Annual Report 2023

Department of Colorectal Surgery

Yukihide Kanemitsu, Shunsuke Tsukamoto, Konosuke Moritani, Yasuyuki Takamizawa, Hiroshi Nagata

Introduction

 The Department of Colorectal Surgery deals with colorectal cancer and allied malignancies in the colon and rectum. Liver metastasis from colorectal cancer is treated in cooperation with the Department of Hepatobiliary and Pancreatic Surgery. Lung metastasis from colorectal cancer is also treated in cooperation with the Department of Thoracic Surgery. Although surgery remains the primary treatment modality for colorectal cancer, multidisciplinary treatments including radiotherapy and chemotherapy are important in advanced cancer. We conduct multidisciplinary meetings with the Department of Gastrointestinal Medical Oncology, the Department of Endoscopy, the Department of Diagnostic Radiology, and the Department of Pathology and Clinical Laboratories every week, and decide the treatment strategy with a multidisciplinary team (MDT) before performing treatment.

The Team and What We Do

 We perform approximately 600 surgeries per year, and we provide the best treatment for each individual case, ranging from minimally invasive surgeries (MIS) such as laparoscopic and robot-assisted surgeries to extensive surgeries such as combined resection of adjacent or metastatic organs (Table 1). As for MIS, we started robot-assisted rectal cancer surgery in 2014 and robot-assisted colon cancer surgery in 2021, both of which are among the largest number of surgeries in Japan. In terms of surgical approach selection, the proportion of robot-assisted surgeries has also become very large overall. In robot-assisted surgery, the da Vinci SP has been used in addition to the conventional da Vinci Xi since 2023.

 On the other hand, we also handle many difficult-to-resect recurrent pelvic cancers and are involved in abdominal and pelvic sarcoma surgery in collaboration with other departments. To achieve curative resection, we also actively perform vascular resection and cytoreductive surgery for peritoneal dissemination.

 We hold weekly conferences with the Department of Endoscopy to discuss and decide on the diagnosis and treatment. In addition, a multidisciplinary team (MDT) meeting is held once a week, in which colorectal surgeons, liver surgeons, respiratory surgeons, medical oncologists, endoscopists, diagnostic radiologists, radiation therapists, and pathologists participate to determine the best treatment plan.

Research Activities

 A multicenter research group centered on JCOG; it is leading investigator-initiated multicenter clinical trials on colorectal cancer.

 In addition, with the support of the Japan Agency for Medical Research and Development (AMED) “Research Project for Utilization of 8K and Other High Definition Image Data,” a national project to develop a new remote surgery-assisted laparoscopic surgery system using 8K technology and to investigate the use of high-definition image data is being conducted in collaboration with NHK Engineering Systems. Since 2002, our hospital and the NHK Foundation have been developing an 8K endoscope system. In 2017, we conducted a clinical trial on 23 patients with colorectal cancer and reported its effectiveness by reducing intraoperative blood loss by 50%. From 2022, the company proceeded to develop remote surgical support for ultra-high-speed communication, enabling the sharing of shake-free images and real-time guidance through on-screen annotation.

 Furthermore, clinical trials were initiated for complete surgical reduction of peritoneal dissemination, in which all lesions are removed, for peritoneal dissemination for which anticancer drugs are ineffective, with the aim of establishing a standard treatment for colorectal cancer with peritoneal dissemination, for which no effective treatment is available.

Clinical Trials

 Our department plays a central role in conducting multi-institutional clinical trials in Japan. Y. Kanemitsu is a representative of the Colorectal Cancer Group of the Japan Clinical Oncology Group (JCOG). Our department is currently participating in eight JCOG studies as shown below.

1. JCOG1502C: A Global Study to Evaluate the Potential Benefit of Adjuvant Chemotherapy for Small Bowel Adenocarcinoma

2. JCOG1503C: Efficacy of aspirin for stage III colorectal cancer: a randomized double-blind placebo-controlled trial

3. JCOG1801: A randomized controlled trial comparing surgery plus adjuvant chemotherapy with preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy for locally recurrent rectal cancer

4. JCOG1805: A randomized controlled trial to examine efficacy of adjuvant chemotherapy for stage II colorectal cancer patients at high risk of developing recurrence according to T-stage and three selected pathological factors.

