Detection of residual stones by peroral direct cholangioscopy in patients with intrahepatic stones after hepaticojejunostomy: a prospective study (with video).

BACKGROUND AND AIMS: The difficulty in radiographic confirmation of the presence of stones remains challenging in the treatment of intrahepatic bile duct (IHBD) stones in patients after hepaticojejunostomy (HJ). Peroral direct cholangioscopy (PDCS) enables direct observation of the bile duct and is useful for detecting and removing residual stones; however, its effectiveness is not clearly established in this clinical context. METHODS: This single-center, single-arm, prospective study included 44 patients with IHBD who underwent bowel reconstruction with HJ during the study period. Stone removal was performed by using short-type double-balloon enteroscopy. After balloon-occluded cholangiography, the double-balloon enteroscopy was exchanged for an ultra-slim endoscope through the balloon overtube for PDCS. The primary end point was the rate of residual stones detected by PDCS. Secondary end points were success rate of PDCS, residual stone removal with PDCS, procedure time for PDCS, procedure-related adverse events, and stone recurrence rate. RESULTS: PDCS was successful in 39 (89%) of 44 patients, among whom residual stones were detected in 16 (41%) (95% CI, 28%-54%). Twelve patients (75%) had residual stones <5 mm. Stone removal was successful in 15 (94%) patients, and median procedure time for PDCS was 16 minutes (interquartile range, 10-26 minutes). The rate of procedure-related adverse events was 7% (3 of 44); all adverse events improved with conservative treatment. During the median follow-up of 2.1 years (interquartile range, 1.4-3.3 years), the overall probability of recurrence-free status at 1, 2, and 3 years was 100%, 92%, and 86%, respectively. CONCLUSIONS: PDCS is a safe and effective procedure for complete stone removal in patients with IHBD stones after HJ.

Virtual indigo carmine chromoendoscopy images: a novel modality for peroral cholangioscopy using artificial intelligence technology (with video).

BACKGROUND AND AIMS: Accurately diagnosing biliary strictures is crucial for surgical decisions, and although peroral cholangioscopy (POCS) aids in visual diagnosis, diagnosing malignancies or determining lesion margins via this route remains challenging. Indigo carmine is commonly used to evaluate lesions during GI endoscopy. We aimed to establish the utility of virtual indigo carmine chromoendoscopy (VICI) converted from POCS images using artificial intelligence. METHODS: This single-center, retrospective study analyzed 40 patients with biliary strictures who underwent POCS using white-light imaging (WLI) and narrow-band imaging (NBI). A cycle-consistent adversarial network was used to convert the WLI into VICI of POCS images. Three experienced endoscopists evaluated WLI, NBI, and VICI via POCS in all patients. The primary outcome was the visualization quality of surface structures, surface microvessels, and lesion margins. The secondary outcome was diagnostic accuracy. RESULTS: VICI showed superior visualization of the surface structures and lesion margins compared with WLI (P < .001) and NBI (P < .001). The diagnostic accuracies were 72.5%, 87.5%, and 90.0% in WLI alone, WLI and VICI simultaneously, and WLI and NBI simultaneously, respectively. WLI and VICI simultaneously tended to result in higher accuracy than WLI alone (P = .083), and the results were not significantly different from WLI and NBI simultaneously (P = .65). CONCLUSIONS: VICI in POCS proved valuable for visualizing surface structures and lesion margins and contributed to higher diagnostic accuracy comparable to NBI. In addition to NBI, VICI may be a novel supportive modality for POCS.

Cysts or necrotic components in pancreatic ductal adenocarcinoma is associated with the risk of EUS-FNA/B complications including needle tract seeding.

BACKGROUND: EUS-FNA/B for pancreatic ductal adenocarcinoma (PDAC) is generally considered to be safe; however, while the incidence is low, there are occurrences of complications. Among these complications, there are serious ones like needle tract seeding (NTS), and it is not known than which types of tumors have the risks of EUS-FNA/B complications. This study aimed to evaluate the risk of EUS-FNA/B complications in patients with PDAC, focusing on morphological features. METHODS: Overall, 442 patients who underwent EUS-FNA/B for solid pancreatic masses between January 2018 and May 2022 in four institutions were retrospectively surveyed. Finally, 361 patients histopathologically diagnosed with PDAC were analyzed. Among these patients, 79 tumors with cysts or necrotic components were compared with 282 tumors without cysts or necrotic components. The incidence and risk of EUS-FNA/B complications including NTS were evaluated. RESULTS: There were 9 (2.4 %) of total EUS-FNA/B complications and 3 (0.8 %) of NTS. The incidence of total complication rate and NTS in tumors with cysts or necrotic components were significantly higher than in those without cysts or necrotic components (total complication 6.3 % vs. 1.4 %, p = 0.026, NTS 3.7 % vs. 0 %, p = 0.01). The transgastric route of puncture (OR: 93.3, 95 % CI: 3.81-2284.23) and the existence of cysts or necrotic components (OR: 7.3, 95 % CI: 1.47-36.19) were risk factors for EUS-FNA/B complications identified by the multivariate analysis. CONCLUSIONS: We should pay attention to the risks of EUS-FNA/B complications, including NTS, when the tumor has cysts or necrotic components.

The efficacy of non-anesthesiologist-administered propofol sedation with a target-controlled infusion system during double-balloon endoscopic retrograde cholangiopancreatography.

