Genetic and Histological Assessment of Surgical Margins in Resected Liver Metastases From Colorectal Carcinoma

Abstract

There have been few reports on the minimum surgical margins (SMs) required for successful liver resection in patients with colorectal metastases. This minimum requirement may be narrower than the previously recommended margin of 10 mm.Objectives: To identify the minimum margins by assessing the presence of micrometastases around the tumor using genetic and histological techniques, and to investigate whether SMs are associated with patterns of tumor recurrence or patient survival. Design: Prospective and retrospective studies.Setting: Tertiary referral cancer center.Patients and Methods: Fifty-eight patients who underwent 62 liver resections for hepatic metastasis from colorectal cancer between December 1, 1996, and November 30, 2000, were included in the study. Tissue samples taken from the tumor, surrounding liver parenchyma, and Glisson pedicle near the tumor were tested for K-ras and p53 mutations using the mutant allelespecific amplification method. For the retrospective study on patient outcomes, 194 patients who had undergone liver resections between 1980 and 2000 were analyzed according to their SMs.Results: Of the 62 sets of samples from liver metastases, 39 were positive for K-ras and p53 gene mutations or both. Micrometastases in the liver parenchyma surrounding colorectal metastases were present in 2.0% (4/199) of tested samples and were located within 4 mm of the tumor border. Micrometastases via Glisson pedicle were more common (14.3% [3/21]), but these were also confined to a short distance from the tumor edge (Յ5 mm). Of the 5 micrometastases detected by genetic analysis, only 2 were confirmed by histopathological examination. The analysis of patient outcomes demonstrated that the incidence of cut-end recurrence (relapse in the bed of resection) decreased from 20.0% to a range of 5.6% to 7.5% when the SM is 2 mm or more. The incidence of definite cut-end recurrence in patients with SMs less than 2 m, 2 to 4 mm, and 5 mm or wider was 13.3% (6/45), 2.8% (1/36), and 0% (0/102), respectively. The SM was not a significant prognostic factor in patient survival.Conclusions: Micrometastases around liver tumors are not common, and most are confined to the immediate vicinity of the tumor border. We propose an SM of 2 mm as a clinically acceptable minimum requirement, which carries approximately a 6% risk of margin-related recurrence. Because liver resection provides the only chance of cure, complete removal of the tumor with a minimum margin is justified when technically unavoidable because of the size, location, number of tumors, or successive resections.

Influence of Margins on Disease Free Survival Following Hepatic Resection for Colorectal Metastasis: A Meta-Analysis

“…Patients with positive margins were excluded from the current meta-analysis and only patients with negative margins were included. Many studies sub-stratified sub-centimeter negative margins into different sub-categories [4,8,10]. For these studies, a weighted mean was calculated using the number of patients in each sub-category and the corresponding percentage survival, to compute percentage survival for the whole <1 cm negative margin sub-group.…”

“…Hepatic resection remains a well accepted modality in the treatment of patients with colorectal liver metastases (CRLM) with 5 year overall survival (OS) ranging from 37 % to 58 % [1][2][3][4] and 5 year disease free survival (DFS) ranging from 11 % to 50 % [3,[5][6][7][8][9][10][11][12][13][14]. Recurrence of the disease after resection still remains a challenge and adversely affects the long term outcomes.…”

“…Although there is a consensus that positive margins portend a worse DFS as compared to negative margins, the extent of negative margins remains controversial. Several studies have documented a DFS advantage of ≥1 cm negative margins over <1 cm negative margins of resection [5,8,10,13]. Whereas others have concluded that the width of negative margin has no influence on DFS [3,6,7,[9][10][11]14].…”

Surgery for colorectal liver metastases: Expanding the boundaries but where have all the patients gone

“…14, 38,39,41 Many scoring systems for predicting the outcome of resection of CRC liver metastases are based on long-lasting retrospective studies that started before new potent chemotherapeutical agents were introduced as well as before refined imaging techniques used today were developed and before sophisticated surgical techniques were routinely used. A special problem arises from the fact that ongoing studies of adjuvant chemotherapy for patients with resected or ablated CRC liver metastases will not be reported for several years.…”

“…Kokudo demonstrated that CRC liver metastases can grow crossing intersegmental planes, without infiltrating the parenchyma and with minimal lateral spread. 41 Based on such observations Kokudo concludes that anatomic resection for CRC liver metastases is neither necessary nor beneficial and that analogy with operations for HCC is not accurate. 65 In another paper Kokudo concludes that there is no significant difference in survival between anatomical major resection and non-anatomical limited resection for CRC liver metastases.…”