Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Does endoscopic sphincterotomy contribute to the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis after endoscopic biliary stenting for malignant biliary obstruction? A multicenter prospective cohort study.

BACKGROUND: There is no consensus on the necessity of endoscopic sphincterotomy (ES) to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after endoscopic stenting in patients with malignant biliary obstruction. We investigated the incidence of PEP after endoscopic biliary stenting for malignant biliary obstruction with or without ES in a multicenter prospective cohort study. METHODS: We enrolled 807 patients who underwent endoscopic biliary stenting for malignant biliary obstruction with a native papilla at 36 hospitals between April 2017 and March 2018. The incidence of PEP in patients with or without ES was compared for subgroups based on stent type, placement method, and patient background. Univariate and multivariate analysis was performed to investigate the incidence of PEP in all stenting patients. RESULTS: Plastic and metal stents (MS) were inserted in 598 and 209 patients, respectively. The incidence of PEP in patients with or without ES was 7.9% and 7.4%, respectively among all stenting patients. The incidences of PEP with or without ES in plastic stent insertion patients, patients with MS insertion, stent insertions across the papilla, stent insertions across the papilla in patients without main pancreatic duct obstruction, and fully covered MS insertions across the papilla were compared. There was no overall significant difference in the incidence of PEP between those with or without ES. Multivariate logistic regression analysis for the incidence of PEP in all stenting patients revealed obstruction of the main pancreatic duct at the pancreatic head and epinephrine spraying on the papilla were significant factors; there was no significant difference in the incidence of PEP between patients with or without ES. CONCLUSION: Endoscopic sphincterotomy may not contribute to the prevention of PEP after endoscopic biliary stenting for malignant biliary obstruction, even in cases of insertion with a fully covered MS across the papilla.

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).

Performance of perioperative antibiotics against post-endoscopic submucosal dissection coagulation syndrome: a multicenter randomized controlled trial.

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

Extracutaneous neutrophilic infiltration of the spleen and lung associated with pyoderma gangrenosum of the skin.

We describe a patient with extracutaneous pyoderma gangrenosum (PG), who presented with chest pain. Histological examination showed extracutaneous neutrophilic infiltration of the spleen and lung, with later findings of PG.

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial.

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

[A case of difficult to diagnose duodenal gastrinoma].

A 42-year-old man, after remission of MALT lymphoma of the small intestine, was repeatedly hospitalized because of abdominal pain and severe dehydration caused by frequent vomiting and watery diarrhea. His symptoms would improve quickly every time when he was fasted and inserted a nasogastric tube. We were unable to find abnormalities on endoscopic examination and computed tomography. He was suspected to have gastrinoma because of active bleeding from a duodenal ulcer. High-level serum gastrin, endoscopic ultrasound, somatostatin receptor scintigraphy, and selective arterial calcium injection test were done. He was diagnosed with pancreatic gastrinoma in the pancreatic head by endoscopic ultrasound fine needle aspiration and subsequently underwent pancreatoduodenectomy. Histopathologic findings showed a 3-mm neuroendocrine tumor located in the duodenal submucosal layer. The presence of metastasis was confirmed in one of the peripancreatic lymph nodes. The pancreatic gastrinoma in the pancreatic head that we initially diagnosed was a lymph node metastasis behind the pancreas. Because additional resection was performed on the duodenum, we were able obtain a diagnosis of duodenal gastrinoma.

[A case of pancreatic neuroendocrine tumor with ring-like enhancement].

An 82-year-old female underwent contrast computed tomography (CT) that revealed multiple ring-like enhanced masses in the pancreatic tail. Additionally, the inside of the masses showed enhancement on contrast endoscopic ultrasound (EUS). She was diagnosed with a pancreatic neuroendocrine tumor on histopathological examination after EUS-guided fine-needle aspiration, and distal pancreatectomy and splenectomy were performed. In the resected specimen, toward the tumor center, tumor cells with lipid droplets and fibrosis were remarkably observed. These rare histopathological features well reflected the image findings of contrast CT and contrast EUS.

