Objective: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer.
Summary Background Data: For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems.
Methods: Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction.
Results: Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination.
Conclusions: Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.
The liver is the most common site for metastatic spread of colorectal cancer as a result of the portal venous drainage of the gastrointestinal tract. The frequency of synchronous liver metastases ranges from 15% to 30%, and a similar percentage of patients develop metachronous liver metastases. 1-4 For these patients, hepatic resection is the only treatment option offering a reasonable chance of long-term survival. 5,6 Patients with potentially resectable but untreated liver metastases have a 3-year survival rate of 20%, and fewer than 3% of patients survive 5 years. 7 Liver resection of metastases of colorectal cancer results in a 3-year survival rate of 30% to 61% and a 5-year survival rate of 16% to 51%, depending on patient selection. 8-12 However, after resection of liver metastases, 38% to 53% of resected patients develop extrahepatic tumor recurrence, probably caused by the release of neoplastic cells into the systemic circulation either before or during hepatic resection. 8,9,13-15 It has always been suspected, but never proven, that mechanical alteration of the liver during resection of liver metastases leads to massive intraoperative tumor cell shedding into the circulation. Detection of this intraoperative tumor cell dissemination could help to modify the technique of liver resection to avoid or reduce the assumed spread of tumor cells. In addition, detection of disseminated tumor cells of colorectal cancer in patients with liver metastases could help to identify patients at risk for tumor relapse, who might benefit from adjuvant therapy regimens. Because of the lack of appropriate detection systems, the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer has not been determined.
Reverse transcriptase-polymerase chain reaction (RT-PCR)-based protocols are sensitive and specific assays for the detection of disseminated cancer cells, allowing the identification of approximately one neoplastic cell in 107 normal peripheral mononuclear blood cells. 16 Cytokeratin 20 transcripts appear to be good targets for the detection of disseminated colorectal cancer cells because they are expressed in gastrointestinal epithelium, urothelium, or Merkel cells and their respective tumors but not in other nontransformed tissues. 17-23 Recently, we demonstrated a significant intraoperative tumor cell dissemination during resection of primary colorectal cancer using cytokeratin 20 RT-PCR for detection of circulating tumor cells of colorectal cancer. 22
The purpose of this study was to determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection of colorectal metastases using cytokeratin 20 RT-PCR.