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.

There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.

No abstract

Detection of cytokeratin reverse transcriptase polymerase chain reaction products in the blood and K-ras or p53 gene mutations in the lymph nodes histologically negative for metastasis may be applicable for clinical use, despite some limitations, and may serve as a useful clinical factor for stratifying patients who are at high or low risk for recurrence after surgery.

No abstract