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BACKGROUND: An "esophageal rosette" (ER) sign is one of the endoscopic findings in primary esophageal achalasia. We investigated whether ER was associated with the therapeutic efficacy of peroral endoscopic myotomy (POEM). METHODS: The clinical characteristics and short-term outcomes of POEM were retrospectively evaluated in 69 patients who underwent the procedure for esophageal achalasia. The patients were divided into two groups according to the presence of an ER sign (ER and non-ER groups). Clinical success was defined as the post-POEM Eckardt score of three or less. RESULTS: On preoperative endoscopy, 55 (79.7%) patients exhibited ER. The patients in the ER group had a longer disease duration than those in the non-ER group (7.4 vs. 2.7 years, P = 0.0011), although the Eckardt scores before POEM were similar between the two groups. No differences were observed in POEM outcomes between the two groups, including procedure time, length of myotomy, hospital stay, and adverse events. The clinical success of POEM was more frequent in the ER group than in the non-ER group (96.2% vs. 78.6%, P = 0.027). Although the changes in the total Eckardt score and integrated relaxation pressure did not differ between the two groups, dysphagia in the Eckardt score significantly improved in the ER group. CONCLUSIONS: The data suggest that POEM for esophageal achalasia with ER could lead to favorable therapeutic outcomes, particularly dysphagia. The presence of ER may help determine the optimal treatment for esophageal achalasia.

DOI： 10.1007/s10388-024-01098-0

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BACKGROUND AND STUDY AIMS: Technical difficulty of endoscopic submucosal dissection (ESD) for colorectal neoplasms has not been resolved. The water pressure method (WPM) is a helpful technique for overcome difficulties with colorectal ESD. We evaluated the efficacy and safety of ESD with WPM (WPM-ESD) for colorectal neoplasms compared with conventional ESD (C-ESD). PATIENTS AND METHODS: This was a single-center, retrospective, observational study. Three hundred and eleven colorectal lesions were allocated into the WPM-ESD and the C-ESD groups, which were compared before and after propensity score matching. The main outcomes were procedure time, proportion of R0 resection, and incidence of adverse events (AEs) in the two groups. RESULTS: The WPM-ESD and C-ESD groups were allocated 134 and 177 lesions, respectively, and propensity score matching analysis created 92 matched pairs. Mean procedure time was significantly shorter in the WPM-ESD group (49 ± 26 vs. 58 ± 42 min, P = 0.032). All lesions were resected in one piece and there was no difference in the proportion of en bloc resection (100% vs. 100%) and R0 resection (92% vs. 96%, P = 0.536) or in incidence of intraoperative perforation (2.2% vs. 2.2%) in the two groups. CONCLUSIONS: WPM for colorectal ESD may shorten procedure time compared with C-ESD without increasing AEs.

DOI： 10.1055/a-2544-2654

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DOI： 10.1055/a-2420-7896

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AIMS: During intraoperative bleeding in endoscopic submucosal dissection (ESD), switching to spray coagulation may be beneficial compared with the continuous use of swift coagulation and can reduce the need for hemostatic forceps. We retrospectively assessed the effectiveness of spray modes on intraoperative bleeding during gastric ESD. METHODS AND RESULTS: A total of 316 bleeding events (156 in the Swift group and 160 in the Spray group) were consecutively recorded. In the Swift group, hemostasis was performed using the swift mode with a retracted tip of the needle-type knife, followed by the hemostatic forceps. In the Spray group, bleeding was treated in a stepwise manner: the swift mode, the spray mode, and the hemostatic forceps. All bleeding events were assigned to one of two groups by an endoscopist who retrospectively reviewed the videos. We compared the use of hemostatic forceps, the total hemostatic time, and the cumulative hemostasis rate between the two groups.The use of hemostatic forceps was significantly lower in the Spray group than in the Swift group (32.7% vs. 13.8%, P < 0.001). There was no significant difference in the total hemostatic time (Swift group, 20 s.; Spray group, 16 s.; P = 0.42), whereas the cumulative hemostasis rate with the knife was significantly higher in the Spray group (P = 0.007). CONCLUSION: The results suggested that spray coagulation from the tip of the needle-type knife could reduce the use of hemostatic forceps. In gastric ESD, spray coagulation may facilitate the hemostasis of intraoperative bleeding.

DOI： 10.1002/jgh3.70002

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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.

DOI： 10.1038/s41598-024-64476-9

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OBJECTIVE: Mucosal incision-assisted biopsy (MIAB) has been introduced as an alternative to endoscopic ultrasound-guided fine needle aspiration for tissue sampling of subepithelial lesions. However, there have been few reports on MIAB, and the evidence is lacking, particularly in small lesions. In this case series, we investigated the technical outcomes and postprocedural influences of MIAB for gastric subepithelial lesions 10 mm or greater in size. METHODS: We retrospectively reviewed cases with the intraluminal growth type of possible gastrointestinal stromal tumors, in which MIAB was performed at a single institution between October 2020 and August 2022. Technical success, adverse events, and clinical courses following the procedure were evaluated. RESULTS: In 48 MIAB cases with a median tumor diameter of 16 mm, the success rate of tissue sampling and the diagnostic rate were 96% and 92%, respectively. Two biopsies were considered sufficient for making the definitive diagnosis. Postoperative bleeding occurred in one case (2%). In 24 cases, surgery has performed a median of two months after MIAB, and no unfavorable findings caused by MIAB were seen intraoperatively. Finally, 23 cases were histologically diagnosed as gastrointestinal stromal tumors, and no patients who underwent MIAB experienced recurrence or metastasis during a median observation period of 13 months. CONCLUSIONS: The data indicated that MIAB appears feasible, safe, and useful for histological diagnosis of gastric intraluminal growth types of possible gastrointestinal stromal tumors, even those of a small size. Postprocedural clinical effects were considered negligible.

