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Background: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. Aims: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. Methods: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. Results: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear β-catenin. The number of H2RSP-positive cells in the invasive front of well- differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. Conclusion: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers. [ABSTRACT FROM AUTHOR]

Abstract Background Open reading frame 58 (ORF58) of varicella-zoster virus (VZV) lies at the 3'end of the Unique long (UL) region and its functional is unknown. In order to clarify whether ORF58 is essential for the growth of VZV, we constructed a deletion mutant of ORF58 (pOka-BACΔ58) from the Oka parental genome cloned into a bacterial artificial chromosome (pOka-BAC). Results The ORF58-deleted virus (rpOkaΔ58) was reconstituted from the pOka-BACΔ58 genome in MRC-5 cells, indicating that the ORF58 gene is non-essential for virus growth. Comparison of the growth rate of rpOkaΔ58 and recombinant wild-type virus by assessing plaque sizes revealed no significant differences between them both in MRC-5 cells and malignant melanoma cells. Conclusion This study shows that the ORF58 gene is dispensable for viral replication and does not affect the virus' ability to form plaques in vitro.

Background: Despite accumulating evidence and recommendations for management of colonic diverticular bleeding (CDB), the changes in its clinical management and outcomes remain unknown., Methods: We performed a retrospective tendency analysis on a biennial basis, a propensity score-matched cohort study between the first and latter half groups, and mediation analyses to compare the diagnostic and treatment methods between January 2010 and December 2019 (CODE BLUE-J Study)., Results: A total of 6575 patients with CDB were included. While the use of colonoscopy as the initial diagnostic procedure declined, the use of computed tomography (CT) increased in both the trend test and before-and-after comparisons. In hemostasis therapy, the use of endoscopic clips declined and band ligation increased. Interventional radiology remained unchanged; however, the number of surgeries decreased over time. The stigmata of recent hemorrhage (SRH) detection rate and length of hospital stay (LOS) improved significantly. Mediation analyses showed that use of a distal attachment and water-jet scope contributed to an improved SRH detection rate, and use of band ligation contributed to preventing rebleeding within 30 days., Conclusions: Management strategies for CDB have changed in the past decade, particularly regarding the increased use of CT and decreased need for surgery. However, the main outcomes, except for the SRH detection rate and LOS, did not improve. The widespread use of distal attachment, water-jet scope, and band ligation could improve outcomes in CDB management., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest to declare relevant to article., (© 2024. Japanese Society of Gastroenterology.)

Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn's disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02-0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7-13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4-8.3, P < 0.001). The 0w-LRG can predict the effectiveness including serum trough levels of ustekinumab during induction treatment for patients with IBD., Competing Interests: Declarations. Competing interests: S. Shinzaki received lecture fees from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and lecture fees and grants from AbbVie GK, Sekisui Medical Co., Ltd.; A. Yonezawa: grants from Shimadzu Corporation and Ayumi Pharma Corporation.; H. Iijima: lecture fees from AbbVie GK and Mitsubishi-Tanabe Pharma Corporation; T. Takehara: grants from Mitsubishi-Tanabe Pharma Corporation, and lecture fees and grants from AbbVie GK. None of the aforementioned are related to this study. The remaining authors do not have any conflicts of interest to disclosure. Ethnics approval and consent to participate: This study was carried out in accordance with the Declaration of Helsinki, and approved by the ethics committee of Osaka University Hospital, the ethics committee of National Hospital Organization Osaka National Hospital, the ethics committee of Osaka Rosai Hospital, the ethics committee of Toyonaka Municipal Hospital, the ethics committee of Japan Community Healthcare Organization Osaka Hospital, the ethics committee of Itami City Hospital, the ethics committee of Suita Municipal Hospital, the ethics committee of Ikeda Municipal Hospital, the ethics committee of Otemae Hospital, the ethics committee of Kansai Rosai Hospital, the ethics committee of Higashiosaka City Medical Center, the ethics committee of Osaka General Medical Center, the ethics committee of Osaka Police Hospital, the ethics committee of Yao Municipal Hospital and the ethics committee of Hyogo Prefectural Nishinomiya Hospital. Written informed consent was obtained from all patients., (© 2024. The Author(s).)

