The Durability of EUS-Guided Chemoablation of Mucinous Pancreatic Cysts: A Long-Term Follow-Up of the CHARM trial.

Pancreatic cancer has known precursor lesions with potential to develop into malignancy over time. At least 20% of pancreatic cancer evolves from mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which are often discovered incidentally.1,2 Current guidelines for the management of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms include long-term surveillance, which is expensive and nontherapeutic, or surgical resection, which is associated with major risk and may not be an option for patients with significant concomitant illness.3.

EMR combined with hybrid argon plasma coagulation to prevent recurrence of large nonpedunculated colorectal polyps (with videos).

BACKGROUND AND AIMS: EMR is the mainstay of therapy for large colorectal polyps. Local recurrence after EMR is common and can be reduced using margin ablation. Our aim was to evaluate recurrence rates when using hybrid argon plasma coagulation (h-APC) ablation after EMR. METHODS: Adult patients (aged 18-89 years) undergoing EMR of nonpedunculated colorectal polyps ≥20 mm were enrolled in a prospective multicenter study. h-APC was used to ablate all defect margins and also the resection surface in selected cases. The primary study outcome was recurrence rates found during the first follow-up colonoscopy. Secondary outcomes were technical success and adverse event rates. RESULTS: EMR with h-APC ablation was used in 101 polyps (84 patients, 46.4% women). EMR with h-APC ablation was technically successful in all cases (median EMR time, 15 minutes; median h-APC ablation time, 4 minutes). Median polyp size was 30 mm (range, 20-60). Resected polyps were either adenomas (68/101 [67.3%]), sessile serrated lesions (27/101 [27%]), or adenocarcinomas (6/101 [6%]). The post-EMR recurrence rate was 2.2% (2/91) (95% confidence interval, .27-7.71). All 6 patients with cancer (intramucosal cancer, 4; T1sm cancer, 2) were found to have complete eradication of the primary tumor after EMR with h-APC, and none had lymph node metastasis. Four serious adverse events occurred in 3 patients (2 delayed bleeding [2.4%], 1 abdominal pain [1.2%], and 1 microperforation [1.2%]. All serious adverse events resolved with either endoscopic or antibiotic treatment only. CONCLUSIONS: EMR with h-APC showed a high technical success rate, low adverse event rate, and very low post-EMR recurrence rates. (Clinical trial registration number: NCT04015765.).

Hybrid argon plasma coagulation-assisted endoscopic mucosal resection for large sessile colon polyps to reduce local recurrence: a prospective pilot study.

BACKGROUND: Endoscopic mucosal resection (EMR) of large, sessile colon polyps often results in incomplete resection with subsequent recurrence. The aim of this prospective pilot study was to evaluate the efficacy and safety of a novel technique, hybrid argon plasma coagulation-assisted EMR (hAPC-EMR), to remove large, sessile polyps. METHODS: 40 eligible patients underwent hAPC-EMR for the removal of one or more nonpedunculated colon polyps ≥ 20 mm. Participants were contacted 30 days post-procedure to assess for adverse events and were recommended to return for a surveillance colonoscopy at 6 months to assess for local recurrence. RESULTS: At the time writing, 32 patients with 35 polyps (median size 27 mm; interquartile range 14.5 mm) resected by hAPC-EMR had undergone the 6-month follow-up colonoscopy. Recurrence rate was 0 % (95 % confidence interval [CI] 0-0) at follow-up. Post-polypectomy bleeding was experienced by three patients (7.5 %; 95 %CI 0.00-0.15), and no patients developed post-polypectomy syndrome. CONCLUSION: These preliminary results showed 0 % local recurrence rate at 6 months and demonstrated the safety profile of hAPC-EMR. A large, randomized, controlled trial is required to confirm these results.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Effects of Blended (Yellow) vs Forced Coagulation (Blue) Currents on Adverse Events, Complete Resection, or Polyp Recurrence After Polypectomy in a Large Randomized Trial.

