Advanced ERCP techniques for the extraction of complex biliary stones: a single referral center's 12-year experience.

OBJECTIVES: Advanced ERCP techniques (AETs) for difficult biliary stones include peroral cholangioscopy (POC) with electrohydraulic/laser lithotripsy (EHL/LL), endoscopic papillary large balloon dilation (EPLBD) and mechanical lithotripsy (ML). We assess the efficacy of AETs. METHODS: A retrospective query for AETs. PRIMARY OUTCOME: Complete duct clearance. Secondary outcome: Complete duct clearance by technique. Statistical Analysis version 9.3 (SAS Inc., Cary, NC). RESULTS: From 1/00 to 10/12, 349 patients were identified of which 222 (80% had prior ERCPs) had AETs. 211 with sufficient follow-up underwent 295 ERCPs; 280 of which were AET's. Index AETs: POC with EHL/LL (n = 46/211, 22%), ML (n = 84/211, 40%), EPLBD with mean balloon size of 11.5 ± 1.7 mm (n = 39/211, 18%) and combination AETs (n = 42/211, 20%). Stone characteristics: 76% had ≥1 stone, 81% extrahepatic and 32% had strictures. Number of stones (mean 2.5 and range 1-20) did not differ among groups. EPLBD had higher percentage (95%) of extrahepatic stones (p = .0003). The 'Combination' and 'POC' groups had larger stones (mean 17.7 mm ±6.4 and 16.8 mm ±6.1, respectively; p < .001). Complete clearance: 209/211 (99%) at index AET 167/211 (79%) or after mean of 2.5 ± 0.7 AETs in 42/211 (20%). Partial clearance: 2/211 (1%). Clearance at index AETs was higher with EPLBD (90%, p = .014). Adverse Events: 7/280 (2.5%). CONCLUSIONS: AETs achieved clearance in 99%. EPLBD had higher clearance at index AET likely owing to higher extrahepatic stones. Larger stones, but not number, were associated with increased combination AETs and total ERCPs.

Increasing Number of Passes Beyond 4 Does Not Increase Sensitivity of Detection of Pancreatic Malignancy by Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

BACKGROUND & AIMS: It is not clear exactly how many passes are required to determine whether pancreatic masses are malignant using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We aimed to define the per-pass diagnostic yield of EUS-FNA for establishing the malignancy of a pancreatic mass, and identify factors associated with detection of malignancies. METHODS: In a prospective study, 239 patients with solid pancreatic masses were randomly assigned to groups that underwent EUS-FNA, with the number of passes determined by an on-site cytopathology evaluation or set at 7 passes, at 3 tertiary referral centers. A final diagnosis of pancreatic malignancy was made based on findings from cytology, surgery, or a follow-up evaluation at least 1 year after EUS-FNA. The cumulative sensitivity of detection of malignancy by EUS-FNA was calculated after each pass; in the primary analysis, lesions categorized as malignant or suspicious were considered as positive findings. RESULTS: Pancreatic malignancies were found in 202 patients (84.5% of the study population). EUS-FNA detected malignancies with 96% sensitivity (95% confidence interval [CI], 92%-98%); 4 passes of EUS-FNA detected malignancies with 92% sensitivity (95% CI, 87%-95%). Tumor size greater than 2 cm was the only variable associated with positive results from cytology analysis (odds ratio, 7.8; 95% CI, 1.9-31.6). In masses larger than 2 cm, 4 passes of EUS-FNA detected malignancies with 93% sensitivity (95% CI, 89%-96%) and in masses ≤2 cm, 6 passes was associated with 82% sensitivity (95% CI, 61%-93%). Sensitivity of detection did not increase with increasing number of passes. CONCLUSIONS: In a prospective study, we found 4 passes of EUS-FNA to be sufficient to detect malignant pancreatic masses; increasing the number of passes did not increase the sensitivity of detection. Tumor size greater than 2 cm was associated with malignancy, and a greater number of passes may be required to evaluate masses 2 cm or less. ClinicalTrials.gov number, NCT01386931.

Interobserver agreement among cytopathologists in the evaluation of pancreatic endoscopic ultrasound-guided fine needle aspiration cytology specimens.

