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R1 Resection by Necessity for Colorectal Liver Metastases: Is It Still a Contraindication to Surgery?

de Haas, Robbert J. MD*†; Wicherts, Dennis A. MD*†; Flores, Eduardo MD*; Azoulay, Daniel MD, PhD*; Castaing, Denis MD*‡§; Adam, René MD, PhD*‡§

doi: 10.1097/SLA.0b013e31818a07f1
Original Articles

Objective: To compare long-term outcome of R0 (negative margins) and R1 (positive margins) liver resections for colorectal liver metastases (CLM) treated by an aggressive approach combining chemotherapy and repeat surgery.

Summary Background Data: Complete macroscopic resection with negative margins is the gold standard recommendation in the surgical treatment of CLM. However, due to vascular proximity or multinodularity, complete macroscopic resection can sometimes only be performed through R1 resection. Increasingly efficient chemotherapy may have changed long-term outcome after R1 resection.

Methods: All resected CLM patients (R0 or R1) at our institution between 1990 and 2006 were prospectively evaluated. Exclusion criteria were: macroscopic incomplete (R2) resection, use of local treatment modalities, and presence of extrahepatic disease. We aimed to resect all identified metastases with negative margins. However, when safe margins could not be obtained, resection was still performed provided complete macroscopic tumor removal. Overall survival (OS) and disease-free survival were compared between groups, and prognostic factors were identified.

Results: Of 840 patients, 436 (52%) were eligible for the study, 234 (28%) of whom underwent R0 resection, and 202 (24%) underwent R1 resection. Number and size of CLM were higher, and distribution was more often bilateral in the R1 group. After a mean follow-up of 40 months, 5-year OS was 61% and 57% for R0 and R1 patients (P = 0.27). Five-year disease-free survival was 29% in the R0 group versus 20% in the R1 group (P = 0.12). In the R1 group, intrahepatic (but not surgical margin) recurrences were more often observed (28% vs. 17%; P = 0.004). Preoperative carcinoembryonic antigen level ≥10 ng/mL and major hepatectomy, but not R1 resection, were independent predictors of poor OS. Size ≥30 mm, bilateral distribution, and intraoperative blood transfusions independently predicted positive surgical margins.

Conclusions: Despite a higher recurrence rate, the contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar to that of R0 resection.

Positive resection margins after hepatectomy for colorectal metastases is considered a poor prognostic factor. In the current study, patients with negative resection margins (R0) were compared with patients in whom a negative resection margin could not be obtained (R1), all treated by an aggressive oncosurgical approach. Despite a higher intrahepatic recurrence rate, comparable survival rates were observed for both groups and, therefore, the contraindication of R1 resection should be revisited in the current era of effective chemotherapy.

From the *AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; †Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; ‡Université Paris-Sud, Villejuif, France; and the §Inserm, Villejuif, France.

Reprints: René Adam, MD, PhD, AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France. E-mail:

© 2008 Lippincott Williams & Wilkins, Inc.