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Original Investigation
July 8, 2020

Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches

Author Affiliations
  • 1James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus
  • 2Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
  • 3Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
  • 4Department of Surgery, University of Verona, Verona, Italy
  • 5Department of Surgery, Ospedale San Raffaele, Milano, Italy
  • 6Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
  • 7Department of Surgery, University of Virginia, Charlottesville
  • 8Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
  • 9Department of Surgery, Stanford University, Stanford, California
  • 10Department of Surgery, Emory University, Atlanta, Georgia
  • 11Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
  • 12Department of Surgery, University of Ottawa, Ottawa, Canada
  • 13Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
  • 14Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
  • 15Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands
  • 16Digestive Disease and Surgery Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio
  • 17Institute of Advanced Surgical Technology and Engineering, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
  • 18Deputy Editor, JAMA Surgery
JAMA Surg. Published online July 8, 2020. doi:10.1001/jamasurg.2020.1973
Key Points

Question  Which patients will develop very early recurrence (VER) (ie, recurrence within 6 months) after resection for intrahepatic cholangiocarcinoma and are the best candidates for neoadjuvant chemotherapy?

Findings  In this multi-institutional cohort study, 196 patients (22.3%) developed VER following resection with a detrimental association with overall survival (5-year overall survival, 8.9%). Two predictive models were developed to identify high-risk patients for VER in the pre- and postoperative setting with a good predictive accuracy in the training as well as the internal and external validation data sets.

Meaning  These data emphasize that VER is common after intrahepatic cholangiocarcinoma resection and highlight the need for an alternative treatment approach (ie, neoadjuvant chemotherapy) for high-risk patients.

Abstract

Importance  Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence.

Objective  To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre- and postoperative setting.

Design, Setting, and Participants  Patients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019.

Main Outcomes and Measures  Two logistic regression models were constructed to predict VER based on pre- and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated.

Results  Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER. The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre- and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets.

Conclusion and Relevance  An easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies.

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