BACKGROUND AND AIMS: Endoscopic ultrasound with fine needle aspiration (EUS-FNA) has become the standard of care in the evaluation of solid pancreatic lesions. Limited data exist on interobserver agreement (IOA) among cytopathologists in assessing solid pancreatic EUS-FNA specimens. This study aimed to evaluate IOA among cytopathologists in assessing EUS-FNA cytology specimens of solid pancreatic lesions using a novel standardized scoring system and to assess individual clinical and cytologic predictors of IOA. METHODS: Consecutive patients who underwent EUS-FNA of solid pancreatic lesions at a tertiary care referral center were included. EUS-FNA slides were evaluated by four blinded cytopathologists using a standardized scoring system that assessed final cytologic diagnosis and quantitative (number of nucleated/diagnostic cells) and qualitative (bloodiness, inflammation/necrosis, contamination, artifact) cytologic parameters. Final clinical diagnosis was based on final cytology, surgical pathology, or 1-year clinical follow-up. IOA was calculated using multi-rater kappa (κ) statistics. Bivariate analyses were performed comparing cases with and without uniform agreement among the cytopathologists followed by logistic regression with backward elimination to model likelihood of uniform agreement. RESULTS: Ninety-nine patients were included (49 % males, mean age 64 years, mean lesion size 26 mm). IOA for final diagnosis was moderate (κ = 0.45, 95 % confidence interval (CI) 0.4 - 0.49) with minimal improvement when combining suspicious and malignant diagnoses (κ = 0.54, 95 %CI 0.49 - 0.6). The weighted kappa value for overall diagnosis was 0.65 (95 %CI 0.54 - 0.76). IOA was slight to fair (κ = 0.04 - 0.32) for individual cytologic parameters. A final clinical diagnosis of malignancy was the most significant predictor of agreement [OR 3.99 (CI 1.52 - 10.49)]. CONCLUSIONS: Interobserver agreement among cytopathologists for pancreatic EUS-FNA specimens is moderate-substantial for the final cytologic diagnosis. The final clinical diagnosis of malignancy was the strongest predictor of agreement. These results have significant implications for patient management and need to be validated in future trials.

Pancreatic Duct Changes in Patients With Chronic Pancreatitis Treated With Polyethylene and Sof-Flex Material Stents: A Blinded Comparison.

OBJECTIVES: Pancreatic stenting is used to improve painful, obstructive chronic pancreatitis. Data suggest that polyethylene stents (PESs) cause stent-associated changes (SACs). Whether a stent composed of more flexible material (Sof-Flex stent [SFS]) is associated with less SAC is unknown. METHODS: This study is a retrospective study of patients who underwent pancreatic duct stenting of at least 1 PES and 1 SFS on separate examinations and had a follow-up pancreatogram at the time of stent removal. The main outcome measurements were assessed for SAC on follow-up pancreatogram and interpreted by 2 radiologists blinded to the clinical data. RESULTS: Stent-associated changes were noted with 28% (13/47) of SFS and with 25% (13/52) of PES (P = 0.65). For 10F stent subgroups, SACs were seen with 25% (6/24) of the SFS compared with 50% (2/4) in the PES. Thirty percent (7/23) of the 8.5F SFS subgroup had SACs versus 29% (2/7) in the PES group (P = 0.887) for 8.5F + 10F combined comparison. CONCLUSIONS: In patients who have had polyethylene or SFSs of varying sizes, approximately 1 in 4 have SACs. Despite the use of a softer stent material for therapeutic stenting, the rate of SACs in the 8.5F and 10F subgroups seems similar between the 2 materials and design.

Variation in learning curves and competence for ERCP among advanced endoscopy trainees by using cumulative sum analysis.

