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Background: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. Methods: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. Discussion: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. Trial registration: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) has made considerable progress in image recognition, especially in the analysis of endoscopic images. The availability of large‐scale annotated datasets has contributed to the recent progress in this field. Datasets of high‐quality annotated endoscopic images are widely available, particularly in Japan. A system for collecting annotated data reported daily could aid in accumulating a significant number of high‐quality annotated datasets. Aim: We assessed the validity of using daily annotated endoscopic images in a constructed reporting system for a prototype AI model for polyp detection. Methods: We constructed an automated collection system for daily annotated datasets from an endoscopy reporting system. The key images were selected and annotated for each case only during daily practice, not to be performed retrospectively. We automatically extracted annotated endoscopic images of diminutive colon polyps that had been diagnosed (study period March–September 2018) using the keywords of diagnostic information, and additionally collect the normal colon images. The collected dataset was devised into training and validation to build and evaluate the AI system. The detection model was developed using a deep learning algorithm, RetinaNet. Results: The automated system collected endoscopic images (47,391) from colonoscopies (745), and extracted key colon polyp images (1356) with localized annotations. The sensitivity, specificity, and accuracy of our AI model were 97.0%, 97.7%, and 97.3% (n = 300), respectively. Conclusion: The automated system enabled the development of a high‐performance colon polyp detector using images in endoscopy reporting system without the efforts of retrospective annotation works. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation. Methods: A multicenter, large‐scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015. Results: ESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra‐ and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%). Conclusions: This trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first‐line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136). [ABSTRACT FROM AUTHOR]

Depth diagnosis is extremely crucial in making a treatment choice between endoscopic resection and surgery in the early stages of cancers. Among several imaging modalities, we use magnifying endoscopy to diagnose lesions by close observation of the findings at mucosal surface layer. In combination with topical staining, magnifying endoscopy enables us to assess the definite pit structure, which referred to as magnifying chromoendoscopy (MCE). The pit pattern classification by MCE was proposed and is now widely accepted as the standard diagnostic criteria for colorectal lesions. Meanwhile, image enhanced endoscopy (IEE) represented by narrow‐band imaging was developed to improve the visibility of surface and vascular findings without dyeing. Recent collaborative work performed by endoscopic experts in Japan yielded the unified diagnostic criteria, the Japan NBI Expert Team (JNET) classification, based on the findings of IEE with magnification. In this review, focusing on MCE and IEE with magnification, we aimed to give an outline of the pit pattern classification and the JNET classification, and further discuss their accuracy rate of depth diagnosis of early colorectal lesions by performing a review of the related literature. Both modalities have a high accuracy rate of nearly 90% for depth diagnosis. IEE with magnification is an ideal modality because it helps observe lesions without dye spraying; however, lesions with JNET type 2B have an inadequate diagnostic ability, which should be complemented by MCE. We conclude that accurate diagnosis is possible by examining lesions using both modalities properly to overcome the limitations of each modality. [ABSTRACT FROM AUTHOR]

Background: The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions.Methods: Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor’s depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor’s features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE, and pCLE (off-line review).Results: A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27-1.0).Conclusions: pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions. [ABSTRACT FROM AUTHOR]

Background and Study Aim: A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt.Patients and Methods: Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes.Results: A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt.Conclusion: The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt. [ABSTRACT FROM AUTHOR]