Histologic diagnosis of pancreatic masses using 25-gauge endoscopic ultrasound needles with and without a core trap: a multicenter randomized trial.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with 25-gauge needles yields small volume samples that are mainly processed for cytology. Using 25-gauge needles with a core trap may overcome this limitation. This trial compared 25-gauge needles with and without a core trap in terms of their ability to obtain histologic samples from solid pancreatic masses. PATIENTS AND METHODS: Consecutive patients with solid pancreatic masses who presented to eight Japanese referral centers for EUS-FNA in April - September 2013 were randomized to undergo sampling with a 25-gauge needle with a core trap (ProCore) or a standard 25-gauge needle. Tissue samples were fixed in formalin and processed for histologic evaluation. For the purpose of this study only samples obtained with the first needle pass were used for comparison of: (i) accuracy for the diagnosis of malignancy, (ii) rate of samples with preserved tissue architecture adequate for histologic evaluation, and (iii) sample cellularity. RESULTS: A total of 214 patients were enrolled. Compared to the first pass with a standard needle (n = 108), the first pass with the ProCore needle (n = 106) provided samples that were more often adequate for histologic evaluation (81.1 % vs. 69.4 %; P = 0.048) and had superior cellularity (rich/moderate/poor, 36 %/27 %/37 % vs. 19 %/26 %/55 %; P = 0.003). There were no significant differences between the two needles in sensitivity (75.6 % vs. 69.0 %, P = 0.337) and accuracy (79.2 % vs. 75.9 %, P = 0.561) for the diagnosis of malignancy. CONCLUSIONS: In patients with solid pancreatic masses, a 25-gauge EUS-FNA needle with a core trap provides histologic samples of better quality than a standard 25-gauge needle. There was no difference in accuracy for the diagnosis of malignancy between the needles. CLINICAL TRIAL NUMBER: UMIN000010021.

[A case of paralytic ileus associated with varicella zoster virus infection].

A 79-year-old woman with a history of pyothorax was admitted with a 4-day history of abdominal distension. Physical examination revealed marked abdominal distention, absent bowel sounds, and a vesicular rash over the left Th8-10 dermatome. Abdominal radiography showed gaseous distension of the colon and ileum. Colonoscopy excluded any obstructive process of the colon. Laboratory findings yielded positive results for serum IgM and IgG against the varicella zoster virus (VZV) . Paralytic ileus associated with the VZV was therefore diagnosed. The ileus improved after conservative treatment with intravenous acyclovir. Although shingles is frequently encountered, it is a rare cause of paralytic ileus. In the future, the VZV should be considered as one of the causes of paralytic ileus, and complete resolution can be achieved with conservative management.

Refractory Choledocholithiasis Causing Endogenous Endophthalmitis: A Case Report.

BACKGROUND Endogenous bacterial endophthalmitis is caused by a breach of the blood-ocular barrier by pathogens originating from distant infective foci. Here, we report a case of endogenous endophthalmitis due to cholangitis complicated by common bile duct stones, which is a rare source of infection. CASE REPORT A 73-year-old man with type II diabetes mellitus underwent endoscopic choledocholithotripsy 20 years ago and laparoscopic cholecystectomy 18 years ago. He had choledocholith-related cholangitis 6, 5, and 1 years previously and 4 times in the last year and underwent endoscopic choledocholithotripsy each time. Three days after the last surgery, the patient developed right endogenous endophthalmitis and vitrectomy was performed. Four months later, the patient relapsed with cholangitis and required surgery for recurrent endophthalmitis. Roux-en-Y choledochojejunostomy was performed with curative intent, and the patient was followed up for 5 years without recurrence of choledocholith, cholangitis, or endophthalmitis. CONCLUSIONS The recommended treatment strategy for patients diagnosed with common bile duct stones or choledocholithiasis is stone extraction. Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic intervention is a widely accepted procedure. However, in cases of recurrent choledocholithiasis, the rate of recurrence increases and the interval between ERCP becomes shorter in proportion to the number of recurrences. In such intractable cases requiring numerous sessions of endoscopic stone removal, bypass Roux-en-Y choledochojejunostomy should be performed to prevent possible rare complications such as endogenous bacterial endophthalmitis.

A case of pyloric gland adenoma with high-grade dysplasia in the duodenum arising from heterotopic gastric mucosa observed over 5 years.

