High risk stigmata and treatment strategy for acute lower gastrointestinal bleeding: a nationwide study in Japan.

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.

Long-term Risks of Recurrence After Hospital Discharge for Acute Lower Gastrointestinal Bleeding: A Large Nationwide Cohort Study.

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.

Association of direct oral anticoagulant and delayed bleeding with pharmacokinetics after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Pharmacokinetic parameters, such as drug plasma level at trough, time to maximum plasma concentration (Tmax), and coagulation factor Xa (FXa) activity generally predict factors for the anticoagulant effects of direct oral anticoagulants (DOACs). Although GI bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacologic parameters. This study aimed to evaluate pharmacologic risk factors for post-ESD bleeding in patients taking DOACs. METHODS: We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions and investigated the association with post-ESD bleeding and pharmacologic factors, including plasma concentration and FXa activity at trough and Tmax. RESULTS: The incidence of post-ESD bleeding was 12.8% (14 of 109; 95% confidence interval [CI], 7.2-20.6). Although plasma DOAC concentration and plasma level/dose ratio at trough and Tmax varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893; P < .001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR], 1.192; 95% CI, 1.020-1.392; P = .027) and high anticoagulant ability analyzed by FXa activity at trough and Tmax (OR, 6.056; 95% CI, 1.094-33.529; P = .039). CONCLUSIONS: The incidence of post-ESD bleeding in patients taking DOACs was high, especially in older patients and with high anticoagulant effects of DOACs. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding.

Outcomes and recurrent bleeding risks of detachable snare and band ligation for colonic diverticular bleeding: a multicenter retrospective cohort study.

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.

Timing of colonoscopy in acute lower GI bleeding: a multicenter retrospective cohort study.

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.

Weekend Effect on Clinical Outcomes of Acute Lower Gastrointestinal Bleeding: A Large Multicenter Cohort Study in Japan.

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 < 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295-1.660; p < 0.001). CONCLUSION: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion.

Predictive factors of the clinical efficacy of ustekinumab in patients with refractory Crohn's disease: tertiary centers experience in Japan.

PURPOSE: Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab. METHODS: We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index < 150 and CRP < 0.3 mg/dL, and factors predictive of the induction and maintenance of dual remission were investigated. The cumulative continuation rates and safety of ustekinumab were assessed. RESULTS: The dual remission rates at weeks 8, 26, 52, and 104 were 31.9%, 37.9%, 47.5%, and 42.6%, respectively. A short disease duration (≤ 2 years) and higher baseline serum albumin levels (≥ 3.1 g/dL) were positively associated with dual remission at weeks 8 and 52. Meanwhile, higher serum CRP levels (≥ 1.19 mg/dL) were negatively associated with dual remission at week 8. The cumulative ustekinumab continuation rate was favorable, and no severe adverse events were found. CONCLUSION: A short disease duration and higher baseline serum albumin levels might be predictive of favorable therapeutic efficacy of ustekinumab in refractory CD. Induction efficacy appears to be lower in patients with higher serum CRP levels.

Early feeding reduces length of hospital stay in patients with acute lower gastrointestinal bleeding: A large multicentre cohort study.

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.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding - A Multicenter Nationwide Study.

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.

Development and validation of a novel model for predicting stigmata of recent hemorrhage in acute lower gastrointestinal bleeding: Multicenter nationwide study.

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.

Treatment strategies for reducing early and late recurrence of colonic diverticular bleeding based on stigmata of recent hemorrhage: a large multicenter study.

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.

Effectiveness and adverse events of endoscopic clipping versus band ligation for colonic diverticular hemorrhage: a large-scale multicenter cohort study.

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.

Efficacy of elobixibat as bowel preparation agent for colonoscopy: Prospective, randomized, multi-center study.

BACKGROUND AND AIM: Elobixibat is a novel ileal bile acid transporter inhibitor. This study aimed to compare the efficacy, tolerability, and safety of the combination of elobixibat and 1 L of polyethylene glycol formulation containing ascorbic acid (PEG-Asc) solution versus the combination of sodium picosulfate and 1-L PEG-Asc solution as bowel preparation for colonoscopy. METHODS: This multi-center, randomized, observer-blinded, non-inferiority study recruited 210 outpatients who were assigned to either the elobixibat plus 1-L PEG-Asc group (group A) or the sodium picosulfate plus 1-L PEG-Asc group (group B). The quality of the bowel cleansing level was assessed by the Boston Bowel Preparation Scale (BBPS) and compared the bowel cleansing level between the groups. Data regarding bowel preparation time, patients' tolerability, and adverse events were also analyzed. RESULTS: Data for 196 patients (99 in group A and 97 in group B) were analyzed finally. BBPS was comparable between group A and B (8.3 ± 0.9 vs. 8.3 ± 0.7; P = 0.88). Consequently, the adequate bowel preparation rate in groups A and B was 95.0% and 99.0%, respectively (-4.0%, 95% CI -9.3 to 1.5). Bowel preparation time in group A was similar to that in group B (348.2 ± 79.8 min vs. 330.8 ± 82.5 min; P = 0.13), whereas, sleep disturbance was significantly less frequent in group A than in group B (10.2% vs. 22.7%; P = 0.02). CONCLUSIONS: The combination of elobixibat and 1-L PEG-Asc can be considered an alternative bowel preparation for colonoscopy considering the equivalent bowel cleansing effect and less frequent sleep disturbance. The Japan Registry of Clinical Trials (jRCTs41180026).

