Regenerative Nodular Hyperplasia of the Liver Related to Chemotherapy: Impact on Outcome of Liver Surgery for Colorectal Metastases

BACKGROUND: Regenerative nodular hyperplasia (RNH) represents the end-stage of vascular lesions of the liver induced by chemotherapy. The goal was to evaluate its incidence and impact on the outcome of patients resected for colorectal liver metastases (CLM). METHODS: Patients who underwent hepatectomy for CLM after six cycles or more of first-line chemotherapy, between January 1990 and November 2006, were included. Detailed histopathologic analysis of the nontumoral liver was performed according to a standard format. RESULTS: From a cohort of 856 resected patients at our institution, 771 (90%) received preoperative chemotherapy. Of these, 146 fulfilled the selection criteria and were included: 24 (16%) received 5-fluorouracil (5-FU) and leucovorin (LV) alone, 92 (63%) had 5-FU/LV and oxaliplatin, 18 (12%) had 5-FU/LV and irinotecan, and 12 (8%) were treated by 5-FU/LV, oxaliplatin, and irinotecan. RNH occurred in 22 of 146 patients (15%). Twenty of these patients (91%) received oxaliplatin, of whom six (30%) had chronomodulated therapy. Patients treated by oxaliplatin more often had RNH compared with oxaliplatin-naïve patients (22 vs. 4%). Although operative mortality was nil, the presence of RNH was associated with increased postoperative hepatic morbidity (50 vs. 29%). Elevated preoperative gamma-glutamyltransferase (GGT) (>80 U/L; >1N) and total bilirubin levels (>15 μmol/L; >1N) were independent predictors of RNH. CONCLUSIONS: Patients with CLM who receive preoperative oxaliplatin have an increased risk of RNH and associated postoperative morbidity. Increased serum GGT and bilirubin are useful markers to predict the presence of RNH.