Colorectal cancer is a common disease entity and the liver represents the most common site of metastases for this cancer. Liver resection is the treatment of choice and the only potentially curative treatment. Extrahepatic disease represents a relative contraindication for resection. Often, patients brought to the operating room for liver resection are found to have additional intra-abdominal disease, cannot be resected, and are therefore subjected to a laparotomy for no benefit. Furthermore, in the majority of patients, tumor recurs due to residual disease undetected at the time of liver resection. Colorectal cancers are glucose avid and whole body positron emission scanning (PET) after administration of the glucose analogue 18F-fluorodeoxyglucose (18F- FDG) has been proposed as a sensitive non-invasive method for detecting metastatic colorectal cancer. Prior studies examining the use of this imagine modality have not systematically compared it to conventional imaging. A major goal of the current proposal is to examine the additional yield of 18F-FDG PET scanning compared with standard scanning modalities in this common clinical setting. The potential of this modality to change clinical therapy by detecting additional metastatic disease and reducing unnecessary surgery will be determined as well as its ability to direct more appropriate resections by finding additional resectable disease not seen by other imaging modalities. In this proposal, metastatic lesions in the liver will be resected, allowing a unique opportunity to determine the limits of detection of 18F-FDG PET scanning for metastatic colorectal tumor. This may have important therapeutic implications since others have proposed the use of whole body FDG- PET scanning to monitor therapeutic benefits and alter therapeutic course of chemotherapeutic and ablative therapies. Finally, glucose transport and glucose utilization by tumors have been correlated to local growth factor levels, tumor metabolism, and aggressiveness in other tumor types. Increased glucose transport and metabolism have been correlated to poor prognosis in other tumor.as. This proposed study allows direct correlation of 18F-FDG PET data with tissue measurements of glucose transport deoxyglucose phosphorylation, tumor proliferation, and long term patient prognosis. This allows correlation of FDG uptake as measured by PET in colorectal metastases to biologic determinants of tumor aggressiveness, and ultimately to clinical behavior of tumors. These studies will not only examine the prognostic implications of FDG-PET but also the biologic basis for prognostic influences. Thus, the specific goals of this application are to determine the clinical ability of 18F- FDG PET in the patient with hepatic colorectal metastases. We will attempt to determine the limits of detection of this modality, to correlate the FDG uptake with tissue markers of altered glucose metabolism and cellular proliferation, and to compare 18F-FDG PET scanning to standard imaging modalities in order to determine whether FDG-PET 1) may positively impact clinical management of the patient with hepatic colorectal metastases, 2) may potentially be useful for monitoring treatment responses for palliative treatments, and 3) may be a useful non-invasive predictor of prognosis.
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