Prognostic significance of the histologic response of perihilar cholangiocarcinoma to preoperative neoadjuvant chemoradiation in liver explants

Heidi D. Lehrke, Julie K. Heimbach, Tsung Teh Wu, Sarah M. Jenkins, Gregory J. Gores, Charles B. Rosen, Taofic Mounajjed

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Perihilar cholangiocarcinoma (pCCA) has a dismal prognosis. Protocols incorporating chemotherapy, radiotherapy, and liver transplantation (LT) have emerged as curative options for unresectable tumors with 70% 5-year survival rates. We aimed to assess the value of extent of residual tumor (ERT) and other pathologic factors following chemoradiation in predicting outcome; 152 liver explants with pCCA treated with neoadjuvant chemoradiation and LT between 1993 and 2013 were reviewed for ERT, pathologic stage, histologic grade, and perineural and lymphovascular invasion. ERT was quantified as the percentage of viable carcinoma in the tumor bed. Tumors were classified into 4 ERT categories: (1) complete/near-complete response (r1% ERT); (2) marked response (>1 to <10% ERT); (3) moderate response (10 to <30% ERT); and (4) minimal response (Z30% ERT). Overall 5-year survival rate was 69%. 5-year disease-free estimate was 74%. 57%, 16%, 18%, and 9% of explants were placed in ERT categories 1, 2, 3, and 4, respectively. ERT correlated significantly with the overall 5-year survival rate and 5-year, disease-free estimate by univariate (P<0.0001) and multivariate analysis (P=0.004 and 0.009, respectively). By multivariate analysis, pathologic stage was also an independent predictor of recurrence (P=0.003). Other variables that correlated with risk of death and recurrence by univariate analysis included perineural (P<0.0001) and lymphovascular invasion (P<0.0001), absence of primary sclerosing cholangitis (P=0.006 and P<0.0001, respectively), and pretreatment CA19-9 level (P=0.001 and 0.02, respectively). Histologic grade did not predict outcome. In summary, ERT independently predicts outcome in pCCA patients following neoadjuvant chemoradiation and LT and can stratify patient prognosis.

Original languageEnglish (US)
Pages (from-to)510-518
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number4
StatePublished - 2016


  • Cholangiocarcinoma
  • Histologic response
  • Liver transplantation
  • Neoadjuvant chemoradiation

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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