Recent Advances in the Treatment of Colorectal Cancer [1st ed.] 978-981-13-3049-0, 978-981-13-3050-6

Table of contents :
Front Matter ....Pages i-viii
Front Matter ....Pages 1-1
Endoscopic Resection of Early Colorectal Cancer (Masayoshi Yamada, Yutaka Saito, Stefano Sansone, Hiroyuki Takamaru, Taku Sakamoto)....Pages 3-15
Colonic Stent: Bridge to Surgery (Yoshihisa Saida)....Pages 17-24
Front Matter ....Pages 25-25
D3 Lymph Node Dissection for Colon and Rectal Cancers (Tatsuro Yamaguchi)....Pages 27-38
Laparoscopic Surgery for Colorectal Cancer (Tetsuro Tominaga, Tsuyoshi Konishi)....Pages 39-48
Robotic-Assisted Laparoscopic Surgery for Rectal Cancer (Tomohiro Yamaguchi, Yusuke Kinugasa)....Pages 49-57
Intersphincteric Resection for Rectal Adenocarcinoma Near the Anus (Yoshito Akagi, Fumihiko Fujita)....Pages 59-70
Chemoradiation for Rectal Cancer (Keiji Koda)....Pages 71-77
Front Matter ....Pages 79-79
Adjuvant Chemotherapy (Toshiaki Ishikawa, Hiroyuki Uetake)....Pages 81-100
Chemotherapy for Metastatic Colorectal Cancer (Takeshi Yamada, Michihiro Koizumi, Seiichi Shinji, Akihisa Matsuda, Yasuyuki Yokoyama, Goro Takahashi et al.)....Pages 101-111
Front Matter ....Pages 113-113
Next-Generation Sequencing for Genetic Diagnosis of Hereditary Colorectal Cancer and Polyposis Syndrome (Hidetaka Eguchi, Yasushi Okazaki)....Pages 115-125
Clinical Management of Hereditary Colorectal Cancer (Kensuke Kumamoto, Hideyuki Ishida)....Pages 127-144

Citation preview

Recent Advances in the Treatment of Colorectal Cancer Hideyuki Ishida Keiji Koda  Editors

123

Recent Advances in the Treatment of Colorectal Cancer

Hideyuki Ishida  •  Keiji Koda Editors

Recent Advances in the Treatment of Colorectal Cancer

Editors Hideyuki Ishida Department of Digestive Tract and General Surgery Saitama Medical Center Saitama Medical University Kawagoe Saitama Japan

Keiji Koda Department of Surgery Teikyo University Chiba Medical Center Ichihara Chiba Japan

ISBN 978-981-13-3049-0    ISBN 978-981-13-3050-6 (eBook) https://doi.org/10.1007/978-981-13-3050-6 Library of Congress Control Number: 2018965168 © Springer Nature Singapore Pte Ltd. 2019 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, express 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

The number of patients with colorectal cancer has been increasing worldwide, and there is a high degree of concern among clinicians and investigators around the globe. The level of colorectal cancer care in Japan is world-class. Meticulous data has been compiled regarding the indications for endoscopic therapy, and techniques and findings that have a global impact have been reported from Japan. Recently, the standard lymph node dissection widely adopted in Japan has been attracting the attention of colorectal surgeons everywhere. The treatment strategies for rectal cancer in Japan and other countries differ greatly: in Japan, there is a history of attaching importance to lateral lymph node dissection for lower rectal cancer, and lateral lymph node dissection is considered one of the options for effective local treatment. The views in Western countries regarding perioperative chemoradiation therapy for lower rectal cancer also differ from those in Japan. Moreover, the Japanese technique of sphincter preservation in lower rectal cancer has become a world leader. Excellent oncological outcomes of laparoscopic surgery and robotic surgery in the treatment of colorectal cancer have also been reported from Japan. In the context of chemotherapy for colorectal cancer, Japan’s excellent results for administering oral agents in combination with injection-based chemotherapy have been widely used in Western countries. There is also a long history of research in the field of hereditary colorectal cancer in Japan, and in recent years the findings obtained using next-generation sequencing have also been reported to the world. Japanese experts in diagnosing and treating of colorectal cancer have reviewed this book, Recent Advances in the Treatment of Colorectal Cancer, and they have added their own experience in 11 relevant areas and real-world clinical situations, as well as added a discussion based on the foreign literature. We sincerely hope that readers will peruse this book carefully, and that they will find it useful in the diagnosis and treatment of colorectal cancer in their everyday practice. Saitama, Japan Chiba, Japan

