Indeterminate Biliary Lesions Research Articles

Diagnostic Process Using Endoscopy for Biliary Strictures: A Narrative Review.

The diagnostic process for biliary strictures remains challenging in some cases. A broad differential diagnosis exists for indeterminate biliary strictures, including benign or malignant lesions. The diagnosis of indeterminate biliary strictures requires a combination of physical examination, laboratory testing, imaging modalities, and endoscopic procedures. Despite the progress of less invasive imaging modalities such as transabdominal ultrasonography, computed tomography, and magnetic resonance imaging, endoscopy plays an essential role in the accurate diagnosis, including the histological diagnosis. Imaging findings and brush cytology and/or forceps biopsy under fluoroscopic guidance with endoscopic retrograde cholangiopancreatography (ERCP) are widely used as the gold standard for the diagnosis of biliary strictures. However, ERCP cannot provide an intraluminal view of the biliary lesion, and its outcomes are not satisfactory. Recently, peroral cholangioscopy, confocal laser endomicroscopy, endoscopic ultrasound (EUS), and EUS-guided fine-needle aspiration have been reported as useful for indeterminate biliary strictures. Appropriate endoscopic modalities need to be selected according to the patient’s condition, the lesion, and the expertise of the endoscopist. The aim of this review article is to discuss the diagnostic process for indeterminate biliary strictures using endoscopy.

Diagnostic Accuracy and Therapeutic Efficacy of Digital Single-Operator Cholangioscopy for Biliary Lesions and Stenosis

Background/Aims: Digital single-operator cholangioscopy (dSOC) has revolutionized bile duct visualization. Interventions like electrohydraulic or laser lithotripsy, inspection of suspicious areas, and targeted biopsies have become possible quick and easy. One main indication for dSOC remains the evaluation of indeterminate biliary strictures. Objective and Methods: We analyzed 180 consecutive dSOCs procedures performed in a high-volume tertiary center to evaluate sensitivity, specificity as well as positive and negative predictive values (PPV and NPV) for indeterminate strictures. Furthermore, technical success and complications were analyzed. Results: In 92–97%, the region of interest was reached and successfully visualized. In 83–100%, targeted biopsies were obtained from the suspicious area. Only the distal bile duct was less successful with only 84 and 62%, respectively. In general, dSOC procedures were safe. Cholangitis was the main complication. Regarding the diagnostic accuracy of dSOC of indeterminate biliary strictures, we found a sensitivity of 0.87 and specificity of 0.88, over all. Within the whole cohort, the investigators’ assessment directly after dSOC had a PPV of 0.63 and a NPV of 0.97. In patients with biliary lesions or stenosis suspicious for malignancy, the dSOC-based visual diagnosis revealed a very high diagnostic accuracy with sensitivity and specificity of 1.0 (95% CI 0.86–1.0) and 0.76 (95% CI 0.56–0.9) with a PPV of 0.77 (95% CI 0.59–0.9) and a high NPV of 1.0 (95% CI 0.85–1.0). Conclusions: Our study demonstrates that dSOC has a high diagnostic accuracy as well as a favorable safety profile. Therefore, dSOC should be discussed as standard of care during endoscopic retrograde cholangiography for indeterminate biliary lesions.

Peroral cholangioscopy-guided forceps biopsy versus fluoroscopy-guided forceps biopsy for extrahepatic biliary lesions.

Background and AimEndoscopic retrograde cholangiopancreatography (ERCP)‐related tissue acquisition, including fluoroscopy‐guided forceps biopsy (F‐FB), is a common technique in diagnosing indeterminate biliary lesions. Recently, peroral cholangioscopy (POCS) and POCS‐guided forceps biopsy (POCS‐FB) has also been used for the diagnosis of indeterminate biliary lesions. However, it is uncertain which of those techniques were superior for the diagnosis of extrahepatic cholangiocarcinoma (ECC). We aimed to evaluate the diagnostic yield and safety of F‐FB for indeterminate biliary lesions compared with POCS‐FB.MethodsPatients who underwent F‐FB or POCS‐FB to evaluate indeterminate biliary lesions between October 2011 and August 2019 were enrolled retrospectively. We carried out propensity score matching to balance these clinical differences between the F‐FB group and POCS‐FB group. In the propensity score‐matched cohort, we compared the diagnostic performance of F‐FB with that of POCS‐FB based on the pathological evaluation. We also evaluate adverse events associated with F‐FB and POCS‐FB.ResultsWe enrolled 113 patients with biliary diseases, and 62 patients were analyzed in the propensity score‐matched cohort. Sensitivity, specificity, and accuracy of F‐FB were 82.4, 100, and 90.3%, and for POCS‐FB, those values were 83.3, 100, and 90.3%, respectively. There were no significant differences in the diagnostic performance between F‐FB and POCS‐FB. There were also no significant differences in the occurrence of adverse events between F‐FB and POCS‐FB (41.9 vs 29.0%, P = 0.289).ConclusionsThe diagnostic yield of F‐FB for ECC is similar to that of POCS‐FB. POCS‐FB is not necessary for the initial pathological diagnosis of indeterminate biliary lesions.

