Combined Versus Separate Sessions of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for the Diagnosis and Management of Pancreatic Ductal Adenocarcinoma with Biliary Obstruction.

BACKGROUND: A single-procedure session combining EUS and ERCP (EUS/ERCP) for tissue diagnosis and biliary decompression for pancreatic duct adenocarcinoma (PDAC) is technically feasible. While EUS/ERCP may offer expedience and convenience over an approach of separate procedures sessions, the technical success and risk for complications of a combined approach is unclear. AIMS: Compare the effectiveness and safety of EUS/ERCP versus separate session approaches for PDAC. METHODS: Study patients (2010-2015) were identified within our ERCP database. Patients were analyzed in three groups based on approach: Group A: Single-session EUS-FNA and ERCP (EUS/ERCP), Group B: EUS-FNA followed by separate, subsequent ERCP (EUS then ERCP), and Group C: ERCP with/without separate EUS (ERCP ± EUS). Rates of technical success, number of procedures, complications, and time to initiation of PDAC therapies were compared between groups. RESULTS: Two hundred patients met study criteria. EUS/ERCP approach (Group A) had a longer index procedure duration (median 66 min, p = 0.023). No differences were observed between Group A versus sequential procedure approaches (Groups B and C) for complications (p = 0.109) and success of EUS-FNA (p = 0.711) and ERCP (p = 0.109). Subgroup analysis (> 2 months of follow-up, not referred to hospice, n = 126) was performed. No differences were observed for stent failure (p = 0.307) or need for subsequent procedures (p = 0.220). EUS/ERCP (Group A) was associated with a shorter time to initiation of PDAC therapies (mean, 25.2 vs 42.7 days, p = 0.046). CONCLUSIONS: EUS/ERCP approach has comparable rates of success and complications compared to separate, sequential approaches. An EUS/ERCP approach equates to shorter time interval to initiation of PDAC therapies.

Annular pancreas: endoscopic and pancreatographic findings from a tertiary referral ERCP center.

BACKGROUND AND AIMS: Annular pancreas is a congenital anomaly whereby pancreatic tissue encircles the duodenum. Current knowledge of endoscopic findings of annular pancreas is limited to small case series. The aim of this study was to describe the endoscopic and pancreatographic findings of patients with annular pancreas at a large tertiary care ERCP center. METHODS: This is a retrospective observational study. Our Institutional Review Board-approved, prospectively collected ERCP database was queried for cases of annular pancreas. The electronic medical records were searched for patient and procedure-related data. RESULTS: From January 1, 1994, to December 31, 2016, 46 patients with annular pancreas underwent ERCP at our institution. Index ERCP was technically successful in 42 patients (91.3%), and technical success was achieved in all 46 patients (100%) after 2 attempts, when required. A duodenal narrowing or ring was found in most patients (n = 39, 84.8%), yet only 2 (4.3%) had retained gastric contents. Pancreas divisum was found in 21 patients (45.7%), 18 of which were complete divisum. Pancreatobiliary neoplasia was the indication for ERCP in 7 patients (15.2%). Pancreatographic findings consistent with chronic pancreatitis were noted in 15 patients (32.6%) at the index ERCP. CONCLUSION: This is the largest series describing the endoscopic and pancreatographic findings of patients with annular pancreas. We found that 45.7% of patients had concurrent pancreas divisum. Endoscopic therapy was successful in most patients at our institution after 1 ERCP, and in all patients after a second ERCP. Nearly one-third of patients had findings consistent with chronic pancreatitis at the time of index ERCP. It is unclear whether this may be a feature of the natural history of annular pancreas.

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass.

BACKGROUND AND AIMS: The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases, yet standard ERCP is not possible because of surgically altered gastroduodenal anatomy. Laparoscopy-assisted ERCP (LA-ERCP) has been proposed as an option, but supporting data are derived from single-center small case series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. METHODS: This is a retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all the following were achieved: reaching the papilla, cannulating the desired duct, and providing endoscopic therapy as clinically indicated. RESULTS: A total of 579 patients (median age, 51; 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (interquartile range [IQR], 109-210), with a median ERCP time of 40 minutes (IQR, 28-56). Median hospital stay was 2 days (IQR, 1-3). Adverse events were 18% (laparoscopy related, 10%; ERCP related, 7%; both, 1%) with the clear majority (92%) classified as mild/moderate, whereas 8% were severe and 1 death occurred. CONCLUSIONS: Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. The ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher because of the added laparoscopy-related events.