Background: Conventional endoscopic resection (CER) for early colorectal neoplasia (CRN) is widely accepted as a minimally invasive treatment. Endoscopic submucosal dissection (ESD) was developed in Japan to resect larger lesions, but ESD was not covered by the Japanese national health insurance until April 2012. In addition, treatment strategies vary considerably among medical facilities. To evaluate the current situation in Japan regarding endoscopic treatment of CRNs measuring ≥20 mm, we conducted a prospective multicenter study at 18 medium-volume and high-volume specialized facilities in cooperation with the Japan Society for Cancer of the Colon and Rectum (JSCCR). Methods: The JSCCR conducted a multicenter, observational study of all patients treated by CER and ESD of CRNs measuring ≥20 mm. Results: From October 2007 to December 2010, CERs and ESDs were performed on 1,845 CRNs (CERs 1,029; ESDs 816). Lesions diagnosed as protruded, flat, and depressed totaled 541, 1224, and 48, respectively. En bloc resection rates and mean procedure times for CER/ESD were 56.9 %/94.5 % ( P < 0.01) and 18 ± 23 min/96 ± 69 min, respectively. The average ESD procedure time was 129 ± 83 min in the ≥40-mm group. As lesion size increased, the CER en bloc resection rate decreased significantly (trend P < 0.01), but the ESD en bloc resection rate remained over 93 %. Perforation and delayed bleeding rates of CER/ESD were 0.8 %/1.6 % ( P < 0.05) and 2 %/2.2 % ( P = 0.3), respectively. Conclusions: The en bloc resection rate for ESD was significantly higher than for CER, although complication rates were fairly low. Despite a longer procedure time, safety of colorectal ESD has improved in various facilities in Japan. However, ESD for lesions measuring ≥40 mm must be performed by experienced endoscopists due to the longer procedure time. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most prevalent cause of cancer-related mortality in Japan, and the incidence of submucosal colorectal cancer is increasing. To reduce colorectal cancer mortality, however, early detection of colorectal cancer is required and adequate diagnosis of depth is needed. Current endoscopes provide high-resolution imaging that result in clear, vivid features of the detected lesions. In particular, when combined with image enhancement, high-magnification endoscopy can provide a detailed analysis of the morphologic architecture of the pit pattern and the capillary pattern in a simple and quick manner. Characteristic colonoscopic findings obtained by a combination of conventional colonoscopy, magnifying chromoendoscopy, and narrow-band imaging are useful for determining the depth of invasion of early-stage colorectal cancers, an essential factor in selecting a treatment modality. [ABSTRACT FROM AUTHOR]

Bleeding, perforation, and residual/local recurrence are the main complications associated with colonoscopic treatment of colorectal tumor. However, current status regarding the average incidence of these complications in Japan is not available. We conducted a questionnaire survey, prepared by the Colorectal Endoscopic Resection Standardization Implementation Working Group, Japanese Society for Cancer of the Colon and Rectum (JSCCR), to clarify the incidence of postoperative bleeding, perforation, and residual/local recurrence associated with colonoscopic treatment. The total incidence of postoperative bleeding was 1.2% and the incidence was 0.26% with hot biopsy, 1.3% with polypectomy, 1.4% with endoscopic mucosal resection (EMR), and 1.7% with endoscopic submucosal dissection (ESD). The total incidence of perforation was 0.74% (0.01% with the hot biopsy, 0.17% with polypectomy, 0.91% with EMR, and 3.3% with ESD). The total incidence of residual/local recurrence was 0.73% (0.007% with hot biopsy, 0.34% with polypectomy, 1.4% with EMR, and 2.3% with ESD). Colonoscopic examination was used as a surveillance method for detecting residual/local recurrence in all hospitals. The surveillance period differed among the hospitals; however, most of the hospitals reported a surveillance period of 3-6 months with mainly transabdominal ultrasonography and computed tomography in combination with the colonoscopic examination. [ABSTRACT FROM AUTHOR]

Background: Capillary patterns (CP) observed by magnifying Narrow Band Imaging (NBI) are useful for differentiating non-adenomatous from adenomatous colorectal polyps. However, there are few studies concerning the effectiveness of magnifying NBI for determining the depth of invasion in early colorectal neoplasms. We aimed to determine whether CP type IIIA/IIIB identified by magnifying NBI is effective for estimating the depth of invasion in early colorectal neoplasms. Methods: A series of 127 consecutive patients with 130 colorectal lesions were evaluated from October 2005 to October 2007 at the National Cancer Center Hospital East, Chiba, Japan. Lesions were classified as CP type IIIA or type IIIB according to the NBI CP classification. Lesions were histopathologically evaluated. Inter and intraobserver variabilities were assessed by three colonoscopists experienced in NBI. Results: There were 15 adenomas, 66 intramucosal cancers (pM) and 49 submucosal cancers (pSM): 16 pSM superficial (pSM1) and 33 pSM deep cancers (pSM2-3). Among lesions diagnosed as CP IIIA 86 out of 91 (94.5%) were adenomas, pM-ca, or pSM1; among lesions diagnosed as CP IIIB 28 out of 39 (72%) were pSM2-3. Sensitivity, specificity and diagnostic accuracy of the CP type III for differentiating pM-ca or pSM1 (<1000 μm) from pSM2-3 (≥1000 μm) were 84.8%, 88.7 % and 87.7%, respectively. Interobserver variability: ? = 0.68, 0.67, 0.72. Intraobserver agreement: ? = 0.79, 0.76, 0.75 Conclusion: Identification of CP type IIIA/IIIB by magnifying NBI is useful for estimating the depth of invasion of early colorectal neoplasms. [ABSTRACT FROM AUTHOR]

