Clinical predictors of significant findings on EUS for the evaluation of incidental common bile duct dilation.

BACKGROUND AND AIMS: Although EUS is highly accurate for the evaluation of common bile duct (CBD) dilation, the yield of EUS in patients with incidental CBD dilation is unclear. METHODS: Serial patients undergoing EUS for incidental, dilated CBD (per radiologist, minimum of >6 mm objectively) from 2 academic medical centers without active pancreaticobiliary disease or significantly elevated liver function test results were evaluated. Multivariable logistic regression identified predictors of EUS with significant findings and a novel prediction model was derived from one center, internally validated with bootstrapping, and externally validated at the second center. RESULTS: Of 375 patients evaluated, 31 (8.3%) had significant findings, including 26 choledocholithiasis, 1 ampullary adenoma, and 1 pancreatic mass. Predictors of significant findings with EUS included age of ≥70 years (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-10.0), non-biliary-type abdominal pain without chronic pain (OR, 6.1; 95% CI, 2.3-17.3), CBD diameter of ≥15 mm or ≥17 mm with cholecystectomy (OR, 6.9; 95% CI, 2.7-18.7), and prior ERCP (OR, 6.8; 95% CI, 2.1-22.5). A point-based novel clinical prediction model was created: age of ≥70 years = 1, non-biliary-type abdominal pain without chronic pain = 2, prior ERCP = 2, and CBD dilation = 2. A score of <1 had 93% (development) and 100% (validation) sensitivity and predicted a <2% chance of having a significant finding in both cohorts while excluding the need for EUS in ∼30% of both cohorts. Conversely, a score of ≥4 was >90% specific for the presence of significant pathology. CONCLUSIONS: Less than 10% of patients undergoing EUS for incidental CBD dilation had pathologic findings. This novel, externally validated, clinical prediction model may reduce low-yield, invasive evaluation in nearly one-third of patients.

High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival.

Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.

Endoscopic ultrasound-guided biliary drainage in benign biliary pathology with normal foregut anatomy: a multicenter study.

BACKGROUND AND AIMS: Biliary drainage using endoscopic ultrasound (EUS-BD) has been developed as a novel technique to obtain biliary access and drainage when ERCP fails. Numerous studies have demonstrated its safety and efficacy specifically pertaining to those with malignant distal biliary obstruction or altered foregut anatomy. The aim of this study is to evaluate the safety and efficacy of EUS-BD in benign indications in patients with normal foregut anatomy. METHODS: We performed a retrospective comparative study from 5 academic medical centers (2008-2018) involving patients with benign biliary obstruction and native foregut anatomy who had an initial failed ERCP with subsequent attempt at biliary decompression via EUS-BD or by repeating ERCP. RESULTS: 36 patients (mean age 61.6 ± 2.2, 38.9% female) who underwent attempted EUS-BD following initial failed ERCP were compared to 50 patients (mean age 62.7 ± 2.3, 73.5% female) who underwent repeat ERCP following an initial failed cannulation. EUS-BD was technically successful in 28 (77.8%) patients with rendezvous being the most common approach (86.1%). A higher level of pre-procedural bilirubin was found to be associated with technical success of EUS-BD (3.65 ± 0.63 versus 1.1 ± 0.4, p value 0.04). Success of repeat ERCP following failed cannulation was 86%. Adverse events were significantly more frequent in the EUS-BD cohort when compared to the repeat ERCP (10 (27.8%) versus 4 (8.0%), p = 0.02, OR 4.32. CONCLUSIONS: EUS-BD remains a viable therapeutic option in the setting of benign biliary disease, with success rates of 77.8%. Adverse events were significantly more common with EUS-BD vs. repeat ERCP, emphasizing the need to perform in expert centers with appropriate multidisciplinary support and to strongly consider the urgency of biliary decompression before considering same session EUS-BD after failed initial biliary access.

Radiologic Predictors of Increased Number of Necrosectomies During Endoscopic Management of Walled-off Pancreatic Necrosis.