BACKGROUND AND AIMS: There are limited data on learning curves and competence in ERCP. By using a standardized data collection tool, we aimed to prospectively define learning curves and measure competence among advanced endoscopy trainees (AETs) by using cumulative sum (CUSUM) analysis. METHODS: AETs were evaluated by attending endoscopists starting with the 26th hands-on ERCP examination and then every ERCP examination during the 12-month training period. A standardized ERCP competency assessment tool (using a 4-point scoring system) was used to grade the examination. CUSUM analysis was applied to produce learning curves for individual technical and cognitive components of ERCP performance (success defined as a score of 1, acceptable and unacceptable failures [p1] of 10% and 20%, respectively). Sensitivity analyses varying p1 and by using a less-stringent definition of success were performed. RESULTS: Five AETs were included with a total of 1049 graded ERCPs (mean ± SD, 209.8 ± 91.6/AET). The majority of cases were performed for a biliary indication (80%). The overall and native papilla allowed cannulation times were 3.1 ± 3.6 and 5.7 ± 4, respectively. Overall learning curves demonstrated substantial variability for individual technical and cognitive endpoints. Although nearly all AETs achieved competence in overall cannulation, none achieved competence for cannulation in cases with a native papilla. Sensitivity analyses increased the proportion of AETs who achieved competence. CONCLUSION: This study demonstrates that there is substantial variability in ERCP learning curves among AETs. A specific case volume does not ensure competence, especially for native papilla cannulation.

Predictors for Surgical Referral in Patients With Pancreatic Cystic Lesions Undergoing Endoscopic Ultrasound: Results From a Large Multicenter Cohort Study.

OBJECTIVE: Endoscopic ultrasound (EUS) plays an integral role in the evaluation of pancreatic cysts lesions (PCLs). The aim of the study was to determine predictors of surgical referral in patients with PCLs undergoing EUS. METHODS: We performed a multicenter retrospective study of patients undergoing EUS for evaluation of PCLs. Demographics, EUS characteristics, and fine-needle aspiration results were recorded. Patients were categorized into surgery or surveillance groups on the basis of post-EUS recommendations. Univariate and multivariate analyses were performed to identify predictors of surgical referral. RESULTS: 1804 patients were included. 1301 patients were recommended to undergo surveillance and 503 patients were referred for surgical evaluation, of which 360 patients underwent surgery. Multivariate analysis revealed the following 5 independent predictors of surgical referral: symptoms of weight loss on presentation (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.44-5.03), EUS findings of associated solid mass (OR, 7.34; 95% CI, 3.81-14.16), main duct communication (OR, 4.13; 95% CI, 1.71-9.98), multilocular macrocystic morphology (OR, 2.79; 95% CI, 1.78-4.38), and fine-needle aspiration findings of mucin on cytology (OR, 3.06; 95% CI, 1.94-4.82). CONCLUSIONS: This study identifies factors associated with surgical referral in patients with PCLs undergoing EUS. Future studies should focus on creation of risk stratification models to determine the need for surgery or enrollment in surveillance programs.

The clinical impact of immediate on-site cytopathology evaluation during endoscopic ultrasound-guided fine needle aspiration of pancreatic masses: a prospective multicenter randomized controlled trial.

OBJECTIVES: Observational data on the impact of on-site cytopathology evaluation (OCE) during endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of pancreatic masses have reported conflicting results. We aimed to compare the diagnostic yield of malignancy and proportion of inadequate specimens between patients undergoing EUS-FNA of pancreatic masses with and without OCE. METHODS: In this multicenter randomized controlled trial, consecutive patients with solid pancreatic mass underwent randomization for EUS-FNA with or without OCE. The number of FNA passes in the OCE+ arm was dictated by the on-site cytopathologist, whereas seven passes were performed in OCE- arm. EUS-FNA protocol was standardized, and slides were reviewed by cytopathologists using standardized criteria for cytologic characteristics and diagnosis. RESULTS: A total of 241 patients (121 OCE+, 120 OCE-) were included. There was no difference between the two groups in diagnostic yield of malignancy (OCE+ 75.2% vs. OCE- 71.6%, P=0.45) and proportion of inadequate specimens (9.8 vs. 13.3%, P=0.31). Procedures in OCE+ group required fewer EUS-FNA passes (median, OCE+ 4 vs. OCE- 7, P<0.0001). There was no significant difference between the two groups with regard to overall procedure time, adverse events, number of repeat procedures, costs (based on baseline cost-minimization analysis), and accuracy (using predefined criteria for final diagnosis of malignancy). There was no difference between the two groups with respect to cytologic characteristics of cellularity, bloodiness, number of cells/slide, and contamination. CONCLUSIONS: Results of this study demonstrated no significant difference in the diagnostic yield of malignancy, proportion of inadequate specimens, and accuracy in patients with pancreatic mass undergoing EUS-FNA with or without OCE.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study.