Role of per-oral pancreatoscopy in the evaluation of suspected pancreatic duct neoplasia: a 13-year U.S. single-center experience.

BACKGROUND AND AIMS: The role of per-oral pancreatoscopy (POP) in the evaluation of occult pancreatic duct (PD) lesions remains limited to case series. The aim of this study was to evaluate the ability of POP to differentiate malignant from benign diseases of the PD. METHODS: Patients who underwent POP between 2000 and 2013 for the evaluation of indeterminate PD strictures, dilatations, or with suspected or known main duct intraductal papillary mucinous neoplasm were identified. Main outcome measurements were visual impression accuracy, POP tissue sampling, efficacy, and safety of POP. RESULTS: During the study period, 79 patients who underwent POP for the evaluation of pancreatic stricture or dilatation were identified. Technical success was achieved in 78 (97%). In the PD neoplasia group (n = 33), the final diagnosis was based on index confirmatory POP-guided tissue sampling in 29 (88%). For the detection of PD neoplasia, POP visual impression had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 87%, 86%, 83%, 91%, and 87%, respectively. When combined with POP-guided tissue sampling, the values were 91%, 95%, 94%, 93%, and 94%, respectively. Of 102 POPs performed, adverse events were noted in 12 (12%) cases. CONCLUSIONS: This study demonstrates a high technical success rate, visual impression accuracy, and tissue sampling capability of POP. Examinations were performed by endoscopists with expertise in pancreatoscopy interpretation, and the results may not be generalizable.

Clinical response to dorsal duct drainage via the minor papilla in refractory obstructing chronic calcific pancreatitis.

Background and study aims Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). Patients and methods 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period. Results Among 16 patients meeting entry criteria, 10 (62.5 %) had a history of unsuccessful endoscopic therapy, and 8 had failed extracorporeal shockwave lithotripsy (ESWL). Clinical success was achieved in 12 patients (75 %). Among these responders, 10 patients (83.3 %) had markedly improved or complete pain relief after the first stent placement, which persisted throughout the follow-up period; 11 patients (91.7 %) were able to discontinue their daily analgesics. Conclusions In selected patients with obstructive chronic calcific pancreatitis, the DPD bypass may be considered as a rescue endoscopic therapy, potentially obviating the need for surgery when standard endoscopic methods and ESWL fail.

Time Sequence Evaluation of Biliary Stent Occlusion by Dissection Analysis of Retrieved Stents.

BACKGROUND AND AIMS: Multiple factors can affect the occlusion of plastic stents. Previous data demonstrate that side holes may induce more biofilm formation probably via microturbulence and bile flow disturbances that could lead to occlusion. These results, however, have not been replicated in subsequent clinical studies with different methods. The objective of this study is to evaluate the physical characteristics of plastic stent occlusion over time. METHODS: This is a plastic stent sequential analysis study. Biliary stents removed via ERCP from February 24, 2015, to June 2, 2015, were included. One hundred and forty-eight retrieved straight-type plastic stents were longitudinally cut by a custom-made cutting device. These dissected stents were then evaluated in detail with regard to the location of stent occlusion and the stent patency period. Location of stent occlusive debris was the primary outcome in this study. RESULTS: Biofilm formations and occlusions by debris were sequentially but separately tallied. Biofilm formations were initially seen around the side hole areas within 30 days and spread to the entire stent by 60 days. Then, occlusion process by debris was mainly initiated by 80 days and progressed to full occlusion by median of 90 days. Although some occlusions were also observed around the side hole areas within 30 days, affected areas were more widely observed after biofilm formation. CONCLUSIONS: This study is the first to attempt to describe the distribution of stent occlusions over time. These observations may help guide future stent development.

