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Objectives: Colorectal cancer is the most prevalent malignant disease in Japan. This study aimed to publish data on colorectal cancer cases registered in 2023, involving initial treatments in 2015. Methods: Participating facilities of the Japanese Society for Cancer of the Colon and Rectum (JSCCR) registered cases treated in 2015 according to the 8th edition of the Japanese Classification of Colorectal Carcinoma. Data sent to the National Registration Committee in 2023 were analyzed. Results: The study analyzed 12,804 cases. Endoscopic treatments were performed in 983 cases, endoscopic treatment followed by surgical resection in 734 cases, and surgeries were carried out in 10,884 cases. Notably, the proportion of laparoscopic surgeries increased significantly from 34.7% in 2010 to 63.5% in 2015. Conclusions: This report details the characteristics, treatment methods, and outcomes of colorectal cancer patients who received initial treatment in 2015 at JSCCR-participating facilities. These data should be helpful for patients to understand their disease accurately and for healthcare professionals to explain colorectal cancer and its treatments to patients.

Abstract Aim To clarify the usefulness of intraoperative lavage cytology in patients undergoing curative resection for pStage II‐III colorectal cancer in a prospective multicenter study. Methods Patients preoperatively diagnosed with stage II‐III colorectal cancer between 2013 and 2017 from 20 hospitals were enrolled. Lavage cytology was performed twice during the surgery. The primary endpoint was the effect of lavage cytology on the 5‐year relapse‐free survival (RFS) in patients with pStage II‐III colorectal cancer. The secondary endpoint was the effect of lavage cytology on the 5‐year overall survival (OS) and peritoneal recurrence. Results A total of 1378 patients were eligible for analysis. The number of patients with pStage II‐III colorectal cancer was 670 and 708, respectively. Fifty‐four patients (3.9%) had positive cytological results. In pStage II patients, the 5‐year RFS rates with positive and negative cytology were 61.1% and 81.6%, respectively (p = 0.023). The 5‐year OS rates were 67.1% and 91.7%, respectively (p = 0.0083). However, there was no difference in RFS or OS between pStage III patients with positive and negative cytology results. The peritoneal recurrence rates were 11.8% and 1.5% in pStage II patients with positive and negative cytology results, respectively (p = 0.032). These rates were 10.5% and 2.5% in patients with stage III disease, respectively (p = 0.022). Conclusion Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II‐III colorectal cancer.

Objectives: Due to its rarity, there is insufficient evidence for managing ASCC patients with distant metastasis. Thus far, the therapeutic strategy for distant metastasis of ASCC is less standardized and requires a more individualized approach. Therefore, it is crucial to obtain information regarding treatment outcomes and prognostic factors following the development of distant metastasis to identify optimal care strategies for better patient outcomes and predict their prognosis. Methods: In the multi-institute cohort study conducted in Japan, we retrospectively assessed 58 ASCC patients with synchronous distant metastasis and 28 ASCC patients with metachronous distant metastasis. Results: When comparing the OS between ASCC patients with synchronous distant metastasis and metachronous distant metastasis, there was no statistically significant difference between the two groups. The OS rate at five years was 37.4% for patients with synchronous distant metastasis and 27.6%; for metachronous distant metastasis. In ASCC patients with synchronous distant metastasis, patients with distant metastasis at multiple sites exhibited extremely worse OS than those at single sites (HR: 4.56, 95% CI: 1.16-18.00, P< 0.0001). In addition, in ASCC patients with metachronous distant metastasis, early recurrence was an independent factor for predicting poor OS in the multivariate analysis (HR: 4.13, 95% CI: 1.22-13.94, P = 0.022). Conclusions: ASCC patients with distant metastasis at multiple sites were a worse prognosis. In addition, early recurrence was identified as an independent prognostic factor for OS among ASCC patients.