Efficacy of digital single-operator cholangioscopy in the visual interpretation of indeterminate biliary strictures: a systematic review and meta-analysis.

Indeterminate biliary strictures remain a significant diagnostic challenge. Digital single-operator cholangioscopy (D-SOC) incorporates digital imaging which enables higher resolution for better visualization and diagnosis of biliary pathology. We aimed to conduct a systematic review and meta-analysis of available literature in an attempt to determine the efficacy of D-SOC in the visual interpretation of indeterminate biliary strictures. Electronic searches were performed using Medline (PubMed), EMBASE, and Cochrane Library. All D-SOC studies that reported the diagnostic performance in visual interpretation of indeterminate biliary strictures and biliary malignancies were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 was used to evaluate the quality of the included studies. All data were extracted and pooled to construct a 2 × 2 table. The visual interpretation of D-SOC was compared to resected surgical specimens or clinical follow-up in the included patients. Pooled sensitivity, specificity, positive predictive value, negative predictive value, prevalence, positive likelihood ratio (+LR), negative likelihood ratio (-LR), and diagnostic odds ratio (OR) were calculated. The summarized receiver operating characteristic (SROC) curve corresponding with the area under the curve (AUC) was also analyzed. The search yielded 465 citations. Of these, only six studies with a total of 283 procedures met inclusion criteria and were included in the meta-analysis. The overall pooled sensitivity and specificity of D-SOC in the visual interpretation of biliary malignancies was 94% (95% CI 89-97) and 95% (95%CI 90-98), respectively, while +LR, -LR, diagnostic OR, and AUC were 15.20 (95%CI 5.21-44.33), 0.08 (95%CI 0.04-0.14), 308.83 (95%CI 106.46-872.82), and 0.983, respectively. The heterogeneity among 6 included studies was moderate for specificity (I2 = 0.51) and low for sensitivity (I2 = 0.17) and diagnostic OR (I2 = 0.00). D-SOC is associated with high sensitivity and specificity in the visual interpretation of indeterminate biliary strictures and malignancies. D-SOC should be considered routinely in the diagnostic workup of indeterminate biliary lesions.

The Expansion of Cholangioscopy: Established and Investigational Uses of SpyGlass in Biliary and Pancreatic Disorders

Direct visualization of bile and pancreatic duct pathology is proving to be beneficial in patients where previous techniques have failed. Recent advancements in technology and the development of the SpyGlass system have led to an increased use of cholangioscopy. It is already known that SpyGlass is beneficial in patients with difficult bile duct stones and indeterminate biliary lesions through the use of targeted lithotripsy and visually guided biopsy. Cholangioscopy allows the visualization of hidden stone and guide wire placement across difficult strictures and selective cannulation of the intrahepatic and cystic ducts. It is also demonstrating its utility in investigational applications such as post-liver transplant and primary sclerosing cholangitis stricture treatment, evaluation of hemobilia, and guided radiofrequency ablation of ductal tumors. In addition to having clinical utility, cholangioscopy may also be cost-effective by limiting the number of repeat procedures. Cholangioscopy overall has similar complication rates compared to other standard endoscopic retrograde cholangioscopy (ERCP) techniques, but there may be higher rates of cholangitis. This could be mitigated with prophylactic antibiotic use, and overall, cholangioscopy has similar complication rates compared to other techniques.

