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Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn’s disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

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. This article reviewed a history of repeated revisions on tumor deposit (TD) definition and categorization in the tumor‐node‐metastasis (TNM) system, which may have 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,” in which all nodular type TDs are individually counted together with positive LNs to derive the final pN. The treatment of TDs should be determined in terms of how it will maximize the prognostic value of TNM classification and its reproducibility, and it is time to 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.

Background The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). Methods The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. Results The five-year relapse-free survival (RFS) rate was the highest in the Mature group ( N  = 638), followed by the Intermediate ( N  = 294) and Immature groups ( N  = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell’s C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. Conclusions Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.

Japanese mortality due to colorectal cancer is on the rise, surpassing 49,000 in 2015. Many new treatment methods have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 for the treatment of colorectal cancer (JSCCR Guidelines 2016) were prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines were prepared by consensus reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches, and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. 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 held by 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 based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2016.

Background Surgical removal of metastasized paraaortic lymph nodes (PALNs) can prolong the survival of certain patients with colorectal cancer (CRC). However, the role of postoperative chemotherapy in such patients remains unknown. Patients and Methods This multicenter retrospective study examined 97 patients with PALN metastasis from CRC who underwent surgical resection at 36 centers in Japan between 2010 and 2015. On the basis of adjuvant chemotherapy (AC) after the lymphadenectomy, patients were classified into non-AC and AC groups (27 and 70 patients, respectively). After the exclusion of patients receiving irinotecan, the latter group was further categorized into 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) subgroups (14 and 52 patients, respectively) according to the use of L-OHP. Background characteristics and postoperative survival were compared among the groups. Results Marked differences were not seen in background characteristics, except for neoadjuvant treatment, between the non-AC and AC groups. The AC group exhibited better recurrence-free survival (RFS; p = 0.009) and overall survival (OS; p = 0.040 by the Wilcoxon test) than the non-AC group. However, RFS and OS of the 5-FU group did not differ from those of the L-OHP group ( p = 0.73 and p = 0.92 by the Wilcoxon test, respectively). Conclusions AC may be associated with improved prognosis of patients after the removal of PALN metastasis from CRC, but L-OHP did not offer additional survival benefits. Prospective studies comparing non-AC with 5-FU- and L-OHP-based AC are needed to confirm these findings.

Background Even after successful Helicobacter pylori eradication, primary or metachronous gastric cancers are sometimes discovered. The endoscopic features of these cancers may be modified by controlling inflammation. Characteristic findings for such lesions in terms of narrow-band imaging with magnifying endoscopy (NBI-ME) and histopathology need to be clarified to allow accurate diagnosis. Methods Distinctive NBI-ME characteristics were examined retrospectively in intramucosal or minimally submucosal and differentiated-type adenocarcinomas from a successful eradication group (42 patients, 50 lesions) and a non-eradicated control group (44 patients, 50 lesions) matched in age and sex. A “gastritis-like” appearance under NBI-ME was characterized by uniform papillae and/or tubular pits with a whitish border, regular or faint microvessels and unclear demarcation, resembling the adjacent noncancerous mucosa. Histological differentiation at the luminal surface of the cancer was evaluated according to Ki-67 immunoreactivity restricted at the middle or lower portion of the tubules. NBI-ME alteration was prospectively confirmed in 29 patients (30 lesions) after eradication therapy. Results The frequency of a “gastritis-like” appearance was 44 % (22/50) for the eradication group, which was significantly higher than the 4 % (2/50) for the control group ( p  < 0.001). In the eradication group, the “gastritis-like” appearance was significantly correlated with histological surface differentiation ( p  < 0.001). In the prospective study, NBI-ME showed changes to heterogeneous papillary microstructures in 43 % (10/23) of the lesions after successful eradication at short-term follow-up. Conclusions Identification of surface maturation under NBI-ME offers a promising approach for accurate diagnosis of early gastric cancers after successful eradication.

More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥1000  μ m (odds ratio (95% confidence interval)=5.56 (2.14–19.10)) and high-grade budding/sprouting (3.14 (1.91–5.21)). Among lesions with a depth of submucosal invasion ≥1000  μ m, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion <1000  μ m. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥1000  μ m and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥1000  μ m and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion <1000  μ m. These findings revealed that a depth of submucosal invasion ≥1000  μ m and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.

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.

Histopathologically, oral squamous cell carcinoma (OSCC) consists of well-defined interfaces with adjacent non-cancerous epithelium. Previously, we found that SCC tissues expressed higher levels of specific proteins at this interface. Ladinin-1 (LAD1) is one of the specific molecules that has increased expressions in cancer fronts; however, its function in OSCC is unknown. Therefore, this study aimed to elucidate the function of LAD1 in human OSCC cells. LAD1 was localized on the actin arc at the distal periphery of cell clusters in the OSCC cell lines HSC-2, HSC-3, and HSC-4. When LAD1 was knocked down, cellular migration was repressed in wound scratch assays but was reversed in three-dimensional collagen gel invasion assays. Characteristic LAD1 localization along actin arcs forming the leading edge of migrating cells was diminished with loss of filopodia formation and ruffling in knockdown cells, in which the expression levels of cell motility-related genes—p21-activated kinase 1 ( PAK1 ) and caveolin-1 ( CAV1 )—were upregulated and downregulated, respectively. LAD1 expression was also associated with the downregulation of vimentin and increased histological differentiation of OSCC. These results suggest that LAD1 is involved in actin dynamics during filopodia and lamellipodia formation, and in maintaining the epithelial phenotype of OSCC cells.

Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC. SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined. For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m. These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.