Background Evaluation of indeterminate biliary strictures typically involves collection and analysis of tissue or cells. Brush cytology and intraductal biopsies that are routinely performed during ...ERCP to assess malignant-appearing biliary strictures are limited by relatively low sensitivity. Objective To study the comparative effectiveness of brushings for cytology and intraductal biopsies in the etiology of biliary strictures. Design Meta-analysis. Setting Referral center. Patients PUBMED and Embase databases were reviewed for studies published to April 2014 where diagnostic correlation of histology was available. Intervention Database and review of study findings. Main Outcome Measurements Sensitivity and specificity. Results The pooled sensitivity and specificity of brushings for the diagnosis of malignant biliary strictures was 45% (95% confidence interval CI, 40%-50%) and 99% (95% CI, 98%-100%), respectively. The pooled diagnostic odds ratio to detect malignant biliary strictures was 33.43 (95% CI, 14.29-78.24). For intraductal biopsies, the pooled sensitivity and specificity were 48.1% (95% CI, 42.8%-53.4%) and 99.2% (95% CI, 97.6%-99.8%), respectively. The pooled diagnostic odds ratio to detect malignant biliary strictures was 43.18 (95% CI, 19.39-95.83). A combination of both modalities only modestly increased the sensitivity (59.4%; 95% CI, 53.7%-64.8%) with a specificity of 100% (95% CI, 98.8%-100.0%). The Begg-Mazumdar and Egger tests indicated a low potential for publication bias. Limitations Inclusion of low-quality studies. Conclusion Our study suggests that both brushings and biopsy are comparable and have limited sensitivity for the diagnosis of malignant biliary strictures. A combination of both only modestly increases the sensitivity.
Background Patients with primary sclerosing cholangitis (PSC) are at risk of developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) may aid diagnosis of CCA. Objective To ...determine the diagnostic utility of FISH for CCA detection in patients with PSC. Design Meta-analysis. Setting Tertiary-care medical center. Patients Patients in studies where histopathologic correlation of CCA was available; 2 × 2 contingency data were constructed. Intervention Database search and review of study findings. Main Outcome Measurements Sensitivity, specificity, likelihood ratio, and pooled diagnostic odds ratio. Results The search yielded 8 studies, involving 828 patients who could be included in our meta-analysis. The pooled sensitivity and specificity of FISH for diagnosis of CCA in patients with PSC were 68% (95% confidence interval CI, 61%-74%) and 70% (95% CI, 66%-73%), respectively. The pooled positive likelihood ratio was 2.69 (95% CI, 1.84-3.97), and the negative likelihood ratio was 0.47 (95% CI, 0.39-0.58). The pooled diagnostic odds ratio was 7.24 (95% CI, 3.93-13.36). For FISH polysomy (6 studies, n = 690), the pooled sensitivity and specificity of FISH were 51% (95% CI, 43%-59%) and 93% (95% CI, 91%-95%), respectively. The heterogeneity indices of I2 measure of inconsistency was 45.9%. Visual inspection of the funnel plot showed low potential for publication bias. Limitations Inclusion of low-quality studies. Conclusion Our study suggests that FISH polysomy is highly specific; however, limited sensitivity of FISH highlights that better markers are required for early detection of CCA in PSC.
Background Malignant biliary obstruction frequently portends a poor prognosis. Palliative treatment with stenting is often required to alleviate symptoms and potentially prevent adverse events. ...Objectives The aims of our study were (1) to evaluate the clinical difference between self-expandable metal stents (SEMSs) and plastic stents (PSs) in both hilar and distal malignant biliary obstruction on occlusion rate and 30-day mortality rate (primary outcomes) and stent insertion success rate, therapeutic failure, reintervention rate, and adverse events (secondary outcomes); (2) to compare unilateral stenting with bilateral stenting in hilar malignant obstruction in terms of occlusion rate and 30-day mortality rate (primary outcomes) and insertion success rate, therapeutic failure, and adverse events (secondary outcomes). Methods PubMed, Embase, and Cochrane databases were searched for studies that provided data about malignant biliary obstruction and stent therapy. We included randomized, controlled trials (RCT), prospective observational cohort, and retrospective case-control studies. The quality of each included RCT study was assessed by the Jadad scale. Mantel-Haenszel odds ratios (ORs) and mean differences were calculated by using a random-effects model. Results Nineteen studies involving 1989 patients (1045 SEMSs and 944 PSs) were included for the comparison of SEMSs and PSs. We also included 7 studies that compared unilateral with bilateral stenting involving 634 patients (346 unilateral and 268 bilateral). Our meta-analysis confirmed that SEMSs are associated with a statistically