Limited diagnostic accuracy and clinical impact of single-operator peroral cholangioscopy for indeterminate biliary stricturesReferring to de Vries A et al. p. 107–114
28 January 2020 (online)
The endoscopic evaluation of indeterminate biliary strictures in patients with and without primary sclerosing cholangitis (PSC) has evolved considerably with the improvement in duodenoscopes. Endoscopic retrograde cholangiopancreatography (ERCP) has become the basis for diagnosis and therapy in patients with this condition.
Throughout the late 1970s and 1980s, various models of peroral cholangioscopy (POCS) under duodenoscopic guidance were developed and demonstrated clear benefits in the diagnosis of minimal biliary mucosal lesions, such a laterally spreading tumors, and in the evaluation of stenosis in PSC. The limiting factors for these early models included their reduced maneuverability owing to their length (> 160 cm), their durability (with a need for excessive maintenance/repair when faced with the challenges of normal operation), and the high financial costs.
Brushing cytology and intraductal ERCP biopsies have been used as methods to obtain tissue for the diagnosis of malignancy. They can however present high false-negative rates, due to a combination of factors including: inadequate sampling, sampling error, and the subtle differences between benign and malignant cells. Ultimately, ERCP shows a low sensitivity (42 %) and negative predictive value (NPV; 50 %) as a diagnostic test . Therefore, a significant proportion of stenoses remains undetermined, which has led to the development of cholangioscopy-based techniques.
Single-operator peroral cholangioscopy (sPOCS)-guided biopsies (using specific biopsy forceps narrow enough to fit through the cholangioscope catheter working channel that still allow for substantial tissue acquisition [SpyBite; Boston Scientific]) of indeterminate biliary lesions have significantly higher accuracy compared with ERCP-guided brushing cytology and standard forceps biopsies (sensitivity: 76.5 % with SpyBite vs. 5.8 % for standard brushings and 29.4 % for biopsies), but negative findings on biopsy with mini-forceps cannot rule out malignancy with a high degree of certainty .
“...we believe that as pathologists, pathology laboratories, and endoscopists gain greater experience with the small samples obtained from the SpyBite biopsies, there will be an increase in diagnostic accuracy.”
Early diagnosis of dysplastic changes and exclusion of cholangiocarcinoma in patients with PSC remains a challenge. Although sPOCS using SpyGlass (Boston Scientific) seems effective in diagnosing indeterminate biliary strictures, there are few studies that have evaluated its role in PSC-related stenosis.
Liu et al.  demonstrated in 2014 that the sensitivity, specificity, NPV, and positive predictive value (PPV) of cholangioscopic targeted biopsy in patients with PSC (75 %, 55 %, 92 %, and 23 %, respectively) and non-PSC (100 %, 25 %, 100 %, and 50 %) are very different. Their overall analysis of the sample showed a sensitivity of 86 %, specificity of 50 %, NPV of 93 %, and PPV of 32 %, which is very different from the results obtained by de Vries et al. , with 15 %, 65 %, 69 %, and 75 %, respectively. These results demonstrate the importance of separate evaluation of the impact of sPOCS on malignancy analysis in indeterminate biliary strictures in patients with and without PSC.
Of relevance is the continuous improvement in the quality of intraductal cholangioscopy equipment. According to Hartman et al. , the first generation of Legacy cholangioscopes achieved 57 % sensitivity with SpyBite biopsies in the diagnosis of indeterminate biliary strictures, compared with 76 % for standard biopsies. The improved digital image quality and wider viewing angle enabled the second generation of DS cholangioscopes to increase the diagnostic sensitivity from 81 % to 100 % .
There is still a discrepancy between the visual impression (88.9 % – 97 %) and confirmatory histology (62.5 % – 85 %), probably due to the above factors, and we believe that as pathologists, pathology laboratories, and endoscopists gain greater experience with the small samples obtained from the SpyBite biopsies, there will be an increase in diagnostic accuracy.
In the publication by de Vries et al. , the analysis of the results is global, and included patients with and without PSC who underwent sPOCS examination with the Legacy and DS cholangioscope versions, factors that may have influenced their results.
Bang et al.  have emphasized the need to optimize sample collection and processing techniques and published a study evaluating onsite and offsite cytopathology support (use of rapid on-site evaluation [ROSE] and the touch imprint cytology [TIC] technique), which demonstrated that there are no differences between accuracy, sensitivity, PPV, and NPV in the diagnosis of indeterminate biliary strictures, with 90 % diagnostic accuracy in both groups, and fewer biopsies being performed (interquartile range 1 – 1.5) with the onsite method.
There is also the benefit of a significant reduction in radiation exposure time when using the digital cholangioscopy platform during the ERCP examination for indeterminate biliary stricture management, as well as the increased accuracy, which has relevance for its clinical impact, but this is dependent on numerous factors, such as the learning curve of the endoscopist, the experience of the pathologist, and on adequate tissue sampling.
In summary, the results of this study by de Vries et al.  rekindle the discussion and, through some questioning, cast doubt on the true value of sPOCS with targeted biopsies in the diagnosis of indeterminate biliary strictures. We must recognize the difficulties of all professionals who, at the time of an examination, face many other factors that influence the final result of the examination (bile duct size, multiple stenoses, fibrosis from previous stent therapy, limited opening of the forceps, significant tissue sampling, inadequate slide preparation, availability of a pathologist in the room, having a pathologist with sufficient expertise in cytopathology, the sPOCS image quality, maneuverability, the length of the procedure, bleeding, and cholangitis). However, the clinical impact of cholangioscopy on the management of these patients is clear, regardless of the pathological confirmation.
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