Background and Aims: We sought to validate the British Society of Gastroenterology (BSG) guidelines for acute lower GI bleeding (ALGIB)., Methods: We analyzed 8956 patients with ALGIB in the Colonic Diverticular Bleeding Leaders Update Evidence From Multicenter Japanese Study (CODE BLUE-J) study and categorized them into 4 groups based on the BSG guidelines. Outcomes included 30-day rebleeding, 30-day mortality, blood transfusion, therapeutic intervention, and severe bleeding., Results: The severe bleeding rates significantly decreased from group I to group IV: 92.1%, 70.1%, 58.7%, and 38.4%. The rate of the need for blood transfusion and 30-day mortality also decreased from group I to group IV. Although outpatient follow-up was recommended in group IV, it had high rates of severe bleeding (38%) and 30-day rebleeding (11%). Notably, for colonic diverticular bleeding, the rate of 30-day rebleeding was 25.5%, even with an Oakland score of ≤8. We identified abdominal pain, diarrhea, and a high white blood cell count as independent factors that differentiate between nonsevere and severe bleeding cases in group IV. Using these factors, we found that the 30-day rebleeding rate in the nonsevere group was 3.6%, suggesting the feasibility of outpatient follow-up in this group. Furthermore, a novel group, Group X, which deviated from the existing 4 groups, had a high severe bleeding rate (70.9%) comparable to that of group II., Conclusions: The BSG guidelines suggest a management approach that can clearly differentiate severity. However, caution is advised when using the Oakland score to triage patients for outpatient follow-up. Additionally, prompt intervention may be necessary for groups not covered by the guidelines., Competing Interests: Disclosure All authors disclosed no financial relationships. This work was partially supported by grants from the Ministry of Health, Labour and Welfare, Japan (grant number 19HB1003), Japan Society for the Promotion of Science KAKENHI grant (JP17K09365 and 20K08366), Smoking Research Foundation, and Takeda Science Foundation, as well as Grants-in-Aid for Research from the National Center for Global Health and Medicine (29-2001, 29-2004, 19A1011, 19A1022, 19A-2015, 29-1025, and 30-1020). The funders had no role in the study design, analysis, or decision to publish the manuscript., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Although several reports have compared the outcomes of self-expandable metallic stent (SEMSs) and transanal decompression tube (TDT) placement for malignant colorectal obstruction (MCO), few studies have compared the radiation exposure (RE) associated with these two procedures. Consequently, we aimed to compare the RE of SEMS and TDT placements for MCO using propensity score matching (PSM) in a multi-center, prospective observational study. Methods: This study investigated the clinical data of 236 patients who underwent SEMS or TDT placement. The air kerma at the patient entrance reference point (K a,r : mGy) and air kerma-area product (P KA ; Gycm 2 ) were measured and compared between SEMS and TDT groups after PSM. Results: After PSM, 61 patients were identified in each group. The median K a,r in the SEMS group was significantly greater than that in the TDT group (77.4 vs. 55.6 mGy; p = 0.025) across the entire cohort. With respect to subgroup analyses by location, in the rectum, the median K a, r and P KA were significantly greater in the SEMS group than in the TDT group (172.9 vs. 34.6 mGy; p = 0.001; and 46.0 vs. 18.1 Gycm 2 ; p = 0.006, respectively). However, in the colon, the RE parameters did not significantly differ between the two groups. Conclusions: TDT might be a more suitable option for decompression in patients with malignant rectal obstruction due to its lower RE and technical advantages. Conversely, SEMS placement is recommended as the first decompression method to treat malignant colonic obstruction, in line with the current guidelines.

Objectives: The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants., Methods: This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closure was considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%., Results: Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8-14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed., Conclusion: Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants., Trial Registration: UMIN Clinical Trial Registry (UMIN000036734)., (© 2024 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system., Methods: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort., Results: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test)., Conclusions: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria., (© 2024. The Author(s).)

The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04-1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04-1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding., (© 2024. The Author(s).)

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation., (© 2024. The Author(s).)

Background: Current evidence on the surgical rate, indication, procedure, risk factors, mortality, and postoperative rebleeding for acute lower gastrointestinal bleeding (ALGIB) is limited., Methods: We constructed a retrospective cohort of 10,342 patients admitted for acute hematochezia at 49 hospitals (CODE BLUE J-Study) and evaluated clinical data on the surgeries performed., Results: Surgery was performed in 1.3% (136/10342) of the cohort with high rates of colonoscopy (87.7%) and endoscopic hemostasis (26.7%). Indications for surgery included colonic diverticular bleeding (24%), colorectal cancer (22%), and small bowel bleeding (16%). Sixty-four percent of surgeries were for hemostasis for severe refractory bleeding. Postoperative rebleeding rates were 22% in patients with presumptive or obscure preoperative identification of the bleeding source and 12% in those with definitive identification. Thirty-day mortality rates were 1.5% and 0.8% in patients with and without surgery, respectively. Multivariate analysis showed that surgery-related risk factors were transfusion need ≥ 6 units (P < 0.001), in-hospital rebleeding (P < 0.001), small bowel bleeding (P < 0.001), colorectal cancer (P < 0.001), and hemorrhoids (P < 0.001). Endoscopic hemostasis was negatively associated with surgery (P = 0.003). For small bowel bleeding, the surgery rate was significantly lower in patients with endoscopic hemostasis as 2% compared to 12% without endoscopic hemostasis., Conclusions: Our cohort study elucidated the outcomes and risks of the surgery. Extensive exploration including the small bowel to identify the source of bleeding and endoscopic hemostasis may reduce unnecessary surgery and improve the management of ALGIB., (© 2023. Japanese Society of Gastroenterology.)

