An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

Efficacy of the traction method for gastric endoscopic submucosal dissection: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: To overcome the technical difficulties associated with gastric endoscopic submucosal dissection (ESD), a novel traction device that can alter the direction of traction was developed. This study compared the efficacy and safety of conventional ESD versus those of traction-assisted gastric ESD. METHODS: Patients with a single gastric epithelial neoplasm were randomized to receive conventional (n = 75) or traction-assisted (n = 73) gastric ESD. The primary outcome was ESD procedure time. RESULTS: There were no differences between the conventional and traction-assisted groups with respect to treatment results or adverse events. The mean procedure time was similar for both groups (78.9 vs 88.3 minutes, respectively; P = .3); however, times for the traction device tended to be shorter for lesions in the lesser curvature of the upper or middle stomach (84.6 vs 123.2 minutes; P = .057). CONCLUSIONS: Traction-assisted ESD for lesions in the lesser curvature of the upper or middle stomach were shorter, thereby reducing the procedure time of conventional ESD. (Clinical trial registration: University Hospital Medial Information Network Clinical Trials Registry, identifier 000044450.).

Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion.

INTRODUCTION: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. METHODS: Participants in the present study comprised patients with severe thrombocytopenia (platelet count <50,000/µL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count ≥50,000/µL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. RESULTS: This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to be lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (-0.17%) than in the platelet transfusion group (6.79%, p = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, p = 0.045). The rate of achievement of platelet counts ≥50,000/µL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, p = 0.005). CONCLUSION: Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: analysis of a nationwide multicenter study.

BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.

Endoscopic N-butyl-2-cyanoacrylate and ethanolamine oleate injection is equivalent to balloon-occluded retrograde transvenous obliteration for preventing gastric variceal bleeding.

OBJECTIVES: Endoscopic injection sclerotherapy (EIS) is effective for temporary hemostasis, but EIS and balloon-occluded retrograde transvenous obliteration (BRTO) have been reported as effective for secondary prophylaxis of gastric varices (GV) bleeding. This study retrospectively compared EIS and BRTO in patients with GV in terms of the efficacy for secondary prevention of GV bleeding and effects on liver function. METHODS: From our database of patients with GV who underwent EIS or BRTO between February 2011 and April 2020, a total of 42 patients with GV were retrospectively enrolled. The primary endpoint was the bleeding rate from GV, which was compared between EIS and BRTO groups. Secondary endpoints were liver function after treatment and rebleeding rate from EV, compared between EIS and BRTO groups. Rebleeding rates from GV and EV and liver function after treatment were also compared between EIS-ethanolamine oleate (EO)/histoacryl (HA) and EIS-HA groups. RESULTS: Technical success was achieved for all EIS cases, but two cases were unsuccessful in the BRTO group and underwent additional EIS. No significant differences in bleeding rates or endoscopic findings for GV improvement were seen between EIS and BRTO groups. Liver function also showed no significant difference in the amount of change after treatment between groups. CONCLUSION: EIS therapy appears effective for GV in terms of preventing GV rebleeding and effects on liver function after treatment. EIS appears to represent an effective treatment for GV.

Nonrecurrence Rate of Underwater EMR for ≤20-mm Nonampullary Duodenal Adenomas: A Multicenter Prospective Study (D-UEMR Study).

BACKGROUND AND AIMS: Endoscopic resection of nonampullary duodenal adenoma is often challenging, and its technique has not yet been standardized. To overcome the practical difficulty of conventional endoscopic mucosal resection, underwater endoscopic mucosal resection (UEMR) was recently developed; therefore, we investigated the effectiveness and safety of UEMR for nonampullary duodenal adenoma. METHODS: A multicenter, prospective cohort study was conducted at 21 institutions in Japan. We enrolled patients with no more than 2 nonampullary duodenal adenomas ≤20 mm in size, who were planned to undergo UEMR. After UEMR, follow-up endoscopies were scheduled at 2 and 12 months after the procedure, and biopsy specimens were taken from the post-UEMR scars. The primary endpoint was the proportion of patients with histologically proven nonrecurrence at follow-up endoscopy and biopsy. RESULTS: A total of 155 patients with 166 lesions underwent UEMR. One patient with a non-neoplastic lesion in the resected specimen and 10 patients with 10 lesions who were lost to follow-up were excluded. Finally, 144 patients with 155 lesions who received all follow-up endoscopies were analyzed for the primary endpoint. The proportion of patients with proven nonrecurrence was 97.2% (n = 140 of 144; 95% confidence interval, 92.8%-99.1%) which exceeded the predefined threshold value (92%). Two cases of delayed bleeding (1.2%) occurred and they were successfully managed by clips. All recurrences were successfully treated by additional endoscopic treatment. CONCLUSIONS: This multicenter, prospective cohort study demonstrated effectiveness and safety of UEMR for nonampullary duodenal adenomas ≤20 mm in size. (University Hospital Medical Network Clinical Trials Registry, Number: UMIN000030414).

