Focused Ultrasound Surgery in Gynecology: Introduction and Application 9811609381, 9789811609381

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Focused Ultrasound Surgery in Gynecology Introduction and Application Felix Wong Lian Zhang Zhibiao Wang

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Focused Ultrasound Surgery in Gynecology

Felix Wong • Lian Zhang • Zhibiao Wang

Focused Ultrasound Surgery in Gynecology Introduction and Application

Felix Wong School of Women’s and Children’s Health The University of New South Wales Sydney NSW Australia

Lian Zhang College of Biomedical Engineering Chongqing Medical University Chongqing China

Zhibiao Wang College of Biomedical Engineering Chongqing Medical University Chongqing China

ISBN 978-981-16-0938-1    ISBN 978-981-16-0939-8 (eBook) https://doi.org/10.1007/978-981-16-0939-8 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 This work is subject to copyright. All rights are solely and exclusively licensed 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Foreword

This book is an eye-opening science book blending cutting-edge science and technology with profound humanity. The book opens with a description of the Haifu® Focused Ultrasound Tumor Therapeutic System. In doing so, the author arouses readers’ attention to practical clinical issues while guiding them on a fascinating science and technology journey. Tracing the arduous path leads to this hard-won breakthrough in modern science and technology. The book represents a significant milestone in the acceptance and popularization of therapeutic HIFU. That is where the value and readability of this book lie. According to Hippocrates of Kos, Father of Medicine, in treating diseases, iron is applied when drugs fail, and fire is applied when the iron fails. Application of iron can deem to be surgery, while utilization of fire can deem to be the medical application of various energies. Haifu® Focused Ultrasound Tumor Therapeutic System is, in essence, a form of energy. Hippocrates also cautioned doctors, “First, do no harm!” is a universally applicable maxim. Therefore, we promote and practice minimally invasive and noninvasive medicine. Haifu® Focused Ultrasound Tumor Therapeutic system is the embodiment of minimally invasive and noninvasive medicine. Mastery of this state-of-the-art minimally invasive and noninvasive technology, a superior weapon against diseases, marks a great leap forward in our strive towards the ultimate goal of “protecting patients’ physical organs, tissues, functions, and mental well-being.” When it comes to treating diseases, including gynecologic tumor treatment, we advocate and abide by the principle of standardized, individualized, humane, and minimally invasive treatment. Furthermore, this rationale conforms to the treatment with Haifu® Focused Ultrasound Tumor Therapeutic System. Particular attention must be given to two types of information, i.e., information on the tumor(s) and information about the patient. Information on the tumor includes the symptoms, sizes and numbers, the effect, and the tumor’s characters. Information about the patient consists of her age, mind, emotion, desires, wishes, marital and fertility status, past health, and family background. Therapies and treatment methods based on these two types of information maximize the benefit of treatment and minimize its harm to patients. v

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The range of applications of the Haifu® Focused Ultrasound Tumor Therapeutic Systems is increasingly more extensive now. In addition to uterine fibroids, adenomyosis, C-scar pregnancy, it is also used to manage other solid tumors such as liver cancer, pancreatic cancer, and retroperitoneal sarcoma. Experience in treating uterine fibroids and adenomyosis with Haifu® Focused Ultrasound Tumor therapeutic system is particularly abundant and fruitful. To date, encouraging long-term treatment outcomes of a 20-center study of HIFU ablation on fibroids have been published in a well-known international journal and a monograph on the HIFU ablation on adenomyoma. The related major project accomplishment release conferences and international academic exchanges have won intense attention and high acclaims worldwide. The experience in treating uterine fibroids with Haifu® Focused Ultrasound Tumor Therapeutic System has awakened us to realize that humanity or humanistic ideology ought to be the guiding morality (philosophy) for medical treatment. In her constant reminder to doctors, Prof. Qiaozhi LIN, pioneer of modern gynecology and obstetrics in China, delivered a similar message, “There are times when you have healed the disease, but the patient does not necessarily feel happy, and worse than that, she/he may become even more anxious and painful, even though HIFU ablation has cured her/his disease. Therefore, we should have overall considerations for the patient.” Victor Bonny, an excellent British gynecologist, also said, “Removing the uterus of a dozen women just because of a benign uterine fibroid is nothing short of a complete surgical failure.” Humanity requires doctors to respect people and respect patients. By protecting their organs, tissues, functions, and mental well-being, we pay our patients the highest possible respect. This medical practice answers patients’ needs as a patient, a woman, and a mother and meets the expectations of the nation, communities, and individuals. It must, therefore, be our lifelong pursuit. Resection or preservation of the organ depends, among other factors, on indications and contraindications. We must avoid rash decisions to resect or preserve an organ. Any such procedure must be with sound evidence and a comprehensive evaluation of the actual situation. The surgical procedure is a technique, and more importantly, a Philosophy and an Art. Sir William Osler, a great medical educator, cautioned that we should avoid the separation of science from humanity and the isolation of technological advancement from humanitarianism. Readers would be delighted to learn that this “Made in China” Haifu® system has been exported to more than 26 countries and regions, benefiting people worldwide. A crown jewel among China’s self-made large medical devices, the Haifu® Focused Ultrasound Tumor Therapeutic System is exactly “China made” and a spirited Chinese brand. Finally, I am happy to introduce Prof. Felix Wong, the lead author of this book, to our readers. Prof. Wong is a gynecological expert, well-known at home and abroad. With a great zest for gynecology and obstetrics in mainland China, he has been actively engaged in academic exchanges, cultivating young doctors and

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promoting good practice in management. We honored him with the Chinese Obstetricians and Gynecologists Association Award (Lin Qiaozhi Award). I want to conclude by congratulating Prof. Felix Wong on successfully completing the first science book introducing high intensity focused ultrasound ablation surgery and applying Haifu® Focused Ultrasound Tumor Therapeutic Systems. Jinghe Lang Chinese Obstetricians and Gynecologists Association China

Preface

This book is written because of the surprise realization that high intensity focused ultrasound ablation surgery (HIFU ablation surgery) would significantly impact operative surgery, especially in Obstetrics and Gynecology. It is an innovative surgery that has been invented and developed in China with recent rapid growth and recognition. It has greatly benefited women with this noninvasive surgery that had remained largely unknown in the western world. The technology involves the destruction of solid tumors, either benign or malignant, by focused ultrasound energy that can penetrate the human body without even a wound in the skin. Despite more than 10 years of intensive research and many publications, hardly any textbook has been written on this topic. Fewer western doctors realize its great potential in managing women with fibroids and adenomyosis and preserving the reproductive functions and organs. After learning from the inventor Professor Zhi Biao Wang, the co-editor of this book, one gradually realizes that because HIFU ablation surgery is not a traditional surgical approach introduced to China from western countries, HIFU ablation surgery took a long time to be recognized and endorsed by the majority of doctors in our O&G fields in China, not to say to doctors in the western countries. Times are to change now, and it is because more and more doctors recognize this new technology, and now up to 26 countries had imported the machine and started treating patients with this surgical approach. However, compared to the number of patients with fibroids and adenomyosis, who might benefit from this noninvasive approach, there are still more patients treated with hysterectomies or myomectomy either by laparoscopy or open surgery. The popularity and impact of this new technology are still minimal, as it is just the beginning. Another major problem of this new technology is the lack of understanding of its merits among doctors and laypeople. It was similar to the beginning of adopting minimally invasive surgery (MIS), which had encountered many disbelief and obstacles among our medical professionals. Only when the demands from patients who had learned of the minimally invasive surgery, the attitudes of surgeons, the governments, and the industries change to endorse minimally invasive surgery. Now MIS becomes a standard approach that benefits women requiring surgery. Therefore, with the staff’s support at HAIFU Medical Technology Company Ltd. and with the information provided from their publications, we manage to coordinate

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the writing of this first introductory book on HIFU ablation surgery in Obstetrics and Gynecology. Compared with minimal access surgery, high intensity focused ultrasound ablation surgery is a clean surgery without smoke or radiation, no medical waste, no blood loss, no leaking of anesthetic gas, and no sharps or chemicals. While patients do not need general anesthesia, enjoy quick recovery to normal activities, no loss of working hours, best of all, many will have their problems solved with one or two hours of noninvasive HIFU ABLATION surgery. Hopefully, this book can also clarify the differences of HAIFU @knife with other increasing non-HIFU ablation products in the China market. Many machines are hyperthermia machines that cannot produce the same therapeutic effects to ablate effectively many solid tumors. On the contrary, they may produce more harm like skin burn, nerve, bladder, and bowel injuries. Without proper documentation in their uses as written in our books, HIFU’s applications and complications might not be known. HIFU may produce side effects impacting the excellent reputation of this noninvasive approach. This book introduces HIFU ablation applications in O&G without too many details in its technology and procedures. Hopefully, it will enable the laypeople to understand this new surgical approach in managing fibroids, adenomyosis, and other gynecological conditions that HIFU can treat. Although this introductory book may appear to be biased, mainly on the products from Chongqing HAIFU Medical Technology Co. Ltd., there is scanty information from other similar HIFU products in the market. We aim to introduce this new HIFU technology without comparing it with other products, thus our apologies for the incompleteness and unbalance in our information. Hopefully, this book may arouse the laymen and young medical professionals interested in this HIFU technology as a noninvasive HIFU ablation approach in their future career development. Sydney, NSW, Australia Chongqing, China  Chongqing, China 

