Raj J. Shah

Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience.

BACKGROUNDnBecause of the low sensitivity of current ERCP-guided tissue sampling methods, management of patients with indeterminate pancreaticobiliary strictures is a challenge. Probe-based confocal laser endomicroscopy (pCLE) enables real-time microscopic visualization of strictures during an ongoing ERCP.nnnOBJECTIVEnTo document the utility, performance, and accuracy of real-time pCLE diagnosis compared with histopathology.nnnDESIGNnProspective observational study within the framework of a multicenter registry.nnnSETTINGnFive academic centers.nnnPATIENTSnThis study involved 102 patients with indeterminate pancreaticobiliary strictures.nnnINTERVENTIONnClinical information, ERCP findings, tissue sampling results, and pCLE videos were collected prospectively. Investigators were asked to provide a presumptive diagnosis based on pCLE during the procedure before pathology results were available. All patients received at least 30 days of follow-up until definitive diagnosis of malignancy was established or 1-year follow-up if index tissue sampling was benign.nnnMAIN OUTCOME MEASUREMENTSnDiagnostic accuracy, sensitivity, specificity of ERCP-guided pCLE compared with ERCP with tissue acquisition.nnnRESULTSnThere were no pCLE-related adverse events in the study. We were able to evaluate 89 patients, of whom 40 were proven to have cancer. The sensitivity, specificity, positive-predictive value, and negative-predictive value of pCLE for detecting cancerous strictures were 98%, 67%, 71%, and 97%, respectively, compared with 45%, 100%, 100%, and 69% for index pathology. This resulted in an overall accuracy of 81% for pCLE compared with 75% for index pathology. Accuracy for combination of ERCP and pCLE was significantly higher compared with ERCP with tissue acquisition (90% vs 73%; P = .001).nnnLIMITATIONSnInvestigators had access to all relevant clinical information, which may have biased the predictive characteristics of pCLE.nnnCONCLUSIONnProbe-based CLE provides reliable microscopic examination and has excellent sensitivity and negative predictive value. The significantly higher accuracy of ERCP and pCLE compared with ERCP with tissue acquisition may support supplementing ERCP with pCLE.

Comparative performance of uncoated, self-expanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial.

BACKGROUNDnThe Wallstent has remained the industry standard for biliary self-expanding metal stents (SEMSs). Recently, stents of differing designs, compositions, and diameters have been developed.nnnOBJECTIVEnTo compare the new nitinol 6-mm and 10-mm Zilver stents with the 10-mm stainless steel Wallstent and determine the mechanism of obstruction.nnnDESIGNnRandomized, prospective, controlled study.nnnSETTINGnNine centers experienced in SEMS placement during ERCP.nnnPATIENTSnA total of 241 patients presenting between September 2003 and December 2005 with unresectable malignant biliary strictures at least 2 cm distal to the bifurcation.nnnMAIN OUTCOME MEASUREMENTnStent occlusions requiring reintervention and death.nnnRESULTSnAt interim analysis, a significant increase in occlusions was noted in the 6-mm Zilver group at the P = .04 level, resulting in arm closure but continued follow-up. Final study arms were 64, 88, and 89 patients receiving a 6-mm Zilver, 10-mm Zilver, and 10-mm Wallstent, respectively. Stent occlusions occurred in 25 (39.1%) of the patients in the 6-mm Zilver arm, 21 (23.9%) of the patients in the 10-mm Zilver arm, and 19 (21.4%) of the patients in the 10-mm Wallstent arm (P = .02). The mean number of days of stent patency were 142.9, 185.8, and 186.7, respectively (P = .057). No differences were noted in secondary endpoints, and the study was ended at the 95% censored study endpoints. Biopsy specimens of ingrowth occlusive tissue revealed that 56% were caused by benign epithelial hyperplasia.nnnCONCLUSIONSnSEMS occlusions were much more frequent with a 6-mm diameter SEMS and equivalent in the two 10-mm arms despite major differences in stent design, material, and expansion, suggesting that diameter is the critical feature. Malignant tumor ingrowth produced only a minority of the documented occlusions.

Classification of probe-based confocal laser endomicroscopy findings in pancreaticobiliary strictures.