Background & Aims: Currently, large, nationwide, long-term follow-up data on acute lower gastrointestinal bleeding (ALGIB) are scarce. We investigated long-term risks of recurrence after hospital discharge for ALGIB using a large multicenter dataset., Methods: We retrospectively analyzed 5048 patients who were urgently hospitalized for ALGIB at 49 hospitals across Japan (CODE BLUE-J study). Risk factors for the long-term recurrence of ALGIB were analyzed by using competing risk analysis, treating death without rebleeding as a competing risk., Results: Rebleeding occurred in 1304 patients (25.8%) during a mean follow-up period of 31 months. The cumulative incidences of rebleeding at 1 and 5 years were 15.1% and 25.1%, respectively. The mortality risk was significantly higher in patients with out-of-hospital rebleeding episodes than in those without (hazard ratio, 1.42). Of the 30 factors, multivariate analysis showed that shock index ≥1 (subdistribution hazard ratio [SHR], 1.25), blood transfusion (SHR, 1.26), in-hospital rebleeding (SHR, 1.26), colonic diverticular bleeding (SHR, 2.38), and thienopyridine use (SHR, 1.24) were significantly associated with increased rebleeding risk. Multivariate analysis of colonic diverticular bleeding patients showed that blood transfusion (SHR, 1.20), in-hospital rebleeding (SHR, 1.30), and thienopyridine use (SHR, 1.32) were significantly associated with increased rebleeding risk, whereas endoscopic hemostasis (SHR, 0.83) significantly decreased the risk., Conclusions: These large, nationwide follow-up data highlighted the importance of endoscopic diagnosis and treatment during hospitalization and the assessment of the need for ongoing thienopyridine use to reduce the risk of out-of-hospital rebleeding. This information also aids in the identification of patients at high risk of rebleeding., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Recently, the use of various endoscopic procedures performed under X-ray fluoroscopy guidance has increased. With the popularization of such procedures, diagnostic reference levels (DRLs) have been widely accepted as the global standard for various procedures with ionizing radiation. The Radiation Exposure from Gastrointestinal Fluoroscopic Procedures (REX-GI) study aimed to prospectively collect actual radiation exposure (RE) data and establish DRLs in gastrointestinal endoscopy units. In this post hoc analysis of the REX-GI study, we established DRLs for each disease site by analyzing cases of gastrointestinal enteral metallic stent placement., Methods: The REX-GI study was a multicenter, prospective observational study conducted to collect actual RE data during gastrointestinal enteral metallic stent placement. To establish DRL values for three disease sites, namely the esophagus, gastroduodenum, and colon, we examined fluoroscopy time (FT; min), number of X-ray images, air kerma at the patient entrance reference point ( K a,r ; mGy), and the air kerma-area product ( P KA ; Gy cm 2 ) during enteral metallic stent placement., Results: Five-hundred and twenty-three stenting procedures were performed. The DRL values of FT (min) and the number of X-ray images for the esophagus/gastroduodenum/colon were 9/16/18 min and 9/15/11 min, respectively. Furthermore, the DRL values of K a,r and P KA for each disease site were 43.3/120/124 mGy and 10.3/36.6/48.4 Gy cm 2 , respectively. Among the procedures, esophageal stents were significantly associated with the lowest values ( P  < 0.001)., Conclusion: The characteristics of RE vary according to disease site among gastrointestinal enteral metallic stent placements. Thus, it is desirable to set DRL values based on the disease site., (© 2023 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: No studies have compared the clinical outcomes of early and delayed feeding in patients with acute lower gastrointestinal bleeding (ALGIB). This study aimed to evaluate the benefits and risks of early feeding in a nationwide cohort of patients with ALGIB in whom haemostasis was achieved., Methods: We reviewed data for 5910 patients with ALGIB in whom haemostasis was achieved and feeding was resumed within 3 days after colonoscopy at 49 hospitals across Japan (CODE BLUE-J Study). Patients were divided into an early feeding group (≤1 day, n = 3324) and a delayed feeding group (2-3 days, n = 2586). Clinical outcomes were compared between the groups by propensity matching analysis of 1508 pairs., Results: There was no significant difference between the early and delayed feeding groups in the rebleeding rate within 7 days after colonoscopy (9.4% vs. 8.0%; p = 0.196) or in the rebleeding rate within 30 days (11.4% vs. 11.5%; p = 0.909). There was also no significant between-group difference in the need for interventional radiology or surgery or in mortality. However, the median length of hospital stay after colonoscopy was significantly shorter in the early feeding group (5 vs. 7 days; p < 0.001). These results were unchanged when subgroups of presumptive and definitive colonic diverticular bleeding were compared., Conclusion: The findings of this nationwide study suggest that early feeding after haemostasis can shorten the hospital stay in patients with ALGIB without increasing the risk of rebleeding., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background and Aim: While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes., Methods: We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE-J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy., Results: A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users ( P  = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users ( P  < 0.001). The rate of SRH with active bleeding was significantly higher in long cap users ( P  < 0.001). Other clinical outcomes did not differ significantly., Conclusion: Compared to that with short caps, long cap-assisted colonoscopy is superior for the diagnosis of acute hematochezia, especially CDB, and the identification of active bleeding., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: Ligation therapy, including endoscopic detachable snare ligation (EDSL) and endoscopic band ligation (EBL), has emerged as an endoscopic treatment for colonic diverticular bleeding (CDB); its comparative effectiveness and risk of recurrent bleeding remain unclear, however. Our goal was to compare the outcomes of EDSL and EBL in treating CDB and identify risk factors for recurrent bleeding after ligation therapy., Methods: We reviewed data of 518 patients with CDB who underwent EDSL (n = 77) or EBL (n = 441) in a multicenter cohort study named the Colonic Diverticular Bleeding Leaders Update Evidence From Multicenter Japanese Study (CODE BLUE-J Study). Outcomes were compared by using propensity score matching. Logistic and Cox regression analyses were performed for recurrent bleeding risk, and a competing risk analysis was used to treat death without recurrent bleeding as a competing risk., Results: No significant differences were found between the 2 groups in terms of initial hemostasis, 30-day recurrent bleeding, interventional radiology or surgery requirements, 30-day mortality, blood transfusion volume, length of hospital stay, and adverse events. Sigmoid colon involvement was an independent risk factor for 30-day recurrent bleeding (odds ratio, 1.87; 95% confidence interval, 1.02-3.40; P = .042). History of acute lower GI bleeding (ALGIB) was a significant long-term recurrent bleeding risk factor on Cox regression analysis. A performance status score of 3/4 and history of ALGIB were long-term recurrent bleeding factors on competing risk regression analysis., Conclusions: There were no significant differences in outcomes between EDSL and EBL for CDB. After ligation therapy, careful follow-up is required, especially in the treatment of sigmoid diverticular bleeding during admission. History of ALGIB and performance status at admission are important risk factors for long-term recurrent bleeding after discharge., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to examine the factors contributing to radiation exposure exceeding the DRL of the transnasal ileus tube placement in this post hoc analysis from the cohort of the REX-GI study., Methods: Patients with transnasal ileus tubes were enrolled in the rex-gi study from may 2019 to december 2020. We investigated the endoscope insertion time (min), procedure time (min), tube insertion length (cm), fluoroscopy time (FT: min), air kerma at the patient entrance reference point (K a.r : mGy), and air kerma-area product (P KA : Gycm 2 ). The third quartile value of the P KA value was calculated as the diagnostic reference level (DRL) value. We explored the factors associated with radiation exposure exceeding the DRL., Results: In the REX-GI study, 496 patients who underwent transnasal ileus tube placement were enrolled. The median age of the patients was 71 years. The median endoscopy insertion time, procedure time, and tube insertion length were 6 min, 20 min, and 170 cm, respectively. The third quartile/median FT, K a.r , and P KA were 18/11.9 min, 99.2/54.4 mGy, and 46.9/28 Gycm 2 , respectively. The third quartile value of P KA (47 Gycm 2 ) was set as the DRL value. There were differences in distribution by the hospital. Compared with procedures under the DRL, the FT (19 vs 10 min), procedure time (25 vs 18 min), and tube insertion length (185 vs 165 cm) were significantly longer for procedures above the DRL., Conclusion: We report the DRL for transnasal ileus tube placement in Japan. A longer procedure time and tube insertion length may be associated with DRL exceedance., Advances in Knowledge: Transnasal ileus tube placement under fluoroscopy guidance is a standard clinical procedure for bowel obstruction. However, the appropriate radiation dose level has not yet been established.We report the (DRL) for transnasal ileus tube placement in Japan. A longer procedure time and tube insertion length may be associated with DRL exceedance.