GOALS: No established methods exist to predict who will require a higher number of endoscopic necrosectomy sessions for walled-off necrosis (WON). We aim to identify radiologic predictors for requiring a greater number of necrosectomy sessions. This may help to identify patients who benefit from aggressive endoscopic management. MATERIALS AND METHODS: This is a multicenter retrospective study of patients with WON at 3 tertiary care centers. WON characteristics on preintervention computed tomography imaging were evaluated to determine if they were predictive of requiring more endoscopic necrosectomy. RESULTS: A total of 104 patients were included. Seventy patients (67.3%) underwent endoscopic necrosectomy, with median of 2 necrosectomies. WON largest transverse diameters (P=0.02), largest coronal diameters (P=0.01), necrosis pattern [likelihood ratio (LR)=17.85, P<0.001], spread (LR=11.02, P=0.01), hemorrhage (LR=8.64, P=0.003), and presence of disconnected pancreatic duct (LR=6.80, P=0.01) were associated with undergoing ≥2 necrosectomies. Patients with septations/loculations were significantly less likely to undergo ≥2 necrosectomies (LR=4.86, P=0.03). CONCLUSIONS: Several computed tomography radiologic features were significantly associated with undergoing ≥2 necrosectomies. These could help identify patients who will undergo a higher number of endoscopic necrosectomy sessions.

Validation of choledocholithiasis predictors from the "2019 ASGE Guideline for the role of endoscopy in the evaluation and management of choledocholithiasis."

BACKGROUND AND AIMS: Identifying patients likely to have CDL is an important clinical dilemma because endoscopic retrograde cholangiopancreatography (ERCP), carries a 5-7% risk of adverse events. The purpose of this study was to compare the diagnostic test performance of the 2010 and 2019 ASGE criteria used to help risk stratify patients with suspected CDL. METHODS: Consecutive patients evaluated for possible CDL from 2013 to 2019 were identified from surgical, endoscopic, and radiologic databases at a single academic center. Inclusion criteria included all patients who underwent ERCP and/or cholecystectomy with intraoperative cholangiogram (IOC) for suspected CDL. We calculated the diagnostic test performance of criteria from both guidelines and compared their discrimination using the receiver operator curve. Univariate and multivariate analysis was used to identify the strongest component predictors. RESULTS: 1098 patients [age 57.9 ± 19.0 years, 62.8% (690) F] were included. 66.3% (728) were found to have CDL on ERCP and/or IOC. When using the 2019 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 65.8, 78.9, 86.3, 54.1, and 70.4%, respectively. Using the 2010 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 50.5, 78.9, 82.5, 44.8, and 60.1%, respectively. The AUC for high-risk criteria using the 2019 guidelines [0.726 (0.695, 0.758)] was greater than for the 2010 guidelines [0.647 (0.614, 0.681)]. The key difference providing the increased discrimination was the inclusion of stones on any imaging modality, which increased the sensitivity to 55.0% from 29.1%. Not including CDL on imaging or cholangitis, a dilated CBD was the strongest individual predictor of CDL on multivariate analysis (OR 3.70, CI 2.80, 4.89). CONCLUSION: Compared to 2010, the 2019 high-risk criterion improves diagnostic test performance, but still performs suboptimally. Less invasive tests, such as EUS or MRCP, should be considered in patients with suspected CDL prior to ERCP.

A multicenter, prospective, inpatient feasibility study to evaluate the use of an intra-colonoscopy cleansing device to optimize colon preparation in hospitalized patients: the REDUCE study.