Felix Wong Lian Zhang Zhi Biao Wang

Declaration of Interest

The experience and knowledge presented in this book was based on the equipment of CQ HAIFU Medical Technology Company Ltd., which may be different from how the HIFU ablation is done using equipment from other companies. Professor Felix Wong is an honorary Professor of the Chongqing Key Laboratory of Ultrasound in Medicine and Engineering and has no relevant financial interests to disclose. Professor Zhibiao Wang is the inventor of the HIFU tumor therapeutic systems in China and on the board of directors of CQ HAIFU Medical Technology Company. He receives salary as a member of the board of directors. Professor Lian Zhang is a Professor at the Chongqing Key Laboratory of Ultrasound in Medicine and Engineering and receives salary from Medical Director of CQ HAIFU Medical Technology Company where he is the Medical Director.

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Contents

1 An Introduction������������������������������������������������������������������������������������������   1 1.1 The HAIFU Knife® ����������������������������������������������������������������������������   2 1.2 The “HAIFU Knife®”��������������������������������������������������������������������������   3 1.2.1 Other Focused Ultrasound Equipment Systems in the Market ��������������������������������������������������������������������������   4 1.2.2 Ultrasound-Guided (USg) HIFU Systems������������������������������   4 1.3 MRgHIFU Systems����������������������������������������������������������������������������   5 1.4 Focused Ultrasound Hyperthermia Therapy and High Intensity Focused Ultrasound Ablation����������������������������������������������  10 1.5 Conclusion������������������������������������������������������������������������������������������  11 References����������������������������������������������������������������������������������������������������  12 2 Sedation and Analgesia for HIFU Ablation ��������������������������������������������  13 2.1 The Choice of Drugs for Sedation and Analgesia������������������������������  13 2.2 First-Line Drugs����������������������������������������������������������������������������������  14 2.3 Second-Line Drugs ����������������������������������������������������������������������������  15 2.4 Other Auxiliary Drugs Should Be Available��������������������������������������  16 2.4.1 Sedation and Analgesia Protocol for HIFU Ablation��������������  17 2.5 Midazolam and Fentanyl Sedation Protocol ��������������������������������������  17 2.6 Other Sedation and Analgesic Regimes: Dexmedetomidine and Remifentanil Sedation Protocol ��������������������������������������������������  18 2.7 Monitoring During HIFU Surgery Under Sedation����������������������������  18 2.8 Treatment of Complications����������������������������������������������������������������  19 2.8.1 Respiratory Depression����������������������������������������������������������  19 2.8.2 Muscle Stiffness����������������������������������������������������������������������  20 2.9 Factors Affecting the Effects of Sedation and Analgesia��������������������  20 References����������������������������������������������������������������������������������������������������  21 3 Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis������  23 3.1 Imaging for Uterine Fibroids��������������������������������������������������������������  23 3.1.1 Ultrasound Imaging����������������������������������������������������������������  23 3.2 Locations of Fibroids��������������������������������������������������������������������������  26 3.2.1 MRI Imaging��������������������������������������������������������������������������  26 3.3 Uterine Adenomyosis��������������������������������������������������������������������������  29

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3.4 Transvaginal Ultrasound Appearances of Adenomyosis��������������������  30 3.5 MRI Appearances of Adenomyosis����������������������������������������������������  31 3.6 Leiomyosarcoma and Endometrial Stromal Sarcoma—MRI Features ����������������������������������������������������������������������������������������������  34 References����������������������������������������������������������������������������������������������������  34 4 Uterine Fibroids and HIFU Ablation ������������������������������������������������������  37 4.1 Symptoms of Uterine Fibroids������������������������������������������������������������  37 4.2 Indications for Treatment��������������������������������������������������������������������  38 4.3 Investigative Methods ������������������������������������������������������������������������  39 4.4 Treatments������������������������������������������������������������������������������������������  40 4.5 HIFU Treatment����������������������������������������������������������������������������������  42 4.6 The USgHIFU Ablation Procedure����������������������������������������������������  43 4.7 The Indications for HIFU Treatment��������������������������������������������������  45 4.8 The Contraindications for HIFU Ablation������������������������������������������  46 4.9 Preparation Before HIFU Ablation ����������������������������������������������������  47 4.9.1 Simulation Test ����������������������������������������������������������������������  47 4.10 Other Preparations������������������������������������������������������������������������������  48 4.11 HIFU Ablation������������������������������������������������������������������������������������  49 4.12 Factors Influencing HIFU Effectiveness ��������������������������������������������  50 4.13 The Types and Locations of Fibroids that Affect HIFU Ablation������  51 4.14 Assessment of the Effectiveness of the Ablation at the End of HIFU Ablation Procedure��������������������������������������������������������������  53 4.15 Post-HIFU Ablation Care��������������������������������������������������������������������  53 4.16 Postoperative Follow-up ��������������������������������������������������������������������  54 4.17 Results of HIFU Ablation on Follow-up��������������������������������������������  54 4.17.1 The Non-perfused Volume Ratio��������������������������������������������  54 4.17.2 The Volume Reduction After HIFU Ablation ������������������������  55 4.18 Other Issues of Fibroid Ablation��������������������������������������������������������  57 4.19 Recurrence of Fibroids������������������������������������������������������������������������  59 4.20 Pregnancy After HIFU Ablation ��������������������������������������������������������  59 References����������������������������������������������������������������������������������������������������  60 5 Adenomyosis and HIFU Ablation������������������������������������������������������������  63 5.1 The Symptoms of Adenomyosis ��������������������������������������������������������  64 5.2 Treatment of Adenomyosis ����������������������������������������������������������������  64 5.2.1 Drug Treatment ����������������������������������������������������������������������  64 5.2.2 Surgical Treatment������������������������������������������������������������������  65 5.2.3 Bilateral Uterine Artery Embolization (UAE)������������������������  66 5.2.4 High Intensity Focused Ultrasound (HIFU) Therapy ������������  66 5.3 Factors Influencing HIFU Effectiveness for Adenomyosis Treatment are Listed as Follow����������������������������������������������������������  67 5.4 Advantages of HIFU Treatment for Adenomyosis ����������������������������  67 5.5 Pregnancy��������������������������������������������������������������������������������������������  69 References����������������������������������������������������������������������������������������������������  69

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6 Complications of HIFU Ablation��������������������������������������������������������������  71 6.1 Fever����������������������������������������������������������������������������������������������������  72 6.2 Pain ����������������������������������������������������������������������������������������������������  72 6.3 Skin Burn Injury ��������������������������������������������������������������������������������  73 6.4 Urinary Tract Injury����������������������������������������������������������������������������  74 6.5 Bowel Injury ��������������������������������������������������������������������������������������  75 6.6 Vaginal Bleeding or Discharge ����������������������������������������������������������  76 6.7 Other Rare Complications or Those Not Reported����������������������������  76 References����������������������������������������������������������������������������������������������������  78 7 Fertility and Pregnancy After HIFU Ablation����������������������������������������  81 7.1 The Reproductive Impact After HIFU Ablation for Uterine Fibroids����������������������������������������������������������������������������  81 7.1.1 HIFU Impact on Ovarian Functions ��������������������������������������  84 7.1.2 HIFU Impact on Uterine Function������������������������������������������  84 7.1.3 Risks of Miscarriage After HIFU Ablation����������������������������  84 7.1.4 The Cesarean Section Rate After HIFU Ablation ������������������  85 7.2 The Reproductive Impact After HIFU Ablation for Adenomyosis������  85 7.3 Conclusion������������������������������������������������������������������������������������������  86 References����������������������������������������������������������������������������������������������������  87 8 Other Issues of HIFU Treatment��������������������������������������������������������������  89 8.1 MRI-Guided and Ultrasound-Guided HIFU Ablation������������������������  89 8.2 HIFU Ablation and HIFU Hyperthermia��������������������������������������������  90 8.3 Malignant Fibroids������������������������������������������������������������������������������  90 8.4 Multiple Fibroids��������������������������������������������������������������������������������  91 8.5 The Cost of HIFU Treatment��������������������������������������������������������������  91 References����������������������������������������������������������������������������������������������������  92 9 Other HIFU Ablation Applications in Gynecology and Related to Obstetrics������������������������������������������������������������������������������������������������  93 9.1 Abnormal Placenta Attachment—Placenta Accreta����������������������������  93 9.2 Cesarean Scar Pregnancy (CSP) ��������������������������������������������������������  96 9.3 Abdominal Wall Endometriosis����������������������������������������������������������  98 References���������������������������������������������������������������������������������������������������� 100