Risk Factors for Non-Ampullary Duodenal Adenocarcinoma: A Systematic Review.

INTRODUCTION: An increase in the incidence of duodenal adenocarcinoma has been recently reported. However, little is known about the risk factors for duodenal adenocarcinoma, which are important for screening purposes. We, therefore, aimed to conduct a systematic review to identify risk factors for non-ampullary duodenal adenocarcinoma. METHODS: A medical literature search was performed using electronic databases, including PubMed, Cochrane Library, Japan Medical Abstracts Society, and Web of Science. Studies that assessed the association between dietary habits, lifestyle behaviors, comorbidities, and non-ampullary duodenal adenocarcinoma were extracted. The Newcastle-Ottawa Scale was used to assess the risk of bias in individual studies, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the quality of evidence across studies included in this review. RESULTS: Out of 1,244 screened articles, 10 were finally selected for qualitative synthesis. In the general population, no consistent risk factors were identified except for Helicobacter pylori positivity, which was considered a risk factor in 2 studies, but the quality of evidence was considered very low because of the high risk of bias. In patients with familial adenomatous polyposis (FAP), Spigelman stage IV at initial endoscopy was considered a consistent risk factor in 3 studies. CONCLUSIONS: There are currently limited data regarding risk factors for non-ampullary duodenal adenocarcinoma, and no conclusive risk factors were identified in the general population. However, in patients with FAP, Spigelman stage IV was identified as a consistent risk factor. Further studies are needed to improve diagnosis and support effective clinical management of this malignancy.

The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer.

BACKGROUND AND AIM: Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. METHODS: We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. RESULTS: There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. CONCLUSIONS: Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.

Bleeding following Endoscopic Submucosal Dissection for Early Gastric Cancer in Surgically Altered Stomach.

INTRODUCTION: Few studies have focused on bleeding following endoscopic submucosal dissection (ESD) in surgically altered stomach. We aimed to reveal the bleeding risk in surgically altered stomach following ESD for early gastric cancer (EGC). METHODS: We enrolled patients with ESD for EGC at 33 institutions between 2013 and 2016. In study 1, we evaluated bleeding risk following ESD in surgically altered stomach, compared with whole stomach. In study 2, we evaluated factors associated with bleeding following ESD in patients with surgically altered stomach. RESULTS: Of 11,452 patients, 445 patients had surgically altered stomach with the bleeding rate following ESD of 4.9%. In study 1, the bleeding risk in surgically altered stomach was not significant (odds ratio [OR], 1.37; 95% confidence interval [CI], 0.87-2.17) in the multivariate logistic regression analysis. No significant results were obtained when the surgically altered stomach was subdivided into various types. In study 2, the multivariate logistic regression analysis revealed that independent risk factors for bleeding following ESD were ischemic heart disease (OR, 7.52; 95% CI, 2.00-28.25) and P2Y12 receptor antagonist (OR, 4.81; 95% CI, 1.21-19.14). DISCUSSION/CONCLUSION: In this nationwide study, we found that the bleeding risk of surgically altered stomach following ESD for EGC did not significantly differ from that of whole stomach. The risk factors for ESD in patients with surgically altered stomach were ischemic heart disease and P2Y12 receptor antagonist.

Influence of hospital volume on bleeding after endoscopic submucosal dissection for early gastric cancer in Japan: a multicenter propensity score-matched analysis.

