Extrahepatic biliary stenoses after hepatic arterial infusion (HAI) of floxuridine (FUdR) for liver metastases from colorectal cancer

Hepatic arterial infusion of floxuridine is an effective treatment for unre sectable hepatic metastases from colorectal cancer. Despite its pharmacolog ical advantage of higher tumor drug concentration with minimal systemic tox icity, hepatic arterial infusion of floxuridine is characterized by regiona l toxicity, including hepatobiliary damage resembling idiopathic sclerosing cholangitis (5-29% of treated cases). Unlike previous reports describing b iliary damage of both intrahepatic and extrahepatic ducts, a case series of extrahepatic biliary stenosis after hepatic arterial infusion with floxuri dine is herein described. Between September 1993 and February 1999, 54 pati ents received intraarterial hepatic chemotherapy based on continuous infusi on of floxuridine (dose escalation 0.15-0.30mg/kg/day for 14 days every 28 days) plus dexamethasone 28mg. Twenty-seven patients underwent laparotomy t o implant the catheter into the hepatic artery, the other 27 patients recei ving a percutaneous catheter into the hepatic artery through a transaxillar y access. Five patients (9.2%) developed biliary toxicity with jaundice and cholangitis (3 cases), alterations of liver function tests and radiologica l features of biliary tract abnormalities. They received from 9 to 19 cycle s (mean 14.5 +/- 6.3 cycles) of floxuridine infusion with a total drug deli vered dose ranging from 20.3 to 41.02mg/kg (mean: 31.4 +/- 13.5mg/kg). Extr ahepatic biliary sclerosis was discovered by computed tomography scan and u ltrasound, followed by endoscopic retrograde cholangiopancreatography and/o r percutaneous cholangiography in 3 cases. Radiological findings included c ommon hepatic duct complete obstruction in 1 case, common hepatic duct sten osis in 2 cases, common bile duct obstruction in 1 case, and intrahepatic b ile ducts dilation without a well-recognized obstruction in 1 case. Two pat ients were treated by sequentially percutaneous biliary drainage and balloo n dilation while 1 patient had an endoscopic transpapillary biliary prosthe sis placed. Percutaneous or endoscopic procedures obtained the improvement of hepatic function and cholestatic indexes without subsequent jaundice or cholangitis. In two patients suppression of floxuridine infusion allowed th e improvement of hepatic function. The present series suggests that in some patients receiving hepatic arteria l infusion of floxuridine extrahepatic biliary stenosis may represent the p rimary event leading to a secondary intrahepatic biliary damage that does n ot correlate with specific floxuridine toxicity but results from bile stasi s and infection, recurrent cholangitis and eventually biliary sclerosis. Ag gressive research for extrahepatic biliary sclerosis is advised, since an e arly nonsurgical treatment of extrahepatic biliary stenosis may prevent an irreversible intrahepatic biliary sclerosis worsening the prognosis of meta static liver disease.