Snare Tip Soft Coagulation vs Argon Plasma Coagulation vs No Margin Treatment After Large Nonpedunculated Colorectal Polyp Resection: a Randomized Trial.

BACKGROUND & AIMS: Thermal treatment of the defect margin after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions reduces the recurrence rate. Both snare tip soft coagulation (STSC) and argon plasma coagulation (APC) have been used for thermal margin treatment, but there are few data directly comparing STSC with APC for this indication. METHODS: We performed a randomized 3-arm trial in 9 US centers comparing STSC with APC with no margin treatment (control) of defects after EMR of colorectal nonpedunculated lesions ≥15 mm. The primary end point was the presence of residual lesion at first follow-up. RESULTS: There were 384 patients and 414 lesions randomized, and 308 patients (80.2%) with 328 lesions completed ≥1 follow-up. The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% with control subjects (no margin treatment). The odds of residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (P = .001 and P = .01, respectively). The difference in odds was not significant between STSC and APC. STSC took less time to apply than APC (median, 3.35 vs 4.08 minutes; P = .019). Adverse event rates were low, with no difference between arms. CONCLUSIONS: In a randomized trial STSC and APC were each superior to no thermal margin treatment after EMR. STSC was faster to apply than APC. Because STSC also results in lower cost and plastic waste than APC (APC requires an additional device), our study supports STSC as the preferred thermal margin treatment after colorectal EMR. (Clinicaltrials.gov, Number NCT03654209.).

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.

PANCREATIC SAFETY IN STUDIES OF THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST ALBIGLUTIDE.

Objective: Albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), reduces glycated hemoglobin with a low risk of hypoglycemia in patients with type 2 diabetes. The relationship between GLP-1RAs and risk of pancreatitis is unresolved. This independent, rigorous, expert review of the albiglutide HARMONY Phase III clinical program examined suspected cases of acute pancreatitis. Methods: An independent pancreatitis adjudication committee (PAC), composed of physicians with expertise in gastroenterology and pancreatic disease, was prospectively established to review cases of suspected acute pancreatitis in the HARMONY studies. Results: Patients treated in Phase III trials with albiglutide (n = 2,365), or active or placebo comparators (n = 2,530), averaged 56 years of age with a mean 8.3-year diabetes duration. Across the 8 studies, the PAC reviewed potential cases of treatment-emergent acute pancreatitis in 43 patients. Definite or probable acute pancreatitis was adjudicated for 11 patients (8 albiglutide; 3 active comparators). Most of these were considered by the PAC to be at least possibly related to study treatment (6 of 8 albiglutide cases and 2 of 3 active comparator cases). Both cases in the active comparator group adjudicated as definite or probable pancreatitis with at least a possible relationship to study treatment were in patients treated with a GLP-1RA. The frequency of pancreatitis was higher among patients treated with albiglutide (6/2,365, 0.3%) than with placebo (0/486, 0%) or active comparators (2/2,062, 0.08%). Conclusion: In the HARMONY Phase III program, adjudicated cases of acute pancreatitis were uncommon. However, within the limitations of available data, the incidence of acute pancreatitis with albiglutide appears to be within the range described for other studies of GLP-1RAs. Abbreviations: AE = adverse event; CI = confidence interval; DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; GLP-1RA = glucagon-like peptide-1 receptor agonist; MH-OR = Mantel-Haenszel odds ratio; OR = odds ratio; PAC = pancreatitis adjudication committee; SAE = serious adverse event; ULN = upper limit of normal.

Evaluation of occult gastrointestinal bleeding.

Occult gastrointestinal bleeding is defined as gastrointestinal bleeding that is not visible to the patient or physician, resulting in either a positive fecal occult blood test, or iron deficiency anemia with or without a positive fecal occult blood test. A stepwise evaluation will identify the cause of bleeding in the majority of patients. Esophagogastroduodenoscopy (EGD) and colonoscopy will find the bleeding source in 48 to 71 percent of patients. In patients with recurrent bleeding, repeat EGD and colonoscopy may find missed lesions in 35 percent of those who had negative initial findings. If a cause is not found after EGD and colonoscopy have been performed, capsule endoscopy has a diagnostic yield of 61 to 74 percent. Deep enteroscopy reaches into the mid and distal small bowel to further investigate and treat lesions found during capsule endoscopy or computed tomographic enterography. Evaluation of a patient who has a positive fecal occult blood test without iron deficiency anemia should begin with colonoscopy; asymptomatic patients whose colonoscopic findings are negative do not require further study unless anemia develops. All men and postmenopausal women with iron deficiency anemia, and premenopausal women who have iron deficiency anemia that cannot be explained by heavy menses, should be evaluated for occult gastrointestinal bleeding. Physicians should not attribute a positive fecal occult blood test to low-dose aspirin or anticoagulant medications without further evaluation.

Cholangiocarcinoma treatment.