BACKGROUND: Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume. METHODS: Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching. RESULTS: A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups. CONCLUSIONS: The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD.

Antithrombotics increase bleeding after endoscopic submucosal dissection for gastric cancer: Nationwide propensity score analysis.

OBJECTIVES: Post-operative bleeding is the most common adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Patients taking antithrombotic agents has increased. We evaluated the influence of antithrombotic agents on delayed bleeding in ESD for EGC. METHODS: This was a post hoc analysis of nationwide, multicenter, retrospective cohort study in Japan. Altogether, 11,452 patients who underwent ESD for EGC in 33 institutions between November 2013 and October 2016 were enrolled. The primary outcome was the incidence of delayed bleeding in patients with or without antithrombotic agents. The secondary outcome was the incidence of delayed bleeding in those who took each antithrombotic agent and the cessation status of its use compared with each matched pair of patients. We used propensity matching and inverse probability of treatment weighting (IPTW) analyses. RESULTS: There were 1353 matched pairs of patients. The incidence of delayed bleeding was 2.8% and 10.7% in those without and with antithrombotic agents, respectively (odds ratio [OR] 4.15, 95% confidence interval [CI] 2.88-5.99; P < 0.001). The IPTW analysis showed similar results (OR 4.21, 95% CI 3.48-5.08; P < 0.001). Antiplatelets, anticoagulants, and their combination increased such incidence. Heparin bridging therapy had high OR (8.80), and the continuation (OR 3.46) and cessation (OR 2.95) of antithrombotic agent use had similar risk. CONCLUSIONS: Antithrombotic agents increased the incidence of delayed bleeding in patients who underwent ESD for EGC. Continuing antithrombotics may be more appropriate than heparin bridging therapy.

Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score.

OBJECTIVE: Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC. DESIGN: This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration. RESULTS: A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c-statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01). CONCLUSIONS: In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

Efficacy of endoscopic preventive procedures to reduce delayed adverse events after endoscopic resection of superficial nonampullary duodenal epithelial tumors: a meta-analysis of observational comparative trials.

BACKGROUND AND AIMS: Although various procedures have been used to prevent serious adverse events after endoscopic resection of the duodenum, their effectiveness has not been determined. In this study, we conducted a systematic review and meta-analysis to determine whether endoscopic preventive procedures reduce delayed adverse events. METHODS: Studies on endoscopic treatment for superficial nonampullary duodenal tumors were selected. We compared the following 2 groups: the closure group, which underwent mucosal sutures and coverage of mucosal defects after resection, and the unclosed group, which did not. The primary outcome was the rate of delayed adverse events, including perforation and bleeding. The pooled risk ratios (RRs) of all outcomes investigated, the 95% confidence intervals (CIs), and P values were calculated. RESULTS: A total of 438 patients from 4 studies were included in the meta-analysis. The pooled overall adverse event rates in the closure group and unclosed group were 3.6% and 21.1%, respectively. This rate was significantly lower in the closure group (RR, 0.19; 95% CI, 0.10-0.38; P < .01; I2 = 0%), and the rate of delayed bleeding was significantly lower in the closure group (RR, 0.14; 95% CI, 0.06-0.33; P < .01; I2 = 0%). Regarding delayed perforation, the RR in the closure group was 0.39 (95% CI, 0.12-1.32; P = .13; I2 = 0%). CONCLUSIONS: Preventive procedures significantly reduced the risk of delayed adverse events by more than 80%. After endoscopic resection of the duodenum, the implementation of preventive procedures, including mucosal sutures and coverage of mucosal defects, to delay adverse events is strongly recommended.

Oral indigo carmine for the detection of colon adenoma.

