Aslanian, Harry R.

Abstract Endoscopic mucosal resection (EMR) techniques for large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) have expanded with the introduction of ablation and cold EMR. This study assessed adverse events (AEs) for the newer EMR techniques, including cold EMR, compared with hot EMR. We conducted a secondary analysis of four prospective multicenter studies of consecutive patients with LNPCPs undergoing EMR from 2019 to 2024. The primary outcome was serious AEs (SAEs) with cold and hot EMR. Secondary outcomes included SAEs in the hot EMR subgroups (no ablation [hEMR], margin ablation [hEMR-m], margin and base ablation [hEMR-mb]). 1762 patients (mean age 65.8; 1890 LNPCPs) were included: 522 cold and 1368 hot EMRs (368 hEMR, 770 hEMR-m, 230 hEMR-mb). SAEs were higher with hot EMR (4.7%, 95%CI 3.6%–5.9%) vs. cold EMR (1.9%, 95%CI 0.9%–3.5%), also for the subgroups of hEMR (6.0%, 95%CI 3.8%–8.9%), hEMR-m (3.9%, 95%CI 2.6%–5.5%), and hEMR-mb (5.2%, 95%CI 2.7%–8.9%). Serious postendoscopic bleeding (PEB) was numerically higher with hot EMR (2.3%, 95%CI 1.6%–3.3%) vs. cold EMR (1.3%, 95%CI 0.5%–2.7%), also for the subgroups of hEMR (3.0%, 95%CI 1.5%–5.3%), hEMR-m (1.9%, 95%CI 1.1%–3.2%), and hEMR-mb (2.6%, 95%CI 1.0%–5.6%). Perforation, intraprocedural and post-procedural, was numerically higher with hot EMR (1.2%, 95%CI 0.7%–2.0%) vs. cold EMR (0.2%, 95%CI 0.0%–1.1%). hEMR-m and hEMR-mb with clipping had lower rates of serious and overall PEB than no clipping. Cold EMR demonstrated lower rates of SAEs, serious PEB, and perforation compared with hot EMR. Perforation and mortality occurred almost exclusively after hot EMR. Hot EMR with margin +/− base ablation did not increase SAEs compared with hot EMR without ablation.

Background Complications of endoscopic mucosal resection (EMR) of large colorectal polyps remain a concern. Objective We aimed to compare safety and efficacy of cold EMR (without electrocautery) to hot EMR (with electrocautery) of large colorectal polyps. Design In this multicentre randomised trial, patients with any large (≥20 mm) non-pedunculated colon polyp were assigned to cold or hot EMR (primary intervention), and to submucosal injection with a viscous or non-viscous solution (secondary intervention) following a 2×2 design. The primary outcome was the rate of severe adverse events (SAEs). The secondary outcome was polyp recurrence. In this study, we report results of the primary intervention. Results 660 patients were randomised and analysed. An SAE was observed in 2.1% of patients in the cold EMR group and in 4.3% in the hot EMR group (p=0.10) (per protocol analysis 1.4 vs 5.0%, p=0.017) with fewer perforations following cold EMR (0%) compared with hot EMR (1.6%, p=0.028). Postprocedure bleeding did not differ (1.5% vs 2.2%, p=0.57). The effect of cold resection was independent of the type of submucosal injection solution, polyp size or antithrombotic medications. Recurrence was detected in 27.6% and 13.6% in the cold and hot EMR groups, respectively (p<0.001). Recurrence was not significantly different for 20–29 mm polyps (18.6% vs 13.4%, p=0.24) and for sessile serrated polyps (14.1% vs 8.5%, p=0.33). Conclusion Universal application of cold EMR did not significantly lower SAEs (unless cold EMR could be completed) and doubled the recurrence rate compared with hot EMR. Trial registration details ClinicalTrials.gov, number: NCT03865537 .

AbstractEUS-guided gallbladder drainage (EUS-GBD) using lumen apposing metal stents (LAMS) has excellent technical and short-term clinical success for acute cholecystitis (AC). The goals of this study were to determine the long-term clinical outcomes and adverse events (AEs) of EUS-GBD with LAMS.A multicenter, retrospective study was conducted at 18 US tertiary care institutions. Inclusion criteria: any AC patient with attempted EUS-GBD with LAMS and minimum 30-day post-procedure follow-up. Long-term clinical success was defined as absence of recurrent acute cholecystitis (RAC) > 30 days and long-term AE was defined as occurring > 30 days from the index procedure.A total of 109 patients were included. Technical success was achieved in 108 of 109 (99.1%) and initial clinical success in 106 of 109 (97.2%). Long-term clinical success was achieved in 98 of 109 (89.9%) over a median follow-up of 140 days (range 30–1188). On multivariable analysis (MVA), acalculous cholecystitis (odds ratio [OR] 15.93, 95% confidence interval [CI] 1.22–208.52, P = 0.04) and the occurrence of a LAMS-specific AE (OR 63.60, 95% CI 5.08–799.29, P <0.01) were associated with RAC. AEs occurred in 38 of 109 patients (34.9%) at any time, and in 10 of 109 (9.17%) > 30 days from the index procedure. Most long-term AEs (7 of 109; 6.42%) were LAMS-specific. No technical or clinical factors were associated with occurrence of AEs. LAMS were removed in 24 of 109 patients (22%). There was no difference in RAC or AEs whether LAMS was removed or not.EUS-GBD with LAMS has a high rate of long-term clinical success and modest AE rates in patients with AC and is a reasonable destination therapy for high-risk surgical candidates.

Abstract Background and study aim Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. Methods This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. Results In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02–1.08]), good access (OR 3.58 [1.94–9.59]), complete submucosal lifting (OR 2.28 [1.36–3.90]), en bloc resection (OR 5.75 [1.48–22.39]), and serrated histology (OR 2.74 [1.35–5.56]). Conclusions Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding.

OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs ( TBX15 , BMP3 ) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86–0.99), 0.71 (0.57–0.85), and 0.72 (0.60–0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77–0.94, P = 0.2). DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.