Direct Single-Operator Cholangioscopy and Intraductal Ultrasonography in Patients with Indeterminate Biliary Strictures: A Single Center Experience.

The evaluation of biliary strictures poses a challenge due to the low sensitivity of standard diagnostic approaches, but the advent of direct single-operator cholangioscopy (DSOC) has revolutionized this paradigm. Our study aimed to assess the diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS), and standard brush cytology in patients with indeterminate biliary strictures (IBS). We reviewed patients who underwent advanced diagnostic evaluation for IBS at our endoscopy unit from January 2018 to December 2022, all of whom had previously undergone at least one endoscopic attempt to characterize the biliary stricture. Final diagnoses were established based on surgical pathology and/or clinical and radiological follow-up spanning at least 12 months. A total of 57 patients, with a mean age of 67.2 ± 10.0 years, were included, with a mean follow-up of 18.2 ± 18.1 months. The majority of IBS were located in the distal common bile duct (45.6%), with malignancy confirmed in 35 patients (61.4%). DSOC and IDUS demonstrated significantly higher accuracies (89.5% and 82.7%, respectively) compared to standard cytology (61.5%, p < 0.05). Both DSOC visualization and IDUS exhibited optimal diagnostic yields in differentiating IBS with an acceptable safety profile.

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 cholangiopancreatography 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.

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.

Endoscopic evaluation of indeterminate biliary strictures: Cholangioscopy, endoscopic ultrasound, or both?

Accurate and timely diagnosis of biliary strictures can be challenging. Because the diagnostic sensitivity and accuracy of standard endoscopic retrograde cholangiopancreatography-based tissue sampling for malignancy are suboptimal, additional endoscopic evaluation by cholangioscopy and/or endoscopic ultrasound (EUS) is often necessary to differentiate between malignant and benign biliary strictures to guide clinical management. While direct visualization by cholangioscopy and/or high-resolution imaging by EUS are often the first step in the evaluation of an indeterminate biliary stricture (IDBS), tissue diagnosis by cholangioscopy-guided biopsy and/or EUS-guided fine-needle tissue acquisition is the preferred modality to establish a diagnosis of malignancy. Because each modality has its own strengths and limitations, selection of cholangioscopy and EUS is best guided by the biliary stricture location and local expertise. Artificial intelligence-assisted diagnosis, biopsy forceps with improved design, contrast-enhanced EUS, and dedicated fine-needle biopsy devices are recent technological advances that may further improve the diagnostic performance of cholangioscopy and EUS in patients with IDBS.

The Role of Cholangioscopy in Biliary Diseases.

Endoscopy plays a central role in diagnostic and therapeutic approaches to biliary disease in both benign and malignant conditions. A cholangioscope is an endoscopic instrument that allows for the direct exploration of the biliary tree. Over the years, technology has improved endoscopic image quality and allowed for the development of an operative procedure that can be performed during cholangioscopy. Different types of instruments are available in this context, and they can be used in different anatomical access points according to the most appropriate clinical indication. The direct visualization of biliary mucosa is essential in the presence of biliary strictures of unknown significance, allowing for the appropriate allocation of patients to surgery or conservative treatments. Cholangioscopy has demonstrated excellent performance in discriminating malignant conditions (such as colangiocarcinoma) from benign inflammatory strictures, and more recent advances (e.g., artificial intelligence and confocal laser endomicroscopy) could further increase its diagnostic accuracy. Cholangioscopy also plays a primary role in the treatment of benign conditions such as difficult bile stones (DBSs). In this case, it may not be possible to achieve complete biliary drainage using standard ERCP. Therapeutic cholangioscopy-guided lithotripsy allows for stone fragmentation and complete biliary drainage. Indeed, other complex clinical situations, such as patients with intra-hepatic lithiasis and patients with an altered anatomy, could benefit from the therapeutic role of cholangioscopy. The aim of the present review is to explore the most recent diagnostic and therapeutic advances in the roles of cholangioscopy in the management of biliary diseases.

Multidisciplinary Approach to Indeterminate Biliary Strictures.

Biliary strictures that remain unclassified after cross-sectional imaging and endoscopic retrograde cholangiopancreatography-based tissue sampling are defined as indeterminate biliary strictures (IDBS). A substantial proportion of biliary strictures fall into this category due to low sensitivity of brush cytology and intraductal biopsy. Over last few decades, several modalities have emerged for the evaluation of IDBS. Of these, cholangioscopy and endosonography are the frontrunners and have cemented their place for the evaluation of IDBS. Both of these modalities are widely available, and therefore, biliary strictures that remain uncharacterized after their utilization represent IDBS in the current era.

Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study.

BACKGROUND AND AIM: Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications. METHODS: This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications. RESULTS: D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal. CONCLUSION: D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.

Identification of endoscopic predictors of biliary malignancy during digital cholangioscopy.

OBJECTIVES: Biliary brushings and biopsies obtained during endoscopic retrograde cholangiopancreatography (ERCP) have a low sensitivity for the diagnosis of malignant biliary strictures. While cholangioscopic analysis is useful, visual criteria have not yet been defined. The aim of this study was to identify visual criteria for the diagnosis of indeterminate biliary strictures (IDBS). METHODS: A multicenter study was conducted based on the analysis of cholangioscopic recordings of IBDS. Diagnostic criteria were identified in a study group and verified in a validation group. RESULTS: Four criteria were identified to be associated with malignancy, one negatively ("endobiliary material," odds ratio [OR] 0.62, 95% confidence interval [CI] 0.41-0.92) and three positively ("vascularized villous projections," OR 1.52, 95% CI 1.03-2.24; "twisted or dilated vessels," OR 2.18, 95% CI 1.47-3.24; and "dark color of the mucosa," OR 1.82, 95% CI 1.23-2.70). Between two playbacks, the mean (95% CI) sensitivity of the observer's visual diagnosis increased from 66.1% (60-72) to 73.8% (69-78) (P = 0.004); in the second playback, the kappa value for interobserver agreement ranged between 0.36 (color) and 0.56 (endobiliary material), with a significant improvement (P = 0.0031-0.0001) between the first and second playbacks. Blind assessment by endoscopists not involved in this study had a diagnostic accuracy of 73% (71.4-74.5). CONCLUSION: The four identified cholangioscopic features are easy to implement in clinical practice and have the potential to increase the level of diagnostic confidence during the workup of IDBS.

Digital Cholangioscopic Interpretation: When North Meets the South.

BACKGROUND: Digital single-operator cholangioscopy (DSOC) (SpyGlass DS™, Boston Scientific, MA, USA) allows for high-definition imaging of the biliary tree. The superior visualization has led to the development of two different sets of criteria to evaluate and classify indeterminate biliary strictures: the Monaco criteria and the criteria in Carlos Robles-Medranda's publication (CRM). Our objective was to assess the interrater agreement (IA) of DSOC interpretation for indeterminate biliary strictures using the two newly published criteria. METHODS: Forty de-identified DSOC video recordings were sent to 15 interventional endoscopists with experience in cholangioscopy. They were asked to score the videos based on the presence of Monaco Classification criteria: stricture, lesion, mucosal changes, papillary projections, ulceration, white linear bands or rings, and vessels. Next, they scored the videos using CRM criteria: villous pattern, polypoid pattern, inflammatory pattern, flat pattern, ulcerate pattern and honeycomb pattern. The endoscopists then diagnosed the recordings as neoplastic or non-neoplastic based on the criteria. Intraclass correlation (ICC) analysis was done to evaluate interrater agreement for both criteria set and final diagnosis. RESULTS: Recordings of 26 malignant lesions and 14 benign lesions were scored. The IA using both the Monaco criteria and CRM criteria ranged from poor to excellent (range 0.1-0.76) and (range 0.1-0.62), respectively. Within the Monaco criteria, IA was excellent for lesion (0.75) and fingerlike papillary projections (0.74); good for tortuous vessels (0.7), mucosal features (0.62), uniform papillary projections (0.53), and ulceration (0.58); and fair for white linear bands (0.4). Within the CRM criteria, the IA was good for villous pattern (0.62), flat pattern (0.62), and honeycomb pattern; fair for ulcerated pattern (0.56), polypoid pattern (0.52) and inflammatory pattern (0.54). The diagnostic IA using Monaco criteria was good (0.65), while the diagnostic IA using CRM was fair (0.58). The overall diagnostic accuracy using the Monaco classification was 61% and CRM criteria were 57%. CONCLUSION: The IOA and accuracy rate of DSOC using visual criteria from both Monaco Criteria and CRM are similar. However, some criteria from both sets suffer from poor IA, thus affecting the overall diagnostic accuracy. More formal training and refinements in visual criteria with additional validation are needed to improve diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02166099.

Aspiration fluid cytology during single operator cholangioscopy with targeted biopsy to improves the diagnostic yield in indeterminate biliary strictures.