About the Authors

Felix Wong  is at present the Adjunct Professor at the University of New South Wales. He was the past Professor and Medical Director of Liverpool Hospital in Sydney, Australia. He had contributed to medical education in Asia Pacific Countries over the past 30 years. In recognition of his contributions to teaching, he received many awards and honors. In 2009, he received the Endos Award in Medical Science and Technology, China, for his excellent achievement in Endoscopic surgery. In 2017, he was granted Lin Qiaozhi Cup by the Chinese Obstetricians and Gynecologists Association (COGA) to recognize his significant contribution to obstetrics and gynecology in China. In 2017, he was honored with Lifetime Achievement Award by Asia-Pacific Association for Gynecologic Endoscopy and Minimally Invasive Therapy (APAGE). In 2018, he was awarded by the European Society for Gynecological Endoscopy (ESGE) for Outstanding Contribution Award. Professor Wong had edited 14 medical books and had published more than 200 papers in  local and international journals. He is currently the Chairman of the China-Asia Pacific Association of Minimally Invasive Gynecologic Oncologists (CA-AMIGO) and Foundation Chairman of China-Australia-Asia Pacific Forum of Minimally Invasive Surgery and Vice President of the World Association of Chinese Obstetricians and Gynecologists. Despite his unique endoscopic contributions, he continues to contribute towards the development of HIFU education and services in China and Asia Pacific Areas.

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About the Authors

Lian  Zhang  graduated from Chongqing Medical University in 1987, studied in UCSD in 1998, and, after returning to China in 2004, worked in the Oncology Center of the Second Hospital Affiliated to Chongqing Medical University. He was one of the chief researchers working to develop HIFU (highintensity focused ultrasound) system. He was in charge of (or participated in) multiple scientific research projects. He was awarded multiple city-level and nationallevel scientific awards. Over the last 10  years, he was at CIRSE, WCIO, SIUMB, PARIS, and among others, as an invited speaker. Prof. Lian Zhang’s research areas and interests extend to anatomy, molecular biology, molecular genealogy, oncology, etc. He has published more than 80 papers in the peered review journals such as Acta Obstet Gynecol Scand., BJOG., Int J Gynaecol Obstet., Circulation, Journal of Clinical Investigation, Radiology, European Radiology, European Journal of Radiology, American Journal of Roentgenology, Ultrasounics Sonochemistry, International Journal of Hyperthermia and Medicine. He is now responsible for training HIFU surgeons or physicians worldwide. He is currently the Secretary General of the International Society of Minimally Invasive and Virtual Surgery, the Secretary General of the Minimally Invasive and Noninvasive Medical Committee of Chinese Medical Doctor Association. He serves as a section editor of the International Journal of Hyperthermia. Zhi Biao Wang, MD, PhD  Professor of ObGyn and Biomedical Engineering, PhD student supervisor, Senior Consultant of ObGyn, Chongqing Medical University; Director of the National Engineering Research Center of Ultrasound Medicine (NERCUM), and the State Key Laboratory of Ultrasound in Medicine and Engineering, respectively; Council member of the International Society of Minimally Invasive and Virtual Surgery (ISMIVS). Professor Wang is the Principal Investigator of the research grant awarded by the National Key Basic Research and Development Program (973 Program) in 2010 and the special fund for the Development of major Scientific Research Equipment awarded by the National Natural

About the Authors

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Science Foundation of China. He was the recipient of the National Science Fund for Distinguished Young Scholars, the second prize of the State Technological Invention Award in 2000, the HLHL (HO LEUNG HO LEE) Advancement Prize in 2008, the second prize of the National Science and Technology Progress Award in 2010, and the National Innovation Award in 2020. Prof. Wang has devoted for decades to the development and clinical implementation of minimally invasive and noninvasive treatment of common gynecological diseases, such as uterine fibroids, adenomyosis, cervicitis, and non-neoplastic epithelial disorders of the vulva. Since 1988, adhering to the medical philosophy of “Treatment-minimize harm to patients,” Professor Wang has a long track record of innovative and original research on the theoretic framework of therapeutic ultrasound, its clinical translation, and clinical development of focused ultrasound therapies. He proposed for the very first time the concept of “Biological Focal Region,” laying the theoretic foundation for clinical application of focused ultrasound ablative therapy. His team successfully developed the world-first High Intensity Focused Ultrasound Tumor Therapeutic System, the JC series with independent intellectual property rights. It led the clinical development and global deployment of HIFU technology, realizing the medical dream of noninvasive extracorporeal treatment of the lesions within the body. At present, a series of ultrasound therapy devices developed by Prof. Wang’s team is being used by more than 2800 hospitals worldwide, having treated more than 150,000 patients with benign and malignant diseases, such as uterine fibroids, liver cancer, breast cancer, and osteosarcoma and more than 2 million patients with nontumor diseases.

Abbreviations

CNS Central nervous system CQ HAIFU Chongqing HAIFU Medical Technology Co. Ltd. CS Cesarean section D&C Dilatation and curettage FIGO International Federation of Gynecology and Obstetrics FUS Focused ultrasound surgery GH Growth hormone GnRH-a Gonadotrophin-releasing hormone analog HCG Human chorionic gonadotrophin HIFU High intensity focused ultrasound HIFUa High intensity focused ultrasound ablation HPL Human placental lactogen MIS Minimally invasive surgery MRI Magnetic resonance imaging RMB Renminbi UAE Uterine arterial embolization

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1

An Introduction

When an object vibrates between 20 and 20,000 Hz, it produces an audible sound. In simple terms, sound is a vibration that can be picked up by our ears. Ultrasound is a sound wave with a frequency higher than 20,000 Hz (Fig. 1.1), which is higher than the upper audible limit of hearing. Thus, it cannot be heard by the human ear. Focused ultrasound is a noninvasive treatment procedure that uses ultrasound waves emitted from a transducer outside the body using its penetration and focusing ability to form a focus inside the body. When ultrasound waves fire, a combination of thermal, cavitation, and mechanical effects of the ultrasonic wave produce instantaneous high temperature at the focal point to cause coagulation necrosis of the target tissue. Focused ultrasound is used for the treatment of benign gynecologic diseases including uterine fibroids [1], adenomyosis [2], cesarean scar pregnancy [3] and placenta accreta [4] as well as liver cancer [5], breast cancer [6], pancreatic cancer [7], bone cancer [8], retroperitoneal sarcoma [9], and other solid tumors [10]. At present, surgery has evolved from open to minimally invasive surgery. We now use minimally invasive surgery to treat many diseases. With the advancement of medical technology and improved quality of life, many people want to be treated with less invasive or even noninvasive techniques. Now we are shifting from “minimally invasive surgery” to “noninvasive surgery.” It is the dream of doctors and patients to minimize harm while achieving therapeutic goals. Therefore, even minimally invasive surgery is not enough to meet all of the treatment requirements for patients. We need to be able to treat diseases in a less invasive way than even laparoscopy or hysteroscopy. This is the method of HIFU ablation to be introduced in this book. The book is written based on many of the information from scientific literature and that of HAIFU knife® surgery produced by Chongqing HAIFU Medical Technologies Co., Ltd.

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 F. Wong et al., Focused Ultrasound Surgery in Gynecology, https://doi.org/10.1007/978-981-16-0939-8_1

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2

1  An Introduction

20,000 Hz (20 kHz)

20 Hz

Range of human hearing Ultrasound Low pitch

0

10

High pitch

100

1000 10000 Frequency (Hz)

100000

1000000

10000000

Fig. 1.1  Ultrasound is a sound wave with a frequency from 20 kHz up to several gigahertz

1.1

The HAIFU Knife®

The “HAIFU knife®,” also known as “focused ultrasound knife,” is the trademark of high intensity focused ultrasound (HIFU) tumor therapeutic system developed by Chongqing HAIFU Medical Technologies Co., Ltd. The English abbreviation “HIFU” used loosely in the book is for any high intensity focused ultrasound treatment, including HAIFU knife® and other HIFU ablation or hyperthermia systems. The HAIFU knife® system is an ultrasound-guided HIFU ablation system that can treat liver cancer, pancreatic cancer, bone tumors, soft tissue tumors, and benign uterine diseases. Other HIFU systems may not have enough experience in these diseased organs. The principle of HIFU is similar to focusing sunlight through a convex lens, but with the ultrasound comes to a focus within the body after safely penetrating the body tissue (Fig. 1.2). The main mechanisms include thermal, cavitational, and mechanical effects. A noninvasive treatment, the HIFU ablation produces a temperature above 60 °C at the focused target tissue within a very short timespan. This action results in coagulation necrosis at the target without inflicting injury to the surrounding tissues. The necrotic tissue is gradually absorbed or becomes a fibrotic scar. The HIFU ablation will not wholly replace open surgery or minimally invasive surgery. Any operation has indications and contraindications, advantages and disadvantages. Abdominal hysterectomy is the treatment of choice for malignant uterine tumors, while uterine fibroids with abundant blood supply and pedunculated subserous fibroids are more suitable for minimally invasive surgery. Since HIFU ablation is a noninvasive treatment that is less harmful to the body than open surgery or minimally invasive surgery, the recovery time after HIFU is much shorter. Thus, if the disease is suitable for HIFU treatment, it should be considered a first choice. To achieve the principle of “minimizing harm to patients,” either HIFU treatment or endoscopic surgery is our treatment.

