Detection of Hematogenic Tumor Cell Dissemination in Patients Undergoing Resection of Liver Metastases of Colorectal Cancer

Abstract

ObjectiveTo determine the extent of pre-and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer. Summary Background DataFor 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. MethodsBlood 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. ResultsTumor 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. ConclusionsDetection 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][14][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 tu...

Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases

“…The most extensive studies were performed by Weitz et al using RT-PCR for the detection of CK-20 transcripts in blood, BM and lymph nodes of patients undergoing surgery of colorectal tumors, as well as resection of liver metastases of colorectal cancer (7,9,10). By analyzing apical lymph nodes, they demonstrated that lymphogenic tumor cell dissemination is a common and frequent event in colorectal cancer preceding hematogenic tumor cell dissemination (7).…”

“…Thus, these patients have a high risk for extrahepatic tumor recurrence as a result of tumor cell dissemination during surgery, most likely caused by mechanical alteration of liver tumors located adjacent to the liver vein. Weitz et al demonstrated that CK-20 RT-PCR transcripts were significantly more often detected in blood samples taken from the central vein during surgery than before and after surgery of liver metastases of colorectal patients, suggesting that liver resection carries an increased risk for intraoperative tumor cell dissemination (10).…”

Perioperative tumor cell dissemination in patients with primary or metastatic colorectal cancer

“…10,11 It is in this population that prognostic markers may identify a subgroup of patients who are at a higher risk for disease relapse and who may also benefit from adjuvant therapy, especially from antitumoral agents with low systemic toxicity such as monoclonal antibodies, which have also proven to be effective against dormant tumor cells. 6,7 In this regard, there are several studies that have demonstrated that tumor cell detection is clearly related to an early relapse and decreased survival of the respective patients. 6,7,12,13 This new prognostic factor may change the surgical management of patients with colorectal liver metastases and may help to individualize the treatment of these patients with systemic or regional chemotherapy.…”

“…The detection of disseminated tumor cells could help to identify a subgroup of patients at risk for disease relapse that could benefit from adjuvant therapy. 6,7 In this context, flow cytometry is one of the methods used to identify subgroups at risk for disease relapse. Flow cytometry allows an accurate quantification of cells and at the same time a multi-parameter characterization of each cell present in the blood samples.…”

Ischemia/Reperfusion Accelerates the Outgrowth of Hepatic Micrometastases in a Highly Standardized Murine Model *

“…9,10 These studies are likely to be relevant for the implantation of tumor cells that are shed into the blood circulation during surgical manipulation. 11 However, in the majority of patients undergoing liver surgery, microscopic tumor cell deposits are already present at the time of surgery, and their detection in the liver parenchyma is associated with tumor recurrence and poor life expectancy. 12,13 At present, it is unknown how I/R in general, and vascular clamping in particular, affects the behavior of these micrometastases.…”