DOI： 10.1002/deo2.264

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BACKGROUND:  The rebleeding risks and outcomes of endoscopic treatment for acute lower gastrointestinal bleeding (ALGIB) may differ depending on the bleeding location, type, and etiology of stigmata of recent hemorrhage (SRH) but have yet to be fully investigated. We aimed to identify high risk endoscopic SRH and to propose an optimal endoscopic treatment strategy. METHODS:  We retrospectively analyzed 2699 ALGIB patients with SRH at 49 hospitals (CODE BLUE-J Study), of whom 88.6 % received endoscopic treatment. RESULTS:  30-day rebleeding rates of untreated SRH significantly differed among locations (left colon 15.5 % vs. right colon 28.6 %) and etiologies (diverticular bleeding 27.5 % vs. others [e. g. ulcerative lesions or angioectasia] 8.9 %), but not among bleeding types. Endoscopic treatment reduced the overall rebleeding rate (adjusted odds ratio [AOR] 0.69; 95 %CI 0.49-0.98), and the treatment effect was significant in right-colon SRH (AOR 0.46; 95 %CI 0.29-0.72) but not in left-colon SRH. The effect was observed in both active and nonactive types, but was not statistically significant. Moreover, the effect was significant for diverticular bleeding (AOR 0.60; 95 %CI 0.41-0.88) but not for other diseases. When focusing on treatment type, the effectiveness was not significantly different between clipping and other modalities for most SRH, whereas ligation was significantly more effective than clipping in right-colon diverticular bleeding. CONCLUSIONS:  A population-level endoscopy dataset allowed us to identify high risk endoscopic SRH and propose a simple endoscopic treatment strategy for ALGIB. Unlike upper gastrointestinal bleeding, the rebleeding risks for ALGIB depend on colonic location, bleeding etiology, and treatment modality.

DOI： 10.1055/a-2232-9630

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Endoscopic hand suturing (EHS) was first developed to firmly close a mucosal defect following endoscopic submucosal dissection and has the potential for expanded applications. This study aimed to investigate the feasibility and safety of EHS in various clinical settings. In this single-center pilot study, 15 patients who had diseases with potential indications for EHS were prospectively recruited. Technical success, clinical success after the procedure, and severe EHS-related adverse events (AEs) were evaluated. EHS was applied for defect closure after gastric subepithelial lesion removal under laparoscopic observation (n = 9), defect closure after rectal endoscopic full-thickness resection (EFTR) (n = 2), defect closure after thoracoscopy-assisted esophageal EFTR (n = 1), mucosal closure for gastric ulcer bleeding (n = 1), mucosal closure after peroral endoscopic myotomy (POEM) (n = 1), and postoperative anastomotic leak (n = 1). EHS was completed without severe AEs and the clinical courses were also favorable in 13 patients (87%). The median suturing time was 61 minutes. In patients with POEM and anastomotic leak, EHS was discontinued because of the narrow lumen. In conclusion, EHS appears feasible and safe in situations.

DOI： 10.1055/a-2284-9492

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[This corrects the article DOI: 10.1055/a-2284-9492.].

DOI： 10.1055/a-2302-6845

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BACKGROUND: Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection (ESD); however, the preoperative evaluation of tumor size is often different from histological assessment. Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD. AIM: To investigate the tumor size discrepancy between endoscopic and pathological evaluations and the influencing factors. METHODS: This was a retrospective study conducted at a single institution. A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected. We first assessed the difference in size with an absolute percentage of the scaling discrepancy. Subsequently, we compared the clinicopathological characteristics of the correct scaling group (> -33% and < 33%) with that of the incorrect scaling group (< -33% or > 33%), which was further subdivided into the underscaling group (-33% or less of the discrepancy) and overscaling group (33% or more of the discrepancy), respectively. As secondary outcome measures, parameters on size estimation were compared between the underscaling and correct scaling groups, as well as between the overscaling and correct scaling groups. Finally, multivariate analysis was performed in terms of the following relevant parameters on size estimation: Pathological size, location, and possible influential factors (P < 0.1) in the univariate analysis. RESULTS: The mean of absolute percentage in the scaling discordance was 21%, and 91 lesions were considered to be incorrectly estimated in size. The incorrect scaling was significantly remarkable in larger lesions (40 mm vs 28 mm; P < 0.001) and less experience (P < 0.001), and these two factors were influential on the underscaling (75 lesions; P < 0.001). Conversely, compared with the correct scaling group, 16 lesions in the overscaling group were significantly small (20 mm vs 28 mm; P < 0.001), and the small lesion size was influential on the overscaling (P = 0.002). CONCLUSION: Lesions indicated for colorectal ESD tended to be underestimated in large tumors, but overestimated in small ones. This discrepancy appears worth understanding for optimal procedural preparation.

DOI： 10.4253/wjge.v16.i3.136

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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.

DOI： 10.1038/s41598-024-55889-7

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BACKGROUND AND AIMS: An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. METHODS: Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. RESULTS: Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). CONCLUSIONS: This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

DOI： 10.1007/s10620-024-08271-6

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Small bowel adenocarcinoma (SBA) is rare, and scant data exist regarding its molecular and clinicopathologic characteristics. This study aimed to clarify the correlation between immunophenotypes, DNA mismatch repair status, genomic profiling, and clinicopathologic characteristics in patients with SBA. We examined 68 surgical resections from patients with primary SBA for immunohistochemical analyses of CK7, CK20, CD10, CDX2, MUC1, MUC2, MUC4, MUC5AC, and MUC6 expression as well as mismatch repair status. Genomic profiling was performed on 30 cases using targeted next-generation sequencing. Tumor mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null based on MUC2, MUC5AC, MUC6, and CD10 immunostaining. The expression of these proteins was categorized into 3 classifications according to their relationship to: (1) tumor location: CK7/CK20, MUC4, and MUC6; (2) histologic type: mucinous adenocarcinoma was positive for MUC2 and negative for MUC6; and (3) TNM stage: CD10 was downregulated, whereas MUC1 was upregulated in advanced TNM stages. CDX2 was a specific marker for SBA generally expressed in the small intestine. MUC1 and MUC4 expression was significantly associated with worse prognosis. MUC2 expression correlated with better prognosis, except for mucinous adenocarcinoma. Although the difference was not statistically significant, gastric-type tumors were more frequently located in the duodenum and were absent in the ileum. APC and CTNNB1 mutations were not found in the gastric-type tumors. The SBA immunophenotype correlated with tumor location, biological behavior, and genomic alterations. Our results suggest that the molecular pathway involved in carcinogenesis of gastric-type SBA differs from that of intestinal-type SBA.

DOI： 10.1097/PAS.0000000000002161

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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.