significant lower risk of occlusion compared with PSs in the short term (OR 0.27; 95% confidence interval CI, 0.13-0.60) and long term (OR 0.38; 95% CI, 0.28-0.53). SEMSs had a lower 30-day occlusion rate than PSs in both hilar malignant obstruction (OR 0.16; 95% CI, 0.04-0.62) and distal malignant obstruction (OR 0.36; 95% CI, 0.14-0.93). SEMSs had a lower long-term occlusion rate compared with PSs in hilar malignant obstruction (OR 0.28; 95% CI, 0.19-0.39) and distal malignant obstruction (OR 0.42; 95% CI, 0.27-0.64). The 30-day mortality rate was similar with SEMSs and PSs (OR 0.74; 95% CI, 0.47-1.17). Therapeutic failure was more likely when using PSs (13%) compared with SEMSs (7%) (OR 0.43; 95% CI, 0.27-0.67). SEMSs required fewer reinterventions compared with PSs (mean difference, -0.49; 95% CI, -0.8 to -0.19). The incidence of cholangitis was statistically lower with SEMSs (8% vs 21%) (OR 0.41; 95% CI, 0.22-0.76). Bilateral stenting for hilar obstruction was not associated with a lower obstruction rate than unilateral stenting (OR 1.49; 95% CI, 0.77-2.89) or a lower 30-day mortality rate (OR 0.73; 95% CI, 0.29-1.79). There was no statistical difference in therapeutic failure (OR 1.47; 95% CI, 0.77-2.89) or cholangitis incidence (OR 0.61; 95% CI, 0.27-1.38). Conclusion SEMSs are associated with a statistically significantly lower occlusion rate, less therapeutic failure, less need for reintervention, and lower cholangitis incidence. There was no statistically significant difference in occlusion rate, therapeutic failure, and cholangitis incidence with bilateral stenting. Guideline recommendations may need to be modified to reflect clear and compelling data demonstrating the benefit of SEMSs in patients with malignant biliary obstruction. Bilateral stenting should be avoided because it has no benefit over unilateral stenting in terms of occlusion rate or therapeutic failure.
Background The most ominous adverse event of primary sclerosing cholangitis (PSC) is development of cholangiocarcinoma (CCA). There is a wide variation in the reported diagnostic yield of bile duct ...brush cytology in PSC strictures. Objective To determine the diagnostic utility of biliary brush cytology for CCA detection in patients with PSC. Design Meta-analysis. Systematic search of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies published up to December 2012. Setting Meta-analysis of diagnostic parameters. Patients A total of 747 patients in studies (both retrospective and prospective) in which histopathologic correlation of CCA was available. Intervention Meta-analysis. Construction of 2 × 2 contingency data. Main Outcome Measurements Sensitivity, specificity, likelihood ratio, and pooled diagnostic odds ratio. Results The search yielded 54 studies of which 11, involving 747 patients, were included in our meta-analysis. The pooled sensitivity and specificity of bile duct brushings for a diagnosis of CCA in patients with PSC were 43% (95% confidence interval CI, 35%-52%) and 97% (95% CI, 95%-98%), respectively. The pooled diagnostic odds ratio to detect CCA was 20.23 (95% CI, 8.75-46.79). The heterogeneity indices of χ2 statistics, I2 measure of inconsistency, and the Cochran Q test were 0.156, 14.4, and 30.5%, respectively. Visual inspection of the funnel plot showed low potential for publication bias. Limitations Inclusion of low-quality studies, study heterogeneity. Conclusion Our study suggests that bile duct brushing is a simple and highly specific technique for detection of CCA in patients with PSC. However, the modest sensitivity from bile duct brushing precludes its utility as a diagnostic tool for early detection of CCA in patients with PSC.
Background EUS has less than optimal interobserver agreement for the diagnosis of chronic pancreatitis. The newly developed Rosemont consensus scoring system includes weighted criteria and stricter ...definitions for individual features. Objective The primary aim was to compare the interobserver agreement of standard and Rosemont scoring. Setting Multiple tertiary-care institutions. Intervention Fifty EUS videos were interpreted by 14 experts. Each expert interpreted the videos on two occasions: First, the videos were read by using standard scoring (9 criteria). Second, after viewing a presentation of the Rosemont classification, the same experts re-read the videos by using Rosemont scoring. Main Outcome Measurements Fleiss' kappa (K) statistics are reported with 95% confidence intervals (CI). Results The interobserver agreement was “substantial” (K = 0.65 95% CI, 0.52-0.77) for Rosemont scoring and “moderate” (K = 0.54 95% CI, 0.44-0.66) for standard scoring; however, the difference was not statistically significant ( P = 0.12). Limitations The sample size does not allow detection of differences in K of <0.25. Conclusion Use of the Rosemont classification did not significantly increase interobserver agreement for EUS diagnosis of chronic pancreatitis compared with standard scoring.
