Background and study aim: Endoscopic ultrasonography-guided transmural gallbladder drainage (EUS-GBD) has been proposed for the management of acute cholecystitis in high risk patients; however, little is known about the long-term outcomes of this treatment. The aim of this study was to evaluate the procedural and long-term outcomes of EUS-GBD with self-expandable metallic stent (SEMS). Patients and methods: Data for this retrospective study were obtained from a prospectively collected EUS database. Patients with acute cholecystitis who were deemed unsuitable for cholecystectomy were included. Study outcomes were technical and clinical success, adverse events, and stent patency. Results: EUS-GBD was technically and clinically successful in 62/63 patients (98.4 %; 95 % confidence interval [CI] 94.9 % – 100 %). Procedural adverse events included duodenal perforation (n = 1, 1.6 %) and self-limiting pneumoperitoneum (n = 2, 3.2 %), all of which resolved with conservative treatment. Long-term outcomes of EUS-GBD were evaluated in 56 patients who were followed for a median of 275 days (range 40 – 1185 days). Late adverse events developed in four patients (7.1 %; 95 %CI 5.7 % – 8.4 %), including asymptomatic distal stent migration (n = 2), and acute cholecystitis due to stent occlusion (n = 2). Two patients with occluded stent were successfully treated endoscopically (reintervention rate of 3.6 %). A total of 54 patients (96.4 %) had no recurrence of acute cholecystitis during follow-up. Median stent patency time was 190 days overall (range 15 – 1185 days) and 458 days (range 151 – 1185 days) for the 28 patients who were alive at the study end. The cumulative stent patency rate was 86 % at 3 years. Conclusions: EUS-GBD with an SEMS for acute cholecystitis showed excellent long-term outcomes and may be a definitive treatment in patients who are unsuitable for cholecystectomy because of advanced malignancy or high surgical risk.

Stereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC. We retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24–36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed. A total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients. LAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.

Surgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma, but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Herein, we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for molecular residual disease (MRD) in patients from the STAMP trial, which compared the efficacy of adjuvant capecitabine (CAP) vs. gemcitabine plus cisplatin (GemCis). Between July 2017 and November 2020, 101 patients were randomized 1:1 to receive GemCis (n = 50) or CAP (n = 51). Efficacy outcomes were analyzed with an extended follow-up of 19 months from the previous report. From a biomarker cohort of 89 patients, longitudinal plasma samples (n = 254) were prospectively collected post-surgery before ACT, and on-ACT at 12 and 24 weeks from cycle 1 day 1 (C1D1). ctDNA was evaluated using a personalized, tumor-informed, 16-plex PCR next-generation sequencing assay and was correlated with clinical outcomes. In the extended follow-up analysis, median disease-free survival (DFS) and overall survival did not significantly differ between the CAP and GemCis groups. Significantly inferior DFS was associated with ctDNA positivity before ACT (hazard ratio [HR] 1.8; p = 0.029), on-ACT at 12 weeks from C1D1 (HR 7.72; p <0.001), on-ACT at 24 weeks from C1D1 (HR 5.24; p <0.001), and anytime post-surgery (HR 3.81; p <0.001). Analysis of pre-treatment to on-treatment ctDNA dynamics revealed that serially ctDNA-negative patients exhibited a significantly longer DFS compared to those with sustained ctDNA positivity (HR 6.7; p <0.001) or those who turned ctDNA positive (HR 5.8; p <0.001). In patients with resected extrahepatic cholangiocarcinoma, ctDNA status and dynamics predicted recurrence during adjuvant therapy, and may help optimize clinical decision-making. The findings from this study highlight the critical role of ctDNA as a prognostic biomarker and monitoring tool for patients with resected extrahepatic cholangiocarcinoma. By demonstrating the superiority of ctDNA to predict disease recurrence compared to conventional biomarkers such as cancer antigen 19-9 and carcinoembryonic antigen, this study underscores its potential in guiding decision-making during adjuvant chemotherapy. These results may be crucial to refine post-surgical treatment strategies and improve patient outcomes. The practical application of ctDNA monitoring could lead to more personalized treatment approaches, enabling timely interventions based on molecular residual disease status. NCT03079427.

Jun-Ho Choi, Dong-Wan Seo, Tae Jun Song, Do Hyun Park, Sang Soo Lee, Sung Koo Lee, and Myung-Hwan Kim. Gut and Liver 1999;0:. https://doi.org/10.5009/gnl19123