DOI： 10.1007/s00535-023-02057-9

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BACKGROUND: Collaborative surgery by both endoscopists and surgeons is considered effective for providing less invasive local resection of gastrointestinal tumors, to offset the limitations of either pure endoscopic treatments or surgical intervention. The clinical outcomes of collaborative surgery were evaluated to investigate the feasibility and safety of this approach. METHODS: In this single-center retrospective observational study, we collected data from consecutive patients who underwent collaborative surgery for lesions located from the laryngopharynx to the anus. The completeness of collaboration, technical success, procedure time, postoperative hospitalization period, and occurrence of adverse events were analyzed. RESULTS: Collaboration surgery was performed for 134 lesions (33 laryngopharyngeal, 2 esophageal, 89 gastric, 8 duodenal and 2 recto-anal) in 131 patients. Collaboration completeness was achieved in 129 lesions (96%). En bloc resection and pathological R0 resection of lesions were achieved in 127 (95%) and 124 (93%) lesions, respectively. The mean procedure time was 188 min. The mean time of discharge was the 11th postoperative day. Five patients (4%) developed relevant postoperative adverse events. CONCLUSIONS: These results indicate that collaborative surgery by endoscopists and surgeons was feasible and safe, and may contribute to providing less invasive treatment than conventional surgery. Collaborative surgery is worth considering as a flexible and reliable surgical option, when cooperation may outperform either treatment alone.

DOI： 10.20524/aog.2024.0921

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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.

DOI： 10.1016/j.cgh.2023.05.021

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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.

DOI： 10.1111/codi.16751

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BACKGROUND: Comprehensive genomic analysis has shown that small bowel adenocarcinoma (SBA) has different genomic profiles from gastric and colorectal cancers. Hence, it is essential to establish chemotherapeutic regimens based on SBA characteristics. The expression of programmed cell death-ligand 1 (PD-L1) and programmed cell death-ligand 2 (PD-L2) in SBA is not fully understood. Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes (TILs); therefore, the status of TILs in the tumor microenvironment (TME) may influence their efficacy. The ratio of FoxP3+ to CD8+ T cells has been reported to be useful in predicting the prognosis of digestive system cancers. AIM: To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues. METHODS: We performed immunohistochemical analysis for PD-L1, PD-L2, CD8, FoxP3, and DNA mismatch repair (MMR) proteins using formalin-fixed, paraffin-embedded tissues from 50 patients diagnosed with primary SBA. The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins, and finally evaluated using the combined positive score (CPS). We assessed CD8+ and FoxP3+ T cells in the intratumoral and tumor-surrounding stroma. Subsequently, we calculated and summed the ratio of FoxP3 to CD8+ T cell counts. Immune-related cell densities were graded as low or high. Immunohistochemical results were compared with clinicopathological factors and patient prognosis. The distribution of cancer-specific survival (CSS) was estimated using the Kaplan-Meier method, and the log-rank test was used to test for significant differences in CSS. A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS. RESULTS: PD-L1 expression was positive in 34% in tumor cells (T-PD-L1) and 54% in tumor-infiltrating immune cells (I-PD-L1) of the cases examined. T-PD-L2 was positive in 34% and I-PD-L2 was positive in 42% of the cases. PD-L1 CPS ≥ 10 and PD-L2 CPS ≥ 10 were observed in 50% and 56% of the cases, respectively. Deficient MMR (dMMR) was 14% of the cases. T-PD-L1, I-PD-L1 and PD-L1 CPS ≥ 10 were all significantly associated with dMMR (P = 0.037, P = 0.009, and P = 0.005, respectively). T-PD-L1, I-PD-L1, and PD-L1 CPS ≥ 10 were all associated with deeper depth of invasion (P = 0.001, P = 0.024, and P = 0.002, respectively). I-PD-L2 expression and PD-L2 CPS ≥ 10 were significantly higher in the differentiated histological type (P = 0.015 and P = 0.030, respectively). The I-PD-L1 and I-PD-L2 levels were significantly associated with better CSS (P = 0.037 and P = 0.015, respectively). CD8-high was significantly associated with less lymph node metastasis (P = 0.047), less distant metastasis (P = 0.024), less peritoneal dissemination (P = 0.034), and earlier TNM stage (P = 0.047). The CD8-high group had better prognosis than the CD8-low group (P = 0.018). FoxP3 expression was not associated with any clinicopathological factors or prognosis. We found that patients with PD-L2 CPS ≥ 10 tended to have worse prognosis in the FoxP3/CD8-low group (P = 0.088). CONCLUSION: The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status. Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.

DOI： 10.3748/wjg.v29.i40.5566

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OBJECTIVES: Stigmata of recent hemorrhage (SRH) directly indicate a need for endoscopic therapy in acute lower gastrointestinal bleeding (LGIB). Colonoscopy would be prioritized for patients with highly suspected SRH, but the predictors of colonic SRH remain unclear. We aimed to construct a predictive model for the efficient detection of SRH using a nationwide cohort. METHODS: We retrospectively analyzed 8360 patients admitted through hospital emergency departments for acute LGIB in the CODE BLUE-J Study (49 hospitals throughout Japan). All patients underwent inpatient colonoscopy. To develop an SRH predictive model, 4863 patients were analyzed. Baseline characteristics, colonoscopic factors (timing, preparation, and devices), and computed tomography (CT) extravasation were extensively assessed. The performance of the model was externally validated in 3497 patients. RESULTS: Colonic SRH was detected in 28% of patients. A novel predictive model for detecting SRH (CS-NEED score: ColonoScopic factors, No abdominal pain, Elevated PT-INR, Extravasation on CT, and DOAC use) showed high performance (area under the receiver operating characteristic curve [AUC] 0.74 for derivation and 0.73 for external validation). This score was also highly predictive of active bleeding (AUC 0.73 for derivation and 0.76 for external validation). Patients with low (0-6), intermediate (7-8), and high (9-12) scores in the external validation cohort had SRH identification rates of 20%, 31%, and 64%, respectively (P < 0.001 for trend). CONCLUSIONS: A novel predictive model for colonic SRH identification (CS-NEED score) can specify colonoscopies likely to achieve endoscopic therapy in acute LGIB. Using the model during initial management would contribute to finding and treating SRH efficiently.

DOI： 10.1111/den.14533

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BACKGROUND: Subclinical stricture after esophageal endoscopic submucosal dissection (ESD) makes the detection and re-ESD of metachronous lesions difficult. This study aimed to investigate the effectiveness of prophylactic steroid use after esophageal ESD for mucosal defects with a circumference less than 75% for the prevention of symptomatic and asymptomatic stricture. METHODS: In 80 retrospectively enrolled patients, we collected paired endoscopic images of a mucosal defects immediately after resection and a scar thereafter. After calculating circumference by image analysis software, all patients were classified into three groups in reference to mucosal defect circumference (MDC; ≤ 50%, 50-75%, ≥ 75%). Frequency of steroid use and symptomatic stricture were compared, and in < 75% MDC patients, a degree of asymptomatic stricture with or without steroid was compared by calculating a scar contraction rate (SCR). RESULTS: In the ≤ 50% (43 patients), 50-75% (27 patients) and ≥ 75% (10 patients) MDC groups, steroids were used in 12%, 59% and 100%, respectively, and symptomatic stricture occurred in 0%, 7% and 40%, respectively. In < 75% MDC patients, SCR in the steroid cohort was significantly lower than that in the nonsteroid cohort (42% vs. 65%, p = 0.002). No steroid-related adverse events occurred. CONCLUSION: Steroid use even for mucosal defects with < 75% circumference appears effective for the reduction of the risk on both symptomatic and asymptomatic stricture after esophageal ESD.