Abstract Background and aims Crohn's disease (CD)‐associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger‐onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD‐associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC. Methods CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD‐associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old). Results Younger‐onset CDAAC (YO‐CDAAC) patients were significantly more likely to have a poor outcome than those with older‐onset CDAAC (OO‐CDAAC) in terms of both disease‐free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09–4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05–3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO‐CDAAC (p = 0.012 and 0.0031, respectively). Conclusions YO‐CDAAC may have a poorer prognosis compared with OO‐CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease.

Abstract Aim The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results The study included 296 patients with ovarian metastasis. The 3‐y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3‐y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P

Abstract Aim To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods This multi‐institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

Abstract Background The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD‐associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse‐free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16–3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28–3.63, p = 0.004). Conclusions Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients.

Abstract Background Patients with ulcerative colitis are reported to be at increased risk of colorectal cancer and are also at high risk of postoperative complications. However, the incidence of postoperative complications in these patients and how the type of surgery performed affects prognosis are not well understood. Methods Data collected by the Japanese Society for Cancer of the Colon and Rectum on ulcerative colitis patients with colorectal cancer between January 1983 and December 2020 were analyzed according to whether total colorectal resection was performed with ileoanal anastomosis (IAA), ileoanal canal anastomosis (IACA), or permanent stoma creation. The incidence of postoperative complications and the prognosis for each surgical technique were investigated. Results The incidence of overall complications was not significantly different among the IAA, IACA, and stoma groups (32.7%, 32.3%, and 37.7%, respectively; p = 0.510). The incidence of infectious complications was significantly higher in the stoma group (21.2%) than in the IAA (12.9%) and IACA (14.6%) groups (p = 0.048); however, the noninfectious complication rate was lower in the stoma group (13.7%) than in the IAA (21.1%) and IACA (16.2%) groups (p = 0.088). Five‐year relapse‐free survival was higher in patients without complications than in those with complications in the IACA group (92.8% vs. 75.2%; p = 0.041) and the stoma group (78.1% vs. 71.2%, p = 0.333) but not in the IAA group (90.3% vs. 90.0%, p = 0.888). Conclusion The risks of infectious and noninfectious complications differed according to the type of surgical technique used. Postoperative complications worsened prognosis.

PURPOSELimited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA.METHODSThis retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests.RESULTSData from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively.CONCLUSIONPatients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

Abstract Aim There have been no reports of searching for metastases to lymph nodes along the accessory middle colic artery (aMCA). The aim of this study was to investigate the metastasis rate of the aMCA for splenic flexural colon cancer. Methods Patients with histologically proven colon carcinoma located in the splenic flexure, clinically diagnosed as stage I‐III were eligible for this study. Patients were retrospectively and prospectively enrolled. The primary endpoint was frequency of lymph node metastasis to the aMCA (station 222‐acc and 223‐acc). The secondary endpoint was the frequency of lymph node metastasis to the middle colic artery (MCA) (station 222‐lt and 223) and left colic artery (LCA) (station 232 and 253). Results Between January 2013 and February 2021, a total of 153 consecutive patients were enrolled. The location of the tumor was 58% in the transverse colon and 42% in the descending colon. Lymph node metastases were observed in 49 cases (32%). The presence of aMCA rate was 41.8% (64 cases). The metastasis rates of stations 221, 222‐lt, and 223 were 20.0%, 1.6%, and 0%, and stations 231, 232, and 253 were 21.4%, 1.0%, and 0%, respectively. The metastasis rates of stations 222‐acc and 223‐acc were 6.3% (95% confidence interval: 1.7%‐15.2%) and 3.7% (95% confidence interval: 0.1%‐19%), respectively. Conclusions This study identified the distribution of lymph node metastases from splenic flexural colon cancer. If the aMCA is present, this vessel should be targeted for dissection, taking into account the frequency of lymph node metastasis.

