Endoscopic Treatment Strategy for Upper GI Tract Neoplasms 9813297360, 9789813297364

Citation preview

Endoscopic Treatment Strategy for Upper GI Tract Neoplasms Junko Fujisaki  Editor

123

Endoscopic Treatment Strategy for Upper GI Tract Neoplasms

Junko Fujisaki Editor

Endoscopic Treatment Strategy for Upper GI Tract Neoplasms

Editor Junko Fujisaki Department of Gastroenterology Cancer Institute Hospital of Japanese Foundation For Cancer Research Ariake, Koto-ku Tokyo Japan

ISBN 978-981-32-9736-4    ISBN 978-981-32-9737-1 (eBook) https://doi.org/10.1007/978-981-32-9737-1 © Springer Nature Singapore Pte Ltd. 2020 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Preface

It goes without saying that the recent developments in the field of gastrointestinal (GI) endoscopy have been remarkable. GI endoscopy has now become indispensable in both the diagnosis and treatment of GI disorder. Especially Endoscopic Submucosal Dissection (ESD) has been developed in Japan. The Cancer Institute Hospital of JFCR in Tokyo is one of the highest-volume centers of cancer treatment in Japan. And we performed about 800 cases of endoscopic therapy for the early-­stage superficial esophageal, gastric, and duodenal cancer. Endoscopic diagnosis is an important factor to the success of endoscopic therapy, especially ESD. This book is standard for endoscopic diagnosis and treatment of the early-stage upper GI cancer in Japan. Almost all cases were referred to the Japanese guideline. Recently, magnified endoscopy with narrow band imaging is popular in the world. And usually, we use such modalities to diagnose early-stage GI cancers. Diagnosis criteria of magnified NBI are different for each part, the esophagus, stomach, and duodenum. In this book, we showed diagnostic endoscopy using magnified NBI and EUS. And then, we suggest therapeutic strategy for early stage of upper GI cancer. Our members, as specialist in their sections, wrote the therapeutic strategy in detail. I am grateful to our members for helping me completely finished this E-book. I also appreciate the help of Miss Kambara, editorial officer in Springer. Moreover, I appreciate Prof. Rikiya Fujita, who has already retired and moved to Hokkaido, for giving me the opportunity to publish this E-book. I hope the endoscopists all over the world will refer to this E-book and Prof. Fujita’s happy life in Sapporo. Tokyo, Japan

Junko Fujisaki

v

Contents

Part I Esophagus 1 Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)��������  3 Keigo Suzuki, Naoki Akazawa, and Junko Fujisaki 2 Esophageal Cancer: Squamous Cell Carcinoma (SCC)���������������������������� 19 Kaoru Nakano, Yoshimasa Horie, Akiyoshi Ishiyama, and Toshiyuki Yoshio 3 Esophageal Benign Tumor���������������������������������������������������������������������������� 37 Seiichi Yakabi and Toshiyuki Yoshio Part II Stomach 4 Gastric Cancer, ESD Absolute Indication, Expanded Indication, and Out of Indication Lesions������������������������������������������������������������������������������ 45 Mitsuko Inuyama, Yoshitaka Tokai, Sho Shiroma, Mitsuaki Ishioka, and Yusuke Horiuchi 5 Gastric Adenoma�������������������������������������������������������������������������������������������� 61 Hiroyuki Hatamori and Yusuke Horiuchi 6 Gastric Polyp: Inflammatory Fibroid Polyp, Hyperplastic Polyp, and Inverted Hamartomatous Polyp������������������������������������������������������������ 65 Ken Namikawa and Toshiaki Hirasawa 7 Gastric Submucosal Tumor (Leiomyoma, GIST, etc.) and LECS������������ 71 Yasunori Yamamoto and Toshiaki Hirasawa Part III Doodenum 8 Duodenal Adenoma���������������������������������������������������������������������������������������� 79 Yohei Ikenoyama and Shoichi Yoshimizu 9 Adenocarcinoma ESD and EMR������������������������������������������������������������������ 85 Atsuko Tamashiro and Shoichi Yoshimizu

vii

Part I Esophagus

1

Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA) Keigo Suzuki, Naoki Akazawa, and Junko Fujisaki

1.1

 ong Segment Barrett’s Esophagus (LSBE), Depth DMM L (Figs. 1.1, 1.2, 1.3, and 1.4)

1.1.1 Case Presentation A 55-year-old male with Barrett’s esophageal adenocarcinoma, 0-IIb + 0-“IIc + IIa”, 82 mm, adenocarcinoma tub1 > tub2 > pT1a (DMM). a

b

Fig. 1.1  Barrett’s esophageal adenocarcinoma derived on the background of long segment Barrett’s esophagus (LSBE). (a) There is an all-round-circumference Barrett’s mucosa ranging from DL 28 to 36 cm, and it is diagnosed as LSBE corresponding to C3M8 in Prague classification. (b) White light images (WLI) revealed a reddish depressed lesion on the 3–6 o’clock side, and flat reddish lesion is observed on the 7–9 o’clock direction. The margin of the lesion is unclear using conventional endoscopy. (c) Indigo carmine spraying emphasizes the reddish lesion and surface irregularities. The edge of the depression in the 4 o’clock direction appears to be the thickness is elevated. However, it is also difficult to identify the margin as WLI K. Suzuki · N. Akazawa · J. Fujisaki (*) Department of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2020 J. Fujisaki (ed.), Endoscopic Treatment Strategy for Upper GI Tract Neoplasms, https://doi.org/10.1007/978-981-32-9737-1_1

3

4

K. Suzuki et al.

c

Fig. 1.1 (continued)

a

b

c

Fig. 1.2 (a) Non-magnifying endoscopy with NBI. It is recognized as a broad brownish area, and the surface structure of this part has an irregular appearance. (b, c) Magnifying endoscopy with (ME-NBI). In the depressed area, irregular mesh-pattern microvessels are observed, and surface structure could not be recognized. In the elevated part surrounding the depressed area, surface structure is irregular. From the endoscopic findings, the lesion was considered to be present in a wide range extending from the 3 o’clock direction to the 9 o’clock direction in the Barrett’s mucosa. And biopsy specimens taken from the lesion were adenocarcinoma, tub1–tub2. The majority of the lesions were flat, and the depth of invasion was thought to be T1a, but since the edge of the depression in the 4 o’clock direction was elevated and it seemed to be a little thick, then we considered that the depth diagnosed T1b

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

5

Fig. 1.3  This is the endoscopic ultrasound (EUS) findings in this case. EUS is performed using the de-aired water repletion technique. The third layer consistent with the elevated lesion has been thinning; it was considered the depth of invasion has reached T1b-SM2. Finally, we diagnosed it as Barrett’s esophageal adenocarcinoma with SM2 invasion, and surgical operation was performed

a

b

SMM DMM

Fig. 1.4 (a) Mapping image of resected specimen by surgical operation. Red lines show the area of adenocarcinoma. The cancer was distributed around the whole circumference, and there was cancer in a wider range than the preoperative diagnosis. The size of the lesion was 82 mm in diameter. (b) Pathological findings in this case. The depth of invasion was SMM in majority of the lesion, but reached DMM partially. There are no findings of SM clinically. Although no venous invasion was observed, infiltration of signet ring cell carcinoma was observed in lymphatic vessels

1.1.2 Discussion In Japan, there is concern that an increase in Barrett’s esophageal adenocarcinoma (BEA) is caused by decreasing Helicobacter pylori infection rate and Westernization of diet [1]. However, in Japan, reports on Barrett’s esophageal cancer are not enough; diagnosis and treatment system have not been established. On the other hand, various evidence behind abundant number of patients has been accumulated in the West countries; there is a difference in the stance of endoscopic method and surgical resection between the West and Japan, and it is difficult to adopt the Western method as it is.

6

K. Suzuki et al.

Barrett’s esophagus is a precursor lesion of adenocarcinoma, and in Europe and the United States, it is reported that carcinogenesis is seen from Barrett’s esophagus at an annual rate of 0.3–0.5% [2, 3]. According to the recent follow-up survey of LSBE by a multicenter from Japan, adenocarcinoma of 1.2% per year occurred, almost the same as previous report [4]. The carcinogenic risk of Barrett’s esophagus is correlated with the size [5]; the risk of carcinogenesis is higher in LSBE compared to short segment Barrett’s esophagus (SSBE). Elevated lesions are observed more than half of the cases whether the developmental location is SSBE or LSBE, but it has been reported that BEA in LSBE has a higher proportion of flat depressed type [6]. There are also reports that lesions showing macroscopic type 0-IIb or accompanying type 0-IIb are more in LSBE [6]. This case is also a flat depressed type which accompanies 0-IIb lesion. Moreover, as in this case, adenocarcinoma arising from LSBE may be difficult to find using an endoscope; their boundary is also unclear with the surrounding weak structure deformed. For that reason, random biopsies performed in 1–2 cm intervals in Barrett’s esophagus in four directions are recommended as a surveillance method in the West. However, random biopsies are not common in Japan, and Endoscopic biopsies are often performed by recognizing with an enoscope. Since magnifying endoscopy is prevalent in Japan, we diagnose the extent of lesions by endoscopic observation using NBI, and endoscopic resection is performed for cases with a depth of invasion within T1a. However, there is another report that range diagnosis was difficult as in this case; especially attention is required for BEA developed on the background of LSBE [7].

1.2

 hort Segment Barrett’s Esophagus (SSBE), S Depth: p-SMM (Figs. 1.5, 1.6, and 1.7)

1.2.1 Case Presentation A 58-year-old male with Barrett’s esophageal adenocarcinoma, 0-IIa, 38 mm, adenocarcinoma, tub1, pT1a (SMM).

1.2.2 Discussion Esophageal adenocarcinoma has been reported to have metastasis at a probability of about 8% even for cancers with depth of invasion M [8, 9]. Therefore, the necessity of additional treatment is judged depending on the result of the presence of vascular invasion and the presence of poorly differentiated component in pathological result after ESD. However, as shown in Table 1.1, it was proved that there was no lymph node metastasis under the condition of vascular invasion negative, no poorly differentiated component, invasion of 3 cm or less, and SM 500 μm or less in a multicenter research in Japan [9].

