High sensitivity of biliary brush cytology after optimization of protocol in patients with suspected perihilar or intrahepatic cholangiocarcinoma: a prospective cohort study with historical control

Aims Endoscopic or percutaneous bile duct brushing is often performed as first step to differentiate between benign and malignant biliary strictures. Although brush cytology has a high specificity (95-100%), the sensitivity for detection of malignancy has been reported to be poor (41-67%) (1-4). This results in repeated diagnostic procedures with potential treatment delay, adverse events, and additional costs. Aim of this study was to evaluate a change in protocol with optimization of obtaining, handling and rating of brush cytology in patients with suspected perihilar or intrahepatic cholangiocarcinoma (pCCA/iCCA).

Methods Patients with suspicion of pCCA or iCCA were prospectively included between June 2021 and June 2023. Preferably 2 brushes and 2-4 intraductal biopsies were taken during the initial procedure. Cells were dislodged in a Cytolyt container within 30 seconds of which two Thinprep slides were prepared. Double reading was routinely performed by two expert cytopathologists. NGS was performed in samples with uncertainty of malignancy. A historical cohort (January 2017-June 2021) was used as control. In this cohort a single brush was performed without intraductal biopsies. The obtained cells were preserved in a Roswell Park Memorial Institute (RPMI) 1640 medium of which four cytospins were done. Double reading and NGS were not routinely performed. In both cohorts morphological diagnosis was assessed according to the Papanicolau society of cytopathology. Both the diagnostic category ‘suspicious for malignancy’ and ‘malignant’ were classified as results compatible with malignant disease. Final diagnosis was confirmed by either histological proof of malignancy or in case unavailable, follow-up compatible with malignant disease. Primary endpoint was the sensitivity before and after implementation of the protocol; secondary endpoints were the sensitivity of the individual steps of the modified protocol in the prospective cohort.

Results In this study, a total of 177 patients were evaluated (62 prospectively and 115 historical controls). The final diagnosis was malignant disease in 166 patients (93.8%). After protocol implementation, the sensitivity raised to 88.3% (95% CI, 76.8-94.8%) versus 50.9% (95% CI, 41.1-60.7%) pre-implementation (difference 37.4%; 95% CI, 23.6-51.2%). Specificity was 100% in both groups (2/2 vs 9/9). Sensitivity of the first brush in the prospective cohort was 78.3% (95% CI, 65.5-87.5%). NGS added value in 3 patients with uncertain results, increasing sensitivity to 83.3% (95% CI, 71.0-91.3%). A second brush was performed in 45 patients; of which one patient benefited from improved diagnostic value. Intraductal biopsies were performed in 34 patients (6 benign, 13 suspicious, 15 malignant, leading to a malignant diagnosis in 3 out of 13 patients with false-negative brush cytology. [1] [2] [3] [4]

Conclusions A modification in the handling of cytopathology, led to a significant improvement in the sensitivity of bile duct brushes to 78% for patients with suspected pCCA or iCCA. Furthermore, adding NGS, use of two brushes, and intraductal biopsies in the initial procedure could further increase sensitivity to 88%.

 

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Conflicts of interest

Jeska A. Fritzsche, Esmée Smit, Otto M. van Delden, Frederike Dijk, Arantza Farina Sarasqueta, Sybren L. Meijer, Anne M. Uyterlinde, Mattheus C.B. Wielenga, IJsbrand A.J. Zijlstra, and Joanne Verheij have no conflicts of interest or financial ties to disclose. Paul Fockens performed as a consultant for Olympus and Cook Endoscopy. Geert Kazemier reports research support and travel fees from SAS Analytics and research grants from KWF, ZonMw, Cancer Center Amsterdam Foundation, and Bennink Foundation outside the submitted research. Heinz-Josef Klümpen performed in advisory board for Janssen, Astra-Zeneca and IPSEN, and received Speaker’s fees from CCO and MedTalks. Cyriel Y. Ponsioen reports research grants from Gilead and Perspectum, performed as a consultant for Pliant, Takeda and Shire, and received speaker’s fees from Tillotts. Roy L.J. van Wanrooij performed as a consultant for Boston Scientific. Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific, and received speaker’s fee from Mylan and Zambon. All outside the submitted work.

• References

• 1 Weber A, von Weyhern C, Fend F, Schneider J, Neu B, Meining A. et al. Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma. World J Gastroenterol 2008; 14 (07) 1097-101
• 2 Volmar KE, Vollmer RT, Routbort MJ, Creager AJ.. Pancreatic and bile duct brushing cytology in 1000 cases: review of findings and comparison of preparation methods. Cancer. 2006; 108 (04) 231-8
• 3 Kobayashi M, Ryozawa S, Araki R, Nagata K, Tanisaka Y, Fujita A. et al. Investigation of Factors Affecting the Sensitivity of Bile Duct Brush Cytology. Internal Medicine 2019; 58 (03) 329-35
• 4 Mehmood S, Loya A, Yusuf MA.. Biliary Brush Cytology Revisited. Acta Cytol 2016; 60 (02) 167-72

Publication History

Article published online:
15 April 2024