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BackgroundThe Japanese Society of Gastroenterology (JSGE) published ‘‘Daicho Polyp Shinryo Guideline 2014′’ in Japanese and a part of this guideline was published in English as “Evidence-based clinical practice guidelines for management of colorectal polyps” in the Journal of Gastroenterology in 2015. A revised version of the Japanese-language guideline was published in 2020, and here we introduce a part of the contents of revised version.MethodsThe guideline committee discussed and drew up a series of clinical questions (CQs). Recommendation statements for the CQs were limited to items with multiple therapeutic options. Items with established conclusions that had 100% agreement with previous guidelines (background questions) and items with no (or old) evidence that are topics for future research (future research questions: FRQs) were given descriptions only. To address the CQs and FRQs, PubMed, ICHUSHI, and other sources were searched for relevant articles published in English from 1983 to October 2018 and articles published in Japanese from 1983 to November 2018. The Japan Medical Library Association was also commissioned to search for relevant materials. Manual searches were performed for questions with insufficient online references.ResultsThe professional committee created 18 CQs and statements concerning the current concept and diagnosis/treatment of various colorectal polyps, including their epidemiology, screening, pathophysiology, definition and classification, diagnosis, management, practical treatment, complications, and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumors/carcinomas).ConclusionsAfter evaluation by the moderators, evidence-based clinical practice guidelines for management of colorectal polyps were proposed for 2020. This report addresses the therapeutic related CQs introduced when formulating these guidelines.

Background Recently in Japan, the morbidity of colorectal polyp has been increasing. As a result, a large number of cases of colorectal polyps that are diagnosed and treated using colonoscopy has now increased, and clinical guidelines are needed for endoscopic management and surveillance after treatment. Methods Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Ten specialists for colorectal polyp management extracted the specific clinical statements from articles published between 1983 and September 2011 obtained from PubMed and a secondary database, and developed the CQs and statements. Basically, statements were made according to the GRADE system. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid. Results The professional committee created 91CQs and statements for the current concept and diagnosis/treatment of various colorectal polyps including epidemiology, screening, pathophysiology, definition and classification, diagnosis, treatment/management, practical treatment, complications and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumor/carcinoma). Conclusions After evaluation by the moderators, evidence-based clinical guidelines for management of colorectal polyps have been proposed for 2014.

Conventional endoscopic resection (CER) is a widely accepted treatment for early colorectal neoplasia; however, large colorectal neoplasias remain problematic, as they necessitate piecemeal resection, increasing the risk of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en bloc resection rate. This study aimed to evaluate local recurrence and its associated risk factors after endoscopic resection (ER) for colorectal neoplasias ≥20 mm. A multicenter prospective study at 18 medium- and high-volume specialized institutions was conducted in Japan. Follow-up colonoscopy was performed after 12 months in cases of complete resection and after 3-6 months in cases of incomplete resection. Local recurrence was confirmed by endoscopic findings and/or pathological analysis. Follow-up colonoscopy was performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years; 885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3% (65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and for ESD, respectively. The relative risks of local recurrence were 0.21 (95% confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95% confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER. Significant factors associated with local recurrence were piecemeal resection, laterally spreading tumors of granular type, tumor size ≥40 mm, no pre-treatment magnification, and ≤10 years of experience in CER, and piecemeal resection only in ESD. En bloc ESD reduces the local recurrence rate for large colorectal neoplasias. Piecemeal resection is the most important risk factor for local recurrence regardless of the ER method used.

