Bilateral verses bilateral with tri-segmental endoscopic drainage using metal stents for high-grade malignant hilar biliary obstructions: A multicenter, randomized controlled trial: BRAVE study (BRAVE study)

Introduction: Bilateral endoscopic drainage with self-expanding metallic stent (SEMS) can be used to manage hilar malignant biliary obstruction (HMBO) more effectively in comparison to unilateral drainage. An increased drainage area is predicted to prolong stent patency and patient survival. However, few reports have described the utility of trisegmental drainage and the benefits of using trisegmental drainage remain unknown. Thus, we launched a randomized clinical trial (RCT) to compare the clinical outcomes between bilateral and trisegmental drainage using SEMSs in patients with high-grade HMBO. Methods and analysis: This study was conducted as a multicenter randomized control trial (RCT) in 8 high-volume medical centers in Japan, and will prove the non-inferiority of bilateral drainage to trisegmental drainage. Patients with unresectable HMBO with Bismuth type IIIa or IV who pass the inclusion and exclusion criteria will be randomized to receive bilateral or trisegmental drainage at a 1:1 ratio. At each center, the on-site study investigators will obtain informed consent from the candidates, and will use an electronic data capture system (REDCap) to input necessary information, and register candidates with the registration secretariat. The primary endpoint is the rate of non-recurrent biliary obstruction (RBO) at 180 days after SEMSs placement. A -10% non-inferiority margin is assumed in the statistical analysis of the primary endpoint. Secondary endpoints include the rate of technical and clinical success, time to recurrent biliary obstruction (TRBO), causes of RBO, procedure-related adverse events (AEs), procedure time, TRBO with or without endoscopic sphincterotomy, overall survival, and the technical and clinical success rates at reintervention. Discussion: If the non-inferiority of bilateral drainage is demonstrated, it is predicted that the procedure time will be shortened and the medical cost will be reduced, which will be beneficial to the patient and the medical economy

A Case of Lobulated and Pedunculated Duodenal Hyperplastic Polyp Treated with Snare Polypectomy

We report herein the case of a lobulated and pedunculated hyperplastic polyp in the third portion of the duodenum causing anemia and occult blood in stools, which was detected by capsule endoscopy (CE) and treated with snare polypectomy. A 71-year-old man was referred to our hospital because of anemia and occult blood in stools. Three months earlier, he had been admitted to another hospital because of hemorrhage from gastric antral vascular ectasia (GAVE). Despite being treated for GAVE, hemoglobin decreased gradually. Esophagogastroduodenoscopy (EGD) and colonoscopy revealed no source of bleeding. However, CE revealed a polyp at the distal duodenum. Barium meal and EGD revealed a lobulated and pedunculated polyp in the third portion of the duodenum. The polyp was treated with snare polypectomy. Histopathological examination of the polyp revealed hyperplasia. After treatment of the polyp, the anemia improved gradually. To our knowledge, there are only 6 reported cases of a duodenal hyperplastic polyp, including our case. The polyp was pedunculated in only 2 cases and lobulated only in our case. Moreover, our case was diagnosed by CE. When a patient presents with anemia or obscure gastrointestinal bleeding undiagnosed by EGD and colonoscopy, CE is useful for detecting the bleeding lesion

Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer

We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer

A Comparison of the Efficacy of Plastic Stent Placement Above and Across the Sphincter of Oddi for Benign Biliary Hilar Stricture

We investigated the efficacy and safety of endoscopic plastic stent (PS) placement for hilar benign biliary strictures (BBSs) and compared cases with PS placement above (inside stent, IS) and across (usual stent, US) the sphincter of Oddi. Patients who underwent initial endoscopic PS placement for hilar BBSs between August 2012 and December 2021 were retrospectively analyzed. Hilar BBSs in 88 patients were investigated. Clinical success was achieved in 81 of these cases (92.0%), including 38 patients in the IS group and 43 patients in the US group. Unexpected stent exchange (uSE) before the first scheduled PS exchange occurred in 18 cases (22.2%). The median time from first stent placement to uSE was 35 days. There was no significant difference in the rate and median time to uSE between the two groups. The rates of adverse events such as pancreatitis or cholangitis in the two groups did not significantly differ. However, the rate of difficult stent removal in the IS group (15.8%) was significantly higher than that in the US group (0%) (p=0.0019). US placement is preferable to IS placement for scheduled stent exchange, as it offers the same effectiveness and risk of adverse events with easier stent removal