BACKGROUND & AIMS: There is debate over the type of electrosurgical setting that should be used for polyp resection. Some endoscopists use a type of blended current (yellow), whereas others prefer coagulation (blue). We performed a single-blinded, randomized trial to determine whether type of electrosurgical setting affects risk of adverse events or recurrence. METHODS: Patients undergoing endoscopic mucosal resection of nonpedunculated colorectal polyps 20 mm or larger (n = 928) were randomly assigned, in a 2 × 2 design, to groups that received clip closure or no clip closure of the resection defect (primary intervention) and then to either a blended current (Endocut Q) or coagulation current (forced coagulation) (Erbe Inc) (secondary intervention and focus of the study). The study was performed at multiple centers, from April 2013 through October 2017. Patients were evaluated 30 days after the procedure (n = 919), and 675 patients underwent a surveillance colonoscopy at a median of 6 months after the procedure. The primary outcome was any severe adverse event in a per patient analysis. Secondary outcomes were complete resection and recurrence at first surveillance colonoscopy in a per polyp analysis. RESULTS: Serious adverse events occurred in 7.2% of patients in the Endocut group and 7.9% of patients in the forced coagulation group, with no significant differences in the occurrence of types of events. There were no significant differences between groups in proportions of polyps that were completely removed (96% in the Endocut group vs 95% in the forced coagulation group) or the proportion of polyps found to have recurred at surveillance colonoscopy (17% and 17%, respectively). Procedural characteristics were comparable, except that 17% of patients in the Endocut group had immediate bleeding that required an intervention, compared with 11% in the forced coagulation group (P = .006). CONCLUSIONS: In a randomized trial to compare 2 commonly used electrosurgical settings for the resection of large colorectal polyps (Endocut vs forced coagulation), we found no difference in risk of serious adverse events, complete resection rate, or polyp recurrence. Electrosurgical settings can therefore be selected based on endoscopist expertise and preference. Clinicaltrials.gov ID NCT01936948.

Factors associated with complete clip closure after endoscopic mucosal resection of large colorectal polyps.

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.

Clip Closure Prevents Bleeding After Endoscopic Resection of Large Colon Polyps in a Randomized Trial.

BACKGROUND & AIMS: Bleeding is the most common severe complication after endoscopic mucosal resection of large colon polyps and is associated with significant morbidity and cost. We examined whether prophylactic closure of the mucosal defect with hemoclips after polyp resection reduces the risk of bleeding. METHODS: We performed a multicenter, randomized trial of patients with a large nonpedunculated colon polyp (≥20 mm) at 18 medical centers in North America and Spain from April 2013 through October 2017. Patients were randomly assigned to groups that underwent endoscopic closure with a clip (clip group) or no closure (control group) and followed. The primary outcome, postprocedure bleeding, was defined as a severe bleeding event that required hospitalization, a blood transfusion, colonoscopy, surgery, or another invasive intervention within 30 days after completion of the colonoscopy. Subgroup analyses included postprocedure bleeding with polyp location, polyp size, or use of periprocedural antithrombotic medications. We also examined the risk of any serious adverse event. RESULTS: A total of 919 patients were randomly assigned to groups and completed follow-up. Postprocedure bleeding occurred in 3.5% of patients in the clip group and 7.1% in the control group (absolute risk difference [ARD] 3.6%; 95% confidence interval [CI] 0.7%-6.5%). Among 615 patients (66.9%) with a proximal large polyp, the risk of bleeding in the clip group was 3.3% and in the control group was 9.6% (ARD 6.3%; 95% CI 2.5%-10.1%); among patients with a distal large polyp, the risks were 4.0% in the clip group and 1.4% in the control group (ARD -2.6%; 95% CI -6.3% to -1.1%). The effect of clip closure was independent of antithrombotic medications or polyp size. Serious adverse events occurred in 4.8% of patients in the clip group and 9.5% of patients in the control group (ARD 4.6%; 95% CI 1.3%-8.0%). CONCLUSIONS: In a randomized trial, we found that endoscopic clip closure of the mucosal defect following resection of large colon polyps reduces risk of postprocedure bleeding. The protective effect appeared to be restricted to large polyps located in the proximal colon. ClinicalTrials.gov no: NCT01936948.

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst Ablation Protocol.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage followed by infusion of paclitaxel is effective for the treatment of mucinous pancreatic cysts. However, complications arise in 3%-10% of patients, presumably linked to the inflammatory effects of ethanol. We aimed to determine whether alcohol is required for effective pancreatic cyst ablation, if removing alcohol from the ablation process would improve complication rates, and whether a multi-agent chemotherapeutic cocktail could increase the rate of complete cyst resolution compared with findings reported from previous trials using alcohol followed by paclitaxel alone. METHODS: Between November 2011 and December 2016, we conducted a single-center, prospective, double-blind trial of 39 patients with mucinous-type pancreatic cysts. Patients were randomly assigned to 1 of 2 groups that underwent EUS-guided pancreatic cyst lavage with either 80% ethanol (control) or normal saline (alcohol-free group). Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after the procedure, and rates of serious and minor adverse events within 30 days of the procedure. RESULTS: At 12 months, 67% of patients who underwent alcohol-free EUS-guided cyst chemoablation had complete ablation of cysts compared with 61% of patients in the control group. Serious adverse events occurred in 6% of patients in the control group vs none of the patients in the alcohol-free group. Minor adverse events occurred in 22% of patients in the control group and none of the patients in the alcohol-free group. The overall rate of complete ablation was 64%. CONCLUSIONS: In this prospective, randomized, controlled trial, we found that alcohol is not required for effective EUS-guided pancreatic cyst ablation, and when alcohol is removed from the ablation process, there is a significant reduction in associated adverse events. A multi-agent chemotherapeutic ablation admixture did not appear to significantly improve rates of complete ablation compared with the current standard of alcohol lavage followed by paclitaxel alone. ClinicalTrials.gov ID: NCT01475331.

Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients.

BACKGROUND & AIMS: Rectal indomethacin, a nonsteroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), based on findings from clinical trials. The European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach. METHODS: We performed a prospective, double-blind, placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center, from March 2013 through December 2014. Approximately 70% of the cohort were at average risk for PEP. Subjects were assigned randomly to groups given either a single 100-mg dose of rectal indomethacin (n = 223) or a placebo suppository (n = 226) during the procedure. The primary outcome was the development of post-ERCP pancreatitis (PEP), defined by new upper-abdominal pain, a lipase level more than 3-fold the upper limit of normal, and hospitalization after ERCP for 2 consecutive nights. RESULTS: There were no differences between the groups in baseline clinical or procedural characteristics. Sixteen patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP (P = .33). Complications and the severity of PEP were similar between groups. Per a priori protocol guidelines, the study was stopped owing to futility. CONCLUSIONS: In a randomized controlled study of consecutive patients undergoing ERCP, rectal indomethacin did not prevent post-ERCP pancreatitis. ClincialTrials.gov no: NCT01774604.

Cost-effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial.

BACKGROUND AND AIMS: The optimal type of stent for the palliation of malignant biliary obstruction in patients with pancreatic adenocarcinoma undergoing neoadjuvant chemoradiotherapy with curative intent is unknown. We performed a prospective trial comparing 3 types of biliary stents-fully covered self-expandable metal (fcSEMS), uncovered self-expandable metal (uSEMS), and plastic-to determine which best optimized cost-effectiveness and important clinical outcomes. METHODS: In this prospective randomized trial, consecutive patients with malignant biliary obstruction from newly diagnosed pancreatic adenocarcinoma who were to start neoadjuvant chemoradiotherapy were randomized to receive fcSEMSs, uSEMSs, or plastic stents during the index ERCP. The primary outcomes were time to stent occlusion, attempted surgical resection, or death after the initiation of neoadjuvant therapy, and the secondary outcomes were total patient costs associated with the stent, including the index ERCP cost, downstream hospitalization cost due to stent occlusion, and the cost associated with procedural adverse event. RESULTS: Fifty-four patients were randomized and reached the primary end point: 16 in the fcSEMS group, 17 in the uSEMS group, and 21 in the plastic stent group. No baseline demographic or tumor characteristic differences were noted among the groups. The fcSEMSs had a longer time to stent occlusion compared with uSEMSs and plastic stents (220 vs 74 and 76 days, P < .01), although the groups had equivalent rates of stent occlusion, attempted surgical resection, and death. Although SEMS placement cost more during the index ERCP (uSEMS = $24,874 and fcSEMS = $22,729 vs plastic = $18,701; P < .01), they resulted in higher procedural AE costs per patient (uSEMS = $5522 and fcSEMS = $12,701 vs plastic = $0; P < .01). Conversely, plastic stents resulted in an $11,458 hospitalization cost per patient due to stent occlusion compared with $2301 for uSEMSs and $0 for fcSEMSs (P < .01). CONCLUSIONS: In a prospective trial comparing fcSEMSs, uSEMSs, and plastic stents for malignant biliary obstruction in patients undergoing neoadjuvant therapy with curative intent for pancreatic adenocarcinoma, no stent type was superior in optimizing cost-effectiveness, although fcSEMSs resulted in fewer days of neoadjuvant treatment delay and a longer time to stent occlusion. (Clincial trial registration number: NCT01038713.).

Endoscopic Management of Large (≥2 cm) Non-pedunculated Colorectal Polyps: Impact of Polyp Morphology on Outcomes.