5. JCOG2004: Randomized Phase II Study of Bevacizumab plus FOLFIRI versus Ramucirumab plus FOLFIRI versus Aflibercept plus FOLFIRI for Metastatic Colorectal Cancer after failure of First-line chemotherapy with Fluoropyrimidine and Oxaliplatin to Explore Predictive Biomarker

6. JCOG2006: A randomized phase II study comparing preoperative adjuvant chemotherapy with mFOLFOX6 versus FOLFOXIRI for resectable locally advanced colon cancer

7. JCOG2010: Single-arm confirmatory trial of the total neoadjuvant therapy and watch and wait strategy for the patients with low rectal cancer

8. JCOG2207: A phase III randomized controlled trial comparing total mesorectal excision and lateral lymph node dissection plus adjuvant chemotherapy with total neoadjuvant therapy followed by total mesorectal excision and selective lateral lymph node dissection for the patients with locoregionally advanced low rectal cancer

Education

 In our resident doctor education, under the guidance of a supervising physician, the residents are trained not only in the acquisition and improvement of skills, but also in a series of medical procedures such as judgment of the indications for surgery, selection of surgical techniques, postoperative management, working as a primary surgeon or assistant surgeon after gaining experience, and postoperative treatment. In addition, we actively instruct resident doctors in the preparation of reports and papers for various research groups and conferences. As part of these efforts, we regularly conduct video conferences to review surgical techniques and research conferences to check the progress of research and provide guidance.

Future Prospects

 The treatment of colorectal cancer has made rapid progress since the wave of new effective drugs in 1996-2003, and is expected to move toward more individualized treatment, which will require the ability to respond to individual diversity. As demands on surgeons increase with the number of surgical indications, they are required to acquire higher skills and develop new and effective treatments. On the other hand, for patients with peritoneal dissemination who have not benefited from these new effective drugs, another approach to treatment development is required, and a prospective study to evaluate the safety of multidisciplinary treatment combining complete reduction surgery (cytoreductive surgery: CRS) and systemic chemotherapy has has just started.

 In the 8K study, fixed-point endoscopic surgery using 8K SuperVision technology will be performed for colorectal cancer patients from 2024 under remote guidance by transmitting images from the 8K endoscopy system between our operating room (Tokyo) and a remote guidance facility (Osaka) via high-speed communication (wired or wireless). Remote surgical guidance using 8K SuperVision technology is useful and is expected to improve endoscopic surgical training for trainee surgeons as well as to address the shortage of young surgeons in non-urban areas.

List of papers published in 2023

Journal

1. Shida D, Kuchiba A, Shibata T, Hamaguchi T, Yamasaki S, Ito M, Kobatake T, Tonooka T, Masaki T, Shiozawa M, Takii Y, Uetake H, Okamura S, Ojima H, Kazama S, Takeyama H, Kanato K, Shimada Y, Murakami Y, Kanemitsu Y. Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910. Cancer science, 114:3352-3363, 2023

2. Ito Y, Hamaguchi T, Takashima A, Mizusawa J, Shimada Y, Shiozawa M, Mizoguchi N, Kodaira T, Komori K, Ohue M, Konishi K, Teraishi F, Kinouchi M, Murata K, Fujita F, Watanabe M, Iinuma G, Ishida F, Saida Y, Matsuda T, Katayama H, Fukuda H, Kanemitsu Y. Definitive S-1/mitomycin-C chemoradiotherapy for stage II/III anal canal squamous cell carcinoma: a phase I/II dose-finding and single-arm confirmatory study (JCOG0903). International journal of clinical oncology, 28:1063-1072, 2023

3. Hashimoto T, Tsukada Y, Ito M, Kanato K, Mizusawa J, Fukuda H, Tsukamoto S, Takashima A, Kanemitsu Y. Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study). BMJ open, 13:e073217, 2023

4. Hashimoto T, Maruyama S, Takii Y, Mizusawa J, Kataoka T, Fukuda H, Tsukamoto S, Takashima A, Hamaguchi T, Kanemitsu Y. A randomized phase II study comparing preoperative mFOLFOX6 versus FOLFOXIRI for locally advanced colon cancer: JCOG2006. Future oncology (London, England), 19:1897-1904, 2023

5. Hashimoto T, Tsukamoto S, Murofushi K, Ito Y, Hirano H, Tsukada Y, Sasaki K, Mizusawa J, Fukuda H, Takashima A, Kanemitsu Y. Total neoadjuvant therapy followed by a watch-and-wait strategy for patients with rectal cancer (TOWARd): protocol for single-arm phase II/III confirmatory trial (JCOG2010). BJS open, 7:zrad110, 2023

6. Imaizumi J, Shida D, Boku N, Igaki H, Itami J, Miyakita Y, Narita Y, Takashima A, Kanemitsu Y. Prognostic factors associated with the transition in treatment methods for brain metastases from colorectal cancer. International journal of clinical oncology, 28:1043-1053, 2023