DOI： 10.1007/s00464-023-09988-7

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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.

DOI： 10.1002/jgh3.12936

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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.

DOI： 10.1016/j.gie.2023.02.014

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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.

DOI： 10.1007/s00535-022-01945-w

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A 78-year-old man was admitted to our hospital with a tarry stool. Esophagogastroduodenoscopy identified tiny oozing on the greater curvature at the antrum. Despite repeated endoscopic hemostasis by coagulation and clipping, rebleeding occurred. On the third rebleeding, we performed endoscopic hand suturing to completely close the ulcer surface. Biopsy showing massive infiltration of eosinophils at the ulcer edge indicated eosinophilic gastritis. After the endoscopic closure by endoscopic hand suturing, the patient had no symptoms of bleeding thereafter and was discharged 19 days after the procedure by taking oral prednisolone. The patient remained well and was continuously treated with a small dose of steroids in outpatient. This is the first case report of the successful application of endoscopic hand suturing to a refractory hemorrhagic ulcer. Further accumulation of clinical experiences is desired to confirm the usefulness of this technique for the prevention of refractory ulcer bleeding.

DOI： 10.1002/deo2.207

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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.

DOI： 10.1016/j.gie.2022.07.025

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Pulmonary involvement associated with inflammatory bowel disease (IBD) are a rare extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), we herein presented two cases. Case 1: 53-year-old man with Crohn's disease treated with mesalazine and azathioprine. Pulmonary nodular shadows were incidentally detected on chest imaging, and revealed granulomas through transbronchial lung biopsy. Case 2: 68-year-old man with ulcerative colitis treated with mesalazine. He presented with fever and respiratory symptoms, and chest imaging showed multiple nodular infiltrates. He was diagnosed with organizing pneumonia by lung biopsy. Both cases were diagnosed to have pulmonary involvement associated with inflammatory bowel disease (IBD) according to multidisciplinary examination including positron emission tomography-computed tomography (FDG-PET) and pathological test. Pulmonary manifestations with IBD may not always require discontinuation of drugs or additional use of steroids or immunosuppressants.

DOI： 10.1016/j.rmcr.2023.101914

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INTRODUCTION: Endoscopic suturing of a mucosal defect is expected to prevent postoperative bleeding after endoscopic submucosal dissection (ESD). Endoscopic suturing causes mucosal deformity, which may interfere with endoscopic surveillance thereafter. We retrospectively investigated long-term chronological changes in mucosal suturing by endoscopic suturing. METHODS: Forty-three patients who underwent endoscopic hand suturing (EHS) after gastric ESD at three institutions were enrolled. First, our hypothesis that the suturing sites healed via inflammation, disappearance of mucosal inversion, and flattening was validated. Subsequently, the duration required to reach each healing step was evaluated. RESULTS: A total of 137 follow-up endoscopies were assessed, in which all cases showed the hypothesized chronological course on the suturing sites. The 95th percentiles of the duration when showing the disappearance of the inflammatory change and the inverted change were 63 days and 15.5 months after the procedure, respectively. DISCUSSION/CONCLUSION: The data show that the mucosal deformity induced by EHS disappeared within 16 months. Endoscopic suturing is thus considered to have a negligible effect on endoscopic surveillance following the procedure.

DOI： 10.1159/000527350

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BACKGROUND: Linked color imaging (LCI) improves detection of colorectal neoplastic lesions during colonoscopy. However, polyps <5 mm in diameter often do not require resection, and the benefits of LCI are unclear for detection of colorectal polyps ≥5 mm that are indicated for endoscopic resection in clinical practice. This randomized controlled trial compared rates of detection of adenoma polyps, stratified by size, for LCI and white light imaging (WLI). METHODS: We compared ADR (5 mm-) and PDR (5 mm-), which were defined as the proportion of patients with at least one adenoma or polyp with a diameter of 5 mm or larger in the LCI and WLI groups. Moreover, we estimated ADR and PDR for diameters between 5 and 10 mm (ADR (5-9 mm), PDR (5-9 mm) ) and for diameters larger than 10 mm (ADR (10 mm-), PDR (10 mm-) ). RESULTS: Data from 594 patients (LCI, n=305; WLI, n=289) were analyzed. ADR (5 mm-) and PDR (5 mm-) were significantly higher in the LCI group than in the WLI group (ADR (5 mm-): P=0.016, PDR (5 mm-): P=0.020). In the assessment of adenoma and polyp size, ADR (5-9 mm) and PDR (5-9 mm) were significantly higher in the LCI group than in the WLI group, although no significant differences were seen in ADR (10 mm-) and PDR (10 mm-) between these groups. CONCLUSIONS: Polyps ≥5 mm, which are indicated for endoscopic treatment, were more easily visualized with LCI mode than with WLI mode. The improvement in detection rate was obvious for polyps <10 mm, which are easier to miss.

DOI： 10.1272/jnms.JNMS.2023_90-117

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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.

DOI： 10.1159/000531646

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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.

DOI： 10.1159/000533744

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DOI： 10.1055/a-1884-0065

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The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

DOI： 10.3748/wjg.v28.i39.5658

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BACKGROUND : Prior studies have shown the effectiveness of both endoscopic band ligation (EBL) and clipping for colonic diverticular hemorrhage (CDH) but have been small and conducted at single centers. Therefore, we investigated which was the more effective and safe treatment in a multicenter long-term cohort study. METHODS : We reviewed data for 1679 patients with CDH who were treated with EBL (n = 638) or clipping (n = 1041) between January 2010 and December 2019 at 49 hospitals across Japan (CODE BLUE-J study). Logistic regression analysis was used to compare outcomes between the two treatments. RESULTS : In multivariate analysis, EBL was independently associated with reduced risk of early rebleeding (adjusted odds ratio [OR] 0.46; P < 0.001) and late rebleeding (adjusted OR 0.62; P < 0.001) compared with clipping. These significantly lower rebleeding rates with EBL were evident regardless of active bleeding or early colonoscopy. No significant differences were found between the treatments in the rates of initial hemostasis or mortality. Compared with clipping, EBL independently reduced the risk of needing interventional radiology (adjusted OR 0.37; P = 0.006) and prolonged length of hospital stay (adjusted OR 0.35; P < 0.001), but not need for surgery. Diverticulitis developed in one patient (0.16 %) following EBL and two patients (0.19 %) following clipping. Perforation occurred in two patients (0.31 %) following EBL and none following clipping. CONCLUSIONS : Analysis of our large endoscopy dataset suggests that EBL is an effective and safe endoscopic therapy for CDH, offering the advantages of lower early and late rebleeding rates, reduced need for interventional radiology, and shorter length of hospital stay.

