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

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

Is hepatic resection justified after chemotherapy in patients with colorectal liver metastases and lymph node involvement?

PURPOSE: For patients with colorectal liver metastases (CLM), regional lymph node (RLN) involvement is one of the worst prognostic factors. The objective of this study was to evaluate the ability of a multidisciplinary approach, including preoperative chemotherapy and hepatectomy, to improve patient outcomes. PATIENTS AND METHODS: Outcomes for a consecutively treated group of patients with CLM and simultaneous RLN involvement were compared with a cohort of patients without RLN involvement. Univariate and multivariate analysis of clinical variables was used to identify prognostic factors in this high-risk group. Results Of the 763 patients who underwent resection at our institution for CLM between 1992 and 2006, 47 patients (6%) were treated with hepatectomy and simultaneous lymphadenectomy. All patients had received preoperative chemotherapy. Five-year overall survival (OS) for patients with and without RLN involvement were 18% and 53%, respectively (P or= 40 years were identified as independent poor prognostic factors. CONCLUSION: Combined liver resection and pedicular lymphadenectomy is justified when RLN metastases respond to or are stabilized by preoperative chemotherapy, particularly in young patients. In contrast, this approach does not benefit patients with celiac and/or para-aortic RLN involvement, even when patients' disease is responding to preoperative chemotherapy

Long-term outcomes after hepatic resection for colorectal metastases in young patients

BACKGROUND: Long-term outcomes after hepatectomy for colorectal liver metastases in relatively young patients are still unknown. The aim of the current study was to evaluate long-term outcomes in patients 40 years old. METHODS: All consecutive patients who underwent hepatectomy for colorectal liver metastases at the authors' hospital between 1990 and 2006 were included in the study. Patients < or = 40 years old were compared with all other patients treated during the same period. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were determined, and prognostic factors were identified. RESULTS: In total, 806 patients underwent hepatectomy for colorectal liver metastases, of whom 56 (7%) were aged < or = 40 years. Among the young patients, more colorectal liver metastases were present at diagnosis, and they were more often diagnosed synchronous with the primary tumor. Five-year OS was 33% in young patients, compared with 51% in older patients (P = .12). Five-year PFS was 2% in young patients, compared with 16% in older patients (P < .001). DFS rates were comparable between the groups (17% vs 23%, P = .10). At multivariate analysis, age < or = 40 years was identified as an independent predictor of poor PFS. CONCLUSIONS: In young patients, colorectal liver metastases seem to be more aggressive, with a trend toward lower OS, more disease recurrences, and a significantly shorter PFS after hepatectomy. However, DFS rates were comparable between young and older patients, owing to an aggressive multimodality treatment approach, consisting of chemotherapy and repeat surgery. Therefore, physicians should recognize the poor outcome of colorectal liver metastases in young patients and should consider an aggressive approach to diagnosis and early treatment

Patients with initially unresectable colorectal liver metastases:is there a possibility of cure?

PURPOSE: Although oncosurgical strategies have demonstrated increased survival in patients with unresectable colorectal liver metastases (CLM), their potential for cure is still questioned. The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure. PATIENTS AND METHODS: All patients with initially unresectable CLM who underwent rescue surgery and had a minimum follow-up of 5 years were included. Cure was defined as a disease-free interval > or = 5 years from last hepatic or extrahepatic resection until last follow-up. RESULTS: Mean age of 184 patients who underwent resection (April 1988 through July 2002) was 56.9 years. Patients had a mean number of 5.3 metastases (bilobar in 76%), associated to extrahepatic disease in 27%. Surgery was possible after one (74%) or more (26%) lines of chemotherapy. Five- and 10-year overall survival rates were 33% and 27%, respectively. Of 148 patients with a follow-up > or = 5 years, 24 patients (16%) were considered cured (mean follow-up, 118.6 months), six (25%) of whom were considered cured after repeat resection of recurrence. Twelve "cured" patients (50%) had a disease-free interval more than 10 years. Cured patients more often had three or fewer metastases less than 30 mm (P = .03) responding to first-line chemotherapy (P = .05). Multivariate analysis identified maximum size of metastases less than 30 mm at diagnosis, number of metastases at hepatectomy three or fewer, and complete pathologic response as independent predictors of cure. CONCLUSION: Cure can be achieved overall in 16% of patients with initially unresectable CLM resected after downsizing chemotherapy. In addition to increased survival, this oncosurgical approach has real potential for disease eradication

Complete pathologic response after preoperative chemotherapy for colorectal liver metastases:myth or reality?

PURPOSE: Complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy is of limited predictive value for complete pathologic response (CPR) and cure of the disease. The objective of this study was to determine predictive factors of CPR as well as its impact on survival. PATIENTS AND METHODS: From January 1985 to July 2006, 767 consecutive patients with CLM underwent liver resection after systemic chemotherapy. Patients with CPR were compared with patients without CPR. RESULTS: Twenty-nine of 767 (4%) patients had CPR, and none of these 29 patients had CCR. Patients with CPR (mean age, 54 years) had a mean number of 3.3 metastases at diagnosis (mean size, 29.3 mm). Objective response and stable disease were observed in 79% and 21% of cases, respectively. Postoperative mortality rate was 0%. After a median follow-up of 52.2 months (range, 1.1 to 193.0 months), overall 5-year survival was 76% for patients with CPR compared with 45% for patients without CPR (P = .004). Independent predictive factors for CPR were: age <or= 60 years, size of metastases <or= 3 cm at diagnosis, carcinoembryonic antigen (CEA) level at diagnosis <or= 30 ng/mL, and objective response following chemotherapy. The probability of CPR ranged from 0.2% when all factors were absent to 30.9% when all were present. CONCLUSION: CPR was observed in 4% of patients with CLM treated with preoperative chemotherapy. However, CPR may occur in almost one-third of objective responders age <or= 60 years with metastases <or= 3 cm and low CEA values. CPR is associated with uncommon high survival rates