Objectives: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics., Methods: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed., Results: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%)., Conclusions: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs., (© 2024 Japan Gastroenterological Endoscopy Society.)

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objectives: Narrow-band imaging (NBI) contributes to real-time optical diagnosis and classification of colorectal lesions. The Japan NBI Expert Team (JNET) was introduced in 2011. The aim of this study was to explore the diagnostic accuracy of JNET when applied by European and Japanese endoscopists not familiar with this classification., Methods: This study was conducted by 36 European Society of Gastrointestinal Endoscopy (ESGE) and 49 Japan Gastroenterological Endoscopy Society (JGES) non-JNET endoscopists using still images of 150 lesions. For each lesion, nonmagnified white-light, nonmagnified NBI, and magnified NBI images were presented. In the magnified NBI, the evaluation area was designated by region of interest (ROI). The endoscopists scored histological prediction for each lesion., Results: In ESGE members, the sensitivity, specificity, and accuracy were respectively 73.3%, 94.7%, and 93.0% for JNET Type 1; 53.0%, 64.9%, and 62.1% for Type 2A; 43.9%, 67.7%, and 55.1% for Type 2B; and 38.1%, 93.7%, and 85.1% for Type 3. When Type 2B and 3 were considered as one category of cancer, the sensitivity, specificity, and accuracy for differentiating high-grade dysplasia and cancer from the others were 59.9%, 72.5%, and 63.8%, respectively. These trends were the same for JGES endoscopists., Conclusion: The diagnostic accuracy of the JNET classification was similar between ESGE and JGES and considered to be sufficient for JNET Type 1. On the other hand, the accuracy for Types 2 and 3 is not sufficient; however, JNET 2B lesions should be resected en bloc due to the risk of cancers and JNET 3 can be treated by surgery due to its high specificity., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan., Methods: We 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., Results: The 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., Conclusions: Of 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., (© 2024. The Author(s).)

Background & Aims: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation., Methods: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN)., Results: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs., Conclusions: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: Limited 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., Methods: This 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., Results: Data 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., Conclusion: Patients 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.