Cholangiocarcinoma (CCA) is a tumor of the bile ducts that usually presents with biliary obstruction and has a poor prognosis. The treatment of CCA is challenging as the tumor is usually diagnosed late and the treatments are not very effective except when complete surgical resection is possible. In carefully selected patients, liver transplant can be a curative therapy. In the majority of cases, complete surgical resection is not possible and palliation is the mainstay of treatment. Stenting, using plastic or metallic stents, allows for biliary drainage. Photodynamic therapy plays a role in palliation and might play a role in adjuvant or neoadjuvant therapy. While radiation and chemotherapy can be beneficial, newer ablative techniques and targeted chemotherapies are promising.

Large colorectal polyps: endoscopic management and rate of malignancy: does size matter?

BACKGROUND AND STUDY AIMS: High rate of malignancy has been reported in large colorectal polyps. However, studies were limited by including surgically resected polypoid lesions, only polyp ≥3 cm, only sessile polyps or carcinoma in situ. The aim of the study was to define the prevalence of invasive carcinoma among colorectal polyps ≥2 cm in diameter detected by colonoscopy and also to study the success of endoscopic resection. PATIENTS AND METHODS: All polypectomies of ≥2 cm colorectal polyps were identified from our endoscopy and pathology database and patients' medical records were reviewed for gross features, techniques of resection, complications, histology, and follow-up. Standard statistical tests were applied for calculating the rates, prevalence, and difference in proportions. RESULTS: Colonoscopic resection of 183 large polyps was performed in 174 patients over a period of 6 years (55% men and 45% women), mean age 64 years (median 67 y and range 25-91 y). The majority of polyps were sessile (84%). Fifty-six percent were located in the right colon. Invasive cancer was found in 10% of polyps. Endoscopic resection was successful in 89% of patients. Postpolypectomy bleeding and perforation was noted in 5% and 2% of patients, respectively. No death was observed. Seventy-eight percent of patients completed >1 year of follow-up after initial polypectomy. Recurrence of adenoma was noted in 12%, which was managed successfully by colonoscopic polypectomy techniques. CONCLUSIONS: The rate of invasive cancer is low among endoscopically resected large colorectal polyps and most of these polyps can be resected successfully via colonoscopy with minimal morbidity and no mortality. A close endoscopic follow-up is required to monitor for recurrence.

Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis.

Cholangiocarcinoma (CCA) is a rare tumor arising from the epithelium of the intrahepatic or the extrahepatic bile ducts. It is rarely diagnosed before 40 years of age except in patients with primary sclerosing cholangitis. CCA is usually clinically silent until the tumor obstructs the bile ducts. Carbohydrate antigen 19-9 is the most commonly used tumor marker, and magnetic resonance cholangiopancreatography is the best available imaging modality for CCA. Endoscopic retrograde cholangiopancreatography and cholangioscopy allow tissue acquisition. Positron emission tomography may play a role in identifying occult metastases. Tissue diagnosis is obtained by brush cytology or bile duct biopsy.

Prophylactic pancreatic stents: does size matter? A comparison of 4-Fr and 5-Fr stents in reference to post-ERCP pancreatitis and migration rate.

BACKGROUND AND AIMS: The ideal pancreatic stent to prevent post-ERCP pancreatitis (PEP) has yet to be determined. The aim of our study was to assess the relative benefit of 4-Fr versus 5-Fr stents in a population at high risk for post-ERCP pancreatitis, and the relative frequency of spontaneous migration. PATIENTS AND METHODS: All patients with prophylactic pancreatic stent (PPS) from 2002 to 2009 were reviewed. Patients were classified into two groups according to stent size and compared based on outcome; spontaneous migration or endoscopic removal. RESULTS: A total of 346 PPS were placed in 308 patients (224 women, 84 men). The average age was 48.9 years. The most common indication for PPS was sphincter of Oddi dysfunction. Needle knife papillotomy was the most common procedure performed. Forty-seven patients had PEP, 4 Fr (14.6%) and 5 Fr (12.9%), with only one case of severe pancreatitis. Factors associated with higher rates PEP were younger age and pancreatic sphincterotomy. Complete follow-up was not available in 37 patients. Spontaneous migration was demonstrated in 115 of the 4 Fr (95.8%) and 134 of the 5 Fr (68.7%). The remaining 66 (five from the 4 Fr and 61 from the 5 Fr), were removed by endoscopy. The mean delay to demonstrate spontaneous migration was 34.2 days. CONCLUSIONS: PPS in high-risk patients reduced the risk of post-ERCP pancreatitis and nearly eliminated severe pancreatitis. No significant difference between the 4 Fr and 5 Fr in reduction of post-ERCP pancreatitis was observed. However, spontaneous migration was more frequent with the 4-Fr stent.

Nonampullary duodenal polyps: characteristics and endoscopic management.

