Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis

HPB (Oxford). 2012 Aug;14(8):514-22. doi: 10.1111/j.1477-2574.2012.00489.x. Epub 2012 May 22.

Abstract

Objectives: Criteria for the selection of patients for adjuvant chemotherapy in intrahepatic cholangiocarcinoma (IHCC) are lacking. Some authors advocate treating patients with lymph node (LN) involvement; however, nodal assessment is often inadequate or not performed. This study aimed to identify surrogate criteria based on characteristics of the primary tumour.

Methods: A total of 58 patients who underwent resection for IHCC between January 2000 and January 2010 at any of three institutions were identified. Primary outcome was overall survival (OS).

Results: Median OS was 23.0 months. Median tumour size was 6.5 cm and the median number of lesions was one. Overall, 16% of patients had positive margins, 38% had perineural invasion (PNI), 40% had lymphovascular invasion (LVI) and 22% had LN involvement. A median of two LNs were removed and a median of zero were positive. Lymph nodes were not sampled in 34% of patients. Lymphovascular and perineural invasion were associated with reduced OS [9.6 months vs. 32.7 months (P= 0.020) and 10.7 months vs. 32.7 months (P= 0.008), respectively]. Lymph node involvement indicated a trend towards reduced OS (10.7 months vs. 30.0 months; P= 0.063). The presence of either LVI or PNI in node-negative patients was associated with a reduction in OS similar to that in node-positive patients (12.1 months vs. 10.7 months; P= 0.541). After accounting for adverse tumour factors, only LVI and PNI remained associated with decreased OS on multivariate analysis (hazard ratio 4.07, 95% confidence interval 1.60-10.40; P= 0.003).

Conclusions: Lymphovascular and perineural invasion are separately associated with a reduction in OS similar to that in patients with LN-positive disease. As nodal dissection is often not performed and the number of nodes retrieved is frequently inadequate, these tumour-specific factors should be considered as criteria for selection for adjuvant chemotherapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms
  • Bile Ducts, Intrahepatic / pathology
  • Bile Ducts, Intrahepatic / surgery*
  • Biliary Tract Surgical Procedures*
  • Blood Vessels / pathology*
  • Chemotherapy, Adjuvant*
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / surgery*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Lymph Node Excision
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Patient Selection*
  • Peripheral Nerves / pathology*
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United States