Dupilumab-Induced Pancreatitis.

Drug-induced pancreatitis (DIP) is a rare cause of pancreatitis with an extensive and growing list of offending medications. Drawing a causative relationship between a medication and pancreatitis can be challenging, requiring a thorough workup to exclude other potential etiologies. By using scoring systems to identify DIP, we have identified another case of suspected DIP. In this study, we present a case of pancreatitis 10 days after initiation of dupilumab. An evaluation for other causes was unrevealing. As dupilumab use increases, providers should be aware of this possible adverse effect.

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions.

BACKGROUND & AIMS: Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. METHODS: We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis. RESULTS: The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria. CONCLUSIONS: In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video).

BACKGROUND AND AIMS: Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). METHODS: We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naïve observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). RESULTS: Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial "width" and "darkness" were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 µm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. CONCLUSIONS: In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.).

Acute Biliary Pancreatitis is Associated With Adverse Outcomes in the Elderly: A Propensity Score-Matched Analysis.

GOALS AND BACKGROUND: In the elderly (age, 65 y or older), acute pancreatitis is most frequently because of gallstones; however, there is a paucity of national estimates evaluating outcomes of acute biliary pancreatitis (ABP). Hence, we utilized a representative population database to evaluate the outcomes of ABP among the elderly. STUDY: The National Readmission Database provides longitudinal follow-up of inpatients for 1 calendar-year. All adult inpatients (18 y or older) with an index primary admission for ABP between 2011 and 2014 were evaluated for clinical outcomes of mortality, severe acute pancreatitis (SAP), and 30-day readmission. Outcomes between age groups (≥65 vs. <65 y) were compared using multivariate and one-to-one propensity score-matched analyses. RESULTS: Among 184,763 ABP admissions, 41% were elderly. Index mortality and SAP rates in the elderly were 1.96% and 21.5%, respectively. Elderly patients underwent more ERCPs (27.5% vs. 23.6%; P<0.001) and less frequent cholecystectomies (44.4% vs. 58.7%; P<0.001). Elderly patients had increased odds of mortality and SAP along with an age-dependent increase in the odds of adverse outcomes; patients aged 85 years or older demonstrated the highest odds of SAP [odds ratio (OR), 1.3; 95% confidence interval (CI): 1.2, 1.4] and mortality (OR, 2.2; 95% CI: 1.7, 2.9) within in the elderly cohort. Propensity score-matched analysis substantiated that mortality (OR, 2.8; 95% CI: 2.2, 3.5) and SAP (OR, 1.2; 95% CI: 1.1, 1.3) were increased in the elderly. CONCLUSIONS: Current national survey reveals adverse clinical outcomes among elderly patients hospitalized with ABP. Consequently, there is a need for effective management strategies for this demographic as the aging population is increasing nationally.

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions.

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss' kappa) and IOR (Cohen's kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was "substantial" (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was "substantial" (κ = 0.78 ±â€Š0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were "substantial" for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ±â€Š0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ±â€Š0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ±â€Š0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events. STUDY REGISTRATION: NCT02516488.

Early Splenic Flexure Intubation Competency Predicts Early Cecal Intubation Competency in Gastroenterology Fellows.

BACKGROUND: Trainees learn colonoscopy skills at varying speeds. We hypothesized that a fellow's ability to reliably reach the splenic flexure early in training could predict the number of procedures required to achieve competency in intubating the cecum. METHODS: This was a retrospective analysis of prospectively collected data. The most proximal site in the colon reached independently by GI fellows was recorded on consecutive colonoscopies. The number of procedures required to achieve splenic flexure intubation rate (SFIR) ≥ 90 % by cumulative summation learning curve and cecal intubation rate (CIR) ≥ 90 % by rolling average was calculated. Fellows were then dichotomized into "Early" versus "Late" learners based on the median number of procedures required to achieve SFIR ≥ 90 %. The number of procedures required to achieve CIR ≥ 90 % was then compared between the groups. RESULTS: Fellows achieved SFIR ≥ 90 % at a median of 37 colonoscopies. Fellows who achieved SFIR competency early achieved CIR ≥ 90 % at a mean of 208 procedures versus 352 procedures in the fellows who achieved SFIR competency late (p = 0.03). CONCLUSIONS: Data from a single academic medical center show that whether a trainee will learn endoscopy quickly compared to his/her peers can be predicted early in their endoscopy training by tracking SFIR. This knowledge could be used to customize endoscopy curriculum.