1.2  The “HAIFU Knife®”

3

Fig. 1.2  Focusing high-intensity ultrasound through the body for fibroid ablation (Courtesy from CQ HAIFU Medical Technology Co. Ltd.)

Fig. 1.3  JC Model: high intensity focused ultrasound (HIFU) tumor therapeutic system for all surgical specialties

1.2

The “HAIFU Knife®”

Several different models of the HAIFU knife® are manufactured by Chongqing HAIFU Medical Technology Co., Ltd., with different appearances and features. These two models (Figs. 1.3 and 1.4) are used commonly to treat solid tumors and organs such as uterine fibroids, uterine adenomyosis, placental accreta, cesarean pregnancy scars, with the larger JC model more suitable for liver tumors, kidney tumors, bone cancers, breast cancers, pancreatic cancers, and soft tissue tumors of the solid tumor type. Over the years, HAIFU knife® has been exported from China to Asia, Europe, Africa, and South America. It is currently operating in 26 countries, including the

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1  An Introduction

Fig. 1.4  JC 200 model: high intensity focused ultrasound (HIFU) tumor therapeutic system for gynecology

United Kingdom, Germany, Italy, Bulgaria, Argentina, Japan, South Korea, Thailand, Saudi Arabia, Jordan, South Africa, and Egypt. Many studies from these countries have shown their effectiveness and safety. In Spain, the Minister of Public Health even declared that the HIFU ablation is the treatment of choice for uterine fibroids and uterine adenomyosis. Many famous hospitals or institutes, including Oxford, the European Institute of Oncology in Milan, Bonn University in Germany, etc., had used HIFU ablation to treat liver cancer, bone metastasis, and pancreatic cancers. The HIFU ablation technique does offer patients a choice when no other treatment is available or exhausted.

1.2.1 O  ther Focused Ultrasound Equipment Systems in the Market The differences between various HIFU systems depend on (1) the image-guided models, (2) ultrasound transducers designs, and (3) mounting positions of the ultrasound transducer. This variation of image guidance and transducer design results in various degrees of treatment effectiveness and safety concerns.

1.2.2 Ultrasound-Guided (USg) HIFU Systems In addition to the above HAIFU knife@ tumor therapeutic systems—JC and JC200 models, which are ultrasound-guided HIFU ablation systems, there are many other types of ultrasound-guided HIFU systems available in the China market, for

1.3  MRgHIFU Systems

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Fig. 1.5  Other USgHIFU systems commercially available in China (1) PRO 2008, (2) HIFUNIT 9000, (3) HIFU 2001, and (4) CZ 901

examples, The PRO 2008 HIFU system produced by Shenzhen Promethe Medical Sci-­ tech co Ltd., the HIFUNIT 9000 system produced by Shanghai Aishen Technology (China) [11], the HIFU-2001 from Shenzhen Wikkon (Huikang Medical Apparatus Co Ltd), and the CZ 901 HIFU tumor therapeutic system from MainYang Sonic electric Ltd. (Fig. 1.5). Due to different designs’ patent issues, and the ultrasound transducer’s location, the therapeutic focused ultrasound systems are two major types based on whether the ultrasound transducer is bottom-mounted or top-mounted at the treatment table. For “HIFU ablation,” patients receiving treatment with models JC, JC200, ExAblate 2000/2100, and Sonalleve HIFU device are required to lie prone, i.e., on their stomach, with the transducer bottom-mounted below the table (Fig. 1.6). The alternative systems are with a top-mounted ultrasound transducer above the operating table. The patient will lie on their back during treatment with the therapeutic head loaded onto the abdomen from above the table. In general, the top-­ mounted HIFU device’s treatment efficiency is low, and it is not easy to obtain the ablative effect.

1.3

MRgHIFU Systems

There are two Magnetic Resonance Imaging-guided (MRg) HIFU systems commercially available in the market, namely the ExAblate system (Insightec Ltd., Haifa, Israel) based on the General Electric MR platform, and the Sonalleve HIFU

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1  An Introduction

Fig. 1.6  Model JC 200 therapeutic focused ultrasound system with the ultrasound transducer below the table

Fig. 1.7  The Sonalleve MRgHIFU system from Philips Healthcare

system (Koninklijke Philips Electronics, Eindhoven, the Netherlands) based on the Phillips MR platform. Both involve a process of volumetric heating of fibroids by HIFU with MRI feedback. The Sonalleve MRgHIFU is a system (Fig. 1.7) developed by Philips Healthcare to treat uterine fibroids [11]. At present, it is also underway for clinical trials and study for bone metastasis [12], prostate cancer [13], and breast cancer [14]. The InSightec ExAblate® 2000 MRI-guided FUS system was the first commercial MRg-FUS system (Fig. 1.8) that received the Food and Drug Administration (FDA) approved FUS device for the treatment of uterine fibroids in America [15]. Since then, it had been utilized in the treatment of uterine fibroids and adenomyosis [16]. Other reports are also available in oncology, including the brain, bone, thyroid, and prostate.

1.3  MRgHIFU Systems

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Fig. 1.8  The InSightec ExAblate® 2000 MRI-guided FUS system

While USgHIFU was the original image-guided system, MRg-FUS(MR-HIFU) was developed to incorporate three-dimensional treatment planning and temperature monitoring at the target zone. These MRgHIFU systems have been demonstrated promising results in the treatment of both uterine fibroids. With accumulating practical experience, a comparison of merits of MRg and USgHIFU systems are tabled as follow: Features Anatomical resolution Target temperature monitoring Cost of HIFU system

MRgHIFU Good Available

USgHIFU Fair Not available

Expensive including MRI set up

MRI chamber and noise Machine space requirement Transducer motility Treatment time, e.g., for a 5 cm fibroid Treatment efficiency Treatment cost Operator

Noisy and isolated Large area

Less expensive without MRI set up Friendly environment Average room area (about 300–400 square ft) Movement needed 1 h (independent of MRI functions) 80–90% Economical Surgeon or gynecologist

Fixed 2–3 h (dependent on MRI functions) 20–50% Expensive Interventional radiologist and surgeon together

In China, there are several companies that produce HIFU machines. Of the different types of USgHIFU systems, their effectiveness and safety depend on the ultrasound transducer design (single-chip vs. phased array) and position (top-­ mounted vs. bottom-mounted).

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1  An Introduction

Single-chip HIFU system has an ultrasonic transducer mediated by a single ceramic piezoelectric chip, and the focus target has a fixed distance and angle. During treatment, it needs to move the transducer mechanically while the B-ultrasound scans the lesion. Multiphased array ultrasound transducer consists of a combination of multielement phased array ultrasound transducers. The target focus is not fixed and can be adjusted according to the location of the lesion. Changing the direction of each probe in the transducer refocuses onto a new position for treatment. Therefore, the multiphased array transducer does not move during the HIFU treatment (Fig. 1.9). However, when the multiphased array is focused, each transducer phase needs to be adjusted in phase to obtain the maximum focus energy, and out of phase in ultrasound wave will deviate and reduce the focused energy at the target (Fig.  1.10). Therefore, single-chip ultrasound transducers are superior to multiphased array transducers in terms of efficiency unless the design of the latter transducer synchronization is perfect.