Background and Aim: Cold snare polypectomy is commonly performed to remove small colorectal polyps. Accidental resection of carcinomas during this procedure has been reported. Herein, we aimed to clarify the clinicopathological features and clinical course of colorectal carcinomas resected by cold snare polypectomy., Methods: This multicenter retrospective cohort study was conducted at 10 Japanese healthcare centers. Of the colorectal lesions resected by cold snare polypectomy between April 2016 and March 2020, lesions pathologically diagnosed as carcinoma were reviewed. Centralized histology (based on the Vienna classification) and endoscopic reviews were performed. The study endpoints were endoscopic features and clinical outcomes of cold snare polypectomy-resected colorectal carcinomas (Vienna category ≥4.2)., Results: We reviewed 74 of the 70 693 lesions resected by cold snare polypectomy. After a central pathological review, 68 lesions were diagnosed as carcinomas. The Japan Narrow-band imaging Expert Team (JNET) classification type 2B, lesion size ≥6 mm, and multinodular morphology were the significant endoscopic predictors of carcinoma resected by cold snare polypectomy. No adverse events related to the procedure occurred. Sixty-three lesions were diagnosed as carcinomas within the mucosal layer, and 34 were curative resections. Of the five carcinoma lesions with submucosal invasion, additional surgery revealed remnant cancer tissues in one lesion. No local or metastatic recurrence was observed during follow-up., Conclusions: Although most of the carcinomas resected by cold snare polypectomy were within the mucosal layer, few lesions invading the submucosa were identified. Careful pre-procedural endoscopic evaluation, especially focusing on the JNET classification and multinodular morphology, is recommended., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

This study aimed to examine occupational radiation exposure to the lens of the eyes during endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, prospective, observational cohort study, we collected data regarding occupational radiation exposure to the lens of the eyes during ERCP. We measured radiation exposure of patients and examined its correlation with occupational exposure. In dosimetrically-measured ERCPs (n = 631), the median air kerma at the patient entrance reference point, air kerma-area product, and fluoroscopy time were 49.6 mGy, 13.5 Gycm 2 , and 10.9 min, respectively. The median estimated annual radiation dose to the lens of the eyes was 3.7, 2.2, and 2.4 mSv for operators, assistants, and nurses, respectively. Glass badge over lead aprons and eye dosimeter results were similar in operators but differed in assistants and nurses. A strong correlation was shown between eye dosimeter measurements and patients' radiation exposure. The shielding rates of the lead glasses were 44.6%, 66.3%, and 51.7% for operators, assistants, and nurses, respectively. This study revealed the actual occupational exposure dose for the lens of the eyes during ERCP and the efficacy of lead glass. Values of radiation exposure to patients can help estimate exposure to the lens of the eyes of medical staff., (© 2023. The Author(s).)