Pyloric gland adenoma (PGA) in the duodenum is a rare gastric phenotype duodenal neoplasm. Although heterotopic gastric mucosa in the duodenum has been recognized as a benign lesion, it is a potential precursor of PGA and gastric phenotype adenocarcinoma. Herein, we present a case follow-up of endoscopic and histological changes in the PGA in the duodenum from low-grade to high-grade dysplasia. PGA was considered to arise from the heterotopic gastric mucosa, because the heterotopic gastric mucosa was observed in the initial examination. It is difficult to distinguish heterotopic gastric mucosa from PGAs, both endoscopically and histologically. This increase in size may be useful for their differentiation. Therefore, endoscopists should not underestimate the growth of the heterotopic gastric mucosa compared to that in the previous examination.

[A case of autoimmune pancreatitis with multifocal mass lesions].

We present a case of a 73-year-old man with multifocal autoimmune pancreatitis (AIP) in the pancreatic head and tail, and who had undergone sigmoidectomy and rectectomy 28 months before presenting to our department. Upon presentation, his serum IgG4 level was elevated at 267mg/dl, but tumor marker levels were within normal ranges. CT and MRI showed two localized pancreatic masses with delayed enhancement, but endoscopic retrograde pancreatography revealed neither stenosis nor dilatation of the main pancreatic duct. FDG-PET examination showed intense uptake in regions concordant with both tumors. The possibility of atypical AIP was a concern, but malignant tumor could not be clinically or radiologically excluded. Endoscopic ultrasonographic fine-needle aspiration biopsy was performed, but no malignant cells were detected. The patient underwent subsequent distal pancreatectomy. Histological evaluation of the tumors showed the presence of many IgG4-positive plasma cells without any evidence of malignancy.

Asystole-induced Bradycardia by Dexmedetomidine during Endoscopic Submucosal Dissection.

Although dexmedetomidine (DEX) is a widely used analgesic and sedative agent for endoscopic procedures, cardiovascular complications, such as bradycardia and hypotension, are frequently experienced. We herein report the first case of asystole-induced bradycardia due to DEX during endoscopic submucosal dissection (ESD). An 81-year-old man without cardiovascular diseases was referred for gastric carcinoma. ESD was started after administering a loading dose of DEX followed by a continuous maintenance infusion of DEX. The patient's heart rate gradually decreased, and then cardiac arrest occurred. DEX has a risk of cardiac arrest, so bradycardia should not be underestimated during sedation with DEX.

Ischemic enteritis resulting from polycythemia vera.

Polycythemia vera is a chronic myeloproliferative disorder characterized by clonal proliferation of bone marrow progenitors. We report a case of ischemic enteritis and bowel obstruction resulting from polycythemia vera. A 76-year-old man was admitted to our hospital with abdominal distention. Contrast-enhanced computed tomography revealed portal vein thrombosis, superior mesenteric vein thrombosis, and dilated small intestinal loops with caliber changes at the end of the ileum. Laboratory data on admission revealed increased leukocyte, red blood cell, hemoglobin, and platelet levels. Polymerase chain reaction analysis for Janus kinase 2 V617F point mutation was positive. Intestinal obstruction due to either bowel adhesion or paralytic ileus secondary to the superior mesenteric artery and vein thrombosis caused by polycythemia vera was diagnosed. For decompression of the small intestinal obstruction, a transnasal ileus tube was placed. Despite conservative therapy, the small intestinal obstruction did not improve remarkably. Therefore, we decided to perform surgical treatment. Operative findings revealed extensive stricture in the ileum. Altogether, 30 cm of the ileum, including the known intestinal strictures, was resected. The pathological findings were consistent with ischemic enteritis. To the best of our knowledge, no case of ischemic enteritis caused by polycythemia vera has been previously reported in the literature.

Perforation of a Gastric Tear during Esophageal Endoscopic Submucosal Dissection under General Anesthesia.

Mallory-Weiss tears (MWT) are occasionally encountered during endoscopic procedures. Esophageal endoscopic submucosal dissection (ESD) is widely performed under general anesthesia to avoid unexpected body movements. We present the case of a 68-year-old woman with squamous cell carcinoma. Although ESD was performed under general anesthesia, a gastric perforation at the MWT caused by gastric inflation was observed after the procedure. The perforation was closed endoscopically, and she was discharged without any sequelae. Although general anesthesia is useful for esophageal ESD, it should be noted that it can cause MWT, and in rare cases, gastric perforation, due to gastric inflation during the procedure.

A case of esophageal squamous cell carcinoma with neuroendocrine, basaloid, and ciliated glandular differentiation.

