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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: Magnifying endoscopy with narrow-band imaging (NBI) is effective for the diagnosis of early gastric cancer (EGC). However, magnifying endoscopy is not yet popular globally because of the required level of skill and lack of availability. To overcome these problems, dual-focus endoscopy (standard- and near-focus (NF) modes) has been developed. In this study, we evaluated the diagnostic performance of NF with second-generation (2G)-NBI (NF-NBI) for the diagnosis of EGC. Methods: This was a secondary analysis of a multicenter randomized controlled trial of 4523 high-risk patients who underwent gastroscopies at 13 institutions in Japan. Patients were randomly assigned to white-light imaging (WLI) followed by 2G-NBI or to 2G-NBI followed by WLI. Lesions suspicious for EGC, newly detected by non-magnifying WLI or 2G-NBI, were subsequently observed with NF-NBI. All detected lesions were biopsied or resected. The diagnostic performance of NF-NBI was compared with the final histology. Results: A total of 870 detected lesions (145 EGC, 725 non-EGC) were analyzed. Overall diagnostic performance for EGC using NF-NBI was accuracy 87.7%, sensitivity 60.7%, specificity 93.1%, positive predictive value 63.8%, and negative predictive value 92.2%. There were no significant differences in diagnostic performance between lesions detected by WLI or 2G-NBI. For lesions diagnosed with high (333 lesions) and low (537 lesions) confidences, accuracy was 92.2% and 84.9%, sensitivity was 64.7% and 58.5%, and specificity was 90.5% and 88.8%, respectively. Conclusion: The diagnostic performance of NF-NBI is good and acceptable for diagnosis of EGC in combination with either WLI or 2G-NBI. [ABSTRACT FROM AUTHOR]

Background: A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. Methods: A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. Results: Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. Conclusion: Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication. [ABSTRACT FROM AUTHOR]

Background and Aims: Although there are guidelines for the management of antithrombotic agents during the periendoscopic period, gaps between various guidelines create a confusing situation in daily clinical practice. The purpose of this study was to examine the current management of antithrombotic agents during the periendoscopic period in Japan. Methods: This is a prospective cohort study in 12 high-volume endoscopy centers in Japan. A total of 970 outpatients receiving antithrombotic agents underwent endoscopies (705 esophagogastroduodenoscopies and 265 colonoscopies) with or without invasive procedures. Main outcome measures are adverse events in these patients. Results: Need for cessation of antithrombotics before endoscopy was mostly determined by non-gastroenterologists (51%) who are unfamiliar with the Japan Gastroenterological Endoscopy Society (JGES) guideline, although cessation periods after endoscopy for most patients were determined by endoscopists (78%). Consequently, most patients underwent endoscopy without cessation (25%) or after a cessation period of 6-7 days (33%), indicating low permeation of the JGES guideline in Japan. Among 970 patients, two patients experienced major complications that may be related to thromboembolic events or gastrointestinal bleeding (95% confidence interval [CI]: 0-0.7%). One of these patients died due to sudden onset ventricular tachycardia. Invasive procedures, including 40 biopsies and two mucosal resections, were performed in 42 patients without cessation of antithrombotics, and no patients experienced major complications (95% CI: 0-8.4%). Conclusions: This study revealed a conflicting clinical environment due to absence of a unified guideline in Japan. Further accumulation of data is mandatory to establish a unified guideline based upon solid evidence. [ABSTRACT FROM AUTHOR]