BACKGROUND: High quality bowel preparation prior to colonoscopy can be difficult to achieve in the inpatient setting. Hospitalized patients are at risk for extended hospital stays and low diagnostic yield due to inadequate bowel preparation. The Pure-Vu System is a novel device intended to fit over existing colonoscopes to improve intra-colonoscopy bowel preparation. The objective of the REDUCE study was to conduct the first inpatient study to evaluate optimization of bowel preparation quality following overnight preparation when using the Pure-Vu System during colonoscopy. METHODS: This multicenter, prospective feasibility study enrolled hospitalized subjects undergoing colonoscopy. Subjects recorded the clarity of their last bowel movement using a 5-point scale prior to colonoscopy. After one night of preparation, all enrolled subjects underwent colonoscopy utilizing the Pure-Vu System. The primary endpoint was improvement of colon cleanliness from baseline to post-cleansing with the Pure-Vu System as assessed by the improvement in Boston Bowel Preparation Scale (BBPS). An exploratory analysis was conducted to assess whether the clarity of the last bowel movement could predict inadequate bowel preparation. RESULTS: Ninety-four subjects were included. BBPS analyses showed significant improvements in bowel preparation quality across all evaluable colon segments after cleansing with Pure-Vu, including left colon (1.74 vs 2.89; p < 0.0001), transverse colon (1.74 vs 2.91; p < 0.0001), and the right colon (1.41 vs 2.88; p < 0.0001). Prior to Pure-Vu, adequate cleansing (BBPS scores of ≥ 2) were reported in 60%, 62%, and 47% for the left colon, transverse colon, and right colon segments, respectively. After intra-colonoscopy cleansing with the Pure-Vu System, adequate colon preparation was reported in 100%, 99%, and 97% of the left colon, transverse colon, and right colon segments, respectively. Subjects with lower bowel movement clarity scores were more likely to have inadequate bowel preparation prior to cleansing with Pure-Vu. CONCLUSIONS: In this feasibility study, the Pure-Vu System appears to be effective in significantly improving bowel preparation quality in hospitalized subjects undergoing colonoscopy. Clarity of last bowel movement may be useful indicator in predicting poor bowel preparation. Larger studies powered to evaluate clinical outcomes, hospital costs, and blinded BBPS assessments are required to evaluate the significance of these findings. Trial registration Evaluation of the Bowel Cleansing in Hospitalized Patients Using Pure-Vu System (NCT03503162).

Dynamic spatiotemporal coordination of neural stem cell fate decisions occurs through local feedback in the adult vertebrate brain.

Neural stem cell (NSC) populations persist in the adult vertebrate brain over a lifetime, and their homeostasis is controlled at the population level through unknown mechanisms. Here, we combine dynamic imaging of entire NSC populations in their in vivo niche over several weeks with pharmacological manipulations, mathematical modeling, and spatial statistics and demonstrate that NSCs use spatiotemporally resolved local feedback signals to coordinate their decision to divide in adult zebrafish brains. These involve Notch-mediated short-range inhibition from transient neural progenitors and a dispersion effect from the dividing NSCs themselves exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that these signals are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis and coordinate specific spatiotemporal correlations.

Performance and Predictors of Migration of Partially and Fully Covered Esophageal Self-Expanding Metal Stents for Malignant Dysphagia.

BACKGROUND & AIMS: Self-expanding metal stents (SEMS) are routinely used to palliate malignant dysphagia. However esophageal SEMS can migrate or obstruct due to epithelial hyperplasia. The aim of this study was to evaluate the rates and factors predicting migration and obstruction, and the nutritional outcomes in partially covered (pc) vs. fully covered (fc) SEMS vs. fcSEMS with antimigration fins (AF) placed for malignant dysphagia. METHODS: A retrospective review of consecutive patients undergoing SEMS placement for malignant dysphagia at three academic medical centers. RESULTS: Among 357 patients, there were 55 (15.4%) stent migrations, 45 (12.6%) obstructions from epithelial hyperplasia, and 20 (5.6%) food impactions. Median overall survival was 79 days (IQR 41,199). The percent weight change/change in albumin at 30 and 60 days after SEMS placement were -2.24%/-0.544 g/dL and -2.98%/-0.55 g/dL, respectively. Stent migration occurred significantly more often with fcSEMS than pcSEMS (25.3% vs 10.9%; P < .003), but there was no difference when either group was compared to fcSEMS-AF (19.3%). The overall rate of epithelial hyperplasia resulting in stent obstruction was low (12.6%) and not different between stent types. Factors associated with increased risk of SEMS migration on multivariable logistic regression included stricture traversability with a diagnostic endoscope (OR, 2.37; 95% CI, 1.29-4.35) and use of fcSEMS (OR, 2.56; 1.31-5.00) or fcSEMS-AF (OR, 2.30, 1.03-5.14). CONCLUSIONS: Traversability of a malignant esophageal stenosis predicts SEMS migration. In these patients with a limited overall survival, pcSEMS are associated with lower rates of stent migration and similar rates of obstruction compared to fcSEMS.