Treatment of esophageal leaks, fistulae, and perforations with temporary stents: evaluation of efficacy, adverse events, and factors associated with successful outcomes.

BACKGROUND: Factors associated with successful endoscopic therapy with temporary stents for esophageal leaks, fistulae, and perforations (L/F/P) are not well known. OBJECTIVES: To evaluate the safety, efficacy, and outcomes of esophageal stenting in these patients and identify factors associated with successful closure. DESIGN: Retrospective. SETTING: Academic tertiary referral center. PATIENTS: All patients with attempted stent placement for esophageal L/F/P between January 2003 and May 2012. INTERVENTION: Esophageal stent placement and removal. MAIN OUTCOME MEASUREMENTS: Factors predictive of therapeutic success defined as complete closure after index stent removal (primary closure) or after further endoscopic stenting (secondary closure). RESULTS: Sixty-seven patients with 132 attempted stents for esophageal L/F/P were considered; 13 patients were excluded. Among the remaining 54 patients, 117 stents were placed for leaks (29 patients; 64 stents), fistulae (15 patients; 36 stents), and perforations (10 patients; 17 stents). Procedural technical success was achieved in all patients (100%). Primary closure was successful in 40 patients (74%) and secondary closure in an additional 5 (83% overall). On short-term (<3 months) follow-up, 27 patients (50%) were asymptomatic, whereas 22 (41%) had technical adverse events, including stent migration in 15 patients (28%). Factors associated with successful primary closure include a shorter time between diagnosis of esophageal L/F/P and initial stent insertion (9.03 vs 22.54 days; P = .003), and a smaller luminal opening size (P = .002). LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: Temporary stents are safe and effective in treating esophageal L/F/P. Defect opening size and time from diagnosis to stent placement appear to be candidate predictors for successful closure.

Impact of preoperative endoscopic ultrasound-guided fine needle aspiration on postoperative recurrence and survival in cholangiocarcinoma patients.

BACKGROUND AND STUDY AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently performed for suspected biliary tumors for diagnosis and staging but carries a theoretical risk of needle-track seeding. We aimed to evaluate the impact of preoperative EUS-FNA on long-term outcomes for patients with cholangiocarcinoma (CCA). PATIENTS AND METHODS: In a retrospective single-center study of consecutive patients with CCA with preoperative EUS-FNA, main outcome measures were overall survival and progression-free survival. RESULTS: In 150 patients with confirmed CCA, 61 underwent preoperative FNA. Median overall survival was 18.5 months (95% confidence limits [CL] 15.4, 25.7): 111 patients died and 39 survived. Of the 150 patients, 119 underwent curative-intent surgical resection, with median progression-free survival of 17.8 months (95% CL 14.5, 22.8); 89/119 patients had tumor recurrence or died, and 30/119 remained alive and disease-free. On multivariable analysis, overall survival was associated with: undergoing curative-intent surgery (hazard ratio [HR] 5.79, P = 0.001), lack of lymph node involvement (HR 1.89, P = 0.011), younger age (HR 1.51 for every 10 years, P < 0.0015), and small tumor size (HR 1.11 for every 1 cm, P = 0.029). For patients undergoing curative-intent surgery, on multivariable analysis, improved progression-free survival was associated with: lack of lymph node involvement (HR 1.88, P = 0.010), smaller tumor size (HR 1.16 for every 1 cm smaller, P = 0.003), and younger age (HR 1.53 for every 10 years, P < 0.001). Number of needle passes showed no statistically significant impact on overall survival. CONCLUSION: Preoperative EUS-FNA in patients with CCA does not appear to adversely affect overall or progression-free survival.