Abstract Tumor deposits (TDs) are discontinuous tumor spread in the mesocolon/mesorectum which is found in approximately 20% of colorectal cancer (CRC) and negatively affects survival. We have a history of repeated revisions on TD definition and categorization in the tumor‐node‐metastasis (TNM) system leading to stage migration. Since 1997, TDs have been categorized as T or N factors depending on their size (TNM5) or contour (TNM6). In 2009, TNM7 provided the category of N1c for TDs in a case without positive lymph nodes (LNs), which is also used in TNM8. However, increasing evidence suggests that these revisions are suboptimal and only “partially” successful. Specifically, the N1c rule is certainly useful for oncologists who are having difficulty with TDs in a case with no positive LNs. However, it has failed to maximize the value of the TNM system because of the underused prognostic information of individual TDs. Recently, the potential value of an alternative staging method has been highlighted in several studies using the “counting method.” For this method, all nodular type TDs are individually counted together with positive LNs to derive the final pN, yielding a prognostic and diagnostic value that is superior to existing TNM systems. The TNM system has long stuck to the origin of TDs in providing its categorization, but it is time to make way for alternative options and initiate an international discussion on optimal treatment of TDs in tumor staging; otherwise, a proportion of patients end up missing an opportunity to receive the optimal adjuvant treatment.

Objectives: Adjuvant chemotherapy for stage II colorectal cancer patients with high-risk factors for recurrence can be useful; however, its advantage in prognosis remains to be controversial. Thus, in this study, we aimed to assess whether a combination of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels can predict the prognosis and advantage of adjuvant chemotherapy. Methods: Using a Japanese nationwide database, in total, 3,688 patients with curative resected stage II colorectal cancer were registered retrospectively between 2008 and 2012 in 24 referral institutions. Patients were classified into three groups as follows: Group A (both non-high levels of CEA and CA19-9), Group B (either high levels of CEA or CA19-9), and Group C (both high levels of CEA and CA19-9). Results: Multivariable Cox regression analysis, adjusting the depth of tumor invasion, number of dissected lymph nodes, tumor differentiation, lymphatic and venous invasion, and other covariates, showed that the 5-year disease-free survival and overall survival were shorter in Group C than in Groups A and B. Furthermore, in Group C, the 5-year disease-free survival rate was improved in the surgery-plus-AC group compared to the surgery-alone group. Conclusions: As with existing high-risk factors for recurrence, the combination assessment of preoperative serum CEA and CA19-9 can predict the prognosis for colorectal cancer. Adjuvant chemotherapy may provide a prolonged disease-free survival advantage in stage II colorectal cancer patients with high levels of both tumor markers.

Abstract Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above‐mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.

Abstract Background Several studies have demonstrated that right-sided tumors have poorer prognosis than left-sided tumors in patients with unresectable colorectal cancer (CRC). The predictive ability of the tumor sidedness in CRC treated with chemotherapy in each sex is unclear. Methods Subjects were 964 unresectable recurrent patients treated with chemotherapy with stage II-III CRC after curative resection between 2004 and 2012. Post-recurrence cancer-specific survival (CSS) for each sex was examined. Results Patients were 603 males (222 right-side tumors (cecum to transverse colon) and 381 left-sided tumors (descending colon to rectum)), and 361 females (167 right-side tumors and 194 left-sided tumors). Right-sided tumors developed peritoneal recurrences in males and females. Left-sided tumors were associated with locoregional recurrences in males and with lung recurrences in females. Right-sided tumors were associated with shorter post-recurrence CSS in both sexes. In males, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.53, P

Objectives: This retrospective study was conducted to clarify the morphological characteristics of colorectal cancer (CRC) in Japanese familial adenomatous polyposis (FAP) patients. Methods: This study was carried out by the study group for FAP of the Japanese Society for Cancer of the Colon and Rectum. FAP patients who underwent surgical resection between 2000 and 2012 were included in the study. Results: Of the 303 patients enrolled, 119 patients without CRC were excluded. Of 523 lesions, 49 lesions with missing morphological information were excluded; hence, only 474 CRC lesions in 178 patients (328 superficial lesions in 122 patients and 146 non-superficial lesions in 92 patients) were included in the study. Depressed lesions accounted for 3.0% of superficial lesions and ulcerated lesions accounted for 84.9% of non-superficial lesions. The depressed superficial lesions were observed only in patients with sparse and attenuated FAP (P = 0.003). The age of the patients at surgery differed between the two groups, with patients with depressed superficial lesions being significantly older than those with non-depressed superficial lesions (P = 0.009). Moreover, the age of the patients at FAP diagnosis differed between the two groups, with patients with ulcerated non-superficial lesions being significantly older than those with protruded non-superficial lesions (P = 0.006). Conclusions: In patients with FAP, depressed superficial CRC lesions rarely developed but were detected in our study group, and ulcerated non-superficial CRC lesions were also present with similar ratios. Clinicians should pay attention to depressed superficial lesions during endoscopic surveillance of FAP patients.