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

a

b

c

d

7

Fig. 1.5  Barrett’s esophageal adenocarcinoma derived on the background of SSBE. (a) Distribution of palisade blood vessels was observed on the 12 o’clock direction, and the elevated lesion is seen in the 3 o’clock direction. (b) Palisade vessels can also be observed on the 6 o’clock direction, and the upper end of the stomach fold can be confirmed at 12 o’clock, so it is a lesion occurring in Barrett’s esophagus. The elevated lesion is also observed in the 3 o’clock direction. Biopsy specimen taken from the lesion is adenocarcinoma, tub1. (c) In indigo carmine spraying, the lesion is considered to be consistent with the elevated change. The margin is clearly visible both on the anal side and the oral side. (d) Using ME-NBI of the blue square area in (c), mesh-patterned microvessels and small ductal structures with unclear vessel pattern are recognized

Figure 1.7a, b shows the depth of invasion of superficial Barrett’s esophagus cancer. Barrett’s mucosa is different from the normal esophagus and has double muscularis mucosae; therefore, the definition of depth of invasion is also different from normal esophageal cancer. In Japan, the depth of invasion of Barrett’s esophageal adenocarcinoma refers to cancer that has reached DMM as T1a, and T1a is further divided into three stages of SMM, LPM, DMM. Barrett’s esophageal adenocarcinoma diagnosis and treatment policies differ between Japan and the West. First, in the diagnosis of Barrett’s esophagus, in Japan, it is decided to recognize palisade vessels and the upper end of stomach folds, but in Europe and the United States, palisade vessels are not used [10, 11]. Furthermore, the definition of depth of invasion is also different between Japan and the West. There is also a difference between treatment methods and diagnostic methods. In Japan, ESD is widely used as a general treatment, and range diagnosis by magnifying endoscopy is common as preoperative diagnosis.

8

K. Suzuki et al.

a

b

1

2

Fig. 1.6 (a) Mapping image of resected specimen by endoscopic submucosal dissection (ESD). Red lines show the area of adenocarcinoma, blue lines show the area of squamous epithelium, and green lines show the area of specialized columnar epithelium. Yellow dots show the distribution of esophageal glands. Since the esophageal glands are presented in the adenocarcinoma, it is considered that the lesion is located on the esophagus. Therefore, it can be diagnosed as Barrett’s adenocarcinoma. (b) The layer of (1) is superficial muscularis mucosae (SMM), and the layer of (2) is deep muscularis mucosae (DMM). Well-differentiated adenocarcinoma (tub1) in the blue square, then depth of invasion limited in SMM

a

b 5 4

Fig. 1.7 (a, b) Characteristics of Barrett’s mucosa include the presence of esophageal proper glands (1), islands of squamous epithelium (2) and histologic palisade vessels (3), double muscularis mucosae (3, 4). Double muscularis mucosae means that SMM which is a newborn muscularis mucosae can be seen in shallower layer than DMM which is the original muscularis mucosae. In Barrett’s esophageal adenocarcinoma, the depth of invasion within DMM is regarded as intramucosal cancer, and the lesion that remains between SMM and DMM is classified as LPM Table 1.1  From [9]

SMM LPM DMM SM 1–500 μm SM 500 μm–

LVI (−) and poorly comp (−) ≦3 cm 3 cm< 0% (0/44 lesions) 0% (0/6 lesions) 0% (0/41 lesions) 0% (0/7 lesions) 0% (0/82 lesions) 0% (0/6 lesions) 0% (0/32 lesions) 11.1% (1/9 lesions) 8.6% (3/35 lesions) 22.2% (4/18 lesions)

LVI (+) or poorly comp (+) 0% (0/1 lesions) 0% (0/2 lesions) 60.0% (9/15 lesions) 16.7% (3/18 lesions) 36.6% (52/142 lesions)

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

9

However, in the United States and Europe, it is common that the coagulation treatment like APC or RFA is performed to not only cancer but also background Barrett mucosa [12].

1.2.3 Discussion This case is Barrett’s esophageal adenocarcinoma on the SSBE background; it corresponds to C2M3 in Prague classification. In this case, the diagnosis can be performed with an endoscopy, and treatment methods can be appropriately selected. And the depth of invasion assessment was performed sufficiently by simultaneous resection by ESD. This case has been followed without additional treatment after ESD treatment and has been observed for more than 5 years, but no recurrence or occurrence of metachronous cancer has been observed. Table  1.1 was quoted from the retrospective study in Japan [9]. Lymph node metastasis was not observed in patients with depth of invasion up to SMM-LPM even though the vascular invasion was positive (0/101:0%). In the DMM cases, there was no lymph node metastasis in cases without vascular invasion and poorly differentiated components (0/88:0%). However, in cases with vascular invasion and poorly differentiated components, lymph node metastasis was confirmed with high probability (9/15:60%). When SM1 was defined as within 500  μm, there is no metastasis in cases in which the size was less than 3 cm and no poorly differentiated components or negative for vascular invasion (0/32:0%).

1.3

SSBE, D  epth: p-T1b, SM2

1.3.1 Case Presentation (Figs. 1.8, 1.9, 1.10, 1.11, 1.12, and 1.13) A 65-year-old male with Barrett’s esophageal cancer, 0-I + IIc, 15 mm adenocarcinoma, tub2 > tub1 > por, pT1b (SM 500 μm).

1.3.2 Discussion An evaluation of the risk of metastasis from esophago-gastric junctional (EGJ) adenocarcinoma is very important. The risk of metastasis of esophageal adenocarcinoma has been reported in a multicenter retrospective study in Japan. This study proposed a new set of criteria for endoscopic resection. Lymphovascular invasion, poorly differentiated type components, and lesion size of more than 30 mm were independent risk factors for lymph node metastasis. No metastasis was observed in patients with mucosal cancer or less than 500  μm submucosal invasion in the absence of other risk factors (Table 1.1).

10

K. Suzuki et al.

a

b

Fig. 1.8  Endoscopic findings. White light images. (a) There was a reddish protruding type lesion in the right side of EGJ. Surface was erosive. SSBE was seen around the lesion. Palisade vessels were seen indicated by a yellow arrow. (b) Oral side of the lesion. Superficial depressed lesion was seen close to the protruded lesion. The size was 15 mm in diameter

a

b

Fig. 1.9  NBI imaging. (a) The lesion was visualized as a brownish area. (b) Oral side of the lesion. Superficial depressed area was visualized as a brownish area. Demarcation line was clear

a

b

Fig. 1.10  Indigo carmine spraying image. (a) Superficial depressed area that surrounded the protruded area was seen. Macroscopic type was 0-I + IIc. (b) Superficial depressed area and clear margin were seen in the oral side

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

a

b

c

d

11

Fig. 1.11  ME-NBI image. (a, b) In protruding area. Surface structure and vessels were unclear. It seems that the surface of the lesion is erosive. (c, d) In oral side, there was a superficial depressed area. Irregular microvessels were seen. Surface structure was unclear

a

b

Fig. 1.12  EUS findings. (a, b) EUS showed a low-echoic, heterogeneous lesion in the first and second layers. The third layer was detected but did not disappear. This lesion seems to be located in the mucosal layer

12

K. Suzuki et al.

b

a

c

d

Fig. 1.13  Histopathological findings. Adenocarcinoma (tub2 > tub1 > por), 0-I + IIc, T1b-SM2 (500 μm), ly1 (D2-40), v1, HM-, VM-. (a) Mapping image of resected specimen. Red line is area of adenocarcinoma. Dotted line is area of SM invasion. (b) With a magnifying lens. High power view ×40. (c) Higher magnification. Superficial depressive area. (d) Higher magnification. High power view ×80. SM invasion was seen under the protruded lesion. The depth of SM invasion was 500 μm

There were several reports about endoscopic diagnosis of invasion depth for superficial Barrett’s esophageal cancers [13]. During endoscopic diagnosis by conventional endoscopy, endoscopic morphology, size, and stiffness of lesions are important to estimate the depth of invasion. Protruding type 0-I, especially sessile lesion and high elevated lesion tend to invade the SM layer. Pedunculated 0-I lesion is usually confined to the mucosa. If the lesion has differentiation of color, mixed macroscopic type, larger size, deeper depression, erosion, and ulceration, the lesion invades more deeply. It was reported that it is difficult to precisely differentiate between T1a-SMM/ LPM and T1a-DMM and to distinguish T1a-DMM/SM1 using EUS [14]. On the other hand, diagnostic accuracy rate SM2/SM3 is relatively high. Because the location of the lesion makes it difficult to scan and Submucosal fibrosis is cause of misdiagnosis of the depth. EUS is of limited value for assessment of mucosal cancers, but was able to accurately estimate the depth of SM invasion. Using both EUS and conventional endoscopy is needed to diagnose ­accurately [15]. In this case, the lesion was reddish, erosive, and protruding type. Macroscopic type is mixed with superficial depressed area around protruding area. SM invasion was highly suspected by endoscopic findings. However, there was no feature of SM invasion by EUS.  We selected ESD.  Pathological diagnosis was non-curative. Additional surgery was performed and no cancer remained.

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

1.4

13

 sophago-Gastric-Junctional Carcinoma (EGJ Ca): E Depth p-M Adenocarcinoma (Figs. 1.14, 1.15, 1.16, 1.17, 1.18, and 1.19)

1.4.1 Case Presentation A 65-year-old male with Esophago-gastric junction adenocarcinoma, 0-IIc, 15 mm, p-M, adenocarcinoma tub1, pT1a,M.

1.4.2 Discussion In our country, there are two guidelines for early cancer in this area. One is gastric cancer guideline for adenocarcinoma, and another is esophageal cancer guideline for

a

b

Fig. 1.14  Endoscopic findings. White light image. There was reddish superficial flat lesion in the gastric side of EGJ. It was close to SCJ. Barrett’s mucosa was not detected around the lesion. (a) Oral side of the lesion. (b) Gastric side of the lesion. Margin of the lesion was unclear

a

b

Fig. 1.15  ME-NBI. The lesion was visualized as a brownish area. Demarcation line was relatively clear. Irregular surface structure were seen in the lesion

14

a

K. Suzuki et al.

b

Fig. 1.16  Indigo carmine spraying image. The lesion was visualized as superficial depressed area. Margin of the lesion was recognized as reddish area. The size was 15 mm in diameter

a

b

Fig. 1.17  EUS findings. EUS showed a low-echoic, heterogeneous lesion in the first and second layers. The third and fourth layers had no change. This lesion seems to be located in the mucosal layer

squamous cell carcinoma. However, criteria of curative SM invasion depth are different; one is 500 μm and another is 200 μm (Table 1.2). Few studies have focused on lymph node metastasis risk of esophageal adenocarcinoma and EGJ adenocarcinoma. Criteria of curative resection are controversial. Recently, the risk of metastasis of superficial esophageal adenocarcinoma has been reported in a multicenter retrospective study in Japan. This study proposed a new set of criteria for endoscopic resection. Mucosal and submucosal cancers with less than 500 μm invasion in the absence of other risk factors (lymphovascular invasion, poorly differentiated components, and lesion size of more than 30 mm) were considered to be no risk for lymph node metastasis. However, this study did not include cardiac cancer. In our institution, we evaluate the lymph node metastasis risk of EGJ adenocarcinoma, including cardiac cancer in ER cases. Our data showed that criteria of endoscopic resection for superficial esophageal adenocarcinoma is suitable for EGJ adenocarcinoma including cardiac cancer.