INTRODUCTION: Sensitivities of various sampling methods to detect malignant biliary strictures remain suboptimal. Irrigation during digital single operator cholangioscopy (dSOC) is done routinely for visualization of the duct. The aim of this study was to evaluate improvement of the sensitivity for detecting malignant biliary strictures when adding aspiration fluid cytology (AFC) from the irrigated fluid during cholangioscopy to cholangioscopic biopsy (CBx). METHODS: We conducted a retrospective analysis of patients at a tertiary medical center who underwent CBx for evaluation of their biliary strictures. We included patients who had aspiration of fluid from the bile duct after CBx and were sent for cytology from January 2017 to October 2017. Diagnosis was made on the basis of final pathology or follow-up over 9 months. RESULTS: Fifty-six patients had CBx obtained, out of which 35 patients had AFC in conjunction. Twenty-two (62%) patients were male and the average age was 65 years. Considering atypical cells as benign, the sensitivity, specificity, positive and negative predictive values (PPV, NPV) for CBx were 62.5%, 100%, 100%, and 76% respectively. When CBx combined with AFC, the above statistics went up to 81.25%, 100%, 100%, and 86.36% respectively. When atypical cells were considered malignant, the sensitivity, specificity, PPV and NPV for CBx were 81.25%, 84.21%, 81.25%, 84.21% and increased to 93.75%, 78.94%, 78.94%, and 93.75% respectively after adding AFC results. CONCLUSION: For patients with biliary stricture, addition of AFC dSOC guided biopsies, significantly improves the sensitivity for detecting malignancy.

Clinical Management of Bile Duct Diseases: Role of Endoscopic Ultrasound in a Personalized Approach.

Biliary diseases are common, but clinical symptoms are often unspecific and direct access and visualization of the biliopancreatic system for diagnostic purpose is difficult. In the last decades endoscopic ultrasound (EUS) has become a primary method in the gastrointestinal tract. It significantly changed the role of endoscopy in diagnostic imaging in the gastrointestinal tract and adjacent organs. EUS has become an effective diagnostic tool in biliary stone disease as well as in the diagnosis of indeterminate biliary strictures. Furthermore, an EUS-directed transmural approach emerged as a safe and effective alternative to ERCP in patients requiring biliary drainage, in particular as a backup method if standard ERCP-approach fails. Development of new techniques, specific accessories and stents during the last decade led to an enormous step forward in terms of efficacy and safety of an EUS-directed approach. In the current article technical and clinical aspects of EUS-guided diagnostic and therapeutic approaches in different clinical indications will be discussed together with a review of the available data.

Performance of digital single-operator cholangiopancreatoscope for biliopancreatic diseases in real life: results from a prospective multicenter study.

OBJECTIVES: Peroralcholangio-pancreatoscopy (POCP) is used for diagnosis and treatment of biliopancreatic disease when standard endoscopy (ERCP) or pre-operative imaging workup failed. We aimed to evaluate the diagnostic and therapeutic performance of POCP in complex biliary and pancreatic diseases. MATERIALS AND METHODS: Patients with indeterminate biliary or pancreatic duct (PD) strictures, and patients with failure of complex biliary or pancreatic stones removal, were enrolled (six centers). The primary endpoint evaluated malignancy diagnostic performances (accuracy, sensitivity, specificity) and therapeutic performances (biliary or pancreatic stones extraction). Secondary endpoints evaluated: technical success in lesion visualization, ease of maneuvering, image quality and 30-days complications. RESULTS: From November 2016 to March 2018, 66 patients were included: 29/37 women/men, median age (IQR): 73 (64-82). Fifty-three patients had diagnostic POCP and 13 patients therapeutic POCP. One endoscopist with one or two endoscopy nurses performed 94% of the POCP. The 'POCP visual impression' of malignancy showed 92.0% sensitivity, 92.9 % specificity and 92.5 % overall accuracy compared with the final diagnosis. 'POCP-guided samples histological analysis' showed 75.0 % sensitivity and 91.6% specificity. The technical success for lesion visualization was 98.5%. The median VAS scores for insertions in bile and PD were respectively 9.0 (8.1-9.6) and 9.0 (8.8-10.0). Median VAS score for access to the lesion and image quality were respectively 9.0 (7.7-9.6) and 9.0 (7.9-9.7). Only three 30-day minor complications occurred without any major complications. CONCLUSIONS: POCP was an effective, safe and easy-to-use tool in routine clinical practice for the management of complex diagnostic and therapeutic biliary and pancreatic diseases (NCT03190343).