Background & Aims: To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period., Methods: Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes., Results: The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan-Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47-45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76-37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection., Conclusions: A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms., Clinical Trial Registration Number: UMIN000010136., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Escherichia coli containing polyketide synthase in the gut microbiota (pks + E coli) produce a polyketide-peptide genotoxin, colibactin, and are suspected to play a role in the development of colorectal neoplasia. To clarify the role of pks + E coli in the early stage of tumorigenesis, we investigated whether the pks status of E coli was associated with the prevalence of colorectal neoplasia. This cross-sectional analysis of data from a prospective cohort in Izu Oshima, Japan included asymptomatic residents aged 40-79 years who underwent screening colonoscopy and provided a stool sample. We identified 543 participants with colorectal neoplasia (22 colorectal cancer and 521 adenoma) as cases and 425 participants with normal colon as controls. The pks status of E coli was assayed using stool DNA and specific primers that detected pks + E coli. The proportion of pks + E coli was 32.6% among cases and 30.8% among controls. Compared with those with pks - E coli, the odds ratio (OR) (95% confidence interval) for participants with pks + E coli was 1.04 (0.77-1.41) after adjusting for potential confounders. No statistically significant associations were observed regardless of tumor site or number of colorectal adenoma lesions. However, stratified analyses revealed increased ORs among participants who consumed cereals over the median intake or vegetables under the median intake. Overall, we found no statistically significant association between pks + E coli and the prevalence of colorectal adenoma lesions among this Japanese cohort. However, positive associations were suggested under certain intake levels of cereals or vegetables., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP., Methods: This was a randomised, double-blind, placebo-controlled, multicentre trial with a two-by-two factorial design done in 11 centres in Japan. Eligible patients were aged 16-70 years and had a history of more than 100 adenomatous polyps in the large intestine, without a history of colectomy. Before the study, patients underwent endoscopic removal of all colorectal polyps of at least 5·0 mm in diameter. Randomisation was done with a minimisation method with a random component to balance the groups with respect to the adjustment factors of sex, age (<30 years vs ≥30 years), or smoking status at the time of entry. Patients and researchers were masked to the treatment group. There were four groups: aspirin (100 mg per day) plus mesalazine (2 g per day), aspirin (100 mg per day) plus mesalazine placebo, aspirin placebo plus mesalazine (2 g per day), or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before 8 month colonoscopy. The primary endpoint was the incidence of colorectal polyps of at least 5·0 mm at 8 months and was assessed in the intention-to-treat population. Safety was assessed in the ITT population. We also did a per-protocol analysis including only patients who took at least 70% of the allocated study drug. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000018736, and is complete., Findings: Between Sept 25, 2015, and March 13, 2017, 104 patients were randomly assigned to receive either aspirin or aspirin placebo (n=52) or mesalazine or mesalazine placebo (n=52). Two patients withdrew from the aspirin plus mesalazine placebo group. 26 (50%) of 52 patients who received no aspirin had colorectal polyps of at least 5·0 mm at 8 months, as did 15 (30%) of the 50 patients who received any aspirin, 21 (42%) of the 50 patients who received no mesalazine, and 20 (38%) of the 52 patients who received any mesalazine. The adjusted odds ratio for polyp recurrence was 0·37 (95% CI 0·16-0·86) in the patients who received any aspirin and 0·87 (95% CI 0·38-2·00) in any who received mesalazine. The most common adverse events were grade 1-2 upper gastrointestinal symptoms in three (12%) of 26 patients who received aspirin plus mesalazine, one (4%) of 24 patients who received aspirin plus mesalazine placebo, and one (4%) of 26 patients who received mesalazine plus aspirin placebo. There was one grade 4 event in the mesalazine plus aspirin placebo group, but not related to the treatment., Interpretation: Low-dose aspirin safely suppressed the recurrence of colorectal polyps larger than 5·0 mm in patients with FAP. These results suggest an effect of low-dose aspirin for FAP and could be an alternative method for preventing colorectal cancer in FAP., Funding: Japan Agency for Medical Research and Development., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Noninvasive colorectal cancer (CRC) screening methods with higher sensitivity for advanced colorectal neoplasia (ACN) than the fecal immunochemical test (FIT) alone are warranted. This study aimed to elucidate the diagnostic performance of a risk stratification score calculated using baseline individual characteristics and its combination with FIT for detecting ACN., Methods: This cross-sectional analysis of data from a prospective cohort in Izu Oshima, Japan, included asymptomatic individuals age 40-79 years who underwent both 2-day quantitative FIT and screening colonoscopy. The 8-point risk score, calculated based on age, sex, CRC family history, body mass index, and smoking history, was assessed. Colonoscopy results were used as reference., Results: Overall, 1,191 individuals were included, and 112 had ACN. The sensitivity and specificity of the 1-/2-day FIT (cutoff: 50-200 ng Hb/mL) for ACN were 17.9%-33.9% (4.9%-22.0% for right-sided ACN) and 91.8%-97.6%, respectively. The risk score's c-statistic for ACN was 0.66, and combining the score (cutoff: 5 points) with 1-/2-day FIT (cutoff: 50-200 ng Hb/mL) yielded a sensitivity and specificity for ACN of 46.4%-56.3% (43.9%-48.8% for right-sided ACN) and 76.6%-80.8%, respectively. The specificity of the risk score and FIT combination for all adenomatous lesions was 82.4%-86.4%., Discussion: The 8-point risk score remarkably increased the sensitivity for ACN, particularly for right-sided ACN. Although the specificity decreased, it was still maintained at a relatively high level. The risk score and FIT combination has the potential to become a viable noninvasive CRC screening option.

