Annual Report 2017
Department of Colorectal Surgery
Yukihide Kanemitsu, Dai Shida, Shunsuke Tsukamoto, Konosuke Moritani, Ryohei Sakamoto, Manabu Inoue
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 Division. Lung metastasis from colorectal cancer is also treated in cooperation with the Department of Thoracic Surgery. Although surgery is still the main treatment modality for colorectal cancer, multidisciplinary treatments including radiotherapy and chemotherapy are important in advanced cancer. We have 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 treatment strategy by a multidisciplinary team (MDT) before treatment is performed.
Our team and what we do
In the Department of Colorectal Surgery, five staff surgeons perform more than 600 colorectal operations per year, which is top-class in Japan, and we always aim to improve a survival rate with safe surgery associated with less complications. The length of hospital stay is as short as seven days after surgery in laparotomy, laparoscopic surgery, and robot-assisted surgery, which allows more patients to receive surgical treatment with fewer beds.
There are five staff surgeons, one chief resident, and four to seven rotating residents. Every morning (7:30-8:30), we have a morning conference and rounds in wards 15A and B. An MDT meeting is held for cancer patients as a form of institutionalised communication every Tuesday morning (7:15-8:00), and a conference is held for the diagnosis of colorectal cancer: colorectal surgeons, endoscopists, and radiologists discuss
the diagnosis for preoperative patients every Tuesday evening (18:30-19:30). Every Wednesday
morning (7:00-7:30), a conference is held for the treatment of colorectal cancer: colorectal surgeons discuss treatments for preoperative and postoperative patients. Twelve to fifteen operations are performed a week in our department.
hRobot-assisted surgery
In our department, we have been performing robot-assisted rectal surgeries, in which robotic surgery technology is applied to rectal cancer treatment, since March 2014. It is considered that rectal cancer surgery using the Da Vinci surgical system enables more intricate and precise operations because the doctor performs surgery under the robotic support. It also enables safer and less invasive surgery since accurate three-dimentional
image data can be obtained. The field of robot-
assisted surgery is expected to play an important role in the next-generation surgery. We have already confirmed the safety and feasibility of this new robot-assisted rectal surgery in the clinical study in 30 patients. Currently, the surgery is performed as a treatment option that is covered by the insurance.
Research activities
Patients with advanced rectal cancers are treated with conventional surgery. Adjuvant chemotherapy is being used in stage III colorectal cancer patients in a clinical setting. Although preoperative radiotherapy is not performed
routinely for advanced rectal cancer, patients with T4b rectal cancers or rectal cancers with multiple lymph node metastases are treated with preoperative chemoradiotherapy and surgery. Patients with symptoms caused by unresectable tumors are treated with palliative surgery including palliative resection, bypass, and stoma before chemotherapy. To evaluate the survival benefit and safety of primary resection plus chemotherapy compared to chemotherapy alone in asymptomatic stage IV colorectal cancer with synchronous unresectable metastatic disease, a randomized controlled trial comparing resection of primary tumor plus chemotherapy with chemotherapy alone in incurable Stage IV colorectal cancer is ongoing (JCOG1007, iPACS). Another randomized controlled trial is ongoing to evaluate the non-
inferiority of overall survival of laparoscopic surgery to open surgery for palliative resection of primary tumor in incurable Stage IV colorectal cancer (JCOG1107, ENCORE). Symptomatic, Stage IV colorectal cancer patients with non-curable metastasis are pre-operatively randomized to either open or laparoscopic colorectal resection. Patients with resectable liver metastasis are treated in cooperation with the Department of Hepatobiliary and Pancreatic Surgery and adjuvant chemotherapy regimens are being evaluated in a clinical trial (JCOG0603 study). To confirm the superiority of perioperative chemotherapy, a randomized phase II/III trial started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional fluorouracil and folinic acid with oxaliplatin (mFOLFOX6) for lower rectal cancer patients with suspected lateral pelvic node metastasis (JCOG1310). The registration for JCOG1502C (a study to examine adjuvant chemotherapy for small bowel adenocarcinoma) and JCOG1503C (a study to examine the efficacy of aspirin for stage III colorectal cancer) began in 2017 and 2018, respectively. In addition, a translational study (JCOG1506A1) to compare the clinical data from previous large-scale clinical trials including more than 4,000 patients and the genetic analysis data of clinical specimens such as surgical specimens and peripheral blood has been initiated in collaboration with the BioBank Japan (BBJ) toward improvement in treatment outcome and individualization of treatment.
