[36, 37] The yield from brush cytology is variable, see more and positive diagnosis ranges from 44–80%.[36, 38] To date, there has been no prospective control study on the yield of tissue acquisition in HCCA. Pooled data from over 800 CCA patients reported sensitivity of 42%, specificity of 98%, and positive predictive value (PPV) of 98% among patients with confirmed cancer.[36] It has been reported that at least five brush passes, removal of the brush and catheter together, and inclusion of washings from the brush catheter may increase yield.[39] Intraductal fine-needle

aspiration (FNA) had a sensitivity of just 34%, with specificity of 100% and PPV of 100%.[36] Although intraductal biopsies have shown the highest GW-572016 yield for detection of malignancy, with a pooled sensitivity of 56%, specificity

of 97%, and PPV of 97%,[36, 39] intraductal biopsy in HCCA stricture is a cumbersome technique and may result in a lower diagnostic yield than the result reported in all CCAs. A “smash prep” protocol showed the overall sensitivity of 76% for all cancers with 100% specificity. The highest diagnostic yields for tissue sampling at Endoscopic retrograde cholangiopancreatography (ERCP) were obtained by using a combination of two or three standard techniques at the same setting. Ponchon et al. found that combining brush cytology (35% sensitivity) and forceps biopsy (43% sensitivity) yielded a sensitivity of 86%.[40] The Indiana group reported a sensitivity of 73% in CCA Megestrol Acetate subset using triple samplings with brush cytology, FNA, and forceps biopsy. The addition of a 2nd or 3rd sampling modality consistently increased diagnostic yield.[41] Therefore, we recommend at least a combination of two techniques such as brushing and forceps biopsy for all suspicious strictures. 5. Carbohydrate

antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are moderately specific for CCA. The presence of cholestasis and cholangitis lower the specificity of serum CA 19-9 Level of agreement: a—63%, b—37%, c—0%, d—0%, e—0% Quality of evidence: II-2 Classification of recommendation: B CA 19-9 and CEA are the two markers best studied with respect to CCA, but their utility is limited by poor sensitivity in early stage malignancy, and marginally elevated levels (> 100U/mL) may be associated with benign conditions.[42-47] Many studies have looked at their diagnostic utility in the setting of both PSC-related CCA and non-PSC-related CCA.[42-47] By using the serum cutoff value of more than 180 U/mL in some large series,[42-49] the sensitivity was moderate at 53%–79% and the specificity was fair to excellent at 83%–98%. However, the specificity of CA 19-9 in diagnosing biliary malignancy is reduced by the presence of either cholangitis or cholestasis.