Background and Aims: Artificial intelligence (AI) is being implemented in colonoscopy practice, but no study has investigated whether AI is cost saving. We aimed to quantify the cost reduction using AI as an aid in the optical diagnosis of colorectal polyps., Methods: This study is an add-on analysis of a clinical trial that investigated the performance of AI for differentiating colorectal polyps (ie, neoplastic versus non-neoplastic). We included all patients with diminutive (≤5 mm) rectosigmoid polyps in the analyses. The average colonoscopy cost was compared for 2 scenarios: (1) a diagnose-and-leave strategy supported by the AI prediction (ie, diminutive rectosigmoid polyps were not removed when predicted as non-neoplastic), and (2) a resect-all-polyps strategy. Gross annual costs for colonoscopies were also calculated based on the number and reimbursement of colonoscopies conducted under public health insurances in 4 countries., Results: Overall, 207 patients with 250 diminutive rectosigmoid polyps (104 neoplastic, 144 non-neoplastic, and 2 indeterminate) were included. AI correctly differentiated neoplastic polyps with 93.3% sensitivity, 95.2% specificity, and 95.2% negative predictive value. Thus, 105 polyps were removed and 145 were left under the diagnose-and-leave strategy, which was estimated to reduce the average colonoscopy cost and the gross annual reimbursement for colonoscopies by 18.9% and US$149.2 million in Japan, 6.9% and US$12.3 million in England, 7.6% and US$1.1 million in Norway, and 10.9% and US$85.2 million in the United States, respectively, compared with the resect-all-polyps strategy., Conclusions: The use of AI to enable the diagnose-and-leave strategy results in substantial cost reductions for colonoscopy., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Intestinal resection with lymph node dissection is the current standard treatment for high-risk lower rectal submucosal invasive cancer after local resection; however, surgery affects patients' quality of life due to stoma placement or impaired anal sphincter function. A recent study demonstrated that adjuvant chemoradiation yields promising results., Methods and Analysis: This study aims to confirm the non-inferiority of adjuvant chemoradiation, consisting of capecitabine and concurrent radiotherapy (45 Gy in 25 fractions), measured by 5-year relapse-free survival (RFS), over standard surgery in patients with high-risk lower rectal submucosal invasive cancer after local resection. The primary endpoint is 5 year RFS. The secondary endpoints are 10 years RFS, 5-year and 10-year overall survival, 5-year and 10-year local RFS, 5-year and 10-year proportion of anus-preservation without stoma, Wexner score, low anterior resection syndrome score, adverse events and serious adverse events. During the 5-year trial period, 210 patients will be accrued from 65 Japanese institutions., Ethics and Dissemination: The National Cancer Center Hospital East Certified Review Board approved this study protocol in October 2018. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Clinical Trials Act. Written informed consent will be obtained from all eligible patients prior to registration. The primary results of this study will be published in an English article. In addition, the main results will be published on the websites of Japan Clinical Oncology Group (www.jcog.jp) and jRCT (https://jrct.niph.go.jp/). As to data curation, it has not been prepared yet., Trial Registration Number: jRCT1031180076., Competing Interests: Competing interests: KS reports grants from reports research funding from Chugai., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Proton beam therapy (PBT) with concurrent chemotherapy is promising for esophageal squamous cell carcinoma (ESCC). The aim of study was to evaluate the outcome of concurrent chemo-proton therapy (CCPT), i.e., PBT with concurrent chemotherapy for cT1 ESCC and the salvage endoscopic therapy for local recurrence., Methods: Patients with clinical T1 ESCC who underwent CCPT (60 GyE) between April 2013 and April 2017 at the National Cancer Center Hospital East were investigated. The efficacy of CCPT at the primary site was evaluated via endoscopy; primary complete response (CR) was defined as disappearance of the tumor lesion/ulcer and absence of cancer cells on biopsy. Endoscopic evaluation was performed with the same protocol of conventional chemoradiotherapy. Local recurrence after CCPT was treated with endoscopic resection for cT1a and with esophagectomy or photodynamic therapy for cT1b+., Results: Of the 44 patients (median age, 70 years) that underwent CCPT, 43 patients (98%) achieved primary CR. Among the 44 patients, the 3-year overall survival rate was 95.2%. Five patients (11%) developed local recurrence without regional lymph node or distant metastasis and received endoscopic resection or photodynamic therapy. All five patients were alive with no recurrence after a median 23 months., Conclusions: The results suggest that CCPT is an effective treatment for cT1 ESCC and careful endoscopic follow-up allows preferable local control with salvage endoscopic treatment.