Endoscopic ultrasound-guided drainage of pancreatic walled-off necrosis using 20-mm versus 15-mm lumen-apposing metal stents: an international, multicenter, case-matched study.

BACKGROUNDS: Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. METHODS: We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). RESULTS: Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P < 0.001), despite having larger WON collections (transverse axis 118.2 vs. 101.9 mm, P = 0.003; anteroposterior axis 95.9 vs. 80.1 mm, P = 0.01). There was no difference in overall adverse events (21.6 % vs. 15.2 %; P = 0.72) and bleeding events (4.9 % vs. 3.4 %; P = 0.54) between the 20-mm and 15-mm LAMS groups, respectively. CONCLUSIONS: The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.

Outcomes of endoscopic treatment of leaks and fistulae after sleeve gastrectomy: results from a large multicenter U.S. cohort.

BACKGROUND: Sleeve gastrectomy is the most commonly performed bariatric surgery in the United States. Leaks after sleeve gastrectomy (SGL) occur in 1% to 3% of patients. Endoscopic therapies are increasingly used for treatment of SGLs, but few data exist on their outcomes. OBJECTIVES: The aim of this study was to assess technical success, leak resolution, and reoperation rates of patients undergoing endoscopic therapy for repair SGLs. SETTING: Eight high-volume academic endoscopy centers. METHODS: Patients undergoing endoscopic therapy for SGLs from 2007 to 2017 were identified. Patients were excluded if the index endoscopic therapy for SGL was performed elsewhere or if no follow-up data were available. Leaks were classified as acute (≤7 d of SG), early (1-6 wk), late (7-12 wk), and chronic (>12 wk). Leak resolution was defined as lack of extraluminal air, extravasation on oral contrast radiography, cross-sectional imaging, or resolution of percutaneous drain output. Demographic and procedural data were recorded as rates of additional therapy, adverse events, and surgical revision. RESULTS: A total of 85 patients met criteria for analysis (70 women, age 42.6 ± 10.8 yr). A total of 295 endoscopic sessions (median 3, range 1-14) were performed across the cohort. SGLs resolved after index endoscopic therapy in 43 (50.1%) patients. The primary outcome of endoscopic resolution of SGL was observed in 62 patients (72.9%). There were 34 (11.5%) PRAE (the majority occurring with self-expandable metal stents), all but 1 of which were managed endoscopically. Surgical revision was required in 23 (21.7%) patients. On univariate analyses independent variables associated with the need for surgical revision included both acute and chronic SGLs (P = .028), loculated subphrenic collections/abscesses (P = .03), and intraabdominal sepsis (P = .03). On multivariable logistic regression using statistically significant predictors from the univariate analyses, acute SGLs were significantly associated with a need for surgical revision (odds ratio 4.8, 95% confidence interval 1.2-18.9, P = .025). CONCLUSION: Endoscopic therapy for SGLs is associated with good clinical success, avoiding the need for surgical revision in 73% of patients, with an acceptable adverse event profile. Patients with acute or chronic SGLs and those with loculated abscesses or intraabdominal sepsis are more likely to undergo surgical revision. Endoscopic therapy is an appropriate first-line modality for the management of SGLs, especially those not classified as acute or chronic.

