 1

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Picture 79.9  Patient 2

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Picture 79.10  Patient 3

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction…

79.8.4 Patient 4 (Picture 79.11a–f ) Age: 52aa—left breast RT Surgery: Bilateral mastectomy + implant (postoperative right RT) Complication: Bilateral outcomes of MSFN, right post-radiotherapy skin suffering

Hybrid conservative regeneration approach: Picture 79.11a–f bilateral debridement (twice) + bilateral breast implant replacement (twice) + dermal substitutes + bilateral lipostructuring (several) + right NAC reconstruction

a

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Picture 79.11  Patient 4

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79.9 Conclusions For all the “MSFN complications” we are committed to try to manage them “conservatively” as the standard technique. We have applied this “conservative hybrid regeneration approach” in all small and major complications, related to the suffering of the skin flap, after mastectomy breast reconstructions, which we observed in the period 2016–2020. Of these, about 50 were serious complications that could be defined as “surgical disasters.” Our success rate with this technique has been above 55%, which means that more than half of the patients, who have had serious MSFN, with the total failure of a reconstruction with implants, not only did not lose their implant, but also maintained a satisfactory and stable hybrid reconstruction. This “conservative hybrid regenerative approach” is a simple, nontraumatic technique, which requires repeated surgical steps, in order to treat serious complications, “surgical disasters” that would have otherwise needed the dismantling of the failed reconstruction with implants and, eventually, the use of autologous tissue flaps. Our effort, on the other hand, is to partially preserve the previous implant reconstruction and start again from this “reconstructive residue” to “restore” the reconstruction in successive stages, making it “hybrid” with an “implant core” surrounded by “regenerated tissue.” The first fundamental step that allows us to access the subsequent ones is to “save the pocket.” This first step is immediately burdened by a rate of more than 25% of failures. Once the result of “saving the pocket” is obtained we can consider ourselves to be over halfway our task, since the subsequent surgical steps are easier and less burdened by complications that can lead to the loss of the implant, which total an additional 20% of the cases overall. Patients that successfully go forth the first step have swift wound healing, can if necessary undergo adjuvant chemotherapy, and regain increasing confidence and optimism in a true

“restoration of the breast” that will proceed in subsequent steps, towards the final result. At the end of this procedure these are happy patients.

References 1. Querci Della Rovere G, Benson JR, Nava M.  Oncoplastic and reconstructive surgery of the breast. Taylor & Francis; 2010. 2. Colwell AS, Taylor EM. Recent advances in implant-­ based breast reconstruction. Plast Reconstr Surg. 2020;145:421–32. 3. Casella D, Di Taranto G, Marcasciano M, Sordi S, Kothari A, Kovacs T, Lo Torto F, Cigna E, Ribuffo D, Calabrese C. Nipple sparing prophylactic mastectomy and immediate reconstruction with TiLoop® Bra mesh in BRCA1/2 mutation carriers: a prospective study of long-term and patient reported outcomes using the Breast-Q. Breast. 2018;39:8–13. 4. Nava MB, Cortinovis U, Ottolenghi J, Riggio E, Pennati A, Catanuto G, Greco M, Rovere GQ. Skin-­ reducing mastectomy. Plast Reconstr Surg. 2006;118(3):603–10. 5. Casella D, Di Taranto G, Marcasciano M, Sordi S, Kothari A, Kovacs T, Lo TF, Cigna E, Calabrese C, Ribuffo D.  Evaluation of prepectoral implant placement and complete coverage with TiLoop Bra Mesh for breast reconstruction: a prospective study on long-­ term and patient-reported BREAST-Q outcomes. Plast Reconstr Surg. 2019;143(1):1e–9e. 6. Onesti MG, Di Taranto G, Ribuffo D, Scuderi N.  ADM-assisted prepectoral breast reconstruction and skin reduction mastectomy: expanding the indications for subcutaneous reconstruction. J Plast Reconstr Aesthet Surg. 2020;73(4):673–80. 7. Jacobs JM, Salzberg CA. Implant-Based breast reconstruction with meshes and matrices: biological vs synthetic. Br J Hosp Med. 2015;76(4):211–6. 8. Sobti N, Ji E, Brown RL, Cetrulo CL Jr, Colwell AS, Winograd JM, Austen WG Jr, Liao EC. Evaluation of acellular dermal matrix efficacy in ­prosthesis-­based breast reconstruction. Plast Reconstr Surg. 2018;141(3):541–9. 9. Darrach H, Kraenzlin F, Khavanin N, Chopra K, Sacks JM.  The role of fat grafting in prepectoral breast reconstruction. Gland Surg. 2019;8(1):61–6. 10. Nava MB, Catanuto G, Rocco N. Hybrid breast reconstruction. Minerva Chir. 2018;73(3):329–33. 11. Robertson SA, Jeevaratnam JA, Agrawal A, Cutress RI.  Mastectomy skin flap necrosis: challenges and solutions. Breast Cancer (Dove Med Press). 2017;9:141–52. 12. Matsen CB, Mehrara B, Eaton A, Capko D, Berg A, Stempel M, Van Zee KJ, Pusic A, King TA, Cody HS 3rd, Pilewskie M, Cordeiro P, Sclafani L, Plitas

79  Management of “Surgical Disasters” After Breast Implants Postmastectomy Reconstruction… G, Gemignani ML, Disa J, El-Tamer M, Morrow M.  Skin flap necrosis after mastectomy with reconstruction: a prospective study. Ann Surg Oncol. 2016;23(1):257–64. 13. Linee Guida: Neoplasie della Mammella. AIOM (Associazione Italiana di Oncologia Medica); 2019. 14. Wilson AR, et  al. The requirements of a specialist breast centre. Eur J Cancer. 2013;49(17):3579–87. 15. Shiffman MA. Breast reconstruction art, science and new clinical techniques. Springer; 2017. 16. Nahabedian MY, Neligan PC. PlasticSurgery; Volume 5: Breast. Elsevier; 2017. 17. Cardoso MJ, Wyld L, Rubio IT, Leidenius M, Curigliano G, Cutuli B, Biganzoli L. EUSOMA position regarding breast implant associated anaplastic large cell lymphoma (BIA-ALC) and the use of textured implants. Breast. 2019;44:90–3.

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18. Nava MB, Catanuto G, Rocco N. 22 Cases of breast implant-associated ALCL: awareness and outcome tracking from the Italian Ministry of Health. Plast Reconstr Surg. 2018;141:777–9. 19. Rancati AO, Angrigiani CH, Hammond DC, Nava MB, Gonzales EC, Dorr JC, Gercovich GF, Rocco N, Rostagno RL. Direct to implant reconstruction in nipple sparing mastectomy: patient selection by preoperative digital mammogram. Plast Reconstr Surg Glob Open. 2017;5(6):e1369. 20. Lemaine V, Hoskin TL, Farley DR, Grant CS, Boughey JC, Torstenson TA, Jacobson SR, Jakub JW, Degnim AC. Introducing the SKIN score: a validated scoring system to assess severity of mastectomy skin flap necrosis. Ann Surg Oncol. 2015;22(9):2925–32.

Stem Cell-Enriched Fat Injection in Aesthetic, Reconstructive Breast Surgery

80

K. Tunc Tiryaki and M. Mustafa Aydınol

80.1 Background

due to surgery, injections, radiotherapy, or any other acquired pathology [3]. Autologous fat grafting is a very popular techMany steps to overcome these problems have nique in plastic surgery for volume augmentation been reported, including meticulous harvesting and improvement of radiated or damaged tissues and injection techniques such as lipostructuring already. Plastic surgeons agree that fat grafting is and lipolayering [4]. Still, in order to deal with a safe procedure with a low complication and these limitations, we need to deepen our underhigh patient satisfaction rate, which can be used standing of the microenvironment and cellular for a variety of aesthetic and reconstructive indi- dynamics of this graft-uptake process. Basic scications [1]. However, significant limitations to entific research suggests that mature adipocytes, traditional fat transplantation remain, such as due to their high cytoplasmic oxygen consumpunpredictability and a variable rate of graft sur- tion, are highly susceptible to hypoxia-induced vival [2]. The lingering clinical confusion associ- apoptosis after grafting. Apoptosis of mature adiated with the viability and predictability of fat pocytes, especially those located in the center of grafting is related to the mechanism of fat sur- the lipoaspirate tissue fragment, leads to eventual vival in the recipient area. For large-volume fat loss of graft volume [5]. Mesenchymal progenitransfers or transfers into a hostile recipient bed, tor cells are more likely to survive the physical the recipient area vascularity might be insuffi- stress and hypoxia and therefore play a vital role cient for the ischemic graft, leading to graft in adipose tissue regeneration through adiponecrosis. This may be particularly true for injec- genic and vascular differentiation as well as tions into areas where the circulation and wound-­ expression of angiogenic, antiapoptotic, and antihealing capacity are impaired by previous fibrosis oxidative factors [6]. There is also clinical data suggesting that the lipoaspirate tends to be deficient in these progenitor cells in comparison to Supplementary Information The online version of this intact fat tissue due to impartial harvesting and chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_80) contains supplementary material, which is available to decantation during the processing. authorized users. K. T. Tiryaki (*) Cadogan Clinic, London, UK M. M. Aydınol Teşvikiye Mahallesi Fulya, Nişantaşı Hospital, Şişli, Turkey

Key Message • Adipogenic and vascular differentiation as well as the expression of angiogenic, antiapoptotic, and antioxidative factors are important for fat graft survival.

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_80

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These observations and clinical limitations have led us to the enrichment of the fat graft, a technique we call stem cell-enriched tissue transfer (SET), or cell-assisted lipotransfer (CAL) as known in the literature [7]. This is a technique, in which lipoaspirated fat graft is enriched with autogenous stromal vascular fraction (SVF). Stromal vascular fraction contains a variety of cells such as pericytes, fibroblasts, and macrophages as well as a heterogeneous population of pluripotent adipose-derived stem cells (ADSC) and vascular progenitor cells as well as preadipocytes. Although the exact mechanism of SVF cells is unknown, it is thought that these cells contribute to graft survival through proangiogenic, antiapoptotic, and proadipogenic effects. Indeed, SVF cells have been shown to promote adipose cell replication, incorporate into vessel walls, and decrease the local inflammatory response [8]. SVF is obtained during the surgery, in the same facility, from excess lipoaspirate using either a collagenase-based isolation technique or a three-step mechanical isolation technique to release the regenerative cells from the fibrous stroma [9]. By combining traditional fat grafting with SVF enrichment, it is possible up to a degree to overcome the problems associated with autologous fat transfer particularly into areas with an impaired environment for fat graft survival. In SET injections, autologous SVF is used to promote angiogenesis during the critical time of tissue engraftment, attempting to improve the survival rate of tissue and reduce postoperative volume loss as well as to reinforce the tissue quality, which is jeopardized by radiation therapy, physical or chemical trauma, and acquired or congenital diseases. Experimental as well as clinical studies suggest a positive relationship between SET injections and improved operative outcomes [7]. Still, the acceptance of this technique around the world is limited due to the lack of long-term clinical data, issues related to cost, regulatory uncertainty, and safety of using a tissue dissociation enzyme mixture [10]. Key Message • SVF has proangiogenic, antiapoptotic, and proadipogenic effects and is shown to improve fat graft survival.

K. T. Tiryaki and M. M. Aydınol

80.2 Isolation Methods Enzymatic digestion using collagenase is the gold standard to isolate adipose SVF.  Even though there are slight variations in the different techniques, they follow the same basic steps. The lipoaspirate is washed using an aqueous salt solution, and a digesting reagent, usually collagenase, is added. An incubation period of 30–60 min is used in a heated shaker. The suspension is then centrifuged and four layers are obtained: the oily liquid, the adipose tissue, the aqueous layer, and the pellet. The pellet is kept and washed out from the active enzyme. Approximately 100,000–1,300,000 nucleated cells per gram of lipoaspirate can be obtained with more than 80% viability. Even though this method is giving remarkably high numbers of cells in the SVF, it also has disadvantages. It is expansive, raises legal and administrative concerns, and is time consuming (90–120  min). Many methods of mechanical isolation of SVF have surfaced as well, like shaking, vibrating, centrifuging, and washing the lipoaspirate manually and in automated device [11], which usually give much inferior cell counts. Considering the digestion, incubation, and centrifugation steps of enzymatic isolation methods, we are using a disposable kit for mechanical digestion, which consists also of three consecutive steps, mechanical mincing, buffer incubation, and centrifugation. This method enables us to harvest around 50% of regenerative cells from the same amount of fat in comparison to enzymatic digestion [9]. The choice of isolation method depends on the patients’ needs. If the patient is having limited amount of fat, there is a need of higher number of cells in SVF like serious radiotherapy damage, or we need a significant amount of fat to be used as graft material, then it is preferable to use enzymatic digestion, since we can obtain higher cell numbers from a limited amount of fat. If we are not restricted by the amount of fat to be digested then mechanical digestion is our preferred method because it is less time consuming, is much more cost effective, and does not require a lab staff and environment.

80  Stem Cell-Enriched Fat Injection in Aesthetic, Reconstructive Breast Surgery

80.2.1 Enzymatic Digestion Once obtained, the lipoaspirate is digested using GMP-graded collagenase NB6 (Serva Electrophoresis, Heidelberg, Germany) at a concentration of 0.1 U/mL and a ratio of 1:1 (v/v). The lipoaspirate is then washed twice in a saline solution and centrifuged at 300 g, for 5 min. The mixture is placed in a shaker at 37 °C for 45 min under constant shaking, finally centrifuged at 300  g for 7  min, and drained through a 70  μm filter. After this, the pellet is resuspended in the desired amount of saline solution to be injected back to the patient.

80.2.2 Mechanical Digestion After fat harvesting, ordinary pistons of 20  cc Luer-lock syringes are replaced with disposable disarmable pistons with concave gaskets. The lipoaspirate is transferred into syringes, connected to a closed unit, harnessing three different sets of blade grids on three different Luer-lock ports on a rotating canal. The lipoaspirate is placed in the first port and passed back and forth

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ten times through the first blade grid containing multiple 1000-μm holes. Changing the direction of the rotating canal and the flow to the second port, the lipoaspirate is passed through the second blade grid containing 750-μm holes and then through the 500-μm hole blade grid until full dissociation. A Ca-Mg balanced buffer solution is added to the lipoaspirate inside the syringes at a ratio of 1:3, incubated and shaken for 10  min. The pistons are then disattached and the syringes with the dissociated lipoaspirate are centrifuged at 2000  g for 10  min with the Luer-lock tips directed inward so that the SVF could be collected in concave gaskets (Fig. 80.1). Finally the pistons are reattached, the supernatant discarded, and the pellet in the gaskets resuspended. This procedure takes around 25 min in comparison to 90–120  min using enzyme digestion, with the downside of harvesting around 1/3 to half the number of cells in the SVF. Whichever isolation technique may be used, at the final stage these cells are either mixed with the fat tissue to be grafted or injected into the damaged skin in order to be able to improve the skin quality. In every case the total number of viable cells is measured by LUNA cell counter (Table 80.1).

After 10 Incubation and Centrifugation

Disposable material

SVF

Cell adhesive gasket

Fig. 80.1  Left: The disposable cubes harnessing three different sized sets of blades, disarmable pistons, concave gaskets, and buffer solution. Right: The SVF pellet concentrated on the gasket with the digested fat to be disposed

Enzymatic isolation Mechanical isolation

45 min at 37 °C

10 min at room temperature

Mincing/filtration with buffer solution

2. Incubation for digestion

1. Addition of the digestive agent Collagenase

Isolation methods

2000 g for 10 min

300 g for 5 min

3. Centrifugation for extraction of the pellet

Table 80.1  Comparison of enzymatic and mechanical SVF isolation methods

Washing with PBS solution No washing

4. Washing the reagent

13.45

33.86

Cell number/cc (×105)

85.82

82.86

Cell viability (%)

83.63%

63.64%

Flow cytometer results CD73+/ CD45−/ CD90+ CD90+ ADSC cell ADSC cell content content 85.31% 82.01%

6.74%

CD73+/CD90+ Endothelial cell content 20.40%

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80  Stem Cell-Enriched Fat Injection in Aesthetic, Reconstructive Breast Surgery

80.3 F  at Grafting Indications for Breast Fat grafting to the breast and chest has numerous indications that can improve volume, shape, feel, projection, and silhouette of the region. Often, the main objective of breast surgeons is to create symmetrical, natural-looking breasts. Beyond just minimizing the need for prosthetic implants, grafts can also aid in aesthetic improvements to flap reconstructions, acquired or congenital chest and breast wall deformities, and aesthetic breast augmentation. Aesthetic breast augmentation: Implantation of artificial breast prostheses is the most frequently performed surgical cosmetic procedure in the USA. Seeing that prosthetic implantation has long been the gold standard, autologous fat grafting offers several advantages including lack of scarring and complications associated with implanting

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foreign material in breasts, but with limited indications and success. Women who desire large, firm, or exceptionally round breasts, or who do not have enough fat to be harvested, are not appropriate candidates for autologous fat transfer. Breast reconstruction: Autologous fat grafting can be used in several ways to reconstruct the breast after mastectomy or lumpectomy, as the main treatment modality in women with small breasts or women who have had a lumpectomy, or as an adjunct to implant or flap reconstruction by smoothing out contour abnormalities [12]. In addition, Rigotti et al. found fat to be particularly useful in women who had undergone radiation therapy after lumpectomy [13]. In our experience set injections are extremely useful in dealing with partial tissue defects, where rigorous rigottomies are followed by tunneled SET injections (Fig. 80.2).