Advances of Peroral Cholangioscopy and EUS for Indeterminate Biliary Lesions

Traditionally, biliary lesions have been considered to be indeterminate when a diagnosis cannot be made after basic laboratory work-up, abdominal imaging and endoscopic retrograde cholangiopancreatography (ERCP) with biliary sampling. Although ERCP is a first-line diagnostic modality for indeterminate biliary lesions, the diagnostic yield of ERCP-based tissue sampling is insufficient. In a recent, peroral cholangioscopy (POC)- guided forceps biopsy and endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) are evolving as reliable diagnostic procedures for indeterminate biliary lesions. In previous studies, EUS-FNA was sensitive and highly specific for diagnosing malignancy in biliary strictures. However, EUS-FNA has several limitations as a routine clinical procedure for all biliary strictures. Newly developed POC systems, such as the SpyGlass direct visualization system and direct POC using an ultra-slim endoscope, have led to excessive improvements in technical performance and diagnostic yields for biliary strictures. However, the performance of POC-guided target biopsy for distal bile duct strictures is technically difficult, and this approach has a limited ability to diagnose biliary strictures caused by non-intraductal, extrinsic compressed malignancies, such as a pancreatic cancer. Therefore, a tailored approach using optimized endoscopic modalities that are specific to the characteristics of a given biliary stricture is needed to achieve a high diagnostic yield for indeterminate biliary lesions.

The ideal technique for processing SpyBite tissue specimens: a prospective, single-blinded, pilot-study of histology and cytology techniques.

Background and study aims Diagnostic sensitivity for indeterminate biliary lesions remains suboptimal. Cytology techniques may mitigate the impediment of small cholangioscopic specimens. Our primary aim was to compare cell block cytology (CB) with standard histology for foregut SpyBite (SB) specimens. Our secondary aim was to assess CB in biliary SB biopsies. Patients and methods This was a two-phase prospective pilot study. In phase one, a prospective pilot study, foregut SB specimens from three sites (4 per site per patient per processing technique) were allocated to CB or histology, and assessed by a single, blinded pathologist. The gold standard comprised two standard forceps (CFB) histological specimens per site per patient. Specimen ease of processing, size and number, adequacy for diagnosis and artefact were evaluated. In phase two, CB was used for consecutive patients with indeterminate biliary lesions, and compared with phase one CB results. Results In phase one, 240 SB foregut biopsies were performed in 10 patients, 227 specimens recorded by pathologist. Specimen origin was identified in 100 % and 97 % of histology and CB batches respectively. Specimens were significantly larger in the histology group (2.02 mm vs 1.49 mm, P < 0.05). There was a trend to less crush artifact with CB, and no difference in processing difficulty. In phase two, 11 patients (63.0 ±12.7 years, 91 % female) underwent SpyGlass (SG) assessment of suspected indeterminate stricture (n = 8) or mass (n = 3), and six underwent SB. All CB specimens were adequate for diagnosis. Specimen parameters were not significantly different from luminal CB outcomes. Conclusions In this pilot study, cell block cytology showed similar results as histological analysis of SpyBite specimens in the analysis of biliary stricture.

Utility of lavage cytology plus targeted biopsy during cholangioscopy for the diagnosis of indeterminate biliary lesions

Utility of lavage cytology plus targeted biopsy during cholangioscopy for the diagnosis of indeterminate biliary lesions

Diagnostic and therapeutic single-operator cholangiopancreatoscopy in biliopancreatic diseases: Prospective multicenter study in Japan.

To assess the utility and safety of single-operator cholangiopancreatoscopy (SOCPS) using the SpyGlass system in widespread clinical application for biliary and pancreatic diseases. This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2% (135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5% (84/89) and 88.2% (15/17), respectively. the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS (bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7% (53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5% (14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2% (23/31) and 42.9% (3/7) of the patients, respectively. Others: SOCPS using the SpyGlass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both SOCPS-guided therapies. The incidence of procedure-related adverse events was 5.4% (8/148). SOCPS with direct visualization and biopsy for diagnosis and SOCPS-directed therapy for biliary and pancreatic diseases can be safely performed with a high success rate. The clinical trial was registered at UMIN CTR (http://www.umin.ac.jp). The registration identification number is UMIN000015155.