Objectives: This study aimed to explore the risk factors associated with cancer cell exfoliation in Stage II and III colorectal cancer (CRC). Methods: This multicenter, prospective, observational study targeted 1,698 patients with cStage II and III CRC who underwent R0 resection between 2013 and 2017. Clinicopathological variables were analyzed for correlations with positive peritoneal lavage cytology (PLC). Results: The positive PLC rate was 2.7% (46/1,694 cases) at laparotomy and 1.6% (25/1,590 cases) after tumor resection. Logistic regression analyses identified that undifferentiated histologies diagnosed by preoperative biopsy specimen, cT4, and pN+ were independent factors that affected the positive PLC at laparotomy. The positive PLC rate at laparotomy was 4.5% (33/736 cases) among the patients with undifferentiated histology and/or cT4. Logistic regression analyses revealed that the presence of ascites and undifferentiated histology by biopsy independently affected positive PLC after tumor resection. Conclusions: The undifferentiated histology and/or T4 indicated by preoperative diagnosis were identified as factors affecting PLC at laparotomy. Furthermore, ascites and preoperative histological type were identified as factors affecting positive PLC after tumor resection. As factors affecting positive PLC, these preoperative findings were found to be equivalent to pathological findings.

Abstract Aim Neuroendocrine tumors (NETs) are one of the subtypes of neuroendocrine neoplasms and are defined as epithelial neoplasms with predominant neuroendocrine differentiation. The aim of this study was to clarify the clinicopathological characteristics of colorectal NETs through a nationwide retrospective study in Japan. Methods This multicenter retrospective cohort study of NETs in Japan was conducted by the study group of the Japanese Society for Cancer of the Colon and Rectum. In this study, we aimed to clarify the characteristics of Japanese patients with colorectal NETs. This cohort study included patients with colorectal NETs who were treated from January 2011 to December 2015. Results Most NETs developed in the lower rectum. Predictive factors of lymph node metastasis included size (>10 mm), depth of invasion (muscular propria or greater), NET grade (NET G2), depressed lesion of the tumor, and lymphovascular infiltration. In particular, depressed lesion of the tumor and lymphovascular infiltration were independent predictive factors of lymph node metastasis. The presence of an increased number of these predictive factors increased the lymph node metastasis rate. Conclusion Surgical resection with lymph node dissection is considered in the colorectal NETs patients with predictive factors of lymph node metastasis, the number of which is correlated with incidence of lymph node metastasis.

Abstract Aim To investigate the usefulness of resection for synchronous peritoneal metastasis from colorectal cancer. Methods The patients who underwent surgery for stage IV colorectal cancer at 16 hospitals between 1991 and 2007 were enrolled in this study. The overall survival rates of patients with synchronous peritoneal metastasis from colorectal cancer with and without R0 resection were compared using a propensity score‐matched analysis. Results Among the 3965 patients with stage IV colorectal cancer, 1169 had synchronous peritoneal metastasis (28.5%). No patients received hyperthermic intraperitoneal chemotherapy (HIPEC) in this study. Among the 1169 patients, 783 had enough clinicopathologic information and went through further analysis. Out of 783 patients, 204 underwent R0 resection. A multivariate analysis revealed that severity of peritoneal metastasis according to the Japanese classification (P