Importance: Single endoscopic examination often misses early gastric cancer (GC), even when both high-definition white light imaging and narrow-band imaging are used. It is unknown whether new GC can be detected approximately 1 year after intensive index endoscopic examination., Objective: To examine whether new GC can be detected approximately 1 year after intensive index endoscopic examination using both white light and narrow-band imaging., Design, Setting, and Participants: This case-control study was a preplanned secondary analysis of a randomized clinical trial involving 4523 patients with a high risk of GC who were enrolled between October 1, 2014, and September 22, 2017. Data were analyzed from December 26, 2019, to April 21, 2021. Participants in the clinical trial received index endoscopy to detect early GC via 2 examinations of the entire stomach using white light and narrow-band imaging. The duration of follow-up was 15 months. The secondary analysis included 107 patients with newly detected GC (case group) and 107 matched patients without newly detected GC (control group) within 15 months after index endoscopy., Interventions: Surveillance endoscopy was scheduled between 9 and 15 months after index endoscopy. If new lesions suspected of being early GC were detected during surveillance endoscopy, biopsies were obtained to confirm the presence of cancer., Main Outcomes and Measures: The primary end point was the rate of new GC detected within 15 months after index endoscopy. The main secondary end point was identification of risk factors associated with new GC detected within 15 months after index endoscopy., Results: Among 4523 patients (mean [SD] age, 70.6 [7.5] years; 3527 men [78.0%]; all of Japanese ethnicity) enrolled in the clinical trial, 4472 received index endoscopy; the rate of early GC detected on index endoscopy was 3.0% (133 patients). Surveillance endoscopy was performed in 4146 of 4472 patients (92.7%) who received an index endoscopy; the rate of new GC detected within 15 months after index endoscopy was 2.6% (107 patients). Among 133 patients for whom early GC was detected during index endoscopy, 110 patients (82.7%) received surveillance endoscopy within 15 months after index endoscopy; the rate of newly detected GC was 10.9% (12 patients). For the secondary analysis of risk factors associated with newly detected GC, characteristics were well balanced between the 107 patients included in the case group vs the 107 patients included in the matched control group (mean [SD] age, 71.7 [7.2] years vs 71.8 [7.0] years; 94 men [87.9%] in each group; 82 patients [76.6%] vs 87 patients [81.3%] with a history of gastric neoplasm). Multivariate analysis revealed that the presence of open-type atrophic gastritis (odds ratio, 6.00; 95% CI, 2.25-16.01; P < .001) and early GC detection by index endoscopy (odds ratio, 4.67; 95% CI, 1.08-20.21; P = .04) were independent risk factors associated with new GC detection., Conclusions and Relevance: In this study, the rate of new GC detected by surveillance endoscopy approximately 1 year after index endoscopy was similar to that of early GC detected by index endoscopy. These findings suggest that 1-year surveillance is warranted for patients at high risk of GC.

Objective: Early detection of gastric cancer has been the topic of major efforts in high prevalence areas. Whether advanced imaging methods, such as second-generation narrow band imaging (2G-NBI) can improve early detection, is unknown., Design: This open-label, randomised, controlled tandem trial was conducted in 13 hospitals. Patients at increased risk for gastric cancer were randomly assigned to primary white light imaging (WLI) followed by secondary 2G-NBI (WLI group: n=2258) and primary 2G-NBI followed by secondary WLI (2G-NBI group: n=2265) performed by the same examiner. Suspected early gastric cancer (EGC) lesions in both groups were biopsied. Primary endpoint was the rate of EGC patients in the primary examination. The main secondary endpoint was the positive predictive value (PPV) for EGC in suspicious lesions detected (primary examination)., Results: EGCs were found in 44 (1.9%) and 53 (2.3%; p=0.412) patients in the WLI and 2G-NBI groups, respectively, during primary EGD. In a post hoc analysis, the overall rate of lesions detected at the second examination was 25% (n=36/145), with no significant differences between groups. PPV for EGC in suspicious lesions was 13.5% and 20.9% in the WLI (50/371 target lesions) and 2G-NBI groups (59/282 target lesions), respectively (p=0.015)., Conclusion: The overall sensitivity of primary endoscopy for the detection of EGC in high-risk patients was only 75% and should be improved. 