ENDOSCOPIC TRANSPAPILLARY GALLBLADDER STENTING VERSUS NO STENTING AND THE RATE OF RECURRENCE IN ACUTE-CALCULOUS-CHOLECYSTITIS PATIENTS DURING COVID-19 SURGICAL LOCKDOWN: A RANDOMIZED TRIAL WITH A 6-MONTH FOLLOW-UP

Background & Aims: Minimal prospective data are available on intraoperative pancreatoscopy (IOP) for the diagnostic work-up of intraductal papillary mucinous neoplasia (IPMN). The aim of the current report is to summarize perioperative impact on patient management from an ongoing 5-year prospective cohort study of IOP in patients with pancreatic surgery for suspected or confirmed IPMN.

Methods: Prospective multicenter study in patients with main pancreatic duct (MPD) diameter >5mm on preoperative imaging and scheduled for surgery for suspected MPD IPMN or mixed-type IPMN in 8 centers from 6 countries. IOP was performed using SpyGlass™ DS Direct Visualization System or SpyGlass™ Discover Digital System (Boston Scientific Corporation, Marlborough, Massachusetts) at the time of the index pancreas resection. This was an observational cohort study in which IOP findings were permitted to be interpreted by and acted upon at the discretion of the local surgical team. Patients had postoperative follow-up before hospital discharge and at 4 weeks. Main endpoint was IOP technical success; secondary endpoints included influence of IOP on the surgical resection plan, and 4-week procedure-related serious adverse events (SAEs).

Results: Overall, 100 patients were included, mean age 68.9±8.8 years and 58% male. On preoperative imaging, 94 (94%) patients had IPMN involving the main duct. MPD dilation was >10 mm in 58%, and 5-9 mm in 42% of patients. The operative approach included 45 pancreaticoduodenectomies, 19 PPPD, 14 distal and 11 total pancreatectomies, and 11 other surgeries. Both open and minimally invasive approaches were utilized: 71 (71%) open, 23 (23%) robotic, and 6 (6%) laparoscopic. IOP was technically successful in 91 (91%) patients. In 25 patients (25%), the initial surgical plan was modified based on IOP findings. Their procedural modifications included one or more of the following: extension (8) or sparing (5) of additional parenchymal resection, avoidance of total pancreatectomy (6), removal of cast, stone, or sludge from the remnant duct (2), conversion to total pancreatectomy (3), or conversion from distal pancreatectomy to a pancreatoduodenectomy. (1). Ninety-eight (98.0%) of patients completed a 4-week follow-up visit, one missed the 4-week visit, and one died. There were 25 reported SAEs related to surgery with Clavien-Dindo classification ≥ III in 15 patients, including one Clavien-Dindo V. None were reported as related to IOP.

Conclusion: In this prospective multicenter study, IOP was technically highly feasible and led to changes in intraoperative decision-making in 25% of surgical patients with IPMN and main duct involvement, especially regarding extension or sparing of pancreatic parenchymal resection. No IOP-related SAEs occurred. (ClinicalTrials.gov number NCT03729453)

Background: Pancreatic fluid collections (PFC) may recur after initial successful endoscopic drainage of walled-off necrosis (WON). The most common reason is due to the presence of a disconnected main pancreatic duct (DPD), which has been noted in up to 40% of patients undergoing EUS-guided drainage. DPD can lead to an increased risk of pancreatic fluid recurrence following transmural stents removal. The primary aim of this study is to assess the role of magnetic resonance cholangiopancreatography (MRCP) for preventing PFC recurrence by evaluating the integrity of the main pancreatic duct.

Methods: This is a single-center retrospective cohort study of patients with WON who underwent EUS-guided drainage with lumen apposing metal stents (LAMS) between August 2014 and May 2022. Patients with pseudocysts or who did not achieve WON resolution were excluded. Patients were divided between two different groups: those with MRCP vs those without MRCP prior to removal of transmural stents. PFC recurrence was defined as a new collection that developed after resolution of WON as documented by cross-sectional imaging and/or endoscopic reports after transmural stent removal. Chi-Square analysis was performed to compare categorical variables. Independent sample t test was performed to compare means of continuous variables. Statistical significance was defined by p-value < 0.05.