Hideyuki Ishida Keiji Koda

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Contents

Part I Endoscopic Treatment 1 Endoscopic Resection of Early Colorectal Cancer���������������������������������   3 Masayoshi Yamada, Yutaka Saito, Stefano Sansone, Hiroyuki Takamaru, and Taku Sakamoto 2 Colonic Stent: Bridge to Surgery��������������������������������������������������������������  17 Yoshihisa Saida Part II Surgical Treatment 3 D3 Lymph Node Dissection for Colon and Rectal Cancers��������������������  27 Tatsuro Yamaguchi 4 Laparoscopic Surgery for Colorectal Cancer������������������������������������������  39 Tetsuro Tominaga and Tsuyoshi Konishi 5 Robotic-Assisted Laparoscopic Surgery for Rectal Cancer������������������  49 Tomohiro Yamaguchi and Yusuke Kinugasa 6 Intersphincteric Resection for Rectal Adenocarcinoma Near the Anus 59 Yoshito Akagi and Fumihiko Fujita 7 Chemoradiation for Rectal Cancer����������������������������������������������������������  71 Keiji Koda Part III Chemotherapy 8 Adjuvant Chemotherapy��������������������������������������������������������������������������  81 Toshiaki Ishikawa and Hiroyuki Uetake

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Contents

9 Chemotherapy for Metastatic Colorectal Cancer���������������������������������� 101 Takeshi Yamada, Michihiro Koizumi, Seiichi Shinji, Akihisa Matsuda, Yasuyuki Yokoyama, Goro Takahashi, Takuma Iwai, Keisuke Hara, Masahiro Hotta, Kohki Takeda, Kohji Ueda, and Hiroshi Yoshida Part IV Hereditary Colorectal Cancer 10 Next-Generation Sequencing for Genetic Diagnosis of Hereditary Colorectal Cancer and Polyposis Syndrome�������������������������������������������� 115 Hidetaka Eguchi and Yasushi Okazaki 11 Clinical Management of Hereditary Colorectal Cancer������������������������ 127 Kensuke Kumamoto and Hideyuki Ishida

Part I

Endoscopic Treatment

Chapter 1

Endoscopic Resection of Early Colorectal Cancer Masayoshi Yamada, Yutaka Saito, Stefano Sansone, Hiroyuki Takamaru, and Taku Sakamoto

Abstract  Endoscopic diagnosis and treatments have made considerable progress in recent years. Endoscopic diagnosis aims to predict oncological characteristics of a lesion based on endoscopic features and also differentiate between malignant and benign tumors. Detailed inspection of lesions is required in order to pursue an accurate endoscopic diagnosis. This can be achieved with image enhanced endoscopy. Multiple strategies are available to achieve endoscopic resection of colorectal lesions, including polypectomy, endoscopic mucosal resection, endoscopic mucosal dissection, and full-thickness resection. Each technique requires different skill-sets and has different frequency of complications. Selection of the appropriate endoscopic treatment is based on oncological indication and technical aspects of each strategy. All endoscopic procedures require expertise which is achieved through adequate training and the availability of appropriate equipment. Keywords  Endoscopic resection · Endoscopic submucosal dissection Colorectal cancer

