Pathology of Cholangiocarcinomas

Round 1

Reviewer 1 Report

Due to regional heterogeneity in risk factors, cholangiocarcinomas are a diverse group of malignancies that arise from the biliary tree and exhibit significant geographic diversity. Extensive genomic and epigenomic characterization in the past 10 years has revealed diverse molecular abnormalities linked to several subtypes of cholangiocarcinoma, a disease that was previously thought to be a single entity. For therapeutic intervention, mutated genes may be selectively targeted. A few examples include trastuzumab for HER2-positive extrahepatic tumors and inhibitors of IDH and FGFR for intrahepatic cancers. Although biliary cancer has been better understood recently, there are still many crucial issues that need to be resolved about its prevention and treatment. The terminology and diagnostic standards for these still need to be standardized, and there is currently no international agreement on the histological categorization of cholangiocarcinoma. Thus, it is imperative to address this problem.

Comments-

1- The author also needs to describe cholangiocarcinoma epidemiology and risk factors.

2- There are several molecular markers in cholangiocarcinoma, that also need to be discussed in the text.

3- The finding that biliary tract tumors are targetable due to specific molecular alterations that may be identified in around 50% of cases in large series has occurred recently, giving patients greater opportunities to be treated even while relapsing and opening the door to personalized medicines. Mutation in iCCAs is therefore probably more prevalent than in eCCAs. Targetable mutations mostly affect FGFR2, BRCA, and IDH1, which account for 20% and 15% of cases, and need to be disused briefly with the methods of detection.

4- Finally, the author also needs to address limitations and future direction. 

Author Response

please see the attachment

Author Response File: Author Response.doc

Reviewer 2 Report

 Pathology of Cholangiocarcinomas

 

This is a short, crisp review on classifications of CCA. It covered all the forms of the disease in questions and gave good information on the modes of invasion, immunophenotyping, and role of the biopsies. Please consider following changes.

 

-          Introduction.

o   Add references to lines 24-27

o   Line 32 - Should it be decreased?

o   Line 32-33 – rephrase it?

o   Line 46 - Now it is combination of chemotherapy and immunotherapy (TOPAZ trial). Change it

-          Capitalize the following headings – 2; 3.1; 3.2; 5.1; 5.2; 6.1; 6.2

-          Line 104, consider changing proposes to be proposed?

-          Consider making a table or a figure to show the differences between iCCA and extra CCA covering sections 3-6. 

Author Response

please see the attachment

Author Response File: Author Response.doc

Round 2

Reviewer 1 Report

The responses and corrections made by author are satisfying.