Tumor

Skin Ultrasound energy beams Ultrasound transducer

Move

Single chip ultrasound transducer

Multiphase array ultrasound transducer

Fig. 1.9  Movement of single-chip and multiphase array ultrasound transducer in actions

Combined waveform Wave 1 Wave 2 Synchronous in phase

180° phase difference

Fig. 1.10  The combined waveform at the target area is a combination of waveforms focused in synchronized phase; a 180° out of phase might negate all the ultrasound energy of each waveform

1.3  MRgHIFU Systems

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The transducers’ position, i.e., whether it is top-mounted and bottom-mounted, is important in terms of skin complications and the frequency of treatment. The top-­ mounted transducer projects ultrasound waves through multilayer interfaces: water bag membrane, membrane to ultrasound media, and ultrasound media to skin. Some ultrasonic energies will then stay at these interfaces, leading to an increase in the temperature at the skin level and increase the risk of skin burns. Therefore, multiple treatment sessions with lower energy are used (thermotherapy) instead of one-off treatment to avoid skin complications. In contrast, a bottom-mounted transducer produces an ultrasound wave in a water tank with degassed water. There is only one interface between the ultrasound transducer and the patient’s skin, i.e., only a single interface retents penetrating acoustic energy. With cold water in the tank that can also cool down and reduce skin temperature at the time of treatment (Fig. 1.11), skin burns’ risk will become minimal. It also allows more energies to be delivered at the focused target during one treatment. With a better understanding of the ultrasound transducer design and energy delivery, in the 1990s, scientists from Chongqing HAIFU Medical Technology Co., Ltd. performed experiments using a system with the transducer above the table, i.e., top-mounted transducer. They found that the usable power was significantly lower than that of a system with the ultrasound transducer located below the treatment table, e.g., bottom-mounted transducer, due to safety issues. Energy from ultrasound transducers placed above the table are theoretically inferior for treatment due to the following reasons: 1. A top-mounted ultrasound transducer requires a sealed water bag to put between the ultrasound transducer and the skin; this sealed water bag interface results in energy loss because of the reflection and absorption of energy by the bag and can also involve burns to the skin. 2. Air bubbles may form between the skin and the sealed water bag during the HIFU treatment. These reflect ultrasound and energy, requiring higher energy power levels with the possibility of inducing pain and skin burns. Ultrasound transducer

Skin Water layer, enclosed inside a bag

Skin

Ultrasonic media layer

Ultrasound transducer

Water layer

Fig. 1.11  The number of interfaces of the top-mounted and bottom-mounted ultrasound transducer

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1  An Introduction

3. The water in the sealed water bag needs to be degassed as well. If not, energy traveling through the water will also be absorbed and may produce gas bubbles which adhere to the ultrasound transducer and surface of the ultrasound monitoring probe. To the former, it hinders ultrasonic wave transmission during treatment. To the latter, it reduces the clarity (quality) of the ultrasonic image. The bottom-mounted HIFU systems overcome these two potential types of gas interferences using automatic cycling of degassed water (oxygen content 50% intramural, subserous

6

Subserous, < 50% intramural

7

Subserous, pudunculated

Other

8

Cervical, parasitic

Hybrid

2-5

27

5

6

4

0 3

1 7 2 2-5

Submucosal and subserous, each with less than half the diameter in the endometrial and peritoneal cavities

Fig. 3.5  The FIGO classification showing locations of fibroids in the uterus

1. Since HIFU treatment is a noninvasive procedure, there will not be any pathological diagnosis of the fibroids made before HIFU ablation. MRI is an essential auxiliary examination to evaluate and determine the nature of the uterine fibroids, and particularly the possibility of malignancy. In patients with heavy or irregular vaginal bleeding, an irregularly thickened endometrium (>15 mm) shown in the MRI scan would suggest the need for endometrial sampling or D&C to exclude uterine lesions or cancer. 2. MRI is accurate to reveal the number, sizes, location, blood supply, and the fibroids’ relationship to surrounding tissues. Preoperative MRI T2WI and contrast T1WI signals can make a preliminary assessment of the susceptibility of the fibroids to HIFU ablation and make a reliable prediction on the difficulty and effectiveness of treatment [1]. MRI shows a clearer picture of uterine fibroids, and according to the locations of fibroids, MRI images show three categories of fibroids—(1) submucosal fibroids, (2) intramural fibroids, and (3) subserosal fibroids (Fig. 3.6). MRI signal intensity depends on the tissue proton density, T1 and T2 relaxation time, so the MRI signal intensity directly reflects the tissue’s characteristics. Many uterine fibroids show homogeneous low signal intensity in the MRI T2WI image. These fibroids consist of closely arranged myomatous cells but lack sufficient intercellular fluid and mucin between cells. Therefore, on the T2WI image, these fibroids appear darker than the surrounding uterine wall, i.e., hypointense signal. Based on the MRI signal intensities, T1-weighted images show isointense signals resembling those of the adjacent myometrium, and T2-weighted images may show low/equal/high signals. Fibroids usually have low T2WI signal intensity, clear

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a

c

3  Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis

b

d

Fig. 3.6  Locations of fibroids: (a): the white arrow indicates type 2 fibroids; (b): the white arrow shows type 2–5 fibroids, black arrows show type 5 fibroids; (c): the white arrow indicates type 2 fibroids, white triangle indicates a type 4 fibroid, and black arrows indicate type 5 fibroids; (d): Multiple fibroids, white arrows show type 0 fibroids

boundaries, and may sometimes have a slightly high signal appearance. However, fibroids in some conditions can present with different T1 and T2 weighting signal intensities. These conditions are (1) calcification shows hypointense signals at T1 and T2, (2) cystic changes are hypointense signals at T1 but hyperintense at T2, (3) mucoid degeneration has slight hyperintense signals at T1 and hyperintense signals at T2. The above various MRI signal intensities have a tremendous and significant influence on the HIFU ablation result. The gold standard for determining benign from malignant tumors is the pathological examination, which has an accuracy reaching 99%. Developments in imaging technology, including color Doppler ultrasound, enhanced MRI and tumor markers, etc., allow accuracy rates approaching 95% or more [2, 3]. Although magnetic resonance imaging features of uterine sarcoma have been described, confusing appearances between uterine leiomyosarcomas and other atypical leiomyomas can make it challenging to make an accurate diagnosis. If malignancy is suspected, surgical treatment is recommended to remove it.

3.3  Uterine Adenomyosis

3.3

29

Uterine Adenomyosis

Imaging has an indispensable role in diagnosing adenomyosis, defining its extent, assisting in planning and evaluating the effect of treatment. Ultrasound, an especially transvaginal ultrasound, is the first-line imaging method for adenomyosis because of its advantages of simplicity, no radiation, easy repeatability. Transabdominal ultrasound is the commonly used ultrasound examination method, and it can display a full picture of the uterus (Fig. 3.7). The transabdominal ultrasound features of adenomyosis are shown in Figs. 3.8 and 3.9. However, these features are susceptible to abdominal wall thickness, degree of bladder distension, and intestinal flatulence. The transvaginal ultrasound scan is one of the commonly used ultrasound investigations in gynecology if it is feasible. Due to the high frequency of transvaginal probe, its proximity to the pelvic organs, and excellent image resolution, it can display the structural characteristics of adenomyosis and its blood flow and any uterine ovarian or pelvic lesions. It is also not affected by bowel gas interference and abdominal wall thickness. A transvaginal scan is superior to a transabdominal ultrasound scan in the detailed observation of adenomyosis.

Fig. 3.7 Transabdominal scan image of diffuse adenomyosis, showing a diffusely and uniformly enlarged uterus in the uterine fundus, anterior wall, and posterior wall of the same thickness. The cervix was of normal size

Fig. 3.8 Transabdominal ultrasound image showed that the echo of the posterior wall adenomyosis

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3  Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis

Fig. 3.9 Transabdominal ultrasound image showed that the anterior uterine muscle layer was significantly thickened, and the echo was uneven. Multiple small echoless areas scattered in the lesion were visible. It was a diffuse anterior wall adenomyosis

3.4

Transvaginal Ultrasound Appearances of Adenomyosis

The main ultrasound features of adenomyosis include uterine enlargement, asymmetry thickening of the anterior and posterior wall of the uterus, uneven echoes, small cysts, or microcysts in the affected muscular layer. Besides, the increase in CDFI blood flow signals is a common manifestation. The blood flow signals in the affected area of the myometrium will present as penetrating vascularity. The ultrasound features of adenomyosis can be listed as follows: 1. The uterus is enlarged, with the asymmetry of the anterior and posterior walls of the uterus. The distribution of adenomyosis lesions can classify into diffuse type, anterior/posterior wall type, and focal type. Regardless of diffuse or focal adenomyosis, the unevenly affected myometrium is the most common ultrasound appearance of adenomyosis. 2. Another specific ultrasound features of adenomyosis is the small cysts in the myometrium (Fig. 3.10). A recent study had shown that the most specific ultrasound feature of transvaginal ultrasound diagnosis of adenomyosis was myometrial cysts (98% specificity), and the most sensitive ultrasound feature is the uneven myometrial echo (88% sensitivity) [4]. Of course, myometrial cysts may also be cystic degeneration in uterine fibroids and need to be identified. 3. Other characteristic ultrasound features are the fan-shaped sound shadow in the myometrium due to the disturbances of echo-enhanced and echo-reduced areas in the adenomyosis (Fig. 3.11). 4. In adenomyosis, due to myofibrosis and hypertrophy of the uterine myometrium, blood vessels in the uterine myometrium have also generally increased. Color Doppler flow imaging (CDFI) showed increased blood flow signals in the uterine myometrial area (Fig. 3.12). The area of increased blood flow signal can reflect the distribution of adenomyosis in the myometrium. At the same time, the CDFI appearance of adenomyosis can also distinguish between adenomyosis and uterine fibroids [5].