1.1  Introduction With the development of new devices and technologies, both endoscopic diagnosis and treatments have made considerable progress. Endoscopic resection is a procedure to remove a lesion under direct vision using an endoscope and endoscopic devices. Since it is a less invasive procedure than conventional surgery, endoscopic resection has attracted attention as an alternative treatment with shorter in-hospital M. Yamada · Y. Saito (*) · H. Takamaru · T. Sakamoto Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan e-mail: [email protected]; [email protected]; [email protected]; [email protected] S. Sansone NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2019 H. Ishida, K. Koda (eds.), Recent Advances in the Treatment of Colorectal Cancer, https://doi.org/10.1007/978-981-13-3050-6_1

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stays. In the late 1960s, Tsuneoka and Uchida firstly described a successful endoscopic resection of 43 gastric polyps using mechanical cutting with a looped wire. Although the low retrieval rate (57%) of the resected specimen was recognized as an issue, their report led to a breakthrough of endoscopic resection [1]. Subsequently, the application of electrocautery has been introduced. Once the polyp stalk is captured with a looped wire (currently known as snare) coagulation can be delivered by high-frequency electrical current from an electrosurgical generator. In addition to pedunculated polyps, endoscopic resection has also been adopted for sessile, flat, and depressed lesions by using an injection of saline into the submucosa under the lesion. This procedure can lift the lesions up making them more amenable to snare resection [2]. Currently, three types of endoscopic resection are mainly performed: (1) polypectomy, (2) endoscopic mucosal resection (EMR), (3) endoscopic submucosal dissection (ESD).

1.2  Treatment Selection Endoscopic diagnosis plays a crucial role in determining treatment strategy (Table  1.1). Treatment pathways are selected according to both oncological and technical aspects. Endoscopic diagnosis aims to predict oncological characteristics of a lesion based on endoscopic features, such as size, and also differentiate between malignant and benign tumors. Endoscopic resection technique is dependent on the endoscopist’s technical skill, with each technique requiring different skill-sets and having different frequency of complications. Therefore, the decision-making process should take into consideration these technical aspects. Endoscopic treatment is only indicated for tumors with no lymph node metastasis. Therefore, endoscopic resection is considered only for adenomas or invasive tumors confined to the superficial layer of the submucosa (less than 1 mm in depth) [3]. Cancers infiltrating the deeper submucosal layers carry a risk of lymph node metastasis; therefore, a surgical intervention is required. Endoscopic treatment can also be offered for rectal neuroendocrine tumors (carcinoid tumors). Table 1.1  Strategy of endoscopic treatment in colorectum Endoscopic diagnosis Adenoma or low grade dysplasia

High grade dysplasia or adenocarcinoma (superficial submucosal invasion) Including cold polypectomy Recurrent lesion c If en-bloc resection is possible a