Abstract Aim The prognostic value of the stage III subclassification system based on the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma has not yet been clarified. This study aimed to develop a modified system with optimal risk stratification and compare its performance with the current staging systems. Methods Clinicopathological data from 6855 patients with stage III colorectal cancers who underwent D3 dissection were collected from a nationwide multicenter database. After determining patient survival rates across 13 divisions based on pathological N stage (N1, N2a, and N2b/N3) and tumor depth (T1, T2, T3, T4a, and T4b), except for T1N2a and T1N2b/N3 due to the small number, we categorized patients into three groups and developed a trisection staging system according to the Akaike information criterion. We then compared the Akaike information criterion of the developed system with those of the current staging systems. Results The T1N1[rank, 1] division (98.5%) had the most favorable prognosis in terms of 5‐year cancer‐specific survival, followed by T2N1[2] (93.9%), T2N2a[3] (92.0%), T3N1[4] (87.0%), T3N2a[5] (78.8%), T4aN1[6] (78.7%), T2N2b/N3[7] (77.8%), T4aN2a[8] (75.2%), T4bN1[9] (73.5%), T3N2b/N3[10] (64.7%), T4aN2b/N3[11] (61.5%), T4bN2b/N3[12] (43.0%), and T4bN2a[13] (42.5%). Compared to the categorizations of the Japanese and tumor‐node‐metastasis systems (Akaike information criterion, 22 684.6 and 22 727.1, respectively), the following stage categorizations were proven to be the most clinically efficacious: T1N1[1]‐T3N1[4], T3N2a[5]‐T4bN1[9], and T3N2b/N3[10]‐T4bN2a[13] (Akaike information criterion, 22 649.2). Conclusion The proposed modified system may be useful in the risk stratification of patients with stage III colorectal cancer who had undergone D3 dissection.

Objectives: In Japan, there are three grades of peritoneal metastasis from colorectal cancer. The grade depends on the extent and number of lesions (P classification). The P classification is useful for its simplicity but lacks objectivity. On the other hand, the peritoneal cancer index (PCI) objectively indicates the peritoneal metastasis grade. However, the evaluation process is complicated clinically. In this study, we compared these two methods and investigated how to improve the P classification's objectivity by referring to PCI. Methods: We investigated 150 cases of synchronous peritoneal metastasis from colorectal cancer. We inspected the correlation between the P classification and the PCI and pointed out the problems which prevented objective evaluation when using the P classification. We also estimated new criteria for extent and number in the P classification. Results: We found the ideal definition for the best alignment between the P classification and the PCI was: ・P1 is metastases confined to one peritoneal region, ・P2 is 19 or fewer peritoneal metastases in two or more regions, and ・P3 is 20 or more metastases in two or more regions. This revision improved the P classification's objectivity and correlated with the PCI. Conclusions: Grading using the P classification was both imprecise and subjective. We propose a new standard value of extent and number in the P classification based on the PCI. This improvement would provide an objective, simple method of grading for peritoneal metastasis from colorectal cancer.

Abstract Tumour-Node-Metastasis (TNM) staging of colorectal cancer (CRC) needs further classification for better treatment because of disease heterogeneity. Although molecular classifications which are expensive and laborious are under study, cost and labour efficient subtyping is desirable. We assessed the combinations of preoperative tumour marker (TM) elevation and tumour lymphovascular invasion (LVI) as a solution. We used the pooled data of 7151 colon cancer (CC) patients and 4620 rectal cancer (RC) patients who received curative surgery between 2004 and 2008 in Japan. The best-matched subtyping for predicting relapse-free survival (RFS) was statistically selected using the c-index and Akaike’s information criterion. This subtyping (TM-LVI), which consisted of three categories by TM elevation status and severity of LVI status, was an independent prognostic factor for RFS of CC (stage IIa, IIIb, and IIIc) and RC (stage I, IIa, IIb, IIIa, and IIIb) and also for disease specific survival of CC (stage IIa, IIb, IIIb, and IIIc) and RC (all stage except for IIc). Although TM-LVI classified CRC patients into low and high recurrence risk groups, the application of adjuvant therapy was not accordance with the TM-LVI status. TM-LVI may be a cost and labour efficient subtyping of colorectal cancer for better treatment strategy.

