SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

MYH polyposis syndrome: clinical findings, genetics issues and management.

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.

Brain metastases as the first sign of colon cancer.

Cerebral metastases from colorectal cancer occur in 8% of cases. Diagnosis is usually made when primary disease and widespread metastases are already known. However, the detection of brain metastases as the first sign of colorectal carcinoma without any liver and/or lung involvement is extremely rare. Central nervous system metastases are more commonly seen in rectal cancer and often occur concurrently with lung metastasis. We report a case of a patient with brain metastases as the first clinical manifestation of an adenocarcinoma of caecum without any other organ involvement.

Contamination of the environment by the current disposal methods of mercury-containing lamps in the state of Minas Gerais, Brazil.

This survey describes the degree of environmental contamination resulting from the current disposal methods of mercury-containing lamps. The territory studied for this purpose is the federal state of Minas Gerais, one of the most populated areas in the Brazilian federation of states. The results of this survey derive in part from answers received to a questionnaire mailed out to industrial firms, commercial business enterprises, hospitals and departments of public work. The sampling technique used was a nonprobabilistic (purposive sampling). Three types of disposal were found to prevail: (1) as an addition to corporate waste disposal (garbage), (2) recycling and (3) disposal by other methods. Overall, our study shows that the majority of mercury lamps are being disposed in the metropolitan area of Belo Horizonte, primarily by the public sector, followed by industrial, commercial and hospital sectors. Although recycling constitutes a relatively high fraction of the disposal methods, we find Federal regulations in Brazil regarding the disposal of hazardous, mercury-containing lamps to be far behind the state of technological achievement. This gap has permitted the adoption of disposal measures that are obsolete, incorrect, and a primary cause for the extensive contamination of the ecosystems with harmful effects to human health.