3.5  MRI Appearances of Adenomyosis

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Fig. 3.10 Transvaginal ultrasound image of an anterior wall adenomyosis showing that the thickened anterior wall and the echo are significantly uneven. There are several small non-echoic cysts and high echoes around the non-echoic area

Fig. 3.11  Transvaginal ultrasound image of adenomyosis shows fan-shaped sound shadows (white arrows) in the uterus, which are straight and thin by many streaks or pencils like sound shadows. These sound shadows are arranged in a fan-shaped or jalousie-like arrangement

3.5

MRI Appearances of Adenomyosis

The classic appearance of MRI for adenomyosis is the diffuse enlargement of the uterus, generally with smooth outer contours, with the lesions more clearly displayed on the T2-weighted image. They are low-signal lesions with poorly defined borders, adjacent to the endometrium, and unclear boundaries. The MRI appearance

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3  Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis

Fig. 3.12  A CDFI image shows typical penetrating blood flow signals into the uterine adenomyosis Fig. 3.13  The MRI picture of diffuse adenomyosis in both the anterior and posterior uterine walls

of adenomyosis depends on adenomyosis lesions and echo features; this disease can classify into diffuse type, anterior/posterior wall type, and focal type. 1 . Diffuse type (Fig. 3.13) 2. Anterior/posterior wall type (Fig. 3.14) 3. Focal (adenomyoma) type (Fig. 3.15)

3.5  MRI Appearances of Adenomyosis

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Fig. 3.14  The MRI picture of diffuse adenomyosis in the posterior uterine wall

Fig. 3.15  The MRI picture of focal adenomyoma in both the anterior and posterior uterine wall. The endometrial-myometrial junction appears normal

Kishi et al. [6] proposed to divide adenomyosis into four subtypes according to the MRI appearances: Subtype I is called internal adenomyosis, which occurs only in the inner layer of the uterus. It shows a thickened endometrium-myometrial junctional zone but does not involves the outer uterine layer. Subtype II is called external adenomyosis, which occurs in the outer uterine layer and does not involve the junctional zone. Subtype III is called intramural adenomyosis, which exists alone in the myometrial layer, and does not involve other structures. Subtype IV includes adenomyosis that has a mixed presentation, including two or three of the above. The adenomyosis has various presentations due to its involvement of different parts of the uterus Adenomyoma appears on the T2-weighted image as a low-­ signaled focal adenomyosis lesion in the muscle layer with an ill-defined border and

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3  Ultrasound and MRI Imaging of Uterine Fibroids and Adenomyosis

may contain small cystic foci with high signals. Sometimes small cystic foci appear brighter on the T1-weighted image [7]. With the increasing use of an MRI scan for adenomyosis, there will be more descriptions of adenomyosis features. The implications of these features may correspond to the histopathological findings well. However, the correlation of these features to the severity of the lesions and their clinical treatment responses should be studied.

3.6

 eiomyosarcoma and Endometrial Stromal Sarcoma— L MRI Features

MRI features of leiomyosarcoma (LMS) include nodular borders, non-perfused areas, hyperintensity areas on T1WI, and quick enhancement at the early arterial phase; and shared MRI features with that of uterine sarcomas include heterogeneous intermediate signal on T2WI, and hyperintensity on DWI with low ADC value, associated with intratumoral hemorrhage and necrosis [8, 9]. Both MRI T2W1 and contrast-enhanced MRI have proven the ability to detect tumor necrosis, which is a significant finding of the rapidly growing malignant uterine neoplasms. In their study, Huang et al. [10] reported that central non-enhancement (CNE) and well-demarcated pocket-like non-enhanced areas have significantly higher diagnostic accuracy than T2WI, T1WI, and T2WI, in the differentiation between leiomyosarcoma and uterine fibroids. Hyperintensity on DWI is also reported to have high sensitivity in differentiation between LMS and uterine fibroids [11]. Endometrial stromal sarcoma (ESS) is the second most common uterine sarcoma. ESS tends to show high signal intensity on T2WI and increased and prolonged contrast enhancement. MRI feature of ESS includes nodular lesions at the tumor margin, or marginal nodules, intramyometrial worm-like nodular extensions [12].

References 1. Cheng H, Wang C, Tian J. Correlation between uterine fibroids with various magnetic resonance imaging features and therapeutic effects of high-intensity focused ultrasound ablation. Pak J Med Sci. 2015;31(4):869. 2. Santos P, Cunha TM. Uterine sarcomas: clinical presentation and MRI features. Diagn Interv Radiol. 2015;21(1):4. 3. Koyama T, et  al. MR imaging of endometrial stromal sarcoma: correlation with pathologic findings. AJR Am J Roentgenol. 1999;173(3):767–72. 4. Tellum T, et al. Development of a clinical prediction model for diagnosing adenomyosis. Fertil Steril. 2018;110(5):957–964.e3. 5. Exacoustos C, et al. Adenomyosis: three-dimensional sonographic findings of the junctional zone and correlation with histology. Ultrasound Obstet Gynecol. 2011;37(4):471–9. 6. Kishi Y, et  al. Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification. Am J Obstet Gynecol. 2012;207(2):114.e1–7.

References

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7. Song SE, et  al. MR imaging features of uterine adenomyomas. Abdom Imaging. 2011;36(4):483–8. 8. Shah SH, et al. Uterine sarcomas: then and now. Am J Roentgenol. 2012;199(1):213–23. 9. Lakhman Y, et al. Differentiation of uterine leiomyosarcoma from atypical leiomyoma: diagnostic accuracy of qualitative MR imaging features and feasibility of texture analysis. Eur Radiol. 2017;27(7):2903–15. 10. Huang Y-T, et  al. Current status of magnetic resonance imaging in patients with malignant uterine neoplasms: a review. Korean J Radiol. 2019;20(1):18–33. 11. Tirumani SH, et  al. Current concepts in the imaging of uterine sarcoma. Abdom Imaging. 2013;38(2):397–411. 12. Ueda M, et al. MR imaging findings of uterine endometrial stromal sarcoma: differentiation from endometrial carcinoma. Eur Radiol. 2001;11(1):28–33.

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Uterine Fibroids and HIFU Ablation

Uterine fibroids are common benign uterine tumors in women of childbearing age, with an incidence ranging from 20 to 40% [1]. They mainly develop from uterine smooth muscle cell proliferation, including a small amount of fibrous connective tissues. The medical terminology is “uterine leiomyoma,” but the condition is commonly known as uterine fibroids by the lay public. The etiology of uterine fibroids is still not fully understood. A large number of clinical observations and experimental research have found that uterine fibroids are hormone-dependent tumors. Estrogen is a major causative factor in the growth of fibroids. Growth hormone (GH) and human placental lactogen (HPL) are also related to fibroids’ growth. Since the upper central nervous system (CNS) controlled ovarian function and hormone metabolism, CNS activity may play an important role in fibroids’ pathogenesis. Uterine fibroids are common in women of childbearing age, widowed, and sexually inactive women. Some studies have also suggested that long-term sexual imbalances might cause chronic pelvic congestion leading to uterine fibroids. In short, the occurrence and development of uterine fibroids are multifactorial.

4.1

Symptoms of Uterine Fibroids

Many patients with uterine fibroids are asymptomatic, with the condition often only identified during routine pelvic examinations or ultrasound examinations. Common clinical symptoms arising from fibroids include 1. Menstrual disorder—this is the most common presenting symptom of uterine fibroids and occurs in more than half of patients with this condition. It can manifest as increased menstrual flow, prolonged menstrual periods, or shorter cycles. Submucosal fibroids and intramural fibroids are the common types of fibroids

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 F. Wong et al., Focused Ultrasound Surgery in Gynecology, https://doi.org/10.1007/978-981-16-0939-8_4