ERCP via gastrostomy vs. double balloon enteroscopy in patients with prior bariatric Roux-en-Y gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the most common bariatric surgery. The performance of ERCP in bariatric RYGB is challenging due to the long Roux limb. We herein compared the indications and technical outcomes of ERCP via percutaneous gastrostomy (GERCP) and double balloon enteroscopy (DBERCP) for patients with prior bariatric RYGB anatomy. METHODS: Between December 2005 and November 2011, consecutive ERCP patients who had undergone RYGB were identified using a prospectively maintained electronic ERCP database. Medical records were abstracted for ERCP indications and outcomes. In most cases, the gastrostomy was done by either laparoscopic or open surgery and allowed to mature at least 1 month before performing ERCP. The choice of route for ERCP was at discretion of managing physician. RESULTS: Forty-four patients (F = 42) with GERCP and 28 patients (F = 26) with DBERCP were identified. The mean age was younger in GERCP than DBERCP (44.8 vs. 56.1, p < 0.001). GERCP patients were more likely to have suspected sphincter of Oddi dysfunction (77 %) as the primary indication whereas DBERCP was suspected CBD stone (57 %). The mean total number of sessions/patient in GERCP and DBERCP was 1.7 ± 1.0 and 1.1 ± 0.4, respectively (p = 0.004). GERCP access to the major papilla was successful in all but two (97 %), whereas duct cannulation and interventions were successful in all. In DBERCP, the success rate of accessing major papilla, cannulation and therapeutic intervention was 78, 63, 56 %, respectively. There was one (3.1 %) post-ERCP pancreatitis in DBERCP. Complications occurred in 11 GERCP procedures (14.5 %) and 10 were related to the gastrostomy. This was significantly higher than that of DBERCP (p = 0.022). CONCLUSIONS: GERCP is more effective than DBERCP in gaining access to the pancreatobiliary tree in patients with RYGB, but it is hindered by the gastrostomy maturation delay and a higher morbidity. Technical improvements in each method are needed.

Prophylaxis with ertapenem in patients with obstructive jaundice undergoing endoscopic retrograde cholangiopancreatography: safety, efficacy, and biliary penetration.

BACKGROUND: Cholangitis and biliary sepsis are rare but serious complications of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study is to investigate the safety, efficacy, and biliary penetration of ertapenem, a newer carbapenem with a long half-life and broad-spectrum antimicrobial activity, for ERCP prophylaxis. METHODS: Patients with obstructive jaundice without cholangitis received a single dose of ertapenem equal to 1 gram intravenously prior to ERCP. A 2-3 mL bile sample was collected after cannulation and prior to contrast injection. Patients were observed for 72 hours for cholangitis or drug-related adverse events. Biliary ertapenem levels were measured using high-performance liquid chromatography (HPLC). RESULTS: Twenty-eight patients (ages 18-87 years, M/F ratio 1:1) were enrolled. Seven had no cholestasis and were included to study ertapenem penetration in unobstructed biliary trees. Cannulation was achieved in all patients. One patient (3.6%) with persistent intrahepatic stones developed cholangitis. No drug-related adverse events were noted. The mean time from ertapenem administration to bile collection was 60 ± 24 minutes. There was a significant negative correlation between serum bilirubin and biliary ertapenem levels (r = -0.542, P = 0.003) with the highest level (6.25 µg/mL) noted in unobstructed biliary systems. CONCLUSION: Ertapenem appears to be a safe and effective prophylaxis in patients with obstructive jaundice undergoing ERCP despite a limited biliary penetration in patients with high-grade obstruction.

Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: association with liver disease.

OBJECTIVE: To determine whether any correlation exists between the phenotype and genotype of 2 Lebanese families with members affected with Wilson disease (WD). BACKGROUND: WD is an autosomal-recessive disorder of copper transport with significant phenotypic diversity. Most patients are compound heterozygous making it difficult to establish a clear link between phenotype and genotype. STUDY: We investigated 14 members from 2 Lebanese families (H and Z) with 5 members affected with WD. Mutation analysis of the ATP7B gene, and clinical assessments were carried out for both families. We also performed a literature search retrieving reported phenotypes of all patients homozygous to mutations in any of the 21 exons of the ATP7B. RESULTS: Patients of the H and Z-families were found homozygous for the respective Asn1270Ser and Pro1273Leu mutations in the adenosine triphosphate (ATP) hinge region of exon 18. Of the healthy members, 6 were heterozygous and 3 had normal sequences. Clinically, 4 patients had liver cirrhosis and 1 had asymptomatic transaminitis. One of the patients also had neurologic symptoms. Screening the literature for patients homozygous for mutations in the ATP hinge region identified 25 patients including ours. The overall prevalence of the hepatic phenotype among patients homozygous for mutation in exon 18 was 80% and was significantly higher than those in exons 7, 14, and 21. CONCLUSIONS: We hereby report the association of liver disease with homozygous mutations in the conserved ATP hinge region of exon 18 of the ATP7B gene.