Fig. 80.2  Lumpectomy, radiotherapy, and chemother- the right breast with simultaneous mastopexy to the left. apy. After the patient was declared clean by the single-­ Preoperative and 2-year postoperative results session oncology of 280 cc SET transfer was performed to

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Key Message • Fat grafting can be used for breast augmentation, breast reconstruction, breast asymmetry, implant rescue, chest wall deformities, reinforcing and improving skin quality, and replacing implants. Congenital Breast Asymmetry: Traditional treatment of congenital asymmetric breasts involves inserting a prosthetic implant into the hypoplastic breast. While results may be satisfactory initially, natural ptosis of the breasts over time may lead to asymmetric breasts years later. Autologous grafts on the other hand have the luxury of changing more naturally over time in the untreated and treated breast. Implant Rescue: Artificial prostheses have a complication rate of 3–20% and occasionally result in implant replacement or removal. Yoshimura et al. described promising results when using ADRC-enriched fat grafts to reconstruct patients after prosthesis removal [14]. It is also our experience that patients who have their implants removed and get immediate fat grafting have extremely high levels of graft retention (Fig. 80.2). Poland Syndrome, Pectus Excavatum, and similar deformities: Autologous fat grafts for patients suffering from chest wall deformities such as Poland syndrome show promising results. Limited scarring with the option of repeat procedures makes fat grafting a useful alternative to silicone prostheses. Autologous fat transfers may be used to supplement custom-made implants or used alone in reconstructing the affected area. Radiated and Ischemic Breast Tissue: Most experts will discourage the use of prosthetic implants in irradiated breasts due to the high occurrence of complications and will instead recommend completely autologous reconstructive procedures. For these patients, ADSC-enriched fat grafting is an ideal reconstructive option for these women. Fat grafting necessitates very small, punctate wounds in the irradiated bed and therefore minimizes the risk of wound problems

K. T. Tiryaki and M. M. Aydınol

and the increased regenerative effect of ADSC enrichment usually gives much superior outcomes in these patients than traditional fat grafting alone. Reconstruction of irradiated breasts may require a second treatment so patient education during the initial consultation is important. In our experience, reinforcing the skin thickness and quality to reverse the radiotherapy damage is a very useful approach. In selected cases it is possible to reconstruct a total mastectomy defect with only SET injection and implant placement (Fig. 80.3). Patients must be told of the achievable outcomes of breast grafting procedures. For example, fat grafting may not entirely replace prosthetic breast placement depending on the patient’s available donor volume of fat and recipient-­site anatomy. Also important is discussing a patient’s family and/or personal cancer history. This is important in deciding which preoperative precautions should be taken as well as indicates what type of long-term follow-up is most appropriate. Key Message • Proper patient informing about achievable outcomes and detailed patient history for fat grafting procedure are mandatory. Implant Removal: With recent developments about the implant-related lymphoma cases, more and more patients want to remove their implants and replace them with their own fat. Given the fact that they have enough fat tissue to be transplanted, this is a great indication for breast fat grafting. Our experience is that the graft uptake after immediate breast implant removal is much higher than primary cases. The technique is similar to primary breast fat injection, without any injections performed into the dead space of the implant capsule. As a rule of thumb, double amount of the volume of explanted devices is supposed to be injected (Fig. 80.4).

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Fig. 80.3 Total mastectomy and radiotherapy. After declared to be free of disease, one session of 270  cc of SET for volume replacement and skin reinforcement was performed. Three months after the left-side injection, a

390 cc, CPG™ 323, gel breast implant was placed with simultaneous right reduction-mastopexy. Preoperative and 1-year postoperative results

80.4 Patient Consultation and Selection

who desire large and firm breast may not be appropriate candidates for autologous fat transfer as fat graft results in a more natural-looking appearance. Similarly, it cannot be overemphasized that fat grafts to the breast are not a viable option for women lacking significant sources of donor fat for liposuction, because the need for fat is much higher when compared to other indications for fat grafting procedures. The ideal patients for breast fat grafting are liposuction

Patients must understand the achievable outcomes of breast grafting procedures. Fat transplantation may not entirely replace prosthetic breast placement, depending on the patient’s available donor volume of fat and recipient-site anatomy. Also important is discussing a patient’s family and/or personal cancer history. Women

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K. T. Tiryaki and M. M. Aydınol

Fig. 80.4  Removal of 195 cc implants and 310 cc SET injection to each breast. Single session, PO 1 year

patients, who do not desire very big volume changes on their breasts. Limitations of the technique: 1. High breast cancer risk 2. Continuous breast cancer relapse risk 3. Patients who desire large and firm breasts 4. Patients with limited autologous fat resources Key Message • The ideal patients for breast fat grafting are liposuction patients, who do not desire very big volume changes on their breasts.

80.5 Surgical Technique 80.5.1 Preferred Donor Site There is no good evidence to clearly define the best donor site for fat grafts. Rohrich et al. found that common harvest areas (abdomen, flank, thigh, medial knee) produce statistically equivalent numbers of viable cells [15]. Von Heimburg et al. found the viability of preadipocytes from the abdomen, breast, and buttock to all be greater than 94% [16]. The abdominal region has been reported as the most common harvest location due to

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patient preference and ease of supine position for graft harvest and delivery [4], but our experience proved contrary. Since the abdomen is the most flask skin area of the body, the donor-­ harvest sequelae are much more common, particularly in inexperienced hands. In our clinical setup, in the first operation we harvest the fat from the lateral and medial thigh as well as love handles with the patient face-down and under general anesthesia. If need arises for a secondary touch-up, we use the abdominal area for harvesting due to its ease, without turning the patient per-operatively, usually under only sedative anesthesia.

80.5.2 Preoperative Hydroexpansion

Fig. 80.5  Preoperative hydroexpansion. In tight-skinned patients, we ask the patients to come to the office 3 and 7  days before surgery to be infiltrated with tumescence solution under local anesthesia in the amount of planned

fat injection. On the upper right picture, the patient is after tumescence injection, on lower right 1 year after 350 cc of traditional fat grafting

If the patient’s skin envelope is very tight, or there is not enough recipient tissue volume, we ask the patients to come to the office 1 week and 3 days before the surgery. In the office setup, the breasts are injected with tumescent solution under local anesthesia in order to release the skin tightness. The amount of tumescence injection is decided upon the planned graft injection volume. Usually a 1:1 ratio of fluid is injected and the patient is sent home with expanded breasts (Fig. 80.5).

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Key Message • Preoperative hydroexpansion with tumescent solution is a technique that can be used to reduce skin tightness to improve the outcome of the procedure and increase fat graft survival.

80.5.3 Donor-Site Preparation Donor sites are marked preoperatively. Additionally, photographic documentation and/ or three-dimensional imaging should be obtained for postoperative comparison. Standard sterile technique is observed during the harvest and conventional prophylactic perioperative antibiotics are typically sufficient. Additionally, it is critical to remember that all grafts contain some amount of fluid, which is introduced into the graft during the harvest process. This fluid will be absorbed postoperatively, and one must account for this loss of volume.

80.5.4 Wetting Solution, Infiltration The composition and quantity of wetting solution injected at the donor site depend on the volume of fat to be harvested, donor site, as well as physician preference. Most surgeons use a standard tumescent solution of 0.5% lidocaine and 1:100,000 epinephrine in 1 L of lactated Ringer’s or 0.9% saline solution. The ratio of solution to epinephrine can vary from 1:80,000 to 1:200,000 and sodium bicarbonate is used if done under sedation or local anesthesia. The ratio of tumescent fluid injected to volume of tissue harvested depends on the site and the volume to be harvested, with large volume cases approaching 1:1. It is demonstrated that the safe dose of lidocaine increases to between 35  mg/kg and 50  mg/kg when used in tumescent fluid (Klein, 1990). Tumescent fluid should be injected evenly throughout the subcutaneous fat in the area to be liposuctioned. It is advisable to resist the temptation to progress through the case and wait the full 10 min.

80.5.5 Cannula Selection Instruments should be chosen to minimize trauma to the donor adipocytes and thus enhance the probability of graft survival. In contrast to sharp tips, blunt tips allow for penetration of tissue while minimizing cell destruction and trauma to the fibrous septa, neurovascular bundles, and dermis. “Multiple opening” cannulae allow for a more resourceful fat collection with each pass. Overall, fat to be grafted should be harvested with 3–4 mm cannula with parcels small enough to pass through a 2  mm injection cannula, whereas 3 mm, sharp, multi-hole cannula seems to be better to harvest fat to be digested, due to the initial damage to the cell niche. It has been shown that fat harvested by sharp cannula contains higher numbers of regenerative cells per ml of lipoaspirate [17].

80.5.6 Harvesting Traditional mechanical liposuction uses machine-­ generated negative pressure to remove the fat as the surgeon pushes the cannula through the adipose tissue. Studies show that mechanical liposuction and manual aspiration yield grafts with similar metabolic activity and ability to generate new adipocytes [18]. There are also “assisted liposuction” devices like ultrasound-assisted liposuction (UAL), power-assisted liposuction (PAL), laser lipolysis systems, and liquid flow-­ assisted liposuction claiming better cell viability and yields. However, given the lack of consensus, we feel that using a particular machine or syringe for harvesting should be based on availability, accessibility, and amount needed. Under any circumstance, care is taken to keep the sterile environment for the graft.

80.5.7 Graft Processing First, the amount of lipoaspirate to manage the volume defect is harvested, and then liposuction is continued for harvesting fat for SVF digestion,

80  Stem Cell-Enriched Fat Injection in Aesthetic, Reconstructive Breast Surgery

which will be discharged after the digestion and isolation. The fat to be grafted is processed to separate healthy adipocytes and ADRCs from unnecessary debris while minimizing damage to the cells [19]. The choice of “cleaning” the fat depends on the amount of graft to be transferred and what kind of structural support is needed. If strong support is needed like in facial deep fat injections, centrifugation is preferable since it gives a drier and denser fat. For breast injections however, wet fat with a significant amount of water serves as a spacer against the skin envelope tension. Therefore in our practice we use centrifugation for 1 min with 1000 rpm for facial injections, but use decantation only for breast grafting. Key Message • Wet fat can be used as a spacer against skin tension and therefore can increase graft survival. If strong support is needed centrifugation is used to make fat denser and drier.

80.5.8 Adding the SVF to the Graft The isolated SVF can be added to the graft in vitro, where some of the graft is spared to be mixed with the SVF solution and injected at the

Fat Tissue is liposuctioned from the patient’s thigh or stomach

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end of the surgery. This is our approach while doing breast injections. It does not prolong the operative time since we give the firstly harvested fat to be digested. Until we finish full harvesting and start injecting the breast, the SVF isolation is usually over, so we mix it with our graft to have a homogenous enriched graft. If we are doing facial fat injections, it is another possibility to finish the procedure and inject the SVF later into the fat-grafted areas as well as intradermally, in the recovery room (Fig. 80.6).

80.5.9 Lipo-Delivery Fat should be injected under light pressure while withdrawing the cannula. Although one must overcorrect for the relative amount of fluid in the graft, it is more important not to overfill the area such that the overlying skin is taut. This pressure may cause ischemia to the recipient bed [3]. Current delivery techniques are based on the belief that to optimize fat graft survival, close proximity to a blood supply is imperative. Grafts placed within 2 mm of an arterial blood supply have minimal necrosis and should be expected to survive [4]. Therefore, delivery techniques that maximize the graft surface area-to-vascularized tissue ratio are preferred. Grafts are most rou-

100 ml tissue is processed to extract SVF for one breast

Lipocube SVF are combined with remaining fat tissue to from a cell-enhanced tissue graft

The graft is injected into the patient’s breast

Fig. 80.6  The first 100–200 cc of fat is digested while the liposuction is continued. The isolated SVF is usually added to the graft in vitro and the mix is injected together

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tinely administered into the subcutaneous space. For breast injections, graft should be injected in the retromammary space or subcutaneous space but not in the mammary gland itself. The literature reports satisfactory clinical experience with injection into the muscle. In our practice, usually three ports of entry are used, one at the mid-­ inframammary fold, one lateral to the breast tissue, and one at the medial edge of the areola. The amount of fat to be injected is divided into three portions and 1/3 is injected to the upper pole, 1/3 to the lower pole, and 1/3 to the retroglandular space (Fig. 80.7). Key Message • During fat injection to breast, graft should not be injected to mammary gland itself. There is also satisfactory clinical experience with injection into the muscle.

In order to be able to treat iatrogenic or radiotherapy-­induced fibrotic bands rigottomies are necessary, which are done in a sponge-release fashion but not incisional releases, which create dead space without vascular support [13].

80.5.11

Postoperative Care

Fine, rapidly absorbed sutures are preferred to close the incisions with dry dressings applied as needed. Edema and bruising are common and are expected to resolve in up to 1 month. Note that due to swelling alone, 30–40% of the initial apparent graft volume will most likely be lost in the first few weeks after surgery [20].

80.5.12

Radiologic Follow-Up

It is often difficult but particularly necessary to layer fat effectively into highly scarred regions.

Benign oil cysts, micro-calcifications, and fat necrosis may occur subsequent to any breast surgery and can be readily distinguishable from malignant lesions. Patients should commit to close postoperative radiology follow-up for 1–3 years following fat grafting to the breast.

Fig. 80.7  Usually three ports of entry are used, one at the mid-inframammary fold, one lateral to the breast tissue, and one at the medial edge of the areola. The amount of fat

to be injected is divided into three portions and 1/3 is injected to the upper pole, 1/3 to the lower pole, and 1/3 to the retroglandular space

80.5.10

Handling Scarred Recipient Beds

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80.6 Complications

80.7 Conclusion

80.6.1 General Complications

Because of two revolutions in the last decade, namely, the recognition of fat tissue as the most important source of stem cells in the human body and the relatively simple techniques of isolating these stem cells from fat, plastic surgeons are emerging as the specific group capable to use body’s own regenerative power. It is getting more and more clear that enriching fat graft with autologous adipose-derived stem cells is a promising strategy to improve the predictability, consistency, and efficacy of fat grafting results. From the safety perspective, our 10-year experience supports the notion that SET does not increase the risk for development of cancer or accelerate the growth of an existing undetected neoplasm. This remark does of course not nullify the theoretical risks associated with the SVF cell yield injection theorized from in vitro studies of adipose-derived stem cell (ASC) trophic factors and their effects in co-cultures with breast cancer cells. However, as per today, there seems no basis for a causal relationship between fat grafting with or without SVF enrichment and breast cancer. According to us, the real limiting factors are twofold: first, the amount of available autologous fat, and second, patients’ unrealistic expectations. Finally, the fact that we can also mechanically isolate 30–50% of stromal vascular cells of that isolated with enzymatic digestion makes the usage of SVF enrichment a much more approachable and viable alternative to traditional fat grafting.

The majority of fat grafting operations are performed without complication with usual risks of pain, infection, bruising, bleeding, edema, numbness, contour irregularity, skin necrosis, hematoma, perforation of an abdominal organ, fat emboli, or even death. Respecting current guidelines, which limit the volume of fat harvested, would guard the surgeon against catastrophic incidences. The majority of fat graft complications result from the volume or manner in which the graft is placed by the physician. Grafting complications have been shown to markedly decrease with physician experience like graft loss, focal fat necrosis, chronic inflammation, infection in graft bed, lipid cysts, and calcifications [1].