OBJECTIVES: Colonoscopy is currently considered the optimal method to detect colorectal neoplasia; however, some adenomas remain undetected. While indigo carmine staining with a dye-spray catheter has demonstrated promising results for reducing the miss rate, we investigated the oral indigo carmine method. The aim of this study was to determine whether oral indigo carmine intake before standard colonoscopy increases the adenoma (and adenocarcinoma) detection rate (ADR) or the mean number of adenomas per patient (MAP). MATERIALS AND METHODS: The oral indigo carmine method was performed from April 2018 to July 2020 in two hospitals. Data were collected in a prospective manner and compared to the conventional group whose data were collected retrospectively and consecutively from January 2016 to March 2018. All data were anonymized. RESULTS: Among the 704 patients included, colonoscopies were completely performed in 693 patients (347 in the indigo group). The ADR did not significantly differ between the groups: 42.3% vs. 40.3% (indigo vs. conventional group; odds ratio: 1.13; 95% confidence interval: 0.9-1.33, p = .33). The MAP was significantly greater in the indigo group (1.15) than that in the conventional group (0.82; p = .009). The cecal intubation rate and time to cecal intubation did not differ between the indigo and conventional group (98.6% vs. 98.3%, p = .83, and 6.2 min vs. 5.9 min, p = .39, respectively). CONCLUSION: The routine use of oral indigo carmine does not lead to a higher ADR despite the higher MAP.

Influence of anticoagulants on the risk of delayed bleeding after gastric endoscopic submucosal dissection: a multicenter retrospective study.

BACKGROUND AND AIMS: Delayed bleeding after gastric endoscopic submucosal dissection (ESD) in patients receiving anticoagulants remains an unpreventable adverse event. Although direct-acting oral anticoagulants (DOACs) have superior efficacy in preventing thromboembolism, their effects on the occurrence of delayed bleeding remain unclear. This study aimed to elucidate the clinical effect of DOACs on delayed bleeding after gastric ESD. PATIENTS AND METHODS: We retrospectively examined 728 patients who received anticoagulants and were treated for gastric neoplasms with ESD in 25 institutions across Japan. Overall, 261 patients received DOACs, including dabigatran (92), rivaroxaban (103), apixaban (45) and edoxaban (21), whereas 467 patients were treated with warfarin. RESULTS: Delayed bleeding occurred in 14% of patients taking DOACs, which was not considerably different in patients receiving warfarin (18%). Delayed bleeding rate was significantly lower in patients receiving dabigatran than in those receiving warfarin and lower than that observed for other DOACs. Multivariate analysis showed that age ≥ 65, receiving multiple antithrombotic agents, resection of multiple lesions and lesion size ≥ 30 mm were independent risk factors, and that discontinuation of anticoagulants was associated with a decreased risk of bleeding. In multivariate analysis among patients taking DOACs, dabigatran therapy was associated with a significantly lower risk of delayed bleeding. CONCLUSIONS: The effects of DOACs on delayed bleeding varied between agents, but dabigatran therapy was associated with the lowest risk of delayed bleeding. Switching oral anticoagulants to dabigatran during the perioperative period could be a reasonable option to reduce the risk of delayed bleeding after gastric ESD.

Endoscopic ultrasonography shear wave as a predictive factor of endocrine/exocrine dysfunction in chronic pancreatitis.

BACKGROUND AND AIM: Chronic pancreatitis (CP) leads to permanent impairment of exocrine and endocrine functions. The endoscopic ultrasonography (EUS)-based Rosemont classification plays an important role in diagnosing CP. However, it is based on subjective judgment. In contrast, EUS shear wave measurement (EUS-SWM) has been established to be a precise method for evaluating tissue hardness. This study aimed to evaluate the utility of EUS-SWM in diagnosing CP and determining exocrine and endocrine dysfunctions. METHODS: We evaluated 40 patients who underwent EUS-SWM between January 2019 and January 2020. They were classified into the normal pancreas and early, probable, and definite CP groups following the Japan Pancreatic Society criteria. EUS-SWM value was compared between the normal pancreas group and the early, probable, and definite CP groups. The relationship between EUS-SWM value and exocrine/endocrine dysfunctions was also assessed. The cut-off value of EUS-SWM for diagnosing CP and exocrine/endocrine dysfunctions was investigated. RESULTS: The EUS-SWM value was positively correlated with the Japan Pancreatic Society criteria stages. The probable and definite CP groups had significantly higher EUS-SWM values than the normal group. The areas under the receiver operating characteristic curve for the diagnostic accuracy of EUS-SWM for CP, exocrine dysfunction, and endocrine dysfunction were 0.92, 0.78, and 0.63, respectively. The cut-off values of 1.96, 1.96, and 2.34 for diagnosing CP, exocrine dysfunction, and endocrine dysfunctions had 83%, 90%, and 75% sensitivity, respectively, and 100%, 65%, and 64% specificity, respectively. CONCLUSIONS: Endoscopic ultrasonography shear wave measurement provides objective assessment and can thus be an alternative diagnostic tool for diagnosing CP and exocrine/endocrine dysfunctions.