Effect of calcineurin inhibitor on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with liver transplantation: a propensity-matched cohort study.

BACKGROUND/AIMS: A calcineurin inhibitor may alter pancreatic function and inflammatory reaction. This study aimed to determine the possible pharmacologic effect of the calcineurin inhibitor, tacrolimus, on pancreatic function, and to determine its preventive effect on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in liver transplantation (LT) patients. METHODS: The serum amylase and lipase values before and after LT were compared. The frequency of post-ERCP pancreatitis was compared between non-LT and LT patients, using propensity score matching method. RESULTS: Median serum amylase values (normal range, 19 to 86 U/L) were 49.0 U/L (38.0 to 68.0) before LT and 27.0 U/L (19.3 to 36.8) after LT, and median serum lipase values (normal range, 7 to 59 U/L) were 40.0 U/L (26.5 to 54.0) before LT and 10.5 U/L (6.0 to 21.0) after LT. Both serum amylase and lipase values significantly decreased after LT (p < 0.001), and to a level comparable to chronic pancreatitis. There was a marginal significant difference between the non-LT and LT groups before the propensity score matching with respect to frequency of post-ERCP pancreatitis (16 [3.2%] in non-LT group vs. 2 [0.9%] in LT group, p = 0.069). After propensity score matching, a marginal significant difference still existed with respect to frequency of post-ERCP pancreatitis (7 [4.8%] in non-LT group vs. 1 [0.7%] in LT group, p = 0.067). CONCLUSION: The immunosuppression with calcineurin inhibitor may reduce not only the pancreatic enzyme dynamics but also inciting inflammatory event including post-ERCP pancreatitis.

Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.

BACKGROUND: Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. METHODS: In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. FINDINGS: Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. INTERPRETATION: Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP. FUNDING: American College of Gastroenterology.

Gastrointestinal bleeding in the setting of anticoagulation and antiplatelet therapy.

GOAL: To review the literature on the significance, risk factors, and management of occult and gross gastrointestinal (GI) bleeding in patients on antiplatelets and/or anticoagulants. STUDY: Relevant original and review articles and their bibliographies were analyzed. Estimates of risks and therapeutic outcomes were obtained from randomized trials, whereas risk factor identification was gathered from cross-control and prospective cohort studies. RESULTS: Antiplatelets and anticoagulants do not diminish the positive predictive value of fecal occult blood testing to find GI pathology. They increase the risk of gross GI bleeding, and predictors of hemorrhage include history of GI bleeding or ulcer disease, higher intensity of anticoagulation, combination therapy, and presence of comorbid conditions. A bleeding site is identified in most patients with peptic ulcer being the most common. In case of significant bleeding, complete or partial reversal of anticoagulation is undertaken on the basis of the balance of risks between bleeding and thromboembolic events. Early endoscopy can reveal lesions requiring endoscopic hemostasis, which can be performed in the setting of low-intensity anticoagulation. In patients with history of peptic disease or bleeding from an acid-related lesion, proton-pump inhibitors and Helicobacter pylori eradication reduce the risk of upper GI bleeding even when antiplatelet therapy is continued. CONCLUSIONS: Predictors of bleeding on antiplatelets and/or antithrombotics therapy have been identified, but formulation and validation of a GI bleeding index for stratification of risk in individual patients is suggested. Reversal of anticoagulation in bleeding patients is associated with a low risk of thromboembolic events and permits the performance of diagnostic and therapeutic endoscopy. Proton-pump inhibitors and H. pylori eradication reduce the risk of rebleeding in those with acid-related disease.