b

Lesion size 20 mm ~10 mm 10~20 mm >20 mm

Strategy Polypectomy ◎a × × × × ×

EMR ○ ◎ ○ ◎ ◎ ○c

ESD × ∆b ○ × ○b ◎

1  Endoscopic Resection of Early Colorectal Cancer

5

Detailed inspection of colorectal lesions is required in order to pursue an accurate endoscopic diagnosis. This can be achieved with image enhanced endoscopy (IEE), which includes optical-digital methods such as narrow band imaging (NBI), blue laser imaging (BLI), optical enhancement (OE), and chromoendoscopy (for pit pattern diagnosis). Standard observation (white light image) is less effective at predicting histological subset [4]. The pit pattern classification, also known as Kudo’s classification, defined the morphology of crypt opening observed on colonic mucosal surface with each histological subset. This classification was developed by Kudo et al. and became widely adopted after the introduction of the optical zoom function in 1990 [5]. Fu and colleagues reported a prospective comparative study between endoscopic diagnosis with non-magnifying and magnifying observation by their pit pattern in comparison with histological diagnosis. They concluded that reliability of Kudo classification for differential diagnosis between neoplastic and non-neoplastic lesions was higher with magnification than with non-magnifying observation (95.6% vs. 84.0%) [6]. Matsuda and colleagues reported a prospective large-scale study including a total of 4215 lesions and demonstrated that the diagnostic sensitivity to submucosal deep invasive carcinoma using modified pit pattern (invasive pattern) was 85.6% [7]. They concluded that invasive pattern is an effective diagnostic method to direct the decision of treatment strategy. Recently, Sakamoto and colleagues performed an online survey comparing diagnostic performance of non-­ magnifying white light endoscopy, magnifying NBI and pit pattern diagnosis. Pit pattern diagnosis revealed significantly higher accuracy [8]. Pit pattern can differentiate between malignant and benign lesions and also predict the degree of tumor invasion and has been widely adopted as the gold standard method [9]. NBI, BLI, and OE highlight surface pattern and vessel pattern of the lesion aiding endoscopic differential diagnosis. It can be used simply by pushing a button on the endoscope and negates the need for dye. Some classifications using these methods have been reported including NICE (NBI International Colorectal Endoscopic) classification and JNET (Japan NBI Expert Team) classification [10, 11]. Several studies showed a high diagnostic accuracy for discriminating neoplasia and non-­ neoplasia, or dysplasia and invasive cancer. Sano et al. first reported a prospective comparative study and demonstrated that the diagnostic accuracy in discriminating neoplasia and non-neoplasia was 95.3% [12]. Ikematsu and colleagues demonstrated that by using disorganized meshed capillary patterns and a vascular or loose vascular patterns enables discrimination between dysplasia/superficial submucosal invasive cancer and deep submucosal invasive cancer [13]. McGill and colleagues reported a meta-analysis on 28 studies (total of 6280 polyps) aiming to evaluate diagnostic accuracy of NBI for polyps of 5 mm or less [14]. NBI showed excellent diagnostic accuracy, 0.92 (95% confidence interval 0.90~0.94). However, considering the experience of the clinicians performing the colonoscopy, it is difficult to extend the interpretation of data to daily practice. Indeed, Kuiper and colleagues reported a prospective trial conducted at the general hospital (non-academic center) in Amsterdam (DISCOUNT trial) [15]. The endoscopists involved in the study had performed more than 2000 colonoscopies but did not routinely use NBI. Sensitivity and specificity to the differential diagnosis for polyps up to 10 mm (high ­confidence)

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were 77% and 79%, respectively. Nineteen percent of patients were assigned incorrect surveillance intervals. Ladabaum and colleagues also described similar results [16]. NBI diagnosis is influenced by the expertise of the endoscopist and training is required in order to acquire and maintain high diagnostic accuracy.

1.3  Endoscopic Treatment Strategy 1. Polypectomy Polypectomy is indicated for lesions up to 10  mm, in particular lesions with stalks resembling mushrooms. A metal loop called a “snare” is passed through the working channel of the scope (Fig. 1.1a–c). This snare is then hooked on the stalk and gently tightened (Fig. 1.1d). Then electrocautery is activated to coagulate and cut the stalk by using high-frequency electric current (Fig. 1.1e, f).

a

b

c Prophylactic loop snare in prevention of bleeding

d

e Loop snare

f

Stalk of the lesion

Snare

Lesion

Snare

Stalk

Image c, d

Image d, e

Fig. 1.1  Polypectomy. (a) A 20 mm sized pedunculated lesion in the descending colon, (b) stalk of the lesion, (c) prophylactic endoloop, (d) snaring on the stalk, (e) excision site, (f) resected specimen

