Kenjiro Kotake

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.

Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years

Background: Colorectal carcinoids are often described as low-grade malignant. However, no study has compared the survival between patients with colorectal carcinoids and those with carcinomas, in a large series. In addition, no global consensus has been established on the crucial determinants of metastasis in colorectal carcinoids. Aim: To determine the predictive factors for metastasis in colorectal carcinoids and clarify their prognosis compared with adenocarcinomas. Methods: Data of all patients diagnosed as having colorectal carcinoids were extracted from a large nationwide database of colorectal tumours, the Multi-Institutional Registry of Large-Bowel Cancer in Japan, for the period from 1984 to 1998. Risk factors for lymph node (LN) metastases and distant metastases were analysed among those who were undergoing surgery, by univariate and multivariate analysis. Cancer-specific survival was also compared between patients with colorectal carcinoids and those with adenocarcinomas registered in the same period. Results: Among the 90 057 cases of colorectal tumours that were diagnosed, a total of 345 cases of carcinoids were identified, including 247 colorectal carcinoids of those undergoing surgery. Risk factors for LN metastasis were tumour size ⩾11 mm and lymphatic invasion, whereas those for distant metastasis were tumour size ⩾21 mm and venous invasion. Colorectal carcinoids without these risk factors exhibited no LN metastasis or distant metastasis. Cancer-specific survival of patients with colorectal carcinoids without metastasis was better than that of those with adenocarcinomas. However, the survival was similar between carcinoids and adenocarcinomas if the tumours had LN metastasis or distant metastasis. Conclusions: The presence of metastasis in colorectal carcinoids could lead to survival that is as poor as in adenocarcinomas. Tumours ⩽10 mm and without lymphatic invasion could be curatively treated by local resection, but others would need radical LN dissection.

Ulcerative colitis‐associated colorectal cancer shows a poorer survival than sporadic colorectal cancer: A nationwide Japanese study

Background: The clinicopathological features of ulcerative colitis‐associated colorectal cancer (UC‐CRC) have not yet been fully clarified, especially in Asian populations. This study aimed to clarify the prognosis and clinicopathological features of UC‐CRC in comparison with sporadic CRC in the Japanese population. Methods: Histologically diagnosed UC‐CRC patients between 1978 to 1998 were extracted from the Multi‐Institutional Registry of Large‐Bowel Cancer in Japan, a large nationwide CRC database, and the clinicopathological features and postoperative survival rates of UC‐CRC patients and sporadic CRC patients were compared. Results: Among the 108,536 CRC patients registered between 1978 and 1998, a total of 169 UC‐CRC patients were identified, including 121 patients who had been treated surgically. The proportion of UC‐CRC patients increased in the period between 1995 and 1998 compared to that between 1978 and 1994. Comparisons with the sporadic CRC patients showed that the UC‐CRC patients were younger, had a higher proportion of multiple cancer lesions, had higher proportions of superficial type lesions and invasive type lesions morphologically, and had higher proportions of mucinous or signet ring cell carcinomas. In stage III, UC‐CRC patients had a poorer survival rate than the sporadic CRC patients (43.3% versus 57.4%, P = 0.0320). Conclusions: UC‐CRC increased over the investigated time periods and showed a poorer survival than sporadic CRC in the advanced stage, while no difference was observed in the early stage. By detecting UC‐CRC at an early stage we can expect a similar postoperative outcomes to that of sporadic CRC. These results stress the importance of surveillance for the early detection of UC‐CRC. Inflamm Bowel Dis 2011

Changes in colorectal Cancer during a 20-year period: An extended report from the multi-institutional registry of large bowel cancer, Japan

