Prospective Observational Study of Exfoliated Peritoneal Tumor Cells in Locally Advanced Rectal Cancer
Prospective Observational Study of Exfoliated Peritoneal Tumor Cells in Locally Advanced Rectal Cancer
During the course of tumor growth and possibly by manipulation during the surgical procedure, cells from rectal tumors may be shed into the peritoneal cavity. Such cells may give rise to local recurrence or contribute to the formation of metastatic disease, specifically in the form of peritoneal carcinomatosis. Detection of cancer cells in the peritoneal cavity at the time of surgery might therefore be of value for prediction of disease recurrence with subsequent prognostic implications for these patients. In this study the investigators aim to determine the presence of exfoliated tumor cells in peritoneal lavage samples from patients undergoing surgery for LARC.
The investigators recently published a study investigating the incidence of exfoliated cancer cells in peritoneal lavage fluid after resection of locally advanced rectal cancer (LARC). DNA isolated from cells obtained by peritoneal lavage was analyzed by denaturing capillary electrophoresis with respect to mutations in hotspots of the K-RAS gene. This gene is mutated in 30% of rectal tumors. Exfoliated tumor cells (as assessed by the presence of mutated DNA) were found in lavage fluid from 19/237 of the patients, and the presence of tumor cells was associated with poor overall survival. Based on these encouraging results the investigators have designed a more comprehensive prospective study, using a novel, validated set of cancer specific DNA methylation - based biomarkers present in the vast majority of all colorectal tumors (sensitivity 94%, specificity 98%).Using these tumor cell associated biomarkers, the investigators aim to determine the presence of exfoliated tumor cells in peritoneal lavage samples from patients undergoing surgery for LARC. Lavage will be performed prior to and after manipulation of the tumor to provide data regarding both spontaneous and iatrogenic tumor cell exfoliation and their respective contribution to patient outcome. If detection of exfoliated tumor cells is predictive of tumor recurrence, this would support an active approach to postoperative chemotherapy, possibly in the form of intraperitoneal chemotherapy.
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