1  Endoscopic Resection of Early Colorectal Cancer

7

Cold polypectomy is the removal of small non-pedunculated polyps without electrocautery [17]. This is usually indicated for lesions less than 10  mm in diameter without findings suggestive of high grade dysplasia or cancer. The main advantage of this technique is the safety profile and similar efficacy to polypectomy with coagulation. The risk of delayed bleeding is 0.1% which is the same as routine biopsy. Cold polypectomy should be avoided in lesions with features suggesting cancer because of insufficient submucosal resection. These features include disappearing lobular appearance, depression, prominent redness or if the lesion is depressed (0-IIc type in Parris classification). 2 . EMR Lesions greater than 10 mm have a higher cancer risk (1.6–10.2%) and therefore should be resected using EMR technique [18]. Similar to polypectomy, it includes the use of a snare. However in order to reduce the risk of perforation, saline is injected into the submucosal layer under the lesion before snaring (Fig. 1.2a, b). After achieving appropriate lifting, snaring and coagulation is performed (Fig. 1.2c–e). Considering its safety, curative ability and possibility of tumor invasion into submucosal layer, EMR is routinely indicated for lesions less than 20 mm [19–21]. a

b

d

e

Lesion

Injection needle

c

Snare Tie the snare

Submucosal fluid injection

Image b

Image c

Image d

Fig. 1.2  EMR. (a) A 13 mm sized superficial lesion in the transverse colon, (b) appropriate lifting by submucosal injection, (c) snare at the 6 o’clock position, (d) snaring, (e) excision site

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3. ESD ESD is used for lesions that are difficult to resect en-bloc via EMR. Similarly to EMR, submucosal injection is performed under the lesion, but the lesion is resected using an electric knife instead of the snare. First, the mucosal incision is performed around the lesion (Fig. 1.3a, b). Then, the submucosal layer of the lesion is dissected under direct vision (Fig.  1.3c, d). Using ESD even large lesions, which would previously have been referred for surgery, can be treated endoscopically with favorable long-term outcomes [22, 23]. High en-bloc resection rates (>90%) have been reported in Japan and other Asian countries [24, 25]. Although there is still technical gap in ESD skills between countries, this high en-bloc resection rate allows detailed pathological diagnosis. 4. Endoscopic full-thickness resection In recent years, an endoscopic full-thickness resection (EFTR) technique has been developed using an over-the-scope clip (OTSC) [26]. It has been proven as a safe and effective method to resect colorectal lesions. The procedural time is similar to EMR and the resected specimen can be histopathologically evaluated a

b

c

d

e

f

Lesion

Injection needle

Electric knife

Submucosal fluid injection

Image b, c

Image b, c, d

Image e

Fig. 1.3  ESD. (a) A large (60  mm in diameter) superficial lesion in the ascending colon, (b) mucosal incision around the lesion, (c) submucosal dissection under the direct vision, (d) last cut, (e) excision site, (f) resected specimen

1  Endoscopic Resection of Early Colorectal Cancer

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in detail as a full-thickness en-bloc specimen is obtained. The main limitation is the difficulty assessing the lateral margin at the time of resection due to the obscurement of visual field by the distal attachment. Laparoscopic endoscopic cooperative surgery (LECS) can also lead to a full-thickness local resection by means of combined use of laparoscope and endoscope [27, 28]. In 2008, Hiki et al. reported seven gastrointestinal stromal tumors treated with LECS [27]. Because of potential risk of tumor cells seeding into peritoneal cavity, LECS is mainly indicated for gastric submucosal tumors. Recently, LECS technique has been modified to non-exposed endoscopic wall inversion methods, which may be a good treatment alternative for difficult ESD cases [28]. Considering the good function preservation after standard partial colectomy, the LECS may have limited value and should be mainly reserved for technically difficult ESD cases. Predictors for difficult ESD include: unstable scope maneuver, severe submucosal fibrosis, non-lifting sign, and lesions located in the sigmoid colon or splenic/ hepatic flexures [29–33]. When present, these factors may indicate a possible role for the EFTR.