PTU-028 Peroral cholangioscopy – experience with conscious sedation

<h3>Introduction</h3> Per-oral Cholangioscopy (POC) offers the facility for direct visualisation of bile ducts, targeted biopsy and interventional techniques including Electro Hydro lithotripsy (EHL). Procedure completion time is often longer than conventional Endoscopic Retrograde Cholangio-Pancreatography (ERCP), patients often require high doses of standard sedation or general anaesthesia. We present our data where POC is performed under conscious sedation. <h3>Method</h3> Retrospective analysis was performed for all POC cases between January 2013 –December 2014. Definitions and endpoints were as used by Kalaitzakis <i><i>et al</i></i>.¹Procedural success was defined as direct visualisation of the lesion enabling tissue sampling. Adequacy of tissue samples were analysed against the final Multidisciplinary meeting (MDM) decision-detailing both benign and malignant diagnosis. <h3>Results</h3> 47 cases of POC were performed in 43 patients. Median age was 63 years (IQR 22–86 years). 31 cases were performed for non stone-related disease (28 for indeterminate lesions 3 for other reasons). 16 patients underwent POC for choledocholithiasis, 9 of which had EHL. All patients had conscious sedation during POC. Median midazolam dose was 7 mg (IQR 5–11 mg), fentanyl 150 mcg (IQR 50–225 mcg). Buscopan was used in 42 cases (range 20–60 mg) and glucagon (1 mg) in 6 cases. Lowest oxygen saturations recorded were 95% (range 95–99%). Where a score of 1 represented maximum discomfort and 5 least, worst comfort score recorded was 3 for a single case. There were 4 failed procedures, 1 due to patient related factors and 3 due to equipment failure. Median procedure time was 86 min (IQR 34–114 min) for non-EHL and 92 min (IQR 76–132 min) for EHL cases. Procedural success was established in in 42 (89%) cases with positive visualisation of the target lesion. For non-stone related disease, 27 were successful (87%). For suspected malignancy, POC performance was again comparable with published data (sensitivity 70%, specificity 93%, positive predictive value 88%, negative predictive value 81%), when compared against the final MDT decision. Overall complication rate was comparable with other published data (6.3%). Over sedation requiring reversal was not encountered in the study. <h3>Conclusion</h3> Diagnostic results and complication rates, in our study, were comparable with published UK outcomes. Our practice demonstrates that POC can be performed under conscious sedation without compromising patient safety, test tolerance or efficacy. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Kalaitzakis E, Webster GJ, Oppong KW, Kallis Y, Vlavianos P, Huggett M, <i>et al</i>. Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones. Eur J Gastroenterol Hepatol. 2012;24(6):656–64

Is single-operator peroral cholangioscopy a useful tool for the diagnosis of indeterminate biliary lesion? A systematic review and meta-analysis

Differentiating between malignant and benign biliary lesions is critical in clinical practice but is difficult. To systematically evaluate the diagnostic performance of single-operator peroral cholangioscopy on indeterminate biliary lesions. A systematic review and meta-analysis. Patients with indeterminate biliary lesions or equivocal ERCP findings. The diagnostic performance of single-operator peroral cholangioscopy onindeterminate biliary lesions. The area under the summary receiver-operating characteristic curve was used as the main indicator for the overall diagnostic performance of single-operator peroral cholangioscopy visualimpression (VI) and SpyBite biopsy (SB). The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were also synthesized. A total of 8 studies met the inclusion criteria, involving 335 patients who had data on VI and 337 who haddata on SB. The area under the curve values on the summary receiver-operating characteristic curve of single-operator peroral cholangioscopy VI and SB were 0.94 (95% confidence interval [CI], 0.92-0.96) and 0.93 (95% CI,0.90-0.95) respectively. The combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 90% (95% CI, 73%-97%), 87% (95% CI, 76%-94%), 7.1 (95% CI, 3.8-13.3), 0.12 (95% CI, 0.04-0.33) for VIand 69% (95% CI, 57%-79%), 98% (95% CI, 92%-99%), 30.1 (95% CI, 8.5-106.9), and 0.32 (95% CI, 0.23-0.44) forSB, respectively. Small number of included studies; comparison with ERCP could not be made. Single-operator peroral cholangioscopy is a good tool for differentiating malignant and benignbiliary lesions. VI is useful for detecting malignant lesion, whereas SB is better at confirming a malignant diagnosis, but VI is not perfect in excluding biliary cancer, nor is SB, and their negative results should be interpreted with caution.