BACKGROUND AND AIMS: The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS: Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS: A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS: Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

ERCP with per-oral pancreatoscopy-guided laser lithotripsy for calcific chronic pancreatitis: a multicenter U.S. experience.

BACKGROUND: In patients with chronic pancreatitis, laser lithotripsy (LL) permits stone fragmentation and removal during ERCP with some advantages over extracorporeal shock-wave lithotripsy (ESWL) and surgery. OBJECTIVES: To evaluate the technical success of LL in pancreatic duct (PD) stones. DESIGN: Retrospective cohort. SETTING: Four tertiary referral centers. PATIENTS: Patients undergoing endotherapy for PD stones. INTERVENTIONS: ERCP with per-oral pancreatoscopy (POP)-guided LL. MAIN OUTCOME MEASUREMENT: Technical success was defined as complete stone clearance. RESULTS: Over 3 years, 28 patients (16 men, 51 years [mean age]) underwent a median of 1 (range, 1-4) POP-LL for PD stones. Baseline parameters included pain requiring hospitalization (n=19, 68%), opiate use (n=14, 50%), or weight loss (n=11, 39%). Before POP-LL, 22 of 28 patients (79%) had a median of 1 (range, 1-5) ERCP, 9 of 28 (32%) underwent a median of 2 (range, 1-3) ESWL sessions, and 5 underwent a median of 1 (range, 1-3) POP-guided electrohydraulic lithotripsy with failed (n=2) or partial (n=3) fragmentation. A median of 2 (range, 1-3) stones sized 15 mm (range, 4-32 mm) were identified in the head (n=9, 32%), neck (n=3, 11%), body (n=9, 32%), tail (n=1, 4%), or multiple sites (n=6, 21%). Technical success occurred in 22 patients (79%) with complete clearance. Partial clearance occurred in 3 (11%). Clinical success at a median of 13 (range, 1-25) months of follow-up was noted in 25 of 28 patients (89%) by improvement in pain (n=25), decreased narcotic use (n=25), or reduced hospitalizations (n=19). Mild adverse events occurred in 8 of 28 (29%). CONCLUSIONS: POP-LL is feasible at expert centers in patients with accessible stones. Although intensive endotherapy is required, most patients achieve stone clearance and clinical improvement.

Endoscopic and surgical treatment of malignant colorectal polyps: a population-based comparative study.

BACKGROUND: Long-term population-based data comparing endoscopic therapy (ET) and surgery for management of malignant colorectal polyps (MCPs) are limited. OBJECTIVE: To compare colorectal cancer (CRC)-specific survival with ET and surgery. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with stage 0 and stage 1 MCPs were identified from the Surveillance Epidemiology and End Results (SEER) database (1998-2009). Demographic characteristics, tumor size, location, treatment modality, and survival were compared. Propensity-score matching and Cox proportional hazards regression models were used to evaluate the association between treatment and CRC-specific survival. INTERVENTIONS: ET and surgery. MAIN OUTCOME MEASUREMENTS: Mid-term (2.5 years) and long-term (5 years) CRC-free survival rates and independent predictors of CRC-specific mortality. RESULTS: Of 10,403 patients with MCPs, 2688 (26%) underwent ET and 7715 (74%) underwent surgery. Patients undergoing ET were more likely to be older white men with stage 0 disease. Surgical patients had more right-sided lesions, larger MCPs, and stage 1 disease. There was no difference in the 2.5-year and 5-year CRC-free survival rates between the 2 groups in stage 0 disease. Surgical resection led to higher 2.5-year (97.8% vs 93.2%; P < .001) and 5-year (96.6% vs 89.8%; P < .001) CRC-free survival in stage 1 disease. These results were confirmed by propensity-score matching. ET was a significant predictor for CRC-specific mortality in stage 1 disease (hazard ratio 2.40; 95% confidence interval, 1.75-3.29; P < .001). LIMITATIONS: Comorbidity index not available, selection bias. CONCLUSIONS: ET and surgery had comparable mid- and long-term CRC-free survival rates in stage 0 disease. Surgical resection is the recommended treatment modality for MCPs with submucosal invasion.

Endoscopic ultrasonography in esophageal cancer leads to improved survival rates: results from a population-based study.