We also carry out basic research in cooperation with scientists at the National Cancer Center Research Institute (NCCRI) and the identification of a suitable treatment based on such a prediction is one of our important goals.
Clinical trials
Our department plays a central role in conducting multi-institutional clinical trials in Japan. Y. Shimada is a representative of the Colorectal Cancer Group of the Japan Clinical Oncology Group (JCOG). Our department is participating in nine phase III JCOG studies.
1) JCOG0603: A randomized study that compares adjuvant modified FOLFOX (5-FU + l-LV +
Oxaliplatin) to surgery alone after hepatic resection for liver metastasis from colorectal cancer. One hundred and seventy patients have been enrolled and recruitment continues.
2) JCOG1007: A randomized controlled trial comparing resection of primary tumor plus chemotherapy with chemotherapy alone in incurable Stage IV colorectal cancer is ongoing.
3) JCOG1018: Randomized phase III study of mFOLFOX7 or CAPOX plus bevacizumab versus 5-Fluorouracil/leucovorin or capecitabine plus bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer is ongoing.
4) JCOG1107: A randomized controlled trial comparing laparoscopic surgery with open surgery in palliative resection of primary tumor in incurable Stage IV colorectal cancer is ongoing.
5) JCOG1310: A phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6
for lower rectal cancer with suspected lateral pelvic node metastasis is ongoing.
6) JCOG1410A: Japanese Observational Study to Evaluate the Accuracy of Preoperative Imaging Diagnosis for Lateral Pelvic Lymph Node Metastasis in Rectal Cancer is ongoing.
7) JCOG1506A: Prognostic or predictive biomarker study in the patients who underwent surgery with/without postoperative chemotherapy for stage II/III colorectal cancer is ongoing.
8) JCOG1502C: A Global Study To Evaluate The Potential Benefit of Adjuvant Chemotherapy for Small Bowel Adenocarcinoma is ongoing.
9) JCOG1503C: Efficacy of aspirin for stage III colorectal cancer: a randomized double-blind placebo-controlled trial is ongoing.
Education
One senior resident and several residents were recruited to our department in 2017. One surgeon from the UK, one medical student from Germany, four surgeons from China, two surgeons from the Philippines, three surgeons from Korea, and one surgeon from Malaysia visited our department for training.
Future prospects
Although Japan has been leading the world in the development of new drugs such as irinotecan and oxaliplatin, it has been far behind in the development of molecular targeted drugs. While the gap is being filled by international collaborative clinical trials, there is no guarantee that innovative new drugs will continue to dramatically improve treatment outcome of cancer patients in the future. Therefore, it is a big but important challenge for clinical oncologists to think and act strategically. Outside of Japan, novel studies using the data from many clinical trials and the data from specimen examination have been carried out one after another. We believe that all the specialists involved in colorectal cancer treatment must work together with their wisdom and experience in order to improve treatment outcome. We will reconfirm the department's research policy that a clinical question is reviewed by all participants and an answer is obtained from a randomized controlled trial, and continue to actively promote clinical trials in the future.
hDevelopment of a new laparoscopic surgical system using 8K Super Hi-Vision technology
At the National Cancer Center Hospital (NCCH), a national research project working on the development of a new laparoscopic surgical system and the utilization of high definition image data using 8K Super Hi-Vision technology has been initiated. With this project, further improvement of the treatment outcome of patients with colorectal cancer is expected in the future.