Identifying Bleeding Etiologies by Endoscopy Affected Outcomes in 10,342 Cases With Hematochezia: CODE BLUE-J Study.

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.

Cumulative evidence for reducing recurrence of colonic diverticular bleeding using endoscopic clipping versus band ligation: Systematic review and meta-analysis.

BACKGROUND AND AIM: Either clipping or band ligation will become the most common endoscopic treatment for colonic diverticular bleeding (CDB). Rebleeding is a significant clinical outcome of CDB, but there is no cumulative evidence comparing reduction of short-term and long-term rebleeding between them. Thus, we conducted a systematic review and meta-analysis to determine which endoscopic treatment is more effective to reduce recurrence of CDB. METHODS: A comprehensive search of the databases PubMed/MEDLINE and Embase was performed through December 2019. Main outcomes were early and late rebleeding rates, defined as bleeding within 30 days and 1 year of endoscopic therapy for CDB. Initial hemostasis, need for transcatheter arterial embolization, or surgery were also assessed. Overall pooled estimates were calculated. RESULTS: Sixteen studies fulfilled the eligibility criteria, and a total of 790 participants were included. The pooled prevalence of early rebleeding was significantly lower for band ligation than clipping (0.08 vs 0.19; heterogeneity test, P = 0.012). The pooled prevalence of late rebleeding was significantly lower for band ligation than clipping (0.09 vs 0.29; heterogeneity test, P = 0.024). No significant difference of initial hemostasis rate was noted between the two groups. Pooled prevalence of need for transcatheter arterial embolization or surgery was significantly lower for band ligation than clipping (0.01 vs 0.02; heterogeneity test, P = 0.031). There were two cases with colonic diverticulitis due to band ligation but none in clipping. CONCLUSION: Band ligation therapy was more effective compared with clipping to reduce recurrence of colonic diverticular hemorrhage over short-term and long-term durations.

Propofol Sedation in the Endoscopy Room versus Operation Room during Endoscopic Submucosal Dissection for Gastric Tumors: A Propensity Score-Matching Analysis.

BACKGROUND/AIMS: The present study was performed to compare the safety of sedation with propofol during endoscopic submucosal dissection (ESD) for gastric tumors under sedation in the endoscopy room by an endoscopist versus sedation in the operation room by an anesthesiologist. METHODS: In total, 638 patients with gastric tumors who underwent ESD from January 2011 to August 2017 at Ureshino Medical Center and Saga Medical Center Koseikan were retrospectively reviewed. The patients were divided into 2 groups: those who underwent ESD in the endoscopy room (Group E, n = 532) and those who underwent ESD in the operation room (Group O, n = 106). Propensity score matching was applied for evaluation. The treatment outcome of ESD and the adverse events of sedation during ESD (desaturation, hypotension, bradycardia, and arrhythmia) were compared between the 2 groups to consider the safety of ESD. RESULTS: The propensity score-matching analysis created 82 matched pairs. Adjusted comparisons between Groups E and O showed similar treatment outcomes of ESD for gastric tumors. There were no significant differences in the treatment outcomes, anesthesia time, and mean propofol dose between the 2 groups. With respect to adverse events, desaturation occurred more often in Group E than Group O (18.3 vs. 3.7%, respectively; p = 0.005). There were no significant differences in other adverse events (hypotension, bradycardia, and arrhythmia) between the 2 groups. CONCLUSION: Sedation with propofol in the operation room might be required to ensure safer application of ESD for gastric tumors. However, a decrease in the desaturation rate was the only disadvantage of sedation in the endoscopy room.

An Investigation of Nine Patients with Gastrointestinal Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors.