BACKGROUND: The advantages of endoscopic ultrasound (EUS) and computed tomography (CT)-positron emission tomography (PET) with respect to survival for esophageal cancer patients are unclear. This study aimed to assess the effects of EUS, CT-PET, and their combination on overall survival with respect to cases not receiving these procedures. METHODS: Patients who were ≥66 years old when diagnosed with esophageal cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare linked database. Cases were split into 4 analytic groups: EUS only (n = 318), CT-PET only (n = 853), EUS+CT-PET (n = 189), and no EUS or CT-PET (n = 2439). Survival times were estimated with the Kaplan-Meier method and were compared with the log-rank test for each group versus the no EUS or CT-PET group. Multivariate Cox proportional hazards models were used to compare 1-, 3-, and 5-year survival rates. RESULTS: Kaplan-Meier analyses showed that EUS, CT-PET, and EUS+CT-PET patients had improved survival for all stages (with the exception of stage 0 disease) in comparison with patients undergoing no EUS or CT-PET. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy, and chemoradiation. Multivariate Cox proportional hazards models showed that receipt of EUS was a significant predictor of improved 1- (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.39-0.59; P < .0001), 3- (HR, 0.57; 95% CI, 0.48-0.66; P < .0001), and 5-year survival (HR, 0.59; 95% CI, 0.50-0.68). Similar results were noted when the results were stratified on the basis of histology and for the CT-PET and EUS+CT-PET groups. CONCLUSIONS: Receipt of either EUS or CT-PET alone in esophageal cancer patients was associated with improved 1-, 3-, and 5-year survival. Future studies should identify barriers to the dissemination of these staging modalities.

Endoscopic retrograde cholangiopancreatography with per oral pancreatoscopy for calcific chronic pancreatitis using endoscope and catheter-based pancreatoscopes: a 10-year single-center experience.

OBJECTIVES: Per oral pancreatoscopy (POP) with electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) permits stone fragmentation and removal during endoscopic retrograde cholangiopancreatography. Our study evaluates the safety and efficacy of POP in patients with main pancreatic duct (PD) stones. METHODS: This was a cohort study of patients undergoing POP with EHL/LL for PD stones between January 2000 and March 2011. Technical success was defined as complete or partial stone clearance, and clinical success as greater than 50% reduction in opiate use, pain, or hospitalizations. RESULTS: Forty-six patients underwent POP for PD stones using a 10F cholangioscope (POP-Endo) (n = 31) or catheter-based system (POP-Cath, n = 15). Electrohydraulic lithotripsy/LL was performed in 39 (85%) of 46 patients. Stone extraction without EHL or LL was performed in 7 (15%) of 46 patients. Technical success for POP-Endo versus POP-Cath was 27 (87%) of 31 versus 15 (100%) of 15 patients (P = 0.29). Complete clearance was achieved in 21 (68%) of 31 versus 11 (73%) of 15 patients, respectively (P = 0.519). Per oral pancreatoscopy-related complications were found in 10%. Follow-up in 43 (93%) of 46 patients was a median of 18 months (range, 1-60 months). Overall clinical success was 74%. CONCLUSIONS: Per oral pancreatoscopy-guided endotherapy leads to partial or complete stone clearance in most patients with PD stones. The technical success rates between POP-Endo versus POP-Cath systems appear similar and are associated with clinical improvement in most patients.

Comparison of endoscopic therapies and surgical resection in patients with early esophageal cancer: a population-based study.

BACKGROUND: Outcome data comparing endoscopic eradication therapy (EET) and esophagectomy are limited in patients with early esophageal cancer (EC). OBJECTIVE: To compare overall survival and EC-related mortality in patients with early EC treated with EET and esophagectomy. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with early EC (stages T0 and T1) were identified from the Surveillance, Epidemiology, and End Results database (1998-2009). Demographics, tumor specific data, and survival were compared. Cox proportional hazards regression models were used to evaluate the association between treatment and EC-specific mortality. INTERVENTION: EET and esophagectomy. MAIN OUTCOME MEASUREMENTS: Mid- (2 years) and long- (5 years) term overall survival and EC-specific mortality, outcomes based on histology and stage, treatment patterns, and predictors of cancer-specific mortality. RESULTS: A total of 430 (21%) and 1586 (79%) patients underwent EET and esophagectomy, respectively. There was no difference in the 2-year (EET: 10.5% vs esophagectomy: 12.7%, P = .27).and 5-year (EET: 36.7% vs esophagectomy: 42.8%, P = .16) EC-related mortality rates between the 2 groups. EET patients had higher mortality rates attributed to non-EC causes (5 years: 46.6% vs 20.6%, P < .001). Similar results were noted when comparisons were limited to patients with stage T0 and T1a disease and esophageal adenocarcinoma. There was no difference in EC-specific mortality in the EET compared with the surgery group (hazard ratio 1.4; 95% confidence interval, 0.9-2.03). Variables associated with mortality were older age, year of diagnosis, radiation therapy, higher stage, and esophageal squamous cell carcinoma. LIMITATIONS: Comorbidities and recurrence rates were not available. CONCLUSIONS: This population-based study demonstrates comparable mid- and long-term EC-related mortality in patients with early EC undergoing EET and surgical resection.