Endoscopic ultrasonography findings of pancreatic parenchyma for predicting subtypes of intraductal papillary mucinous neoplasms

Background and Aims: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS). Methods: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma. Results: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P Conclusions: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN

Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure

Background To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. Methods A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. Results The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5–43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. Conclusion Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy. Endoscopic biliary stent placement with endoscopic retrograde cholangiography (ERCP) for the treatment of malignant biliary obstruction (MBO) has been widely accepted as an effective drainage method because it is less invasive and safe and has a high success rate (1–3). However, MBO is treated using percutaneous transhepatic biliary drainage (PTBD) or surgical bypass because of difficulties related to endoscopic access to the bile duct following gastrointestinal reconstruction. However, these methods are associated with marked adverse event (AE) rates [1,2,3]. Recently, balloon-assisted endoscopy (BAE) facilitates ERCP in patients with surgically altered anatomy. As for a double-balloon enteroscope (DBE), a short-type DBE (sDBE) is especially useful because it allows the use of many standard ERCP accessories. The success rates of reaching the target site and ERCP-related interventions associated using these endoscopes range from 73–100% and 85–100%, respectively [4, 5]. We previously reported that the success rate of reaching the target site and biliary intervention was 93.8% and 95.7%, respectively, in patients with benign hepaticojejunostomy (HJ) anastomotic stricture [6]. However, inaccessibility of the target site may occur due to severe postoperative adhesions or a long insertion time (i.e., > 60 min). Furthermore, previous reports have shown that the success rate of BAE in MBO cases was significantly lower than that in benign biliary diseases [7, 8]. Few reports have investigated the outcome of BAE for MBO in patients with surgically altered anatomy. Additionally, the risk factors for clinical failure are not well-established. Thus, we retrospectively evaluated the outcomes of endoscopic treatment for MBO using sDBE in patients with surgically altered anatomy and identified risk factors for clinical failure

Optimal liver drainage rate for survival in patients with unresectable malignant hilar biliary obstruction using 3D-image volume analyzer

Background: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. Objectives: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. Design: This study was a single-center retrospective cohort study. Methods: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. Results: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with 80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p Conclusion: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report

BACKGROUND Gastric linitis plastica (GLP) is a subset of gastric cancer with a poor prognosis. It is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies, and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for GLP has been recently reported. Meanwhile, autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic syndrome. We herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with GLP. CASE SUMMARY An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after eating. His laboratory data revealed high levels of serum carbohydrate antigen 19-9 and immunoglobulin-G4. Endoscopic examinations showed giant gastric folds and reddish mucosa; however, no epithelial changes were observed. The gastric lumen was not distensible by air inflation, suggesting GLP. Computed tomography showed the thickened gastric wall, the diffuse enlargement of the pancreas, and the peripancreatic rim, which suggested autoimmune pancreatitis (AIP) coexisting with GLP. Because the pathological findings of the endoscopic biopsy showed no malignancy, he underwent an EUS-FNB and was diagnosed with GLP. He received chemotherapy for unresectable gastric cancer due to peritoneal metastasis, after which both the gastric wall thickening and diffuse enlargement of the pancreas were improved. CONCLUSION An EUS-FNB for GLP with a negative endoscopic biopsy is useful, and AIP may develop as a paraneoplastic syndrome

Efficacy of low dose rectal diclofenac for preventing post‐endoscopic retrograde cholangiopancreatography pancreatitis: Propensity score‐matched analysis

Background Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) decreases the incidence of post‐ERCP pancreatitis (PEP). However, the efficacy of low dose rectal NSAIDs for preventing PEP remains controversial. Methods We performed a retrospective study of 301 patients with native papilla and a body weight of Results A total of 66 pairs of patients in each group were selected. The patients and procedural‐related factors were similar in both groups. In total, 15 patients (11.4%) developed PEP: 12.1% (8/66) in the NSAIDs group and 10.6% (7/66) in the control group (Odds ratio (OR) 1.2; 95% confidence interval (CI) 0.4–3.5; P = 0.78). There was no significant difference in incidence of other adverse events related to ERCP between the two groups. Conclusions Prophylactic administration of a 25 mg dose of rectal diclofenac did not reduce the incidence of PEP in patients with a native papilla and a body weight of <50 kg in this study and a certain dose of rectal NSAIDs, such as a 100‐mg dose, should be administered regardless of body weight to prevent PEP