List of papers published in January 2017 - March 2018
Journal
1. Kobayashi H, Ishida H, Ueno H, Hinoi T, Inoue Y, Ishida F, Kanemitsu Y, Konishi T, Yamaguchi T, Tomita N, Matsubara N, Watanabe T, Sugihara K. Childbirth after surgery for familial adenomatous polyposis in Japan. Surg Today, 47:233-237, 2017
2. Kobayashi H, Ishida H, Ueno H, Hinoi T, Inoue Y, Ishida F, Kanemitsu Y, Konishi T, Yamaguchi T, Tomita N, Matsubara N, Watanabe T, Sugihara K. Association between the age and the development of colorectal cancer in patients with familial adenomatous polyposis: a multi-institutional study. Surg Today, 47:470-475, 2017
3. Ohue M, Iwasa S, Kanemitsu Y, Hamaguchi T, Shiozawa M, Ito M, Yasui M, Katayama H, Mizusawa J, Shimada Y. A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study). Jpn J Clin Oncol, 47:84-87, 2017
4. Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Kinugasa Y, Komori K, Ohue M, Ota M, Akazai Y, Shiozawa M, Yamaguchi T, Bandou H, Katsumata K, Murata K, Akagi Y, Takiguchi N, Saida Y, Nakamura K, Fukuda H, Akasu T, Moriya Y. Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial. Ann Surg, 266:201-207, 2017
5. Tanaka M, Kanemitsu Y, Shida D, Ochiai H, Tsukamoto S, Nagino M, Moriya Y. Prognostic Impact of Intra-abdominal/Pelvic Inflammation After Radical Surgery for Locally Recurrent Rectal Cancer. Dis Colon Rectum, 60:827-836, 2017
6. Yamadera M, Ueno H, Kobayashi H, Konishi T, Ishida F, Yamaguchi T, Hinoi T, Inoue Y, Kanemitsu Y, Tomita N, Ishida H, Sugihara K. Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan. Surg Today, 47:690-696, 2017
7. Kanemitsu Y, Komori K, Shida D, Ochiai H, Tsukamoto S, Kinoshita T, Moriya Y. Potential impact of lateral lymph node dissection (LLND) for low rectal cancer on prognoses and local control: A comparison of 2 high-volume centers in Japan that employ different policies concerning LLND. Surgery, 162:303-314, 2017
8. Suto T, Watanabe M, Endo T, Komori K, Ohue M, Kanemitsu Y, Itou M, Takii Y, Yatsuoka T, Shiozawa M, Kinugasa T, Ueno H, Takayama T, Masaki T, Masuko H, Horie H, Inomata M. The Primary Result of Prospective Randomized Multicenter Trial of New Spray-Type Bio-absorbable Adhesion Barrier System (TCD-11091) Against Postoperative Adhesion Formation. J Gastrointest Surg, 21:1683-1691, 2017
9. Sasaki T, Ito Y, Ohue M, Kanemitsu Y, Kobatake T, Ito M, Moriya Y, Saito N. Postoperative Chemoradiotherapy After Local Resection for High-Risk T1 to T2 Low Rectal Cancer: Results of a Single-Arm, Multi-Institutional, Phase II Clinical Trial. Dis Colon Rectum, 60:914-921, 2017
10. Yamazaki N, Koga Y, Taniguchi H, Kojima M, Kanemitsu Y, Saito N, Matsumura Y. High expression of miR-181c as a predictive marker of recurrence in stage II colorectal cancer. Oncotarget, 8:6970-6983, 2017
11. Tanaka M, Kanemitsu Y, Ueno H, Kobayashi H, Konishi T, Ishida F, Yamaguchi T, Hinoi T, Inoue Y, Tomita N, Ishida H, Sugihara K. Prognostic impact of hospital volume on familial adenomatous polyposis: a nationwide multicenter study. Int J Colorectal Dis, 32:1489-1498, 2017