Duct Diameter and Size of Stones Predict Successful Extracorporeal Shock Wave Lithotripsy and Endoscopic Clearance in Patients With Chronic Pancreatitis and Pancreaticolithiasis.

OBJECTIVES: The need for endoscopic therapy before extracorporeal shock wave lithotripsy (SWL) to facilitate pancreatic duct stone removal is unclear. Predictive factors associated with successful fragmentation and subsequent complete duct clearance are variable. We hypothesize pancreatic duct strictures and large stones, but not pre-SWL endotherapy, correlate with successful fragmentation and complete duct clearance. METHODS: A retrospective cohort study of patients with pancreaticolithiasis who underwent SWL and endoscopic retrograde cholangiopancreatography between January 2009 and June 2014 was evaluated. RESULTS: Thirty-seven patients were treated. Technical success (TS) of fragmentation was achieved in 22 patients (60%). Technical success was associated with fewer stones and SWL sessions and smaller stone and duct size. By multivariate logistic regression, only duct dilation was associated with TS. Endoscopic success of complete duct clearance was achieved in 29 patients (80%). Endoscopic success was more frequent with stones 12 mm or less and with successful TS. By multivariate logistic regression, stones greater than 12 mm were associated with endoscopic failure. CONCLUSIONS: Pre-SWL endotherapy does not affect stone fragmentation. Patients with a dilated duct (>8 mm) and pancreatic stones 12 mm or greater were associated with unsuccessful TS and endoscopic success, respectively, and may benefit from early referral for surgical decompression.

Endoscopic Transpapillary Gallbladder Stent Placement Is Safe and Effective in High-Risk Patients Without Cirrhosis.

BACKGROUND: Endoscopic transpapillary gallbladder stent (ETGS) placement is a proposed minimally invasive alternative to cholecystectomy in high-risk patients with symptomatic gallbladder disease. AIMS: To describe the safety and efficacy of ETGS placement in 29 consecutive patients without cirrhosis. METHODS: A retrospective analysis of consecutive ETGS cases from 2005 to 2013 at a referral center was undertaken. RESULTS: The mean age was 70 years (range 40-91), and 62 % were hospitalized. The most common indication for ETGS was acute calculus cholecystitis (52 %). Comorbidities precluding cholecystectomy included advanced cancer (45 %), severe cardiopulmonary disease (21 %), and advanced age/frailty (17 %). Eighty-six percent of the patients had an ASA class of III or IV, and the Charlson comorbidity index was >3 in 55 %. An ETGS was successfully placed in 22 patients (76 %) with 18 being successful on the first attempt. A percutaneous rendezvous approach was required to obtain cystic duct access in six patients (21 %). During a mean follow-up of 376 days, a sustained clinical response was noted in 90 % of the patients with a stent placed. No peri-procedural complications were noted. However, two patients developed delayed complications of abdominal pain and cholangitis. Six patients were alive with their original stent still in place at a mean follow-up of 2.5 years. CONCLUSIONS: ETGS is an effective and safe alternative to cholecystectomy in high-risk patients. Technical success can be facilitated by a percutaneous rendezvous technique. Our data and those of others suggest that scheduled stent exchanges may not be required unless a clinical change occurs.

Intraprocedural quality in endoscopic retrograde cholangiopancreatography: a meta-analysis.