Role of balloon-assisted cholangioscopy in a multiethnic cohort to assess complex biliary disease (with videos)

Cholangioscopy is used to diagnose and treat various biliary lesions. Balloon-assisted cholangioscopy (BAC) has mostly been reported in Asian patients with large bile ducts. To assess the feasibility and accuracy of performing BAC in complex biliary diseases in Australian patients. Prospective observational study. A single Australian tertiary referral hospital. Fifty-nine consecutive patients (55 non-Asian ethnicity). BAC using ultrathin endoscopes. Procedural success rates, diagnostic accuracy, and adverse event rates. Fifty-nine patients underwent 76 BAC procedures for indeterminate biliary lesions, ampullary adenomas, and difficult stone disease. The technical success rate was 93%. The median bile duct diameter was 7mm (range, 2-20). Of 34 indeterminate biliary strictures, 22 appeared benign and 12 malignant on BAC appearance alone. All benign-appearing strictures were confirmed benign, whereas 9 of 12 malignant-appearing strictures were confirmed malignant by biopsy sampling or follow-up (sensitivity 100% [95% CI, 66%-100%], specificity 88% [95% CI, 69%-97%], positive predictive value 75% [95% CI, 42%-93%], negative predictive value 100% [95% CI, 82%-100%]). BAC appearance correctly diagnosed indeterminate masses as benign (4/4) or malignant (3/3). Eight patients were assessed for bile duct extension of ampullary adenomas and 5 of 6 had biliary stones cleared directly or with holmium laser lithotripsy. Adequate histopathologic specimens were obtained from 31 of 39 (79%) attempted biopsy specimens. The adverse event rate was 8%. A single-center, single endoscopist experience. In a largely non-Asian cohort with smaller bile ducts, BAC can be performed with high success and acceptable adverse event rates. BAC is particularly useful in differentiating benign from malignant indeterminate biliary lesions.

Role of SpyGlass Peroral Cholangioscopy in the Evaluation of Indeterminate Biliary Lesions

Accurate diagnosis of indeterminate biliary lesions is essential for treatment planning. The currently available techniques have some limitations in evaluating indeterminate biliary lesions. SpyGlass single-operator peroral cholangioscopy system has been developed to overcome these limitations. The aim of this retrospective study was to evaluate the diagnostic accuracy of SpyGlass visual assessment and SpyBite biopsy in patients with indeterminate biliary lesions. We conducted a retrospective analysis of data from 36 patients with indeterminate biliary strictures or filling defects who had inconclusive results on the cross-sectional imaging study from September 2010 to October 2013. Four patients were excluded because of the presence of a metastatic mass and an ampulla of Vater cancer. Thirty-two patients (19 men, mean age 63.7 years) with indeterminate biliary lesions underwent SpyGlass cholangioscopy. The cholangioscopy procedure with SpyGlass was technically successful in all of the cases except for one case because of the intraprocedural breakage of the SpyGlass optic probe (96.8%, 31/32). The biopsy specimens from nineteen patients were obtained using SpyBite forceps. The sensitivity, specificity, and overall accuracy of SpyGlass visual assessment and SpyBite biopsy for the diagnosis of malignancy were 100% (21/21) and 64.2% (9/14), 90% (9/10) and 100% (5/5), and 96.7% (30/31) and 73.6% (14/19), respectively. Procedure-related complications were noted in three cases; postsphincterotomy bleeding in one case and mild pancreatitis in two cases. SpyGlass cholangioscopy with SpyBite biopsy is highly accurate and safe for differentiating malignant lesions from benign lesions in patients with indeterminate biliary lesions.

Peroral video cholangioscopy to evaluate indeterminate bile duct lesions and preoperative mucosal cancerous extension: a prospective multicenter study

Despite the development of peroral video cholangioscopy (PVCS), no prospective multicenter studies have been undertaken to investigate the diagnostic accuracy of PVCS in biliary tract diseases. Therefore, the aim of this study was to clarify the accuracy of PVCS in evaluating biliary tract lesions. This study was a prospective multicenter study at five tertiary referral centers in Japan and included 87 eligible patients with biliary tract diseases who underwent PVCS. The study evaluated the ability of PVCS to diagnose indeterminate biliary tract diseases, detect mucosal cancerous extension preoperatively in extrahepatic bile duct cancers, and predict adverse events. The use of PVCS appearance alone correctly distinguished benign from malignant indeterminate biliary lesions in 92.1 % of patients whereas biopsy alone was accurate in 85.7 %. In extrahepatic bile duct cancer, mucosal cancer extended histologically at least 20 mm in 34.7 % (17/49) of patients. The accuracy rate of PVCS to evaluate the presence or absence of mucosal cancerous extension by endoscopic retrograde cholangiography (ERC) alone, ERC with PVCS, and ERC with PVCS + biopsy were 73.5 %, 83.7 %, and 92.9 %, respectively. Adverse events were seen in 6.9 % of PVCS patients, but no serious complications were observed. PVCS enhanced the accurate diagnosis of biliary tract lesions by providing excellent resolution in combination with biopsy.