12. Goto S, Hasegawa S, Hida K, Uozumi R, Kanemitsu Y, Watanabe T, Sugihara K, Sakai Y. Multicenter analysis of impact of anastomotic leakage on long-term oncologic outcomes after curative resection of colon cancer. Surgery, 162:317-324, 2017
13. Nakamura K, Nonaka S, Nakajima T, Yachida T, Abe S, Sakamoto T, Suzuki H, Yoshinaga S, Oda I, Matsuda T, Sekine S, Kanemitsu Y, Katai H, Saito Y, Hirota S. Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis. Endosc Int Open, 5:E137-E145, 2017
14. Ueno H, Kanemitsu Y, Sekine S, Ishiguro M, Ito E, Hashiguchi Y, Kondo F, Shimazaki H, Mochizuki S, Kajiwara Y, Shinto E, Yamamoto J. Desmoplastic Pattern at the Tumor Front Defines Poor-prognosis Subtypes of Colorectal Cancer. Am J Surg Pathol, 41:1506-1512, 2017
15. Tsukamoto S, Kanemitsu Y, Shida D, Ochiai H, Mazaki J. Comparison of the clinical results of abdominoperanal intersphincteric resection and abdominoperineal resection for lower rectal cancer. Int J Colorectal Dis, 32:683-689, 2017
16. Nishiumi S, Kobayashi T, Kawana S, Unno Y, Sakai T, Okamoto K, Yamada Y, Sudo K, Yamaji T, Saito Y, Kanemitsu Y, Okita NT, Saito H, Tsugane S, Azuma T, Ojima N, Yoshida M. Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry. Oncotarget, 8:17115-17126, 2017
17. Shida D, Tagawa K, Inada K, Nasu K, Seyama Y, Maeshiro T, Miyamoto S, Inoue S, Umekita N. Modified enhanced recovery after surgery (ERAS) protocols for patients with obstructive colorectal cancer. BMC Surg, 17:18, 2017
18. Wada S, Inoguchi H, Hirayama T, Matsuoka YJ, Uchitomi Y, Ochiai H, Tsukamoto S, Shida D, Kanemitsu Y, Shimizu K. Yokukansan for the treatment of preoperative anxiety and postoperative delirium in colorectal cancer patients: a retrospective study. Jpn J Clin Oncol, 47:844-848, 2017
19. Tsukamoto S, Nishizawa Y, Ochiai H, Tsukada Y, Sasaki T, Shida D, Ito M, Kanemitsu Y. Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study. Jpn J Clin Oncol, 47:1135-1140, 2017
20. Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, Hamaguchi T, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kawano H, Kinugasa Y, Kokudo N, Murofushi K, Nakajima T, Oka S, Sakai Y, Tsuji A, Uehara K, Ueno H, Yamazaki K, Yoshida M, Yoshino T, Boku N, Fujimori T, Itabashi M, Koinuma N, Morita T, Nishimura G, Sakata Y, Shimada Y, Takahashi K, Tanaka S, Tsuruta O, Yamaguchi T, Yamaguchi N, Tanaka T, Kotake K, Sugihara K. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol, 23:1-34, 2018
21. Shida D, Tsukamoto S, Ochiai H, Kanemitsu Y. Long-Term Outcomes After R0 Resection of Synchronous Peritoneal Metastasis from Colorectal Cancer Without Cytoreductive Surgery or Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol, 25:173-178, 2018
22. Hamaguchi T, Shimada Y, Mizusawa J, Kinugasa Y, Kanemitsu Y, Ohue M, Fujii S, Takiguchi N, Yatsuoka T, Takii Y, Ojima H, Masuko H, Kubo Y, Mishima H, Yamaguchi T, Bando H, Sato T, Kato T, Nakamura K, Fukuda H, Moriya Y. Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial. Lancet Gastroenterol Hepatol, 3:47-56, 2018