1.4  T  reatment Outcomes and Indication of EMR, Piecemeal EMR and ESD The indications for EMR and ESD are still debated. The purposes of endoscopic treatments are: (1) complete resection of the lesion and (2) pathological evaluation of the resected specimen. Therefore, if a complete resection (en-bloc R0 resection) can be obtained with EMR, this technique is preferable. A meta-analysis of 15 studies showed only 63% (95% CI: 51.50–73.52) of en-bloc resections using the EMR technique to resect large (>2 cm) colorectal polyps (mean size of the polyps was 22.48 ± 4.52 mm) [34]. Furthermore, risk factors for recurrence after EMR include large size (>40 mm), use of argon plasma coagulation, and piecemeal resection (>5 pieces) [35–38]. Notably, a meta-analysis showed no statistical difference between EMR and ESD in the en-bloc resection rate of 10 mm), and do not have depressed areas (Table 1.2,

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Table 1.2  LST-G with no risk of submucosal invasion LST-G (n = 414) No large nodulea No large nodulea, No depressed area No large nodulea, No depressed area, 10 mm

a

Fig. 1.4  Representative images of LST-G with no risk of submucosal invasion

Fig. 1.4). Indeed, Shigita and collages studied the clinical significance and validity of the sub-classification of LST-G and reported that in the granule size group of 10 cm

5 cm 5 cm from the tumor did not improve the staging accuracy or survival benefit [13]. To date, there is no evidence to suggest any association between longitudinal resection margin and oncological outcomes [14]. Increase in the longitudinal resection margin tends to increase the number of harvested lymph nodes [11, 14]. Thus, considering the low frequency of lymph node metastasis beyond 10 cm from the tumor, a 10-cm longitudinal resection margin seems adequate for T3 and T4 colon cancers. For cecal cancer, right hemicolectomy is not necessarily required, and ileocecal resection may be adequate. Similarly, for sigmoid colon cancer, left hemicolectomy is not necessarily required, and sigmoidectomy may often be adequate.

3.3  D3 Lymph Nodes Dissection for Rectal Cancer 3.3.1  J apanese Categorization of Regional Lymph Nodes That Drain the Rectum According to the Japanese Classification of Colorectal Carcinoma, regional lymph nodes for lower rectal cancer located below the peritoneal reflection include lateral, pericolic, intermediate, and main nodes. Lateral lymph nodes are located outside the mesorectal fascia and are categorized into the following four nodes: (1) internal

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T. Yamaguchi

ObN

EIA

ObA

Ob-Nodes

CIA DII-Nodes PII-Nodes IIA

CI-Nodes

Fig. 3.4  A schema of lateral lymph nodes for lower rectal cancer. CIA, common iliac artery; CI-Nodes, common iliac nodes; DII-Nodes, distal internal iliac nodes; EIA, external iliac artery; IIA, internal iliac artery; ObA, obturator artery; ObN, obturator nerve; Ob-Nodes, obturator nodes; PII-Nodes, proximal internal iliac nodes

iliac; (2) common iliac; (3) obturator; and (4) external iliac. The internal iliac nodes are further categorized into proximal and distal internal iliac nodes (Fig. 3.4).

3.3.2  M  esorectal Excision and Distal Margin for Rectal Cancer Since the proposal by Heald et al., total mesorectal excision is the standard surgical procedure for rectal cancer in Western countries [15]. However, there is no clear consensus on the need for TME for all rectal cancers. Shirouzu et al. investigated distal spread of >600 rectal cancer specimens and found that 10% of all the specimens and only 3.8% of curative surgery specimens showed distal spread; moreover, the extent of distal spread was within 1 cm in most specimens [16]. In a study by Ono et al., the distal spread was within 3 cm in upper rectal cancer and within 2 cm in lower rectal cancer [17]. Therefore, TME is not necessarily required for rectal cancer. Indeed, tumor-specific mesorectal excision is the typical approach to rectal cancer surgery in Japan. The Japanese classification recommends 3- and 2-cm distal margin for upper and lower rectal cancers, respectively.