Objectives: We surveyed and reported low protective equipment usage and insufficient knowledge among endoscopy-fluoroscopy departments in Japan in 2020. Two years later, we conducted a follow-up survey of doctors, nurses, and technologists in Japan., Methods: We conducted a questionnaire survey on radiation protection from May to June 2022. The participants were medical staff, including doctors, nurses, and radiological and endoscopy technicians in endoscopy-fluoroscopy departments. The questionnaire included 17 multiple-choice questions divided into three parts: background, equipment, and knowledge., Results: We surveyed 464 subjects from 34 institutions. There were 267 doctors (58%), 153 nurses (33%), and 44 technologists (9%). The rate of wearing a lead apron was 98% in this study. The rates of wearing a thyroid collar, lead glasses, and radiation dosimeter were 27%, 35%, and 74%, respectively. The trend of the protective equipment rate was similar to that of our previous study; however, radiation dosimetry among doctors was still low at 58%. The percentage of subjects who knew the radiation exposure (REX) dose of each procedure was low at 18%. Seventy-six percent of the subjects attended lectures on radiation protection, and 73% knew about the three principles of radiation protection; however, the concept of diagnostic reference levels was not well known (18%). Approximately 60% of the subjects knew about the exposure dose increasing cancer mortality (63%) and the 5-year lens REX limit (56%)., Conclusions: There was some improvement in radiation protection equipment or education, but relatively little compared to the 2020 survey of endoscopy departments., Competing Interests: The author Mamoru Takenaka is an AE of Digestive Endoscopy. The author Ichiro Oda is an AE of Digestive Endoscopy. The author Yousuke Nakai is an AE of Digestive Endoscopy. The author Seiichiro Abe is an AE of DEN Open. The rest of the authors declare no conflict of interest., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: While angioectasia is an important cause of acute hematochezia, relevant clinical features remain unclear. This study aims to reveal risk factors, clinical outcomes, and the effectiveness of therapeutic endoscopy for patients with acute hematochezia due to angioectasia., Methods: This retrospective cohort study was conducted at 49 Japanese hospitals between January 2010 and December 2019, enrolling patients hospitalized for acute hematochezia (CODE BLUE-J study). Baseline factors and clinical outcomes for angioectasia were analyzed., Results: Among 10,342 patients with acute hematochezia, 129 patients (1.2%) were diagnosed with angioectasia by colonoscopy. The following factors were significantly associated with angioectasia: chronic kidney disease, liver disease, female, body mass index < 25, and anticoagulant use. Patients with angioectasia were at a significant increased risk of blood transfusions compared to those without angioectasia (odds ratio [OR] 2.61; 95% confidence interval [CI] 1.69-4.02). Among patients with angioectasia, 36 patients (28%) experienced rebleeding during 1-year follow-up. The 1-year cumulative rebleeding rates were 37.0% in the endoscopic clipping group, 14.3% in the coagulation group, and 32.8% in the conservative management group. Compared to conservative management, coagulation therapy significantly reduced rebleeding risk (P = 0.038), while clipping did not (P = 0.81). Multivariate analysis showed coagulation therapy was an independent factor for reducing rebleeding risk (hazard ratio [HR] 0.40; 95% CI 0.16-0.96)., Conclusions: Our data showed patients with angioectasia had a greater comorbidity burden and needed more blood transfusions in comparison with those without angioectasia. To reduce rebleeding risk, coagulation therapy can be superior for controlling hematochezia secondary to angioectasia., (© 2022. Japanese Society of Gastroenterology.)

