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Digital single-operator cholangioscopy for indeterminate biliary stricture: Enthusiasm or still evolving for unmet need?

      Abbreviation:

      DSOC (digital single-operator cholangioscopy)
      ERCP is the standard of care for the diagnosis of benign or malignant biliary strictures. However, given the nature of fluoroscopic-guided tissue acquisition, brushing cytology or forceps biopsy during ERCP may be suboptimal for the diagnosis of biliary strictures. A meta-analysis reported that the pooled sensitivity and specificity of brushing for malignant biliary strictures were only 45% (95% CI, 40%-50%) and 99% (95% CI, 98%-100%), respectively, and for intraductal biopsy were only 48.1% (95% CI, 42.8%-53.4%) and 99.2% (95% CI, 97.6%-99.8%), respectively. In combination, there was only a modest increase in sensitivity (up to 54.9%).
      • Navaneethan U.
      • Njei B.
      • Lourdusamy V.
      • et al.
      Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis.
      Indeterminate biliary strictures may be considered when the initial radiologic evaluation and ERCP with brush cytology and/or forceps biopsy do not reveal a definitive diagnosis.

      Parsa N, Khashab MA. The role of peroral cholangioscopy in evaluating indeterminate biliary strictures. Clin Endosc. Epub 2019 Jul 16.

      Sometimes, diagnosis can be challenging, even with many types of modalities, including MRCP or EUS-guided fine-needle biopsy. Early cholangioscopy platforms were developed as “mother-daughter” systems that required 2 endoscopes and 2 operators. They were not widely used because of prolonged procedure times, difficult manipulation, poor quality of view, and fragile endoscopes. To overcome these issues, single-operator cholangioscopy was developed for direct visualization of the biliary epithelium, with promising results in 91% of procedural successes and 71% sensitivity and 100% specificity for diagnosing malignancy.
      • Chen Y.K.
      • Pleskow D.K.
      SpyGlass single-operator peroral cholangiopancreatoscopy system for the diagnosis and therapy of bile-duct disorders: a clinical feasibility study (with video).
      However, visualization with this type of optic endoscope should have been improved. Subsequently, digital single-operator cholangioscopy (DSOC) was launched and has yielded improved clinical data. Navaneethan et al
      • Navaneethan U.
      • Hasan M.K.
      • Kommaraju K.
      • et al.
      Digital, single-operator cholangiopancreatoscopy in the diagnosis and management of pancreatobiliary disorders: a multicenter clinical experience (with video).
      reported that the sensitivity and specificity of visual impressions with the use of DSOC for malignancy were 90% (95% CI, 69.9%-97.2%) and 95.8% (95% CI, 79.8%-99.3%), respectively.
      • Navaneethan U.
      • Hasan M.K.
      • Kommaraju K.
      • et al.
      Digital, single-operator cholangiopancreatoscopy in the diagnosis and management of pancreatobiliary disorders: a multicenter clinical experience (with video).
      Turowski et al
      • Turowski F.
      • Hugle U.
      • Dormann A.
      • et al.
      Diagnostic and therapeutic single-operator cholangiopancreatoscopy with SpyGlassDS: results of a multicenter retrospective cohort study.
      reported 95.5% sensitivity and 94.5% specificity for malignancy.
      In the current issue of Gastrointestinal Endoscopy, Jang et al
      • Jang S.
      • Stevens T.
      • Kou L.
      • et al.
      Efficacy of digital single-operator cholangioscopy and factors affecting its accuracy in the evaluation of indeterminate biliary stricture.
      present a single-center retrospective observational study involving 105 patients who underwent DSOC for the evaluation of indeterminate biliary strictures. The overall accuracy of visual interpretation and bile duct specimens was 89.5% and 83.2%, respectively, for the diagnosis of malignant biliary strictures. Sensitivity and specificity were highest with experienced endoscopists. In patients with a definitive diagnosis of malignant biliary strictures, the combination of brush cytology and intraductal biopsies had 80.5% sensitivity, compared with 47.1% for brush cytology alone. Despite the lack of standardization for visual assessment and biopsy protocol, the authors nevertheless provide important findings for the learning curve for DSOC and modifiable factors affecting the accuracy of DSOC for indeterminate biliary strictures, especially hyperbilirubinemia. In this study, endoscopists with per-oral cholangioscopy experience of ≥25 cases fared much better than did those with cholangioscopy experience <25 cases in visual interpretation of DSOC. Furthermore, an operator with substantial cholangioscopy experience (>50 cases) was 11 times more likely to obtain an accurate bile duct sample than was a novice operator with <25 cases of experience. Severe hyperbilirubinemia negatively affected visual and bile duct sampling accuracy, whereas advanced operator experience was associated with a positive effect on visual and bile duct sampling accuracy.
      As the authors acknowledged in their study limitations, this was not a well-designed prospective study; heterogeneity may have been present, and the definition of indeterminate biliary stricture was not clear. Overall visual diagnostic accuracy was almost 89.5%; however, the authors did not provide any information about visual findings and did not define the visualization criteria for benign or malignant biliary strictures. Additionally, the number of biopsy specimens was not standardized. In a recent prospective comparative study, obtaining 3 biopsy specimens from the biliary stricture resulted in correct diagnosis in 90% of cases.

