Still elusive: Developments in the accurate diagnosis of indeterminate biliary strictures

Indeterminate biliary strictures pose a significant diagnostic dilemma for gastroenterologists.Despite advances in endoscopic techniques and instruments,it is difficult to differentiate between benign and malignant pathology.A positive histological diagnosis is always preferred prior to high risk hepatobiliary surgery,or to inform other types of therapy.Endoscopic retrograde cholangiopancreato-graphy with brushings has low sensitivity and despite significant improvements in instruments there is still an unacceptably high false negative rate.Other methods such as endoscopic ultrasound and cholangioscopy have improved diagnostic quality.In this review we explore the techniques available to aid accurate diagnosis of indeterminate biliary strictures and obtain accurate histology to facilitate clinical management.

Current endoscopic approach to indeterminate biliary strictures

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome. Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.

Eosinophilic cholangitis is a potentially underdiagnosed etiology in indeterminate biliary stricture

To investigate presence and extent of eosinophilic cholangitis (EC) as well as IgG4-related disease in patients with indeterminate biliary stricture (IBS).METHODSAll patients with diagnosis of sclerosing cholangitis (SC) and histopathological samples such as biopsies or surgical specimens at University Hospital Frankfurt from 2005-2015 were included. Histopathological diagnoses as well as further clinical course were reviewed. Tissue samples of patients without definite diagnosis after complete diagnostic work-up were reviewed regarding presence of eosinophilic infiltration and IgG4 positive plasma cells. Eosinophilic infiltration was as well assessed in a control group of liver transplant donors and patients with primary sclerosing cholangitis.RESULTSone hundred and thirty-five patients with SC were included. In 10/135 (13.5%) patients, no potential cause of IBS could be identified after complete diagnostic work-up and further clinical course. After histopathological review, a post-hoc diagnosis of EC was established in three patients resulting in a prevalence of 2.2% (3/135) of all patients with SC as well as 30% (3/10) of patients, where no cause of IBS was identified. 2/3 patients with post-hoc diagnosis of EC underwent surgical resection with suspicion for malignancy. Diagnosis of IgG4-related cholangitis was observed in 7/135 patients (5.1%), whereas 3 cases were discovered in post-hoc analysis. 6/7 cases with IgG4-related cholangitis (85.7%) presented with eosinophilic infiltration in addition to IgG4 positive plasma cells. There was no patient with eosinophilic infiltration in the control group of liver transplant donors (n = 27) and patients with primary sclerosing cholangitis (n = 14).CONCLUSIONEC is an underdiagnosed benign etiology of SC and IBS, which has to be considered in differential diagnosis of IBS.

Clinical approach to indeterminate biliary strictures:Clinical presentation,diagnosis,and workup

Despite advances in cross-sectional imaging and endoscopic technology,bile duct strictures remain a challenging clinical entity.It is crucial to make an early determination of benign or malignant nature of biliary strictures.Early diagnosis not only helps with further management but also minimizes mortality and morbidity associated with delayed diagnosis.Conventional imaging and endoscopic techniques,particularly endoscopic retrograde cholangiopancreatography(ERCP)and tissue sampling techniques play a key in establishing a diagnosis.Indeterminate biliary strictures(IDBSs)have no definite mass on imaging or absolute histopathological diagnosis and often warrant utilization of multiple diagnostics to ascertain an etiology.In this review,we discuss possible etiologies,clinical presentation,diagnosis,and management of IDBSs.Based on available data and expert opinion,we depict an evidence based diagnostic algorithm for management of IDBSs.Areas of focus include use of traditional tissue sampling techniques such as ERCP with brush cytology,intraductal biopsies,fluorescence in situ hybridization and flow cytometry.We also describe the role of endoscopic ultrasound(EUS)-guided fine needle aspiration and biopsies,cholangioscopy,confocal laser endomicroscopy,and intraductal EUS in management of IDBSs.

Endoscopic ultrasonography can diagnose distal biliary strictures without a mass on computed tomography

AIM:To assess the diagnostic ability of endoscopic ultrasonography(EUS)for evaluating causes of dista biliary strictures shown on endoscopic retrograde chol angiopancreatography(ERCP)or magnetic resonance cholangiopancreatography(MRCP),even without iden tifiable mass on computed tomography(CT). METHODS:The diagnostic ability of EUS was retro spectively analyzed and compared with that of routine cytology(RC)and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP a Dokkyo Medical School Hospital from December 2005 to December 2008,without any adjacent mass or ec centric thickening of the bile duct on CT that could cause biliary strictures.Findings considered as benign strictures on EUS included preservation of the normasonographic layers of the bile duct wall,irrespective of the presence of a mass lesion.Other strictures were considered malignant.Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples,and by clinical follow-up for>10 mo in 16 cases. RESULTS:Seventeen patients(50%)were finally di- agnosed with benign conditions,including 6"normal" subjects,while 17 patients(50%)were diagnosed with malignant disease.In terms of diagnostic ability,EUS showed 94.1%sensitivity,82.3%specificity,84.2% positive predictive value,93.3%negative predictive value(NPV)and 88.2%accuracy for identifying ma- lignant and benign strictures.EUS was more sensi- tive than RC(94.1%vs 62.5%,P=0.039).NPV was also better for EUS than for RC(93.3%vs 57.5%,P= 0.035).In addition,EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9(94.1%vs 53%,P=0.017).On EUS,biliary stricture that was fi- nally diagnosed as malignant showed as a hypoechoic, irregular mass,with obstruction of the biliary duct and invasion to surrounding tissues. CONCLUSION:EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT.Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Peroral cholangioscopy:Update on the state-of-the-art

Peroral cholangioscopy(POC)is an endoscopic procedure that allows direct intraductal visualization of the biliary tract.POC has emerged as a vital tool for indeterminate biliary stricture evaluation and treatment of difficult biliary stones.Over several generations of devices,POC has fulfilled additional clinical needs where other diagnostic or therapeutic modalities have been inadequate.With adverse event rates comparable to standard endoscopic retrograde cholangioscopy and unique technical attributes,the role of POC is likely to continue expand.In this frontiers article,we highlight the existing and growing clinical applications of POC as well as areas of ongoing research.

Choledochoscopy:An update

Choledochoscopy,or cholangioscopy,is an endoscopic procedure for direct visualization within the biliary tract for diagnostic or therapeutic purposes.Since its conception in 1879,many variations and improvements are made to ensure relevance in diagnosing and managing a range of intrahepatic and extrahepatic biliary pathologies.This ranges from improved visual impression and optical guided biopsies of indeterminate biliary strictures and clinically indistinguishable pathologies to therapeutic uses in stone fragmentation and other ablative therapies.Furthermore,with the evolving understanding of biliary disorders,there are significant innovative ideas and techniques to fill this void,such as nuanced instances of biliary stenting and retrieving migrated ductal stents.With this in mind,we present a review of the current advancements in choledochoscopy with new supporting evidence that further delineates the role of choledochoscopy in various diagnostic and therapeutic interventions,complications,limitations and put forth areas for further study.