INTRODUCTION/AIMS: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events (irAEs), of which there is little information in the literatures. The objective of this study was to characterize the clinical features of gastrointestinal irAEs (GI irAEs). MATERIALS AND METHODS: From a total of 250 patients who were administered anti-PD-1 antibodies (nivolumab and pembrolizumab), we retrospectively identified 9 patients with grade 2 or higher GI irAE based on medical records. Patient characteristics, clinical features, imaging and pathological findings, and treatment course were evaluated. RESULTS: Grade 2 or higher GI irAEs were observed in 9 (3.6%) patients. Of the 9 patients who experienced GI irAE, 8 were male, and mean age was 63.2 years. Five patients received nivolumab and 4 received pembrolizumab. The GI irAEs observed were diarrhea in 7 patients and bloody stool in 2 patients. Grade 2 GI irAEs were identified in 3 patients and grade 3 GI irAEs in 6 patients. The average time from ICI administration to the onset of GI irAEs was 22.2 weeks (range 7-56 weeks) for nivolumab and 19.7 weeks (range 11-28 weeks) for pembrolizumab. Endoscopic findings showed ulcerative colitis-like findings in 3 of 7 patients, and pathological examination revealed crypt epithelial cell apoptosis in 6 of 7 patients. Eight of the 9 patients received steroids, and 2 patients received infliximab additionally. All GI irAEs were manageable. CONCLUSIONS: Because of the lack of specific clinical, imaging, and pathological findings, information of ICI use was indispensable for diagnosis. Although GI irAEs are controllable by steroid and infliximab, further studies regarding management strategy will be needed.

Colorectal endoscopic mucosal resection with submucosal injection of epinephrine versus hypertonic saline in patients taking antithrombotic agents: propensity-score-matching analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) to remove colon polyps is increasingly common in patients taking antithrombotic agents. The safety of EMR with submucosal saline injection has not been clearly demonstrated in this population. AIMS: The present study aimed to evaluate the efficacy and safety of submucosal injection of saline-epinephrine versus hypertonic saline in colorectal EMR of patients taking antithrombotic agents. METHODS: This study enrolled 204 patients taking antithrombotic agents among 995 consecutive patients who underwent colonic EMR from April 2012 to March 2018 at Ureshino Medical Center. Patients were divided into two groups according to the injected solution: saline-epinephrine or hypertonic (10%) saline (n = 102 in each group). Treatment outcomes and adverse events were evaluated in each group and risk factors for immediate and post-EMR bleeding were investigated. RESULTS: There were no differences between groups in patient or polyp characteristics. The main antithrombotic agents were low-dose aspirin, warfarin, and clopidogrel. Propensity-score matching created 80 matched pairs. Adjusted comparisons between groups showed similar en bloc resection rates (95.1% with saline-epinephrine vs. 98.0% with hypertonic saline). There were no significant differences in adverse events (immediate EMR bleeding, post-EMR bleeding, perforation, or mortality) between groups. Multivariate analyses revealed that polyp size over 10 mm was associated with an increased risk of immediate EMR bleeding (odds ratio 12.1, 95% confidence interval 2.0-74.0; P = 0.001). CONCLUSIONS: Two tested solutions in colorectal EMR were considered to be both safe and effective in patients taking antithrombotic agents.

Risk Factors for Delayed Hemorrhage after Colonic Endoscopic Mucosal Resection in Patients Not on Antithrombotic Therapy: Retrospective Analysis of 3,844 Polyps of 1,660 Patients.

BACKGROUND/AIMS: Colonic endoscopic mucosal resection (EMR) is safe for patients without antithrombotic therapy; however, EMR is associated with several risks. This study was performed to evaluate the risk of delayed hemorrhage in patients undergoing EMR without antithrombotic therapy. METHODS: In the present retrospective single-center study, 1,792 patients without antithrombotic therapy underwent colonic EMR from March 2012 to December 2016 at the Saga Medical Centre Koseikan. Risk factors were evaluated with respect to patient and lesion characteristics, the endoscopist's experience, and preventive hemoclips. Delayed hemorrhage was defined as bleeding for which emergency endoscopic hemostasis was applied >24 h after EMR. RESULTS: Among the 1,792 patients, 1,660 with 3,844 tumors were evaluated. Delayed hemorrhage occurred in 43 patients (2.6%) and 46 polyps (1.2%). Preventive hemoclips were applied in 996 patients (60.0%). Univariate analysis indicated that delayed hemorrhage occurred more frequently in young patients (3-39 years, p < 0.001, 40-59 years, p = 0.005) compared to > 60 years and in association with large polyps (> 10 mm, p = 0.003), hemoclip (p = 0.019), and pedunculated polyps (p = 0.024). Multivariate analysis indicated that risk factors for hemorrhage were young age (age of 3-39 years p < 0.001, 40-59 years, p = 0.005) and large polyps (> 10 mm, p < 0.001). The risk of delayed hemorrhage was increased by an estimated 8% with a 1-mm increase in polyp size. CONCLUSION: The present study suggests that young age (under 60 years old) and large polyp size are risk factors for causing delayed hemorrhage after colonic EMR in patients without antithrombotic therapy.

[Recalcitrant pouchitis treated by budesonide foam:a case report].

This report presents the case of a 54-year-old man who had undergone restorative proctocolectomy with ileal pouch-anal anastomosis 15 years previously because of acute severe ulcerative colitis. After the operation, he experienced recalcitrant pouchitis and recurrent ulcer bleeding. There was a marked improvement in his symptoms following the administration of twice-daily budesonide 2mg foam injection for two months. Budesonide foam is suggested as a new therapy for pouchitis.