Gastroenterology trainees can easily learn histologic characterization of diminutive colorectal polyps with narrow band imaging.

BACKGROUND & AIMS: Little is known about how teaching gastroenterology trainees polyp patterns by using narrow band imaging (NBI) affects their ability to characterize the histology of diminutive colorectal polyps. We developed and tested a tool to teach trainees to characterize the histology of diminutive polyps by using NBI. METHODS: Twelve gastroenterology trainees with varying levels of colonoscopy experience watched a teaching tool that described the NBI criteria to distinguish polyp histology. The trainees then watched 80 videos of NBI examination of diminutive polyps, recording their predictions of polyp histology and their degree of confidence. After each video, an expert provided feedback about actual polyp histology and the NBI criteria that supported each diagnosis. Twelve weeks later, without training or feedback during the interval, the trainees watched the same videos and predicted histologies of the polyps. Performance was evaluated by comparing predicted classification with actual histologic findings. Cumulative sum analysis was used to determine the learning curve for each trainee. RESULTS: Trainees made significant improvements in accuracy and the proportion of high-confidence predictions as they progressed through video blocks during the first session (P < .001). With active feedback, all trainees predicted polyp histologies with >90% accuracy, with a negative predictive value >90% for adenomatous histology. A median of 49 videos was required to achieve competency. For diagnoses made with high confidence, trainee performance exceeded 90% during the first and second sessions. Interobserver agreement was substantial (session 1, κ = 0.71; session 2, κ = 0.70). CONCLUSIONS: We developed a computer-based tool, combined with short videos and active feedback, to train gastroenterologists to identify polyp histology by using NBI. After training, gastroenterology trainees characterized the histology of diminutive polyps with ≥ 90% accuracy.

ERCP with probe-based confocal laser endomicroscopy for the evaluation of dominant biliary stenoses in primary sclerosing cholangitis patients.

BACKGROUND AND STUDY AIM: The incidence of cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) ranges between 7 and 14 %. Despite using multiple tissue sampling modalities, detection of CCA remains a challenge. Probe-based confocal laser endomicroscopy (pCLE) has been utilized to visualize subepithelial biliary mucosa in patients with indeterminate strictures. We assessed the technical feasibility and operating characteristics of pCLE in a cohort of PSC patients with dominant biliary strictures (DS). PATIENTS AND METHODS: This was a chart review of a prospectively maintained database at a single tertiary referral center of 15 PSC patients with 21 dominant stenoses undergoing pCLE. A data collection sheet included demographics, ERCP, cholangioscopy, pCLE (Miami criteria), tissue sampling results, and follow-up to 12 months or liver transplantation. Operating characteristics for pCLE and ERCP tissue sampling were calculated. RESULTS: Sufficient visualization of DS by pCLE was achieved in 20/21 (95 %). pCLE sensitivity, specificity, PPV, and NPV were 100 % (95 % CI 19.3-100 %), 61.1 % (95 % CI 35.8-82.6 %), 22.2 % (95 % CI 3.5-59.9 %), and 100 % (95 % CI 71.3-100 %), respectively, in detecting neoplasia. In comparison, concomitant tissue sampling yielded sensitivity, specificity, PPV, and NPV of 0 % (95 % CI 0-80.7 %), 94.4 % (95 % CI 72.6-99.1 %), 0 % (95 % CI 0-83.5 %), and 89.5 % (95 % CI 66.8-98.4 %), respectively. CONCLUSIONS: pCLE achieves a high technical success rate in patients with PSC and DS. This single center, small series, suggests that pCLE may have a high sensitivity and negative predictive value to exclude neoplasia. If verified in larger prospective studies, the technology may be utilized to risk stratify dominant strictures in patients with PSC.