PTH-065 Diagnostic and Therapeutic Utility of Spyglass single Operator Peroral Cholangioscopy for Indeterminate Biliary Lesions: A Single Centre Experience in Scotland

IntroductionThe SpyGlass single-operator peroral cholangioscopy is a promising technique designed to overcome some of the limitations of conventional peroral cholangioscopy. We aimed to evaluate the diagnostic utility of the SpyGlass...

PTU-045 Diagnostic Utility of Single-User Peroral Cholangioscopy for Indeterminate Biliary Strictures in Sclerosing Cholangitis

IntroductionSingle-user peroral cholangioscopy (SOC) has been reported to be useful in the differential diagnosis of indeterminate biliary lesions, but its diagnostic utility in sclerosing cholangitis(SC) has not been evaluated.MethodsFifty-one consecutive...

Su1398 Direct Retrograde Cholangioscopy (DRC) for Diagnosis of Indeterminate Biliary Lesions

Despite progress in biliary imaging etiology of biliary lesions remains indeterminate in up to 50% of some patient groups. Direct retrograde cholangioscopy (DRC) with use of an ultra-slim endoscope offers high resolution video imaging and might thereby significantly improve diagnostic validity.

SpyGlass® single-operator peroral cholangioscopy in the evaluation of indeterminate biliary lesions: a single-center, prospective, cohort study

SpyGlass single-operator peroral cholangioscopy appears to be a promising technique to overcome some limitations of conventional peroral cholangioscopy. We aimed to prospectively evaluate the SpyGlass system in a cohort of patients with indeterminate biliary lesions. Patients with indeterminate strictures or filling defects at endoscopic retrograde cholangiopancreatography (ERCP) were consecutively enrolled. After SpyGlass visual evaluation, targeted biopsies were taken with the SpyBite and histopathological assessment was made by two experienced gastrointestinal pathologists. SpyBite-targeted biopsy results were evaluated by assessing agreement with surgical specimens and by evaluation of final, clinical follow-up-based diagnosis. Fifty-two patients participated in the study. In 7 cases, definite diagnosis (stones, varices) was made by SpyGlass endoscopic evaluation. In 42 of the remaining 45 cases, material suitable for histopathology assessment was provided by the SpyBite. Overall, a definite diagnosis was made in 49 (7 + 42; 94 %) cases. Agreement of SpyBite biopsy results with surgical specimen diagnosis was found in 38/42 (90 %) cases; sensitivity, specificity, and positive and negative predictive values were 88, 94, 96, and 85 %, respectively. Procedure-related complications consisted of one case of mild cholangitis and one case of mild pancreatitis. In our series, the SpyGlass system allowed adequate biopsy sampling and definite diagnosis with high accuracy in the vast majority of patients with indeterminate biliary lesions. Its use was associated with a low complication rate. Further refinements of the technique are warranted, but the SpyGlass system has the potential to become a diagnostic standard for the assessment of indeterminate biliary lesions.

Comparison of the diagnostic accuracy of peroral video-cholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings for indeterminate biliary lesions: a prospective study

