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Abstract Background and Objective Studies in humans and mice have demonstrated that the gut hormone glucagon-like peptide 2 (GLP-2) promotes gallbladder relaxation and refilling. Here, we assessed the effect of exogenous GLP-2 on gallbladder motility in the fasted state of healthy men with and without infusion of the potent gallbladder-contracting hormone cholecystokinin (CCK). Methods In a randomized, double-blind, placebo-controlled, crossover study, 15 male participants (mean [SD]: age 24.7 [3.6] years; body mass index 22.9 [1.6] kg/m2) underwent 4 experimental days receiving 2 infusions on each day: either CCK (0.4 pmol × kg−1 × min−1, time 0-180 minutes) + GLP-2 (10 pmol × kg−1 × min−1, time 30-240 minutes), CCK + placebo, placebo + GLP-2, or placebo + placebo, respectively. Gallbladder volume was measured at baseline and throughout the 4-hour study day using ultrasonography. Results Compared to placebo + placebo, GLP-2 + placebo did not affect gallbladder volume, but when infused in combination with CCK, GLP-2 completely abolished the strong gallbladder-contracting effect seen during CCK + placebo infusion, restoring baseline levels of gallbladder volume. Conclusion Exogenous GLP-2 counteracts exogenous CCK-induced gallbladder emptying in healthy men, pointing to a possible therapeutic potential for GLP-2 as a relaxing modulator of gallbladder smooth muscle tone (eg, as a bridge to surgery in biliary colic). The effect may also explain the gallbladder-related adverse events reported for GLP-2 receptor agonists used in the treatment of short bowel syndrome. Clinical Trial Registration number NCT04651868

PurposeThis study aims to evaluate the feasibility and efficacy of chemotherapy combined with irreversible electroporation (IRE) in patients with locally advanced gallbladder carcinoma (GBC) presenting as gallbladder masses.Materials and MethodsPatients with unresectable GBC masses of size greater than 2 cm and less than 6 cm without evidence of distant metastases and with no contraindication to general anaesthesia will be enrolled in the study. They will be randomized using computer generated table into two arms with 1:1 allocation ratio to include 15 patients in each group. Group I will be the chemotherapy alone arm and Group II will be the combined image-guided irreversible electroporation of the tumour and chemotherapy arm. The primary outcome assessed shall be the clinical benefit rate (complete response, CR; partial response, PR and stable disease, SD) based on the mRECIST criteria and overall survival. The secondary outcome shall be feasibility and safety of the procedure and quality of life pre and post procedure. The quality of life will be assessed by a questionnaire as given by EORTC-Quality of Life Group before starting therapy and 4 weeks after completion of therapy.Expected Gain of KnowledgeThe combined local and systemic effects of irreversible electroporation and systemic chemotherapy respectively may improve the outcomes in inoperable cases of gallbladder carcinoma.Trial RegistrationClinical Trials Registry – India (https://ctri.nic.in/Clinicaltrials/advancesearchmain.php). Identifier: CTRI/2021/05/033803. Primary Register of the International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/).Graphic Abstract

ObjectiveThe optimal management of acute cholecystitis in patients at very high risk for cholecystectomy is uncertain. The aim of the current study was to compare endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) to percutaneous cholecystostomy (PT-GBD) as a definitive treatment in these patients under a randomised controlled trial.DesignConsecutive patients suffering from acute calculous cholecystitis but were at very high-risk for cholecystectomy were recruited. The primary outcome was the 1-year adverse events rate. Secondary outcomes include technical and clinical success, 30-day adverse events, pain scores, unplanned readmissions, re-interventions and mortalities.ResultsBetween August 2014 to February 2018, 80 patients were recruited. EUS-GBD significantly reduced 1 year adverse events (10 (25.6%) vs 31 (77.5%), p<0.001), 30-day adverse events (5 (12.8%) vs 19 (47.5%), p=0.010), re-interventions after 30 days (1/39 (2.6%) vs 12/40 (30%), p=0.001), number of unplanned readmissions (6/39 (15.4%) vs 20/40 (50%), p=0.002) and recurrent cholecystitis (1/39 (2.6%) vs 8/40 (20%), p=0.029). Postprocedural pain scores and analgesic requirements were also less (p=0.034). The technical success (97.4% vs 100%, p=0.494), clinical success (92.3% vs 92.5%, p=1) and 30-day mortality (7.7% vs 10%, p=1) were statistically similar. The predictor to recurrent acute cholecystitis was the performance of PT-GBD (OR (95% CI)=5.63 (1.20–53.90), p=0.027).ConclusionEUS-GBD improved outcomes as compared to PT-GBD in those patients that not candidates for cholecystectomy. EUS-GBD should be the procedure of choice provided that the expertise is available after a multi-disciplinary meeting. Further studies are required to determine the long-term efficacy.Trial registration number NCT02212717

Incidentally detected gallbladder polyps (GBPs) and gallbladder wall thickening (GBWT) are frequently encountered in clinical practice. However, characterizing GBPs and GBWT in asymptomatic patients can be challenging and may result in overtreatment, including unnecessary follow-ups or surgeries. The Korean Society of Abdominal Radiology (KSAR) Clinical Practice Guideline Committee has developed expert recommendations that focus on standardized imaging interpretation and follow-up strategies for both GBPs and GBWT, with support from the Korean Society of Radiology and KSAR. These guidelines, which address 24 key questions, aim to standardize the approach for the interpretation of imaging findings, reporting, imaging-based workups, and surveillance of incidentally detected GBPs and GBWT. This recommendation promotes evidence-based practice, facilitates communication between radiologists and referring physicians, and reduces unnecessary interventions.