2G-NBI did not increase EGC detection rate over conventional WLI. The impact of a slightly better PPV of 2G-NBI has to be evaluated further., Trial Registration Number: UMIN000014503., Competing Interests: Competing interests: MM received grants from Olympus during the study period. TY received personal fees and non-financial support from Olympus, outside this study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We previously conducted transcriptome analysis of a paired specimen of normal and esophageal squamous cell carcinoma (ESCC) tissues and found that mRNA expression of cystatin A (CSTA), a member of the cystatin superfamily, was perturbed in tumors compared with that in the background mucosa. However, little is known about the significance of CSTA expression in ESCC.The mRNA expression of CSTA was evaluated by qRT-PCR using 28 paired frozen samples of tumor and nontumor mucosae. The protein expression of CSTA was evaluated by the immunostaining of formalin-fixed, paraffin-embedded sections of ESCC samples from 59 patients who underwent surgery, and its relationship with clinical features was analyzed.The mRNA expression of CSTA was significantly decreased in ESCC compared with that in matched normal mucosa (P < .0001). The protein expression of CSTA was limited in stratum granulosum and stratum spinosum but not in stratum basal in normal esophageal mucosa. It was reduced in all ESCC tissue samples compared with normal tissues; however, CSTA expression levels in tumors showed considerable variation. Of the 59 samples, 20 did not express CSTA, whereas 39 clearly expressed it. The expression of CSTA in tumors was significantly associated with pT classification (deeper tumor invasions) (P = .0118) and advanced TNM stages (P = .0497). In CSTA-positive tumor samples, CSTA-expressing cancer cells often expressed Ki67, a proliferation marker, which was in sharp contrast to normal mucosa, where Ki67-expressing cells were limited to the basal layer and did not express CSTA. Furthermore, CSTA expression was observed in all 22 lymph node metastases analyzed.Relatively high levels of CSTA expression in tumors were correlated with tumor progression and advanced cancer stage, including lymph node metastasis.

Background & Aims: We aimed to develop and validate a risk scoring system to determine the risk of severe lower gastrointestinal bleeding (LGIB) and predict patient outcomes., Methods: We first performed a retrospective analysis of data from 439 patients emergently hospitalized for acute LGIB at the National Center for Global Health and Medicine in Japan, from January 2009 through December 2013. We used data on comorbidities, medication, presenting symptoms, and vital signs, and laboratory test results to develop a scoring system for severe LGIB (defined as continuous and/or recurrent bleeding). We validated the risk score in a prospective study of 161 patients with acute LGIB admitted to the same center from April 2014 through April 2015. We assessed the system's accuracy in predicting patient outcome using area under the receiver operating characteristics curve (AUC) analysis. All patients underwent colonoscopy., Results: In the first study, 29% of the patients developed severe LGIB. We devised a risk scoring system based on nonsteroidal anti-inflammatory drugs use, no diarrhea, no abdominal tenderness, blood pressure of 100 mm Hg or lower, antiplatelet drugs use, albumin level less than 3.0 g/dL, disease scores of 2 or higher, and syncope (NOBLADS), which all were independent correlates of severe LGIB. Severe LGIB developed in 75.7% of patients with scores of 5 or higher compared with 2% of patients without any of the factors correlated with severe LGIB (P < .001). The NOBLADS score determined the severity of LGIB with an AUC value of 0.77. In the validation (second) study, severe LGIB developed in 35% of patients; the NOBLADS score predicted the severity of LGIB with an AUC value of 0.76. Higher NOBLADS scores were associated with a requirement for blood transfusion, longer hospital stay, and intervention (P < .05 for trend)., Conclusions: We developed and validated a scoring system for risk of severe LGIB based on 8 factors (NOBLADS score). The system also determined the risk for blood transfusion, longer hospital stay, and intervention. It might be used in decision making regarding intervention and management., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The long-term recurrence of lower gastrointestinal bleeding (LGIB) and associated mortality have not been studied extensively. We investigated rates of recurrence of LGIB, mortality, and associated risk factors., Methods: In a retrospective study, we analyzed data from 342 patients hospitalized for overt LGIB at the National Center for Global Health and Medicine in Japan from December 2004 through June 2013. All patients underwent colonoscopy. We assessed Charlson comorbidity index scores and the use of nonsteroidal anti-inflammatory