Genetic study on mode of tumor spread from colorectal metastasis in the liver -standardization of surgical procedure

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To clarify most reasonable procedures for the surgical resection of colorectal liver metastases, we have conducted a genetic and histological study. Using a genetic diagnosis, tumor supread inside the hepatic parenchyma and Glisson's were investigated. Impact of K-ras and p-53 mutations on patient survival after liver resection was also studied. From 1996 through 2002,58 patients underwent 62 liver resections for hepatic metastasis from colorectal cancer. Tissue samples taken from the tumor, the surrounding liver parenchyma, and Glisson's pedicle near the tumor were tested for K-ras and p-53 mutations using the mutant allele-specific amplification method. This cohort was followed up until January 2004, and patient survival was analyzed. Of the 62 sets of samples from liver metastases, 39 were positive for K-ras and/or p53 gene mutations. Micrometastases in the liver parenchyma surrounding colorectal metastases were present in 2.0% (4/199) of tested samples and were located within 4 mm from the tumor border.Micrometastases via Glisson's pedicle were more common (14.3%:3/21), but they were also confined to a short range from the tumor edge (【less than or equal】 5mm). Three-year survival rate of patients without mutations of either gene was 94% while that of patients with mutation of wither gene was 67% (p=0.177 logrank). Three-year survival rate of patients with K-ras mutation had significantly poor prognosis comapring to that of patients without mutation (p=0.045).Micrometastases around the liver tumors are not common and most are confined to the immediate vicinity of the tumor border. Surgical margin of 2 mm appears to be a clinically acceptable minimum requirement with an approximately 5% risk of margin-related recurrence. K-ras mutation in the metastatic lesion was related to a poor patient outcome after liver resection.