Anatomic location of Barrett's esophagus recurrence after endoscopic eradication therapy: development of a simplified surveillance biopsy strategy.

BACKGROUND AND AIMS: Surveillance endoscopy is recommended after endoscopic eradication therapy (EET) for Barrett's esophagus (BE) because of the risk of recurrence. Currently recommended biopsy protocols are based on expert opinion and consist of sampling visible lesions followed by random 4-quadrant biopsy sampling throughout the length of the original BE segment. Despite this protocol, some recurrences are not visibly identified. We aimed to identify the anatomic location and histology of recurrences after successful EET with the goal of developing a more efficient and evidence-based surveillance biopsy protocol. METHODS: We performed an analysis of a large multicenter database of 443 patients who underwent EET and achieved complete eradication of intestinal metaplasia (CE-IM) from 2005 to 2015. The endoscopic location of recurrence relative to the squamocolumnar junction (SCJ), visible recurrence identified during surveillance endoscopy, and time to recurrence after CE-IM were assessed. RESULTS: Fifty patients with BE recurrence were studied in the final analysis. Seventeen patients (34%) had nonvisible recurrences. In this group, biopsy specimens demonstrating recurrence were taken from within 2 cm of the SCJ in 16 of these 17 patients (94%). Overall, 49 of 50 recurrences (98%) occurred either within 2 cm of the SCJ or at the site of a visible lesion. Late recurrences (>1 year) were more likely to be visible than early (<1 year) recurrences (P = .006). CONCLUSIONS: Recurrence after EET detected by random biopsy sampling is identified predominately in the distal esophagus and occurs earlier than visible recurrences. As such, we suggest a modified biopsy protocol with targeted sampling of visible lesions followed by random biopsy sampling within 2 cm of the SCJ to optimize detection of recurrence after EET. (Clinical trial registration number: NCT02634645.).

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.).

Use of a Transparent Cap Increases the Diagnostic Yield in Antegrade Single-Balloon Enteroscopy for Obscure GI Bleed.

BACKGROUND AND AIMS: Single-balloon enteroscopy (SBE) is utilized in the evaluation of obscure gastrointestinal bleeding, but 40-50% of these patients experience continued GI blood loss, in part due to missed lesions. The utilization of a transparent cap attached to the end of the endoscope can improve mucosal visualization in other endoscopic applications, but has not yet been evaluated in SBE. The aim of this study was to evaluate the impact of a cap on the diagnostic yield of SBE. METHODS: Consecutive adult patients scheduled for anterograde SBE for the evaluation of obscure GI bleeding were screened for inclusion from 2014 to 2017. Patients were randomized to SBE with or without a transparent cap. The primary outcome was the proportion of enteroscopies in which a P2 lesion (high potential for bleeding) was identified. RESULTS: A total of 90 patients (65.7 ± 12.7 years old, 47.7% female) were analyzed. There were significantly more P2 arteriovenous malformations identified in the cap group (14.8% vs. 0%, p = 0.02). Additionally, the use of a cap was associated with a significantly greater depth of small bowel insertion (191.9 cm vs. 156.2 cm, p = 0.01). There was one perforation in the group without a cap, successfully treated with clip placement, and no adverse events in the cap group. CONCLUSIONS: The use of a transparent cap during SBE performed for the evaluation of obscure gastrointestinal bleeding may be an important, safe augmentation to standard SBE techniques.

A randomized controlled trial evaluating general endotracheal anesthesia versus monitored anesthesia care and the incidence of sedation-related adverse events during ERCP in high-risk patients.

