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The role of down staging treatment in the management of locally advanced intrahepatic cholangiocarcinoma: Review of literature and pooled analysis
Ann Hepatobiliary Pancreat Surg 2020 Feb;24(1):6-16
Published online February 29, 2020;
Copyright © 2020 Korean Association of Hepato-Biliary-Pancreatic Surgery.

Sivesh Kamarajah1, Francesco Giovinazzo1, Keith J. Roberts1, Pankaj Punia2, Robert P. Sutcliffe1, Ravi Marudanayagam1, Nikolaos Chatzizacharias1, John Isaac1, Darius F. Mirza1, Paolo Muiesan1, and Bobby VM Dasari1

Departments of 1Hepatobiliary and Pancreatic Surgery, and 2Oncology, Queen Elizabeth Hospital, Birmingham, UK
Received September 13, 2019; Revised November 2, 2019; Accepted November 14, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Backgrounds/Aims: Approximately 60-80% of patients with intrahepatic cholangiocarcinoma (iCCA) are not suitable for surgical resection due to advanced disease at presentation. This review assesses the role of surgical resection followed by down staging treatment in the management of patients with locally advanced iCCA.
Methods: A systematic review and pooled analysis were performed of the relevant published studies published between January 2000-December 2018. The primary outcome measure was overall survival. Secondary outcome measures were rates of clinical benefit, margin-negative (R0) resections, overall and surgery-specific complications, and post-operative mortality.
Results: Eighteen cohort studies with 1880 patients were included in the review. The median overall survival in all patients was 14 months (range, 7-18 months). Patients undergoing resection following down staging had significantly longer survival than those who did not (median: 29 vs. 12 months, p<0.001). The Clinical Benefit Rate with this strategy (complete response+partial response+stable disease) was 64% (244/383), ranging from 33-90%. Thirty-eight percent of the patients underwent resections with a 60% R0 resection rate and 6% postoperative mortality.
Conclusions: Although the evidence to support the benefits of NAT for iCCA is limited, the review supports the use of down staging treatment and also surgical resection in the cohort with response to NAT in order to improve long-term survival in patients with locally advanced iCCA.
Keywords : Intrahepatic; Cholangiocarcinoma; Locally advanced; Down staging; Surgery