OBJECTIVES: In 2006, the American College of Gastroenterology (ACG)/the American Society for Gastrointestinal Endoscopy (ASGE) Taskforce on Quality in Endoscopy published quality indicators for the major gastrointestinal procedures. Our primary aim was to use the published literature to assess current endoscopic retrograde cholangiopancreatography (ERCP) intraprocedural performance and compare it to the targets set by the ACG/ASGE taskforce. Our secondary aim was to determine whether performance varies across different health-care settings (academic and community), study designs (prospective and retrospective), and trainee participation. METHODS: A PubMed and EMBASE literature search from 1/1/2006 to 2/1/2013 was conducted. Articles were selected based on title, abstract, full text, and reporting of success rates for the intraprocedural quality indicators. Success rates, represented as numerical proportions, were collected from each study. For each success rate, a standard error and a 95% confidence interval (CI) was calculated. A random-effects meta-analysis model was used to weight each study, and a cumulative, weighted success rate (or effect size) for each indicator was determined. Random-effects meta-regression was then used to examine the impact of study setting, design, and trainee involvement on each quality indicator. RESULTS: A total of 8,005 articles were initially retrieved. Following the application of predefined criteria, 52 articles remained. The cumulative, weighted bile duct cannulation success rate was 89.3% (95% CI 0.866-0.919); pancreatic duct cannulation was 85.0% (95% CI 0.813-0.886); precut utilization rate was 10.5% (95% CI 0.087-0.123); common bile duct stone extraction rate was 88.3% (95% CI 0.825-0.941); and the rate of successful biliary stenting below the common bile duct bifurcation was 97.5% (95% CI 0.967-0.984). Subgroup analysis with meta-regression showed no statistically significant differences between academic and community settings, prospective and retrospective study designs, and trainee participation on success across bile duct cannulation, precut utilization, and common bile duct stone extraction (insufficient observations/variance for pancreatic duct cannulation and biliary stent placement). CONCLUSIONS: ERCP intraprocedural quality is in good standing. On the basis of this analysis, the two targets that could be potentially revised are precut utilization and biliary stenting. This analysis was confined to the published literature and therefore, in general, reflects the ERCP performance of institutions, primarily academic, that are conducting clinical research. Thus, it is difficult to generalize this performance assessment to the broader ERCP community as a whole.

Impact of an incomplete colonoscopy referral program on recommendations after incomplete colonoscopy.

BACKGROUND: There are limited data on recommendations and adherence to complete colon evaluation (CCE) after incomplete colonoscopy (IC). AIMS: Our objectives were to (1) identify recommendations and adherence to recommendations after IC, (2) determine the diagnostic yield of CCE after IC, and (3) determine the effect of an IC referral program on recommendations for CCE. METHODS: We conducted a retrospective review of IC procedures at a teaching hospital over two time periods (January 1 to May 1 2004 and July 1 to November 1 2010). A referral process for repeat colonoscopy after IC was instituted in April 2009. Outcomes included (1) recommendations (2) adherence, and (3) yield of CCE after IC. RESULTS: A total of 222 patients underwent at least one IC (overall rate of 2.5 %). In 120 patients (54.1 %), CCE was recommended within 1 year; the rate did not change from 2004 to 2010. Patients with IC due to poor preparation were more likely to have specific CCE recommendations (85.5 vs. 72.2 %, P = 0.03) and recommendations of endoscopic follow-up (76.3 vs. 10.4 %, P < 0.0001) than those with IC due to difficult anatomy. When IC was due to difficult colonoscopy, there was increase in endoscopic follow-up recommended (16.3 vs. 2.8 %, P = 0.01) in 2010 compared to 2004. Adherence to recommendations was similar regardless of modality recommended, inpatient/outpatient status, polyps on initial exam, or extent of initial exam. Polyp detection rate was greater utilizing colonoscopy than barium enema (34.3 vs. 3.6 %, P < 0.0001). CONCLUSIONS: There is a lack of consensus in management strategies for patients after IC. Implementation of a referral program has had minimal impact on provider recommendations.