DOI： 10.1055/a-1705-0921

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BACKGROUND: Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). METHODS: We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. RESULTS: The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. CONCLUSIONS: SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.

DOI： 10.1186/s12885-022-09824-6

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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.

DOI： 10.1016/j.gie.2021.12.023

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BACKGROUND: Endocytoscopy (ECS) aids early gastric cancer (EGC) diagnosis by visualization of cells. However, it is difficult for non-experts to accurately diagnose EGC using ECS. In this study, we developed and evaluated a convolutional neural network (CNN)-based system for ECS-aided EGC diagnosis. METHODS: We constructed a CNN based on a residual neural network with a training dataset comprising 906 images from 61 EGC cases and 717 images from 65 noncancerous gastric mucosa (NGM) cases. To evaluate diagnostic ability, we used an independent test dataset comprising 313 images from 39 EGC cases and 235 images from 33 NGM cases. The test dataset was further evaluated by three endoscopists, and their findings were compared with CNN-based results. RESULTS: The trained CNN required 7.0 s to analyze the test dataset. The area under the curve of the total ECS images was 0.93. The CNN produced 18 false positives from 7 NGM lesions and 74 false negatives from 28 EGC lesions. In the per-image analysis, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 83.2%, 76.4%, 92.3%, 93.0%, and 74.6%, respectively, with the CNN and 76.8%, 73.4%, 81.3%, 83.9%, and 69.6%, respectively, for the endoscopist-derived values. The CNN-based findings had significantly higher specificity than the findings determined by all endoscopists. In the per-lesion analysis, the accuracy, sensitivity, specificity, PPV, and NPV of the CNN-based findings were 86.1%, 82.1%, 90.9%, 91.4%, and 81.1%, respectively, and those of the results calculated by the endoscopists were 82.4%, 79.5%, 85.9%, 86.9%, and 78.0%, respectively. CONCLUSIONS: Compared with three endoscopists, our CNN for ECS demonstrated higher specificity for EGC diagnosis. Using the CNN in ECS-based EGC diagnosis may improve the diagnostic performance of endoscopists.

DOI： 10.1186/s12876-022-02312-y

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DOI： 10.1186/s12876-022-02259-0

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BACKGROUND: It is unclear whether prophylactic endoscopic closure after colorectal endoscopic submucosal dissection (ESD) reduces the risk of postoperative adverse events due to variability in lesion characteristics. Therefore, we conducted a retrospective study using propensity score matching to evaluate the efficacy of prophylactic clip closure in preventing postoperative adverse events after colorectal ESD. METHODS: This single-center retrospective cohort study included 219 colorectal neoplasms which were removed by ESD. The patients were allocated into the closure and non-closure groups, which were compared before and after propensity-score matching. Post-ESD adverse events including major and minor bleeding and delayed perforation were compared between the two groups. RESULTS: In this present study, 97 and 122 lesions were allocated to the closure and non-closure groups, respectively, and propensity score matching created 61 matched pairs. The rate of adverse events was significantly lower in the closure group than in the non-closure group (8% vs. 28%, P = 0.008). Delayed perforation occurred in two patients in the non-closure group, whereas no patient in the closure group developed delayed perforation. In contrast, there were no significant differences in other postoperative events including the rate of abdominal pain; fever, white blood cell count, and C-reactive protein; and appetite loss between the two groups. CONCLUSIONS: Propensity score matching analysis demonstrated that prophylactic closure was associated with a significantly reduced rate of adverse events after colorectal ESD. When technically feasible, mucosal defect closure after colorectal ESD may result in a favorable postoperative course.

DOI： 10.1186/s12876-022-02202-3

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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.

DOI： 10.1002/ueg2.12197

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BACKGROUND: The incidence of internal hernias has recently increased in concordance with the popularization of laparoscopic surgery. Of particular concern are internal hernias occurring in Petersen's space, a space that is surgically created after treatment for gastric cancer and obesity. These hernias cause devastating sequelae, such as massive intestinal necrosis, fatal Roux limb necrosis, and superior mesenteric vein thrombus. In addition, protein-losing enteropathy (PLE) is a rare syndrome involving gastrointestinal protein loss, although its relationship with internal Petersen's hernias remains unknown. CASE SUMMARY: A 75-year-old man with a history of laparotomy for early gastric cancer developed Petersen's hernia 1 year and 5 mo after surgery. He was successfully treated by reducing the incarcerated small intestine and closure of Petersen's defect without resection of the small intestine. Approximately 3 mo after his surgery for Petersen's hernia, he developed bilateral leg edema and hypoalbuminemia. He was diagnosed with PLE with an alpha-1 antitrypsin clearance of 733 mL/24 h. Double-balloon enteroscopy revealed extensive jejunal ulceration as the etiology, and it facilitated minimum bowel resection. Pathological analysis showed extensive jejunal ulceration and collagen hyperplasia with nonspecific inflammation of all layers without lymphangiectasia, lymphoma, or vascular abnormalities. His postoperative course was unremarkable, and his bilateral leg edema and hypoalbuminemia improved after 1 mo. There was no relapse over the 5-year follow-up period. CONCLUSION: PLE and extensive jejunal ulceration may occur after Petersen's hernia. Double-balloon enteroscopy helps identify and resect these lesions.

DOI： 10.12998/wjcc.v10.i1.323

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Esophageal submucosal hematoma is a rare disease mainly caused by mechanical stimulation to the esophageal wall. We reported a case of esophageal submucosal hematoma after transesophageal echocardiography (TEE) which was performed during cardiovascular surgery. The stimuli of TEE insertion under general anesthesia and the perioperative use of multiple antithrombotic agents were considered as a possible cause. This is the first report of esophageal submucosal hematoma related to TEE, and endoscopic ultrasonography should be carefully performed in patients, particularly at bleeding tendency and without consciousness.