BACKGROUND AND STUDY AIMSnThe accurate diagnosis of indeterminate pancreaticobiliary strictures presents a clinical dilemma. Probe-based confocal laser endomicroscopy (pCLE) offers real-time in vivo microscopic tissue examination that may increase sensitivity for the detection of malignancy. the objective of this study was to develop and validate a standard descriptive classification of pcle in the pancreaticobiliary system.nnnPATIENTS AND METHODSnA total of 102 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with pCLE to assess indeterminate pancreaticobiliary strictures were enrolled in a multicenter registry; 89 of these patients were evaluable. Information and data on the following were collected prospectively: clinical, ERCP, tissue sampling, pCLE, and follow-up. A uniform classification of pCLE findings (Miami Classification) was developed, consisting of a set of image interpretation criteria. Thereafter, these criteria were tested through blinded consensus review of 112 randomized pCLE videos from 47 patients, and inter-observer variability was assessed in 42 patients .nnnRESULTSnA consensus definition of the specific criteria of biliary and pancreatic pCLE findings for indeterminate strictures was developed. Single-image interpretation criteria did not have a high enough sensitivity for predicting malignancy. However, combining two or more criteria significantly increased the sensitivity and predictive values. The characteristics most suggestive of malignancy included the following: thick white bands (>20 µm), or thick dark bands (>40 µm), or dark clumps or epithelial structures. These provided sensitivity, specificity, positive predictive value, and negative predictive value of 97%, 33%, 80%, and 80% compared with 48%, 100%, 100%, and 41% for standard tissue sampling methods. Inter-observer variability was moderate for most criteria.nnnCONCLUSIONnThe Miami Classification enables a structured, uniform, and reproducible description of pancreaticobiliary pCLE. Combining individual characteristics improves the sensitivity for the detection of malignancy.

Multicenter comparison of the interobserver agreement of standard EUS scoring and Rosemont classification scoring for diagnosis of chronic pancreatitis

BACKGROUNDnEUS 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.nnnOBJECTIVEnThe primary aim was to compare the interobserver agreement of standard and Rosemont scoring.nnnSETTINGnMultiple tertiary-care institutions.nnnINTERVENTIONnFifty 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.nnnMAIN OUTCOME MEASUREMENTSnFleiss kappa (K) statistics are reported with 95% confidence intervals (CI).nnnRESULTSnThe 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).nnnLIMITATIONSnThe sample size does not allow detection of differences in K of <0.25.nnnCONCLUSIONnUse of the Rosemont classification did not significantly increase interobserver agreement for EUS diagnosis of chronic pancreatitis compared with standard scoring.

Multicenter randomized trial of the spiral Z-stent compared with the Wallstent for malignant biliary obstruction.

BACKGROUNDnThe industry standard since 1990 for self-expanding biliary metallic stents has been the Wallstent. In 1998 the Spiral Z-stent was released. This randomized trial compared the Z-stent with the Wallstent in the treatment of malignant biliary obstruction.nnnMETHODSnPatients with unresectable malignant biliary obstruction distal to the bile duct bifurcation were randomized to receive a 10-mm diameter Wallstent or a 10-mm diameter Z-stent.nnnRESULTSnA total of 145 patients were randomized; 13 were excluded. Sixty-four patients who received a Z-stent and 68 who had a Wallstent are included in the analysis. Tumors responsible for bile duct obstruction were pancreatic cancer (108), cholangiocarcinoma (15), metastatic cancer (6), and papillary cancer (3). Metallic stents were successfully placed in all patients. Seven technical problems were encountered during placement of the Z-stent and 5 with the Wallstent. There were 21 occlusions requiring reintervention (8 Z-stent, 13 Wallstent; p = 0.30). Median time to reintervention was the following: Z-stent, 162 days; Wallstent, 150 days (p = 0.22). A total of 104 patients died of progressive disease or other cause; 7 patients remain alive with patent stents. The overall calculated median patency rates were: Z-stent, 152 days; Wallstent, 154 days (p = 0.90).nnnCONCLUSIONSnThe Spiral Z-stent is comparable with the Wallstent in terms of placement, occlusion rates, and overall patency. Occasional early occlusion of both stents suggests tumor characteristics instead of the size of the mesh openings in the stents as important factors.

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

BACKGROUND AND AIMSnThe 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.nnnMETHODSnConsecutive 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.nnnRESULTSnA total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipples 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.nnnCONCLUSIONSnCyst 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.