Results: A total of 127 patients with diagnosis of WON were identified, of whom 47 had MRCP performed during endoscopic management (Table 1). In patients without MRCP, 13/80 (16.2%) had PFC recurrence vs 0/47 (0%; p=0.004) in those with MRCP performed. MRCP identified DPD in 12 (25.5%) patients, all of whom were managed with indefinite drainage with double-pigtail plastic stents (DPPS) without PFC recurrence. Those without MRCP, DPD was suspected in 17 patients, all of whom were managed with long term DPPS. In the remaining 63 (78.7%) patients without MRCP or mention of ductal integrity, PFC recurrence was noted in 13 (20.6%) (Figure 1). PFC recurrence was noted in all patients who were neither evaluated, nor had pancreatic duct integrity addressed. PFC recurrence was identified at a median interval of 201 days after transmural stents were removed. Among those with PFC recurrence, 11 patients (85%) had undiagnosed DPD, which was later confirmed after PFC recurrence (9 by MRCP, 2 by CT). Of these, 9 patients (82%) were managed with indefinite DPPS and 2 (18%) with percutaneous drains, all without further PFC recurrence.

Conclusion: In this study, patients with WON who underwent EUS-guided drainage had a lower rate of PFC recurrence when MRCP assessment for main pancreatic duct integrity guided removal vs retention of transmural stents. This difference was largely driven by the identification of DPD with MRCP and appropriate endoscopic management.

Background: Symptomatic PFCs are treated with transmural endoscopic placement of plastic or metal stents, with subsequent stent removal after PFC resolution. However, a subset of patients develops recurrent PFC and needs additional interventions. To prevent these outcomes, some studies have evaluated the role of leaving permanent transmural DPPS with conflicting results. In this systematic review and meta-analysis, we aimed to compare the efficacy and safety of leaving permanent DPPS vs. standard stent removal (SSR) in patients who had endoscopic transmural drainage and resolution of PFC.

Methods: A medical librarian conducted a comprehensive search of MEDLINE, EMBASE, and Cochrane Central, from database inception through September 2022. Studies comparing outcomes of permanent DPPS and SSR were included, as well as single arm studies with ≥10 patients with DPPS. Studies with <6 months of follow-up after PFC resolution, published as abstract alone, and not in English, were excluded. Two independent reviewers selected studies, extracted data, and assessed risk of bias. We evaluated the following outcomes after PFC resolution: A) PFC recurrence; B) need for re-interventions; C) adverse events after DPPS; and D) technical success for placement of DPPS. Meta-analysis was carried out using random-effect models. Pooled proportions were calculated to summarize the prevalence of outcomes and are reported with 95% confidence intervals (CI). A subgroup analysis was conducted based on type of PFC (disconnected pancreatic duct vs. other) and initial stent type (metal vs. plastic).

Results: A total of 16 studies met eligibility criteria, encompassing 1285 patients. Of these, 9 were comparative studies (including 2 RCTs) and 7 were single arm studies. Patients who underwent SSR at time of PFC resolution had 4.6 greater odds (95%CI 1.9-10.9; I² 45%) of developing a recurrent PFC as compared to those who had permanent transmural DPPS (23% [95%CI 14-31%] vs. 3% [95%CI 1-6%]). In addition, the SSR group had 2.8 greater odds (95%CI 1.3-6.2; I² 0%) of re-interventions than those in the DPPS group (14% [95%CI 7-20%] vs. 2% [95%CI 0-4%]). The treatment effect of DPPS on PFC recurrence and reinterventions did not change in subgroup analysis. Pooled long-term adverse events included 6% spontaneous migration (95%CI 3-9%), 2% bleeding (95%CI 1-3%), 1% perforation (95%CI 0-2%), 1% ulcer formation (95%CI 0-2%), and 2% other (95%CI 0-3%). The overall rate of technical success of DPPS placement was 93% [95%CI 86-99%); however, this was lower for patients who had metal vs. plastic stent at index endoscopic drainage (70% [95%CI 47-92%] vs. 99% [95%CI 98-100%]).

Conclusions: This meta-analysis suggests that permanent transmural DPPS after PFC resolution is safe and superior to standard stent removal in reducing the risk of PFC recurrence and reinterventions.

