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.

[Case report:multiple gastrointestinal stromal tumors of the small intestine associated with von Recklinghausen disease].

Abdominal ultrasonography revealed a low echoic mass in the upper abdomen of a 65-year-old man. He was referred to our department, where abdominal CT revealed a tumor with a 30-mm contrast effect on the distal side of the inferior part of the duodenum. Endoscopy revealed a submucosal tumor in the same region, and ultrasonic endoscopy showed a low echoic mass with a clear boundary derived from the muscle layer. The duodenum was partially resected based on a diagnosis of suspected gastrointestinal stromal tumors (GIST), and the skin tumor was simultaneously resected. An elastic, soft, 30-mm tumor mass was found in the upper duodenum during surgery, and small nodules of 3-5mm were identified throughout the 110-cm length of the jejunum at intervals of 20-30cm. The histopathological diagnosis was GIST and immunostaining showed the mass to be c-kit and CD34 positive. We diagnosed the skin tumor as a neurofibroma (von Recklinghausen disease). Mutational analysis of c-kit in the resected specimen showed no mutation, therefore suggesting that imatinib would not be effective. Since the nodules remaining in the small intestine might also be GIST, we established a policy of regular imaging assessments.

Construction of a Model for Predicting the Severity of Diverticular Bleeding in an Elderly Population.

Objective To identify the risk factors for severe diverticular bleeding in an elderly population. Methods Using a comprehensive computerized hospital database, severe and non-severe diverticular bleeding cases were compared for 19 factors: the age, sex, body mass index, comorbid conditions (hypertension, cardiovascular disease, cerebrovascular disease, and chronic renal failure, including those undergoing dialysis), history of diverticular bleeding, use of low-dose aspirin, use of antiplatelet agent besides aspirin, use of anticoagulant agent, use of prednisolone, use of non-steroidal anti-inflammatory drugs, use of cyclooxygenase-2 selective inhibitors, changes in vital signs, hypoalbuminemia, bilateral diverticula, identification of bleeding lesion, and rebleeding. Severe bleeding was defined as the need for blood transfusion, emergency surgery, or vascular embolization. Patients A total of 258 patients were admitted for lower gastrointestinal bleeding between August 2010 and July 2020, among whom 120 patients over 65 years old diagnosed with diverticular bleeding were included in this study. Results Fifty-one patients (43%) had severe diverticular bleeding. Independent risk factors for severe diverticular bleeding were as follows: change in vital signs [odds ratio (OR), 5.23; 95% confidence interval (CI), 1.9-14.4; p=0.0014], hypoalbuminemia (OR, 12.3; 95% CI, 1.97-77.3; p=0.0073), bilateral diverticula (OR, 3.47; 95% CI, 1.33-9.02; p=0.011), and rebleeding (OR, 5.92; 95% CI, 2.21-15.8; p<0.001). The area under the receiver operating characteristic curve was 0.79 after cross validation. Conclusion Severe diverticular bleeding in elderly population may be predicted by changes in their vital signs, hypoalbuminemia, bilateral diverticula, and rebleeding.

Modified BEST-J Score Model Predicts Bleeding after Endoscopic Submucosal Dissection with Fewer Factors.

This study constructed a simplified post-endoscopic submucosal dissection (ESD) prediction model with a prognostic nutritional index (PNI). A total of 449 patients who underwent gastric ESD was included, divided with a ratio of 2:1, and assigned to the model or validation cohort. A prediction model of post-ESD (modified BEST-J score) was constructed using the model cohort. The modified BEST-J score was evaluated by comparing its accuracy to the BEST-J score in the validation cohort. Within 4 weeks of ESD, melena, hematemesis, or a 2 g/dL or greater decrease in hemoglobin level that required esophagogastroduodenoscopy was defined as post-ESD bleeding. In the model cohort, 299 patients were enrolled and 25 (8.4%) had post-ESD bleeding. Independent risk factors for post-ESD bleeding were use of P2Y12RA, tumor size > 30 mm, location of lesion at lower one-third of the stomach, and PNI ≤ 47.9. Constructing the modified BEST-J score based on these variables, the sensitivity, specificity, and positive likelihood ratio were 73.9%, 78.1%, and 3.37. When comparing the modified BEST-J score to the BEST-J score in the validation cohort, no significant difference was observed by ROC-AUC (0.77 vs. 0.75, p = 0.81). Modified BEST-J score can predict post-ESD bleeding more simply, with the same accuracy as the BEST-J score.

A multicenter prospective study of the treatment and outcome of patients with gastroduodenal peptic ulcer bleeding in Japan.

Gastroduodenal peptic ulcers are the main cause of nonvariceal upper gastrointestinal bleeding (UGIB). We believe that recent advances in endoscopic techniques and devices for diagnosing upper gastrointestinal tract tumors have advanced hemostasis for UGIB. However, few prospective multicenter studies have examined how these changes affect the prognosis. This prospective study included 246 patients with gastroduodenal peptic ulcers treated at 14 participating facilities. The primary endpoint was in-hospital mortality within 4 weeks, and the secondary endpoints required intervention and refractory bleeding. Subsequently, risk factors affecting these outcomes were examined using various clinical items. Furthermore, the usefulness of the risk stratification using the Glasgow-Blatchford score, rockall score and AIMS65 based on data from the day of the first urgent endoscopy were examined in 205 cases in which all items were complete there are two periods. Thirteen (5%) patients died within 4 weeks; and only 2 died from bleeding. Significant risk factors for poor outcomes were older age and severe comorbidities. Hemostasis was required in 177 (72%) cases, with 20 cases of refractory bleeding (2 due to unsuccessful endoscopic treatment and 18 due to rebleeding). Soft coagulation was the first choice for endoscopic hemostasis in 57% of the cases and was selected in more than 70% of the cases where combined use was required. Rockall score and AIMS65 predicted mortality equally, and Glasgow-Blatchford score was the most useful in predicting the requirement for intervention. All scores predicted refractory bleeding similarly. Although endoscopic hemostasis for UGIB due to peptic ulcer had a favorable outcome, old age and severe comorbidities were risk factors for poor prognosis. We recommend that patients with UGIB should undergo early risk stratification using a risk scoring system.