Background and Aim: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm., Methods: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions., Results: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors., Conclusion: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm., (© 2019 Japan Gastroenterological Endoscopy Society.)

Background and Aims: Although colonoscopy is the criterion standard for detection of colorectal adenomas, some adenomas are missed. Full-spectrum endoscopy (FUSE) allows for observation with a 330-degree angle of view, which is expected to decrease the miss rate. However, no consensus has been reached regarding the superiority of FUSE over standard forward-viewing colonoscopy (SFVC) for detection of adenomas; we therefore compared new-generation FUSE and SFVC regarding colorectal adenoma miss rate (AMR) in this, the first reported randomized control trial using new-generation FUSE., Methods: We enrolled individuals aged 40 to 75 years who had been referred for screening, surveillance, fecal occult blood test positivity, or symptoms in a prospective randomized trial of tandem colonoscopy in 8 institutions. Patients were randomly assigned (1:1) via computer-generated stratified randomization. Neither the endoscopists nor patients were blinded to the allocation. The primary endpoint was AMR per patient (AMR-PP)., Results: We enrolled 345 patients and included 319 in the per-protocol analyses. AMR-PP was significantly lower with FUSE (11.7%; 95% confidence interval [CI], 8.0%-15.4%) than with SFVC (22.9%; 95% CI, 17.5%-28.3%; P < .001). AMR-PP for lesions ≤5 mm in size was significantly lower with FUSE (10.4%; 95% CI, 6.5%-14.3%) than with SFVC (20.0%; 95% CI, 14.4%-25.6%; P = .0057). Furthermore, AMR-PP in the ascending colon was significantly lower with FUSE (4.3%; 95% CI, 1.4%-7.2%) than with SFVC (10.6%; 95% CI, 6.1%-15.1%; P = .0212)., Conclusions: FUSE is superior to SFVC regarding both AMR-PP and AMR; additionally, AMR-PP is both significantly lower with FUSE than SFVC for lesions ≤5 mm in size and in the ascending colon. (Clinical trial registration number: UMIN000020448.)., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aim: The Japan narrow-band imaging (NBI) Expert Team (JNET) was organized to unify four previous magnifying NBI classifications (the Sano, Hiroshima, Showa, and Jikei classifications). The JNET working group created criteria (referred to as the NBI scale) for evaluation of vessel pattern (VP) and surface pattern (SP). We conducted a multicenter validation study of the NBI scale to develop the JNET classification of colorectal lesions., Methods: Twenty-five expert JNET colonoscopists read 100 still NBI images with and without magnification on the web to evaluate the NBI findings and necessity of the each criterion for the final diagnosis., Results: Surface pattern in magnifying NBI images was necessary for diagnosis of polyps in more than 60% of cases, whereas VP was required in around 90%. Univariate/multivariate analysis of candidate findings in the NBI scale identified three for type 2B (variable caliber of vessels, irregular distribution of vessels, and irregular or obscure surface pattern), and three for type 3 (loose vessel area, interruption of thick vessel, and amorphous areas of surface pattern). Evaluation of the diagnostic performance for these three findings in combination showed that the sensitivity for types 2B and 3 was highest (44.9% and 54.7%, respectively), and that the specificity for type 3 was acceptable (97.4%) when any one of the three findings was evident. We found that the macroscopic type (polypoid or non-polypoid) had a minor influence on the key diagnostic performance for types 2B and 3., Conclusion: Based on the present data, we reached a consensus for developing the JNET classification., (© 2018 Japan Gastroenterological Endoscopy Society.)

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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.

During colonoscopy, small and diminutive colorectal polyps are commonly encountered. It is estimated that at least one adenomatous polyp is detected in almost half of all patients undergoing screening colonoscopy. In contrast, the 'predict, resect, and discard' strategy for diminutive and small colorectal polyps is a current topic especially in Western countries. 'Is this an acceptable policy in Japan?' Herein, we report the results of a questionnaire survey with regard to the management of diminutive colorectal polyps, including the thoughts of Japanese endoscopists regarding the 'predict, resect, and discard' strategy. At the moment, we propose that this strategy should be used by skilled endoscopists only., (© 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.)