DOI： 10.1159/000525036

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BACKGROUND AND AIMS: Noninvasive, imaging diagnosis of gastrointestinal mesenchymal tumors (GIMTs) is still difficult. This study aimed to develop a novel diagnostic method of GIMTs via endoscopic ultrasonography (EUS) using circularity. METHODS: In a derivation series, we retrospectively collected 50 GIMTs 2-5 cm in diameter of two institutions. After selecting one EUS still image showing the maximal area per lesion, two endoscopists who were blind to the histological diagnosis assessed circularity, a surrogate indicator of roundness (range, 0-1; 1 = a true circle), with an image-analyzing software. Median circularity of three types of GIMT was compared, and the cutoff value to differentiate a group from other groups was presented by drawing a receiver operating characteristic curve. Subsequently, we assessed the diagnostic ability of circularity in 91 GIMTs which were retrospectively collected from the other two institutions by using the optimal cutoff value presented in the derivation series. RESULTS: The circularity in leiomyomas indicated 0.70 and was significantly lower than that of gastrointestinal stromal tumors (0.89), schwannomas (0.90), and their combined group. When leiomyomas were diagnosed as the circularity of <0.8305, which was presented as the optimal cutoff value, the diagnostic accuracy, sensitivity, and specificity in the validation series were 73.6%, 80.0%, and 72.4%, respectively. CONCLUSION: The data demonstrated that leiomyomas significantly exhibited more distortion than other GIMTs. That implies that the difference in shape, which is objectively determined as circularity, is useful to noninvasively discriminate leiomyomas from other GIMTs.

DOI： 10.1159/000523881

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BACKGROUND AND AIMS: Surgery is recommended in early gastric cancer (EGC) after noncurative endoscopic submucosal dissection (ESD), although observation can be an alternative. We aimed to develop a tailor-made treatment strategy for noncurative EGCs by comparing the lymph node metastasis risk (LNMR) and the surgical risk. METHODS: We retrospectively identified 485 patients with differentiated-type, noncurative EGCs removed by ESD and classified them into two groups: a surgery-preferable group and an observation-preferable group, according to the clinical courses. Subsequently, LNMR and surgery-related death risk were assessed using a published scoring system and a risk calculator for gastrectomy, respectively. Finally, we investigated the optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to efficiently allocate these cases into either of two groups, surgery-preferable or observation-preferable. RESULTS: In 485 patients (surgery in 322, observation in 163), 57 and 428 patients were classified into the surgery-preferable group and the observation-preferable group, respectively. The optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to allocate the cases to the two preferable groups was 7.85 with the highest area under the curve (0.689). When cases with >7.85 LNMR over the surgery-related death risk were allocated into the surgery-preferable group and vice versa, the discriminability was 73.2%, which was sufficiently higher than that in the clinical decision (44.5%). CONCLUSION: Personalized comparison of LNMR and surgery-related death risk is helpful to provide a favorable treatment option for each patient with EGCs after noncurative ESD.

DOI： 10.1159/000523972

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Prevention of postoperative anastomotic leakage in rectal surgery is still required. This study investigated the feasibility of endoscopic hand suturing (EHS) on rectal anastomosis ex vivo. By using isolated porcine colon, we prepared ten anastomoses 6-10 cm from the virtual anus. Then, we sutured anastomoses intraluminally by EHS, which involved a continuous suturing method in 5 cases and a nodule suturing method with extra corporeal ligation in 5 cases. Completeness of suturing, number of stitches, procedure time and presence of stenosis were investigated. Furthermore, the degree of stenosis was compared between the two suturing methods. In all cases, EHS were successfully completed. The median number of stitches and procedure time was 8 and 5.8 min, respectively. Stenosis was created in all continuous suturing cases whereas none was seen in nodule suturing cases. The shortening rate was significantly greater in the continuous suturing method than in the nodule suturing method. Intraluminal reinforcement of rectal anastomosis by EHS using nodule suturing with extra corporeal ligation is feasible without stenosis, which may be helpful as a countermeasure against possible postoperative anastomotic leakage in rectal surgery.

DOI： 10.1038/s41598-021-01396-y

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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.

DOI： 10.14309/ajg.0000000000001413

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BACKGROUND: Three-dimensional (3D) visualization offers better depth recognition than two-dimensional (2D) imaging, thus helping to provide more useful information. We compared 3D and 2D endoscopy with regard to endoscopic recognition and endoscopic submucosal dissection (ESD) marking for superficial gastric neoplasia. METHODS: ESD marking was performed on half of a neoplasia margin under 2D observation and the on other half under 3D observation for 28 gastric lesions (26 early gastric cancers and 2 adenomas). The accuracy of ESD marking was evaluated based on the distance between the pathological and endoscopic neoplasia margins measured on histology sections of ESD specimens. The technical ease of ESD marking and endoscopic lesion recognition (lesion morphology, lesion extent, and comprehensive endoscopic cognition) were assessed using visual analog scale (VAS) questionnaires. RESULTS: The mean distance between the pathological and endoscopic margins under 3D observation (1.03 ± 0.80 mm) was significantly (p = 0.002) shorter than that under 2D observation (1.94 ± 1.96 mm). The VAS for technical ease of ESD marking under 3D observation was significantly better (p < 0.01) than that under 2D observation. The VAS for all aspects of endoscopic recognition under 3D observation was significantly better (p < 0.01) than under 2D observation. CONCLUSIONS: 3D flexible endoscopy achieved more accurate endoscopic recognition and ESD marking for superficial gastric neoplasia than a 2D approach in a clinical setting of ESD.

DOI： 10.1007/s00464-020-08124-z

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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.

DOI： 10.1038/s41598-021-99832-6

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BACKGROUND: Three-dimensional (3D) technology has been used in many fields, including flexible endoscopy. We evaluated the usefulness of 3D visualization for endoscopically diagnosing superficial gastric neoplasia. METHODS: Twelve participants (4 novices, 4 trainees and 4 experts) evaluated two-dimensional (2D) and 3D endoscopic still images of 28 gastric neoplasias, obtained before ESD with white-light imaging (WLI) and narrow-band imaging (NBI). Assessments of the delineation accuracy of tumor extent and tumor morphology under 2D and 3D visualization were based on the histopathological diagnosis of ESD specimens. Participants answered visual analog scale (VAS) questionnaires (0-10, worst to best) concerning the (a) ease of recognition of lesion morphology, (b) lesion extent and (c) comprehensive endoscopic cognition under 2D and 3D visualization. The endpoints were the accuracy of tumor extent and morphology type and the degree of confidence in assessing (a)-(c). RESULTS: The delineation accuracy of lesion extent [mean (95% confidence interval)] with WLI under 3D visualization [60.2% (56.1-64.3%)] was significantly higher than that under 2D visualization [52.3% (48.2-56.4%)] (P < 0.001). The accuracy with NBI under 3D visualization [70.3% (66.8-73.7%)] was also significantly higher than that under 2D visualization [64.2% (60.7-67.4%)] (P < 0.001). The accuracy of the morphology type with NBI under 3D visualization was significantly higher than that under 2D visualization (P = 0.004). The VAS for all aspects of endoscopic recognition under 3D visualization was significantly better than that under 2D visualization (P < 0.01). CONCLUSIONS: Three-dimensional visualization can enhance the diagnostic quality for superficial gastric tumors.