Introduction: Weekend admissions showed increased mortality in several medical conditions. This study aimed to examine the weekend effect on acute lower gastrointestinal bleeding (ALGIB) and its mortality and other outcomes., Methods: This retrospective cohort study (CODE BLUE-J Study) was conducted at 49 Japanese hospitals between January 2010 and December 2019. In total, 8,120 outpatients with acute hematochezia were enrolled and divided into weekend admissions and weekday admissions groups. Multiple imputation (MI) was used to handle missing values, followed by propensity score matching (PSM) to compare outcomes. The primary outcome was mortality; the secondary outcomes were rebleeding, length of stay (LOS), blood transfusion, thromboembolism, endoscopic treatment, the need for interventional radiology, and the need for surgery. Colonoscopy and computed tomography (CT) management were also evaluated., Results: Before PSM, there was no significant difference in mortality (1.3% vs. 0.9%, p = 0.133) between weekend and weekday admissions. After PSM with MI, 1,976 cases were matched for each admission. Mortality was not significantly different for weekend admissions compared with weekday admissions (odds ratio [OR] 1.437, 95% confidence interval [CI] 0.785-2.630; p = 0.340). No significant difference was found with other secondary outcomes in weekend admissions except for blood transfusion (OR 1.239, 95% CI 1.084-1.417; p = 0.006). Weekend admission had a negative effect on early colonoscopy (OR 0.536, 95% CI 0.471-0.609; p &lt; 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295-1.660; p &lt; 0.001)., Conclusion: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB)., Methods: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS., Results: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS., Conclusions: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background and Aims: We aimed to determine the optimal timing of colonoscopy and factors that benefit patients who undergo early colonoscopy for acute lower GI bleeding., Methods: We identified 10,342 patients with acute hematochezia (CODE BLUE-J study) admitted to 49 hospitals in Japan. Of these, 6270 patients who underwent a colonoscopy within 120 hours were included in this study. The inverse probability of treatment weighting method was used to adjust for baseline characteristics among early (≤24 hours, n = 4133), elective (24-48 hours, n = 1137), and late (48-120 hours, n = 1000) colonoscopy. The average treatment effect was evaluated for outcomes. The primary outcome was 30-day rebleeding rate., Results: The early group had a significantly higher rate of stigmata of recent hemorrhage (SRH) identification and a shorter length of stay than the elective and late groups. However, the 30-day rebleeding rate was significantly higher in the early group than in the elective and late groups. Interventional radiology (IVR) or surgery requirement and 30-day mortality did not significantly differ among groups. The interaction with heterogeneity of effects was observed between early and late colonoscopy and shock index (shock index <1, odds ratio [OR], 2.097; shock index ≥1, OR, 1.095; P for interaction = .038) and performance status (0-2, OR, 2.481; ≥3, OR, .458; P for interaction = .022) for 30-day rebleeding. Early colonoscopy had a significantly lower IVR or surgery requirement in the shock index ≥1 cohort (OR, .267; 95% confidence interval, .099-.721) compared with late colonoscopy., Conclusions: Early colonoscopy increased the rate of SRH identification and shortened the length of stay but involved an increased risk of rebleeding and did not improve mortality and IVR or surgery requirement. Early colonoscopy particularly benefited patients with a shock index ≥1 or performance status ≥3 at presentation., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Treatment strategies for colonic diverticular bleeding (CDB) based on stigmata of recent hemorrhage (SRH) remain unstandardized, and no large studies have evaluated their effectiveness. We sought to identify the best strategy among combinations of SRH identification and endoscopic treatment strategies., Methods: We retrospectively analyzed 5823 CDB patients who underwent colonoscopy at 49 hospitals throughout Japan (CODE-BLUE J-Study). Three strategies were compared: find SRH (definitive CDB) and treat endoscopically, find SRH (definitive CDB) and treat conservatively, and without finding SRH (presumptive CDB) treat conservatively. In conducting pairwise comparisons of outcomes in these groups, we used propensity score-matching analysis to balance baseline characteristics between the groups being compared., Results: Both early and late recurrent bleeding rates were significantly lower in patients with definitive CDB treated endoscopically than in those with presumptive CDB treated conservatively (<30 days, 19.6% vs 26.0% [P < .001]; <365 days, 33.7% vs 41.6% [P < .001], respectively). In patients with definitive CDB, the early recurrent bleeding rate was significantly lower in those treated endoscopically than in those treated conservatively (17.4% vs 26.7% [P = .038] for a single test of hypothesis; however, correction for multiple testing of data removed this significance). The late recurrent bleeding rate was also lower, but not significantly, in those treated endoscopically (32.0% vs 36.1%, P = .426). Definitive CDB treated endoscopically showed significantly lower early and late recurrent bleeding rates than when treated conservatively in cases of SRH with active bleeding, nonactive bleeding, and in the right-sided colon but not left-sided colon., Conclusions: Treating definitive CDB endoscopically was most effective in reducing recurrent bleeding over the short and long term, compared with not treating definitive CDB or presumptive CDB. Physicians should endeavor to find and treat SRH for suspected CDB., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study aimed to evaluate the efficacy of perioperative antibiotics against post-endoscopic submucosal dissection (ESD) coagulation syndrome (PECS) in patients undergoing colorectal ESD., Methods: A prospective, multicenter, randomized controlled, parallel, superiority trial was conducted at 21 Japanese tertiary institutions. Patients with superficial colorectal lesions ≥20 mm and those undergoing ESD management for a single lesion were eligible. Patients with perforation during and after ESD were withdrawn. Before the ESD procedure, participants were randomly assigned (1:1) to either undergo conventional treatment (nonantibiotic group) or investigational treatment (antibiotic group). In the antibiotic group, 3 g of ampicillin-sulbactam was administered just before, 8 hours after, and the morning after ESD. The primary endpoint was the incidence of PECS. The onset of PECS was defined as localized abdominal pain (both spontaneous pain and tenderness) and fever (≥37.6°C) or inflammatory response (leukocytosis [≥10,000 cells/μL] or elevated C-reactive protein level [≥.5 mg/dL])., Results: From February 5, 2019 to September 7, 2020, 432 patients were enrolled and assigned to the antibiotic group (n = 216) or nonantibiotic group (n = 216). After withdrawal of 52 patients, 192 in the antibiotic group and 188 in the nonantibiotic group were analyzed. PECS occurred in 9 of 192 patients (4.7%) in the antibiotic group and 14 of 188 patients (7.5%) in the nonantibiotic group, with an odds ratio of .61 (95% confidence interval, .23-1.56; P = .29)., Conclusions: Perioperative use of antibiotics was not effective in reducing the incidence of PECS in patients undergoing colorectal ESD. (Clinical trial registration number: UMIN000035178.)., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Direct and indirect clipping treatments are used worldwide to treat colonic diverticular bleeding (CDB), but their effectiveness has not been examined in multicenter studies with more than 100 cases., Objective: We sought to determine the short- and long-term effectiveness of direct versus indirect clipping for CDB in a nationwide cohort., Methods: We studied 1041 patients with CDB who underwent direct clipping (n = 360) or indirect clipping (n = 681) at 49 hospitals across Japan (CODE BLUE-J Study)., Results: Multivariate analysis adjusted for age, sex, and important confounding factors revealed that, compared with indirect clipping, direct clipping was independently associated with reduced risk of early rebleeding (<30 days; adjusted odds ratio [AOR] 0.592, p = 0.002), late rebleeding (<1 year; AOR 0.707, p = 0.018), and blood transfusion requirement (AOR 0.741, p = 0.047). No significant difference in initial hemostasis rates was observed between the two groups. Propensity-score matching to balance baseline characteristics also showed significant reductions in the early and late rebleeding rates with direct clipping. In subgroup analysis, direct clipping was associated with significantly lower rates of early and late rebleeding and blood transfusion need in cases of stigmata of recent hemorrhage with non-active bleeding on colonoscopy, right-sided diverticula, and early colonoscopy, but not with active bleeding on colonoscopy, left-sided diverticula, or elective colonoscopy., Conclusions: Our large nationwide study highlights the use of direct clipping for CDB treatment whenever possible. Differences in bleeding pattern and colonic location can also be considered when deciding which clipping options to use., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Diagnostic reference levels (DRLs) are required to optimize medical exposure. However, data on DRLs for interventional fluoroscopic procedures are lacking, especially in gastroenterology. This study aimed to prospectively collect currently used radiation doses and help establish national DRLs for fluoroscopy-guided gastrointestinal procedures in Japan., Methods: This multicentre, prospective, observational study collected actual radiation dose data from endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), balloon-assisted enteroscopy (BAE), enteral metallic stent placement, and enteral tube placement from May 2019 to December 2020. The study outcomes were fluoroscopy time (FT: min), air kerma at the patient entrance reference point (K a,r : mGy), air kerma area product (P KA : Gycm 2 ), and radiation dose rate (RDR: mGy/min). Additionally, the basic settings of fluoroscopy equipment and the factors related to each procedure were investigated. This study was registered in the UMIN Clinical Trial Registry (UMIN 000036525)., Findings: Overall, 12959 fluoroscopy-guided gastrointestinal procedures were included from 23 hospitals in Japan. For 11162 ERCPs, the median/third quartile values of K a,r (mGy), P KA (Gycm 2 ), and FT (min) were 69/145 mGy, 16/32 Gycm 2 , and 11/20 min, respectively. Similarly, these values were 106/219 mGy, 23/41 Gycm 2 and 17/27 min for 374 interventional EUSs; 53/104 mGy, 16/32 Gycm 2 and 10/15 min for 523 metallic stents; 56/104 mGy, 28/47 Gycm 2 , and 12/18 min for 599 tube placements; and 35/81 mGy, 16/43 Gycm 2 and 7/15 min for 301 BAEs, respectively. For the overall radiation dose rate, the median/third quartile values of RDR were 5.9/9.4 (mGy/min). The RDR values at each institution varied widely., Interpretation: This study reports the current radiation doses of fluoroscopy-guided gastrointestinal procedures expressed as DRL quantities. This will serve as a valuable reference for national DRL values., Funding: This work was supported by a clinical research grant from the Japanese Society of Gastroenterology., Competing Interests: None of the authors has any competing interests arising from this research., (© 2021 The Author(s).)