Background and aim:
Identifying patients at high-risk for ERCP-related adverse events, including pancreatitis, is essential for post-endoscopic discharge management. This study aims to assess two strategies, a urinary trypsinogen-2 (UT-2) dipstick combined with an ERCP discharge tool (based on patient- and procedure-related risk factors), for identifying patients with an increased risk of developing post-ERCP adverse events.
Methods:
Between August 2018 and March 2021, 268 patients undergoing ERCP were enrolled in this multicenter prospective cohort study. All patients received NSAID prophylaxis unless contra-indicated; PD stent placement was at the endoscopist's discretion. The UT-2 dipstick was performed two hours after the start of the ERCP. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the UT-2 dipstick, the discharge tool and combined strategies for all ERCP-related adverse events were calculated. All adverse events were defined according to the Cotton criteria and included post-ERCP pancreatitis, cholangitis, perforation and hemorrhage. Performance of all strategies for post-ERCP pancreatitis alone was a secondary outcome measure.
Results:
The 259 patients who met inclusion criteria comprised of 109 males (42%) with a median age of 68.7 (interquartile range [IQR] 54.6-76.9) and median BMI of 25.6 (IQR 23.1-29.4). Median ERCP duration was 24 minutes (IQR 14-38). In total, twenty-eight (11%) adverse events were observed, of which 16 (6%) were post-ERCP pancreatitis. The combination of discharge tool and UT-2 dipstick tested on 228 patients outperformed the individual strategies for all adverse events with a sensitivity of 54% (95% CI 33-75), specificity of 80% (74-86), PPV of 25% (17-34) and NPV of 94% (91-96) (Table 1). The observation group had a 25% (13/53) adverse event rate and the discharge group a 6% (11/175) adverse event rate (Figure 1). For post-ERCP pancreatitis alone, the performance of the combined strategies had a sensitivity of 64% (35-87), specificity of 79% (73-85), PPV of 17% (11-25) and NPV of 97% (94-99). This differentiated between a 17% (9/53) post-ERCP pancreatitis risk in the observation group and a 3% (5/175) risk in the discharge group.
Conclusions:
The combination of UT-2 dipstick and discharge tool performs better than either of the two strategies alone in predicting post-ERCP adverse events, with a 25% post-ERCP adverse event risk in the theoretical observation group and 6% in the early discharge group, facilitating post-ERCP discharge management. Future research should focus on redefining risk factors for adverse events in the era of improved prophylaxis. In addition, larger validation studies assessing UT-2 dipstick performance for post-ERCP pancreatitis are expected in the near future.
Registry number: Dutch Registry for Clinical Trials (NL 8486)

Background and aims: Endoscopic transpapillary gallbladder stenting (ETGS) has been proposed as one of the bridging options before surgery in acute cholecystitis (AC) patients whose cholecystectomy (CCY) could not be performed or deferred. We performed a randomized trial with a 6-month follow-up to compare the rate of recurrence in AC patients with deferred CCY between those who received and did not receive ETGS.
Methods: Between 2020-2022, eligible AC patients who were surgical candidates but could not have an early CCY during COVID-19 surgical lockdown, were randomized into group A (received ETGS) and group B (did not receive ETGS). Definitive CCY was performed after 3 months or later in both groups. We compared the rate of recurrent AC while waiting for CCY at 1, 3 and 6 months between the two groups.
Results: Of 95 patients with AC, 80 eligible patients were randomized into group A(n=40) and group B(n=40). Patients with early CCY(n=10), hemodynamic instability(n=4) and gallbladder perforation(n=1) were excluded. Nine patients(22.5%) in group A underwent ERCP just to receive ETGS. In group B, 22 patients(65%) underwent ERCP for stone extraction but did not receive ETGS. In group A, technical and clinical success rates were 90%(36/40) and 100%(36/36), respectively (Table). Among 36 patients who achieved ETGS, 21 patients had successful ETGS under fluoroscopy whereas 15 patients required additional cholangioscopy guidance for cystic duct cannulation. Four patients had an unsuccessful ETGS due to failure to pass the guidewire through the tortuous cystic duct(n=3) and inability to pass the stent through the small cystic duct(n=1). At 1 month, the rate of recurrence in group A was lower than those in group B but did not reach statistical significance [0%(0/40) vs. 7.5%(3/40);p=0.08]. At 3 and 6 months, group A had significantly lower rate of recurrence when compared to group B [0%(0/40) vs. 17.5%(7/40);p=0.006 and 0%(0/23) vs. 42.8%(9/21);p=0.001, respectively]. During 3-6 months, 17/40 and 19/40 patients received definitive surgery in group A and B, respectively. Kaplan-Meier analysis showed that the rate of recurrence in group A was significantly lower than those in group B (p=0.001) during follow-up (median 185 days;range 91-726 days) (Figure). Of those(n=80), 7 and 2 patients developed recurrence within 3 months (at day 11, 22, 29, 62, 78, 86, 90) and during 3-6 months (at day 137, 148), respectively. The management for recurrence included antibiotic only(n=6), percutaneous cholecystostomy(n=2) and urgent CCY(n=1).
Conclusions: ETGS could prevent recurrent AC in the patients with acute calculous cholecystitis whose CCY was deferred during COVID-19 surgical lockdown. Majority of recurrence developed within 3 months in those who did not receive ETGS. At 6-12 months, those who still waiting for surgery, ETGS was still effective to prevent recurrence.