DOI： 10.1186/s12876-021-01829-y

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BACKGROUND: Gastrointestinal muscular sampling is useful in the histological assessment of functional gastrointestinal disorders. We devised a new sampling method to obtain a large volume of muscle tissues and then investigated the feasibility and safety of endoscopic muscular resection with a ligation device in an in vivo porcine model. METHODS: After establishing a submucosal tunnel, a rubber band was placed on the muscle tissue by sucking the exposed muscle layer. Thereafter, the established pseudopolyp was removed using an electrocautery snare, and the entry site of the submucosal tunnel was closed endoscopically. This procedure was performed at three sites in the esophagus and stomach of two pigs. The technical success, histology, and survival rate on postoperative day 7 were examined postoperatively. RESULTS: We successfully completed the mentioned procedure in 11 of the 12 sites (92%), without the occurrence of severe adverse events. The median diameters of obtained tissues from the esophagus and stomach, respectively, were 5 mm and 10 mm. Histologically, both the inner and outer muscle layers were included in all specimens. The postprocedural course was found uneventful in both pigs during the observatory period. CONCLUSIONS: Endoscopic muscular resection using a ligation device enabled us to obtain large and thick muscle tissue samples. This approach may facilitate more precise histological assessments of functional gastrointestinal disorders.

DOI： 10.1272/jnms.JNMS.2021_88-602

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A non-neoplastic epithelium (NE) often appears in gastric cancer (GC). We explored the histological features of NE in comparison between HP-eradicated and HP-infected GCs. We enrolled 40 HP-eradicated and 40 HP-infected GCs matched by size, macroscopic and histological type. NE was classified into full gland type and surface type; the former was a non-neoplastic gland isolated within cancer, and the latter was NE on the surface of the cancer. Surface type was additionally divided into NE at the cancer margin (marginal surface type) and NE inside cancer (internal surface type). The primary endpoints were the frequency and the length ratio (the ratio to cancer length) of NE. The secondary endpoints were the relationships between NE and clinicopathological factors, including endoscopic findings of a gastritis-like appearance (GLA), reddish depressed lesion (RDL), and white nodular mucosa (WNM). The frequency and length ratio of the internal surface type in HP-eradicated GCs were significantly higher (82.5% vs 50%, P = 0.005) and larger (11.6 ± 10.6 vs 4.2 ± 9.9, P < 0.001) than those in HP-infected GCs, and the increase was more significant according to the passage of time since HP eradication. The frequency and length ratio of marginal surface type and full gland type were not significantly different between the two groups, but the coexistence of internal surface and full gland types was statistically significant (p < 0.001). The frequencies of GLA, RDLs, and WNM in HP-eradicated GCs were significantly higher than those in HP-infected GCs. GLA-positive GCs were covered more widely by internal surface type than GLA-negative GCs (13.3% vs. 6.6%, P = 0.003). Various types of NE were noted in gastric cancer, and the internal surface type of NE was shown to be significantly linked to HP-eradicated cancer and GLA.

DOI： 10.1371/journal.pone.0248333

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With advancements in the development of flexible endoscopes and endoscopic devices and the increased demand for minimally invasive treatments, the indications of therapeutic endoscopy have been expanded. Methods of endoscopic treatment used for tissue removal, hemostasis, and dilatation are as follows. Endoscopic submucosal dissection (ESD) is considered the gold standard curative method for removal of gastrointestinal node-negative neoplasms, regardless of their size or the presence of ulcer formation. Laparoscopic endoscopic cooperative surgery (LECS), which incorporates ESD, was introduced for removal of lesions in deeper layers. Another technique is endoscopic full-thickness resection, which is challenging without the assistance of laparoscopy. In terms of hemostasis, management of iatrogenic bleeding after endoscopic treatment is an important issue. Shielding methods and suturing techniques have been introduced for large mucosal defects after ESD, and their efficacy has been investigated clinically. Peroral endoscopic myotomy (POEM) is a new alternative surgical approach for minimally invasive treatment of esophageal achalasia. Furthermore, endoscopic fundoplication after POEM was devised to prevent post-POEM gastroesophageal reflux disease. Many endoscopic treatments, including ESD, LECS, and POEM, have been introduced in Japan. With the aging of the population, more attention will be directed toward therapeutic endoscopy for elderly patients, because it is less invasive. Development of endoscopic treatments with expanded indications is expected.

DOI： 10.1272/jnms.JNMS.2021_88-109

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BACKGROUND: An appropriate traction of the target lesion is a key for a safe and secure ESD procedure. We proposed the flexible traction method (F-trac) which provided an optimal traction using an endoscopic hand-suturing (EHS) and investigated the usefulness of this technique for gastric ESD in-vivo porcine model. METHODS: In the F-trac method, a lesion was suspended by pulling proximal side of endoscope which was connected to the contralateral side with a barbed suture using the EHS technique just before starting the submucosal dissection. A single endoscopist performed conventional ESD (C-ESD) and F-trac ESD alternately for a total of ten simulating lesions of 3 cm in diameter in a live porcine stomach. The pig was rotated so that each lesion was positioned in the direction of the gravity. The procedure time, technical accuracy, adverse events, and the number of additional injection to the submucosal layer during dissection were evaluated. RESULTS: The total ESD procedure time in the F-trac group was significantly shorter than in C-ESD group (19.0 min vs. 30.6 min, p = 0.039). There were no significant differences between both groups in muscular layer damage, sample damage, perforation, and intraoperative bleeding. The number of additional injection in the F-trac group was significantly fewer than that in C-ESD group (0 times vs. 4.4 times, p = 0.027). CONCLUSIONS: In gastric ESD, F-trac might be useful for shortening the total procedure time. This method can facilitate optimal traction without disturbing the endoscopic visualization and the movement of endoscope.