Efficacy and Safety of Digital Single-Operator Cholangioscopy in the Diagnosis of Indeterminate Biliary Strictures by Targeted Biopsies: A Systematic Review and Meta-Analysis.

BACKGROUND: Biliary strictures are frequently encountered in clinical practice. The determination of their nature is often difficult. This study aims to systematically evaluate the efficacy and safety of the second generation of digital single-operator cholangioscopy (SpyGlass DS, DSOC) in indeterminate biliary strictures (IBDS) through biopsies. METHODS: All relative studies published in Medline, the Cochrane Library, Web of Science, and EMBASE were included. The diagnostic tests for IBDS were compared to the surgical histology, autopsy, or long-term clinical follow-up. The methodological quality of the included studies was evaluated by the Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS-2). RESULTS: A total of 11 studies, which involved 356 patients diagnosed through biopsies, were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.74 (95% CI: 0.67-0.80), 0.98 (95% CI: 0.95-1.00), 10.52 (95% CI: 5.45-20.32), 0.31 (95% CI: 0.23-0.41), and 65.18 (95% CI: 26.79-158.61), respectively. The area under the curve (AUC) was 0.9479, and the pooled adverse event rate was 7%. The sensitivity and specificity in the heterogeneity analysis were I2 = 48.1% and I2 = 25.4%, respectively. CONCLUSION: SpyGlass DS is a safe and effective technique for IBDS. However, future randomized trials are needed to determine optimal number of biopsies.

Clinical impact of digital cholangioscopy in management of indeterminate biliary strictures and complex biliary stones: a single-center study.

AIMS: Endoscopic management of indeterminate strictures and complex stones remains a challenge, for which the latest generation single-operator digital cholangioscope (SpyGlass DS) has shown promising results. We aimed to study the clinical impact of single-operator digital cholangioscope at our tertiary academic center. METHODS: We retrospectively reviewed all digital cholangioscopies performed from June 2015 to May 2018. Patient characteristics, procedure characteristics, and post-procedural patient outcomes were recorded. RESULTS: A total of 50 patients (26 men, average age 61.4 years) underwent 67 procedures. Indications were biliary stones (21/50, 42%), strictures and primary sclerosing cholangitis surveillance (22/50, 46%), and miscellaneous (7/50, 14%). The average procedure time was 82 ± 29 min (99.5 min for stones and 74.2 min for strictures). Stone clearance was achieved in 19/21 (90.47%) cases, with electrohydraulic lithotripsy employed in 16/21 and repeat cholangioscopy necessary in 9/21. Malignant strictures (10) were differentiated from benign (12) in all cases both in patients with primary sclerosing cholangitis (9) and in those without (13), based on visual cholangioscopic features (sensitivity and specificity 100%), single-operator digital cholangioscope-directed biopsies (sensitivity 60% and specificity 100%), and brush cytology (sensitivity 37.5% and specificity 100%). Complications included one post-sphincterotomy bleeding and one post-procedural cholangitis despite antibiotic prophylaxis, but no procedure-related mortality. CONCLUSION: Single-operator digital cholangioscope had a high success rate and a low rate of complications for management of indeterminate strictures and difficult biliary stones. Visual cholangioscopic features of biliary strictures had excellent diagnostic accuracy, and targeted biopsies outperformed brush cytology. Early implementation of cholangioscopy for select indications leads to successful patient outcomes and reduces diagnostic delays, cost, and risks of repeat endoscopic retrograde cholangiopancreatographies.

Practical Management of Indeterminate Biliary Strictures.

Indeterminate biliary strictures pose a diagnostic and therapeutic challenge. Although underlying malignancy is a primary concern, biliary strictures may result from benign processes. An accurate diagnosis is paramount to define the treatment strategy and minimize morbidity. The limitations of traditional endoscopic retrograde cholangiopancreatography-based tissue acquisition with cytology brushings are well-documented. Endoscopic retrograde cholangiopancreatography is generally unable to determine a stricture's etiology. Complementary advanced endoscopic imaging and multimodal tissue acquisition have evolved. Careful consideration of the clinical presentation, location of the stricture, and interpretation of imaging constitute the most optimal approach for diagnosis and management.

Role of fluorescence in situ hybridization in diagnosing cholangiocarcinoma in indeterminate biliary strictures.