Background ERCP is frequently used in patients with primary sclerosing cholangitis (PSC) for cancer surveillance and treatment of dominant strictures. Objective To evaluate the prevalence and risk ...factors for ERCP-related adverse events in patients with PSC. Design Retrospective analysis of ERCPs performed from 1998 to 2012. Setting Referral center. Patients A total of 294 consecutive patients with PSC who underwent a total of 657 ERCPs. Interventions ERCP. Main Outcome Measurements ERCP-related adverse events and predictive factors were determined by univariate and multivariate analyses. Results ERCP use in patients with PSC showed a significant increase during the second half of the study period (2006-2012) compared with the first half (1998-2005) (437 vs 220 procedures; P = .04). Primary cannulation was successful in 634 procedures (96.6%) or in 271 of 294 patients (92.2%). Access to the bile duct was achieved with a needle-knife in 19 procedures (2.9%), whereas ERCP was unsuccessful in 4 of 657 procedures (0.6%), and successful percutaneous drainage was performed. Post-ERCP pancreatitis (PEP) was diagnosed in 8 (1.2%), cholangitis in 16 (2.4%), and bleeding in 4 (0.7%) procedures. Overall, risk of any adverse event was 28 of 657 (4.3%) procedures. On multivariate analysis, performing biliary sphincterotomy (odds ratio OR 5.04; 95% confidence interval CI, 2.01-12.60; P = .001) and passage of a guidewire into the pancreatic duct (OR 4.54; 95% CI, 1.44-14.30; P = .010) were independently associated with an increased risk of any adverse event. Limitations Retrospective study. Conclusion Cholangitis appears to be the most common adverse event despite intraprocedural antibiotic use. There was a low risk of adverse events in patients with PSC undergoing ERCP.
Background and Aims Digital cholangioscopes provide higher-resolution imaging of the pancreatobiliary tract compared with fiberoptic instruments. The role of a new, digital, single-operator ...cholangiopancreatoscopy (SOC) system for diagnosis and treatment of pancreatobiliary disorders in clinical practice is not known. Methods We performed a multicenter, observational study of 105 consecutive patients with suspected pancreatobiliary disorders. The main outcome measures were (1) sensitivity and specificity of SOC visual appearance and biopsies in the diagnosis of indeterminate biliary strictures and (2) achieving complete duct clearance in patients with biliary or pancreatic duct stones. Results A total of 98 cholangioscopy and 7 pancreatoscopy procedures were performed in 105 patients. Superior views of the ductal lumen and mucosa were obtained in all 44 patients with indeterminate biliary strictures. Among the 44 patients who underwent SOC-guided biopsies, the specimen was adequate for histologic evaluation in 43 patients (97.7%). The sensitivity and specificity of SOC visual impression for diagnosis of malignancy was 90% (95% confidence interval CI, 69.9%-97.2%) and 95.8% (95% CI, 79.8%-99.3%), respectively. The sensitivity and specificity of SOC-guided biopsies for diagnosis of malignancy was 85% (95% CI, 64.0%-94.8%) and 100% (95% CI, 86.2%-100%). In patients with biliary or pancreatic duct stones (N = 36), complete duct clearance with stone removal in 1 session was accomplished in 86.1% of patients (31/36). Three patients (2.9%) experienced SOC-related adverse events that included cholangitis in 2 patients and postprocedure pancreatitis in 1 patient. Conclusions SOC has become an integral part of the ERCP armamentarium and has high accuracy in the evaluation of indeterminate biliary strictures. Complete stone clearance was achieved in all but 1 patient with challenging biliary or pancreatic duct stones. (Clinical trial registration number: NCT01815619 .)
Background Ascertaining the nature of biliary strictures is challenging. The role of volatile organic compounds (VOCs) in bile in determining the cause of biliary strictures is not known. Objective ...To identify potential VOCs in the headspaces (gas above the sample) of bile in patients with malignant biliary strictures from pancreatic cancer. Design Prospective cross-sectional study. Setting Referral center. Patients Prospective study in which bile was aspirated in 96 patients undergoing ERCP for benign and malignant conditions. Main Outcome Measurements Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze the headspace and to build a predictive model for pancreatic cancer. Results The headspaces from 96 bile samples were analyzed, including 24 from patients with pancreatic cancer and 72 from patients with benign biliary conditions. The concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and trimethylamine TMA) were increased in patients with pancreatic cancer compared with controls ( P < .05). By using receiver-operating characteristic curve analysis, we developed a model for the diagnosis of pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl sulfide, and acetaldehyde. The model 10.94 + 1.8229* log (acetaldehyde) + 0.7600* log (acetone) − 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) − 2.1401 * log (trimethylamine) ≥ 10 identified the patients with pancreatic cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9% specificity. Limitations Sample size. Conclusions The measurement of biliary fluid VOCs may help to distinguish malignant from benign biliary strictures. Further studies are warranted to validate these observations. (Clinical Trial Registration Number NCT01565460 .)
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