BACKGROUND: Guidelines for endoscopic resection and surveillance of nonampullary duodenal (NAD) polyps are still not well-defined. OBJECTIVE: To describe the characteristics of NAD polyps and evaluate the role of endoscopic management. DESIGN: Retrospective review. SETTING: Tertiary-care academic center. PATIENTS: This study involved 59 patients with NAD polyps. INTERVENTION: Endoscopic polypectomy, biopsy, and argon plasma coagulation. MAIN OUTCOME MEASUREMENTS: Complete polypectomy, complications, and recurrence. RESULTS: Ninety-six endoscopies were performed. The mean patient age was 62.8 years. The mean (+/- standard deviation) polyp size was 17.2 mm +/- 1.6 mm. The mean follow-up time was 26 months. Most lesions were sessile, solitary, and located in the descending duodenum. The procedure most often performed was submucosal injection followed by snare polypectomy. Adenomas were found in 68% of lesions overall and in 84% of lesions >2 cm. Successful resection was accomplished in 93% of cases on the initial attempt. Multiple endoscopies were needed in 5% of cases. The overall complete resection rate was 98%. Recurrence was documented in 37% of cases. Complications occurred in 5.2% of patients. Polyps of >2 cm were associated with higher rates of adenoma and a higher incidence of recurrence. Colon adenomas were found in 53% of patients with duodenal adenomas. LIMITATIONS: Retrospective review. Not all patients underwent colonoscopy. CONCLUSION: NAD polyps were large, sessile, and more commonly found in the second portion of the duodenum. They are more likely to be adenomatous when the lesion size is >2 cm. Despite successful endoscopic management, over one third of lesions demonstrated recurrence.

ERCP in the management of biliary complications after cholecystectomy.

Open cholecystectomy has been associated historically with 0.2% to 0.5% risk of postoperative biliary injury. Laparoscopic cholecystectomy, which has become the first-line surgical treatment of calculous gallbladder disease, has been associated with a 2.5-fold to fourfold increase in the incidence of postoperative bile duct injury. The biliary endoscopist can expect to see a varied spectrum of complications after cholecystectomy by either technique, including postoperative biliary strictures, bile leaks, and retained calculi in the biliary tree. Proper diagnosis and treatment are paramount in ensuring a satisfactory outcome after bile duct injury. Endoscopic retrograde cholangiopancreatography (ERCP) has become the primary modality for treatment and effectively manages most bile duct injuries.

Endoscopic management of upper esophageal strictures after treatment of head and neck malignancy.

BACKGROUND: Dysphagia, usually due to proximal esophageal strictures, is a debilitating complication of therapy (surgery, radiotherapy, or chemotherapy) for head and neck malignancy. Scant attention has been given in the literature to the endoscopic management of these proximal esophageal strictures. OBJECTIVE: Our purpose was to assess the technical and functional outcomes of endoscopic management of proximal esophageal strictures after therapy for head and neck cancers. DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: Consecutive patients undergoing endoscopy and dilation of proximal esophageal strictures caused by chemoradiation or surgery for head and neck malignancy. MAIN OUTCOME MEASUREMENT: Technical and functional success after endoscopic dilation. RESULTS: Twenty-four patients were included. The mean age of patients was 70.4 years (range 42 to 82 years). The primary tumor site was larynx in 10 patients, oropharynx or hypopharynx in 4 patients, upper esophagus in 4 patients, and other sites in the remainder. Technical success (a luminal diameter of 42F or greater) was achieved in 80% of patients. Adequate dysphagia relief was achieved in 84% of patients whose esophageal stricture was dilated at least up to 42F. The average follow-up was 22 months (range 1-96 months). Repeat dilation was needed in 58% of patients. No complications or death occurred during the study period. LIMITATIONS: Retrospective design and highly selected patient population. Dysphagia assessment in conjuction with a speech pathologist was not performed in all patients. Results may not be applicable to other settings. CONCLUSION: In this case series, proximal esophageal strictures after treatment of head and neck malignancy were amenable to antegrade endoscopic dilation; however, no patient in our study had complete lumen obstruction. Repeat dilations are often needed and are effective in achieving and maintaining adequate dysphagia relief.

Endoscopy in the management of choledocholithiasis.

Choledocholithiasis (bile duct stones) occurs in 10% to 15% of patients with cholelithiasis. Endoscopic retrograde cholangiopancreatography and biliary sphincterotomy, combined with the use of a variety of available accessories (eg, mechanical lithotriptors), are highly effective in managing most common bile duct stones. The combination of biliary sphincterotomy and papillary balloon dilation allows removal of many stones without the need for mechanical lithotripsy. Large stones may require additional expertise and the use of cholangioscopy with intraductal lithotripsy. Some patients, especially those with intrahepatic stones, require the help of an interventional radiologist or a biliary surgeon. The availability of endoscopists, radiologists, and surgeons interested in and experienced with biliary diseases will allow successful and safe therapy to be tailored to the individual patient.