Biliary Sclerosis after Hepatic Arterial Infusion Pump Chemotherapy for Patients with Colorectal Cancer Liver Metastasis: Incidence, Clinical Features, and Risk Factors

Abstract

Hepatic arterial infusion pump chemotherapy (HAIPC) contributes to the prolonged survival of selected patients with colorectal cancer liver metastases (CRCLM). The most clinically important adverse event after HAIPC with floxuridine (FUDR) is biliary sclerosis (BS). Little is known about the etiology of BS. HAIPC was administered to 475 consecutive patients who received HAIPC on prospective protocols from 1991 to 2008. The incidence, clinical features, variables related to demographics, comorbidity, medical history, CRCLM, surgery, chemotherapy, and laboratory data were reviewed. An analysis of factors potentially associated with BS, defined as a biliary stricture related to HAIPC requiring stent placement, was performed. The incidence of BS was 5.5% (16 of 293) in patients receiving HAIPC as an adjuvant therapy after hepatectomy, and 2% (2 of 100) in patients receiving HAIPC with FUDR for unresectable disease. The common hepatic duct was the site most frequently affected (87.5%). In patients receiving adjuvant HAIPC, BS was associated with abnormal postoperative flow scans (18.8% vs. 1.8%, P = 0.006), postoperative infectious complications (50.0% vs. 14.8%, P = 0.002), and larger dose/cycle/weight of FUDR (2.6 vs. 2.0 mg/cycle/kg, P = 0.025) than patients without BS. No patient died directly of BS. Median survival was not compromised by the development of BS (BS vs. non-BS: 61.0 months [range 6.2-171.6 months] vs. 47.2 months [range 2.4-200.8 months], P = 0.316, respectively). BS is an uncommon complication after HAIPC and does not compromise survival if adequately salvaged by stenting or dilatation. Surgical complications as well as type and dose of intra-arterial chemotherapy may contribute to the development of BS.