Introduction: The bleeding source of hematochezia is unknown without performing colonoscopy. We sought to identify whether colonoscopy is a risk-stratifying tool to identify etiology and predict outcomes and whether presenting symptoms can differentiate the etiologies in patients with hematochezia., Methods: This multicenter retrospective cohort study conducted at 49 hospitals across Japan analyzed 10,342 patients admitted for outpatient-onset acute hematochezia., Results: Patients were mostly elderly population, and 29.5% had hemodynamic instability. Computed tomography was performed in 69.1% and colonoscopy in 87.7%. Diagnostic yield of colonoscopy reached 94.9%, most frequently diverticular bleeding. Thirty-day rebleeding rates were significantly higher with diverticulosis and small bowel bleeding than with other etiologies. In-hospital mortality was significantly higher with angioectasia, malignancy, rectal ulcer, and upper gastrointestinal bleeding. Colonoscopic treatment rates were significantly higher with diverticulosis, radiation colitis, angioectasia, rectal ulcer, and postendoscopy bleeding. More interventional radiology procedures were needed for diverticulosis and small bowel bleeding. Etiologies with favorable outcomes and low procedure rates were ischemic colitis and infectious colitis. Higher rates of painless hematochezia at presentation were significantly associated with multiple diseases, such as rectal ulcer, hemorrhoids, angioectasia, radiation colitis, and diverticulosis. The same was true in cases of hematochezia with diarrhea, fever, and hemodynamic instability., Discussion: This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Outcomes of acute lower gastrointestinal bleeding have not been compared according to hospital capacity. We aimed to perform a propensity score-matched cohort study with path and mediation analyses for acute hematochezia patients. Hospitals were divided into high- versus low-volume hospitals for emergency medical services. Rebleeding and death within 30 days were compared. Computed tomography, early colonoscopy (colonoscopy performed within 24 h), and endoscopic therapies were included as mediators. A total of 2644 matched pairs were yielded. The rebleeding rate within 30 days was not significant between high- and low-volume hospitals (16% vs. 17%, P = 0.44). The mortality rate within 30 days was significantly higher in the high-volume cohort than in the low-volume cohort (1.7% vs. 0.8%, P = 0.003). Treatment at high-volume hospitals was not a significant factor for rebleeding (odds ratio [OR] = 0.91; 95% confidence interval [CI], 0.79-1.06; P = 0.23), but was significant for death within 30 days (OR = 2.03; 95% CI, 1.17-3.52; P = 0.012) on multivariate logistic regression after adjusting for patients' characteristics. Mediation effects were not observed, except for rebleeding within 30 days in high-volume hospitals through early colonoscopy. However, the direct effect of high-volume hospitals on rebleeding was not significant. High-volume hospitals did not improve the outcomes of acute hematochezia patients., (© 2021. The Author(s).)

Background: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA., Methods: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins., Results: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression., Conclusion: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA., (© 2021. The Author(s).)

