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

• Published in: HPB (Oxford, England) England), 2012-08, Vol.14 (8), p.514-522
• Main Authors: Fisher, Sarah B, Patel, Sameer H, Kooby, David A, Weber, Sharon, Bloomston, Mark, Cho, Clifford, Hatzaras, Ioannis, Schmidt, Carl, Winslow, Emily, Staley, Charles A, Maithel, Shishir K
• Format: Article
• Language: English
• Subjects: 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; Gastroenterology and Hepatology; Humans; intrahepatic cholangiocarcinoma; Kaplan-Meier Estimate; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Lymph Node Excision; lymphadenectomy; Lymphatic Metastasis; lymphovascular invasion; Male; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Original; Patient Selection; perineural invasion; Peripheral Nerves - pathology; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States
• ISSN: 1365-182X; 1477-2574
• DOI: 10.1111/j.1477-2574.2012.00489.x

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.