80.6.2 Fat Grafting and Breast Cancer Patients should undergo a breast imaging workup prior to grafting to confirm that no breast cancer is present. Doing so will help mitigate the impact that any coincidental concurrence of grafting and cancer would have on the physician and patient. Physicians should inform patients that should they develop breast cancer, grafting would not hinder any conventional cancer treatment options. Long-term follow-up in several breast lipo-graft and CAL patients shows no increased recurrence or new development of cancer [1]. Furthermore, fat grafting does not hinder early cancer diagnosis when rigorous pre- and postoperative surveillance is performed. Mammography remains the most accurate tool for monitoring breasts after grafting procedures. While some may be concerned that necrosis or calcifications hinder screening, experienced radiologists generally have no problems distinguishing between calcifications caused by surgery.

Key Message • SET does not increase the risk for cancer development nor accelerate the growth of an existing neoplasm. Amount of available ­autologous fat and unrealistic patient expectations are two major limiting factors.

References 1. Delay E, Garson S, Tousson G, Sinna R.  Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J. 2009;29(5):360–76.

1240 2. Toledo LS, Mauad R.  Fat injection: a 20-year revision. Clin Plast Surg. 2006;33(1):47–53, vi. 3. Nguyen A, Pasyk KA, Bouvier TN, Hassett CA, Argenta LC. Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. Plast Reconstr Surg. 1990;85(3):378–86; discussion 87-9. 4. Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997;24(2):347–67. 5. Kato H, Mineda K, Eto H, Doi K, Kuno S, Kinoshita K, et  al. Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months. Plast Reconstr Surg. 2014;133(3):303e–13e. 6. Naderi N, Wilde C, Haque T, Francis W, Seifalian AM, Thornton CA, et  al. Adipogenic differentiation of adipose-derived stem cells in 3-dimensional spheroid cultures (microtissue): implications for the reconstructive surgeon. J Plast Reconstr Aesthet Surg. 2014;67(12):1726–34. 7. Tiryaki T, Findikli N, Tiryaki D.  Staged stem cell-­ enriched tissue (SET) injections for soft tissue augmentation in hostile recipient areas: a preliminary report. Aesthet Plast Surg. 2011;35(6):965–71. 8. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-­ Grove CJ, Bovenkerk JE, et  al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1292–8. 9. Tiryaki T. In vitro investigation of the effect of stromal vascular fraction isolated by mechanical and enzymatic methods on wound healing. J Ist Faculty Med. 2020;83(3):241–6. 10. McCarthy RC, Breite AG, Dwulet FE.  Biochemical analysis of crude collagenase products used in adipose derived stromal cell isolation procedures and development of a purified tissue dissociation enzyme mixture. International Federation for Adipose Therapeutics and Science (IFATS). 11. Aronowitz JA, Lockhart RA, Hakakian CS.  Mechanical versus enzymatic isolation of stro-

K. T. Tiryaki and M. M. Aydınol mal vascular fraction cells from adipose tissue. Springerplus. 2015;4:713. 12. Spear SL, Boehmler JH, Bogue DP, Mafi AA. Options in reconstructing the irradiated breast. Plast Reconstr Surg. 2008;122(2):379–88. 13. Rigotti G, Marchi A, Stringhini P, Baroni G, Galie M, Molino AM, et  al. Determining the oncological risk of autologous lipoaspirate grafting for post-­ mastectomy breast reconstruction. Aesthet Plast Surg. 2010;34(4):475–80. 14. Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/ stromal cells. Aesthet Plast Surg. 2008;32(1):48–55; discussion 6-7. 15. Rohrich RJ, Sorokin ES, Brown SA.  In search of improved fat transfer viability: a quantitative analysis of the role of centrifugation and harvest site. Plast Reconstr Surg. 2004;113(1):391–5. discussion 6-7 16. von Heimburg D, Hemmrich K, Haydarlioglu S, Staiger H, Pallua N. Comparison of viable cell yield from excised versus aspirated adipose tissue. Cells Tissues Organs. 2004;178(2):87–92. 17. Tonnard P, Verpaele A, Peeters G, Hamdi M, Cornelissen M, Declercq H.  Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013;132(4):1017–26. 18. Leong DT, Hutmacher DW, Chew FT, Lim TC. Viability and adipogenic potential of human adipose tissue processed cell population obtained from pump-assisted and syringe-assisted liposuction. J Dermatol Sci. 2005;37(3):169–76. 19. Conde-Green A, Kotamarti VS, Sherman LS, Keith JD, Lee ES, Granick MS, et al. Shift toward mechanical isolation of adipose-derived stromal vascular fraction: review of upcoming techniques. Plast Reconstr Surg Glob Open. 2016;4(9):e1017. 20. Aronowitz JA, Ellenhorn JD.  Adipose stromal vascular fraction isolation: a head-to-head comparison of four commercial cell separation systems. Plast Reconstr Surg. 2013;132(6):932e–9e.

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Moustapha Hamdi and Lisa Ramaut

81.1 Introduction 81.1.1 The Concept of Fat Grafting The procedure of fat grafting has been developed and refined over the years and numerous applications were explored to be implemented in clinical practice. Coleman introduced a now widely adapted method of harvesting adipose tissue in syringes to refine it by centrifugation in a closed system. The supernatant oil and the aqueous part at the bottom are discarded to isolate the viable fat cells. This method intended to reduce the postoperative volume loss by concentrating fat cells and removing debris that interferes with the early survival of the adipocytes. In other methods this is achieved by sedimentation or washing the lipoaspirate with saline [1]. This centrifugation

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_81) contains supplementary material, which is available to authorized users. M. Hamdi (*) · L. Ramaut Plastic Surgery Department, Brussels University Hospital—Vrije Universiteit Brussel (VUB), Brussels, Belgium e-mail: [email protected]; Lisa. [email protected]

step was investigated by Kim et  al., who concluded that a centrifugation of 3000 rounds per minute (rpm) for 3 min is ideal, since cell viability declines after 5 min of centrifugation [2]. The infiltrative solution used to prepare donor site for liposuction also affects cell viability by hydro-­ dissection of fat cells before aspiration, thus reducing trauma to adipocytes. Also, the use of local anesthetics in the infiltrative solution is investigated for their effect on cell viability. Lipofilling can be used by itself in breast reconstruction in patients that are not eligible for free flap or implant reconstruction. It can also be used as an adjunct to a free flap or implant reconstruction or to fill defects after mastectomy, lumpectomy, or partial breast reconstruction. After mastectomy, a tissue expander can put in the mastectomy pocket to preserve the breast envelope in delayed reconstruction. The well-­ vascularized fibrous capsule that is formed around the expander improves the viability and structure of grafted fat by providing nutritional and structural support. Khouri et al. introduced the BRAVA device, which relies on external expansion by applying negative pressure by an external device on the thoracic wall. A well-­vascularized three-dimensional scaffold is formed within the breast pocket that is later filled with fat grafting. This poses the advantage that no prosthetic material needs to be implanted to prepare the pocket for fat grafting [3].

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_81

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81.1.2 Safety Concerns of Fat Grafting The safety of fat grafting to the breast has been a concern since the procedure was introduced in clinical practice. Initially it was stated that the fibrotic changes in fat grafting would interfere with mammography imaging to detect breast cancer. Later it was stated that fat grafting did not induce more microcalcifications on medical imaging than mastopexy or breast reduction procedures and should therefore no longer be banned from clinical practice. The question whether fat grafting in oncological patients can be considered safe is still discussed extensively since in  vitro findings suggest that adipocytes and fibroblasts are tumorigenic. The discovery of adipose-derived stem cells in adipose tissue introduced an additional concern regarding their interaction with primary breast cancer cells. Nevertheless, many years of experience later, no clinical evidence has yet shown that more oncological recurrence is observed in the fat-grafted breast. Close monitoring of patients with a history of breast cancer is always advisory and should also include monitoring of the reconstructed breast [1, 4].

81.1.2.1 The Concept During fat grafting to either flap reconstruction or mastectomy skin, the major challenges are to reconstruct the IMF and to reduce the pressure on the overlying skin by the injected fat. The IMF is defined as pseudoligamentous collagen bundles lining the edge of the mammary gland at the intersection of the anterior breast capsule with the superficial thoracic fascia. The latter is connected to the deep fascia through a thick network of connective tissue fibers that does not contain adipose tissue. The connective tissue fibers that connect the pectoralis fascia to the skin create the adherence that is visible as a fold [5, 6]. During mastectomy, the subcutaneous reticular network at the inframammary fold is often damaged or lost. There is no discussion that reconstruction of this fold is key to

obtain a natural-looking reconstructed breast. The open technique was introduced in 1977 by Pennisi, who anchored a dermal-fatty-fascia flap to the deeper muscular fascia under open incision. Modifications of this technique were made by anchoring to the periosteum, using a shorter incision, reconstructing through the mastectomy pocket, and suturing a lower thoracic advancement flap to the posterior capsule. A better definition of the fold can also be obtained by liposuction of this area. The first percutaneous method by Handel and Jensen involved the marking of the IMF with needles dipped in methylene blue to orient where the interrupted unresorbable sutures should be put internally to anchor the fascia superficialis and subcutaneous tissue to the thoracic wall. Further definition can be achieved by radial capsulectomy in the lower pole with a running suture to create a fold from the superficial fascia at the level of the fifth intercostal space [7]. The main concerns in IMF reconstruction are a visible scar, suture failure, migration of the fold, or flattening of the fold over time. The idea to recruit tissue as a thoracoabdominal flap and suspend it to the periosteum of the ribs is a technique that can also be applied in primary reconstruction or to resolve bottoming out. Although useful to create a fold, this flap might fail to produce sufficient projection in the breast. To obtain this, suspending of the tissues to a higher level will cause enough bulge and tension to project the breast tissue or fat graft forward. This can be achieved by placing percutaneous sutures around the entire footprint of the breast in what is called the percutaneous pursestring suture or Hamdi’s Hammock. Key Messages • Creation of a well-defined inframammary fold is key to provide natural and symmetrical results in breast reconstruction. The fold is often lost during oncologic surgery or adjuvant treatment. • The inframammary fold is reconstructed by introducing resorbable PDS sutures through

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small stab incisions around the footprint of the patient characteristics from a case series of 180 breast. patients. The PPSS was used as an adjunct to free • The percutaneous purse-string suture is flap breast reconstruction in 150 cases and with designed to complement lipofilling of the lipofilling only in 30 cases. Patients had an averbreast. The IMF and projection are easily age age of 56 (range 26–68), BMI of 26.9 (range obtained without the need for additional inci- 18–31), and a reoperation rate of 14%. Eight sions or scars. patients were unable to fully stop smoking at the • The PDS sutures resorb over a period of time of the surgery. 6  months, leaving fibrotic adherences that Patients are prepared preoperatively by mark­provide lasting internal support in the recon- ing the breast footprint and orienting the IMF structed breast. evenly with the contralateral side, taking into • The breast projection improves as a result of account that sutures will be placed somewhat the forward bulge in the fat graft, which is below the footprint in order to recruit upper confined within the new breast footprint. abdominal tissue. • Possible complications are suture failure, suture infection, or insufficient fat graft retention. Sufficient fat graft take is necessary for 81.2.2 Lipofilling the PPSS to improve breast projection. The procedure can be repeated with an interval of Patients are positioned supine with their arms at least 3 months. tucked at the sides, since abduction of the arms • The percutaneous purse-string suture is a can distort the appearance of the breast. The method that provides long-lasting and estheti- selected donor site is infiltrated with adrenaline/ cally pleasing results for IMF reconstruction xylocaine solution and the lipoaspirate is coland improved projection in breast-­lected in 10 cc Luer-Lock syringes for centrifureconstructive surgery. gation at 1200 rpm for 1 min. The watery portion is discarded and the syringes are connected to the infiltration cannula. The lipofilling is completed 81.2 Surgical Technique when a sufficient volume correction is obtained. Remaining retracting fibrous bands are resolved 81.2.1 Patient Selection with subcision before continuing to the IMF and Preparation reconstruction. Patients are screened for comorbidities and contraindications for fat grafting and a decent donor site is selected for liposuction. Active smokers are asked to quit at least 1 month before surgery and at least 1  month after surgery to increase micro-vascularization and improve wound healing. Patients are informed about postoperative pain, potential risks of general anesthesia, suture infection, suture failure, and theoretical possibility of pneumothorax. They are also informed about the interindividual variability of fat graft resorption and that sometimes multiple fat grafting sessions are needed. Table 81.1 summarizes

81.2.3 IMF Reconstruction Small stab holes are created using a 19-gauge needle or 15-blade around the footprint of the breast (Fig.  81.1). A PDS 2.0 suture is passed around the circumference of the footprint of the breast, by introducing a lipofilling cannula through an incision and tunneling it subcutaneously to the next. The suture is placed in a retrograde fashion through the cannula, which should be frequently flushed with saline to remove tissue remnants. The cannula is then

Total

Lipofilling only

Flap + lipofilling

Patients

Partial breast reconstruction

Total breast reconstruction

Reconstructive surgery Total DIEP/SIEA flap TMG flap Pedicled flap Total

With BRAVA Without BRAVA With BRAVA Without BRAVA

Table 81.1  Patients’ characteristics

53 (38–68) 51 (40–62) 56 (28–68)

12

180

56 (41–61)

3

3

54 (36–68)

52 (33–54) 48 (38–62) 52 (32–68)

32 3 30

12

Average age in years (range) 56 (28–68) 55 (36–67)

No. 150 115

26.9 (18–31)

28 (21–31)

25 (24–28)

29 (28–31)

28 (23–32)

23 (18–28) 23 (18–28) 27.8 (23–31)

Average BMI (range) 26.8 (18–31) 28 (21–31)

8 (4.4%)

(0%)

0 (0%)

0 (0%)

1 (8.3%)

2 (1.6%) 0 (0%) 1 (3.3%)

Smoking No. (%) 7 (4.6%) 5 (4.4%)

128 (71%)

12 (100%

3 (100%)

0 (0%)

2 (1.6%)

22 (86%) 3 (100%) 17 (57%)

1.75 (1–6)

2 (1–2)

2 (1–2)

4 (4–5)

4 (4–5)

1.6 (1–3) 2 (1–3) 3 (1–6)

Number of lipofilling Radiotherapy sessions (range) No. (%) 111 (74%) 1.5 (1–3) 86 (74%) 1.4 (1–3)

25 (14%)

0 (0%)

1 (33%)

3 (100%)

11 (92%)

3 (9.3%) 2 (66%) 15 (50%)

Redo purse-string No. (%) 10 (6.6%) 5 (4.3%)

1 (0.5%)

0 (0%)

Purse-string-related complications No. (%) Pain 1 (0.6%) Pain 1 (0.8%)

34 (11–48)

24 (36–48)

24 (12–48)

36 (12–36)

36 (24–48)

32 (13–36) 28 (12–36) 32 (24–48)

Follow-up average in months (range) 35 (11–48) 36 (11–48)

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81  Enhancing Flap Breast Reconstruction with the Percutaneous Purse-String Suture and Fat Grafting

Fig. 81.1  Small stab incisions are made around the footprint of the breast to introduce the PDS sutures led by the cannula. (Artwork courtesy of © L. Ramaut, MD 2021)

a

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withdrawn which tunnels the PDS suture subcutaneously. Cannula between 7 and 20  cm in length can be used for this purpose. The loop commences in the axillary holes where the knot can be easily hidden. The first superficial pass around the footprint runs right under the deep dermal plane along the IMF and just superficial to the pectoral muscle at the upper pole of the breast. The second pass goes along the deep subcutaneous tissue along the lateral side of the breast and the IMF and passes deep to the pectoralis major muscle along the superior pole of the breast (Fig. 81.2). The sutures are tied buried in the deep tissues in the axillary region. The incisions are closed with 5-0 nylon and covered by a Tegaderm bandage (3M Health Care, St. Paul, MN). The newly formed breast is supported by applying Microfoam tape (3M Health Care, St. Paul, MN) in an upward supporting fashion without putting too much tension on the grafted fat.

b

Fig. 81.2 (a) The sutures are passed in two planes: one superficial suture running subdermal at the inframammary fold and superficial to the pectoralis major muscle. The second suture runs in the deeper subcutaneous plane and underneath the pectoralis muscle in the superior pole of

the breast. (b) When the sutures are tied, the fat graft bulges forward within the compressed breast footprint. The suspension of the tissues in the lower pole defines the inframammary fold. (Artwork courtesy of © L. Ramaut, MD 2021)

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81.2.4 Postoperative Care Patients are prescribed to wear a supportive bra without underwire for 4 weeks starting one week after the procedure. They are asked to avoid abduction of the arms past 90° and sleep on their backs during the first 2  weeks after surgery. Patients are advised to avoid cold contact and pressure on the grafted breast. Antibiotic coverage is given for 5 days after the surgery. They can be discharged as soon as there is adequate pain control and good mobilization the same day or the day after the surgery. Patients are informed that a tense sensation and pain are normal in the postoperative period. The sutures are resorbable and will be replaced by fibrotic tissue over the course of several months. The percutaneous purse-string suture can produce some irregular dimpling from the thread, but this resolves over time when the resorption process is initiated. If the suture would fail or the definition of the fold is not satisfactory,

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the PPSS can be repeated. The lipofilling procedure can also be repeated if necessary. (Video of the surgical technique is available as electronic supplementary material.)