7. Matsuzaki J, Kato K, Oono K, Tsuchiya N, Sudo K, Shimomura A, Tamura K, Shiino S, Kinoshita T, Daiko H, Wada T, Katai H, Ochiai H, Kanemitsu Y, Takamaru H, Abe S, Saito Y, Boku N, Kondo S, Ueno H, Okusaka T, Shimada K, Ohe Y, Asakura K, Yoshida Y, Watanabe SI, Asano N, Kawai A, Ohno M, Narita Y, Ishikawa M, Kato T, Fujimoto H, Niida S, Sakamoto H, Takizawa S, Akiba T, Okanohara D, Shiraishi K, Kohno T, Takeshita F, Nakagama H, Ota N, Ochiya T. Prediction of tissue-of-origin of early stage cancers using serum miRNomes. JNCI cancer spectrum, 7:pkac080, 2023

8. Ogata D, Tsutsui K, Namikawa K, Moritani K, Nakama K, Jinnai S, Takahashi A, Tsukamoto S, Kanemitsu Y, Yamazaki N. Treatment outcomes and prognostic factors in 47 patients with primary anorectal malignant melanoma in the immune therapy era. Journal of cancer research and clinical oncology, 149:749-755, 2023

9. Kobayashi Y, Shida D, Boku N, Yasui K, Nakamura Y, Kudose Y, Imaizumi J, Kanemitsu Y. Prognostic Factors of Bone Metastases From Colorectal Cancer in the Era of Targeted Therapy. Diseases of the colon and rectum, 66:401-409, 2023

10. Takamizawa Y, Shida D, Horie T, Tsukamoto S, Esaki M, Shimada K, Kondo T, Kanemitsu Y. Prognostic Role for Primary Tumor Location in Patients With Colorectal Liver Metastases: A Comparison of Right-Sided Colon, Left-Sided Colon, and Rectum. Diseases of the colon and rectum, 66:233-242, 2023

11. Yasui K, Shida D, Ahiko Y, Takamizawa Y, Moritani K, Tsukamoto S, Kanemitsu Y. Risk of non-colorectal cancer-related death in elderly patients with the disease: A comparison of five preoperative risk assessment indices. Cancer medicine, 12:2290-2302, 2023

12. Horie T, Kanemitsu Y, Takamizawa Y, Moritani K, Tsukamoto S, Shida D. Prognostic differences between oligometastatic and polymetastatic disease after resection in patients with colorectal cancer and hepatic or lung metastases: Retrospective analysis of a large cohort at a single institution. Surgery, 173:328-334, 2023

13. Seishima R, Okabayashi K, Ikeuchi H, Uchino M, Futami K, Noguchi T, Ohge H, Iseki Y, Watanabe K, Itabashi M, Okamoto K, Toiyama Y, Ogino T, Nakamura M, Yamada K, Wakai T, Sato Y, Kimura H, Takahashi K, Hida K, Kinugasa Y, Ishida F, Okuda J, Daito K, Koyama F, Ueno H, Yamamoto T, Yamamoto S, Hanai T, Maemoto A, Arakaki J, Komori K, Akagi Y, Shida D, Yamaguchi S, Matsuda K, Maeda K, Noake T, Nezu R, Sasaki S, Hasegawa J, Sunami E, Kanemitsu Y, Katsumata K, Uehara K, Kiyomatsu T, Suto T, Kazama S, Yamada T, Goi T, Ishihara S, Ajioka Y, Sugihara K. Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study. The American journal of gastroenterology, 118:1248-1255, 2023

14. Imaizumi J, Moritani K, Takamizawa Y, Inoue M, Tsukamoto S, Kanemitsu Y. A review of 14 cases of perianal Paget's disease: characteristics of anorectal cancer with pagetoid spread. World journal of surgical oncology, 21:17, 2023

15. Kajiwara Y, Oka S, Tanaka S, Nakamura T, Saito S, Fukunaga Y, Takamatsu M, Kawachi H, Hotta K, Ikematsu H, Kojima M, Saito Y, Yamada M, Kanemitsu Y, Sekine S, Nagata S, Yamada K, Kobayashi N, Ishihara S, Saitoh Y, Matsuda K, Togashi K, Komori K, Ishiguro M, Kuwai T, Okuyama T, Ohuchi A, Ohnuma S, Sakamoto K, Sugai T, Katsumata K, Matsushita HO, Yamano HO, Eda H, Uraoka T, Akimoto N, Kobayashi H, Ajioka Y, Sugihara K, Ueno H. Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study. Gastrointestinal endoscopy, 97:1119-1128.e5, 2023

