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Biomedical subjects

Peter J Hewett

Publications and source records attributed to Peter J Hewett.

5 recordsLinked to original sources

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells.

PURPOSE: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. EXPERIMENTAL DESIGN: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin gamma2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. RESULTS: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. CONCLUSION: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer.

Adult↗

Detection of occult metastasis in lymph nodes from colorectal cancer patients: a multiple-marker reverse transcriptase-polymerase chain reaction study.

INTRODUCTION: Lymph node status is a key factor for disease staging and is the main determinant for adjuvant therapy of colorectal cancer. The current staging procedure is unable to identify occult metastasis in lymph nodes, which is likely to be an important cause of treatment failure in some early-stage patients. The detection of occult metastasis could identify a patient subgroup at risk for disease relapse that would benefit from adjuvant therapy. The purpose of this study was to establish and test a multimarker reverse transcriptase-polymerase chain reaction assay for the molecular detection of occult metastases in lymph nodes. METHODS: Forty-four patients with colorectal cancer and 14 patients with benign bowel diseases undergoing colonic resection were enrolled in the study. Reverse transcriptase-polymerase chain reaction was used to detect expression of three epithelial markers, carcinoembryonic antigen, cytokeratin 20, and guanylyl cyclase C, in fresh colorectal lymph node tissue. RESULTS: Forty-six of 47 (97.9 percent) histologically positive lymph nodes were also positive by reverse transcriptase-polymerase chain reaction. Of 221 histologically negative nodes, 97 (43.9 percent) were positive for at least one of the three markers by reverse transcriptase-polymerase chain reaction: 24.9 percent for carcinoembryonic antigen, 16.7 percent for cytokeratin 20, and 24.9 percent for guanylyl cyclase C. Among these were 13 of 20 stage I and II cases, implying a staging shift to stage III by molecular diagnosis of occult metastasis. Fifty-nine additional nodes were found to be positive for occult metastases in 22 of 24 stage III and IV patients. CONCLUSIONS: These results indicate that occult metastases are detectable by reverse transcriptase-polymerase chain reaction in histologically negative lymph nodes from colorectal cancer. The use of a panel of three markers improves the specificity of the method.

Adenocarcinoma↗

Effect of port composition on tumor cell adherence: an in vivo model.

INTRODUCTION: We have reported previously on an in vitro model to examine tumor cell adherence to metal and plastic laparoscopic ports and to port sites through which they had been passed. This demonstrated that increased numbers of tumor cells were found both on metal ports compared with plastic ports and on the port sites through which metal ports had passed. In this study, the in vivo adherence of such cells to ports and port sites was investigated. METHODS: LIM 1215 tumor cells were injected under direct vision into the pelvises of 16 30-kg female pigs (range, 15-70 x 106 cells). A total of 12 ports were inserted through each anterior abdominal wall (6 metal and 6 plastic), and these were either left in situ for 30 minutes (nondisplaced) or were removed twice and replaced through the original wound (displaced). RESULTS: Increasing the tumor cell inoculum resulted in increased deposition of tumor cells on both ports (P = 0.002) and on the port sites (P = 0.017). Significantly more tumor cells adhered to metal ports than to plastic ports (P = 0.04), although this failed to reach significance for the sites through which metal ports had been passed (P = 0.066). Although displacement of ports did not increase the number of tumor cells that adhered to ports (P = 0.45), this did result in more tumor cells being deposited on the port sites (P = 0.01). CONCLUSIONS: These data suggest that minimizing the number of tumor cells within the abdominal cavity, using plastic ports, and securing ports to prevent inadvertent displacement would be expected to reduce the number of tumor cells deposited in port sites during operative laparoscopy. This may be beneficial in reducing the incidence of port-site metastases after laparoscopic surgery for gastrointestinal malignancies.

Animals↗