The diagnostic accuracy of peroral video-cholangioscopy for indeterminate biliary lesions has not been determined in a prospective study. To evaluate and compare the diagnostic accuracy of the peroral video-cholangioscopic visual findings for indeterminate biliary lesions with that of the cholangioscopy-guided forceps biopsy findings. Prospective cohort study. Tertiary-care referral center. Patients who showed indeterminate biliary lesions on endoscopic retrograde cholangiography underwent peroral video-cholangioscopy for diagnosis. Each patient underwent peroral video-cholangioscopy with cholangioscopy-guided forceps biopsy. The accuracy of diagnosis by the peroral video-cholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings compared with that of the final diagnosis by other methods (malignant or benign). Thirty-three patients were enrolled, and the final diagnoses revealed that the lesions were malignant in 21 patients. All procedures were technically successful, and fine views were obtained in all patients. Procedure-related complications occurred in 2 patients (6.1%), but these complications were mild. The sensitivity, specificity, and accuracy were 100%, 91.7%, and 97.0%, respectively, for the peroral video-cholangioscopic visual findings and 38.1%, 100%, and 60.6%, respectively, for the cholangioscopy-guided forceps biopsy findings, and a significant difference was observed in the accuracy (P = .0018). This was not a blinded study. No comparison was made with other diagnostic modalities involving tissue sampling. The diagnostic accuracy of the peroral video-cholangioscopic visual findings for indeterminate biliary lesions was excellent and significantly higher than that of the cholangioscopy-guided forceps biopsy findings. The accuracy of the cholangioscopy-guided forceps biopsy was insufficient, but the technique had an excellent specificity.

Establishing a Diagnosis in Indeterminate Pancreaticobiliary Strictures: Is Confocal Laser Endomicroscopy the Answer?

Despite the advances that have been made in diagnostic modalities during recent years, the differentiation between benign and malignant pancreaticobiliary strictures remains a significant diagnostic challenge. Conventional cancer markers are of limited diagnostic utility and radiologic assessment with cross-sectional imaging may not provide a definitive diagnosis in the absence of a mass lesion [1–3]. Endoscopic evaluation has, for many years, relied heavily on cholangiographic appearance and biliary brush cytology, which, despite a specificity approaching 100 %, shows a low sensitivity of 15–57 % for malignancy [4]. Confocal laser endomicroscopy (CLE) provides microscopic information on mucosal tissue in real time and aims to enhance the diagnostic accuracy of endoscopic examination. Employing technology designed to prevent light scattering, CLE generates highly focused images of very small mucosal areas [5, 6]. It has been used in detecting dysplasia/cancer in various settings, such as colorectal polyps, inflammatory bowel disease, and Barrett’s esophagus [7–9]. A CLE probe has been devised fitting in the working channel of a cholangioscope or in a catheter that can be inserted through the working channel of a standard duodenoscope under fluoroscopic or cholangioscopic guidance allowing examination of indeterminate biliary strictures. Fluorescein is given intravenously 2–3 min prior to mucosal imaging allowing also for visualization of blood vessels [10]. In recent years, a number of studies have attempted to determine the performance characteristics of this modality for the differentiation of benign and malignant pancreaticobiliary strictures [10–13]. Also, data from a multicenter prospective study were used to reach a consensus definition of biliary and pancreatic probe-based CLE [13]. Characteristics most suggestive of malignancy included thick dark bands ([40 lm), thick white bands ([20 lm), dark clumps, or epithelial structures, whereas thin dark or white bands were suggestive of benign lesions (Miami classification criteria). It has been shown that combining two or more criteria for malignancy significantly increases the sensitivity and predictive values of the method [13]. In the largest study investigating the performance characteristics of CLE in indeterminate biliary lesions, a total of 89 patients were included [12]. Utilizing the Miami classification criteria, CLE was found to have a sensitivity of 98 %, a specificity of 67 %, and a negative and positive predictive value of 97 and 71 %, respectively. It compared favorably with conventional histopathology that had a sensitivity, specificity, negative and positive predictive values of 45, 100, 69, and 100 %, respectively [12]. The excellent sensitivity and negative predictive value of CLE in indeterminate pancreaticobiliary strictures suggest that it could be an important adjunct to ERCP for distinguishing benign from malignant disease and that it may be used to guide biopsy sampling. Integrating this very promising new technology into every-day clinical practice involves defining not only its performance characteristics but also interobserver agreement for the perceived final diagnosis and for the different diagnostic criteria applied. In the initial validation of the Miami classification criteria, three criteria indicative of malignancy and one indicative of benign strictures showed moderate interobserver agreement as suggested by significant Fleiss kappa values between 0.40 and 0.60 [13]. Apart from these findings, however, data on interobserver E. Kalaitzakis (&) Department of Gastroenterology, Skane University Hospital, 221 85 Lund, Sweden e-mail: evangelos.kalaitzakis@medicine.gu.se; kalvag@hotmail.com