Abstract Aim To investigate the effectiveness of the institutional medical structure and of the implemented clinical practice guidelines for improving colon cancer surgical outcomes. Methods We conducted a web‐based questionnaire survey among departments registered at the National Clinical Database in Japan from October 2014 to January 2015 to assess the association between quality indicators (QIs), including structure and process indicators (clinical practice guideline adherence), and the risk‐adjusted odds ratio for operative mortality (AOR) after right hemicolectomy for colorectal cancer during the study period. Results Among the 2064 departments registering at least one colorectal surgery during the study period, we obtained responses from 814 departments (39.4%). Our analysis on data from 22 816 patients with right hemicolectomy demonstrated that three structural QIs (certification of training hospitals by the Japanese Society of Gastroenterological Surgery and the presences of board‐certified gastroenterological and colorectal surgeons) were associated with significantly lower AOR (P

Objectives: The necessary and sufficient length of the distal resection margin (l-DRM) for rectosigmoid cancer remains controversial. This study evaluated the validity of the 3-cm l-DRM rule for rectosigmoid cancer in the Japanese classification of colorectal cancer. Methods: We retrospectively reviewed 1,443 patients with cT3 and cT4 rectosigmoid cancer who underwent R0 resection in Japanese institutions between 1995 and 2004. We identified the optimal cutoff point of the l-DRM affecting overall survival (OS) rate using a multivariate Cox regression analysis model. Using this cutoff point, the patients were divided into two groups after balancing the potential confounding factors of the l-DRM using propensity score matching, and the OS rates of the two groups were compared. Results: A multivariate Cox regression analysis model revealed that the l-DRM of 4 cm was the best cutoff point with the greatest impact on OS rate (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.00-1.84; P = 0.0452) and with the lowest Akaike information criterion value. In the matched cohort study, the OS rate of patients who had l-DRM of 4 cm or more was significantly higher than that of patients who had l-DRM < 4 cm (n = 402; 5-year OS rates, 87.6% vs. 80.3%, respectively; HR, 1.60; 95% CI, 1.09-2.31; P = 0.0136). Conclusions: For cT3 and cT4 rectosigmoid cancer, l-DRM of 4 cm may be an appropriate landmark for a curative intent surgery, and we were unable to definitively confirm the validity of the Japanese 3-cm l-DRM rule.

Abstract Aim We investigated the clinical impact of D3 lymph node dissection preserving left colic artery (LCA) compared to D3 without LCA preservation using data from JCOG0404. LCA preservation is expected to maintain adequate blood supply, which is effective in preventing anastomotic leakage, intestinal paralysis, and bowel obstruction. Whether D3 with LCA preservation (Group A) improves clinical outcomes following resection of sigmoid colon cancer compared to D3 without LCA preservation (Group B) is unclear. Methods Procedure type was identified from photographs of the surgical field collected for central surgical review in JCOG0404. Clinical outcomes were compared between each procedure. Results Among the 1057 randomized patients in JCOG0404, 631 patients receiving sigmoid colectomy or anterior resection were included in the subgroup analysis. Group A comprised of 135 patients and Group B of 496 patients. Patient backgrounds did not differ between groups. Median operative time, blood loss, anastomotic leakage, and intestinal paralysis were not remarkably different (Group A vs Group B: 185 vs 186 minutes, 60 vs 50 mL, 3.0% vs 5.0%, and 2.2% vs 3.8%). More overall postoperative complications occurred in Group B than Group A (21.6% vs 9.6%, P = .022). Five‐year relapse‐free survival (RFS) and overall survival (OS) tended to be better in Group A than Group B (RFS: 83.7% and 80.5%, HR 0.80 [95% CI 0.51‐1.26], OS: 96.3% and 91.1%, HR 0.41 [95% CI 0.19‐0.89]). Conclusions Short‐ and long‐term outcomes tend to be better in Group A than Group B, indicating that preservation of LCA could be an alternative treatment.