drugs, low-dose aspirin, other antiplatelet drugs, or warfarin. Rebleeding, the total number of rebleeding episodes, and mortality were measured. The Cox proportional hazards model was used to estimate hazard ratios (HRs)., Results: Rebleeding occurred in 84 patients, at a mean follow-up time of 19 months. The cumulative percentages of patients with rebleeding at 1 and 5 years were 19% and 46%, respectively. During the follow-up period, 29 patients (39%) had secondary rebleeding and 18 patients (62%) had subsequent rebleeding. Multivariate analysis showed age 65 years and older (HR, 1.7; P = .04) and the use of nonsteroidal anti-inflammatory drugs (HR, 2.0; P < .01) and nonaspirin antiplatelet drugs (HR, 1.8; P < .05) as independent risk factors for rebleeding. Dual therapy had a higher risk than single therapy (adjusted HR, 1.8; P < .05). During the mean follow-up period of 28 months, 21 patients died (2 from bleeding). Cumulative mortality rates at 1 and 5 years were 4.2% and 13%, respectively. Mortality was associated significantly with age ≥65 years (P < .05), Charlson comorbidity index score, and warfarin use., Conclusions: Based on a retrospective analysis of patients with LGIB, 46% of all patients have rebleeding, and the overall mortality rate is 13% within 5 years after hospitalization. Besides age ≥65 years, use of antithrombotic drugs increases the risk of bleeding recurrence and mortality among patients with LGIB., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Stool cultures are expensive and time consuming, and the positive rate of enteric pathogens in cases of nosocomial diarrhea is low. The 3-day rule, whereby clinicians order a Clostridium difficile (CD) toxin test rather than a stool culture for inpatients developing diarrhea >3 days after admission, has been well studied in Western countries. The present study sought to validate the 3-day rule in an acute care hospital setting in Japan., Methods: Stool bacterial and CD toxin test results for adult patients hospitalized in an acute care hospital in 2008 were retrospectively analyzed. Specimens collected after an initial positive test were excluded. The positive rate and cost-effectiveness of the tests were compared among three patient groups., Patients: The adult patients were divided into three groups for comparison: outpatients, patients hospitalized for ≤3 days and patients hospitalized for ≥4 days., Results: Over the 12-month period, 1,597 stool cultures were obtained from 992 patients, and 880 CD toxin tests were performed in 529 patients. In the outpatient, inpatient ≤3 days and inpatient ≥4 days groups, the rate of positive stool cultures was 14.2%, 3.6% and 1.3% and that of positive CD toxin tests was 1.9%, 7.1% and 8.5%, respectively. The medical costs required to obtain one positive result were 9,181, 36,075 and 103,600 JPY and 43,200, 11,333 and 9,410 JPY, respectively., Conclusion: The 3-day rule was validated for the first time in a setting other than a Western country. Our results revealed that the "3-day rule" is also useful and cost-effective in Japan.

Background: Endoscopic resection is an adequate treatment for subgroups of patients with early gastric cancer. Endoscopic submucosal dissection (ESD) represents a recent advance and leads to good results when adequately indicated. There is great experience with this technique in Japan and it is gaining acceptance among Western endoscopists. We present the first gastric ESD series performed in Brazil., Methods: Patients with well-differentiated adenocarcinomas macroscopically classified as early cancer, less than 30 mm with no ulcer or scar, were included. ESD was performed with an insulated-tip knife and electrosurgical unit with endocut mode. Clinicopathological aspects and morbidity were evaluated. The study was approved by the local ethics committee and informed consent was obtained from all participant subjects., Results: From October 2005 to July 2007, 160 patients received surgical treatment for gastric cancer; 44 patients (27.5%) had early gastric cancer. In this latter group, 15 procedures (ESD) were performed in 12 patients. The mean size of the lesions was 16.8 mm. Almost half of the lesions were located in the proximal third of the stomach and the mean elapsed time for the procedure was 140 min. In 80% of the cases resection was en bloc and 80% of the resections were considered curative. We had three perforations, which were managed clinically, and no bleeding., Conclusion: When adequately indicated, ESD is a safe and feasible technique.