Chemotherapy, liver injury, and postoperative complications in colorectal liver metastases.
BACKGROUND
Systemic chemotherapy (CTx) is increasingly used before surgery for colorectal liver metastases (CRC-LM). However, CTx may cause liver injury like steatosis, steatohepatitis, and sinusoidal injury which may be associated with postoperative morbidity. Some recent data have even shown an increased mortality in patients with CTx-associated steatohepatitis. We, therefore, analyzed our recent experience with potential hepatic injury and its association with CTx and morbidity in patients undergoing surgery for CRC-LM.


METHODS
From 2001 to 2007, 179 patients underwent primary liver resection for CRC-LM. Sufficient non-tumorous liver parenchyma could be re-evaluated for this study in 102 patients. In these 102 patients (66% male, median age 62 years, median BMI 26, 8% diabetics (IDDM)), liver injury was classified using established criteria for steatosis and sinusoidal dilatation (SD) and then compared with preoperative CTx and postoperative outcome. Fifty-eight percent of the operations were (extended) hemihepatectomies (ExtRes), 42% segmental or wedge resections (LimRes). Before resection, 66% had received CTx (33% FU-based (FU), 19% oxaliplatin-based (Oxa), 12% irinotecan-based (Iri), and 3% Oxa+Iri). The interval between CTx and surgery was always ≥4 weeks.


RESULTS
Mortality was 3/102 (2.9%). Any complication occurred in 48%, hepatic insufficiency in 5.9%, and liver-related complications in 24%. Hepatic steatosis >20% was found in 37% (half of them with steatosis >50%). BMI correlated with the frequency of steatosis. Steatosis >20% was more frequent in patients with preoperative chemotherapy but did not depend on the chemotherapy regimen. No relevant risk factor for grades 2 and 3 SD was found. The specific use of Oxa or Iri did not significantly correlate with hepatic injury. Neither a CTx per se nor the different CTx regimens nor the extent of hepatic injury showed any negative influence on mortality, complication rates, or hepatic insufficiency. Patients with IDDM had a higher mortality (25% vs 1% without IDDM; p<0.02), increased complication rate (75% vs 46%; p=0.11), a higher rate of hepatic insufficiency (25% vs 4%; p<0.02), and more liver related complications (50% vs 21%; p=0.06). Patients undergoing ExtRes had a higher overall (p<0.01) and liver-related (p=0.05) complication rate compared to LimRes. None of the 34 patients with preoperative Oxa or Iri died or developed hepatic insufficiency.


CONCLUSIONS
In our experience, hepatic injury (steatosis) was influenced by BMI and by preoperative CTx. Neither preoperative CTx nor liver injury increased perioperative morbidity. Patients with IDDM were at a rather high perioperative risk.
Department of Surgery, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany. frank.makowiec@uniklinik-freiburg.de
Frank
F
Makowiec
Simone
S
Möhrle
Hannes
H
Neeff
Oliver
O
Drognitz
Gerald
G
Illerhaus
Oliver G
OG
Opitz
Ulrich T
UT
Hopt
Axel
A
zur Hausen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D011183:Postoperative Complications; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends
D000970:Antineoplastic Agents