81.2.5 Limitations and Complications The percutaneous nature of this technique has the advantage of being scarless, but also demands meticulous technique from the surgeon. The cannula should be passed with caution, keeping the direction of the passage perpendicular to the thoracic wall to prevent thoracic trauma and pneumothorax. Patients should be closely monitored postoperatively for pain, suture failure, and suture infection. The PPSS will not provide sufficient projection when the fat graft is showing a high resorption rate after the surgery. In these patients, the lipofilling procedure should be repeated with an interval of at least 3 months. At this point, the PPSS suture can be repeated as well.

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81.3 Clinical Cases 81.3.1 Case 1 a

b

c

Fig. 81.3  A 41-year-old patient who underwent bilateral free transverse myocutaneous gracilis (TMG) flap breast reconstruction. The reconstruction was completed with lipofilling and PPSS procedure. (a) Preoperative view. (b)

Preoperative markings show the required corrections: fat grafting at upper and lower pole with creation of the IMF at the left side. (c) Result at 2 years postoperatively

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81.3.2 Case 2 a

b

Fig. 81.4  A 68-year-old patient who had mastectomy and irradiation. The patient did not accept a free DIEP flap and she asked for BRAVA fat grafting breast reconstruction. She underwent five sessions of fat grafting and two

c

PPSS procedures during the third and fourth sessions of fat grafting. (a–c) Preoperative views. The patient used the BRAVA external expansion system for 8 h daily during 3 weeks before fat grafting session

81  Enhancing Flap Breast Reconstruction with the Percutaneous Purse-String Suture and Fat Grafting

a

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b

c

Fig. 81.5  Difference in IMF definition and breast projection without and with the PPSS procedure (same patient in Fig. 81.2). (a) Lateral view shows the patient after the second fat grafting session without the PPSS procedure. Notice

a

b

the loss of projection and lack of IMF definition. (b) The patient during surgery after the third session of fat grafting with PPSS procedure. (c) Lateral view after 6 weeks postoperatively (fat grafting with PPSS procedure)

c

Fig. 81.6  The results at 3 years postoperatively (since the beginning of the reconstruction) and 3 months after the last session (fifth session but without PPSS) of fat grafting

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81.3.3 Case 3 a

b

c

d

e

f

Fig. 81.7 A 53-year-old patient who had a breast reconstruction with DIEP flap on the left side. Seven years later, she has breast cancer on the right side and she underwent immediate breast reconstruction with a free myocutaneous gracilis (TMG) flap. In the second phase, the IMF was reconstructed using PPSS procedure with fat grafting to complete the reconstruction. (a) Preoperative view. (b) Preoperative view shows the required corrections: fat graft-

ing at upper and lower poles with creation of the IMF on the right side. (c) The PDS suture was passed at the level of IMF after injection of 50 cc of fat. (d) The PPSS is passed to the breast footprint and knotted at the anterior axillary line. (e) The old IMF was disrupted by subcision using a 18G needle. (f) Further fat injection (60 cc) was done and the procedure was completed. (g) Postoperative result at 9 months with stable IMF and adequate breast symmetry

81  Enhancing Flap Breast Reconstruction with the Percutaneous Purse-String Suture and Fat Grafting

g

Fig. 81.7 (continued)

81.4 Discussion The position and definition of the inframammary fold are paramount in obtaining a natural appearance in the reconstructed breast. Fat grafting alone often lacks the support from retaining ligaments present in natural breast tissue. In the percutaneous purse-string suture technique, a resorbable PDS thread serves as an internal underwire that not only defines the IMF but also reduces the breast footprint. This redistributes the volume of the breast conus in a forward fashion and this extra bulge creates the needed projection in the fat-grafted breast. The amount of projection is adjustable and complementary lipofilling can be added in a second stage. No large incisions are necessary in this technique, which makes it perfect to combine with fat grafting which leaves minimal scars. The technique of PPSS can also be applied when increased projection and IMF definition are needed in procedures like mastopexy and breast reduction. The technique does not involve the need of extra specialized instruments. The two passes of the PDS suture in two levels enhance the suspension of the breast mound since it is locked in different planes. The first pass is locking the footprint in a subdermal plane,

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recruiting upper abdominal tissue, while the second pass runs in a deeper subcutaneous plane and under the pectoralis major muscle at the superior pole of the breast. In this manner, the injected fat will be contained within a limited breast base without putting increased stress on the skin. The sutures will resorb over 6 months to be replaced by fibrosis which will sustain the suspension. It is also postulated that the cannula passages cause fibrosis as well that might function as small retaining ligaments, but studies should be performed to investigate the extent of these phenomena and long-term results in both histology and morphometry [8]. The proximity between surgical instruments and thoracic wall entails a risk of causing a pneumothorax during the procedure. To prevent this, a blunt cannula should be used with its tip kept parallel to the thoracic wall. When the cannula exits the incision, it should be curved upwards and away from the thorax. On this regard the PPSS differs from Khouri’s technique where a needle is used for this purpose. This entails a higher risk of causing pneumothorax, as described in their series. Khouri also uses liposuction to further define the IMF, which is made up of recruited abdominal tissue. The first mention of the use of sutures to sculpt the breast was in 2015 by Abboud et al., who used V-Loc barbed sutures for glandular suspension in a technique called power-­ assisted liposuction mammaplasty (PALM) [9]. More recently, Visconti and Salgarello investigated the use of dual-anchor cog threads with fat grafting for breast augmentation with a standardized patient outcome measurement tool (the Breast-Q). They concluded threads to be useful in defining boundaries in the new breast footprint, adjusting the IMF position and increasing breast projection compared to their control group. The threads were used to define the footprint only in the lower pole of the breast [10]. The similarities and differences of these techniques are summarized in Table 81.2.

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Table 81.2  Comparison of different techniques described by Khouri, Hamdi, Abboud, and Visconti using threads in breast surgery Type of suture One smooth PDS suture

Suture guidance Sharp needle

Suture position Around breast footprint

Hamdi

Two smooth PDS sutures

Curved lipofilling cannula

Around breast footprint superficial and deep plane

Abboud

Barbed PDS sutures

Around breast footprint

Visconti

Barbed sutures

Straight lipofilling cannula Sharp needle

Effect Suspension of upper abdominal tissue and IMF Suspension of upper abdominal tissue and IMF, breast footprint compression Glandular suspension

IMF

IMF compression

Khouri

81.5 Conclusion A well-defined inframammary fold and sufficient breast projection are key to obtain a natural appearance in the reconstructed breast. The percutaneous purse-string suture with fat grafting is a valuable technique available to plastic surgeons aiming to achieve lasting results with minimal scars.

References 1. Kasem A, Wazir U, Headon H, Mokbel K.  Breast lipofilling: a review of current practice. Arch Plast Surg. 2015;42(2):126–30. 2. Kim I, Yang J, Lee D, Chung H, Cho B. Evaluation of centrifugation technique and effect of epinephrine on fat cell viability in autologous fat injection. Aesthet Surg J. 2009;29(1):35–9. 3. Khouri RK, Rigotti G, Khouri RK Jr, Cardoso E, Marchi A, Rotemberg SC, Baker TJ, Biggs TM.  Tissue-­ engineered breastreconstruction with Brava-assisted fat grafting: a 7-year, 488-patient, multicenter experience. Plast Reconstr Surg. 2015;135(3):643–58.

4. Waked K, Colle J, Doornaert M, Cocquyt V, Blondeel P.  Systematic review: the oncological safety of adipose fat transfer after breast cancer surgery. Breast. 2017;31:128–36. 5. Bogetti P, Craver L, Spagnoli G, Devalle L, Boriani F, Bocchiotti MA, Renditore S, Baglioni E.  Aesthetic role of the surgically rebuilt inframammary fold for implant-based breast reconstruction after mastectomy. J Plast Reconstr Aesthet Surg. 2007;60(11):1225–32. 6. Boutros S, Kattash M, Wienfeld A, Yuksel E, Baer S, Shenag S. The intradermal anatomy of the inframammary fold. Plast Reconstr Surg. 1998;102(4):1030–3. 7. Kraft CT, Rendon JL, Koutz CA, Miller MJ.  Inframammary fold reconstruction in the previously reconstructed breast: a comprehensive review. Plast Reconstr Surg. 2019;143(4):1019–29. 8. Hamdi M, Anzarut A, Hendrickx B, Ortiz S, Zeltzer A, Kappos EA.  Percutaneous purse-string suture: an innovative percutaneous technique for inframammary fold creation and improved breast projection in reconstructive surgery. Aesthet Surg J. 2018;38(12):1298–303. 9. Abboud MH, Dibo SA.  Power-Assisted Liposuction Mammaplasty (PALM): a new technique for breast reduction. Aesthet Surg J. 2016;36(1):35–48. 10. Visconti G, Salgarello M.  Dual-anchor cog threads in fat grafting breast augmentation: a novel scarless method for defining breast footprint and enhancing shape. Plast Reconstr Surg. 2019;143(4):1039–49.

Lipomodeling for Breast-­ Conservative Treatment Sequelae

82

Emmanuel Delay and Richard Vaucher

Key Messages • Radiotherapy after conservative treatment can be very harmful for the skin and the sequelae breast. • The first session of fat grafting must be done carefully. A low quantity of fat must be transferred to avoid fat necrosis. • Fasciotomy is often needed to free adherences but must also be done carefully in the beginning of the reconstruction. • When the sequelae are important multiple sessions may be needed to reduce the deformities. • Fat grafting is a reliable technique with really good results but must need a learning curve.

E. Delay (*) Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Lyon, France Lyon, France e-mail: [email protected] R. Vaucher Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Lyon, France e-mail: [email protected]

82.1 Introduction Aesthetics and functional sequelae of conservative treatment of breast cancer are real challenges for the surgeon [1]. Options offered to patients, such as flaps, were often disabling and disproportionate to the breast deformity [1]. In fact, they were associated with new scar and long surgery and recovery. Breast-conservative treatment in association with implant augmentation and radiotherapy is not recommended with high risk of capsular contractures or asymmetry. At the end of the treatment of their cancer and most often, few years after, patients are very eager for surgical correction of their deformity in order to erase or attenuate the visible signs of their disease so they reintegrate the breast unto their body image. Very good results were achieved with fat transfer in breast reconstruction [2, 3]. Finding that fat transfer was effective and innocuous, we proposed using it to correct therapeutic sequelae of the breast. This decision was supported by an imaging study conducted on breast reconstruction-­ associated fat grafting. This study showed no deleterious effects on breast imaging [4]. This chapter aims to present the information that should be given to the patients and the precautions that should be taken before carrying out this procedure, the surgical technique, the results which may be expected, the advantages and drawbacks of the technique, eventual radiologic

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_82

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modifications after lipomodeling, and in the end the medicolegal aspect linked to a coincidence between the appearance of a local recurrence and fat transfer.

82.2 J ustification of This Surgical Approach The use of fat transfer in breast surgery is an old concept [5]. More recently, and from the early days of modern liposuction, Illouz and Fournier suggested using the aspirated fat to obtain moderate breast augmentations. Bircoll presented a similar approach and drew attention to the advantages of this technique: simplicity, no scar, early return to normal activity, and no implants without talking about the secondary benefit of liposuction of the donor areas. Bircoll’s articles resulted immediately in many very outspoken opposing reactions. The critics underlined the fact that fat injections in a native breast could produce microcalcifications and cysts, making a cancer difficult to detect. Although Bircoll explained in his replies that the calcifications after fat transfer are different in localization and radiologic aspect than those seen in tumors and that after the same aspect are encountered and they do not affect breast screening, the debates remained negative for fat grafting to the breast. In 1998, the purposes of the authors’ research subject on fat transfer to the breast were to improve the technique to decrease fat necrosis and to tackle the taboo that suspended any work in breast fat grafting. Observing the efficacy and success that fat grafting had when transferred to the face, in aesthetic surgery and in treatment of facial sequelae after injury or cancer treatments, the authors came up with the idea to use this technique in breast reconstruction. First of all, they applied fat transfers to breast reconstructions with total autologous latissimus dorsi flap [6]. Afterward they widened the indications for most of the patients who had undergone a breast reconstruction by autologous latissimus dorsi flap where the risk of local recurrence was considered very

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low and a better result was desired, with a better cleavage, better breast form, and consistency. It restored satisfactory breast volume for most of the cases, but for some of them the volume was insufficient and the opposite breast had to be reduced. The protocol was initially offered to voluntary patients who agreed to undergo strict surveillance. The authors conducted an imaging study using a mammogram, ultrasound, and MRI [4] that showed that the impact on breast imaging did not interfere with cancer surveillance. For this reason, they progressively widened fat grafting indication for different breast reconstruction cases, and then for thoracic mammary malformations, to the breast conservation treatment, and more recently to cosmetic breast surgery. The first presentations to the French Society for Plastic and Reconstructive Surgery and worldwide received the same hostile polemic as the earlier work in 1987. The authors responded point for point, and with every presentation, people started to admit the benefits and the fear of interference with cancer surveillance diminished. Today, fat grafting is adopted as a procedure used in breast reconstruction [4, 7].

82.3 Patient Information The first consultation should expose the patient’s medical history and her expectations. Each patient is informed in detail by informed consent form about the operation, advantages, and possible complications. Each patient is given precise, detailed information both orally and in written form (a specific information sheet) that comprehensively explains the modality of the procedure, its advantages, drawbacks, and possible complications. We particularly emphasize that fat loss is normal during the early months and that the procedure has to be repeated if the patient has major sequelae. Also we inform the patient that the result can alter with major gain or loss of weight. Postoperative bruising is a common complication after fat grafting, which can be impressive at first, but diminish after few weeks.

82  Lipomodeling for Breast-Conservative Treatment Sequelae

During meticulous clinical examination, the conserved breast is compared with the opposite breast and the areas that require correction are identified and marked with the patient standing. The symmetry of the breasts is assessed, their overall volume and fullness, the position of the nipple-areola complex, the severity of loss of substance and volume, and depressed or retractile scars if any. The quantity of fat to be harvested and transferred is also assessed, as well as the need for any complementary measures such as restoration of symmetry, tattooing, and/or a nipple graft. The adipose areas where the fat will be harvested are identified. Abdominal fat is most often used, as harvesting in this area does not require a change in the patient’s position during the procedure; the second site is the trochanteric region (saddlebags), often combined with harvesting from the inside of the knees and thighs. It is important that the patient’s weight should be stable at the time of the procedure, as the ­transferred fat retains the memory of its origins, and if the patient loses weight after lipomodeling, she will lose some of the benefit of the procedure. As part of the protocol and following the French health agency recommendation, all patients undergo full imaging including mammography, ultrasound, and MRI before as well as 1 year after the procedure (without the MRI). The potential risk of local recurrence is clearly explained to the patient, as well as the risk that a cancer may occur coincidentally with lipomodeling. It is also explained that in the event of recurrence, mastectomy with immediate reconstruction will be performed. The only relative contraindications to fat grafting in conservative breast therapy are:

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82.4 Surgical Technique The lipomodeling technique used in the sequelae of conservative treatment is derived from that used in breast reconstruction [8]. It aims to transfer fat from an area with excess adipose tissue to the conserved breast that presents a deformity or is lacking in volume. The procedure is carried out in the surgical suite under general anesthesia. Conventional prophylactic antibiotics are usually given perioperatively. The patient is installed and draped so that she can be moved from a supine to a semi-sitting position if fat is harvested from abdominal and suprailiac deposits. If fat is harvested from the trochanteric or subgluteal area or the inside of the thighs, the patient is placed in a prone position and is then turned over and entirely redraped for fat injection. Fat is harvested with a blunt 3  mm cannula (Fig. 82.1) after preliminary infiltration of serum with adrenalin (1 mg of adrenalin in 500 mL of saline). Abdominal fat is harvested through four cardinal incisions around the navel. In the flanks, a suprailiac incision is made on each side. For the gluteal and trochanteric regions, the incisions lie in the subgluteal folds. We use 10  mL Luer-­ Lock® syringes. With the finger, the operator makes a moderate, gradual depression that creates a differential of a few cubic centimeters between the aspirated fat and the piston in order to minimize damage to the adipocytes.