Background and Aim Although colorectal laterally spreading tumors (LSTs) can be classified into four subtypes, the histopathological characteristics are known to differ among these subtypes. We therefore performed a logistic regression analysis to determine whether the risk of pathological T1 cancer of large colorectal LSTs can be predicted based on factors such as endoscopic findings in a large group of patients enrolled in a multicenter study in Japan. Methods In the main study, we assessed 1236 colorectal adenomas or early cancers that were classified as LSTs measuring 20 mm or more in diameter and treated endoscopically. Logistic regression analysis was performed to determine whether factors such as the subtype of LST could be used to predict the risk of pathological T1 cancer. A validation study of 356 large colorectal LSTs was conducted to confirm the validity of the results obtained in the main study. Results The locations and tumor diameter of the LSTs in the main study were found to differ significantly according to the LST subclassification (P

Objective: The treatment policy of colorectal cancer in elderly patients is controversial due to a lack of specific guidelines. To clarify the present management of colorectal cancer for aged patients, a questionnaire survey was conducted by the Japanese Society for Cancer of the Colon and Rectum. Methods: Questionnaire forms were sent to the 430 member institutions of the Japanese Society for Cancer of the Colon and Rectum. Results: The response rate of the surgical department to the questionnaire was 39%. Performance status was used for preoperative assessments, and electrocardiogram and ultrasonic cardiograms were conducted for cardiovascular evaluations in many institutions. The same extent of surgical procedures was often adopted for elderly and younger patients, and the frequency of a laparoscopic procedure was the same regardless of a patient's age. A simultaneous hepatectomy for hepatic metastasis was considered in one-third of institutions. In many institutions, intersphincteric resection for patients with possible sphincter-saving surgery was not considered for elderly patients with low rectal cancer. Conclusion: Japanese Society for Cancer of the Colon and Rectum member institutions often used the same surgical treatment strategies for both elderly and younger patients with the exception of performing intersphincteric resection.

Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non‐polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC.

A new histological classification of neuroendocrine tumors (NET) was established in WHO 2010. ENET and NCCN proposed treatment algorithms for colorectal NET. Retrospective study of NET of the large intestine (colorectal and appendiceal NET) was performed among institutions allied with the Japanese Society for Cancer of the Colon and Rectum, and 760 neuroendocrine tumors from 2001 to 2011 were re-assessed using WHO 2010 criteria to elucidate the clinicopathological features of NET in the large intestine. Next, the clinicopathological relationship with lymph node metastasis was analyzed to predict lymph node metastasis in locally resected rectal NET. The primary site was rectum in 718/760 cases (94.5%), colon in 30/760 cases (3.9%), and appendix in 12/760 cases (1.6%). Patients were predominantly men (61.6%) with a mean age of 58.7 years old. Tumor size was less than 10 mm in 65.4% of cases. Proportions of NET G1, G2, G3, and MANEC were 88.4%, 6.3%, 3.9%, and 1.3%, respectively. Of the 760 tumors, 468 were locally resected, and 292 were surgically resected with lymph node dissection. Rectal NET showed a higher proportion of NET G1, and colonic and appendiceal NET was more commonly G3 and MANEC. Of the 292 surgically resected cases, 233 NET G1 and G2 located in the rectum were used for the prediction of lymph node metastasis. Lymphatic and blood vessel invasion were independent predictive factors of lymph node metastasis. NET G2 cases showed more frequent lymph node metastasis than that seen in NET G1 cases, but this was not an independent predictor of lymph node metastasis. Of the 98 surgically resected cases less than 10 mm in size, we found 9 cases with lymph node metastasis (9.2%). All cases were NET G1, and 8 of 9 cases were positive either for lymphatic invasion or blood vessel invasion. Using the WHO classification, we found NET in the large intestine showed a tumor-site–dependent variety of histological and clinicopathological features. Risk of lymph node metastasis in rectal NET was confirmed even in lesions smaller than 10 mm. Concordant assessment of vascular invasion will be required to estimate lymph node metastasis in small lesions.