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4  Uterine Fibroids and HIFU Ablation

that cause such symptoms. Subserosal fibroids rarely cause menstrual disturbances. 2. Abdominal mass and pressure symptoms—fibroids can grow to such a size they may mimic a pregnancy. The finding is especially apparent in the early morning when the bladder is full. Such masses are solid, movable, and free from pain during palpation. Fibroids reaching a specific size can cause pressure symptoms to the surrounding organs. Anterior uterine wall fibroids close to the bladder can produce urinary frequency and urgency. Large cervical fibroid can compress the bladder, which can, in turn, block the urine outflow causing urinary retention. Posterior uterine fibroids, especially at the cervix, can compress the rectum and cause weak bowel movements and discomfort at defecation. Large, broad ligament fibroid can compress the ureter and even cause hydronephrosis, i.e., swelling of the kidney. 3. Pain—under normal circumstances, uterine fibroids do not cause pain. Some patients however may have lower abdominal distension and low back pain. When a pedunculated fibroid undergoes torsion or develops red degeneration, it can produce acute abdominal pain. Fibroids can often associate with endometriosis or adenomyosis simultaneously; in such situations, patients can also have pain during menstruation. 4. Increased vaginal discharge—any submucosal fibroid will cause vaginal discharge. Such fibroids will enlarge the uterine cavity’s sizes, the number of endometrial glands, and pelvic congestion thus causing increased whitish vaginal discharge—leucorrhea. Endometrial or cervical submucosal fibroids can develop ulcers, infections, necrosis, bloody, or purulent vaginal discharge. 5. Infertility and miscarriage—large-sized uterine fibroids can cause deformation of the uterine cavity, impacting embryo implantation, embryo growth, and development. Fibroids close to the tubal lumen can compress the tubal openings and give rise to a closed tubal lumen. Submucosal fibroids can hinder embryo implantation or delay the entry of sperm into the tubal lumens. These fibroids may lead to infertility. 6. Anemia—fibroids can cause increased menstrual flow or prolonged irregular vaginal bleeding. Therefore, severe anemia is more common in patients with large fibroids and submucosal fibroids. 7. Polycythemia—a small number of patients with large uterine fibroids may develop increased numbers of red blood cells (polycythemia). It is likely due to ectopic hormones produced by the fibroid tumor. 8. Hypoglycemia is a low sugar level in the blood, probably related to ectopic hormones, loss of appetite, anemia, and weakness. The patient may feel dizziness and fainting at work.

4.2

Indications for Treatment

Asymptomatic and small fibroids usually do not need any treatment. However, patients could have HIFU treatment for the following indications:

4.3  Investigative Methods

39

1. Due to their different positions and sizes, fibroids can cause moderate or severe clinical symptoms, e.g., heavy bleeding and pressure symptoms, some of which are sufficiently disturbing or debilitating to require treatment; 2. Fibroids may lead to difficulty in patients to get pregnant. Thus, treatment may be suitable for patients of reproductive age with infertility or miscarriage problems; 3. When patients have severe psychological burdens due to fibroids and their associated symptoms, they should have treatment to reduce their mental stress. 4. Young patients with multiple small fibroids may wish to consider therapy to decrease the risk of subsequent problems as they get old.

4.3

Investigative Methods

Before treatment, patients should have investigations for the presence of uterine fibroids and confirm the need for medical or surgical treatment. 1. Ultrasound: Ultrasound examination is the most commonly used diagnostic method at present. It is cheap, convenient, quick, and easy to perform. It can readily display an enlarged uterus with an irregular shape, together with the number, locations, and sizes of fibroids. It can also show a fibroid’s content, whether it is wholly solid, liquefied, or cystic. Ultrasound can identify whether there is degeneration, calcifications, or possibly suspected malignant changes in the fibroid. It is also helpful in distinguishing fibroids from ovarian tumors or other pelvic masses. As demonstrated by ultrasound imaging, fibroids’ details are fully described in Chap. 3 in this book. 2. Hysteroscopy: Hysteroscopy can be used to directly observe the uterine cavity, with or without abnormal growths thus contributing to the diagnosis of submucosal fibroids. Because of the need to use a distending medium like saline or dextrose into the uterine cavity through the cervix, some patients may feel pain and discomfort if diagnostic hysteroscopy is performed without a sedative analgesic. 3. Laparoscopy: Fibroids should be distinguished from ovarian tumors or other pelvic masses, then sometimes laparoscopic examination is performed. This procedure allows direct observation of uterine size, morphology, site of the tumor, and judgment of the nature of the problem. However, laparoscopy requires general anesthesia, hospitalization, and is an invasive surgery. It is the last resort in the list of investigations. 4. Magnetic Resonance Imaging (MRI): MRI allows a high diagnostic accuracy of uterine fibroids. It can clearly show the size, number, location, and relationship of fibroids to adjacent tissues and is especially useful for differential diagnosis of benign and malignant uterine fibroids. However, such imaging is expensive and takes about 15–30 min for the examination. MRI machines are also noisy and used in an isolated room. Thus, it is not suitable for patients that have claustrophobia. It is also not permitted for patients with metal implants that could be

40

4  Uterine Fibroids and HIFU Ablation

affected by the strong electromagnetic field of MRI. As demonstrated by MRI imaging, fibroids’ details are fully described in Chap. 3 in this book.

4.4

Treatments

Treatment can be either by observation or surgery, depending on the patients’ age, symptoms, sizes, and locations of the fibroid/s. 1. Conservative management by follow-up observation If the patient has small fibroids, say 5 cm or below, but with no apparent clinical symptom and no malignant transformation signs, they can be observed regularly at follow-up visits. If fibroids continue to grow or clinical symptoms develop, conservative management should cease, and the patient should have treatment. 2. Medical treatment with drugs The following medications are used to treat symptomatic fibroids: (a) Gonadotropin-releasing hormone agonist (GnRH-a, e.g., leuprorelin)— GnRH-a is not suitable for long-term continuous use. It is for preoperative or postoperative adjuvant treatment. It is usually limited to 3–6 monthly cycles to avoid producing severe menopausal symptoms or osteoporosis associated with the low estrogen status. (b) Mifepristone—Mifepristone is a progesterone antagonist. In recent years, it has been clinically used to treat uterine fibroids to reduce fibroids’ size. However, the fibroids tend to regrow again after the drug treatment stops. (c) Danazol—Danazol is used for the preoperative treatment of unsuitable uterine fibroids to reduce their size. However, uterine fibroids often regrow after the drug stops. Danazol has many side effects caused by its androgenic action, e.g., weight gain, acne, hoarseness of voice, etc. It can also sometimes cause severe liver damage [2]. (d) Tamoxifen—Tamoxifen inhibits fibroid growth. However, long-term use in individual patients may increase some uterine fibroids’ size and may even induce endometriosis or endometrial cancer [3]. (e) Androgen drugs—Drugs in this category include testosterone (methyltestosterone) and testosterone propionate. They can inhibit the growth of fibroids. However, patients may develop masculinizing features. 3. Surgical treatment Conventional surgical treatment includes myomectomy and hysterectomy, using either the abdominal, transvaginal, or endoscopic (hysteroscopic or laparoscopic) approach. The surgical procedure’s choice depends on the patient’s age, fertility desire, sizes, number, and locations of fibroids. Other factors to be considered include the surgeon’s skill, the range of techniques he/she has competence in, and whether the patient is suffering any other medical conditions. (a) Myomectomy—Myomectomy is performed by cutting open the uterine wall, removing the fibroid from its pseudo-capsule, and then suturing the uterine wound. It is mainly used for younger women under the age of 40

4.4 Treatments

41

because they would like to conserve the uterus and preserve fertility by this surgical procedure. These surgical indications are large fibroids, menorrhagia, pressure symptoms, infertility due to fibroids, large submucosal fibroids, and fast-growing fibroids without malignancy features. However, there remains a problem of fibroid recurrence after this surgery. The recurrence rate is about 50% within 5 years [4]. (b) Hysterectomy—Hysterectomy can be performed for patients with severe symptoms but without fertility desire. It can also be for fibroids that have features of malignant transformation. The hysterectomy is to remove the uterus and the cervix and retain one or both appendices. Bilateral fallopian tubes and ovaries are removed together in patients of older age, particularly those after menopause. There are three main approaches to removing the uterus: laparoscopy, vaginal, or open abdominal surgery. Hysterectomy includes either total hysterectomy (cervix removed) or subtotal hysterectomy (cervix conserved). In older women, total hysterectomy is more appropriate to reduce the risk of cervical malignancy or repeated surgeries. Pap smear before the operation should be performed to exclude cervical malignancy. Subtotal hysterectomy can be offered to younger women to avoid sexual dysfunction or genital prolapse after surgery. (c) Uterine arterial embolization (UAE)—This procedure is performed by inserting an arterial catheter into the uterine arteries via the femoral artery at the groin and injecting embolic particles to block the blood supply to the uterine fibroid. It achieves a reduction in fibroids’ sizes by atrophy or, ideally, even causes fibroids’ disappearance. However, 5% of patients have a risk of premature ovarian failure after UAE surgery. There are also rare reports of pelvic infections, bowel obstruction, and accidental thrombosis threats in other major blood vessels [5]. (d) Laparoscopy—Laparoscopic hysterectomy or myomectomy is a common surgical technique for treating fibroids today. Laparoscopic surgery refers to using a cold light source to provide illumination after introducing a laparoscope into the abdominal cavity. Through the laparoscope, the operating surgeons observe and operate within the abdominal cavity while watching on a dedicated monitor to perform either myomectomy or hysterectomy to treat uterine fibroids. (e) High intensity focused ultrasound(HIFU)or Focused ultrasound surgery (FUS)—By taking advantage of the ultrasound ability to penetrate tissue and focusing capacity to create a high temperature over 65 °C within the target area, HIFU/FUS induces coagulation necrosis of the fibroid. Fibroids after HIFU ablation can be gradually absorbed and then shrink in size, and then fibroids-related symptoms would progressively relieve. It applies to patients with symptomatic uterine fibroids, severe psychological burdens, and fertility requirements. By keeping uterine integrity, HIFU/FUS has the advantages of noninvasiveness, rapid postoperative recovery, and repeatability. When HIFU/FUS compares to traditional open surgery and laparoscopy, it has the following differences as listed in Table 4.1