INTRODUCTION:There is considerable concern about whether endoscopic resection (ER) before additional surgery (AS) for T1 colorectal cancer (CRC) has oncologically potential adverse effects. Therefore, the aim of this study was to compare the long-term outcomes, including overall survival (OS), of patients treated with AS after ER vs primary surgery (PS) for T1 CRC using a propensity score-matched analysis from a large observational study.METHODS:This study investigated 6,105 patients with T1 CRC treated with either ER or surgical resection between 2009 and 2016 at 27 high-volume Japanese institutions, with those undergoing surgery alone included in the PS group and those undergoing AS after ER included in the AS group. Propensity score matching was used for long-term outcomes of mortality and recurrence analysis.RESULTS:After propensity score matching, 1,219 of 2,438 patients were identified in each group. The 5-year OS rates in the AS and PS groups were 97.1% and 96.0%, respectively (hazard ratio: 0.72, 95% confidence interval: 0.49-1.08), indicating the noninferiority of the AS group. Moreover, 32 patients (2.6%) in the AS group and 24 (2.0%) in the PS group had recurrences, with no significant difference between the 2 groups (odds ratio: 1.34, 95% confidence interval: 0.76-2.40, P = 0.344).DISCUSSION:ER before AS for T1 CRC had no adverse effect on patients' long-term outcomes, including the 5-year OS rate. ER is a viable first-line treatment option for endoscopically resectable T1 CRC.

INTRODUCTION:To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009.METHODS:We enrolled 4,667 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,257 patients with local resection alone [group A], 1,512 patients with additional surgery after local resection [group B], and 1,898 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively.RESULTS:Any of the risk factors were present in 3,751 patients. The LNM incidence was 10.4% (95% confidence interval 9.4-11.5) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.3) in those without risk factors (P < 0.01). In group A, the incidence of recurrence was 3.6% in patients with risk factors, but it was only 0.4% in patients without risk factors (P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.6%.DISCUSSION:Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

BackgroundThe clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan.MethodsWe analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum.ResultsThe median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7–100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA.ConclusionsOf the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.

Background It is not clear what kind of drug is appropriate to heal NSAID-induced enteropathy. Several reports showed the preventive effect of prostaglandin analogue or inducer using healthy subjects who took NSAIDs. However there was no report for healing effect and for patients. The aim of this study was to evaluate the healing effect of rebamipide in patients with NSAIDs-induced enteropathy. In addition, we evaluated for nutritional parameter. Methods This study was conducted as a randomized, double-blinded, placebo-controlled, multicenter trial. Study protocol was approved by each hospital’s ethical committees. Patients with LDA and/or NSAID more than 3 months were enrolled. Patients with enteropathy were divided into the placebo and the rebamipide groups. Rebamipide 100 mg three times daily was administered during 4 weeks. Capsule endoscopies were performed at 0 and 4 week. The number of small intestinal ulcer and erosion were evaluated. Total protein was analyzed as nutritional parameter. Results Sixty one participants were completed this study. Change in number of small intestinal erosion in the rebamipide group was −2.5 ± 3.4, and 2.1 ± 3.9 in the placebo group ( P  < 0.0001). Change in number of small intestinal ulcer in the rebamipide group was −0.5 ± 1.6, and 0.1 ± 0.7 in the placebo group ( P  = 0.024). Change in serum total protein levels in the rebamipide group was 0.06 ± 0.36, and −0.27 ± 0.34 in the placebo group ( P  = 0.0005). Conclusions Rebamipide has not only the healing effect for NSAIDs-induced enteropathy compared with placebo, but the improvement of nutritional condition. These results showed a tentative therapeutical strategy for chronic NSAIDs users.

Background: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. Methods: Fifty-three patients with colorectal neoplasms who underwent AFI were enrolled. The AFI intensity (F index) was compared with the pathological findings and gene alterations. The F index was calculated using an image analysis software program. The pathological findings were assessed by the tumor crypt density, cell densities, and N/C ratio. The aberrant methylation of p16, E-cadherin, Apc, Runx3, and hMLH1 genes was determined by a methylation-specific polymerase chain reaction. The aberrant expression of p53 and Ki-67 was evaluated by immunohistochemical staining. Results: An increased N/C ratio, the aberrant expression of p53, Ki-67, and the altered methylation of p16 went together with a lower F index. The other pathological findings and the methylation status showed no association with the F index. Conclusions: AFI reflects the nuclear enlargement of tumor cells, the cell proliferation ability, and the altered status of cell proliferation-related genes, indicating that AFI is a useful and practical method for predicting the dysplastic grade of tumor cells and cell proliferation.

Background Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. Methods In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. Result Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P  = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. Conclusion We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.