3  D3 Lymph Node Dissection for Colon and Rectal Cancers

35

3.3.3  I ndications for Lateral Lymph Node Dissection for Rectal Cancer D3 dissection entails complete lymphadenectomy of lateral lymph nodes as well as main nodes. The local recurrence rate after rectal cancer surgery was reported to be >30% since three decades or more [18, 19]. Local recurrence of rectal cancer typically causes severe pain and neurological disturbance, which impairs the quality of life of the patient. Since the late 1960s, lateral lymph node dissection has been performed in Japan to reduce the risk of local recurrence [18, 20, 21], while neoadjuvant chemoradiotherapy followed by surgery is established as a standard treatment strategy based on evidence from clinical trials in Western counties [15]. Currently, lateral lymph node dissection with autonomic nerve preservation is widely performed for rectal cancer to achieve the twin objectives of curability and functional preservation [22, 23]. The reported incidence of lateral lymph node metastasis in patients with lower rectal cancer ranges from 10 to 25% (Table 3.1) [24–27], which is comparable with that of intermediate node (inferior mesenteric artery nodes) metastasis [2]. However, lateral lymph node metastasis is rarely observed in cases of upper rectal cancer in

Table 3.1  Published reports pertaining to lateral lymph node dissection Lateral lymph node metastasis Author Year (%) Moriya Y et al. 1989 42/231 (18.9) [21] Sugihara K 1996 23/238 (10.6) et al. [22] Moriya Y et al. 1997 62/448 (13.8) [24] Hida J et al. 1997 [29] Mori T et al. 1998 40/157 (25.5) [23] Ueno H et al. 2001 53/250 (21.2) [30] Shirouzu K 2001 47/303 (15.5) et al. [31] Shimoyama M 2003 9/66 (13.6) et al. [32] Ueno M et al. 2005 41/222 (18.5) [33] Sugihara K 2006 129/930 (13.9) et al. [26] Kobayashi 2009 117/784 (14.9) et al. [27]

5-year survival Local recurrence rate in LLDM rate in LLDM (%) (%) 49 (DFS)

Overall local recurrence rate (%) 27/174 (15.5)

49.3

6/23 (26.1)

12/214 (5.6)

43 (DFS)

17/62 (27.4)

42/448 (9.4)

25 37.3 39.1

4/54 (7.4) 25/44 (56.8) 12/152 (7.9)

38.9

2/9 (22.2)

6/66 (9.1)

41.7

15/34 (44.1)

37/222 (16.7)

45.8

33/129 (25.6)

158/1977 (8.0)

47.7

28/117 (23.9)

82/784 (10.5)

36

T. Yamaguchi

which the lower border is located proximal to the peritoneal reflection and also in ≤T2 stage lower rectal cancer [26]. Therefore, the indication for lateral lymph node dissection in Japan is T3-T4 rectal cancer, wherein the lower border is located distal to the peritoneal reflection [2]. Recently, Japanese Clinical Oncology Group (JCOG) demonstrated the significance of lateral lymph node dissection for lower rectal cancer. The JCOG0212 trial was a randomized controlled trial to confirm that the results of mesorectal excision alone are not inferior to those of mesorectal excision with lateral lymph node dissection. The incidence of lateral lymph node metastasis in the study population was 7% even in patients with lower rectal cancer who showed no signs of lateral lymph node metastasis on preoperative evaluation. The trial failed to demonstrate the noninferiority of mesorectal excision alone over mesorectal excision with lateral lymph node dissection [28]. Therefore, for lower rectal cancer with the lower border located distal to the peritoneal reflection and the depth of tumor invasion being up to mascularis propria or deeper, lateral lymph node dissection as part of D3 lymph node dissection is recommended even in the absence of any signs of lateral lymph node metastasis on preoperative evaluation [2]. However, several issues pertaining to lateral lymph node dissection for lower rectal cancer need to be resolved. (1) Comparison to neoadjuvant chemoradiotherapy: Randomized controlled trials to compare lateral lymph node dissection and neoadjuvant chemoradiotherapy have not been conducted. (2) Preoperative diagnosis of lymph node metastasis: Although lymph nodes