Challenges in Diagnosing Biliary Stricture

Petros C. Benias, MD; David L. Carr-Locke, MD


February 27, 2012


Despite advances in imaging and endoscopic tools, accurate diagnosis and staging of biliary tumors remain difficult. Use of ERCP or endoscopic ultrasonography (EUS) to differentiate benign from malignant biliary strictures can have variable sensitivity. Often, making an accurate diagnosis requires repeated imaging and sampling of the suspected lesion, as was demonstrated in this case.

When performed with different brushing and biopsy techniques, ERCP-based methods have been shown to have diagnostic yields of 35%-70%. In contrast, EUS-guided fine-needle aspiration has been shown to have slightly higher diagnostic yield in pancreatic cancer, but it may not necessarily increase the sensitivity in diagnosing hepatobiliary cancer. In an overall analysis of 22 studies (2472 patients), the sensitivities of brush cytology and intraductal biopsy were only 49% and 66%, respectively.[1]A recent comparison of the current standards of ERCP and EUS again showed that the sensitivity for ERCP-guided biopsies ranged widely even within the study (36%-75%), depending on the sampling method.[2]

Confocal laser endomicroscopy (CLE) is a new technique in endoluminal imaging that offers very high magnification and resolution, approximating that of white-light microscopy. Its use has been better investigated in colonic neoplasia, Barrett esophagus, and other malignant or premalignant conditions.[3,4,5]Several studies have also supported its use in the evaluation of malignant biliary abnormalities.[6,7,8]Confocal laser endomicroscopy is a new approach that may improve the diagnosis of indeterminate biliary strictures, and recent advances have allowed such a system to be delivered as a probe.

Probe-based CLE depends on the use of fluorescein as a contrast dye, although other agents, such as cresyl violet and acriflavine, have been investigated.[9] Because fluorescein remains mostly intravascular, it highlights small and large blood vessels, including the smallest capillaries. After injection of fluorescein, cholangiocarcinomas show a specific pattern of neovascularization that is not found in benign strictures. Understandably, such angiogenesis and neovascularization has been reported to be an essential step in the progression and development of cholangiocarcinomas.[10]

In general, 2 different patterns were identified and evident in this patient. The first was a dark-grey background with no identification of mucosal structures and with large white streaks that resemble fluorescein-filled, tortuous, dilated, and saccular vessels with inconsistent branching. The second was a reticular pattern of different grey scales or small dark-grey villous structures with no white streaks. After applying these hallmarks as defined, the sensitivity, specificity, and overall diagnostic accuracy for the detection of neoplasia were found to be 83%, 88%, and 86%, respectively.[6,7]

Current data suggest that this new technology represents a promising approach for further differentiation of strictures and stenosis in the biliary and perhaps also the pancreatic system. The low accuracy in diagnosing biliary cancers might be improved by gaining more detailed information about benign or malignant epithelium in vivo. The most recent multicenter experience suggests that probe-based CLE in suspicious biliary strictures can have a sensitivity of 98% and a specificity of 67%.[8]Nevertheless, those results are limited by the fact that this is the only study of this magnitude and that it involved multiple centers in which the participating physicians were unblinded, potentially affecting the predictive characteristics of probe-based CLE. Further studies are needed to understand the true clinical importance of this new imaging modality.


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