Impact of Radiofrequency Ablation on Malignant Biliary Strictures: Results of a Collaborative Registry

AbstractBackgroundnRadiofrequency ablation of malignant biliary strictures has been offered for the last 3xa0years, but only limited data have been published.AimnTo assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation.MethodsBetween April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting.ResultsA total of 69 patients (22 male, aged 66.1xa0±xa013.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma (nxa0=xa045), pancreatic cancer (nxa0=xa019), gallbladder cancer (nxa0=xa02), gastric cancer (nxa0=xa01), and liver metastasis from colon cancer (nxa0=xa03). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3xa0mm. There was a statistically significant improvement in stricture diameter post-ablation (pxa0<xa00.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95xa0% 1.03–5.38)]. Seven patients (10xa0%) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46xa0months (6.2–25xa0months).ConclusionRadiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival.n

Interobserver Agreement for Single Operator Choledochoscopy Imaging: Can We Do Better?

Background. The SpyGlass Direct Visualization System (Boston Scientific, Natick, MA) is routinely used during single operator choledochoscopy (SOC) to identify biliary lesions or strictures with a diagnostic accuracy up to 88%. The objective of this study was to determine the interobserver agreement (IOA) of modified scoring criteria for diagnosing biliary lesions/strictures. Methods. 27 SPY SOC video clips were reviewed and scored by 9 interventional endoscopists based on published criteria that included the presence and severity of surface structure, vasculature visualization, lesions, and findings. Results. Overall IOA was “slight” for all variables. The K statistics are as follows: surface (K = 0.12, SEu2009=u20090.02); vessels (K = 0.14, SEu2009=u20090.02); lesions (K = 0.11, SEu2009=u20090.02); findings (K = 0.08, SEu2009=u20090.03); and final diagnosis (K = 0.08, SEu2009=u20090.02). The IOA for “findings” and “final diagnosis” was also only “slight.” The final diagnosis was malignant (11), benign (11), and indeterminate (5). Conclusion. IOA using the modified criteria of SOC images was slight to almost poor. The average accuracy was less than 50%. These findings reaffirm that imaging criteria for benign and malignant biliary pathology need to be formally established and validated.

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.u200aIOA 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 (49u200a% males, mean age 64 years, mean lesion size 26u200amm). IOA for final diagnosis was moderate (κu200a=u200a0.45, 95u200a% confidence interval (CI) 0.4u200a–u200a0.49) with minimal improvement when combining suspicious and malignant diagnoses (κu200a=u200a0.54, 95u200a%CI 0.49u200a–u200a0.6). The weighted kappa value for overall diagnosis was 0.65 (95u200a%CI 0.54u200a–u200a0.76). IOA was slight to fair (κu200a=u200a0.04u200a–u200a0.32) for individual cytologic parameters. A final clinical diagnosis of malignancy was the most significant predictor of agreement [OR 3.99 (CI 1.52u200a–u200a10.49)]. 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.

Per-oral video cholangiopancreatoscopy with narrow-band imaging for the evaluation of indeterminate pancreaticobiliary disease

BACKGROUND AND AIMSnCholangiopancreatoscopy for evaluating pancreaticobiliary pathology is currently limited by suboptimal optics. The aim of this study was to characterize the operating characteristics of per-oral video cholangiopancreatoscopy with narrow-band imaging (POVCP) findings in indeterminate pancreaticobiliary disease and to describe their association with neoplasia.nnnMETHODSnData from consecutive patients undergoing POVCP for the evaluation of indeterminate pancreaticobiliary disease at a single tertiary care center were analyzed. Two experienced investigators had previously agreed on POVCP findings and terminology that were documented in endoscopy reports. Endoscopic procedural data from POVCPs performed between January 2006 and April 2015 and clinical data were abstracted from the endoscopic database and electronic medical records. Study endpoints included tissue-proven neoplasia or benign disease withxa0≥1 year of follow-up.nnnRESULTSnA total of 109 patients were identified; 13 were excluded because of the presence of stone disease, known pancreaticobiliary malignancy, or presumed benign disease withxa0≤1 year of follow-up. Most patients (85%) underwent POVCP for biliary disease and 15% underwent POVCP for a pancreatic cause. Tortuous and dilated vessels (Pxa0< .001), infiltrative stricture (Pxa0< .001), polypoid mass (Pxa0= .003), and the presence of fish-egg lesions (Pxa0= .04) were found to be significantly associated with neoplasia. The overall POVCP impression had a high sensitivity (85%) and negative predictive value (89%) in assessing for the presence of neoplasia.nnnCONCLUSIONSnPer-oral video cholangiopancreatoscopy is effective in the evaluation of indeterminate pancreaticobiliary disease. Tortuous and dilated vessels, infiltrative stricture, polypoid mass, and the presence of fish-egg lesions are significantly associated with neoplasia.