PURPOSE This study was designed to examine trends of colorectal cancer in relation to age, gender, site, and survival during the past 20 years. METHODS The multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum offered 87,695 surgical cases with invasive adenocarcinoma during 1978 to 1997 for analysis. We calculated survival rates and used the Cox’s proportional hazard model for cases during 1978 to 1994. RESULTS The number of cases showed a 2.5-fold increase with consistent male predominance confined to the distal colon and the rectum. Colon cancer in the last five-year period was more likely right-sided for females (odds ratio, 1.26; 95 percent confidence interval, 1.16–1.38) and males (odds ratio, 1.16; 95 percent confidence interval, 1.06–1.25) compared with the first period. Cancers in younger patients were more likely at Stage III to IV in the late 1990s if the cancers were in the distal colon, the rectum (for both genders), or the proximal colon (for females). Survival was improved except for cases with proximal colon cancer of Stage IV. In the multivariate analysis, hazard ratios for death in the postoperative five years were 0.65, 0.59, and 0.58 for proximal colon, distal colon, and rectal cancers, respectively, in the last five-year period compared with those in the first period. Reduced hazard ratio for females was the largest for proximal colon cancer with Stage I to II. CONCLUSION Although surgical outcome was largely improved, delayed presentation or diagnosis in younger patients remained a problem. Preferential localization in the proximal colon and survival benefit for females should be investigated.

Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease?

Objective:To evaluate whether lateral pelvic lymph nodes (LNs) in low rectal cancer are metastatic disease or part of regional LNs that are amenable to curative resection. Background:It is highly controversial whether lateral pelvic LNs should be considered as regional or distant disease, although the American Joint Committee on Cancer (AJCC) defines internal iliac LNs as regional LNs of rectal cancer. Methods:Data of patients with stage I to III low rectal cancer who underwent curative resection from 1978 to 1998 were extracted from the multi-institutional registry of large bowel cancer in Japan. Patients with only mesorectal LN metastasis were classified as the mesorectal-LN group. Patients with lateral pelvic LN metastasis localized to or extending beyond the internal iliac area were classified as the internal lateral pelvic lymph nodes (LPLN) group and external-LPLN group, respectively. Overall survival (OS) and cancer-specific survival (CSS) were compared between the groups. Results:Lateral pelvic LN dissection was performed in 5789 (50%) of 11,567 patients. Overall, 3905 (34%), 411 (3.6%), and 244 (2.1%) patients were classified as the mesorectal-LN, internal-LPLN, and external-LPLN groups, respectively. When the mesorectal LN group was subdivided as defined by the AJCC, both 5-year OS and CSS were not significantly different between the N2a and internal-LPLN groups (OS: 45% vs 45%, P = 0.9585; CSS: 51% vs 49%, P = 0.5742), and the N2b and external-LPLN groups (OS: 32% vs 29%, P = 0.3342; CSS: 37% vs 34%, P = 0.4347). OS and CSS were significantly better in the external-LPLN group than in stage IV patients who underwent curative resection (OS: 29% vs 24%, P = 0.0240; CSS: 34% vs 27%, P = 0.0117). Conclusions:Lateral pelvic LNs can be considered as regional LNs in low rectal cancer, although metastasis extending beyond the internal iliac area is associated with poorer survival.

Colorectal cancer statistics in Japan: data from JSCCR registration, 1974–1993

Abstract Japanese colorectal cancer statistics from 1974 to 1993 are reported, based on the accumulated data registered by the member institutions of the Japan Society for Cancer of the Colon and Rectum (JSCCR). Both colon and rectal cancers were more prevalent in men than in women. In both sexes, colonic cancers were more prevalent than rectal cancers, and a greater increasing trend was seen in colonic cancers. Moderately differentiated adenocarcinoma seemed to have increased in recent years. The resectability and operative death rates improved slightly, but the ratio of stage I + II/III + IV cancers (both colonic and rectal) did not change at all during the 20-year period reported. The yearly improved survival in both colonic and rectal cancers, particularly in stages II and III, may well reflect improved surgical techniques.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial)

BACKGROUND S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600mg/day and LV: 75mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALS.GOV: NCT00660894.This phase III study, ACTS-CC, is the first study in which demonstrated the efficacy of S-1, an oral fluoropyrimidine, as adjuvant chemotherapy for stage III colon cancer by confirming its noninferiority to UFT/LV in terms of disease-free survival. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer.