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4  Uterine Fibroids and HIFU Ablation

Table 4.1  Comparisons of surgical treatment vs. HIFU ablation (FUS) Approach Nature Surrounding healthy tissues Uterus Wound Treatment time General anesthesia Recovery time Adhesions

Traditional open surgery Cut wound Maximal harm

Laparoscopic surgery (MIS) Cut wounds Minimal harm

May remove the uterus Large wound Long General anesthesia with intubation 3 months 50–90%

May remove the uterus Small wounds Long General anesthesia with intubation 4–6 weeks 10–30%

HIFU ablation (FUS) Focused ultrasound Nearly no harm Uterus and its functions conserved No wound Short to moderate No need for general anesthesia   non-­ pedunculated submucosal fibroids  >  intramural fibroids  >  non-pedunculated subserosal fibroids and pedunculated subserosal fibroids (slowest). The submucosal fibroids, intramural fibroids, and non-pedunculated subserosal fibroids have a 50–60% volume reduction after 6 months. The submucosal fibroids are the fastest to shrink because of transvaginal drainage of the entire fibroid. However, the pedunculated subserosal fibroids can only be absorbed slowly and even not absorbed. At present, there has been no reported case of pedunculated subserous fibroid found shed into the abdominal cavity. Therefore, pedunculated submucosal or subserosal fibroids are also suitable for ultrasound ablation. Still, for patients with pedunculated subserosal fibroids at the fundal location, ultrasound ablation should be performed with caution because of the surrounding bowels or vital tissues.

4.18  Other Issues of Fibroid Ablation

a

b

Before HAIFU knife @ treatment

Day 1 after HIFU ablation

57

c

8 months after HIFU ablation

Fig. 4.6  The MRI images showed the reabsorption of a submucous fibroid over 8 months. (a) Showed a type II submucosal fibroid before HIFU ablation; (b) showed the ablated type II submucosal fibroid 1 day after treatment; (c) showed the ablated submucosal fibroid almost disappeared in 8 months follow-up

Compared to traditional surgical removal, HIFU ablation does not remove the fibroid, only stopping it from growing and then slowly shrinking it. HIFU treatment enables maximum ablation of up to 90–95% of uterine fibroids and relief of associated symptoms. The criteria to determine the effectiveness or success rate also depend on the extent of clinical symptom relief and the results of imaging examinations using MRI and ultrasonography. It is important to assess the likelihood of success of HIFU treatment before operation. There were reports that a few cases in which the results of treatment were not ideal. As this ultrasonic ablation involves no wound, no trauma, no bleeding, and minimal damage to the body, even a treatment failure will not affect the body. It will also not preclude other treatment options or a repeat of the HIFU ablation from being undertaken.

4.18 Other Issues of Fibroid Ablation HIFU ablation has been used to treat patients for more than 20 years. During this HIFU ablation technique, standardized ablation protocols based on increasing clinical experience have been developed. It is now a very safe treatment with minimal complication rates. However, a few issues need to be addressed to ensure safety and success before and after HIFU ablation. (a) Patients with acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and recurrent subacute attacks are relatively sensitive to ultrasound’s mechanical effects. Pain in the treatment area is prone to occur during HIFU ablation treatment; thus, any reduced dose intensity may affect the therapeutic

58

4  Uterine Fibroids and HIFU Ablation

effect. The effect of ultrasonic ablation on pelvic inflammatory disease is unclear, especially whether it will increase the inflammatory response. ­Therefore, it is proposed that ultrasound ablation therapy should be performed after the inflammation is treated and settled. The appropriate dose intensity should be carefully controlled during the subsequent HIFU treatment. However, to what extent an anti-inflammatory treatment can be beneficial to HIFU ablation remains unclear. (b) Patients with surgical scars have scar tissue that has a strong absorption capacity for ultrasonic energy. Current techniques and protocols are acceptable for the treatment of scar widths of up to 15 mm. However, if the scar width exceeds 15 mm, the ultrasound energy shows diminished behind the scar tissue, especially after multiple surgical incisions or scars that had infection after surgery. We do not know how safe and how controllable ultrasound ablation can be at these scars. It is noteworthy that at this time, the scar within the acoustic pathway will have strong absorption of therapeutic ultrasound energy, and patients can easily complain of pain in the abdominal wall or burning skin thus affecting the ablation dose intensity and increased unsafety factors. Therefore, appropriate therapeutic dose intensity with adequate cooling time and controlled ablation time can be used, then the incidence of burns can be reduced. However, whether it can be suitably safe and effective for a T2WI hyperintense fibroid over an obese abdominal wall with a thick layer of fat (big body mass index) needs further study. (c) Patients after a history of abdominal liposuction may have extensive scar formation in the subcutaneous tissue, especially in the puncture channel, then the scar tissue absorption of ultrasound is stronger. While liposuction also extensively damages the cutaneous nerves, it may affect the skin’s sensation, and skin damage may occur because it cannot experience the pain. Therefore, patients can only be strongly advised about this problem and willing to bear the risk of treatment. (d) Patients with severe anemia: Hemoglobin should be corrected to at least above 7 g/dL, and ultrasound ablation can be performed in patients without any symptoms caused by anemia. The main unsafe factors in patients with very severe anemia are unresponsive and unable to timely and accurately reflect the treatment experience during sedation, leading to severe adverse reactions. However, if the patient refuses blood transfusion because of the fear of blood contamination, intravenous iron infusion, and control of menorrhagia may be adopted to raise the hemoglobin level before HIFU treatment. Due to various clinical conditions, some patients with hemoglobin less than 60 g/L had been subjected to ultrasound ablation with good results. Nevertheless, care should be taken to adjust the depth of sedation, establish a reasonable plan, and make a good judgment by experienced HIFU surgeons. (e) Patients with medical illnesses are to be treated with care. Patients with a history of hypertension need to control blood pressure to a stable level before undergoing ultrasound ablation. Those with a history of cardiac disease or congenital heart disease should have the cardiac function assessed to be stable and has no obvious clinical symptoms. Ultrasound ablation can be performed with

4.20  Pregnancy After HIFU Ablation

59

close monitoring of cardiac function during HIFU ablation, and subsequent hospital stay is necessary to ensure patient safety. Patients with hyperthyroidism should be carefully assessed by a comprehensive physical examination and laboratory tests before surgery. It is often necessary to check tracheal displacement and compression, electrocardiogram, etc., to check for any abnormal cardiac function. Under the control of an endocrine specialist, the patient can be treated with ultrasound ablation after the disease becomes stable. (f) No shrinkage of fibroids: After the HIFU ablation, some fibroids do not shrink in size. Usually, fibroids shrink slowly in size. The degree of shrinking however varies from person to person. Using an MRI image, if fibroids are associated with tissue necrosis, no blood flow/perfusion in the MRI scan, with symptoms improvement, such as reduced menstrual flow, improved dysmenorrhea, HIFU treatment can be considered successful. If the fibroid’s reexamination shows no shrinkage, that may be due to the following situations. After HIFU ablation, necrosis of fibroid tissue is complete, but the absorption decreases slowly. If there are no clinical symptoms, follow-up observations continue to monitor its progress. In the case of fibroid volume has reduced, but the remaining tumor edge has increased. In this situation, the fibroid may not shrink further or increase slowly in size. Further evaluation is needed, and possibly additional HIFU treatment or surgery may be required because of undiagnosed uterine sarcoma risks.

4.19 Recurrence of Fibroids The pathogenesis of uterine fibroids is not yet clear and may relate to the uterine myometrium’s high sensitivity to estrogen. Proper diet, exercise, sleep, and emotional control are advisable. For young patients with no plan of pregnancy, they should have strict contraception. They should also take fewer soy products, honey, and others rich in phytoestrogens. Regular follow-up examinations are necessary to monitor any recurrence. The recurrence rate of fibroids evaluated up to 24 months after HIFU treatment was lower than or comparable to other uterus-preserving operations like the myomectomy. The reported recurrence rate was 7.4% at 12  months, 14–21.7% after 24  months [24]. Follow-up data after 5  years is still not available. The reported cumulative recurrence rate after 5 years is 32% for uterine artery embolization and 5.7–33% for myomectomy. So far, HIFU ablation showed a lower recurrence and re-intervention rate (