Optimizing endoscopic diagnosis of biliary strictures of undetermined etiology: a practical guide based on the new ASGE guidelines

Determining etiology of biliary strictures may be a diagnostic challenge involving multiple procedures and ensuing delays in therapeutic management (1). Delays in diagnosis have been shown to have an impact on survival; indeed, the 5-year survival rate for cholangiocarcinoma is 10%, and early diagnosis is correlated with an increase in survival rate (1).

The diagnostic work-up aims to distinguish between benign causes, such as inflammatory stricture, chronic pancreatitis, primary sclerosing cholangitis, and IgG4-related sclerosing cholangitis, and malignant causes such as cholangiocarcinoma and pancreatic cancer (2). Cross-sectional imaging often fails to distinguish between benign and malignant causes, especially in the absence of a mass, making endoscopic tissue acquisition essential (2).

The aim of the guidelines proposed by the American Society of Gastrointestinal Endoscopy (ASGE) is to advise on the correct use of the various techniques and tools currently available to increase the diagnostic yield, avoiding multiple costly interventions and optimizing overall management for patients with biliary strictures of undetermined etiology.

Current endoscopic tools allowing tissue acquisition are limited in number and still have a relatively low sensitivity in this setting (2,3). Tissue can be obtained by the following techniques:

• Intraductal cytology using endoscopic retrograde cholangio-pancreatography (ERCP) and fluoroscopy-guided brushings,
• Intraductal biopsy using ERCP and fluoroscopy guided biopsy forceps,
• Cholangioscopy-guided biopsy using dedicated through-the-cholangioscope biopsy forceps and
• Endoscopy ultrasound (EUS) guided tissue sampling by EUS-fine-needle aspiration (EUS-FNA) or fine-needle biopsy (EUS-FNB).

The ASGE’s first recommendation is to perform a fluoroscopy-guided biopsy in addition to a brush cytology. A meta-analysis of 21 observational studies showed that the sensitivity of the brush cytology plus fluoroscopy-guided biopsy was better (0.66) compared to brush cytology alone (0.40) (4). However, it should be noted that intraductal biopsies require some expertise and the ASGE recommends performing them in a tertiary center. In the meta-analysis, there was no significant difference in the occurrence of adverse events (AEs) between the group that performed brush cytology only and the group that performed intraductal biopsies, nevertheless two serious AE were reported related to the use of intraductal biopsies (prolonged bleeding and perforation). Furthermore, the literature does not show any significant cost difference between the two techniques. It should be noted that adding intraductal biopsies often helps in avoiding multiple endoscopic procedures to obtain a diagnostic sample (5,6).

Regarding the second recommendation, the ASGE advises the use of cholangioscopy-guided biopsies under specific conditions: (I) proximal biliary strictures where there is a high probability of adequate drainage of the segment upstream the stricture or (II) previous ERCP with inconclusive diagnosis and (III) performed in a tertiary center with the required experience and equipment.

Biopsies guided by cholangioscopy demonstrate higher sensitivity compared to those performed during ERCP (7). During cholangioscopy, optimal drainage of the biliary segment must be ensured to prevent infectious AE related to saline instillation (8). Some experts prefer to perform the cholangioscopy at a second time to ensure effective drainage during an initial ERCP and avoid increased intraductal pressure (7).

Diagnostic yield is also enhanced by interpreting morphological aspects of the stricture. Malignant strictures often exhibit specific characteristics, such as nodular masses, irregular mucosa, and severe neovascularization that can obstruct the lumen. These features not only can suggest malignancy, albeit still with low reproducibility, but can also guide biopsies and improve diagnostic accuracy (9).

Finally, regarding the financial aspect, although the addition of cholangioscopy increases procedure costs, when performed in an expert center by experienced endoscopists, it can prevent multiple ERCPs for diagnostic purposes and present higher cost-effectiveness (5).

The third and final recommendation from the ASGE is to use EUS in the diagnosis of strictures of undetermined etiology in certain conditions: (I) previous ERCP without a definitive diagnosis and (II) distal biliary strictures or (III) presence of lymphadenopathy or metastatic disease on cross-sectional imaging.

A meta-analysis by Chiang et al. showed that the combination of EUS and ERCP was more sensitive than ERCP alone, and that EUS had a lower AE rate (9,10). The studies also showed no significant difference in cost between performing EUS in addition to ERCP, when performed during the same session (11). The diagnostic yield is particularly high in cases of distal biliary strictures and in patients with a mass or suspicious lymph nodes, where FNA or FNB can be performed, saving time and avoiding multiple ERCP procedures (12).

Experts have also considered intraductal ultrasound (IDUS) and confocal laser endomicroscopy as additional tools to help in the diagnosis of strictures of undetermined etiology.

In previous ASGE guidelines, IDUS was highlighted as a promising technique for localizing malignant lesions with specific features such as a wall thickness greater than 9 mm, heterogeneous echotexture, and an irregular mass margin (13). A study demonstrated an increased sensitivity of transpapillary biopsies guided by IDUS compared to transpapillary biopsies alone (90.8% vs. 76.9%) (14). However, further studies are required before its routine clinical implementation.

Confocal laser endomicroscopy has also been evaluated and may provide a high negative predictive value for malignant lesions, based on the appearance of thickened black bands of collagen fibers and thickened vessel walls, as described in the Miami classification (15). Nevertheless, this classification suffers from poor inter-observer agreement, high costs and limited availability, which may hinder its clinical utility (15).

Future studies are needed to provide high-quality data and improve the endoscopic management of patients with strictures of undetermined etiology. Moreover, the role of technological advancements in tissue acquisition devices and the potential applications of artificial intelligence and molecular biology should be further explored. Various futures methods of investigation are investigated and may be proposed for the future ASGE recommendation (3).

To summarize, the ASGE suggest combining ERCP with fluoroscopic guided biopsy and brush cytology for biliary strictures of undetermined etiology. Depending on the location of the stricture and available expertise, cholangioscopy or EUS may also be considered.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-449/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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