Number of Lymph Nodes Retrieved is an Important Determinant of Survival of Patients with Stage II and Stage III Colorectal Cancer

OBJECTIVE The number of lymph nodes retrieved is recognized to be a prognostic factor of Stage II colorectal cancer. However, the prognostic significance of the number of lymph nodes retrieved in Stage III colorectal cancer remains controversial. METHODS The relationship between the number of lymph nodes retrieved and clinical and pathological factors, and significance of the number of lymph nodes retrieved for prognosis of Stage II and III colorectal cancer were investigated. A total of 16 865 patients with T3/T4 colorectal cancer who had R0 resection were analysed. RESULTS The arithmetic mean of the number of lymph nodes retrieved of all cases was 20.0. The number of lymph nodes retrieved were varied according to several clinical and pathological variables with significant difference, and the greater difference was observed in scope of nodal dissection. Survival of Stages II and III was significantly associated with the number of lymph nodes retrieved. Five-year overall survival of the patients with ≤ 9 of the number of lymph nodes retrieved and those with >27 differed by 6.4% for Stage II colon cancer, 8.8% for Stage III colon cancer, 12.5% for Stage II rectal cancer and 10.6% for Stage III rectal cancer. With one increase in the number of lymph nodes retrieved, the mortality risk was decreased by 2.1% for Stage II and by 0.8% for Stage III, respectively. The cut-off point of the number of lymph nodes retrieved was not obtained. CONCLUSIONS The number of lymph nodes retrieved was shown to be an important prognostic variable not only in Stage II but also in Stage III colorectal cancer, and it was most prominently determined by the scope of nodal dissection. A cut-off value for the number of lymph nodes retrieved was not found, and it is necessary to carry out appropriate nodal dissection and examine as many lymph nodes as possible.

Overview of colorectal cancer in Japan

BACKGROUND AND PURPOSE: In Japan, the incidence of colorectal cancer has increased remarkably since World War II, and interest in this cancer has grown rapidly among Japanese clinicians and pathologists. As a result, the Japanese Society for Cancer of the Colon and Rectum started a multi-institutional registry of colorectal cancer in 1980. The purpose of this report is to present an overview of the actual state of surgical and pathologic aspects of colorectal cancer treated in the leading hospitals in Japan. MATERIALS AND METHODS: Registry files of clinical and pathologic findings for 38,369 patients treated between 1974 and 1986 with five-year follow-up information and 26,360 patients treated between 1991 and 1994 with no follow-up information were reviewed. RESULTS: Numbers of registered patients have increased annually, reflecting a trend toward an increasing incidence of this cancer in Japan. Colon cancer increased more than rectal cancer in both genders. Resection of the primary lesion was achieved in more than 97 percent of patients who underwent surgical operation recently. The curative resection rate has improved from 65.1 to 79.1 percent for colon cancer and from 71.4 to 80.4 percent for rectal cancer between the 1974 and 1979 and the 1991 and 1994 periods, and operative mortality of those has decreased from 1.8 and 2 percent to 0.5 and 0.5 percent, respectively. There was a trend toward a decrease in locally advanced cancer in terms of cancer invasion into the bowel wall. Stage IV colon cancer also decreased from 22.9 to 16.6 percent with time. The five-year survival rate of each pTNM stage has gradually been improving and was especially evident for patients with Stages I, II, and III of rectal cancer. Overall five-year survival rates for colorectal cancer patients currently exceeds 60 percent. CONCLUSION: The overall incidence of colorectal cancer and the ratio of colon cancer to rectal cancer patients in Japan are increasing. Results of surgical treatment are satisfactory with respect to curative resection rate, operative mortality, and the five-year survival rate. Registry data of the Japanese Society for Cancer of the Colon and Rectum are useful for reporting the actual state of diagnosis, treatment, and end results of colorectal cancer in Japan.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial

Background:The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis.Methods:Patients aged 20–80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m−2 per day as tegafur; LV, 75 mg per day on days 1–28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1–28, every 42 days, 4 courses). Treatment status and safety were evaluated.Results:Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of ⩾grade 3 AEs were 16% and 14%, respectively.Conclusion:Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.