–– Carcinoma without remission and suspicious lesions of the breast (ACR3 or ACR4) –– Less than 2  years after ending all the treatment High risk of local recurrence (inflammatory breast, high grade of carcinoma, sarcoma) is a controverted subject, but not a formal contraindication.

Fig. 82.1  Fat is harvested, with a blunt 3 mm cannula, in the postero-external thigh

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Both deep and superficial fats are harvested. At the end of the procedure, the harvesting site is often recontoured by liposuction for a better cosmetic result. When harvesting is completed, the same cannula is used to inject 7.5  mg naropin® (ropivacaine hydrochloride) with an equal volume of physiological in order to avoid postoperative pain during the first 24 h. As harvesting continues, the instrument nurse prepares the syringes for centrifugation. They are sealed with a plastic cap, the piston is withdrawn, and they are placed in the centrifugator in batches of 15 s at 3000 revs/min. After purification, the fat separates into three layers (Fig. 82.2a, b): –– A top layer of oil resulting from cell lysis (chylomicrons and triglycerides) –– A bottom layer of blood residues –– A middle layer of purified adipocytes: this is the valuable part that will be used for transfer a

After preparation of the fat, several punctate incisions are made with the bevel of a pink trocar in order to create a crosswork of tunnels for the transfer of fatty tissue. The fat is then injected in its new site using special disposable fine 1.5  mm cannulas. Deep tunnels must be made in all planes, from the ribs to the skin, following the preoperative markings and forming a three-­dimensional honeycomb. The fat must be injected while the cannula is withdrawn. Care must be taken to avoid using too much pressure, and the fat should be injected in small quantities as if it were spaghetti (the “fat spaghetti” principle) (Fig. 82.2c). This is because of the risk that necrotic cysts will form if too much fat volume is injected (centripetal revascularization does not allow survival of largesized fragments, which become the site of central necrosis with liquefaction and cyst formation). At some point of the procedure, when there is a hard grip under the scar or in any b

c

Fig. 82.2  Centrifugation and injection. (a) Centrifugator. Syringes are placed in the centrifugator for 15 s (3000 revs/ minutes). (b) Fat after purification. (c) The “fat spaghetti” principle of fat grafting with a 1.5 mm cannula

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enables made-to-measure corrections of the sequelae of conservative treatment. If correction is not sufficient, one or even two further sessions can be carried out after an interval of 3 months.

82.6 Results In a personal series of 100 consecutive patients who had undergone breast-conservative treatment and had correction by fat grafting for deformities of their breast, and precise follow-up [5]: Fig. 82.3 Fasciotomy

localization in the breast, we often realized fasciotomy with the bevel of a pink trocar to free the adherences (Fig.  82.3). We usually do it near the end of fat grafting. If possible, volume should be overcorrected. As about 30% of fat is reabsorbed, 140% of the desired volume should be transferred. But very often after conservative treatment, overcorrection is not possible as the tissue receiving the fat is fibrotic. It is advisable not to attempt to continue, but to program another surgery. During the second session, because of the anti-fibrotic effect of the fat, larger quantities can often be transferred. At the end of the procedure, the fat grafting area is covered with a simple dressing.

82.5 Postoperative Care The patient leaves the unit on the same day or the day after the procedure, with class 1 analgesics. The dressing on the breast is changed every 48 h by a private nurse or by the patient herself. Major bruising of the harvesting site is common and this is generally the most painful area in the immediate postoperative period. The breast is also swollen but bruising is less marked. At the harvesting site, bruising clears in 3 weeks, sometimes leaving some firmer nodular areas that return to normal in the months after the procedure, and more rapidly if the patient rubbed them. The breast attains its definitive volume 4  months after the procedure, but from the first month it begins to feel soft. This technique

–– 97% of the cases were evaluated between acceptable and excellent after fat grafting on the point of view of the surgeon (72% excellent) and 94% of the patients were considering the result between satisfying and very satisfying (only 5% were not satisfied with the correction of the breast). –– 60 patients needed only one surgery, 35 needed two interventions (35%), and only five patients needed a third operation to complete the restoration of the breast (5%). –– We experienced only 3% of complications such as minor infections, successfully treated with antibiotics. –– No difficulty was encountered with the clinical or imaging examination follow-up: 11 microbiopsies were performed after 1  year and only two patients were diagnosed as relapse (2%) whereas the relapse percentage expected was 9% on a 11-year follow-up on this particular study. For the record, seven lesions on the contralateral side were found during the follow-up.

82.7 Fat Grafting Advantages The benefits are seen in better perspective if we remember that until the progress of fat grafting, there was no technique that satisfactorily corrected moderate morphological deformities after conservative treatment of breast cancer. Often patients with limited breast deformities were therefore not treated [1]. Other techniques had many potential complications and were difficult to perform considering the limited breast deformity.

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82.7.1 Autologous Tissues The adipose tissue is autologous and there are no secondary problems as those seen in the case of implants.

82.7.2 Reproducible Technique Fat harvesting and reinjection are clear concepts easily understood by patients. However, for surgeons, there is a learning curve with impact on the result quality and rate of fat necrosis. The technique needs to be precise and delicate, and with proper training, it can be easily performed by an experienced surgeon. Once the learning curve is complete, the technique becomes very reproducible [9].

82.7.3 Low Cost This technique does not require a significant investment. The costs are limited to cannulas, syringes, and a centrifuge that can prepare the fat graft in a sterile fashion. Comparing these costs to others in the oncologic domain, they are less expansive given the quality-of-life improvement and the increasing demand.

82.7.4 Limited Invasiveness Fat is harvested and injected through small incisions that need easy postoperative care. Patients recover and return to their activities quickly.

82.7.5 Low Complications True complications are extremely rare. Risk of hematoma is nonexistent. Risk of pneumothorax is very low, and diagnosis should be expected if desaturation occurs during the procedure. In that case, a chest radiograph can be performed, and if needed, the pneumothorax can be drained. To prevent this complication, the injection of the fat must be done in a paralleled plane to the thoracic wall by two incisions in the IMF.

E. Delay and R. Vaucher

Fat embolism can occur theoretically if fat is injected into a vessel with high pressure. It can be prevented by using blunt cannulas with a side opening, and by injecting only while retracting the cannula. On the experience of 5000 cases of fat grafts of the breast of the first author (Emmanuel Delay), we never had fat embolism. The short-term risk is mainly represented by infection. It is prevented as much by strict aseptic conditions and by administration of a dose of prophylactic antibiotic. Infection is diagnosed in a standard fashion through clinical observation. Local infection may also appear around the nipple-areola complex, shown by redness of the surrounding skin. It can be treated without difficulty by usual antibiotics and local application of ice. Long-term complications are the risk of fat necrosis and irregularities of the donor site. Fat necrosis can appear if the volume is way too important in an area that cannot accept that much quantity. Fat necrosis is easily managed with punctures at the office.

82.7.6 Adjustable Volume The harvested and transferred volume is decided according to the volume deficit. It is easy to adjust the harvest fat to the deficit.

82.7.7 Secondary Benefit Secondary benefits are linked to the liposuction with body contouring amelioration, especially if the procedure is repeated.

82.7.8 Improvement of Skin Trophicity Color, elasticity, and pliability were the most common improvements notified during follow­up consultations. The improvement was observed especially in case of severe sequelae on irradiated tissue.

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82.8 Fat Grafting Disadvantages

82.8.2 Experience-Dependent Results

82.8.1 Several Surgeries

The aesthetic results are influenced by the surgeons’ experience. It is difficult to appreciate at first the overcorrection required. Approximately 70% of the fat will be integrated depending on the patient.

If the deformity is significant, repeated sessions will be required. If tissue has been irradiated, its lack of elasticity limits the amount of fat that can be injected. Repeated sessions are sometimes planned from the start if the volume to be corrected is significant. In this case, the patient must be clearly informed of the need for complementary sessions, which in practice are performed at intervals of 3 months. However, this drawback is generally well accepted, because it comes with the secondary benefit of repetitive liposuction (see Fig. 82.4(a–d), Fig. 82.5(a–d), and Fig. 82.6(a–d)).

82.8.3 Time-Consuming Harvesting Manual harvesting is known to be less damaging to the adipocytes than mechanical aspiration [10]. The downside is that harvesting is long and good team organization is needed. The instrumentation nurse prepares the fat grafts by centrifugation while the rest of the team continues the harvesting.

a

c

b

d

Fig. 82.4 (a and b) 49-year-old patient, 2 years after tumorectomy and radiotherapy. (c and d) Result 6 months after one session of lipomodeling the right breast (240 mL) and mammaplasty on the left side

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a

c

b

d

Fig. 82.5 (a and b) Patient after one session of lipomodeling (97 mL). Skinny patient with strong sequelae of radiotherapy. (c and d) Result 6 months after a second session of lipomodeling (140 mL)

82.8.4 Pain Pain in the breast is not very severe, but it can be quite intense at the harvesting site. We always use infiltration of diluted naropin® in the harvesting tunnels using the harvesting cannula. On the day after the procedure, ordinary class 1 analgesics such as paracetamol are usually sufficient.

82.8.5 Edema and Ecchymosis Edema and ecchymosis are frequent at the donor and the receiving sites, and are due to local trauma caused by tunneling for harvesting or reinjection. Bruising persists for about 2–3 weeks depending on the patient. The final result can be seen in 3–4  months after surgery. On the breast, some bruises resolve

in about 2 weeks, and the edema caused by the procedure resolves in about 1 month. Volume is stable after about 3–4 months.

82.9 R  adiological Aspect After Breast-Conservative Treatment Sequelae It is important to be familiar with radiological appearance as potential microcalcifications and fat nodules were the major criticisms raised against fat transfer. Over the last 20 years radiological techniques have considerably improved, enabling much more precise diagnosis of the breast parenchyma and of any abnormalities. In addition, the development of small-gauge and large-gauge needle core biopsies since 1990 provides a histological result that is as reliable as a

82  Lipomodeling for Breast-Conservative Treatment Sequelae

a

c

b

d

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Fig. 82.6 (a and b) Preoperative view: 45-year-old patient after tumorectomy and radiotherapy. (c and d) Result 1 year after lipomodeling (250 cc) and mammaplasty of the left breast

surgical biopsy, using a percutaneous technique under local anesthesia. In the majority of cases, these biopsies give a definitive diagnosis without the drawbacks of surgery and can easily be proposed if any breast abnormality is considered suspicious. With our team of radiologists, we have taken particular care to define precisely all images that may be encountered after fat grafting for the sequelae of conservative treatment of breast cancer. The following images can be seen after breast lipomodeling: 1. Microcalcifications The formation of calcifications can be considered as a normal consequence of fat grafting as it concerns 20% of patients 1 year after surgery. They are also a normal and frequent effect of any breast surgery. The calcifications that appear after breast surgery or fat grafting do not have any diagnosis or therapeutic con-

sequences because their radiologic aspects are benign. 2. Fat necrosis Fat necrosis may appear, but they can be avoided if the surgical technique is respected [4]. We consider that clinical fat necrosis is generally linked more often to a lack of experience. Fat necrosis can be diagnosed more often on the mammograms or ultrasounds as oil cyst for which the diagnosis is obvious: round, regular microcalcifications with a radiolucent center classified ACR 2. They are not suspect, and they are different to those linked to potential relapse. Less frequently we can notice an image of a mixed complex cyst: liquid and pseudo-solid component, but also in this case the diagnosis of fat necrosis is easily made. Radiologists with a particular interest in mammography are familiar with these images, as it must not be forgotten that fat necrosis, like microcalcifications, appears

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after all types of breast surgery: biopsy, conservative treatment, breast reduction, breast reconstruction, or liposuction. It is easy to give the benign or malignant diagnosis on mammogram, ultrasound, or MRI [7]. If there is the slightest doubt, the diagnosis is made by micro- or macro-biopsy and histologic examination. If there is any doubt, an expert opinion should not be searched, but certainly it should be obtained through histologic examination.

82.10 Medicolegal Aspects The rate of local recurrence after conservative treatment is 1.5% per year, or 5–10% of patients at 5 years’ follow-up [7]. Most of the time, we perform fat grafting in patients who have had a breast-conservative treatment with significant deformities (depression of the skin, dystopia of the areola complex or lack of volume). The incidence of coincidence between tumor relapse and fat graft transfer is potentially spontaneously high. The patient who seeks advice for correction of the sequelae of conservative treatment often considers herself cured of her cancer. Therefore, before lipomodeling is performed, the patient must be informed that she is at risk of local recurrence, whether she can decide knowingly the benefits of fat grafting. She also needs to be informed of the importance of breast imaging investigations before and after surgery. Moreover, the patient must be informed that in the case of relapse after conservative treatment, total mastectomy is indicated with immediate reconstruction.

82.11 Conclusion Reconstructive surgery after conservative treatment is delicate and difficult because of radiation sequelae and also because of the wide range of postsurgical deformities affecting both the skin and the gland itself. The results of partial recon-

structions for sequelae of conservative treatment are often disappointing and their treatment may sometimes raise problems, which are sometimes more difficult to solve than the case with mastectomy. Lipomodeling is a response to the reconstructive needs for these deformities. It is a simple technique that needs a learning curve to avoid the formation of fat necrosis nodules. Fat grafting gives very good results regarding breast volume, softness of the breast, trophicity of the breast tissues, and consistency, avoiding implants or flaps. The fat graft volume transferred must be appropriate to the receiving site. If the deformity is significant or the receiving tissue is thin, it is better to perform several surgeries and incorporate fasciotomies. The results are stable after approximately 3  months. Microcalcifications or fat necrosis frequently can occur after lipomodeling. They are similar to those induced by any other type of breast surgery, including the initial conservative treatment. The imaging studies showed that the screening is always possible after this type of surgery, in a multidisciplinary team. For a radiologist experienced in breast imaging, they do not lead to confusion with possible images of a breast cancer recurrence. If there is the slightest doubt, or any suspicious image, a biopsy must be done to confirm or not the diagnosis.

References 1. Delay E, Gosset J, Toussoun G, Delaporte T, Delbaere M. [Post-treatment sequelae after breast cancer conservative surgery]. Ann Chir Plast Esthet. 2008;53:135–52. 2. Delay E.  Lipomodeling of the reconstructed breast. In: Spear SL, editor. Surgery of the breast: principles and art. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2006. p. 930–46. 3. Delay E, Delaporte T, Sinna R. [Breast implant alternatives]. Ann Chir Plast Esthet. 2005;50:652–72. 4. Pierrefeu-Lagrange AC, Delay E, Guerin N, Chekaroua K, Delaporte T. [Radiological evaluation of breasts reconstructed with lipomodeling]. Ann Chir Plast Esthet. 2006;51:18–28. 5. Delay E, Gosset J, Toussoun G, Delaporte T, Delbaere M. [Efficacity of lipomodelling for the management

82  Lipomodeling for Breast-Conservative Treatment Sequelae of sequelae of breast cancer conservative treatment]. Ann Chir Plast Esthet. 2008;53:153–68. 6. Delay E, Gounot N, Bouillot A, Zlatoff P, Rivoire M.  Autologous latissimus breast reconstruction: a 3-year clinical experience with 100 patients. Plast Reconstr Surg. 1998;102:1461–78. 7. Gosset J, Guerin N, Toussoun G, Delaporte T, Delay E. [Radiological evaluation after lipomodelling for correction of breast conservative treatment sequelae] Ann Chir Plast Esthet. 2008; 53:178–89.

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8. Delay E, Guerid S, Meruta A. Indications and controversies in lipofilling for partial breast reconstruction. Clin Plast Surg. 2018;45:101–10. 9. Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997;24:347–67. 10. Delay E. Correction of partial breast deformities with the lipomodeling technique. Chapter 78. In: Kuerer H, editor. Kuerer’s Breast Surgical oncology. New York: Mac Graw-Hill; 2010. p. 815–25.

Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction

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Delay Emmanuel and Frobert Paul

Key Messages • In case of total delayed breast reconstruction using autologous latissimus dorsi flap with lipomodelling, patients should be carefully selected depending on their fat deposits, on the shape and size of the contralateral breast, and on the patient acceptance of multiple surgeries. • Autologous latissimus dorsi flap is the most reliable procedure for autologous breast reconstruction. • Lipomodelling as a complement to autologous latissimus dorsi flap helps to avoid the initial or secondary insertion of an underlying implant to counterbalance the lack of volume. • With each lipomodelling session, more fat grafts can be transferred. • This surgery is a surgery with very satisfying results if the case selection is good and the surgeon is experienced with fat grafting.

D. Emmanuel (*) Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Cancer Institute, Lyon, France Lyon, France e-mail: [email protected] F. Paul Unité de Chirurgie Plastique et Reconstructrice, Centre Léon Bérard, Cancer Institute, Lyon, France e-mail: [email protected]

83.1 Introduction Amongst various techniques of breast reconstruction, autologous latissimus dorsi flap is one of the most reliable procedures with a poor complication rate. Surgical procedure is well standardized, and allows to harvest various fat areas attached to the muscle [1]. This technique can be used in almost every case of breast cancer, especially when free flaps are unsuitable. However, in 30% of the cases (thin patients or after secondary muscle atrophy), the final volume of the breast may be found insufficient [2]. In these patients, a common strategy is the initial or secondary insertion of an underlying implant, but the procedure is no longer autologous and the patients may suffer specific side effects associated with prosthesis placement [3, 4]. Alongside, fat grafting is a perfect and constant tool in breast surgery refinements and has a major role when used as a complement for breast reconstruction with different flaps [5–10]. A lot of different methods for fat harvesting, purification, and transfer have been described. If most plastic surgeons stick to Coleman’s principles, we have refined these principles to our daily practice to make it more efficient [11, 12]. In the author’s protocol, fat grafting appears to be a perfect complement to autologous immediate or delayed breast reconstruction based on autologous latissimus dorsi flap [13–16].

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Additional lipomodelling is performed in the whole reconstructed breast area at 2  months to get the satisfying shape. In some cases, extra fat grafting sessions can be performed to get the expected breast volume and correct any skin irregularity. The aim of this chapter is to describe surgical technique, advantages and disadvantages of lipomodelling in the case of breast reconstruction with autologous latissimus dorsi flap, and results we can obtain with this technique.

83.2 Technique

The areas of the breast that need to be specifically treated are defined by meticulous clinical examination and marked out on the patient. In our department, we have carried out a three-­ dimensional morphologic study, as well as the usual two-dimensional photographs, and we find this to be advantageous in assessing the quantity of fatty tissue to be transferred and the amount that will be resorbed.

83.2.2 Fat Harvest

Before surgery, the patient is marked in a standing position. The technique of the autologous latissimus dorsi The breast base and the inframammary fold flap has been described previously [1, 2, 17, 18]. are drawn, and the donor sites are marked. In our context, we consider that the first stage Harvesting fat graft from the abdominal area of breast reconstruction has been performed with facilitates patient positioning, but fat harvesting autologous latissimus dorsi flap in immediate or can also be performed in prone position to allow delayed breast reconstruction. lipomodelling of latissimus dorsi donor site. This Lately, we developed a new technique to mini- procedure helps to reduce any skin irregularity in mize donor-site morbidity with shorter scar: the the back, and reduces donor-site morbidity. short-scar latissimus dorsi flap. This is a new interesting technical note for any Because lipomodelling is usually combined surgeon performing breast reconstruction based with other procedures (either liposuction of the on latissimus dorsi flap. Lipomodelling of the inframammary fold, reconstruction of the nipple-­ back reduces donor-site morbidity. areola complex, or contralateral symmetrization), Usually, first donor sites are iliac fat pad, troit is generally performed under general chanteric fat pad, internal aspect of the thigh, and anaesthesia. then abdominal tissues (Fig. 83.1). The first lipomodelling session is usually perThe surgeon begins to harvest the fat. During formed 2 months after latissimus dorsi flap. fat harvest, the operating nurse has time to preLess extensive lipomodelling or follow-up pare the fat grafts while surgery is continued. The (second or third) sessions can be performed under fat grafts are harvested using a blunt 3.5-mm-­ local anaesthesia. diameter cannula linked to 10  mL Luer-lock syringes after infiltration 1:1 with saline and epinephrine solution (1 mg epinephrine in 500 mL saline). 83.2.1 Preoperative Planning The harvesting step is performed by two surPatients are informed about the operative tech- geons (senior surgeon and junior surgeon) nique and its risks and potential complications simultaneously to save time and to be more efficient. and are given an informed consent form. The incisions are performed with a number 15 We recommend our patient to be at ideal weight at the time of surgery because the fat that blade, and their position depends on the site to be is transferred “remembers” its origins, and if the harvested. The surgeon creates a small and propatient loses weight after the lipomodelling pro- gressive negative pressure (2–3  mL) in the syringe using the hand in order to reduce the cedure, the benefit will be partially lost.

83  Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction

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Fig. 83.1  Fat harvesting in delayed right-breast reconstruction: epinephrine solution infiltration (left side), harvesting manually with 10 mL syringe (right side)

Fig. 83.2  Centrifugation of the syringes during 15 s at 3000 rotations per minute

trauma exerted to the adipose tissue. At the end of the procedure, a Naropin (Ropivacaine) 75  mg 50% solution is infiltrated in order to decrease the post-operative pain in the first 24 h after surgery. The incisions are closed by points of rapid absorbable sutures. The harvested fat is treated by centrifugation at 3000 rotations per minute for 15 s (Figs. 83.2 and 83.3). Compared to Coleman protocol, we consider that the centrifugation time has to be reduced to shorten the procedure. Longer centrifugation time has not proven its benefit and on the contrary can damage fat cells. Also, in the author’s protocol, during the first step of breast reconstruction (autologous latissi-

mus dorsi flap) the fat has already been transferred directly into the pectoralis major muscle.

83.2.3 Fat Transfer Fat grafts can be transferred using a 2 mm blunt single-hole cannula linked to 10  mL syringes filled with purified fat grafts (Fig. 83.4). Small incisions are made in the breast with a 17-gauge trocar, which gives sufficient access, while the minimal, punctuate residual scar will be almost invisible. Multiple incisions are made all around the breast and through previous scars, so they can be honeycombed with numerous microtunnels for the fat transfer.

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Fig. 83.3  Preparation of fat syringes to be transferred

Fig. 83.4  Fat transfer in the right reconstructed breast, and also in the latissimus dorsi donor site

83  Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction

The fat grafts are transferred from the deep to the superficial planes into a criss-cross pattern. The fat is injected in all layers: subcutaneous tissues, pectoral muscle, and latissimus dorsi flap. The volume of fat to be transferred has to be planned preoperatively to achieve symmetry. The quantity to be transferred should be overestimated because 30% of the volume transferred will be resorbed. The 140% rule should be applied: if 100 mL is the final quantity desired, 140 mL of fat should be transferred. However, when the receiving tissues are saturated with fat and can absorb no more, there is no point in continuing the process; otherwise it might result in an area of fat necrosis. It is better to carry out a second session a few months later, which will be much easier. The reconstructed breast can be improved with a new lipomodelling session, lateral l­iposuction, and, if the inframammary fold is not satisfying enough, inframammary fold liposuction. Also, balancing surgery can be considered, such as breast reduction or mastopexy. It is important, when performing breast reduction or mastopexy, to keep in mind that the reconstructed breast is not going to have very good central projection, so the balancing should diminish the projection of the contralateral breast. If needed, another fat transfer session can be performed 3  months later, until a satisfactory result is obtained.

83.2.4 Post-operative Cares At the end of each surgery, the authors cover the breast with a Vaseline-impregnated dressing and then a noncompressive dressing. We protocolled this procedure to be an ambulatory surgery when performed alone. If any other surgery is combined—such as contralateral mastoplasty—the hospital stay depends on the combined surgery (one-night stay for mastoplasty). For fat transfer oral painkillers are prescribed. The dressing is changed every 48  h during 7–10 days. Often the donor sites are marked by ecchymosis, and usually they are the most painful after

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surgery; they disappear 2–3 weeks after surgery. The breast also has mild ecchymosis and oedema. The final result after each surgery can be evaluated after 3 months.

83.3 Indications of Lipomodelling In our experience, fat grafting is performed at each step of breast reconstruction: –– At the first stage, latissimus dorsi is performed, and combined to fat transfer in the pectoralis muscle and in the thoracoabdominal skin and subcutaneous tissues. –– At the second stage, contralateral mastoplasty is performed and fat transfer is performed in all the layers of the reconstructed breast and also on the latissimus dorsi donor site. –– At the third stage, nipple-areola complex reconstruction is realized and, if needed, an additional fat graft can potentially be performed if satisfactory volume is not yet reached. A 3-month period is respected between each stage. In our daily practice, autologous latissimus dorsi flap with the adjunction of fat grafting surpassed abdominal flaps for numerous reasons. We believe to have better results, with lower rates of complication, reduced operative time, and less drawbacks. In fact we use lipomodelling in all cases of breast reconstruction with autologous latissimus dorsi flap to correct any skin irregularities or volume asymmetry.

83.4 Contraindications of Lipomodelling Contraindications of lipomodelling are extremely unusual. The most difficult cases are remarkably thin patients, but even in these rare cases we are always able to perform at least one session of lipomodelling.

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83.5 Results In our team, we have now performed more than 5000 cases of breast reconstruction with this protocol confirming the results we have published in 2010 about 200 patients [11] and confirmed by other teams [19, 20]. The median age at the time of lipomodelling was 48.7 years (range 18–72 years) (Table 83.1). The median duration of follow-up for the 200 patients was 14.5  months (range 4–52  months). The patients were offered lipomodelling at an average of 11.7  months (range 4  months to 6 years) after the latissimus dorsi reconstruction. A review of patient records revealed that 11% had a history of tobacco use and 71% had received radiotherapy to the breast area. This rate increased to 88.3% in the subgroup of patients undergoing delayed breast reconstruction. The median body mass index (BMI) of the patients was 23.1 (range 17–35.5) with a median body weight of 60.7 kg and a median height of 162  cm. No important weight variations of the patients were observed between latissimus dorsi flap reconstruction and the first lipomodelling session. The BMI at the first lipomodelling session was 23 (range 16.7–37.7); the patients lost an average of 270 g between the two procedures. Of the 200 patients included in the study, 145 (73%) had delayed breast reconstruction (DBR) Table 83.1  Patient characteristics [11] Age BMI Immediate breast reconstruction (IBR) Delayed breast reconstruction (DBR) Left-breast reconstruction Right-breast reconstruction Bilateral breast reconstruction

48.7 (18–72) 23.1 (17–35.5) 145 (73%) 54 (27%) 107 (53.5%) 93 (46.5%) 14 (7%)

and 54 (26.5%) immediate breast reconstruction (IBR) after breast cancer surgery. One patient (0.5%) underwent reconstruction of the breast and the upper thorax for management of sequelae after surgical treatment of an Ewing sarcoma of the second rib (Table 83.2). There was a slight predominance of left-breast reconstruction (53.5%) over right breast (46.5%). Fourteen patients (7%) had bilateral involvement. In total, 244 lipomodelling sessions were performed. A total of 37 patients had at least two sessions and seven patients had three sessions of lipomodelling (Table 83.3). Complications were reported in three patients: two cases of minor local infection, easily controlled by antibiotics and by removal of the suture corresponding to the redness, and one case of pneumothorax requiring pleural drainage. Five patients had clinical signs of cytosteatonecrosis, though with no serious morphological or diagnostic consequences. They presented as a palpable nodule. They were all easily managed (Table 83.4). Of the 200 breast reconstructions analysed, 9 (4.5%) were rated by the clinical team as satisfac-

Table 83.3 Number of sessions, reoperations, and resorption rate [11] Number of sessions of lipomodelling Only one session Two sessions Three sessions Total number of patients Total number of sessions Clinical resorption rate

163 30 7 200 244 20–30%

Table 83.4  Complications [11] Minor local infection Pneumothorax Cytosteatonecrosis (oil cyst) Total

2 (1%) 1 (0.5%) 5 (2.5%) 8 (3.5%)

Table 83.2  Complementary treatment, and type of reconstruction for the 200 patients [11] Nb of pers. IBR DBR Other Total

Tobacco 2 20 0 22

Chemotherapy 6 90 1 97

Hormonotherapy 5 77 1 83

Radiotherapy 13 128 1 142

Total 54 145 1 200

26.5% 73% 0.5% 100%

83  Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction

tory and 191 (95.5%) as very satisfactory. No medium or poor results were reported. The study showed that patients were satisfied (20%) or very satisfied (80%) with the results (Figs. 83.5 and 83.6). The results can be considered as very high, probably because we apply the principle of “if a patient is not happy with the result, we propose a new session of lipomodelling”. As a consequence, none expressed dissatisfaction. The secondary cosmetic benefit derived from the liposuction also increased patient satisfaction with the procedure.

83.6 Discussion Lipomodelling is a useful complement to autologous latissimus dorsi flap reconstruction of the breast. Using this procedure, it has been possible to extend the indications for flap reconstruction

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in our patients (95%) and also to improve the quality of breast reconstruction. Currently, we propose the latissimus dorsi flap and lipomodelling to almost every patient. Now, with the second stage of lipomodelling, we can complete the lack of volume during the second surgery and also propose this technique to more patients. The principle of latissimus dorsi flap reconstruction has been modified and the autologous tissue flap is now used as a recipient site for further fat cell injections. Preliminary radiological studies have demonstrated the absence of deleterious consequences for breast radiological follow-up, thus permitting to extend the indications for breast lipomodelling. In the author’s protocol, breast implants are never used to achieve a complete autologous reconstruction. Latissimus dorsi plus breast implant has been widely used, but we consider it not to be the first-­ line treatment. Breast implant drawbacks such as capsular contraction, implant rupture, and breast

a

Fig. 83.5 (a) 44-Year-old patient who underwent a left-­ operative view after left delayed breast reconstruction breast mastectomy for invasive ductal carcinoma and with autologous latissimus dorsi flap and one session of adjuvant radiation therapy. Preoperative view. (b) Post-­ lipomodelling (390 cc). Result at 1-year follow-up

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b

Fig. 83.5 (continued)

D. Emmanuel and F. Paul

83  Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction

implant-associated anaplastic large-cell lymphoma led us to avoid the combination of ALD and breast implant, considering that the volume that brings the implant can be replaced by fat grafting with more benefits and less drawbacks. Also, the constant necessity of breast implant replacement forces the patient to undergo several surgeries while growing old which sometimes leads to surgical procedure for the elderly whereas lipomodelling helps to finish permanently the breast reconstruction. Free abdominal flaps are considered by numerous authors to be the gold standard for breast reconstruction, but the higher technical nature and the significant risk of complete flap loss make it unacceptable for some patient, and sometimes unsuitable considering the patient morphology. Lipomodelling is simple, safe, and reproducible, which makes it available for use in many indications of breast-reconstructive and plastic surgery. The technique thus has been appearing as one of the most considerable advances in breastreconstructive surgery since the mid-1990s.