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

15

b

a

c

d

Fig. 1.18  Histopathological findings. Adenocarcinoma (tub1), 0-IIc, 15 × 12 mm, T1a-M, ly0, v0, HM0, VM0. (a) Mapping image of resected specimen. Red line is area of adenocarcinoma. Green line is area of squamous epithelium. Esophageal glands were seen under columnar epithelium (○). (b) With a magnifying lens. No.8. (c) Higher magnification. Area of SCJ. (d) Higher magnification. Tumor extension under the squamous epithelium was seen in the oral side

Location of adenocarcinoma A

Siewbert typeII

CC

B or C

BEA

A + B

EGJ adenocarcinoma

B + C + D

Few Reported

Esophageal adenocarcinoma

EGJ

Reported

Evaluate the metastasis risk of “Esophageal adenocarcinoma” Independent risk factors

Ly, or v, positive or

Ishihara et. al. J Gastroenterol 52: 800-808, 2017

YES

Poorly component

No

Lesion size >30mm

SM >500µm invasion

or

High risk

YES No

Low risk

Fig. 1.19  Location of adenocarcinoma

In this case, endoscopic findings showed that the lesion is located in the gastric side of EGJ, and SSBE was not detected around the lesion. Before ER, gastric cancer guideline seemed to be suitable for this lesion. However, after ER, pathological

16

K. Suzuki et al.

Table 1.2  LN metastasis and depth of tumor [18] “LN metastasis and depth of tumor “invasion” M/SMM/LPM MM/DMM SM 1-200 µm 201-500 µm 501 µm–

BEA n=53 0/19 0/17 0/5 0/3 2/9 (22.2%)

CC n=67 0/49 0/8 0/5 0/5

Total 0/68 0/17 0/13 0/8 2/14 (14.2%)

BEA: Barrett’s esophageal adenocarcinoma CC: Cardiac Caner

findings showed that there were esophageal glands under the columnar epithelium, and it means that there was SSBE around the lesion. So the classification of this lesion is Barrett’s esophageal adenocarcinoma in EGJ, but there was no guideline for Barrett’s esophageal adenocarcinoma. Recently, new criteria of ER for esophageal adenocarcinoma were proposed, and our data showed that the criteria are suitable for EGJ adenocarcinoma including cardiac cancer [16]. New criteria for EGJ mentioned above are suitable for this case. Pathological diagnosis showed curative resection [17].

References 1. Hongo M, Nagasaki Y, Shoji T. Epidemiology of esophageal cancer: orient to occident. Effects of chronology geography and ethnicity. J Gastroenterol Hepatol. 2009;24:729–35. 2. Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365:1375–83. 3. Desai T, Krishnan K, Samala N, et al. The incidence of oesophageal adenocarcinoma in nondysplastic Barrett’s oesophagus: a meta-analysis. Gut. 2012;61:970–6. 4. Matsuhashi N, Sakai E, Ohata K, et al. Surveillance of patients with long-segment Barrett’s esophagus: a multicenter prospective cohort study in Japan. J Gastroenterol Hepatol. 2017;32:409–14. https://doi.org/10.1111/jgh.13491. Epub 2016 Jul 15 5. Rudolph RE, Vaughan TL, Storer BE, et al. Effect of segment length on risk for neoplastic progression in patients with Barret esophagus. Ann Intern Med. 2000;132:612–20. 6. Fujisaki J, Omae M, Shimizu T, et  al. Endoscopic findings of superficial Barrett’s esophageal adenocarcinoma–picking up the lesion at the early stage. Stomach Intesitne. 2016;51(10):1229–310. 7. Kuribayashi S, Kawada A, Hosaka H, et al. Endoscopic diagnosis and treatment of Barrett’s esophagus or Barrett’s adenocarcinoma. J Gastroenterol. 2015;57(1):3–14. 8. Dunbar KB, Spechler SJ. The risk of lymph-node metastasis in patients with high-grade dysplasia or intramucosal carcinoma in Barrett’s esophagus: a systematic review. Am J Gatroenterol. 2012;107(6):850–62. 9. Ishihara R, Oyama T, Seiichiro A, et al. Risk of metastasis in adenocarcinoma of the esophagus: a multicenter retrospective study in a Japanese population. J Gastroenterol. 2017;52(7):800–8. 10. The Japan Esophageal Society. Guidelines for diagnosis and treatment of carcinoma of the esophagus. 2017. 11. Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2013;63:7–42.

1  Esophageal Cancer: Barrett’s Esophageal Adenocarcinoma (BEA)

17

12. Pech O, May A, Manner H, et al. Long term outcome of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology. 2014;146:652–60. 13. Yoshinaga S, Oda I, Tanaka Y, et  al. Endoscopic diagnosis of superficial Barrett’s esophageal cancers—depth diagnosis (in Japanese abstract in English). Stomach Intestine. 2016;51:1311–20. 14. Arima M, Tada M, Tanaka Y, et al. Endoscopic ultrasonography in the diagnosis of Barrett’s esophageal cancer. Stomach Intestine. 2011;46:1852–60. 15. Oda I, Kusano M, Abe S, et al. Endoscopic diagnosis of tumor depth of adenocarcinoma at the esophagogastric junction. Stomach Intestine. 2009;44:1155–62. 16. Japan Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part 1. Esophagus. 2017;14:1–36. 17. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14:101–12. 18. Akazawa N, Fujisaki J. Lymph node metastasis risk in superficial esophagogastric junction adenocarcinoma. Digestive Disease Week 2019, San Diego, CA, USA, May 2019.

2

Esophageal Cancer: Squamous Cell Carcinoma (SCC) Kaoru Nakano, Yoshimasa Horie, Akiyoshi Ishiyama, and Toshiyuki Yoshio

2.1

EP-LPM: Wide Lesion (Figs. 2.1, 2.2, 2.3, 2.4, and 2.5)

2.1.1 Case Presentation A 65-year-old male with superficial esophageal carcinoma. 0-IIc, 41 mm, Squamous cell carcinoma, pT1a (LPM).

2.1.1.1 Preoperative Examination A white light imaging (WLI) endoscopy showed a 2/3 circumference rough reddish depressed area with keratinization on the right wall of middle to lower thoracic

a

b

Fig. 2.1 K. Nakano · Y. Horie · A. Ishiyama · T. Yoshio (*) Department of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2020 J. Fujisaki (ed.), Endoscopic Treatment Strategy for Upper GI Tract Neoplasms, https://doi.org/10.1007/978-981-32-9737-1_2

19

20

K. Nakano et al.

esophagus. There was no granular change or nodule within the depressed area. Predicted depth of tumor invasion was lamina propria mucosa (LPM) (Fig. 2.1). On narrow-band imaging (NBI) without magnification, the lesion was recognized as a brownish area. Using magnifying endoscopy with narrow-band imaging (ME-NBI), type B1 vessels were observed in the visible part of the lesion. Predicted depth of tumor invasion was epithelium (EP) or LPM (Fig. 2.2). After iodine staining, the lesion became well-demarcated manifesting as an unstained area with a positive pink color sign in accordance with the reddish area on WLI. The size of the widest part of the lesion was beyond 2/3 circumference (Fig. 2.3).

2.1.1.2 Preoperative Diagnosis The lesion was a superficial depressed type (0-IIc), 40 mm in size, and 2/3 circumference on the right wall of middle to lower thoracic esophagus. Predicted depth of tumor invasion was comprehensively LPM. Biopsy specimen in the previous hospital revealed squamous cell carcinoma. a

b

Fig. 2.2

a

Fig. 2.3

b

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

21

2.1.1.3 Treatment We performed esophageal ESD using SB Knife Jr.® (Sumitomo Bakelite Co., Tokyo, Japan), Dual Knife® (Olympus Medical Systems, Tokyo, Japan), and the insulated tip knife nano (IT nano®) (Olympus Medical Systems, Tokyo, Japan) as a cutting device. At first, we recognized the demarcation line of the lesion with NBI and iodine staining, after that, we put the marking around the lesion by snare tip (Fig. 2.4a). And then, a solution in which 0.4% sodium hyaluronate solution (Mucoup®, Boston Scientific Co., Tokyo, Japan and Seikagaku Co., Tokyo, Japan) and saline were mixed in a ratio of 1:1 was injected to the submucosal layer; mucosal cutting and submucosal dissection were performed. The mucosal defect after ESD was 4/5 circumference in this case (Fig. 2.4b). For preventing the stenosis after ESD, a solution prepared by dissolving 80 mg of triamcinolone acetonide (Kenacort, Bristol-Myers Squibb Co., New York, USA) in 18 ml saline was injected to the remaining submucosal layer inside of the mucosal defect (Fig. 2.4c).

a

b

c

d

Fig. 2.4

22

K. Nakano et al.

On the follow-up examination 3 months after ESD, a whitish scar was observed identically concordantly with the mucosal defect after ESD. There was no stenosis, so a panendoscope was able to pass smoothly (Fig. 2.4d).

2.1.1.4 Histopathological Diagnosis Formalin-fixed specimen was thoroughly washed with water and stained with iodine. The size of the lesion was 41 mm × 31 mm (Fig. 2.5a). At low-power magnification of the deepest site of the tumor, squamous cell carcinoma forming tumor nests showed downgrowth toward the mucosal lamina propria. Tumor nests did not reach the muscularis mucosa (Fig. 2.5c, d). The depth of tumor invasion was pT1a-LPM, and the infiltrative growth pattern was INFa. There was no lymphovascular invasion. Resection margin was negative. Finally, the histopathological diagnosis was as follows. Gross type: 0-IIc, Size: 41 × 31 mm, Histology: moderately differentiated squamous cell carcinoma, Invasion depth: pT1a-LPM, ly0, v0, HM0, VM0. A curative resection was achieved.

