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Original Investigation
October 2016

Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis

Author Affiliations
  • 1Hepatobiliary Surgery Unit, A. Gemelli Hospital, Catholic University of the Sacred Heart, Rome, Italy
  • 2Division of General Surgery A, Department of Surgery, University of Verona, Verona, Italy
  • 3Liver Unit, San Raffaele Hospital, Milan, Italy
  • 4Department of Digestive and Hepatobiliary Surgery, Mauriziano Umberto I Hospital, Turin, Italy
  • 5Unit of Hepatobiliary Surgery and Liver Transplantation, Cardarelli Hospital, Naples, Italy
  • 6Department of Medical and Surgical Sciences, Surgical Clinic, Brescia University, Brescia, Italy
  • 7Department of Surgery, Maggiore Hospital, Bologna, Italy
  • 8Department of Surgery and Transplantation, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
JAMA Surg. 2016;151(10):916-922. doi:10.1001/jamasurg.2016.1769
Key Points

Question  What is the prognostic association of the lymph node (LN) ratio with overall survival after liver resection for hilar cholangiocarcinoma?

Findings  In this Italian multicenter study, an LN ratio exceeding 0.20 was the only independent prognostic factor for overall survival in N1 patients after liver resection for hilar cholangiocarcinoma. However, overall survival of N0 patients was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.

Meaning  The LN ratio was an accurate prognostic factor after liver resection for hilar cholangiocarcinoma, but it was influenced by the total number of retrieved LNs.

Abstract

Importance  The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined.

Objectives  To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging.

Design, Setting, and Participants  Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014.

Main Outcome and Measures  Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up.

Results  One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004).

Conclusions and Relevance  An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.

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