Single-operator cholangioscopy: more good numbers, with a few caveats

The finding of an indeterminate biliary stricture (IDBS) is not uncommon; it is often defined as a stricture for which definitive diagnosis remains elusive following standard evaluation with transabdominal imaging and endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology. The yield of ERCP techniques for detecting malignancy remains low; in a recent meta-analysis, the pooled sensitivities of brush cytology and forceps biopsy were 45 % and 48.1 %, respectively. Combining the two methods increased sensitivity modestly, to 59.4 % [1]. Mischaracterization of IDBSs can have a significant impact on patient outcomes by leading to unnecessary surgery or delays in oncological therapy. Peroral cholangioscopy (POCS) affords direct visualization of biliary strictures and facilitates tissue sampling guided by endoscopic views.

At the present time, single-operator POCS (sPOCS) and direct POCS employing an ultraslim gastroscope to directly access the bile ducts are most widely used [2]. The number and proportion of publications in the past 10 years featuring sPOCS suggests that it has become the dominant platform [3].

sPOCS-guided biopsy was shown in a recent prospective randomized multicenter study to be more sensitive than ERCP brush cytology (68.2 % vs. 21.4 %; P < 0.01) [4]. The diagnostic utility of a visual impression of malignancy during POCS has been well studied; a systematic review of multiple POCS platforms involving 20 studies reported the pooled sensitivity for detecting malignancy at 67 % – 100 %, which was higher than that for cholangioscopy-guided biopsy (38 % – 100 %). The specificity in both groups was high (73 % – 100 % vs. 75 % – 100 %) [3]. When visual impression was analyzed for fiberoptic sPOCS (4 studies, 235 patients), sensitivity was 78 % – 100 %, specificity was 77 % – 93 %, and accuracy was 80 % – 94 %. For digital sPOCS (2 studies, 74 patients), the values were 83 % – 90 %, 89 % – 96 %, and 87 % – 93 %, respectively. In the analysis of guided biopsy for fiberoptic sPOCS (7 studies, 303 patients), sensitivity was 49 % – 100 %, specificity 94 % – 100 %, and accuracy 73 % – 100 %; for digital sPOCS (2 studies, 72 patients) sensitivity was 80 % – 85 %, specificity 100 %, and accuracy 93 % [3].

...this prospective multicenter cohort study showed excellent diagnostic utility and safety for single-operator peroral cholangioscopy in patients with indeterminate biliary strictures, tempered by a few caveats.

The study of Almadi et al. [5] in this issue of Endoscopy is a prospective post-market cohort study from 20 sites in Asia, the Middle East, and Africa of sPOCS reporting the achievement of definitive diagnosis of IDBSs by visual impression and via targeted biopsies under direct cholangioscopic visualization. The study documented 290 procedures in 289 consecutive patients. Two versions of the single-operator cholangioscope were used: the multipart SpyGlass Legacy fiberoptic system, used in 173/289 (58.9 %) of the patients, and its replacement, the one-piece SpyGlass DS digital device, used for the remaining 116 patients.

The authors’ primary study endpoint was defined as procedural success, derived from three metrics: ability to visualize the stricture; ability to provide a visual impression of malignancy; and ability to obtain forceps biopsies adequate for histology, if desired. They reported high success rates in visualizing the stricture (98.6 %), in providing a visual impression of whether it was malignant vs. benign (87.2 %), and in biopsy adequacy for analysis (92.9 %), giving an overall procedural success rate of 241/290 (83.1 %). The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, and 77.2 % accuracy compared with the final diagnosis. sPOCS-guided biopsies showed 75.3 % sensitivity, 100 % specificity, and 86.5 % accuracy. The image quality for both devices combined was described as “excellent” in 48.6 % and “good” in 35.5 %, with significantly higher rates of “excellent” scores for the DS system. Five serious adverse events occurred (1.7 %, 95 % confidence interval 0.5 % – 4.0 %); three patients developed cholangitis despite antibiotic prophylaxis, and one each had acute pancreatitis and bleeding. No mortality occurred.

This study was billed as a “large prospective multinational real-life experience” of POCS utility in the evaluation of IDBSs, but several points bear closer scrutiny.

The definition of IDBS used for study entry is unclear; as stated above, the absence of a definitive diagnosis following abdominal imaging and stricture cytology is frequently used. In this study, 39.8 % had not undergone prior ERCP; the authors allude to the use of a less stringent definition of IDBS that “typically would be encountered in clinical practice.” Nonetheless, we are beginning to see randomized studies employing a similar definition of IDBS, such as that of Gerges et al. [4].

In a prospective study across multiple sites that evaluated subjective primary endpoints (visual impression of malignancy, image quality), standardizing the reporting parameters via pre-enrolment training and alignment would be expected to increase the objectivity of findings. This however was not performed. A backdrop of lack of uniformity and poor interobserver agreement for interpreting the visual impression of biliary strictures [2] adds further potential value to standardization of training.

Two recent retrospective studies from the USA and the Netherlands comparing the diagnostic accuracy of sPOCS with other techniques in patient populations that included a significant proportion of primary sclerosing cholangitis (PSC; 39.1 % and 40 %, respectively) found that sPOCS did not increase the diagnostic sensitivity for cholangiocarcinoma over that of ERCP with brush cytology [6] [7]. No patients with PSC were enrolled in the study of Almadi et al.; the outcomes therefore may not be generalizable to cohorts containing significant numbers of patients with PSC.

The subject of this editorial is a post-marketing registry study that was sponsored and funded by the manufacturer of the sPOCS system. Full disclosure was made, and it was declared that three employees of the manufacturer were co-authors, one of whom performed data management and statistical analysis. That there was manufacturer involvement in multiple aspects of a study focused on the performance of a medical device should give pause for thought to readers of the paper, in considering the extent to which this involvement might shape the outcomes of the study. A Cochrane review found that manufacturer-sponsored drug and device studies more often had favorable efficacy results and conclusions than those funded by non-industry sources, consistent across a wide range of diseases and treatments [8]. In exploring how this propensity occurs, the authors opined that “overly positive outcomes” may occur through biasing choices in study design, conduct, data coding and analysis, reporting, and selective publication.

In conclusion, this prospective multicenter cohort study showed excellent diagnostic utility and safety for sPOCS in patients with IDBSs, tempered by a few caveats. Nonetheless, the large number of patients enrolled from multiple centers and countries, and the consistency of its results with that of other studies adds to the generalizability of its findings, and therefore to its ultimate value.

Publication History

Article published online:
24 June 2020

• References

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