Background & Aims: Little is known about the long-term outcomes of patients with submucosal invasive colorectal cancer who undergo endoscopic or surgical resection. We performed a retrospective analysis of long-term outcomes of patients treated for submucosal colon and rectal cancer., Methods: We collected data on 549 patients with submucosal colon cancer and 209 patients with submucosal rectal cancer who underwent endoscopic or surgical resection at 6 institutions over a median follow-up period of 60.5 months. Patients were classified into one of 3 groups: low-risk patients undergoing only endoscopic resection (group A), high-risk patients undergoing only endoscopic resection (group B), and high-risk patients undergoing surgical resection that included lymph node dissection (group C). We assessed recurrence rates, 5-year disease-free survival, and 5-year overall survival. Cox regression analysis was used to compare recurrences., Results: The rates of recurrence, disease-free survival, and overall survival in group A for submucosal colon and rectal cancer were 0% versus 6.3% (P < .05), 96% versus 90%, and 96% versus 89%, respectively. For group B, these values were 1.4% versus 16.2% (P < .01), 96% versus 77% (P < .01), and 98% versus 96%, respectively; local recurrence was observed in 5 patients (one with submucosal colon cancer and 4 with submucosal rectal cancer). Tumor location was the only factor that contributed significantly to disease recurrence and death (hazard ratio, 6.73; P = .045). For group C, these values were 1.9% versus 4.5%, 97% versus 95%, and 99% versus 97%, respectively., Conclusions: The risk for local recurrence was significantly higher in high-risk patients with submucosal rectal cancer than in patients with submucosal colon cancer when treated with only endoscopic resection. The addition of surgery is therefore recommended for patients with submucosal rectal cancer with pathologic features indicating a high risk of tumor progression; University Hospital Medical Network Clinical Trials Registry, Number: UMIN 000008635., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Concurrent chemoradiotherapy with 5-fluorouracil plus mitomycin C has been established as a standard therapy for non-metastatic anal squamous cell carcinoma in the West. However, there have been few reports of chemoradiotherapy for anal squamous cell carcinoma in Japan. We retrospectively investigated seven consecutive anal squamous cell carcinoma patients who were treated with concurrent chemoradiotherapy consisting of 5-fluorouracil plus mitomycin C with a total irradiation of 59.4 Gy. The patients consisted of two males and five females. Clinical stages II/IIIA/IIIB accounted for four, one and two patients, respectively. Full-dose irradiation was completed in all patients. Median relative dose intensities of 5-fluorouracil and mitomycin C were both 99%. All patients achieved complete response. At a median follow-up of 37.5 months, one patient experienced local recurrence. The most common grade 3/4 acute toxicities were dermatitis in 100% and anal pain in 71%. There was no treatment-related death. Concurrent chemoradiotherapy appears to be tolerable and effective in Japanese patients with anal squamous cell carcinoma.

We carried out a retrospective questionnaire survey of 792 submucosal colorectal carcinoma (CRC) cases from 15 institutions affiliated with the Colorectal Endoscopic Resection Standardization Implementation Working Group in Japanese Society for Cancer of the Colon and Rectum. In these cases, endoscopic resection (ER) and surveillance was carried out without additional surgical resection. Local recurrence or metastasis was observed in 18 cases. Local submucosal recurrence was observed in 11 cases, and metastatic recurrence was observed in 13 cases. Among the 15 cases in which the depth of submucosal invasion was measured, two cases showed depth less than 1000 µm, which has other risk factors for metastasis. Metastatic recurrence was observed in the lung, liver, lymph node, bone, adrenal glands, and the brain; in some cases, metastatic recurrence was observed in multiple organs. Death due to primary disease was observed in six cases. The average interval between ER and recurrence was 19.7 ± 9.2 months. In 16 cases, recurrence was observed within 3 years after ER. Thus, validity of ER without additional surgical resection for cases with the conditions that the depth of submucosal invasion is less than 1000 µm and the histological grade is well or moderately differentiated adenocarcinoma with no lymphatic and venous involvement was proven., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)