BACKGROUND AND AIMS: ERCP is a complex procedure often performed in patients at high risk for sedation-related adverse events (SRAEs). However, there is no current standard of care with regard to mode of sedation and airway management during ERCP. The aim of this study was to assess the safety of general endotracheal anesthesia (GEA) versus propofol-based monitored anesthesia care (MAC) without endotracheal intubation in patients undergoing ERCP at high risk for SRAEs. METHODS: Consecutive patients undergoing ERCP at high risk for SRAEs at a single center were invited to participate in this randomized controlled trial comparing GEA and MAC. Inclusion criteria were STOP-BANG score ≥3, abdominal ascites, body mass index ≥35, chronic lung disease, American Society of Anesthesiologists class >3, Mallampati class 4 airway, and moderate to heavy alcohol use. Exclusion criteria were preceding EUS, emergent ERCP, tracheostomy, unstable airway, gastric outlet obstruction or delayed gastric emptying, and altered foregut anatomy. The primary endpoint was composite incidence of SRAEs: hypoxemia, use of airway maneuvers, hypotension requiring vasopressors, sedation-related procedure interruption, cardiac arrhythmia, and respiratory failure. Secondary outcomes included procedure duration, cannulation success, in-room time, and immediate adverse events. RESULTS: Two hundred patients (mean age, 61.1 ± 13.6 years; 36.5% women) were randomly assigned to GEA (n = 101) or MAC (n = 99) groups. Composite SRAEs were significantly higher in the MAC group compared with the GEA group (51.5% vs 9.9%, P < .001). This was primarily driven by the frequent need for airway maneuvers in the MAC group. Additionally, ERCP was interrupted in 10.1% of patients in the MAC group to convert to GEA because of respiratory instability refractory to airway maneuvers (n = 8) or significant retained gastric contents (n = 2). There were no statistically significant differences in cannulation, in-room, procedure, or fluoroscopy times between the 2 groups. All patients undergoing GEA were successfully extubated in the procedure room at completion of ERCP, and Aldrete scores in recovery did not differ between the 2 groups. There were no immediate adverse events. CONCLUSION: In patients at high risk for SRAEs undergoing ERCP, sedation with GEA is associated with a significantly lower incidence of SRAEs, without impacting procedure duration, success, recovery, or in-room time. These data suggest that GEA should be used for ERCP in patients at high risk for SRAEs (Clinical trial registration number: NCT02850887.).

The Diagnostic Yield of Malignancy Comparing Cytology, FISH, and Molecular Analysis of Cell Free Cytology Brush Supernatant in Patients With Biliary Strictures Undergoing Endoscopic Retrograde Cholangiography (ERC): A Prospective Study.

BACKGROUND: Routine cytology of biliary stricture brushings obtained during endoscopic retrograde cholangiopancreatography (ERCP) has suboptimal sensitivity for malignancy. We compared the individual and combined ability of cytology, fluorescence in situ hybridization (FISH) analysis and PCR-based mutation profiling (MP) to detect malignancy in standard biliary brushings. METHODS: We performed a prospective study of patients undergoing ERCP using histology or 1 year follow-up to determine patient outcomes. MP was performed on free-DNA from biliary brushing specimens using normally discarded supernatant fluid. MP examined KRAS point mutations and tumor suppressor gene associated loss of heterozygosity mutations at 10 genomic loci. FISH examined chromosome specific gains or losses. RESULTS: A total of 101 patients were included in final analysis and 69% had malignancy. Cytology had 26% sensitivity and 100% specificity for malignancy. Using either FISH or MP in combination with cytology increased sensitivity to 44% and 56%, respectively. The combination of all 3 tests (cytology, FISH, and MP) had the highest sensitivity for malignancy (66%). There was no difference in the specificity of cytology, FISH or MP testing when examined alone or in combination. MP improved diagnostic yield of each procedure from 22% to 100%; FISH improved yield to 90%. MP detected 21 malignancies beyond that identified by cytology; FISH detected an additional 13. The combination of FISH and MP testing detected an additional 28 malignancies. CONCLUSIONS: Both MP and FISH are complimentary molecular tests that can significantly increase detection of biliary malignancies when used in combination with routine cytology of standard biliary brush specimens.

Health-related quality of life and long-term outcomes after endoscopic therapy for walled-off pancreatic necrosis.

