BACKGROUND:Cholangiocarcinoma is a very aggressive tumor with poor survival.Therefore,early diagnosis and surgical resection are of paramount importance.Its diagnosis is difficult because access to the tumor is not easy.Biopsy is possible only for intrahepatic cholangiocarcinoma,which accounts for 10% of cases.Routine brush cytology from endoscopic retrograde cholangiopancreatography(ERCP) has a high specificity of 100% but unfortunately a low sensitivity of 30%.In this review we briefly describe new diagnostic techniques applicable to ERCP brush cytology specimens and targeting the genetic background of the disease,in particular fluorescence in situ hybridization(FISH) and digital image analysis(DIA).DATE SOURCES:The PubMed database up to 2011 was used for the retrieval of relevant articles.The search terms FISH,fluorescence in situ hybridization,DIA,digital image analysis and cholangiocarcinoma were used.Both original and review articles were used.RESULTS:FISH identifies cells with chromosomal abnormalities,mainly numerical aberrations,using a mixture of fluorescencelabeled probes.FISH offers a higher sensitivity than routine cytology,retaining a high level of specificity.The DIA criterion for malignancy is demonstration of aneuploidy.This technique increases the sensitivity to 40%,but the specificity remains low.Preliminary data from application to other tumors suggest that combination of FISH and DIA may be of further benefit.CONCLUSIONS:The new techniques offer a significantly enhanced diagnostic efficacy in the evaluation of ERCP brush specimens.Apart from contributing to a more timely diagnosis,their wider application to cholangiocarcinoma may also facilitate the genetic study of the disease and add to our understanding of oncogenesis at the molecular level,with the prospect of identifying targets for novel therapeutic interventions. BACKGROUND: Cholangiocarcinoma is a very aggressive tumor with poor survival. Prior, early diagnosis and surgical resection are of paramount importance. It is difficult because access to the tumor is not easy. Biopsy is possible only for intrahepatic cholangiocarcinoma, which accounts for 10% Routine brush cytology from endoscopic retrograde cholangiopancreatography (ERCP) has a high specificity of 100% but unfortunately a low sensitivity of 30%. In this review we briefly describe new diagnostic techniques applicable to ERCP brush cytology specimens and targeting the genetic background of the disease, in particular fluorescence in situ hybridization (FISH) and digital image analysis (DIA). DATE SOURCES: The PubMed database up to 2011 was used for the retrieval of relevant articles. The search terms FISH, fluorescence in situ hybridization, DIA, digital image analysis and cholangiocarcinoma were used. Both original and review articles were used .RESULTS: FISH identifies cells with c FH offers a higher sensitivity than routine cytology, retaining a high level of specificity. DIA criterion for malignancy is demonstration of aneuploidy. This technique increases the sensitivity to 40%, but the specificity remains low. Preliminary data from application to other tumors suggest that combination of FISH and DIA may be further benefits. CONCLUSIONS: The new techniques offer a significantly enhanced diagnostic efficacy in the evaluation of ERCP brush specimens. Part from contributing to a more timely diagnosis, their wider application to cholangiocarcinoma may also facilitate the genetic study of the disease and add to our understanding of oncogenesis at the molecular level, with the prospect of identifying targets for novel therapeutic interventions.