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83.7 Conclusion Because the autologous latissimus dorsi flap is a very-well-vascularized flap, lipomodelling appears as a perfect complement of the autologous latissimus dorsi flap. It can be used during the first step of breast reconstruction and also in adjunction during the second or third procedure. Through its exceptional reliability, this technique can be proposed in almost every case of breast reconstruction. The principle of latissimus dorsi flap reconstruction has been modified and the autologous latissimus dorsi flap is now considered as a recipient site for fat grafting or a matrix to accept fat transfer. Using this protocol, it has been possible to extend the indications for flap reconstruction in our patients and also to improve the quality of breast reconstruction. Thanks to this protocol, the autologous latissimus dorsi flap has found a renewed success, and is a first-line technique for autologous breast reconstruction.

a

Fig. 83.6 (a) 48-Year-old patient who underwent a left-­ breast mastectomy for invasive ductal carcinoma. Preoperative view. (b) Post-operative view after left

delayed breast reconstruction with autologous latissimus dorsi flap and one session of lipomodelling (210  cc). Result at 1-year follow-up

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b

Fig. 83.6 (continued)

D. Emmanuel and F. Paul

83  Lipomodelling as a Useful Complement to Autologous Latissimus Dorsi Flap Breast Reconstruction

References 1. Delay E, Florzac AS, Frobert P. [Breast reconstruction with the autologous latissimus dorsi flap]. Ann Chir Plast Esthet. 2018;63(5–6):422–36. 2. Delay E, Gounot N, Bouillot A, Zlatoff P, Comparin JP. [Breast reconstruction with the autologous latissimus dorsi flap. Preliminary report of 60 consecutive reconstructions]. Ann Chir Plast Esthet. 1997;42(2):118–30. 3. Demiri EC, Dionyssiou DD, Tsimponis A, Goula C-O, Pavlidis LC, Spyropoulou G-A.  Outcomes of Fat-Augmented Latissimus Dorsi (FALD) flap versus implant-based latissimus dorsi flap for delayed post-­ radiation breast reconstruction. Aesthet Plast Surg. 2018;42(3):692–701. 4. Santanelli di Pompeo F, Laporta R, Sorotos M, Pagnoni M, Falesiedi F, Longo B.  Latissimus dorsi flap for total autologous immediate breast reconstruction without implants. Plast Reconstr Surg. 2014;134(6):871e–9e. 5. Delay E, Guerid S. The role of fat grafting in breast reconstruction. Clin Plast Surg. 2015;42(3):315–23, vii. 6. Delay E, Meruta AC, Guerid S. Indications and controversies in total breast reconstruction with lipomodeling. Clin Plast Surg. 2018;45(1):111–7. 7. Delay E.  Chapter 66: Lipomodelling of the reconstructed breast. In: Spear SL, editor. Surgery of the breast—principles and art. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 930–46. 8. Bonomi R, Betal D, Rapisarda IF, Kalra L, Sajid MS, Johri A.  Role of lipomodelling in improving aesthetic outcomes in patients undergoing immediate and delayed reconstructive breast surgery. Eur J Surg Oncol. 2013;39(10):1039–45. 9. Hamza A, Lohsiriwat V, Rietjens M.  Lipofilling in breast cancer surgery. Gland Surg. 2013;2(1):7–14. 10. Chan CW, McCulley SJ, Macmillan RD. Autologous fat transfer—a review of the literature with a focus on breast cancer surgery. J Plast Reconstr Aesthetic Surg. 2008;61(12):1438–48.

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11. Sinna R, Delay E, Garson S, Delaporte T, Toussoun G. Breast fat grafting (lipomodelling) after extended latissimus dorsi flap breast reconstruction: a preliminary report of 200 consecutive cases. J Plast Reconstr Aesthetic Surg. 2010;63(11):1769–77. 12. Delay E, Garson S, Tousson G, Sinna R.  Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J. 2009;29(5):360–76. 13. Delay E, Gounot N, Bouillot A, Zlatoff P, Rivoire M.  Autologous latissimus breast reconstruction: a 3-year clinical experience with 100 patients. Plast Reconstr Surg. 1998;102(5):1461–78. 14. Delay E, Jorquera F, Pasi P, Gratadour AC. Autologous latissimus breast reconstruction in association with the abdominal advancement flap: a new refinement in breast reconstruction. Ann Plast Surg. 1999;42(1):67–75. 15. Thekkinkattil DK, Salhab M, McManus PL. Feasibility of autologous fat transfer for replacement of implant volume in complicated implant-­ assisted latissimus dorsi flap breast reconstruction. Ann Plast Surg. 2015;74(4):397–402. 16. Zhu L, Mohan AT, Vijayasekaran A, Hou C, Sur YJ, Morsy M, et al. Maximizing the volume of latissimus dorsi flap in autologous breast reconstruction with simultaneous multisite fat grafting. Aesthet Surg J. 2016;36(2):169–78. 17. Olivari N.  The latissimus flap. Br J Plast Surg. 1976;29(2):126–8. 18. Bostwick J, Nahai F, Wallace JG, Vasconez LO. Sixty latissimus dorsi flaps. Plast Reconstr Surg. 1979;63(1):31–41. 19. Economides JM, Song DH.  Latissimus Dorsi and Immediate Fat Transfer (LIFT) for complete autologous breast reconstruction. Plast Reconstr Surg Glob Open. 2018;6(1):e1656. 20. Brondi RS, de Oliveira VM, Bagnoli F, Mateus EF, Rinaldi JF. Autologous breast reconstruction with the latissimus dorsi muscle with immediate fat grafting: long-term results and patient satisfaction. Ann Plast Surg. 2019;82(2):152–7.

Revision Surgery with Fat Grafting After Implant and Flap Breast Reconstruction

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Ara A. Salibian, Jordan D. Frey, and Nolan S. Karp

Key Messages • Fat grafting is a safe adjunctive technique in both implant- and autologous-based revisionary breast reconstruction for the correction of contour deformities and volume discrepancies. • Correction of significant contour deformities and volume deficits often requires multiple treatments, which should be discussed with patients preoperatively. • Marking areas of contour deformities preoperatively, while patients are standing, is critical to define the border of recipient areas that can otherwise become distorted on the operating room table. • Atraumatic technique should be utilized for fat harvest, processing, and deposition with fat transfer in small, even aliquots to maximize viability and minimize resorption and undesired complications.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_84) contains supplementary material, which is available to authorized users. A. A. Salibian · J. D. Frey · N. S. Karp (*) Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, NY, USA e-mail: [email protected]; [email protected]

• Autologous fat transfer is particularly useful for treating superior pole hollowing and implant step-off deformities. • In revision of implant-based reconstruction, fat should be evenly transferred throughout the subcutaneous mastectomy flap plane while avoiding entry into the implant pocket. • New masses or concerning radiographic findings after fat grafting should be evaluated in conjunction with breast surgery, oncology, and radiology teams.

84.1 Introduction Autologous fat grafting has become a widely performed procedure throughout reconstructive breast surgery [1], especially as a tool for revising primary reconstructions. Its safety as an adjunctive technique has been clinically demonstrated in breast surgery [2, 3] as has its efficacy in secondary breast contouring [4]. Autologous fat transfer is of particular utility in correcting contour deformities in both implant- and autologous-­based reconstructions, as well as in addressing volume discrepancies. The applications of fat grafting, however, extend further in revisionary breast surgery and can be used to address multiple additional deformities including rippling, implant palpability and visibility, damaged skin, and overall breast shape.

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Several modifications to the Coleman technique [5] for fat grafting have been described, and many different methods of fat transfer can be utilized successfully in breast reconstruction revisions. Adherence to basic principles of both fat grafting and revision breast surgery is needed to best achieve a natural-looking breast, regardless of the method of reconstruction, while minimizing minor complications and avoiding threatening the reconstruction. Specific transfer techniques can then be tailored to individual deformities to optimize results for each patient. The concept of breast reconstruction beyond solely the primary reconstructive modality has become popularized through the idea of the “bioengineered breast” [6], which combines multiple reconstructive and revisionary tools to achieve the most natural result. Though primarily a thought design for implant-based reconstruction, application of autologous fat transfer to all modalities of breast reconstruction has the ability to provide more natural and aesthetically pleasing results that cannot be achieved with an implant or flap alone. Understanding when fat grafting is needed and how to safely perform fat transfer in the setting of prior reconstruction will allow one to fully maximize the potential of each original reconstructive technique.

84.2 General Techniques and Considerations Fat grafting protocols are similar for revision of both implant and autologous breast reconstructions with minor variances in actual fat transfer to recipient sites. Principles of atraumatic harvest, processing, and transfer are followed in all cases. In general, we prefer to wait a minimum of 3 months after definitive reconstruction to allow for resolution of postoperative edema, softening of tissue, and better appreciation of final contour irregularities that need to be addressed. Prior to surgery, in addition to standard discussion of risks of autologous fat transfer, patients are counseled that some percentage of resorption is guaranteed and that immediate postoperative result will not always reflect the longer

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term outcome. Typically, around 50% of small-­ volume fat grafting to the breast is retained [4]. Patients must be aware that while being a powerful tool, fat grafting often requires multiple consecutive procedures to achieve the desired results, particularly in more dramatic deformities or when trying to correct volume discrepancies. In addition, a preoperative discussion of what deformities can and cannot be addressed with fat grafting is important to set appropriate patient expectations. Finally, patients should be aware that fat necrosis can present as small palpable nodules as this can be alarming in the setting of post-oncologic care. Patients should be counseled that while these are typically benign findings, they should be discussed with their provider postoperatively to determine the need for further workup. Preoperative evaluation of breast deformities amenable to fat grafting should include an analysis of the specific boundaries and depth of the deformity as well as a rough estimate of the volume required to fill the defect. Attention should be focused on individual areas while still taking into account the shape and appearance of the breast as a whole. On the day of surgery, it is important to mark the patient standing preoperatively, to accurately determine the borders of recipient sites that can become distorted with the patient supine. Donor sites for fat grafting should be assessed in conjunction with patient preference. Fat graft retention and viability have not been correlated with specific donor sites [7]. Potential donor sites include the abdomen, flanks, lateral and medial thighs, buttocks, and back. Body habitus, body mass index, and localized adiposity should be assessed to determine which and how many donor sites will be needed to obtain the necessary fat to achieve the desired results. Scars, trauma, and prior surgery should all be taken into account. Patient positioning in the operating room is dependent on donor sites to be harvested and typically is either only supine, or prone followed by supine if the back or buttocks are to be utilized. Fat transfer after harvest is preferentially performed with the patient in the seated position to better visualize preoperative contour deformi-

84  Revision Surgery with Fat Grafting After Implant and Flap Breast Reconstruction

ties and more accurately place fat in the appropriate recipient beds.

84.2.1 Fat Harvesting A tumescent technique [8] is preferred to minimize blood loss. Infiltration access sites are hidden in well-concealed areas (groin creases, bikini line, etc.) and a tumescent solution is infiltrated using a tumescent cannula to an endpoint of tissue turgor and skin blanching. Ideally, liposuction is delayed for at least 15–20  min after tumescence injection to allow for the full vasoconstrictive effect of epinephrine. Handheld or suction-assisted (senior author’s preferred technique) liposuction can be used for fat harvesting. We prefer 3–4  mm liposuction cannulas for efficiency and given the reported beneficial effects of larger cannulas on fat graft viability [8]. Fat harvest is performed from the deep subcutaneous layer of fat to avoid visible skin dimpling and minimize contour deformities, taking care to avoid over-liposuction in a single area. Similarly, areas of fascial adhesions should be avoided to minimize disruption of natural contours. Contour and symmetry are constantly checked to prevent overharvest in a single area.

84.2.2 Lipoaspirate Processing In accordance with guidelines set forth by the Food and Drug Administration, minimal manipulation of the lipoaspirate is performed during the processing phase. Several different methods of lipoaspirate processing are available including centrifugation, telfa rolling, gravity filtration, and hand-washing filtration. Studies have demonstrated conflicting results on the impact of different processing techniques on fat grafting outcomes with regard to volume retention and adverse events [8, 9]. Regardless of the specific method utilized, one should ensure that fat is handled atraumatically, to minimize shear and damage to adipocytes that can subsequently compromise graft retention. The senior author’s preference is to use a combined hand-washing and

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filtration system for autologous fat processing. Fat is then transferred to either 3 or 6 mL syringes depending on the volume of fat to be grafted.

84.2.3 Fat Grafting to Recipient Sites Injection entry sites are marked preoperatively, taking care to ensure that incisions are hidden. Well-concealed areas typically include the inframammary fold, anterior axillary line, and medial and lateral breast folds. Incisions in the upper medial breast should be avoided. Cannula size depends on the area to be grafted; however, 16- or 17-gauge Coleman cannulas with single distal, lateral ports are typically utilized for fat transfer. Injection typically is performed with the patient in the sitting or near-sitting position with the waist flexed to better visualize the preoperative contour deformities. Multiple passes are made during fat transfer with injection of 0.1–0.2  cc with each cannula pass [5]. Layering in small aliquots with an even distribution will maximize contact of the grafted fat with surrounding vascularized tissue and subsequently minimize ischemic complications such as fat necrosis. Care is taken to avoid injection of fat boluses that result in large palpable bumps that are poorly incorporated as well as subdermal injection that can cause visible and palpable deformities. An endpoint of slight overcorrection is usually achieved to account for some fat resorption and contour settling as swelling decreases.

84.2.4 Other Considerations Utilization of additional techniques can be useful to optimize the desired results with fat grafting. Percutaneous rigotomy allows for expansion of the skin envelope previously restricted by scar tethering to fill out contour deformities [10]. This technique is routinely utilized to optimize the recipient bed prior to fat transfer. We prefer to use an 18-gauge hypodermic needle to carefully lyse scar bands and create a more optimal bed for grafted fat. Care must be taken not to injure the implant or create excessive bleeding.

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Fat grafting can also be useful in the setting of prior radiotherapy. Autologous fat transfer has been demonstrated to aid in the treatment of radiation-­ induced tissue damage at a cellular level [11]. Fat grafting in a radiated field, however, must be performed with caution given the poor vascularity of the recipient bed and increased risk of local ischemic complications such as fat necrosis. Multiple rounds of fat grafting are often needed in these situations.

84.3 F  at Grafting After Implant Reconstruction The use of autologous fat to enhance implant-­ based reconstruction is a powerful tool that can help achieve more natural results while overcoming the shortcomings of implants. Autologous fat is typically placed within the subcutaneous layer of the mastectomy flap, taking care to avoid either too superficial or too deep an injection. When fat grafting around an implant, staying out of the implant pocket is critical to best achieve the desired contour results while minimizing the potential for contamination. Fat deposited into the implant pocket is “lost” in a potential space and increases the risks of introducing bacteria around the prosthesis. Damaging the prosthesis with injection cannulas is also possible. The surgeon must constantly be cognizant of the location of the cannula tip to maintain deposition of fat in the subcutaneous plane. The primary role of fat grafting in implant-­ based reconstruction is improving the shape of the breast mound while correcting more focal contour deformities. The most common contour deformity is seen in the upper breast pole. With implant-based reconstruction, and in particular with smooth, round implants, the natural slope of the upper breast is difficult to reconstruct. Often this results in a superior step-off deformity at the transition of the implant and native breast tissue, which is cosmetically unappealing. This deformity is especially apparent in thinner patients or after a more aggressive mastectomy (Fig. 84.1). Fat grafting is an excellent means of blending this transition point to create a smooth slope of

Fig. 84.1  Autologous fat grating in the subcutaneous plane of the superior pole of the breast in prepectoral implant-based breast reconstruction patients can help improve upper pole contour and fullness

the breast and a more natural, aesthetically acceptable result. Contour deformities can also occur secondary to other etiologies. A size discrepancy between the implant and skin envelope will create similar transition points between the prosthesis and native chest wall. Uneven mastectomy flaps can additionally result in unnatural contours, all of which are typically amenable to fat grafting. Implant rippling can be camouflaged with fat grafting in the subcutaneous plane, which can be utilized in combination with other techniques to

84  Revision Surgery with Fat Grafting After Implant and Flap Breast Reconstruction

address this deformity such as implant size and plane change and acellular dermal matrix placement. Autologous fat transfer can also be used to treat implant edge palpability and visibility in areas lacking adequate overlying soft-tissue coverage. Scar contracture deformities of the breast resulting from wound healing issues, fat necrosis, and radiation can also be treated with autologous fat grafting after performing the appropriate release of contracted tissue [12]. Multiple procedures will often be required in these cases to satisfactorily release all scarred tissue and fill in the resultant defects with fat. Size discrepancies often require greater fill volumes and may need multiple treatments. Volume augmentation with fat grafting is more difficult after implant-based reconstruction as opposed to autologous reconstruction given the limited planes for fat placement. Fat transfer can be diffusely injected into the subcutaneous mastectomy flaps and native chest subcutaneous tissue to increase overall volume. Care should be taken to ensure even distribution to preserve natural breast shape. In subpectoral reconstruction, the fat can also be grafted directly into the pectoralis muscle to correct contour deformities and adjust volume. Fat grafting as an adjunctive therapy is particularly useful in prepectoral reconstructions, which are becoming more widely performed. As the additional layer of pectoralis muscle is no longer covering the upper breast as with dual-­ plane and total submuscular reconstruction, the superior pole step-off and hollowness can be more readily noticeable with implant placement above the pectoralis muscle. Lack of upper pole fullness as well as a step-off deformity is a common complaint in prepectoral reconstructions, particularly with thinner patients. Adjunctive fat grafting can be very useful in blending the transition from implant to native chest as well as providing upper pole volume, and is routinely advocated in revisions or at the time of implant exchange after prepectoral reconstruction [13]. However, caution must be taken in low-BMI patients with thin mastectomy flaps as the potential recipient space for fat transfer is limited with

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Fig. 84.2  Appropriate upper pole contour in prepectoral implant-based breast reconstruction can be difficult to achieve in thin patients. A step-off deformity of the superior pole can be noted in such patients

only a minute distance between the skin and implant capsule (Figs. 84.2 and 84.3).