2.1.2 Discussion 2.1.2.1 Treatment Algorithm According to the Japanese guidelines for the treatment of esophageal cancer, T1a-­ epithelium (EP) or T1a-lamina propria mucosae (LPM) squamous cell carcinoma (SCC) less than 3/4 circumference without lymph node metastasis or distant metastasis is an absolute indication for endoscopic resection (ER), while EP/LPM more than 3/4 circumference is indicated ER accompanying preventive treatment for stricture [1, 2]. The lesion in this case was consistent with the criteria and was an indication for ER.

a

c

Fig. 2.5

b

d

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

23

The curability of ER for esophageal squamous cell carcinoma (ESCC) without clinical metastasis was decided by pathological evaluation about depth of invasion, presence or absence of residual tumor, and lymphovascular invasion. For this case, ER was achieved curative because of pathologically diagnosed pT1a-LPM with negative horizontal and vertical margin and without lymphovascular invasion. This patient is alive without relapse within 1 year.

2.1.2.2 Prevention of Esophageal Stenosis Stricture The Japanese guidelines for the treatment of esophageal cancer strongly recommend to perform some kind of strategies to prevent esophageal stenosis stricture [2]. Serial endoscopic balloon dilation (EBD), endoscopic triamcinolone injection (ETI), and oral prednisolone administration after ESD have been reported to be effective [3–6]. Since there is no report comparing and examining which method is superior in many cases, a phase III study of oral steroid administration versus ETI local steroid injection therapy for the prevention of esophageal stenosis stricture after endoscopic submucosal dissection (ESD) (JCOG1217) is ongoing. As significant complications, intraoperative perforation with EBD, delayed perforation with ETI, and systemic infection with oral prednisolone administration could occur; informed consent is important. In our hospital, we select ETI and/or oral prednisolone administration depending on the area of the mucosal defect after ESD for esophageal cancer with broad high circumference. In this case, after ESD for 2/3 circumference lesion, the mucosal defect became 4/5 in circumference. Because we judged that the risk of stenosis after ESD was high, triamcinolone was injected to submucosa in and around post ESD ulcer and could prevent esophageal stenosis.

2.2

 ndoscopic Resection with Additional E Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: ER + CRT Presentation (Figs. 2.6, 2.7, and 2.8)

2.2.1 Case Presentation A 67-year-old male with superficial esophageal carcinoma, 0-IIc, 21mm squamous cell carcinoma, pT1b (SM2). In this case, endoscopy revealed a reddish superficial depressed lesion (0-IIc) in white light imaging (WLI), located in the middle thoracic esophagus. In narrow band imaging (NBI), we could recognize the lesion as brownish area, suggesting the lesion as esophageal squamous cell carcinoma (ESCC). The lesion did not have obvious irregularity showing protruding over 1 mm (0-I) or excavated (0-III) area indicating SM2 invasion; however, the lesion had some large granules and one of them was thick in the depressed area. When the air was deflated, the thick area caused a change of curvature in esophageal wall in the center of the lesion, suggesting it the deepest part of the lesion. Although we could not exclude the possibility of SM2  in the deepest area, we diagnosed the depth of invasion as MM/SM1  in WLI. In magnifying endoscopy with NBI, type B2 vessels were widely observed in

24

K. Nakano et al.

a

b

d

e

c

Fig. 2.6 (a) WLI showed a reddish superficial depressed lesion (0-IIc). The lesion did not have obvious irregularity; however, the lesion had some large granules and one of them was thick. (b) When the air was deflated, the thick area caused a change of curvature in esophageal wall in the center of the lesion. (c) In narrow band imaging (NBI), we could recognize the lesion as brownish area, suggesting the lesion as esophageal squamous cell carcinoma (ESCC). (d) In magnifying endoscopy with NBI, type B2 vessels were widely observed in the area of large granule. (e) After iodine staining, it was shown that the lesion was an unstained area with positive pink color sign

a

b

Fig. 2.7  In endoscopic ultrasound (EUS) findings, the tumor was visualized as a low echoic area touching and pushing down the third layer of seven layers without thinning

the area of large granule; however, type B3 vessels were not observed even in the deepest area. Magnifying endoscopic findings suggested the depth of invasion as MM/SM1, although we could not exclude SM2 because of low existing rate of B3 vessels in SM2. By endoscopic ultrasound (EUS), the tumor was visualized as a low echoic area touching and pushing down the third layer of seven layers without thinning, indicating the tumor depth as MM/SM1 in thick area. Considering them, we clinically diagnosed MM/SM1 and treated by ESD.

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

a

25

b

c Fig. 2.8 (a) Mapping image of resected specimen by ESD. Red lines show the area of SCC. Blue lines show the dysplasia. (b, c) In pathology, most of the lesion was limited in MM; however, the deepest part invaded into submucosa by 300 μm only in an area of 2 mm (T1b-SM2, ly1, v0, HM0, VM0)

The pathological diagnosis was T1b-SM2, ly1, v0, HM0, VM0. Most of the lesion was limited in MM; however, the deepest part invaded into submucosa by 300 mm only in an area of 2 mm. We recommended additional chemoradiotherapy (CRT) or esophagectomy. This patient underwent CRT, and he is alive without relapse in 2 years.

2.2.2 Discussion The rate of lymph node (LN) metastasis after esophagectomy for ESCC in the depth of epithelium (EP), lamina propria mucosae (LPM), muscularis mucosa (MM), submucosa (SM) 1, SM2, and SM3 were 0%, 0%, 8%, 11%, 30%, and 61% [7]. From the risk of LN metastasis, ESCC with EP/LPM invasion are indicated for endoscopic resection (ER), and ESCC with MM/SM1 invasion are defined relative indication for ER [2, 8]. The standard treatment for ESCC with SM2 is esophagectomy or CRT. In our hospital, ER is performed in not only clinically diagnosed EP/LPM ESCC but also MM/SM1 ESCC. We usually observe patients without additional treatment, when pathological diagnoses of the lesion are without lymphovascular invasion, SM2 invasion, or vertical margin positive. However, with either of them, we consider additional esophagectomy or CRT. Recent advances in ER, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have enabled the effective removal of the primary lesions. In particular, ESD has a significantly high R0 resection rate, even if the lesion spreads wide or invades slightly into submucosa. The phase II trial (JCOG9708) suggested that definitive CRT (D-CRT) can be a good treatment option revealing the overall survival rate following D-CRT was comparable to surgery in patients with stage I ESCC [9]. However, its higher risk of locoregional failure compared with surgery remains a concern [10].

26

K. Nakano et al.

We recently have reported the efficacy of combined ER and CRT (ER-CRT) for T1 ESCC compared to D-CRT.  By treating the primary lesion with ER, we can obtain an accurate pathological diagnosis and can select an appropriate treatment strategy, which enables us to avoid unnecessary surgery and CRT.  Moreover, no patient has developed locoregional failure in the ER-CRT group, although 26% of patients developed in the D-CRT group. Thus, the 5-year relapse-free survival in the ER-CRT group was significantly more favorable than that in the D-CRT group [11]. We think ER-CRT is an effective and minimally invasive treatment that can be new option for ESCC with SM invasion. Shimizu et al. first reported favorable outcome of ER-CRT in small number of cases [12]. And multicenter prospective phase II trial (JCOG0508) also reported that ER-CRT for T1b ESCC is considered to be comparable to surgery in efficacy [13]. Furthermore, ER-CRT required a lower RT dose compared to D-CRT, which reduces the risk of late toxicity.

2.3

 M-SM1 (Additional Operation Case After ESD) M (Figs. 2.9, 2.10, and 2.11)

2.3.1 Case Presentation A 73-year-old male, 0-IIc, 58 mm squamous cell carcinoma, pT1a (MM).

a

b

c

d

e

f

Fig. 2.9 (a) In the white light imaging (WLI) endoscopy, there was a reddish depressed lesion. (b) The lesion had an elevated part at posterior wall side. (c) An elevated part of the lesion looked hard with weak extension. (d) In the NBI endoscopy, the lesion was recognized as a brownish area. We judged this elevated part (red line) the deepest area in this lesion. (e) In the ME-NBI, type B2 vessels were seen in this elevated area, but type B3 vessels could not be seen. (f) After iodine staining, it was shown that the lesion was an unstained area with positive pink color sign (arrow)

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

27

Fig. 2.10  In the endoscopic ultrasound (EUS) findings, the tumor was visualized as though pushing down MM as identical to the site of elevation in the depressed area

a b

Fig. 2.11 (a) The mapping image of the resected specimen by ESD. Red lines show the area of squamous cell carcinoma. (b) The pathological diagnosis was pT1a-MM, ly0, v0, HM0, VM0

2.3.2 Discussion Endoscopic resection (ER) is standard treatment for esophageal squamous cell carcinoma (ESCC) invading epithelium (EP) and lamina propria mucosae (LPM) layer. But if depth of tumor invasion is muscularis mucosa (MM) or shallow layer of submucosa (less than 200 μm under the MM; SM1), it requires additional treatment depending on the pathological findings. The risk of LN (lymph node) metastasis after ER of ESCC invading MM an SM1 was 2.24% and 11.7%, respectively [1]. In the ESCC invading MM, incidence of LN metastasis rate was 41.7% (5/12) in case of lymphatic invasion (ly) positive and was 10.3% (4/38) in case of ly negative. Therefore, ly was significantly associated with LN metastasis [7]. Another risk

