Current clinical problems in colorectal cancer (CRC) diagnostics and therapeutics include the disease complexity, tumor heterogeneity, and resistance to targeted therapeutics. In the present study, we examined 171 CRC adenocarcinomas from Greek patients undergoing surgery for CRC to determine the frequency of KRAS, BRAF, and PIK3CA point mutations from different areas of tumors in heterogeneous specimens. Ninety two out of 171 (53.8%) patients were found to bear a KRAS mutation in codons 12/13. Of the 126 mutations found, 57.9% (73/126) were c.38G>A mutations (p.G13D) and 22.2% (28/126) were c.35G>T (p.G12V). Remarkably, RAS mutations in both codons 12 and 13 were recorded in the same tumor by pyrosequencing. Moreover, differences in KRAS mutations between tumor center and periphery revealed tumor heterogeneity in 50.7% of the specimens. BRAF c.1799T>A (V600E) mutations were moderately detected in 4/171 (2.3%) specimens, whereas most PIK3CA mutations were revealed by pyrosequencing 6/171 (3.5%). Remarkable tumor heterogeneity is revealed, where double mutations of KRAS in the same tumor and different KRAS mutation status between tumor core and margin are detected with high frequency. It is expected that these findings will have a major impact in cancer diagnosis and personalized therapies.
Laparoscopic adrenalectomy is beneficial in many patients with subclinical Cushing syndrome because it reduces arterial blood pressure, body weight, and fasting glucose levels. Prospective randomized studies are needed to compare laparoscopic adrenalectomy with a conservative approach and to confirm these results.
Background: The aim of this study was to analyse retrospectively the long-term results of patients who were operated for adenocarcinoma of the pancreatic head and identify significant prognostic factors. Methods: Eighty patients who were surgically treated for adenocarcinoma of the pancreatic head between 1995 and 2006 met the inclusion criteria and were subject to retrospective analysis. Possible prognostic factors were evaluated and independent predictors of survival were determined. Results: A classic Whipple procedure was performed in 47 patients and a pyloruspreserving pancreatoduodenectomy in 32 patients; one patient underwent total pancreatectomy. Five-year survival rate in this group of patients was 13.6%. Median survival time was 24 months. Univariable analysis demonstrated stage of disease, tumour size and grade and nodal status as significant predictive factors of survival. Multivariable analysis indicated tumour size, nodal status and disease stage as significant prognostic indicators in terms of survival. Conclusions: Long-term survival in pancreatic cancer is still very low. Prognostic factors include differentiation of the tumour, disease stage and nodal status. So far, there has been no reliable method that can accurately predict which patient will mostly benefit from surgical resection. This means that pancreatic cancer resection should nearly always be attempted.
Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell lines that also showed an EMT phenotype for HRAS. In this study we report a molecular profile for a BRAF oncogenic mutation BRAFV600E in colon using the Illumina 45,000 gene microarray. Key differentially expressed genes have been identified from the array analysis further verified by qPCR analysis. Ingenuity pathway analysis such as microsatellite instability, kinase signalling, apoptosis, WNT and Integrin signalling is presented. MutBRAF transforms cells through cross talk with developmental pathways Hedgehog and Wnt, as well as by deregulation of colorectal cancer related kinase pathways, like PI3K. Differential gene expression of BRAFV600E in colon as compared to those associated with RAS oncogenes is presented, as well as similarities and differences between oncogenic BRAF signatures in colon as compared to thyroid and melanoma are highlighted. Novel selected genes/pathways are validated in cell lines and clinical samples bearing BRAFV600E and may serve as markers/targets for personalised diagnosis/therapy/resistance of colorectal cancer.
Locally advanced colorectal tumors represent about 5-22% of all colorectal cancers at the time of presentation. Specifically in the case of right colon cancer, the percentage of adjacent structure involvement ranges between 11% and 28%. Organs that are most frequently invaded by right colonic tumors are the duodenum and the pancreatic head. We report the case of a 36-year old man with locally advanced right colonic cancer, invading the head of the pancreas and the superior mesenteric vein, who was successfully treated in our department with right hemicolectomy, pancreatoduodenectomy and short resection of the superior mesenteric vein with an end-to-end anastomosis, and remains alive and well, free of disease, nine years after the operation.
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