BACKGROUND AND AIM: Brush cytology, the conventional method to diagnose cholangiocarcinoma, has been plagued by low diagnostic sensitivity and false-negative results. This paper aims to study the clinical utility of fluorescence in situ hybridization (FISH) in enhancing identification of malignant biliary strictures. METHODS: Brush cytologic specimens collected from endoscopic retrograde cholangiopancreatography for biliary strictures in a tertiary hospital in Singapore from March 2013 to July 2015 were examined by FISH technique using UroVysion probe set in this study. RESULTS: Thirty patients were chosen with five patients having multiple FISH performed due to indeterminate results. The diagnoses for biliary strictures were 13 (43.3%) cholangiocarcinomas, seven (23.3%) pancreatic cancers, seven (23.3%) benign biliary strictures, and three (10%) primary sclerosing cholangitis. Conventional brush cytology had sensitivity of 53.8% with specificity of 82.4%. FISH had sensitivity of 30.8% with specificity of 100%. When FISH results were interpreted in cases with negative or atypical brush cytology, two patients had positive FISH results and cholangiocarcinomas. Based on this pilot study, FISH increased sensitivity of brush cytology in detection of cholangiocarcinoma from 53.8% to 69.2% while preserving specificity of 82.4%. CONCLUSION: Compared with conventional cytology with low sensitivity, FISH may help to increase sensitivity on top of brush cytology while maintaining high specificity.

Eosinophilic cholangitis is a potentially underdiagnosed etiology in indeterminate biliary stricture.

AIM: To investigate presence and extent of eosinophilic cholangitis (EC) as well as IgG4-related disease in patients with indeterminate biliary stricture (IBS). METHODS: All 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. RESULTS: one 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). CONCLUSION: EC is an underdiagnosed benign etiology of SC and IBS, which has to be considered in differential diagnosis of IBS.

A Review of Probe-Based Confocal Laser Endomicroscopy for Pancreaticobiliary Disease.

Confocal laser endomicroscopy (CLE) is a novel in vivo imaging technique that can provide real-time optical biopsies in the evaluation of pancreaticobiliary strictures and pancreatic cystic lesions (PCLs), both of which are plagued by low sensitivities of routine evaluation techniques. Compared to pathology alone, CLE is associated with a higher sensitivity and accuracy for the evaluation of indeterminate pancreaticobiliary strictures. CLE has the ability to determine the malignant potential of PCLs. As such, CLE can increase the diagnostic yield of endoscopic retrograde cholangiopancreatography and endoscopic ultrasound, reducing the need for repeat procedures. It has been shown to be safe, with an adverse event rate of ≤1%. Published literature regarding its cost-effectiveness is needed.

Role of CD15 expression in dysplastic and neoplastic tissue of the bile duct - a potential novel tool for differential diagnosis of indeterminate biliary stricture.

BACKGROUND AND AIMS: CD15 is expressed by various cancer types; among these are intrahepatic and perihilar cholangiocarcinoma (CCA). The aim of this study was to elucidate CD15 expression in distal CCA as well as in dysplastic biliary tissue and to determine its prognostic significance. METHODS AND RESULTS: Tissue samples from patients with intrahepatic (iCCA, n = 22), perihilar (pCCA, n = 7) and distal CCA (dCCA, n = 15), who underwent surgical resection in the period from 2010 to 2015 were evaluated for CD15 expression. Tissue of synchronous lymph node metastasis (n = 13), CCA-associated dysplasia (n = 20), dysplasia in intraductal biopsies (n = 10) and benign proliferations (n = 12), as well as inflammatory biliary lesions (n = 28) and non-inflammatory bile ducts (n = 23), were evaluated equally for CD15 expression. CD15 was found to be expressed highly in iCCA (81.8%), pCCA (85.7%), dCCA (73.3%), CCA-associated dysplasia (70.0%), dysplasia in intraductal biopsies (100%) and metastatic tissue (84.6%). CD15 expression was negative in 58 of 64 benign bile duct alterations resulting in an overall sensitivity and specificity of CD15 in CCA of 80.7 and 90.6% patients, respectively. CD15 expression was correlated significantly with a decreased overall survival in patients with CD15-positive CCA associated dysplasia (P = 0.003). However, CD15 expression in the invasive tumour component was not correlated with clinical outcome. CONCLUSION: CD15 is a sensitive and specific marker for intraepithelial and invasive neoplasias of the bile duct. Therefore, it can be helpful in the delineation of dysplastic and neoplastic biliary cells from non-neoplastic tissue, which frequently causes a diagnostic problem in indeterminate biliary stricture.