The incidence of non-ampullary duodenal cancer in Japan: The first analysis of a national cancer registry.

BACKGROUND AND AIM: Although duodenal cancer is rare, no epidemiological research on this disease has been conducted in Asian countries. We aimed to elucidate the incidence and clinical features of duodenal cancer in Japan using a large-scale national database. METHODS: Data of patients with primary duodenal cancer diagnosed from January 1, 2016, to December 31, 2016, were extracted from the Japanese national cancer registry. Excluding malignant neoplasm of the Vater's ampulla, we calculated the incidence among the population as a crude number of patients with duodenal cancer divided by the total Japanese population in 2016. We performed multivariate analyses using logistic regression models to identify risk factors for advanced cancer, defined as metastatic cancer or local invasion to adjacent organs. RESULTS: Data on 3005 patients were included. The incidence of duodenal cancer was 23.7 per 1 000 000 person-years. In total, 56.4% of cases were detected at the localized stage. In the localized cancer group, endoscopic resection was more frequently performed (48.0%), whereas in the advanced cancer group, surgery and chemotherapy were the major treatment options (39.3% and 41.5%, respectively). Multivariate analyses identified age ≥80 years (odds ratio [OR], 1.489; 95% confidence interval [CI], 1.113-1.992; P = 0.007), incidental detection (OR, 2.325; CI, 1.623-3.331; P < 0.0001), and precise examination for symptomatic patients (OR, 10.561; CI, 7.416-15.042; P < 0.0001) as independent risk factors for advanced cancer. CONCLUSIONS: Our study revealed the incidence of duodenal cancer in Japan. However, localized cancer was the major tumor stage at detection, resulting in a high rate of endoscopic resection.

Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan.

BACKGROUND AND AIM: This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS: We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated. RESULTS: Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1). CONCLUSION: We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

Novel endoscopic ultrasonography imaging technique for visualizing microcirculation without contrast enhancement in subepithelial lesions: Prospective study.

OBJECTIVES: Detective flow imaging for endoscopic ultrasonography (DFI?EUS) is a new imaging modality developed for detecting fine vessels without using ultrasound contrast agents. This study aimed to evaluate its utility by comparing it with a type of directional power Doppler (eFLOW) for subepithelial lesions (SELs). METHODS: Between January 2019 and January 2020, 28 patients with SELs undergoing DFI?EUS and eFLOW?EUS were enrolled. DFI?EUS and eFLOW?EUS assessing the vascularity in SELs were compared in terms of the rates of identification of intratumoral vessels. We also investigated how large vessels were depicted in both modalities based on surgical specimens as well as the detection rates of intratumoral vessels in gastrointestinal stromal tumors (GISTs) and non?GISTs using either DFI?EUS or eFLOW?EUS. RESULTS: Among 28 patients, 23 with pathological confirmation by EUS?guided fine?needle aspiration biopsy (EUS?FNAB) specimens were included. Of those 23 patients, the 10 who underwent surgical resection were selected for analysis. The rate of detection of intratumoral vessels in SELs was significantly higher on DFI?EUS (80%) than on eFLOW?EUS (30%) (P\xA0=\xA00.03). Comparison with surgical specimens revealed that detection rate for vessels with maximum size of less 1000\xA0µm was higher in DFI?EUS (66%) than that in eFLOW?EUS (0%). GIST patients had significantly higher positive rates (90%) of intratumoral vessels than non?GIST patients (31%) on DFI in 23 cases including EUS?FNAB specimens (P\xA0=\xA00.045). CONCLUSIONS: Detective flow imaging?EUS is more sensitive for depicting intratumoral vessels than eFLOW?EUS. Evaluation of intratumoral vessels on DFI?EUS is useful for identifying GISTs without contrast agents.