16. Ouchi A, Inoue M, Sato Y, Takamizawa Y, Kinoshita T, Moritani K, Komori K, Tsukamoto S, Shimizu Y, Kanemitsu Y. Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure? Japanese journal of clinical oncology, 53:386-392, 2023

17. Fuyama K, Ogawa M, Mizusawa J, Kanemitsu Y, Fujita S, Kawahara T, Sakamaki K, Oba K. Impact of correlations between prioritized outcomes on the net benefit and its estimate by generalized pairwise comparisons. Statistics in medicine, 42:1606-1624, 2023

18. Ito T, Takayanagi D, Sekine S, Hashimoto T, Shimada Y, Matsuda M, Yamada M, Hamamoto R, Kato T, Shida D, Kanemitsu Y, Boku N, Kohno T, Takashima A, Shiraishi K. Comparison of clinicopathological and genomic profiles in anal squamous cell carcinoma between Japanese and Caucasian cohorts. Scientific reports, 13:3587, 2023

19. Nagano N, Ichihashi Y, Komatsu T, Matsuzaki H, Hata K, Watanabe T, Misawa Y, Suzuki M, Sakamoto S, Kagami Y, Kashiro A, Takeuchi K, Kanemitsu Y, Ochiai H, Watanabe R, Honda K, Urano Y. Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis. Chemical science, 14:4495-4499, 2023

20. Ueno H, Hase K, Shiomi A, Shiozawa M, Ito M, Sato T, Hashiguchi Y, Kusumi T, Kinugasa Y, Ike H, Matsuda K, Yamada K, Komori K, Takahashi K, Kanemitsu Y, Ozawa H, Ohue M, Masaki T, Takii Y, Ishibe A, Watanabe J, Toiyama Y, Sonoda H, Koda K, Akagi Y, Itabashi M, Nakamura T, Sugihara K. Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping. The Lancet regional health. Western Pacific, 33:100680, 2023

21. Kataoka K, Takahashi K, Takeuchi J, Ito K, Beppu N, Ceelen W, Kanemitsu Y, Ajioka Y, Endo I, Hasegawa K, Takahashi K, Ikeda M. Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases. The British journal of surgery, 110:864-869, 2023

22. Kojima M, Yokota M, Yanagisawa N, Kitamura S, Amemiya K, Kawano S, Tsukada Y, Sakuyama N, Nagayasu K, Hashimoto T, Nakashima K, Jiang K, Kanemitsu Y, Fujita F, Akiba J, Notohara K, Itakura J, Sekine S, Sakashita S, Sakamoto N, Ishikawa S, Nakanishi Y, Yao T, Liang WY, Lauwers GY, Ito M, Sakamoto K, Ishii G, Ochiai A. Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer. The American journal of surgical pathology, 47:1122-1133, 2023

23. Hashimoto T, Takayanagi D, Yonemaru J, Naka T, Nagashima K, Machida E, Kohno T, Yatabe Y, Kanemitsu Y, Hamamoto R, Takashima A, Shiraishi K, Sekine S. A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer. British journal of cancer, 129:1176-1183, 2023

24. Kobayashi H, Kotake K, Kawasaki M, Kanemitsu Y, Kinugasa Y, Ueno H, Maeda K, Suto T, Itabashi M, Funahashi K, Ozawa H, Koyama F, Noura S, Ishida H, Ohue M, Kiyomatsu T, Ishihara S, Koda K, Baba H, Kawada K, Hashiguchi Y, Goi T, Toiyama Y, Tomita N, Sunami E, Akagi Y, Watanabe J, Hakamada K, Nakayama G, Sugihara K, Ajioka Y. A proposed new Japanese classification of synchronous peritoneal metastases from colorectal cancer: A multi-institutional, prospective, observational study conducted by the Japanese Society for Cancer of the Colon and Rectum. Annals of gastroenterological surgery, 7:765-771, 2023

25. Tsukamoto S, Ouchi A, Komori K, Shiozawa M, Yasui M, Ohue M, Nogami H, Takii Y, Moritani K, Kanemitsu Y. A multicenter prospective observational study of lymph node metastasis patterns and short-term outcomes of extended lymphadenectomy in right-sided colon cancer. Annals of gastroenterological surgery, 7:940-948, 2023

26. Terasaki M, Tsuruoka K, Tanaka T, Maeda H, Shibata M, Miyashita K, Kanemitsu Y, Sekine S, Takahashi M, Yagishita S, Hamada A. Fucoxanthin Inhibits Development of Sigmoid Colorectal Cancer in a PDX Model With Alterations of Growth, Adhesion, and Cell Cycle Signals. Cancer genomics & proteomics, 20:686-705, 2023