BACKGROUND: The sedation method used during double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) differs among countries and/or facilities, and there is no established method. This study aimed to evaluate the efficacy of non-anesthesiologist-administered propofol (NAAP) sedation using a target-controlled infusion (TCI) system during DB-ERCP. METHODS: This retrospective study was conducted between May 2017 and December 2020 at an academic center. One hundred and fifty-six consecutive patients who underwent DB-ERCP were sedated by gastroenterologists using diazepam (n = 77) or propofol with a TCI system (n = 79), depending on the period. The primary endpoint was a comparison of poor sedation rates between the two groups. Poor sedation was defined as a condition requiring the use of other sedative agents or discontinuation of the procedure. Secondary endpoints were sedation-related adverse events and risk factors for poor sedation. RESULTS: Poor sedation occurred significantly more often in the diazepam sedation group (diazepam sedation, n = 12 [16%] vs. propofol sedation, n = 1 [1%]; P = 0.001). Vigorous body movements (3 or 4) (diazepam sedation, n = 40 [52%] vs. propofol sedation, n = 28 [35%]; P = 0.038) and hypoxemia (< 85%) (diazepam sedation, n = 7 [9%] vs. propofol sedation, n = 1 [1%]; P = 0.027) occurred significantly more often in the diazepam sedation group. In the multivariate analysis, age < 70 years old (OR, 10.26; 95% CI, 1.57-66.98; P = 0.015), BMI ≥ 25 kg/m2 (OR, 11.96; 95% CI, 1.67-85.69; P = 0.014), and propofol sedation (OR, 0.06; 95% CI, 0.01-0.58; P = 0.015) were associated factors for poor sedation. CONCLUSIONS: NAAP sedation with the TCI system during DB-ERCP was safer and more effective than diazepam sedation.

A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents.

Background: This study aimed to assess the completion rate and postoperative bleeding incidence of endoscopic submucosal dissection (ESD) for gastric tumors under continuous antithrombotic therapy. Methods: A prospective observational study was conducted including 88 patients with 100 gastric lesions who underwent gastric endoscopic submucosal dissection (ESD) and received continuous antithrombotic therapy. Additionally, retrospective data on gastric ESD in 479 patients with 534 lesions who did not receive antithrombotic therapy were collected for comparison. Results: The en bloc resection rates (100% in the continuous antithrombotic therapy group vs. 100% in the non-antithrombotic therapy group) and complete resection rates (97.0% vs. 96.3%, respectively) were high and comparable between the groups. No significant differences were found in the specimen size or procedure time. Perforation rates were low (0% vs. 2.3%, respectively) and were not significantly different between the groups. However, postoperative bleeding occurred significantly more frequently in the continuous antithrombotic therapy group (10.2% vs. 4.2%, respectively) than in the non-antithrombotic therapy group. The subgroup analysis revealed a higher incidence of postoperative bleeding in patients receiving thienopyridine derivatives. Conclusions: Continuous administration of antithrombotic agents, especially thienopyridines, increased the risk of postprocedural hemorrhage following gastric ESD. These findings support the need for careful consideration of pharamcological management before ESD, aligning with the current guidelines.

MicroRNA-34a-5p: A pivotal therapeutic target in gallbladder cancer.

Gallbladder cancer incidence has been increasing globally, and it remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

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% drainage (n = 23) (450 days versus 224 days, p = 0.0033, log-rank test). TRBO was 201 (95% CI: 155-327) days and did not differ significantly by liver drainage rate. Multivariate Cox proportional hazards regression analysis revealed >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 < 0.0001) as significant prognostic factors. 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. Trail registration: Okayama University Hospital, IRB number: 2108-011.

MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway.

Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.

Hemosuccus Pancreaticus Due to the Rupture of a Pseudoaneurysm That Developed in an Intraductal Papillary Mucinous Neoplasm.

A 76-year-old woman with branch duct intraductal papillary mucinous neoplasm (IPMN) was admitted with epigastric pain and vomiting. She had received warfarin due to a history of deep vein thrombosis. A blood test showed decreased serum hemoglobin and elevated serum amylase. Contrast-enhanced computed tomography revealed acute pancreatitis and formation of a pseudoaneurysm in the IPMN. We suspected rupture of a pseudoaneurysm and performed trans-catheter angiography. Angiography showed extravasation from the posterior superior pancreaticoduodenal artery, and coil embolization was performed. It is important to be alert for the formation of pseudoaneurysm in patients with cystic neoplasms.

Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography for the Treatment of Common Bile Duct Stones in Patients with Roux-en-Y Gastrectomy: Outcomes and Factors Affecting Complete Stone Extraction.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in patients with Roux-en-Y gastrectomy (RYG) remains technically challenging. METHODS: Seventy-nine RYG patients (median 79 years old) underwent short-type double-balloon enteroscopy-assisted ERCP (sDBE-ERCP) for CBD stones at three referral hospitals from 2011-2020. We retrospectively investigated the treatment outcomes and potential factors affecting complete stone extraction. RESULTS: The initial success rates of reaching the papilla of Vater, biliary cannulation, and biliary intervention, including complete stone extraction or biliary stent placement, were 92%, 81%, and 78%, respectively. Of 57 patients with attempted stone extraction, complete stone extraction was successful in 74% for the first session and ultimately in 88%. The adverse events rate was 5%. The multivariate analysis indicated that the largest CBD diameter ≥ 14 mm (odds ratio (OR), 0.04; 95% confidence interval (CI), 0.01-0.58; p = 0.018) and retroflex position (OR, 6.43; 95% CI, 1.12-36.81; p = 0.037) were independent predictive factors affecting complete stone extraction achievement. CONCLUSIONS: Therapeutic sDBE-ERCP for CBD stones in a relatively elderly RYG cohort, was effective and safe. A larger CBD diameter negatively affected complete stone extraction, but using the retroflex position may be useful for achieving complete stone clearance.