BACKGROUND AND AIM: Walled-off pancreatic necrosis (WON) frequently develops after necrotizing pancreatitis. Endoscopic drainage has become the preferred modality for symptomatic or infected WON. The aim of the present study was to assess health-related quality of life (HR-QOL) and long-term outcomes in patients undergoing endoscopic drainage for WON. METHODS: Patients undergoing endoscopic drainage of WON from January 2006 to May 2016 were identified. Data recorded included demographic information, and the incidence of long-term sequelae including pancreatic endocrine and exocrine insufficiency. Attempts were made to contact all patients. HR-QOL was assessed using the SF-36 questionnaire. RESULTS: Eighty patients were analyzed, 41 (51.3%) of whom completed the SF-36. One-year all-cause mortality was 6.2%, and disease-related mortality was 3.7%. A notable proportion of patients developed exocrine insufficiency (32.5%), endocrine insufficiency (27.7%), and long-term opiate use (42.5%). Development of exocrine insufficiency was predictive of lower total SF-36 scores (P = 0.016). Patients with WON had better HR-QOL compared with cohorts of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In patients developing exocrine insufficiency versus healthy controls, poorer scores in the physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), and emotional role (P = 0.029) domains were observed. Exocrine insufficiency patients had better HR-QOL than the IBS and IBD cohorts, although these differences were less pronounced. CONCLUSION: After undergoing endoscopic drainage for WON, patients have relatively preserved HR-QOL. The subset of patients that develop exocrine insufficiency have significantly poorer HR-QOL compared to healthy controls, although not to the degree of chronic gastrointestinal disorders such as IBS and IBD.

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.

The importance of early recognition in management of ERCP-related perforations.

BACKGROUND: Iatrogenic perforations related to endoscopic retrograde cholangiopancreatography (ERCP) are rare events, carrying with it a mortality of up to 8%. Given the rarity of this adverse event, there remains limited data and continued uncertainties when choosing therapeutic strategies. Our aims were to evaluate the management of ERCP-related perforations and compare outcomes based on timing of recognition. METHODS: The endoscopic databases of two tertiary care centers were interrogated to identify consecutive adult patients who sustained ERCP-related perforation over a 10-year period from 2006 to 2016. Electronic medical records were reviewed to extract demographic data, perforation type, management strategies, clinical data, and patient outcomes. RESULTS: 14,045 ERCP's were performed during our 10-year study period. Sixty-three patients (average age 62.3 ± 2.38 years, 76% female) with ERCP-related perforations were included. Stapfer I perforations were found in 14 (22.2%) patients, Stapfer II in 24 (38.1%), and Stapfer III and IV perforations were identified in 16 (25.4%) and 9 (14.28%), respectively. Forty-seven (74.6%) perforations were recognized immediately during the ERCP, whereas 16 (25.4%) were recognized late. Endoscopic therapy was attempted in 35 patients in whom perforations were identified immediately, and was technically successful in 33 (94.3%). In all, 4 (1 immediate/ 3 delayed) patients required percutaneous drainage and 9 (5 immediate/ 4 delayed) surgery. Length of hospital stay, ICU admission were significantly shorter and incidence of SIRS was significantly lower when perforation was recognized immediately. CONCLUSIONS: Immediate recognition of ERCP-related perforations leads to more favorable patient outcomes; with lower incidence of SIRS, less need for ICU level care, and shorter hospital stay.

Utility of Endoscopic Ultrasound in Evaluating Local Recurrence After Surgery for Pancreatic Cancer.

Pancreatic adenocarcinoma recurrence after surgery (PARaS) is associated with poor outcomes. PARaS is locoregional in 50%-80%, effecting the resection bed and adjacent lymphatics.1-3 Detection of PARaS via endoscopic ultrasound (EUS) is challenging because recurrent malignancy is difficult to distinguish from normal postoperative changes. Diagnosing PARaS is important, because salvage chemotherapy/radiation improves survival.4,5 The purpose of this investigation is to determine the clinical utility of EUS fine-needle aspiration (FNA) in patients with suspected PARaS.