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.

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.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

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.

Metachronous gastric metastasis from lung primary, with synchronous pancreatic neuroendocrine carcinoma.

The finding of gastric metachronous metastasis, several years after the diagnosis of primary lung large cell carcinoma is rare and incidental. Even more extremely rare is the finding of a synchronous primary pancreas cancer. EUS-FNA with immunohistochemistry is useful for diagnosing metastatic lesions and differentiating those from synchronous primary lesions.

Prospective Assessment of the Performance of a New Fine Needle Biopsy Device for EUS-Guided Sampling of Solid Lesions.

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) remains the most common EUS-guided tissue acquisition technique. This study aimed to evaluate the performance of a new Franseen tip fine needle biopsy (FNB) device for EUSguided sampling of solid lesions and compare it with the historical FNA technique. METHODS: Acquire® 22 G FNB needle (Boston Scientific Co., Natick, MA, USA) was used for solid tumor sampling (Study group). Tissue was collected for rapid on-site evaluation, and touch and crush preparations were made. Historical EUS-FNA samples obtained using Expect® 22 G FNA needle (Boston Scientific Co.) were used as controls (Control group). All specimens were independently evaluated by two cytopathologists blinded to the formal cytopathological diagnosis. RESULTS: Mean cell block histology scores were significantly higher (p=0.046) in the FNB group (51 samples) despite a significantly lower (p<0.001) mean number of passes compared to the FNA group (50 specimens). The overall diagnostic yields for the FNB vs. FNA groups were 96% vs. 88%. The degree of tumor differentiation was adequately assessed in all cell block qualifying lesions in the FNB group. Two patients developed post-FNB abdominal pain. CONCLUSION: The new Franseen tip FNB device provides histologically superior and cytologically comparable specimens to those obtained by FNA, but with fewer passes.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Does cyst growth predict malignancy in branch duct intraductal papillary mucinous neoplasms? Results of a large multicenter experience.

BACKGROUND: Cyst growth of BD-IPMNs on follow-up imaging remains a concerning sign. AIMS: To describe cyst size changes over time in BD-IPMNs, and determine whether cyst growth rate is associated with increased risk of malignancy. METHODS: This is a retrospective study performed at two high volume tertiary centers. Mean cyst size at baseline (MCSB) and mean growth rate percentage (MGRP) were calculated. Rapid cyst growth was defined as MGRP ≥30%/year. Patient and cyst related characteristics were studied. RESULTS: 160 patients were followed for a median of 27.4 (12-114.5) months. MCSB was 15.1 ±â€¯8.0 mm. During follow-up, 73 (45.6%) showed any cyst size increase, of which 15 cysts (9.4%) exhibited MGRP ≥30%/year. Rapid cyst growth was not associated with patient or cyst characteristics. Cyst fluid molecular analysis from 101 cysts showed KRAS mutation in 26. Compared to KRAS-negative cysts, neither MCSB (16.0 mm vs. 17.7 mm; p = 0.3) nor MGRP (3.9%/year vs. 5.8%/year; p = 0.7) was significantly different. Eighteen patients underwent surgery; 15 (83%) had LGD, and 3 had advanced neoplasia. Two cysts with LGD and one cyst with advanced neoplasia had MGRP ≥30%/year. CONCLUSION: Increase in BD-IPMNs size was not associated with the known high risk patient or cyst-related characteristics. Rapid growth of BD-IPMNs was not associated with advanced neoplasia on surgical pathology.

Prospective evaluation of the performance and interobserver variation in endoscopic ultrasound staging of rectal cancer.

BACKGROUND: Treatment and prognosis of patients with rectal adenocarcinoma (RAC) are dependent on accurate locoregional staging. OBJECTIVES: The aim of this study was to measure the performance characteristics of rectal endoscopic ultrasound (EUS) compared with surgical pathology, and to assess the interobserver variation of rectal EUS in the staging of RAC. PATIENTS AND METHODS: Patients referred for rectal EUS staging of a recently diagnosed RAC were prospectively enrolled between 2012 and 2016. Tandem EUS exams were performed by two independent endosonographers (ES1 and ES2) blinded to each other's findings. RESULTS: Ninety-five patients were enrolled. Seventy-five (79%) underwent curative intent tumor resection, including 30 without neoadjuvant therapy. In this latter group, the sensitivity, specificity, and accuracy of transrectal ultrasonography staging were 75, 83, and 82% for uT1; 50, 65, and 58% for uT2; 56, 81, and 73% for T3; 72, 44, and 63% for N0, and 38, 75, and 63% for N1, respectively. Experienced operators rendered a more accurate N stage and were less likely to overstage compared with less experienced ones (P=0.01 and 0.02, respectively). Overall, T staging agreement between endosonographers was substantial (κ=0.61) and N stage agreement was moderate (κ=0.45). CONCLUSION: Rectal EUS is more accurate in staging T1 and T3 tumors compared with T2 tumors. Interobserver agreement of rectal EUS in rectal cancer staging is generally good.