Successful Resolution of Fecal Impaction During Endoscopy Using a Looped Guidewire.

Fecal impaction is the impaired excretion of a large fecal mass, and mild cases are treated by enema and osmotic laxatives. However, treatment-resistant cases need more invasive alternatives. A woman in her 60s presented with abdominal discomfort. Her abdomen was soft and without tenderness. Computed tomography revealed a large mass of feces in her sigmoid colon and no intestinal dilatation proximal to the mass. Endoscopy confirmed a fecal mass occupying the lumen. A glycerin enema, oral administration of polyethylene glycol, and enteral administration of amidotrizoic acid during colonoscopy were ineffective. We maneuvered a guidewire to form a loop at the tip of an endoscope, with which we subdivided the mass for successful removal. The patient's abdominal discomfort disappeared immediately. Endoscopic disimpaction is far less invasive than surgery and should be considered when treating fecal impaction cases, without severe obstructive colitis, which are nonresponsive to conservative treatment.

Obstructive cholangitis by mucus from an intraductal papillary mucinous neoplasm with pancreatobiliary fistula treated by endoscopic septotomy and direct peroral cholangioscopy: a case report.

Intraductal papillary mucinous neoplasms (IPMNs) occasionally form a fistula to adjacent organs, resulting in obstructive jaundice and cholangitis due to mucus obstruction. Although some procedures such as endoscopic nasobiliary drainage are attempted, they often do not work adequately because of high mucus viscosity. Herein, we report the case of an 87-year-old man with obstructive cholangitis treated by endoscopic septotomy and mucus suction with direct peroral cholangioscopy using conventional endoscopy. The patient incidentally showed a branched-type IPMN in the pancreatic head on computed tomography (CT) approximately 10-years ago. Although the patient's tumor had grown slowly and he occasionally developed cholangitis, he did not want surgery. He was admitted to our hospital because of cholangitis by mucus obstruction with a PB fistula. Endoscopic retrograde cholangiopancreatography (ERCP) and septotomy were performed. Septotomy made the duodenal papilla a large orifice, thereby facilitating spontaneous drainage of mucus. In addition, conventional endoscopy with a large working channel enabled direct access into the orifice and smooth mucus suction, thereby alleviating his cholangitis. In conclusion, septotomy and direct peroral cholangioscopy using conventional endoscopy could be useful to control biliary tract infection and obstructive jaundice due to mucus obstruction from an IPMNs with PB fistula.

Case of pseudo-Meigs' syndrome caused by gastric cancer-related metastatic ovarian tumor with prolonged survival.

A 48-year-old woman presented with bilateral enlarged ovaries, ascites, bilateral pleural effusion, and advanced gastric cancer. Pleural fluid cytology did not reveal malignant cells. Oophorectomy, performed as a palliative procedure, was followed by rapid resolution of the pleural effusion and ascites. The patient was diagnosed with pseudo-Meigs' syndrome, and underwent chemotherapy followed by partial gastrectomy. At the last follow-up, 84 mo following oophorectomy, she was alive, and free of disease recurrence, despite not receiving any further treatment. Pseudo-Meigs' syndrome should be considered in patients with bilateral ovarian tumors, ascites and pleural effusion, and treatment such as oophorectomy may result in symptomatic improvement and better prognosis in similar patients.

Three cases of mediastinal pancreatic pseudocysts.

A rare complication of acute or chronic pancreatitis is the formation of a mediastinal pancreatic pseudocyst (MPP), which is caused by tracking of pancreatic fluids through anatomical openings of the diaphragm into the mediastinum. Herein, we report the imaging characteristics of three cases of this condition. Our results revealed three features in common: (i) the connection between the mediastinum and the pancreatic cystic lesion; (ii) the presence of pleural effusions; and (iii) imaging findings consistent with chronic pancreatitis, such as pancreatic atrophy and calcifications and dilatation and/or stricture of main pancreatic duct (MPD). Serial diameter changes of the MPD and of the adjacent pseudocysts were necessary for the determination of the therapeutic strategy used in each case.

Retinoic acid receptor alpha dominant negative form causes steatohepatitis and liver tumors in transgenic mice.

Although attention has focused on the chemopreventive action of retinoic acid (RA) in hepatocarcinogenesis, the functional role of RA in the liver has yet to be clarified. To explore the role of RA in the liver, we developed transgenic mice expressing RA receptor (RAR) alpha- dominant negative form in hepatocytes using albumin promoter and enhancer. At 4 months of age, the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes, including VLCAD, LCAD, and HCD, were down-regulated; on the other hand, peroxisomal beta-oxidation and its related enzymes, including AOX and BFE, were up-regulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinoma and adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RAR alpha/ beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.