84.4 F  at Grafting After Autologous Reconstruction Secondary fat grafting after microsurgical breast reconstruction has also been shown to be a useful technique for refinement of free flap reconstruction with low complication rates [14]. Autologous fat transfer in these cases can similarly be used for correction of contour deformities. For example, rib harvest for recipient vessel exposure can result in medial chest depressions that can be

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Fig. 84.3  Preoperative (above) and postoperative (below) photographs of a patient with prior implant-based breast reconstruction after fat grafting. 30 cc and 40 cc of autolo-

gous fats were injected in the subcutaneous plane of the right and left breasts, respectively, to improve upper pole contour

treated with fat grafting. Autologous fat transfer can also be used to help blend the flap into the native footprint of the breast. Step-offs between the edges of the flap and the native breast skin, particularly with thinner mastectomy flaps or excessive lateral and superior dissection, can create transition points that respond well to release and filling. Fat necrosis and subsequent liquification or excision can also result in defects and subsequent contour deformities. Fat grafting can later be used to restore contour in these areas; however, extra care must be taken to ensure transfer of small, evenly layered aliquots and to avoid overfilling given the inherent ischemic nature of the recipient bed. Volume augmentation is additionally achievable with fat grafting after autologous reconstruction. Fat can be transferred into the mastectomy flaps, the flap itself, or the pectoralis major to increase volume. As with implant-based reconstruction, scar contractures secondary to local postoperative tissue complications or radia-

tion therapy can also be filled with autologous fat grafting.

84.4.1 Postoperative Care Patients are typically discharged home on the same day of surgery with pain medications and a short course of oral antibiotics for implant-based revisions. Pressure on the recipient sites is avoided for 6 weeks postoperatively and patients typically return to normal activities after 2 weeks. Compression garments can be used for donor sites as needed.

84.5 Complications The most common complications after fat grafting are minor, local sequelae of fat deposition including oil cysts and fat necrosis [3, 15]. We have found an overall rate of complications of

84  Revision Surgery with Fat Grafting After Implant and Flap Breast Reconstruction Table 84.1 Characteristics and complications after autologous fat grafting in breast reconstruction Patients Agea BMIa Oil cyst Wound healing delay Fat necrosis Major infection Minor infection

n (%) 234 47.8 25.3 14 (6.0) 1 (0.4) 3 (1.3) 2 (0.9) 2 (0.9)

BMI body mass index Adapted from Cohen et al. [3] a Mean

9.4% out of 234 cases of autologous fat grafting after breast reconstruction at our institution [3]. Of these, the majority were oil cysts (6.0%) with a fat necrosis rate of 1.3% (Table  84.1). Fat necrosis can be minimized by avoiding transfers of large aliquots and evenly distributing fat throughout the recipient bed. While these complications are typically of little clinical consequence, they can be a nuisance to both patient and provider if they result in palpable masses or imaging findings that result in concern for neoplastic changes or instigate additional workup. Studies have demonstrated fewer radiographic abnormalities with fat grafting compared to other common breast surgeries [16]. Following a stepwise algorithm for management of concerning clinical and radiographic findings is critical [17]. Communication with the breast surgeon, oncologist, and radiologist in the postoperative period is equally important for the optimal management of fat grafting patients in the oncologic setting. Undercorrection of the deformity is likely the most common postoperative complaint. Patient should be counseled preoperatively on resorption and high likelihood of needing multiple procedures to achieve the desired results. Other complications are rare and include infection, contour deformities, hematoma, implant rupture, pedicle damage, and pneumothorax. Donor-site complications are similarly rare and include contour deformities, asymmetry, hematoma, paresthesias, infection, and inadvertent trauma to intra-­ abdominal structures.

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84.6 Conclusion Fat grafting is a powerful tool in the revision of both implant and autologous breast reconstruction. Contour deformities are most readily addressed using fat transfer, though correction of volume discrepancies, skin quality, implant camouflage, and breast shaping are all achievable with autologous fat grafting. Fat grafting has been particularly useful in augmenting soft-tissue coverage and ameliorating step-off deformities with the re-emergence in popularity of prepectoral implant placement. Multiple procedures are often required in more difficult cases, taking into account resorption rates as well as the importance of avoiding overinjection to decrease the risk of fat necrosis. Adherence to the basic principles of atraumatic fat harvest, processing, and transfer, as well as proper assessment and understanding of the deformities to be corrected, will allow the surgeon to maximize the efficacy of this technique while minimizing any associated complications.

References 1. Kling RE, Mehrara BJ, Pusic AL, et  al. Trends in autologous fat grafting to the breast: a national survey of the American Society of Plastic Surgeons. Plast Reconstr Surg. 2013;132:35–46. 2. Gutowski KA, Force AFGT.  Current applications and safety of autologous fat grafts: a report of the ASPS fat graft task force. Plast Reconstr Surg. 2009;124:272–80. 3. Cohen O, Lam G, Karp N, Choi M. Determining the oncologic safety of autologous fat grafting as a reconstructive modality: an institutional review of breast cancer recurrence rates and surgical outcomes. Plast Reconstr Surg. 2017;140:382e–92e. 4. Choi M, Small K, Levovitz C, et al. The volumetric analysis of fat graft survival in breast reconstruction. Plast Reconstr Surg. 2013;131:185–91. 5. Coleman SR.  Structural fat grafting: more than a permanent filler. Plast Reconstr Surg. 2006;118:108S–20S. 6. Maxwell GP, Gabriel A.  Bioengineered breast: concept, technique, and preliminary results. Plast Reconstr Surg. 2016;137:415–21. 7. Rohrich RJ, Sorokin ES, Brown SA.  In search of improved fat transfer viability: a quantitative analysis of the role of centrifugation and harvest site. Plast Reconstr Surg. 2004;113:391–5; discussion 396–397.

1284 8. Strong AL, Cederna PS, Rubin JP, Coleman SR, Levi B. The current state of fat grafting: a review of harvesting, processing, and injection techniques. Plast Reconstr Surg. 2015;136:897–912. 9. Ruan QZ, Rinkinen JR, Doval AF, et al. Safety profiles of fat processing techniques in autologous fat transfer for breast reconstruction. Plast Reconstr Surg. 2019;143:985–91. 10. Khouri RK, Smit JM, Cardoso E, et al. Percutaneous aponeurotomy and lipofilling: a regenerative alternative to flap reconstruction? Plast Reconstr Surg. 2013;132:1280–90. 11. Rigotti G, Marchi A, Galie M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg. 2007;119:1409– 22; discussion 1423–1404. 12. Momoh AO, Colakoglu S, de Blacam C, Curtis MS, Lee BT.  The forked liposuction cannula: a novel approach to the correction of cicatricial contracture deformities in breast reconstruction. Ann Plast Surg. 2012;69:256–9.

A. A. Salibian et al. 13. Sbitany H, Lee KR.  Optimizing outcomes in 2-stage prepectoral breast reconstruction utilizing round form-stable implants. Plast Reconstr Surg. 2019;144:43S–50S. 14. Weichman KE, Broer PN, Tanna N, et al. The role of autologous fat grafting in secondary microsurgical breast reconstruction. Ann Plast Surg. 2013;71:24–30. 15. Kaoutzanis C, Xin M, Ballard TN, et al. Autologous fat grafting after breast reconstruction in postmastectomy patients: complications, biopsy rates, and locoregional cancer recurrence rates. Ann Plast Surg. 2016;76:270–5. 16. Rubin JP, Coon D, Zuley M, et  al. Mammographic changes after fat transfer to the breast compared with changes after breast reduction: a blinded study. Plast Reconstr Surg. 2012;129:1029–38. 17. Knackstedt RW, Gatherwright J, Ataya D, Duraes EFR, Schwarz GS.  Fat grafting and the palpable breast mass in implant-based breast reconstruction: incidence and implications. Plast Reconstr Surg. 2019;144:265–75.

Safety of Autologous Fat Transplantation in Oncological Postmastectomy Breast Reconstruction: A Prospective Study

85

Fabio Santanelli di Pompeo, Benedetto Longo, and Michail Sorotos

Key Messages • Autologous fat transplantation can be used either alone or together with other reconstructive autologous, implant-based, or mixed procedures. • Concerns regarding the oncological safety of AFT are based on experimental studies. • Results of experimental studies have not yet been translated into concrete results in clinical studies.

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-­3-­030-­77455-­4_85) contains supplementary material, which is available to authorized users. F. Santanelli di Pompeo (*) Department of Plastic Surgery, University of Rome, Rome, Italy e-mail: [email protected] B. Longo Division of Plastic and Reconstructive Surgery, Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy M. Sorotos Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, PhD School of Translational Medicine of Development and Active Ageing, University of Salerno, Salerno, Italy e-mail: [email protected]

• As of today, clinical evidence points towards the safety of autologous fat transplantation. • Further research is needed to clarify the oncological safety of AFT.

85.1 Introduction Autologous fat transplantation (AFT) is nowadays considered an important tool in postmastectomy breast reconstruction [1, 2]. It can be used either alone or together with other reconstructive techniques, autologous, implant based, or mixed. The first report of AFT dates to 1893, when the German surgeon Gustav Neuber described the technique of fat grafting beneath atrophic scars [3]. Soon after, Vincent Czerny proposed the use of AFT in breast surgery by using a lipoma to reconstruct a postmastectomy defect [3]. It was not until 1997, when Coleman et al. described a new technique regarding fat harvesting, purification, and injection, that AFT was diffused and became a mainstream tool in plastic and reconstructive surgery [4]. Despite its popularity, AFT immediately raised concerns regarding its negative influence on postoperative imaging controls. It was considered that necrosis or calcification of AFT might simulate or hide cancer, although prospective studies have demonstrated the opposite [5]. At

© Springer Nature Switzerland AG 2022 A. Kalaaji (ed.), Plastic and Aesthetic Regenerative Surgery and Fat Grafting, https://doi.org/10.1007/978-3-030-77455-4_85

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the same time, it has been postulated that an interaction between adipocytes, adipokines, and stroma can be a potential actor in breast cancer tumorigenesis [6]. Also, currently there are still concerns regarding adipose-derived mesenchymal stem cells (ADMSCs) that play a crucial role in the restorative process of AFT making this procedure so successful in breast reconstruction, and their interaction with breast cancer cells. ADMSCs secrete growth factors, cytokines, and chemokines that sustain an inflammatory state whose interaction with microenvironments of wounds and tumors could contribute to the progression of tumor genesis and metastasis [7]. This chapter presents current indications and applications of AFT for breast reconstruction, oncological risk of this procedure after breast cancer surgery, and results of our prospective study on the safety and effectiveness on the use of AFT in postmastectomy breast reconstruction patients.

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parison with the same technique without fat grafting, no additional take-backs and no prolonged total treatment period were required to achieve pleasing aesthetic results [1]. In 2014, we presented breast reconstruction with the latissimus dorsi flap and immediate AFT without implants for complete autologous reconstruction of small- to medium-sized breasts with inadequate abdominal donor area for DIEP flap breast reconstruction [2]. Surgery can be done under local anesthesia with sedation or general anesthesia and duration of surgery ranges from 1 h to more based on other adjunctive procedures. Local anesthesia is used to infiltrate the access points followed by a small incision of 2–3 mm of length near the donor area. We usually use basket cannulas of 2.4  mm and syringes of 10 cc to aspirate fat. The fat collected is then being centrifuged according to “Coleman” technique. Fat is infiltrated in the recipient area by 1 cc syringes with the simplified lipostructure technique that uses a three-way connector to create a sterile connection of a 1 cc syringe, a 10 cc 85.2 Autologous Fat syringe, and the infiltration cannula [8]. Complications of this procedure include fat Transplantation and Breast resorption, infection, aesthetic irregularities, and Reconstruction fat embolism. While AFT seems to be a very simAutologous fat transplantation can be used for ple procedure the unpredictable retention rates both total and partial breast reconstruction. have led to investigations into the effects of each Breast reconstruction with AFT is indicated when part of the process, aspiration, processing, and the surgical defect is due to a quadrantectomy, for infiltration. Fat resorption depends on many varitotal breast reconstruction following nipple-­ ables such as infiltration technique, patient’s sparing mastectomy (NSM) in women with characteristics, and previous radiotherapy. In our small- to medium-volume breasts, and when study we aimed to define a fat grafting protocol patients ask for liposuction. On the other hand, for successful reconstruction following NSM and AFT is contraindicated in women with big breasts to assess its reliability in irradiated and nonirradithat would necessitate a big number of AFT ses- ated patients. Twenty-one patients were prospecsions, when the patient does not have representa- tively enrolled and stratified in Group A (11 tive donor sites with sufficient adipose tissue. nonirradiated) and Group B (10 irradiated) NSMs AFT can be used to offer aesthetic refinements to comparing clinical and aesthetic outcomes. The other types of breast reconstruction and for vol- groups were homogeneous in terms of demoume increase of the vascularized autologous graphics (p  >  0.05), while number of sessions, matrix (DIEP, TRAM, SIAE, LD, TDAP). In mean volume of the first two treatments, and 2015, we presented our experience in delayed overall injected volume showed significant difaugmented DIEP flaps with large fat-volume ferences (p  4  mm diameter) seemed to have a protective effect [1] (Box 91.1). The Inter Society Gluteal Fat Grafting Task Force (ISGFGTF) followed swiftly with an advisory that all GAFG should be done in the subcutaneous plane. Nonetheless, after the advisory was issued there have been at least 10 additional GFG deaths in the state of Florida alone. Investigation of these cases had surprising revelations. First of all, the assumption that large cannula size conferred a protective effect was debunked. Large cannulas (>4 mm diameter) were used in all the mortality cases subsequent to the ASERF recommendations.

Box 91.1 Mortality

Gluteal Augmentation by Fat Graft (GAFG) has the highest mortality rate of any esthetic Plastic Surgery Procedure.

Contrary to assumptions that deaths were related to improperly trained surgeons doing the procedure, several Board-Certified Plastic Surgeons also had fatalities. More troubling is the assertion by some of these well-trained surgeons that they had intended to inject in the subcutaneous space. How can a well-trained surgeon avoid submuscular injection and injury to the inferior gluteal vein in what is essentially a blind procedure? (Box 91.2). In 2018, the ISGFGTF organized a large cadaveric demonstration with an international cast of expert injectors to study the safety of various injection techniques. The first author was chosen as one of the injectors,

and the only one using a 5 mm diameter) and injecting them in large depots into the buttocks. The work of Yoshimura [18] demonstrates zones of survival in a fat graft and provides experimental confirmation that small ( 32 kg/m2 Age older than 60 year old Hemoglobin level > 12 mg/dl Additional risk factors? Other:

Yes No

More than three affirmative answers: Careful evaluation and risk assessment More than five affirmative answers: Surgery must be delayed/canceled

importantly, those who must not be operated, are the first measures we must take. Particular care should be taken with patients who present a condition that increases the risk of thromboembolic events [3, 4]. Avoid surgery in patients with history of thromboembolic events or thrombophilia. Delay surgery in patients with a recent hospitalization (less than a month) for at least 2 months. On the initial assessment, if the Caprini score (Table 96.2) is greater than 6, then surgery should be deferred until the risk factors are controlled [3, 4]. Patients who have traveled more than 6  h should delay surgery at least 5  days after the flight [3, 4]. For DVT prophylaxis in candidates for surgery, we suggest the administration of low molecular-weight heparin (Enoxaparin: 0.5–1  mg/kg/day) subcutaneously for 7  days if the Caprini score is less than 6. For all patients, Intermittent pneumatic compression boots are used during the entire procedure as well as immediate postoperative compression stockings for 6–11  days; since the use of LMWH or unfractionated heparin plus mechanical prophylaxis has been shown to be more effective in preventing VTE in patients than LMWH alone (Table 96.3). Patients older than 60  years old and patients with BMI greater than 32 should be excluded from high-definition liposculpture. For patients

96  Safety for Advanced Body Contouring: The Darkest Hour Table 96.2  Caprini Risk Assessment model 1 point

2 points

3 points

•  Age 41–60 years •  Varicose veins •  History of inflammatory bowel disease • Obesity •  Sepsis (