28

K. Nakano et al.

factor for LN metastasis in case of MM and SM1 invasion was high among the group that included endoscopic findings such as type 0-I or 0-III and size of 50 mm or more and pathological findings such as poorly differentiated ESCC and INFb or INFc [15]. When these findings are included by pathological result in case of MM or SM1, we should consider the additional treatment after ER. Esophagectomy and definitive CRT are standard treatments for ESCC after ER with risk of LN metastasis. Esophagectomy with three-field LN dissection is a highly invasive treatment and associated with increased mortality [16]; however, it is difficult to accurately diagnose LN metastasis before operation. A Japanese phase II trial (JCOG0508) reported that the 3-year overall survival (OS) rate was 90.7% in 87 patients who had the lesion invading pT1b with negative resection margin or invading pT1a with lymphovascular invasion–prophylactic CRT group; therefore, ER-CRT therapy for T1b ESCC is considered to be comparable to surgery in efficacy [13]. We need to anticipate the risk of LN metastasis from pathological findings of specimen resected by endoscopy and finally decide the additional treatment taking into consideration the age and general condition. This case was a 57-year-old male (Fig. 2.12). In the white light imaging (WLI) endoscopy, there was a reddish depressed lesion. The lesion had an elevated part at posterior wall side. This part looked hard with weak extension. So we judged this part the deepest area in this lesion. In the NBI endoscopy, the lesion was recognized as a brownish area. In the magnifying endoscopy with NBI in this lesion, type B2 vessels were found in this elevated area, but type B3 vessels could not be seen. Therefore, we diagnosed depth of invasion was MM or SM1. In the endoscopic ultrasound (EUS) findings, the tumor was visualized as though pushing down MM as identical to the site of elevation in the depressed area. From EUS findings, diagnosed depth of invasion was MM, and ESD was performed. In the pathological findings, the lesion has invaded MM and had ly invasion. The final pathological diagnosis was squamous cell carcinoma, 52 mm × 40 mm, T1a-MM, ly0, v0, VM0, HM0. He selected esophagectomy as an additional treatment and had no LN metastasis. a

b

c

e

f

g

Fig. 2.12 (a–g) Typical findings under ME-NBI

d

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

29

2.3.2.1 The JES Classification The Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating invasion depth of superficial esophageal squamous cell carcinomas. Diagnostic criteria of the JES classification are based on the degree of microvascular irregularity in the target lesion observed by magnifying endoscopy. Intrapapillary capillary loops (IPCL) are a basic unit of microvasculature in the squamous mucosal surface. The microvascular irregularity is evaluated for the presence or absence of each of the following morphological factors: weaving, dilatation, irregular caliber, and different shape. Microvessels are classified as type A if they have three or fewer factors and type B if they have all four. Type B is then subclassified into B1, B2, and B3 based on the running pattern or degree of dilatation of severely irregular microvessels. The JES classification criteria are summarized in Table 2.1 and mentions details as follows: Type A: Abnormal microvessels without severe irregularity (Fig. 2.12a). Type B: Abnormal microvessels with severe irregularity or highly dilated abnormal vessels. B1 is defined as type B vessels with a loop-like formation (Fig. 2.12b). The B1 vessels normally appear as dot-like microvessels in a target area under NBI endoscopic observation with low or no magnification. B2 is defined as type B vessels without a loop-like formation that have a stretched and markedly elongated transformation. The B2 vessels often show a multilayered arrangement or an irregularly branched/running pattern (inside a white circle, Fig. 2.12c).

Table 2.1  Summary of the criteria of JES magnifying endoscopic classification Type of vessels Definitions A Normal IPCL or abnormal microvessels without severe irregularitya B1 B2 B3

Abnormal microvessels with severe irregularity or highly dilated abnormal vessels

Type B vessels with a loop-like formationb Type B vessels without a loop-like formation

Invasive depth No invasion

T1a-EP or T1a-LPM T1a-MM or T1b-SM1 Highly dilated vessels T1b-SM2 whose calibers appear to or deeper be more than three times that of usual B2 vesselsc

Histology Normal epithelium inflammation, and LGIN HGIN and invasive SCC

EP epithelium, LPM lamina propria mucosae, MM muscularis mucosae, SM submucosa, LGIN low-grade intraepithelial neoplasia, HGIN high-grade intraepithelial neoplasia, SCC squamous cell carcinoma a The caliber of type A vessels is about 7–10 μm b The caliber of B1 vessels is around 20 μm c The caliber of B3 vessels is often larger than 60 μm

30

K. Nakano et al.

B3 is defined as highly dilated abnormal vessels whose caliber appears to be more than three times that of the usual B2 vessels, and B3 vessels often appear green (or cyan) in color (white arrows, Fig. 2.12d).

2.3.2.2 Auxiliary Criteria of the JES Classification Avascular Area (AVA) AVA was originally defined as a low or no vascularity area surrounded by stretched irregular vessels such as B2 or B3 vessels. The definition of AVA does not include the stretched irregular vessels in this classification. Thus, AVA is surrounded by all subtypes of type B microvessels including B1 vessels. Since a diameter of AVA is positively correlated with the histological invasion depth of SESCC, the AVA was categorized into three types as follows: AVA-small (smaller than 0.5 mm in diameter: Fig. 2.12e), AVA-middle (0.5 mm or between 0.5 and 3 mm: Fig. 2.12f), and AVAlarge (3 mm or larger: Fig. 2.12g). Any types of AVA (small, middle, and large) surrounded by B1 vessels are suggestive of T1a-EP or T1a-LPM SCC. AVA-­middle and AVA-large surrounded by B2 or B3 vessels are suggestive of T1a-MM or SM1 and T1b-SM2 invasive SCC, respectively. Typical AVAs are shown by white dotted lines.

2.4

 M-SM1 (Follow-Up Case After ESD) (Figs. 2.13, 2.14, M 2.15, 2.16, and 2.17)

2.4.1 Case Presentation A 67-year-old male, 0-IIc, squamous cell carcinoma, 35 mm, pT1a (MM). A white light imaging (WLI) endoscopy showed a half circumferential rough reddish depressed area on the right wall of the lower thoracic esophagus. Since the lesion had an elevated portion in the anal side of the depressed area with certain thickness (arrow), we predicted that the depth of tumor invasion was muscularis mucosa (MM) (Fig. 2.13).

Fig. 2.13

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

31

In narrow band imaging (NBI) without magnification, the lesion was recognized as a brownish area (Fig. 2.14a, b). Using magnifying endoscopy with narrow band imaging (ME-NBI), we could observe type B2 vessels in the elevated portion and a vascular area (Fig. 2.14c) and type B1 vessel in other area (Fig. 2.13d). By NBI findings, we predicted that the depth of tumor invasion was MM or SM1 invading the upper third of the submucosal layer. After iodine staining, the lesion was well delineated as iodine unstained area with pink color sign. The lesion extended more than half in circumference in the widest part (Fig. 2.15). The elevated portion was not folded when we deflated the air (Fig. 2.15a, b). The lesion was a superficial depressed type, 0-IIc, 30 mm in size on the right wall of the lower thoracic esophagus. Predicted depth of tumor invasion was comprehensively MM. Pathological diagnosis in the previous hospital was squamous cell carcinoma in biopsy specimen. Enhanced CT scan of neck, chest, and abdomen showed that there was no lymph node metastasis or distant metastasis. From the above, we diagnosed this lesion as cT1N0M0 cStage0 in Japanese classification of esophageal cancer, 11th edition [1], and as indication for endoscopic resection (ESD).

a

b

c

d

Fig. 2.14

32

a

K. Nakano et al.

b

Fig. 2.15

a

b

c

Fig. 2.16

We treated this lesion by ESD using Dual Knife (Olympus Medical Systems, Tokyo, Japan). At first, we recognized the demarcation line of the lesion with NBI and iodine staining; after that, we placed marking dots around the lesion by Dual Knife (Fig. 2.16a). And then, we injected 0.2% sodium hyaluronate solution which

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

33

a b

c HE staining

d Desmin

Fig. 2.17

was diluted MucoUp in half (MucoUp, Boston Scientific Co., Tokyo, Japan) to the submucosal layer, incised around the lesion and dissected submucosa. The mucosal defect after ESD was 3/4 circumference in this case (Fig. 2.16b). To prevent the stenosis after ESD, 80  mg of triamcinolone acetonide (Kenacort, Bristol-Myers Squibb Co., New  York, USA) was injected to the remaining submucosa in and around the mucosal defect. On the follow-up examination, the ESD ulcer had healed without stenosis in 2 months after ESD (Fig. 2.16c). In pathology, the size of the lesion was 33 mm × 22 mm (Fig. 2.17a). The tumor nests formed by squamous cell carcinoma touched muscularis mucosa in the deepest site of the tumor in low power magnification at the elevated area in endoscopy (Fig. 2.17c, d). The depth of tumor invasion was pT1a-MM, and the infiltrative growth pattern was INFb. There was no vascular invasion. Resection margin was negative. Finally, the histopathological diagnosis was as follows. Gross type: 0-IIc, Size: 33 × 22 mm, Histology: moderate differentiated squamous cell carcinoma, Pathological diagnosis: pT1a-MM, ly0,v0, HM0, VM0.

2.4.2 Discussion We treat T1a-EP/LPM ESCC by endoscopic resection (ER), since lymph node metastasis (LNM) is rare. For T1a-MM and T1b-SM1 ESCC, we regarded them as relative indication for ER due to the risk of LNM, although it is possible to resect by ER [15, 16] with negative margin. The reported rates of LNM based on the specimens of surgical operation for T1a-MM ESCC with or without lymphovascular invasion (LVI) were 33–42% and 6–10%, respectively, and for T1b-SM1 ESCC with or without LVI, the rates were 18–100% and 15–17%, respectively [17, 18].

34

K. Nakano et al.

On the one hand, in ER cases, retrospective studies have reported that ESCC with MM invasion had only 0–4.2% of LNM, which was much lower than that of surgical cases [12, 15, 19]. Especially, all cases with MM without LVI did not have LNM, although the number of cases was small (0/42) [19]. The difference of LNM rate is considered to be caused by the difference in treating resected specimen. We usually cut surgical specimens in every 5 mm, while we cut ER specimens in every 2 mm. Considering the low risk of metastasis in patients with MM invasion without LVI, local treatment such as ER is adequate for these patients. For pT1a-MM ESCC with LVI, Shimizu et al. reported the five-year survival rate of ER combined with CRT was 100% [12], although the number of cases was limited. Then multicenter phase II trial (JCOG0508) was conducted to evaluate the efficacy and the safety of this combination therapy for T1 ESCC [13]. The efficacy of esophagectomy for the patients of non-curative resection after ER has been reported as an additional treatment [20]; thus, additional surgery is one of the good choices if the patient’s general condition permits. In our hospital, we indicate ER for ESCC with preoperative depth of T1a-MM/ T1b-SM1 as the first line treatment. After pathological evaluation, we conduct additional CRT or surgery, when the lesion has risk factors, such as LVI, SM2 invasion, or positive vertical margin, considering the patient’s condition. In this case, since the pathological diagnosis was pT1a-MM ESCC without LVI, we followed up this patient without additional treatment, checking LN and distant metastasis by neck, chest, and abdominal CT, EGD, and tumor marker (SCC, CEA) in every 6 months. This patient is alive without recurrence for 1 year.