Esophageal carcinomas have multidirectional differentiation abilities and different histological components have been reported. Herein, we report a case of esophageal carcinoma with four different differentiations. A 64-year-old man was referred to our hospital for treatment of an esophageal tumor detected during an esophagogastroduodenoscopy, which revealed an elevated lesion accompanied by a slightly depressed lesion in the middle of the esophagus. Examination of the biopsy specimen obtained from the elevated lesion revealed an adenocarcinoma, while that from the depressed lesion revealed a squamous cell carcinoma. Fluorodeoxyglucose-position emission tomography and enhanced computed tomography showed an esophageal carcinoma in the middle of the esophagus with no signs of metastasis. The preoperative diagnosis was adenosquamous cell carcinoma classified as T2N0M0 according to the TNM classification (seventh edition). Thoracoscopic esophagectomy was performed. Examination of the resected specimen revealed esophageal squamous cell carcinoma with neuroendocrine, basaloid, and ciliated glandular differentiation. Although they may be totipotent, an esophageal carcinoma consisting of four components is extremely rare. Moreover, ciliated glandular differentiation is rarely observed in the esophagus, except in individuals with bronchial esophageal duplication cysts and adenocarcinoma arises from a Barrett's esophagus.

Sleep dysfunction in Japanese patients with gastroesophageal reflux disease: prevalence, risk factors, and efficacy of rabeprazole.

BACKGROUND AND AIM: Several studies performed in Western countries demonstrate the association between sleep dysfunction and gastroesophageal reflux disease (GERD), especially when nighttime heartburn is present. The purpose of this study was to examine the prevalence and risk factors of sleep dysfunction, and the effect of rabeprazole on reflux symptoms and sleep dysfunction in Japanese GERD patients. METHODS: A total of 134 GERD patients, including 82 patients with non-erosive reflux disease (NERD), were enrolled. Patients received rabeprazole 10 mg daily for 8 weeks. Patients were asked to complete both a frequency scale for symptoms of GERD (FSSG) questionnaire and a Pittsburgh Sleep Quality Index (PSQI) questionnaire at baseline and 8 weeks after treatment. RESULTS: Sleep dysfunction defined as a PSQI score >5.5 was found in 70 (52.2%) of the GERD patients. NERD was significantly associated with sleep dysfunction compared to erosive reflux disease (OR 2.18, 95% CI 1.05-4.53). However, other factors, including nighttime heartburn, were not associated with sleep dysfunction. Rabeprazole treatment significantly decreased both the FSSG and the PSQI score. CONCLUSION: The prevalence of sleep dysfunction was high among GERD patients. NERD was identified as a risk factor for sleep dysfunction. Use of a proton-pump inhibitor led to an effective decrease in sleep dysfunction. These results suggest a different pathogenesis of sleep dysfunction in Japanese GERD patients compared to GERD patients in Western countries. However, acid plays an important role in sleep dysfunction in all patients with GERD.

[A case of hepatocellular carcinoma with portal vein thrombus(Vp3)and lung metastases(stage IVB),which responded completely to treatment with Tegafur/Uracil].

A 65-year-old woman who had diffuse hepatocellular carcinoma(HCC)with tumor thrombus of right portalvein(Vp3) and lung metastases(Stage IVB)was treated by single-agent therapy with tegafur/uracil(UFT). As a result, primary and metastatic tumors were not recognized by diagnostic imaging, with a noted decrease of AFP, AFP-L3 and PIVKA-II. Generally, oral chemotherapy for HCC is not recommended because of the low response rate. However, there have been some reports including the present case which have showed a marked response with UFT. We thus conclude that UFT can be an option with low risk of crucial adverse effects in the treatment of selected HCC patients.

[A case of congenital esophageal stenosis that remained untreated until adulthood and was improved by endoscopic balloon dilatation].

A 20-year-old man had suffered from dysphagia since primary school. Upper gastrointestinal and endoscopy examinations revealed severe circumferential stenosis of the upper intra-thoracic esophagus. Secondary stenosis due to factors such as inflammation did not appear present, so congenital esophageal stenosis (CES) was diagnosed. Dysphagia improved after two endoscopic balloon dilatations. Almost all cases of CES are treated in baby-hood, and individuals who remain untreated until adulthood are rare. Check ups and diagnoses should be made taking CES into consideration, even in adults.