      Bang JY, Navaneethan U, Hasan M, et al. Optimizing outcomes of single-operator cholangioscopy-guided biopsies based on a randomized trial. Clin Gastroenterol Hepatol. Epub 2019 Jul 24.

      Could we routinely perform DSOC for indeterminate biliary strictures according to the current study? Let us consider the following cases, in which 2 common clinical scenarios are possible for DSOC according to the location of an indeterminate biliary stricture.

      Distal biliary stricture

      A 63-year-old man presented with intrapancreatic (distal) biliary stricture, hyperbilirubinemia, and enhancement of the bile duct on enhanced CT scan. Outside ERCP with brushing cytology was negative for malignancy. What would be your next step? In distal indeterminate biliary strictures, evaluation with EUS may be first considered for a pancreatic head mass. Importantly, no obvious mass on the pancreas head on CT may be revealed as a pancreatic mass on EUS.
      • Weilert F.
      • Bhat Y.M.
      • Binmoeller K.F.
      • et al.
      EUS-FNA is superior to ERCP-based tissue sampling in suspected malignant biliary obstruction: results of a prospective, single-blind, comparative study.
      If EUS dose not contribute to the diagnosis of indeterminate biliary stricture, ERCP with DSOC as the next step could be considered.

      Proximal biliary stricture

      A 28-year-old man with primary sclerosing cholangitis presented with a newly developed biliary stricture in the hilar portion. In this situation, ERCP with DSOC may be considered first, rather than EUS-guided tissue acquisition, because of concerns regarding seeding malignancy along the needle tract.
      • Heimbach J.K.
      • Sanchez W.
      • Rosen C.B.
      • et al.
      Trans-peritoneal fine needle aspiration biopsy of hilar cholangiocarcinoma is associated with disease dissemination.
      As such, ERCP with DSOC may be the first-line or second-line diagnostic tool for indeterminate biliary strictures, depending on stricture location. However, manipulation and visual interpretation of DSOC by novice operators may be challenging. After adequate clinical experience with DSOC (>25–50 cases) and stratification of the highest yield (proximal common bile duct, normal serum bilirubin), ERCP with DSOC may be an essential component of the endoscopic “toolbox” for indeterminate biliary stricture. However, as shown in this study, DSOC can still miss 10% of malignant lesions by visualization or biopsy. Therefore, further visual and technical improvement with narrow-band imaging (such as artificial intelligence–based diagnosis) and ultraslim caliber with a wider working channel of DSOC in future versions may be required for first-line diagnosis of indeterminate biliary strictures. Although DSOC reduces the number of procedures by up to 31% and saves approximately 5% of allocated costs for the treatment of difficult bile duct stones and diagnosis of indeterminate biliary strictures,
      • Deprez P.H.
      • Garces Duran R.
      • Moreels T.
      • et al.
      The economic impact of using single-operator cholangioscopy for the treatment of difficult bile duct stones and diagnosis of indeterminate bile duct strictures.
      there is also a reimbursement problem for DSOC; therefore, ERCP with DSOC is not widely used in some countries.
      Collectively, additional prospective studies should be performed to determine possible associations between bilirubin level and endoscopist experience level and the visual and bile duct sample accuracy of DSOC.
      In summary, this study provides valuable data and is a step forward toward the incorporation of DSOC into clinical practice. Although endoscopists are becoming enthusiastic about DSOC, given the plethora of positive results, skepticism remains regarding the technical proficiency and performance required for the current versions of DSOC. Do, however, salute the new era of DSOC with passion, but remain calm!

      Disclosure

      All authors disclosed no financial relationships relevant to this publication.

      References

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        • Njei B.
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        Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis.
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