References 1. Japan Esophageal Society (Ed). Japanese classification of esophageal cancer. 11th ed. part I. Esophagus. Tokyo: Kanehara Co. Ltd.; 2017;14:1–36. 2. Japan Esophageal Society (Ed). Guidelines for diagnosis and treatment of carcinoma of the esophagus. 4th ed. (In Japanese). Tokyo: Kanehara Shuppan; 2017. 3. Katada C, et al. Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions. Gastrointest Endosc. 2003;57:165–9. 4. Inoue H, Minami H, Sato Y, et al. Technical feasibility of circumferential ESD and preventive balloon dilation. Stomach Intestine. 2009;44:394–7. 5. Hashimoto S, et  al. The efficacy of endoscopic triamcinolone injection for the prevention of esophageal stricture after endoscopic submucosal dissection. Gastrointest Endosc. 2011;45:222–7. 6. Yamaguchi N, et al. Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma. Gastrointest Endosc. 2011;73:1115–21. 7. Endo M, Yoshino K, Kawano T, et  al. Clinicopathologic analysis of lymph node metastasis in surgically resected superficial cancer of the thoracic esophagus. Dis Esophagus. 2000;13:125–9. 8. Kuwano H, Nishimura Y, Oyama T, et  al. Guidelines for diagnosis and treatment of carcinoma of the esophagus April 2012 edited by the Japan Esophageal Society. Esophagus. 2015;12:1–30.

2  Esophageal Cancer: Squamous Cell Carcinoma (SCC)

35

9. Kato H, Sato A, Fukuda H, et al. A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan clinical oncology group study (JCOG9708). Jpn J Clin Oncol. 2009;39:638–43. 10. Cooper JS, Guo MD, Herskovic A, et  al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999;281:1623–7. 11. Yoshimizu S, Yoshio T, Akiyoshi I, et al. Long term outcomes of combined endoscopic resection and chemoradiotherapy for esophageal squamous cell carcinoma with submucosal invasion. Dig Liver Dis. 2018;50(11):1255–6. 12. Shimizu Y, Kato M, Yamamoto J, et  al. EMR combined with chemoradiotherapy: a novel treatment for superficial esophageal squamous-cell carcinoma. Gastrointest Endosc. 2004;59:199–204. 13. Minashi K, Nihei K, Mizusawa J, et  al. Efficacy of endoscopic resection and selective chemoradiotherapy for stage I esophageal squamous cell carcinoma. Gastroenterology. 2019;157(2):382–90. 14. Japan Esophageal Society (Ed.). Japanese classification of esophageal cancer. Tokyo: Kanehara Co. Ltd; 2008. 15. Katada C, Muto M, Momma K, et al. Clinical outcome after endoscopic mucosal resection for esophageal squamous cell carcinoma invading the muscularis mucosae—a multicenter retrospective cohort study. Endoscopy. 2007;39:779–83. 16. Shimizu Y, Tsukagoshi H, Fujita M, et al. Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae or deeper. Gastrointest Endosc. 2002;56:387–90. 17. Eguchi T, Nakanishi Y, Shimoda T, et al. Histological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases. Mod Pathol. 2006;19:475–80. 18. Akutsu Y, Uesato M, Shuto K, et  al. The overall prevalence of metastasis in T1 esophageal squamous cell carcinoma. A retrospective analysis of 295 patients. Ann Surg. 2013;257:1032–8. 19. Yamashina T, Ishihara R, Nagai K, et al. Long-term outcome and metastatic risk after endoscopic resection of superficial esophageal squamous cell carcinoma. Am J Gastroenterol. 2004;108:544–51. 20. Saeki H, Watanabe M, Mine S, et al. Esophagectomy for superficial esophageal cancer after non-curative endoscopic resection. J Gastroenterol. 2015;50:406–13.

3

Esophageal Benign Tumor Seiichi Yakabi and Toshiyuki Yoshio

3.1

Case Presentation (Figs. 3.1, 3.2, and 3.3)

A 55-year-old male, esophageal granular cell tumor. In this case, we could recognize a yellow colored tumor in the posterior wall of the middle thoracic esophagus, and the tumor shows steep rise covered with normal epithelium. We could also recognize depression area in the central part of the tumor with white light endoscopy. Using NBI, we could recognize IPCL with regular shape showing surface epithelium was normal. EUS also showed that the tumor was a

b

Fig. 3.1  Endoscopic submucosal dissection for esophageal granular cell tumor. (a) White light endoscopy: there was a yellow elevated lesion with depressed area in the central part of the lesion. And the shape of the tumor looks like molariform. The size was about 7 mm. (b) NBI endoscopy: the tumor was covered with normal mucosa, and regular shape vessel was observed

S. Yakabi · T. Yoshio (*) Department of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2020 J. Fujisaki (ed.), Endoscopic Treatment Strategy for Upper GI Tract Neoplasms, https://doi.org/10.1007/978-981-32-9737-1_3

37

38

a

S. Yakabi and T. Yoshio

b

Fig. 3.2  In endoscopic ultrasound (EUS) findings, tumor was recognized as a low echoic lesion, and margin was clear (a). And tumor was connected to the second and third layers of the esophagus (b)

a

b

HE

c

S-100

Fig. 3.3  Resected specimen. (a) Pathological diagnosis: granular cell tumor. Most of the tumor was still in the mucosal layer, but some parts of the tumor had slight invasion into the SM layer. Size 7 × 5 mm (b). S-100 (+) (c), CD34 (−), Mib-1 index 2, pT1a. a

b

Fig. 4.1 (a) WLI showed a yellowish superficial depressed type lesion (white arrow) around 16 mm at the lesser curvature of middle gastric body. The grade of endoscopic gastric atrophy was severe that made difficult to detect the lesion. (b) Chromoendoscopy using indigo carmine dye. The margins of the lesion are delineated clearly

M. Inuyama · Y. Tokai · S. Shiroma · M. Ishioka · Y. Horiuchi (*) Department of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2020 J. Fujisaki (ed.), Endoscopic Treatment Strategy for Upper GI Tract Neoplasms, https://doi.org/10.1007/978-981-32-9737-1_4

45

46

M. Inuyama et al.

a

b

Fig. 4.2 (a) Narrow band imaging (NBI) endoscopic findings. The lesion was recognized as well-­ demarcated area with color change. (b) By using magnifying NBI, the cancerous area showed an irregular vessel pattern (right side of dotted line)

a

b

Fig. 4.3 (a) Mapping image of resected specimen by endoscopic submucosal dissection (ESD). Red lines show the area of adenocarcinoma. The size of resected specimen was 38 × 32 mm. The lesion size was 16 × 15 mm, indicated by red line. Type 0-IIc, 16 × 15 mm, tub1 > tub2, pT1a (M), pUL0, Ly0, V0, pHM0, pVM0. (b) Pathological findings: well-differentiated adenocarcinoma limited in mucosa (M)

4.1.2 Discussion Endoscopic treatment is the accepted treatment option for early gastric cancer in which the possibility of lymph node metastasis is extremely low [1, 2]. In Japanese gastric cancer treatment guidelines 2014 (ver. 4), it is stated that EMR/ESD is indicated as a standard treatment (absolute indication) for the following tumor: differentiated-­type adenocarcinoma without ulcerative findings, of which the depth of invasion is clinically diagnosed as T1a and the diameter is ≤20 mm [3]. Moreover,

4  Gastric Cancer, ESD Absolute Indication, Expanded Indication, and Out of …

47

based on the Japan Clinical Oncology Group study (JCOG0607), in Japanese gastric cancer treatment guidelines 2018 (ver. 5; published previously in Japanese), absolute indication for ESD was expanded for the tumor that is shown to have no or lower risks of lymph node metastasis than the risks of mortality from surgery [4–6]. Therefore, the following were added as the absolute indication for ESD: >20 mm ulcer-negative and ≤30 mm ulcer-positive differentiated-type adenocarcinoma, of which the depth of invasion is clinically diagnosed as T1a [4]. When the histopathologic findings of the specimens resected by ESD fulfilled the following criteria, the resection is determined as endoscopic curability (eCura) A: en bloc resection, any size of ulcer-negative and ≤30  mm ulcerpositive differentiated-type adenocarcinoma, of which the depth of invasion is pT1a, negative horizontal/vertical margin, and no lymphovascular infiltration; eCura B: en bloc resection, negative horizontal/vertical margin, no lymphovascular infiltration, ≤20  mm ulcer-negative undifferentiated-type adenocarcinoma, of which the depth of invasion is pT1a, or ≤30 mm differentiated-type adenocarcinoma, of which the depth of invasion is pT1b (SM1, por, pT1a(M) (Histological Mixed Type).