DOI： 10.1007/s00464-020-07850-8

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BACKGROUND/AIMS: Three-dimensional (3D) flexible endoscopy, a new imaging modality that provides a stereoscopic view, can facilitate endoscopic hand suturing (EHS), a novel intraluminal suturing technique. This ex-vivo pilot study evaluated the usefulness of 3D endoscopy in EHS. METHODS: Four endoscopists (two certified, two non-certified) performed EHS in six sessions on a soft resin pad. Each session involved five stitches, under alternating 3D and two-dimensional (2D) conditions. Suturing time (sec/session), changes in suturing time, and accuracy of suturing were compared between 2D and 3D conditions. RESULTS: The mean suturing time was shorter in 3D than in 2D (9.8±3.4 min/session vs. 11.2±5.1 min/session) conditions and EHS was completed faster in 3D conditions, particularly by non-certified endoscopists. The suturing speed increased as the 3D sessions progressed. Error rates (failure to grasp the needle, failure to thread the needle, and puncture retrial) in the 3D condition were lower than those in the 2D condition, whereas there was no apparent difference in deviation distance. CONCLUSION: 3D endoscopy may contribute to increasing the speed and accuracy of EHS in a short time period. Stereoscopic viewing during 3D endoscopy may help in efficient skill acquisition for EHS, particularly among novice endoscopists.

DOI： 10.5946/ce.2019.207

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There is the East-West paradox in prevalence and phenotype of colonic diverticula, but colonic diverticular bleeding (CDB) is the most common cause of acute lower gastrointestinal bleeding worldwide. Death from CDB can occur in elderly patients with multiple comorbidities, thus the management of CDB is clinically pivotal amid the aging populations in the East and West. Colonoscopy is the key modality for managing the condition appropriately; however, conventional endoscopic hemostasis by thermal coagulation and clipping cannot achieve the expected results of preventing early rebleeding and conversion to intensive intervention by surgery or transcatheter arterial embolization. Ligation therapy by endoscopic band ligation or endoscopic detachable snare ligation has emerged recently to enable more effective hemostasis for CDB, with an early rebleeding rate of approximately 10% and very rare conversion to intensive intervention. Ligation therapy might in turn reduce long-term rebleeding rates by eliminating the target diverticulum itself. Adverse events have been reported with ligation therapy including diverticulitis of the ascending colon in less than 1% of cases and perforation of the sigmoid colon in a few cases, thus more data are necessary to verify the safety of ligation therapy. Endoscopic hemostasis is indicated only for diverticulum with stigmata of recent hemorrhage (SRH), but the detection rates of SRH are relatively low. Therefore, efforts to increase detection are also key for improving CDB management. Urgent colonoscopy and triage by early contrast-enhanced computed tomography may be candidates to increase detection but further data are necessary in order to make a conclusion.

DOI： 10.1111/den.13547

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INTRODUCTION: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. OBJECTIVE: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. METHODS: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. RESULTS: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. CONCLUSIONS: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

DOI： 10.1371/journal.pone.0241337

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BACKGROUND AND AIM: Helicobacter pylori infection is a primary cause of gastroduodenal ulcers. To investigate whether there is an association between H. pylori infection and small intestinal mucosal injury. METHODS: Patients were selected from a general pool of subjects who underwent capsule endoscopy for current or past obscure gastrointestinal bleeding. Characteristics including age, gender, history, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acid suppressant, diagnosis, and H. pylori infection were investigated. Patients infected with H. pylori had positive test result, ranging 30 days before to 30 days after capsule endoscopy. Patients diagnosed with inflammatory diseases, malignant tumors, etc. were excluded. All video images were re-evaluated to count small intestinal mucosal breaks. Eligible patient variables were compared. RESULTS: A total of 92 patients (30 infected with H. pylori/62 uninfected) were eligible. By univariate analysis of the number of mucosal breaks, patients treated with NSAIDs were found to have more mucosal breaks than patients untreated (38%: 8/21 vs. 18%: 13/71; p = 0.004), and the possible association was detected between patients infected with H. pylori and those who were not (67%: 14/21 vs. 37%: 26/71; p = 0.081). When comparing the H. pylori infected and uninfected patients, the rate of patients with mucosal breaks was greater in infected patients (47%: 14/30 vs. 11%: 7/62; p = 0.001). After excluding patients treated with NSAIDs, the number of mucosal breaks was also greater in patients infected with H. pylori (1.2 ± 1.5 vs. 0.38 ± 0.62; p = 0.001). CONCLUSION: There is a possibility that H. pylori infection induces small intestinal mucosal injury.

DOI： 10.1159/000494415

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GOALS: The aim is to elucidate the efficacy and safety of double-balloon endoscopy (DBE) for small bowel capsule endoscopy (SBCE) retrieval from small bowel stricture and to follow the outcome of the stricture where the SBCE was entrapped. BACKGROUND: The retention of SBCE is a serious adverse event and most retained capsules are retrieved by surgery. There is still no report analyzing the follow-up of patients with stricture after retrieval of entrapped SBCEs by DBE. METHODS: This study was designed a retrospective cohort study. Subjects were 12 consecutive patients with small bowel stricture where retrieval of entrapped SBCE was attempted using DBE. Success rate of the SBCE retrieval by DBE, surgical rate of the small bowel stricture, adverse events of DBE, and outcomes in the follow-up period were evaluated. RESULTS: Diagnoses were Crohn's disease, nonsteroidal anti-inflammatory drugs-induced enteropathy, ischemic enteritis, and carcinoma in 8, 2, 1, and 1 patients, respectively. SBCE was successfully retrieved in 11 of the 12 patients (92%). No adverse events were encountered in all endoscopic procedures such as retrieval of SBCEs and dilation of the strictures. Nine of the 12 patients (75%) did not undergo surgical treatment for the stricture where SBCE was entrapped through the follow-up period (mean, 1675±847 d). CONCLUSIONS: Retrieval of SBCEs using DBE was safe, had a high success rate, and was useful to evaluate the need for surgery. Seventy-five percent of patients with small bowel stricture where the SBCE was entrapped did not require surgery through approximately 5 years.

DOI： 10.1097/MCG.0000000000000335

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J02824&link_issn=&doc_id=20180907460003&doc_link_id=10.11231%2Fjaem.38.807&url=https%3A%2F%2Fdoi.org%2F10.11231%2Fjaem.38.807&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J05332&link_issn=&doc_id=20150318050008&doc_link_id=10.19020%2FJ05332.2015186574&url=https%3A%2F%2Fdoi.org%2F10.19020%2FJ05332.2015186574&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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