BackgroundIt is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8–15 mm based on preoperative ultrasound.MethodsThe independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables.ResultsIndependent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0–0.2), [0.2–0.5), [0.5–0.8) and [0.8–1] according to the total points of [− 337, − 234], [− 197, − 145], [− 123, − 108], and [− 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively.ConclusionA BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8–15 mm undergoing cholecystectomy based on preoperative ultrasound.

BackgroundWith the increasing realization of the importance of gallbladder function, choledochoscopic gallbladder-preserving surgery has been advocated for benign gallbladder diseases. However, limited information is available regarding the use of endoscopic gallbladder-preserving surgery (EGPS) for patients with benign gallbladder diseases. The aim of this study was to evaluate the feasibility of EGPS for benign gallbladder diseases.MethodsBetween June 2020 and January 2021, 22 patients with gallbladder stones and/or gallbladder polyps were treated with EGPS. The main outcome measures included the rate of complications, residual gallbladder stones, and gallbladder stone recurrence.ResultsIn this study, transgastric EGPS was successfully performed in 22 patients (13 female, 9 male) with benign gallbladder diseases, and included 8 cases of multiple gallstones, 4 cases of gallbladder polyps with gallstones, 6 cases of multiple gallbladder polyps, 2 cases of single gallstone, and 2 case of singe gallbladder polyp. The median time of transgastric EGPS was 118 min. During hospitalization, 4 patients suffered localized peritonitis (4/22, 18.2%), and these patients successfully recovered after conservative medical treatment. None of the patients experienced massive bleeding, delayed bleeding, diffuse peritonitis, or any other serious complications. During the median follow-up of 4 months, 1 patient suffered residual gallstone, while no gallstone recurrence or deaths related to transgastric EGPS occurred in any patients.ConclusionsTransgastric EGPS appears to be a feasible treatment method in selected patients with benign gallbladder diseases. However, as it is a new technique, further studies are needed to explore the long-term effectiveness of transgastric EGPS.

Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m2 on day 1 and oxaliplatin 100 mg/m2 on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7–5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6–7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61–1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5–11·5] in the chemotherapy alone group and 9·5 months [7·6–11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69–1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3–4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7–7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1–4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53–1·00; p=0·049). Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. None.

Background Gallbladder carcinoma (GBC) has a dismal prognosis even after curative resection. The objective of the study was to evaluate the effect of adjuvant chemotherapy in patients with GBC undergoing curative resection in a randomized control trial (RCT). Methods A single-center open-labeled prospective RCT was done from January 2012 to June 2018. R0 curative resected GBC patients were randomized in 1:1 to either surveillance alone (control group) or adjuvant chemotherapy (gemcitabine and cisplatin (GemCis group)) for 6 cycles. The primary outcome was disease-free survival (DFS), and the secondary outcomes were overall survival (OS) and toxicity profile. Results On the evaluation of 362 patients with GBC, 50 patients were enrolled in each control or GemCis group. Per protocol (PP), it comprised 96 patients. The demographic and clinical profile was similar between the two groups except in the lower nodal stage where patients were higher in the control group ( p  = 0.01). Recurrences were similar between groups (control 44% vs GemCis 56%; p  = 0.23). On the intention to treat (ITT), analyses of median DFS (not reached vs. 24 months, p  = 0.14) and OS (not reached vs. 31 months, p  = 0.10) were similar between groups. On PP, analyses of median DFS (not reached vs. 24 months, p  = 0.16) and OS (not reached vs. 31 months, p  = 0.09) were similar between groups. The common toxicity profile was hematological followed by gastrointestinal symptoms. Conclusions Adjuvant GemCis therapy for 6 cycles does not improve DFS or OS than R0 surgery alone patients with GBC. Trial Registration NCT02778308 ( https://www.clinicaltrials.gov )

Size of gallbladder polyps (GP) is considered as a relevant risk factor for neoplastic polyps. However, the definitive impact is an ongoing debate. Current German and European guidelines recommend surveillance for GP > 6 mm and cholecystectomy for GP > 10 mm over a period of two to five years. We aimed to analyze the dynamic growth of gallbladder polyps. Patients at Hanover Medical School who underwent sonography from 2001 to 2020 were retrospectively evaluated for growth rate (GR) of detected GP independent of the underlying primary disease. Only patients with at least one follow-up as well as accurate GP size data were included in the study. A number of 253 patients with GP were eligible. Median follow-up was 66 months (24-209 months). Median GR was -0.3 mm/year (IQR 0.79). A subgroup analysis (polyp size 6-10 mm) showed a positive GR in 20.3% of the cases with a median GR of 0.09 mm/year (IQR 0.17). Of note, in 46% of the patients GP were not detectable at follow-up exam. Overall, two patients reached the indication for cholecystectomy (0.8%), whereas only a single patient developed histologically confirmed gallbladder cancer (0.4%). Logistic regression analysis did not reveal any risk factors associated with GP growth. The majority of GP, which should be monitored within the current follow-up strategy, are no longer detectable sonographically over time or show a decreasing growth behavior. Only a minority shows a very slow positive GR and only a minority of patients develop malignancy.