4.5.2 Discussion Differentiated-type dominant mixed-type (D-MT) gastric cancers are defined as differentiated-type cancers containing undifferentiated-type components. Current guideline prescribes that D-MT cancers are dealt with as differentiated-type cancers a

b

Fig. 4.15 (a) 0-IIc type mucosal cancer. On posterior wall of gastric antrum, there is a combined reddish and whitish superficial depressed lesion (yellow arrow head). (b) After indigo carmine spraying. Indigo carmine spraying made it easier to identify the margin of the lesion (yellow arrow)

56

M. Inuyama et al.

a

b

Fig. 4.16 (a, b) Magnifying endoscopy with narrow band imaging (ME-NBI) findings. There are ME-NBI findings of “mesh pattern” (yellow arrow) and “wavy microvessels” (red arrow). These findings may suggest that the lesion is mixed-histological-type early gastric cancer

a

b

12

c

Fig. 4.17  Pathological findings: 0-IIc, 38 × 27 mm, tub2 > por, pT1a(M), pUL0, Ly0, V0, pHM0, pVM0. (a) Mapping of the histological findings for the lateral extent and invasion depth in the endoscopically resected specimen. Red lines indicate differentiated-type component, and blue line indicates undifferentiated-type component. Undifferentiated-type component is over 20 mm. (b, c) Histological findings. There are combined findings of moderately differentiated adenocarcinoma component (a) and poorly differentiated adenocarcinoma component (b)

and regarded as lesions of noncurative resection if the undifferentiated-type component measures at least 20 mm. In our report [7], among all D-MT cancers performed ESD, the frequency of the D-MT gastric cancers with undifferentiated-type component measuring ≧20 mm is 12.2%. Regarding magnifying endoscopy with narrow band imaging (ME-NBI) findings, in case presentation, we detected mesh pattern and wavy microvessels. To date, there have been no reports regarding endoscopic findings including ME-NBI in distinguishing the MT from pure differentiated-type gastric cancers and no reports concerning about detecting undifferentiated-type component measuring ≧20  mm from D-MT gastric cancer. On the other hand, ME-NBI findings of

4  Gastric Cancer, ESD Absolute Indication, Expanded Indication, and Out of …

57

differentiated type are reported as “loop pattern” and “mesh pattern” [17], and ME-NBI findings of undifferentiated type are reported as “expanded intervening part,” “wavy microvessels,” and “corkscrew pattern” [18, 19]. Therefore, these ME-NBI findings may be useful to diagnose the lesion as MT in preoperative endoscopic examination. In addition to this, by using ME-NBI, there may be possibility of diagnosing whether there is undifferentiated-type component measuring ≧20 mm or not in MT cancers. Further studies are needed to diagnose MT gastric cancers correctly by preoperative endoscopic examination such as ME-NBI.

4.6

 L+, Undifferentiated Type, T1b Case (Figs. 4.18, 4.19, U 4.20, and 4.21)

4.6.1 Case Presentation A 51-year-old female, 0-IIc, 17 mm, por, pT1b(SM2).

4.6.2 Discussion 4.6.2.1 Endoscopic Diagnosis of Ulcer Scar in Undifferentiated-Type Cancer Diagnosis of the ulcerative findings is definitely important because it has an effect on the diagnosis of the expanded indication for ESD in undifferentiated-type early gastric cancer. However, it is sometimes difficult to rely only on conventional endoscopy. Endoscopic ultrasonography (EUS) is one of the methods to diagnose not only invasion but also ulcerative findings. In undifferentiated-type cancers, Okada reported that 75% (42/56) of the non-ulcerative findings mucosal lesion diagnosed by EUS before a

b

Fig. 4.18 (a) The lesion is located at greater curvature of gastric angle. It is indicated with white arrow. The lesion is discolored superficial depressed. (b) There is a remarkable reddish spot which is suspected a biopsy scar in the center of the lesions. The histopathology of the biopsy taken from the lesion at the previous hospital is signet-ring cell carcinoma (sig)

58

a

M. Inuyama et al.

b

Fig. 4.19 (a) Spraying indigo carmine view, the margin of depressed area is clear. The lesion is indicated with white arrow. (b) The shallow depressive area spreads to the anal and oral side of the deep depression in closing image (allow)

a

b

Fig. 4.20 (a) In NBI view, the color of the lesion seems brownish compared with background mucosa. (b) In high magnification with NBI, corkscrew pattern is recognized. This finding means disappearance of microsurface and remarkable disordered irregular microvessels

ESD corresponded to pathological non-ulcerative findings mucosal lesion [19] (Table  4.2). Therefore, additional EUS may be effective for diagnostic accuracy before ESD in some cases. At this case, EUS was not performed. Additional EUS before ESD might help the diagnosis of the ulcerative findings and SM invasion.

4.6.2.2 Treatment Evaluation of Endoscopic Resection in Undifferentiated-Type Cancer eCura system is used for evaluation after endoscopic resection. eCura C is a required surgical treatment. eCura C is classified into eCura C-1 and eCura C-2. eCuraC-2 means the lesions which have possibility of high lymph node metastasis (LNM).

4  Gastric Cancer, ESD Absolute Indication, Expanded Indication, and Out of …

a

M SM

59

b

Fig. 4.21  Pathological diagnosis of ESD: M, Gre, resected specimens 45 × 38 mm, Type 0-IIc, lesion’s size 17 × 17 mm, por, pT1b1(SM2), pUL1, Ly0, V0, pHM0, pVM0. Treatment evaluation: eCura C-2. (a) Here is the macro image with mapping. Cancer is indicated as red lines. Laparoscopic pylorus-preserving gastrectomy was performed after ESD because the lesion was undifferentiatedtype cancer with SM 700 μm invasion and UL1. As a result, no lymph node metastasis was seen. (b) Cancer invades the SM layer histopathologically. Muscularis mucosae is thick and it is overstretched to the upper side. This is a finding of ulcer scar Table 4.2  Diagnostic accuracy of endoscopic ultrasonography (EUS) in undifferentiated-type lesions 20 mm in diameter or smaller; indications for ESD [19] Pathological depth Diagnosis for EUS (n=81)

M UL0

M UL1

SM

MP

Total

EUS-M/SM1 UL0

42

6

8

0

56

EUS-M/SM1 UL1

1

4

1

1

7

EUS-SM2

0

1

17

0

18

EUS-MP

0

0

0

0

0

Total

43

11

26

1

81

Possibility of expanded indication of ESD (M)

eCuraB

Therefore, if the evaluation is eCura C-2, surgical operation should be performed as standard treatment. This case was evaluated eCura C-2 and surgical operation was performed. It is reported that the rate of LNM in undifferentiated-type cancer in which is over 20 mm with SM invasion and/or ulcerative findings is 14.0% [13]. This case had no LNM. About 5 years has passed after surgical operation with no recurrence.

60

M. Inuyama et al.

References 1. Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut. 2001;48:225–9. 2. Gotoda T, Yanagisawa A, Sasako M, et  al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer. 2000;3:219–25. 3. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20:1–19. 4. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (ver. 5). Japan: Kanehara & Co., Ltd; 2018. p. 20–4. 5. Hasuike N, Ono H, Boku N, et al. A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer (cT1a): the Japan Clinical Oncology Group study (JCOG0607). Gastric Cancer. 2018;21:114–23. 6. Hirasawa T, Gotoda T, Miyata S, et  al. Incidence of lymph node metastasis and the feasibility of endoscopic resection for undifferentiated-type early gastric cancer. Gastric Cancer. 2009;12:148–52. 7. Horiuchi Y, Fujisaki J, Yamamoto N, et  al. Undifferentiated-type component mixed with differentiated-­type early gastric cancer is a significant risk factor for endoscopic non-curative resection. Dig Endosc. 2018;30:624–32. 8. Gastric cancer treatment guidelines. 15th ed. 2018 Jan (Japanese). 9. Takizawa K, Takashima A, Kimura A, et al. Phase II clinical trial of endoscopic submucosal dissection for early gastric cancer of undifferentiated type: Japan Clinical Oncology Group study JCOG1009/1010. Jpn J Clin Oncol. 2013;43(1):87–91. 10. Okada K, Fujisaki J, Yoshida T, et al. Long-term outcomes of endoscopic submucosal dissection for undifferentiated-type early gastric cancer. Endoscopy. 2012;44:122–7. 11. Yamamoto Y, Fujisaki J, Hirasawa T, et al. Therapeutic outcomes of endoscopic submucosal dissection of undifferentiated-type intramucosal gastric cancer without ulceration and preoperatively diagnosed as 20 millimeters or less in diameter. Dig Endosc. 2010;22:112–8. 12. Horiuchi Y, Fujisaki J, Yamamoto N, et al. Accuracy of diagnostic demarcation of undifferentiated-type early gastric cancers for magnifying endoscopy with narrow-band imaging: endoscopic submucosal dissection cases. Gastric Cancer. 2016;19:515–23. 13. Sekiguchi M, Oda I, Taniguchi H, et al. Risk stratification and predictive risk-scoring model for lymph node metastasis in early gastric cancer. J Gastroenterol. 2016;51:961–70. 14. Choi J, Kim SG, Im JP, et al. Endoscopic prediction of tumor invasion depth in early gastric cancer. Gastrointest Endosc. 2011;73:917–27. 15. Abe S, Oda I, Shimazu T, et al. Depth-predicting score for differentiated early gastric cancer. Gastric Cancer. 2011;14:35–40. 16. Nagahama T, Yao K, Imamura K, et al. Diagnostic performance of conventional endoscopy in the identification of submucosal invasion by early gastric cancer: the “non-extension sign” as a simple diagnostic marker. Gastric Cancer. 2017;20:304–13. 17. Yagi K, Namakura A, Sekine A, et al. Magnifying endoscopy with narrow band imaging for early differentiated gastric adenocarcinoma. Dig Endosc. 2009;20:115–22. 18. Nakayoshi T, Tajiri H, Matsuda K, et al. Magnifying endoscopy combined with narrow band imaging system for early gastric cancer: correlation of vascular pattern with histopathology (including video). Endoscopy. 2004;12:1080–4. 19. Okada K, Fujisaki J, Kasuga A, et  al. Diagnosis of undifferentiated-type early gastric cancers by magnification endoscopy with narrow-band imaging. J Gastroenterol Hepatol. 2011;26:1262–9.