Background: Colorectal cancer (CRC) is one of the most frequently occurring cancers in Japan, and thus a wide range of methods have been deployed to study the molecular mechanisms of CRC. In this study, we performed a comprehensive analysis of CRC, incorporating copy number aberration (CRC) and gene expression data. For the last four years, we have been collecting data from CRC cases and organizing the information as an “omics” study by integrating many kinds of analysis into a single comprehensive investigation. In our previous studies, we had experienced difficulty in finding genes related to CRC, as we observed higher noise levels in the expression data than in the data for other cancers. Because chromosomal aberrations are often observed in CRC, here, we have performed a combination of CNA analysis and expression analysis in order to identify some new genes responsible for CRC. This study was performed as part of the Clinical Omics Database Project at Tokyo Medical and Dental University. The purpose of this study was to investigate the mechanism of genetic instability in CRC by this combination of expression analysis and CNA, and to establish a new method for the diagnosis and treatment of CRC. Materials and methods: Comprehensive gene expression analysis was performed on 79 CRC cases using an Affymetrix Gene Chip, and comprehensive CNA analysis was performed using an Affymetrix DNA Sty array. To avoid the contamination of cancer tissue with normal cells, laser micro-dissection was performed before DNA/RNA extraction. Data analysis was performed using original software written in the R language. Result: We observed a high percentage of CNA in colorectal cancer, including copy number gains at 7, 8q, 13 and 20q, and copy number losses at 8p, 17p and 18. Gene expression analysis provided many candidates for CRC-related genes, but their association with CRC did not reach the level of statistical significance. The combination of CNA and gene expression analysis, together with the clinical information, suggested UGT2B28, LOC440995, CXCL6, SULT1B1, RALBP1, TYMS, RAB12, RNMT, ARHGDIB, S1000A2, ABHD2, OIT3 and ABHD12 as genes that are possibly associated with CRC. Some of these genes have already been reported as being related to CRC. TYMS has been reported as being associated with resistance to the anti-cancer drug 5-fluorouracil, and we observed a copy number increase for this gene. RALBP1, ARHGDIB and S100A2 have been reported as oncogenes, and we observed copy number increases in each. ARHGDIB has been reported as a metastasis-related gene, and our data also showed copy number increases of this gene in cases with metastasis. Conclusion: The combination of CNA analysis and gene expression analysis was a more effective method for finding genes associated with the clinicopathological classification of CRC than either analysis alone. Using this combination of methods, we were able to detect genes that have already been associated with CRC. We also identified additional candidate genes that may be new markers or targets for this form of cancer.

We report a very rare case of extensive ductal carcinoma in situ (DCIS) of the breast with secretory features in a 30-year old Japanese woman. The patient presented with a nodule in the lower inner quadrant of the left breast measuring approximately 2-3 cm, accompanied by an irregular tumor shadow with segmental microcalcification on mammography. These findings suggested malignancy, and excisional biopsy was performed following core needle biopsy. Pathological diagnosis was that of DCIS with secretory features. A treatment plan of simple mastectomy and sentinel lymph node biopsy was chosen. Most previous reports have only described invasive secretory carcinoma of the breast. We have only been able to find 2 case reports of non-invasive secretory lesion in the English literature to date. Because the characteristics of this lesion are not widely known, we thought it important to share our findings.

Purpose. To assess the accuracy of high-resolution MR imaging as a means of evaluating mural invasion and lymph node metastasis by colorectal carcinoma in surgical specimens. Materials and Methods. High-resolution T1-weighted and T2-weighted MR images were obtained in 92 surgical specimens containing 96 colorectal carcinomas. Results. T2-weighted MR images clearly depicted the normal colorectal wall as consisting of seven layers. In 90 (94%) of the 96 carcinomas the depth of mural invasion depicted by MR imaging correlated well with the histopathologic stage. Nodal signal intensity on T2-weighted images (93%) and nodal border contour (93%) were more accurate than nodal size (89%) as indicators of lymph node metastasis, and MR imaging provided the highest accuracy (94%–96%) when they were combined. Conclusion. High-resolution MR imaging is a very accurate method for evaluating both mural invasion and lymph node metastasis by colorectal carcinoma in surgical specimens.