A multicenter, U.S. experience of single-balloon, double-balloon, and rotational overtube-assisted enteroscopy ERCP in patients with surgically altered pancreaticobiliary anatomy (with video).

BACKGROUND: Data on overtube-assisted enteroscopy to facilitate ERCP in patients with surgically altered pancreaticobiliary anatomy, or long-limb surgical bypass, is limited. OBJECTIVE: To evaluate and compare ERCP success by using single-balloon (SBE), double-balloon (DBE), or rotational overtube enteroscopy. DESIGN: Consecutive patients identified retrospectively. SETTING: Eight U.S. referral centers. PATIENTS: Long-limb surgical bypass patients with suspected pancreaticobiliary diseases. INTERVENTION: Overtube-assisted enteroscopy ERCP. MAIN OUTCOME MEASUREMENTS: Enteroscopy success: visualizing the pancreaticobiliary-enteric anastomosis or papilla. ERCP success: completing the intended pancreaticobiliary intervention. Clinical success: greater than 50% reduction in abdominal pain or level of hepatic enzyme elevations or resolution of jaundice. RESULTS: From January 2008 through October 2009, 129 patients had 180 enteroscopy-ERCPs. Anatomy was Roux-en-Y: gastric bypass (n = 63), hepaticojejunostomy (n = 45), postgastrectomy (n = 6), Whipple procedure (n = 10), and other (n = 5). ERCP success was 81 of 129 (63%). Enteroscopy success: 92 of 129 (71%), of whom 81 of 92 (88%) achieved ERCP success. Reasons for ERCP failure (n = 48): afferent limb entered but pancreaticobiliary anastomosis and/or papilla not reached (n = 23), cannulation failure (n = 11), afferent limb angulation (n = 8), and jejunojejunostomy not identified (n = 6). Select interventions: anastomotic stricturoplasty (cautery ± dilation, n = 16), stone removal (n = 21), stent (n = 25), and direct cholangioscopy (n = 11). ERCP success rates were similar between Roux-en-Y gastric bypass and other long-limb surgical bypass and among SBE, DBE, and rotational overtube enteroscopy. Complications were 16 of 129, 12.4%. LIMITATIONS: Retrospective study. CONCLUSION: (1) ERCP is successful in nearly two-thirds of long-limb surgical bypass patients and in 88% when the papilla or pancreaticobiliary-enteric anastomosis is reached. (2) Enteroscopy success in long-limb surgical bypass is similar among SBE, DBE, and rotational overtube enteroscopy methods. (3) Referral of long-limb surgical bypass patients who require ERCP to high-volume institutions may be considered before more invasive percutaneous or surgical alternatives.

Molecular therapy for hepatic injury and fibrosis: where are we?

Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.

Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice.

Our previous study demonstrated that polycationic liposomes are highly stable in the bloodstream and represent an effective agent for liver gene delivery. We report here that liposome-mediated extracellular superoxide dismutase (EC-SOD) gene delivery successfully prevented acute liver injury in mice. The therapeutic efficacy of EC-SOD gene delivery by polycationic liposomes was determined against the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in a mouse model of acute liver injury caused by D-galactosamine and lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD plasmid led to a striking increase in superoxide dismutase activity in the medium. The transfected cells had much less cell death after reactive oxygen species exposure compared with untransfected or control plasmid-transfected cells. In a model of acute liver injury, serum alanine aminotransferase levels in mice receiving portal vein injections of EC-SOD lipoplexes were much lower than in those receiving normal saline, liposomes alone, or control lipoplexes. Liver histology confirmed that there was less cell death in the EC-SOD lipoplex-treated group. Quantitative reverse transcriptase polymerase chain reaction showed a 55-fold increase in human EC-SOD gene expression in the liver of mice injected with EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated mice was higher than in the control groups; this was associated with higher liver glutathione levels and reduced lipid peroxidation. In conclusion, polycationic liposome-mediated EC-SOD gene delivery protects against reactive oxygen species toxicity in vitro and against lipopolysaccharide-induced acute liver injury in D-galactosamine-sensitized mice.