5

Gastric Adenoma Hiroyuki Hatamori and Yusuke Horiuchi

5.1

 ase Presentations: Gastric adenoma (Figs. 5.1, 5.2, C and 5.3)

A 64-year-old female with gastric adenoma. a

b

Fig. 5.1  A 64-year-old female with gastric adenoma, lesser curvature of the lower body. (a) White light endoscopy (WLI). A well-demarcated reddish depressed area, 10  mm in diameter, was observed at the lesser curvature of the lower gastric body (arrows). The depression was mild and biopsy scar was observed in the depressed area. The surrounding mucosa was atrophic. (b) Chromoendoscopy with indigo carmine. With dye spraying, the margin of the depressed area (arrows) was more clearly visualized. The margin was relatively clear, and the irregularity of the margin was mild

H. Hatamori · Y. Horiuchi (*) Department of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2020 J. Fujisaki (ed.), Endoscopic Treatment Strategy for Upper GI Tract Neoplasms, https://doi.org/10.1007/978-981-32-9737-1_5

61

62

H. Hatamori and Y. Horiuchi

a

b

c

Fig. 5.2 (a) Non-magnifying endoscopy with NBI.  The depressed area was recognized as a brownish area. The margin of the lesion was clear. (b, c) Magnifying endoscopy with NBI. In the depressed area, regular microsurface pattern with tubular structure was observed. In microvascular pattern, fine network pattern with mild dilation and tortuosity was present, but difference in caliber and various shapes and elongation was absent. Biopsy specimen taken from the depressed area was histologically diagnosed as low-grade adenoma, corresponding to category 3 in Vienna classification. We performed endoscopic submucosal dissection (ESD) because depressed morphology of low-grade adenoma suggests the potential of coexistence of cancer

a

b

c

Fig. 5.3 (a) Mapping image of resected specimen by ESD. Red lines show the area of adenoma. Histology: low-grade adenoma (7 × 5 mm), corresponding to category 3 in Vienna classification. (b, c) Pathological findings: Intestinal metaplasia was observed in the surrounding mucosa. In high magnification, tumor is composed of high-columnar cells with elongated hyperchromatic nuclei on the basal layer. Coexistence of carcinoma was not observed

5.2

Discussion

Gastric adenoma is a benign epithelial neoplastic tumor with a glandular organization. It is characterized by localized proliferation of adenomatous epithelium with tubular and/or papillary structures [1, 2]. Gastric adenoma is regarded as a precancerous lesion and divided into low-grade adenoma (LGA, corresponding to category 3 in the Vienna classification) and high-grade adenoma (HGA, category 4.1) [3]. The risk of progression to gastric cancer increases with the histological severity, and the risk of progression from LGA to gastric cancer has been reported to be relatively low (3–9%) [4, 5].

5  Gastric Adenoma

63

According to the revised Vienna classification, depending on the overall size of the lesion and general factors such as the patient’s age and complications, either endoscopic resection (ER) or follow-up is recommended for LGA, while endoscopic resection or surgical local resection is recommended for HGA [6]. A forceps biopsy is performed to obtain a precise histological diagnosis for determining treatment strategy, but some discrepancies can exist between forceps samples and resected specimens [7–10]. Recent study showed that in gastric lesions initially diagnosed as low-grade dysplasia (category 3) on forceps biopsy specimen, discrepancy between pre-treatment histology and post-endoscopic resection results was 37%, and 34% of these lesions initially diagnosed as low-grade dysplasia were finally diagnosed as high-grade dysplasia (category 4) or invasive cancer (category 5) [11]. Therefore, initial findings of LGA on forceps biopsy cannot exclude the presence of HGA or carcinoma. The depressed morphology, surface erosions, surface erythema, and lesion size have been reported to be suggestive of malignancy [1, 11, 12]. Kasuga et al. reported that in gastric lesions initially diagnosed as LGA, reclassified diagnoses to HGA and carcinoma were significantly more frequent in depressed lesions (17.5% and 34.9%, respectively) than in protruding lesions (4.8% and 26.2%, respectively). Results of multivariate analysis showed that lesion size larger than 20  mm (P  5 cm

Indication for open gastrectomy

Tumor size < 2 cm

Malignant findings (a)

No EUS-FNAB and no malignant finding (a)

Relative indication for LECS Periodic follow-up

Quoted from [3] Solid lines indicate standard diagnostic and therapeutic methods. Dotted lines indicate optional arms SMT submucosal tumor, GIST gastrointestinal stromal tumor, LECS laparoscopic and luminal endoscopic cooperative surgery a Ulceration, irregular margins, and rapid growth in endoscopic examinations b Necrosis, hemorrhage, irregularity of margins, abundant blood flow on computed tomography (CT), heterogeneous parenchyma, irregular margins, and enlarged regional lymph nodes on EUS c Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is preferable but not essential

wall, LECS was developed by Hiki et al. as a technique that combines laparoscopic gastric resection with luminal endoscopic submucosal dissection (ESD) [4]. Using the LECS procedure, we can preserve the gastric wall, nerves, and feeder vessels, and these benefits would preserve gastric function and improve the patient’s postoperative quality of life. Laparoscopic wedge resection for lesions located near the esophago-gastric junction (EGJ) or pyloric ring is technically difficult. We can maximize the advantages of LECS for tumors located at the EGJ. However, these techniques are limited by the size of the tumor; LECS can be applied to a tumor that is ≦5 cm in diameter. In addition, a tumor occupying over half the circumference of the EGJ should be excluded from the indication for LECS because of high risk of postoperative leakage or anastomotic stenosis [1]. LECS is safe and feasible for gastric SMT because of its reasonable operation time, low blood loss, acceptable complication rate, and lack of recurrence.

7  Gastric Submucosal Tumor (Leiomyoma, GIST, etc.) and LECS

75

References 1. Palazzo L, Landi B, Cellier C, et al. Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumors. Gut. 2000;46:88–91. 2. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–62. 3. Matsuda T, Nunobe S, Hiki N, et al. Society for the study of laparoscopy and endoscopy cooperative surgery. Endoscopy. 2017;49:476–83. 4. Hiki N, Yamamoto Y, Fukunaga T, et al. Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal tumor dissection. Surg Endosc. 2008;22:1729–35.

Part III Doodenum

8

Duodenal Adenoma Yohei Ikenoyama and Shoichi Yoshimizu

8.1

Case Presentations (Figs. 8.1, 8.2, 8.3, 8.4, and 8.5)

A 60-year-old male, Duodenal adenoma.

a

b

Fig. 8.1  A 60-year-old man with a 10-mm superficial non-ampullary duodenal epithelial tumor in the second part of the duodenum. (a) White light endoscopy (WLI). A 10-mm a whitish well-­ circumscribed elevated lesion was observed on the outer wall of the anal side in the second portion. The macroscopic type was diagnosed as 0-Is. Most of the lesions were observed as white villi (milk-­white mucosa), but only a part of the lesion had a mild redness area (white arrows). (b) Chromoendoscopy with indigo carmine. By indigo carmine spraying, the margin of the lesion was clarified. It was a smooth surface elevated lesion with no nodule and depressed area

Y. Ikenoyama · S. Yoshimizu (*) Department of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2020 J. Fujisaki (ed.), Endoscopic Treatment Strategy for Upper GI Tract Neoplasms, https://doi.org/10.1007/978-981-32-9737-1_8

79

80

a

Y. Ikenoyama and S. Yoshimizu

b

c

Fig. 8.2 (a) Non-magnifying endoscopy with NBI. The border of the lesion was clear, and most of the lesion had milk-white mucosa. However, the milk-white mucosa disappeared in the reddish area in WLI; it was recognized as a brownish area in NBI. (b) Magnifying endoscopy with NBI (yellow line). In the part with milk-white mucosa, we recognized a regular microsurface pattern with even villus structure. Microvascular pattern was absent due to the effect of uniformly milk-­ white mucosa. (c) Magnifying endoscopy with NBI (blue line). Milk-white mucosa disappeared, and we recognized an irregular microvascular pattern with dilatation, meandering, and caliber change, and an irregular microsurface pattern with uneven villus structure. We performed endoscopic mucosal resection under endoscopic diagnosis as Vienna classification (VCL) category 3 with partial category 4

a

b

Fig. 8.3  Pathological diagnosis: VCL category 3 with partial category 4 (low-grade adenoma with partially severe atypia). (a) Tumor is a tubular structure; it shows irregular arrangement and expansion of ducts. (b) In higher power field, it is composed of high-columnar cell of small intestine type with homogeneous and elongated nuclear on the basal layer. It is diagnosed as intestinal tubular adenoma

8  Duodenal Adenoma

a

81

b

Fig. 8.4 (a) Case 1. Irregular microvascular pattern. Example of VCL category 4 with an irregular microvascular pattern and an irregular microsurface pattern. The micro blood vessels in the uneven villus structure was dilatation, meandering, and caliber change. (b) Case 2. Network microvascular pattern. Example of VCL category 4 with a network microvascular pattern and an absent microsurface pattern

Fig. 8.5  A case of positive non-lifting sign due to biopsy scar. The biopsy scar was located in the center of the lesion. Although submucosal injection was performed, the lesion did not elevate. As biopsy scar may make it difficult to en bloc resect by EMR, unnecessary biopsies should be avoided as much as possible

82

8.2

Y. Ikenoyama and S. Yoshimizu

Discussion

In recent years, opportunities to encounter superficial non-ampullary duodenal epithelial tumors (SNADETs) are increasing because screening esophagogastroduodenoscopy (EGD) is used worldwide. EGD is the most sensitive method for early detection of SNADETs, and early detection is the best strategy for improving patients’ survival. However, SNADETs are a rare clinical entity [1]. Therefore, there is no adequate evidence of endoscopic diagnosis and therapeutic strategy, and its clinicopathological features have not yet been clarified. Many unresolved problems remained compared to esophagus, stomach, and other organ tumors. A Japanese multicenter case series study reported the analysis of clinicopathological findings of 364 patients with 396 SNADETs. The most common location of SNADETs was second portion in 75%, the mean tumor diameter was 18 ± 4 mm, and the color was white or isochromatic in 60%. The majority of the macroscopic type was elevated lesions (0-I or 0-IIa) in 83%, and the depressed type (0-IIc) lesions were 17% [2]. SNADETs were histologically graded based on the Vienna classification (VCL), such as category 3 (low-grade adenoma/neoplasia), category 4.1 (high-grade adenoma/neoplasia), category 4.2 (non-invasive neoplasia), or category 5 (invasive neoplasia) [3]. We consider that VCL category 3 has low risk of progression to adenocarcinoma and follow-up is acceptable, but VCL category 4.1 has high risk of progression to adenocarcinoma. Therefore, SNADETs with VCL category 4.1 or more should be treated immediately, and endoscopic resection (ER) or surgical resection is performed in many cases. Thus, a preoperative differential diagnosis of VCL category 3 or 4 is significant in determining therapeutic strategy. The duodenal biopsy is useful as a method of preoperative differential diagnosis between VCL category 3 and 4, but the duodenal biopsy has possibility to develop a scar with severe fibrosis in the submucosa. We sometimes experience the case with a positive non-lifting sign due to the biopsy scar during submucosal injection for ER. Thus, biopsy scar makes it difficult to en bloc resect by ER. In addition, it is often difficult to distinguish VCL category 3 from category 4 by biopsy specimen only [4]. It is reported that diagnostic accuracy of preoperative endoscopic diagnosis using magnifying endoscope with narrow band imaging (ME-NBI) is higher than that of preoperative biopsy (accuracy rate: endoscopic diagnosis 75%, biopsy diagnosis 68%, p