Life threatening nontraumatic tension gastrothorax.

Tension gastrothorax is a rare condition, which poses a diagnostic dilemma and can be mistaken for a tension pneumothorax. Awareness of the risk factors, clinical presentation, and radiology findings of tension gastrothorax can help with the prompt identification and successful management of this life-threatening condition.

Additional flap on plastic stents for improved antimigration effect in the treatment of post-cholecystectomy bile leak.

Background and study aims: In plastic stent insertion for treatment of post-cholecystectomy bile leak, stent migration may be more common due to the absence of a shelf to anchor the stent. We evaluated how adding a flap to straight plastic stents for this indication might influence the rate of stent migration when compared to use of conventional plastic stents. Patients and methods: This is a retrospective study including patients referred for ERCP for treatment of post-cholecystectomy bile leak. Patients with a customized anti-migration flap stent had the additional flap created on the distal end of straight plastic stents, intended to aid in anchoring in the distal supra-sphincteric biliary duct. The primary endpoint is stent migration events. The secondary endpoint is bile leak resolution after first ERCP session. Results: Thirty-two patients were treated with the experimental additional flap stents and 225 patients were treated with standard straight biliary stents. The total failure rate of bile leak resolution after a single endoscopic treatment for all treated was 10.5 % (27/257) and the total stent migration rate for all enrolled was 15.2 % (39/257). Stent migration rate was lower in the additional flap stent group than in the conventional group (3.1 % vs. 16.9 %, respectively, P  = 0.04). Furthermore, significantly more patients had resolution of their bile leak after the first ERCP session in the group with the additional flap (100 % vs. 88 %, respectively, P  = 0.03). Conclusion: A plastic biliary stent with an extra flap may have improved performance with regard to stent migration and resolution of bile leak over standard plastic biliary stents.

Post-ERCP Bleeding in the Era of Multiple Antiplatelet Agents.

Background/Aims: This study aimed to determine the risk of post-endoscopic retrograde cholangiopancreatography (post-ERCP) bleeding among patients taking antiplatelet agents (APAs), particularly in the era of multiple APAs. Methods: The primary outcomes were the frequency, type, and severity of ERCP-related bleeding according to the use of APAs. Results: The frequencies of post-ERCP bleeding among the four different groups were 16 of 2,083 (0.8%) in the no drug group, 12 of 256 (4.7%) in the aspirin group, 3 of 48 (6.3%) in the single APA group, and 4 of 48 (8.3%) in the multiple APA group (p＜0.001). In the univariate analysis, post-ERCP bleeding was associated with age, pull-type sphincterotomy, and APA and was inversely associated with balloon dilation of the biliary orifice. In the multivariate analysis, pull-type sphincterotomy (odds ratio [OR], 7.829; 95% confidence interval [CI], 1.411 to 43.453; p=0.019) and country (Korea: OR, 0.124; 95% CI, 0.042 to 0.361; p＜0.001) were associated with post-ERCP bleeding. Conclusions: The frequency of post-ERCP bleeding was statistically higher in patients on any APA within 6 days prior to ERCP. However, in the multivariate analysis, APA use was not associated with post-ERCP bleeding. Until a large, adequately powered study to detect differences is performed, caution is recommended when considering invasive procedures during ERCP in patients on APAs.

A double-reprocessing high-level disinfection protocol does not eliminate positive cultures from the elevators of duodenoscopes.

BACKGROUND AND STUDY AIM: Duodenoscopes have been the source of serious infection, despite correct performance of high-level disinfection (HLD). This study aimed to observe the impact of performing HLD twice on the rate of positive cultures from duodenoscope elevators. METHODS: We performed double HLD (DHLD; i. e. complete manual cleaning followed by automated reprocessing, with the entire process repeated) and then randomly cultured the elevators of our duodenoscopes on about 30 % of occasions. RESULTS: DHLD was associated with positive elevator cultures for any microorganism in 9.4 % of cases, with a 0.8 % rate of known pathogens (627 cultures) between May 2015 and February 2016. After February 2016, and in association with changing the precleaning fluid, as well as use of a new FDA-recommended cleaning brush, the rate of positive cultures for any microorganism after DHLD was 4.8 % and 0.2 % for known pathogens (420 cultures). In a third phase, characterized by a change in personnel performing DHLD and retirement of a duodenoscope with a high rate of positive cultures, the rate of positive cultures for any microorganism was 4.9 % (783 cultures) and the rate of positive culture for known pathogens was 0.3 %. To our knowledge, no duodenoscope transmission of infection occurred during the study interval. CONCLUSIONS: DHLD resulted in a low rate of positive cultures for known pathogens and for organisms of low pathogenic potential, but did not eliminate these, from duodenoscope elevators. Additional improvements in HLD protocols and/or duodenoscope design are needed.