BACKGROUND AND AIMS: Referrals for endoscopic management of large non-pedunculated (NP) colorectal polyps have increased as new techniques have emerged. The outcomes for referred large NP polyps based on the polyp morphology were investigated METHODS: A retrospective review of patients referred for large (≥20 mm) NP polyp management from January 2010 through June 2014 was completed. Polyp morphology was classified as either a NP polyp with depression (M1) or NP polyp with no depression (M0). Differences in treatment, histology, adverse events, outcomes at follow-up including residual disease, and need for surgical treatment were determined by morphology for all NP polyps ≥20 mm in size. RESULTS: One-hundred and sixty-nine M1 and 136 M0 polyps ≥20 mm were removed endoscopically during the review period. Mean size was 31.9 ± 11.0 mm in M1, and 26.8 ± 9.5 mm in M0 group (p < 0.0001). En bloc resection was possible in 18.3 % of M1 and 30.9 % of M0 lesions (p = 0.011) with endoscopic submucosal dissection used in 13 and 2.2 % of polyps, respectively (p < 0.0001). Residual polyp was found in 26.5 % (27/102) of M1 and 13.6 % (12/88) of M0 patients at surveillance colonoscopy (p = 0.029). On multivariate analysis, piecemeal resection and M1 morphology showed significant association with residual polyp (OR 4.23, 95 % CI 1.23-14.59, p = 0.022, and OR 2.15, 95 % CI 1.004-4.62, p = 0.049, respectively). CONCLUSION: Effective endoscopic management of large NP colorectal polyps, especially polyps without depression (M0), can be accomplished in the great majority of patients. Polyp morphology, particularly the presence or absence of depression, is a useful tool which influenced treatment, histology, and outcomes.

Radiofrequency ablation for long- and ultralong-segment Barrett's esophagus: a comparative long-term follow-up study.

BACKGROUND: The safety, efficacy, and durability of radiofrequency ablation (RFA), with or without EMR, have been established for long-segment Barrett's esophagus (LSBE). Ablating ultralong-segment Barrett's esophagus (ULSBE) may be associated with increased stricture formation, eradication failure, and treatment session requirements. OBJECTIVES: Our primary objective was to compare eradication and stricture rates between LSBE (≥3 to <8 cm) and ULSBE (≥8 cm). Our secondary objective was to evaluate treatment durability and session requirements. DESIGN: Retrospective review of prospectively collected data. SETTING: Tertiary care facility. PATIENTS: A total of 72 patients (34 ULSBE, 38 LSBE; mean Barrett's segment length of 10.8 and 4.7 cm) underwent RFA between August 2005 and September 2010. Mean follow-up was 45 and 34 months, respectively. MAIN OUTCOME MEASUREMENTS: Eradication and complication rates for ULSBE and LSBE. RESULTS: Eradication rates for dysplasia (90% vs 88%, P = 1.0) and intestinal metaplasia (IM) (77% vs 82%, P = .77) were similar. ULSBE patients required more overall (P < .01) and circumferential (P < .01) RFA; however, stricture rates were identical (14%). There was no dysplasia recurrence, and IM recurrence was similar (ULSBE, 23%; LSBE, 16%; P = .52). At 3 years, IM remained eradicated in 65% of ULSBE and 82% of LSBE, without maintenance RFA. On multivariate regression analysis, increasing Barrett's length was associated with a reduced likelihood for eradicating IM (odds ratio 0.87; 95% CI, 0.75-1.00), but not dysplasia (odds ratio 1.13; 95% CI, 0.95-1.35). LIMITATIONS: Single center. CONCLUSION: ULSBE can be treated in its entirety at each session with efficacy and safety comparable to LSBE. ULSBE requires more effort to achieve IM eradication, and RFA is less durable in maintaining this eradication at 3-year follow-up.

Pancreaticoduodenectomy for the treatment of groove pancreatitis.

BACKGROUND AND AIM: Groove pancreatitis is a segmental form of chronic pancreatitis that can be treated with pancreaticoduodenectomy (PD), although outcome studies for this approach are lacking. We performed an assessment of pain symptoms, need for opioids, and weight gain following PD for symptomatic groove pancreatitis. METHODS: The study was a retrospective case series describing all patients with groove pancreatitis who underwent PD at our medical center. The primary outcome was the change in pain level and opioid use following PD. RESULTS: Five patients underwent PD for treatment of groove pancreatitis. Patients' perception of pain, using a 10-point visual analog scale, improved after surgery from 5.0 to 0.2. Opioid analgesics, as measured by oral morphine equivalents, dropped from 77.6 to 0 mg daily, with all five patients being completely free of opioids post-operatively. Weight loss ceased in all five patients, with an overall mean weight gain of 15.4 pounds post-operatively. CONCLUSIONS: PD reduces pain and opioid analgesic use in groove pancreatitis. This intervention should be considered for patients with this condition.