Background and Aims: It is essential for endoscopists, technologists, and nurses to understand radiation protection. However, protective equipment usage is still low, and there is little awareness of radiation protection in practice., Methods: We conducted a questionnaire survey on radiation protection from January to February 2020. The participants were medical staff, including medical doctors, nurses, and radiological and endoscopy technician in endoscopy-fluoroscopy departments. The questionnaire included 14 multiple-choice questions divided among three parts: background, equipment, and knowledge., Results: We surveyed a total of 282 subjects from 26 institutions. There were 168 medical doctors (60%), 90 nurses (32%), and 24 technologists (9%). Although almost all staff members (99%) always wore a lead apron, only a few wore a thyroid collar (32%) and lead glasses (21%). The rate of wearing a radiation dosimeter was insufficient (69%), especially among doctors (52%). A few subjects knew the radiation exposure dose of each procedure (15%), and slightly over half had attended lectures on radiation protection (64%) and knew about the three principles of radiation protection (59%). Protection adherence did not differ by years of experience, knowledge of fluoroscopy, awareness of radiation exposure doses, or attendance at basic lectures on radiation protection. However, medical doctors who were aware of the radiation exposure dose of each procedure were significantly more likely to wear dosimeters than those who were not (p = 0.0008)., Conclusion: Medical staff in endoscopy departments in Japan do not have enough radiation protection equipment or education., Competing Interests: The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Although optimal treatment of superficial esophageal squamous cell carcinoma (SCC) requires accurate evaluation of cancer invasion depth, the current process is rather subjective and may vary by observer. We, therefore, aimed to develop an AI system to calculate cancer invasion depth., Methods: We gathered and selected 23,977 images (6857 WLI and 17,120 NBI/BLI images) of pathologically proven superficial esophageal SCC from endoscopic videos and still images of superficial esophageal SCC taken in our facility, to use as a learning dataset. We annotated the images with information [such as magnified endoscopy (ME) or non-ME, pEP-LPM, pMM, pSM1, and pSM2-3 cancers] based on pathologic diagnosis of the resected specimens. We created a model using a convolutional neural network. Performance of the AI system was compared with that of invited experts who used the same validation video set, independent of the learning dataset., Results: Accuracy, sensitivity, and specificity with non-magnified endoscopy (ME) were 87%, 50%, and 99% for the AI system and 85%, 45%, 97% for the experts. Accuracy, sensitivity, and specificity with ME were 89%, 71%, and 95% for the AI system and 84%, 42%, 97% for the experts., Conclusions: Most diagnostic parameters were higher when done by the AI system than by the experts. These results suggest that our AI system could potentially provide useful support during endoscopies.

Introduction: Recently, the use of various endoscopic procedures under X-ray fluoroscopic guidance, such as endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasonography (EUS), enteral endoscopy and stenting, has been rapidly increasing because of the minimally invasive nature of these procedures compared with that of surgical intervention. With the spread of CT and fluoroscopic interventions, including endoscopic procedures under X-ray guidance, high levels of radiation exposure (RE) from medical imaging have led to major concerns throughout society. However, information about RE related to these image-guided procedures in gastrointestinal endoscopy is scarce, and the RE reference levels have not been established. The aim of this study is to prospectively collect the actual RE dose and to help establish diagnostic reference levels (DRLs) in the field of gastroenterology in Japan., Methods and Analysis: This is a multicentre, prospective observational study that is being conducted to collect the actual RE from treatments and diagnostic procedures, including ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. We will measure the total fluoroscopy time (min), the total dose-area product (Gycm 2 ) and air-kerma (mGy) of those procedures. Because we are collecting the actual RE data and identifying the influential factors through a prospective, nationwide design, this study will provide guidance regarding the DRLs of ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement., Ethics and Dissemination: Approval was obtained from the Institutional Review Board of Toyonaka Municipal Hospital (25 April 2019). The need for informed consent will be waived via the opt-out method of each hospital website., Trial Registration Number: The UMIN Clinical Trials Registry, UMIN000036525., Competing Interests: Competing interests: None declared., (© 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 and Aims: Diagnosing esophageal squamous cell carcinoma (SCC) depends on individual physician expertise and may be subject to interobserver variability. Therefore, we developed a computerized image-analysis system to detect and differentiate esophageal SCC., Methods: A total of 9591 nonmagnified endoscopy (non-ME) and 7844 ME images of pathologically confirmed superficial esophageal SCCs and 1692 non-ME and 3435 ME images from noncancerous lesions or normal esophagus were used as training image data. Validation was performed using 255 non-ME white-light images, 268 non-ME narrow-band images/blue-laser images, and 204 ME narrow-band images/blue-laser images from 135 patients. The same validation test data were diagnosed by 15 board-certified specialists (experienced endoscopists)., Results: Regarding diagnosis by non-ME with narrow-band imaging/blue-laser imaging, the sensitivity, specificity, and accuracy were 100%, 63%, and 77%, respectively, for the artificial intelligence (AI) system and 92%, 69%, and 78%, respectively, for the experienced endoscopists. Regarding diagnosis by non-ME with white-light imaging, the sensitivity, specificity, and accuracy were 90%, 76%, and 81%, respectively, for the AI system and 87%, 67%, and 75%, respectively, for the experienced endoscopists. Regarding diagnosis by ME, the sensitivity, specificity, and accuracy were 98%, 56%, and 77%, respectively, for the AI system and 83%, 70%, and 76%, respectively, for the experienced endoscopists. There was no significant difference in the diagnostic performance between the AI system and the experienced endoscopists., Conclusions: Our AI system showed high sensitivity for detecting SCC by non-ME and high accuracy for differentiating SCC from noncancerous lesions by ME., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: None

Background: Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP)., Objective: To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps., Design: Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355)., Setting: 30 Japanese institutions., Patients: Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp., Intervention: Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy., Measurements: The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP)., Results: A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group., Limitation: An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously., Conclusion: Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP., Primary Funding Source: Japanese Gastroenterological Association.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: None