Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

<p>Abstract</p> <p>Background</p> <p>The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data.</p> <p>Methods</p> <p>Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable.</p> <p>Results</p> <p>On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour.</p> <p>Conclusion</p> <p>The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted.</p

Poorer outcome in stromal HIF-2α- and CA9-positive colorectal adenocarcinomas is associated with wild-type TP53 but not with BNIP3 promoter hypermethylation or apoptosis

Stromal expression of hypoxia inducible factor 2α (HIF-2α) and carbonic anhydrase 9 (CA9) are associated with a poorer prognosis in colorectal cancer (CRC). Tumour cell death, regulated by a hypoxic stromal microenvironment, could be of importance in this respect. Therefore, we correlated apoptosis, TP53 mutational status and BNIP3 promoter hypermethylation of CRC cells with HIF-2α- and CA9-related poor outcome. In a series of 195 CRCs, TP53 mutations in exons 5–8 were analysed by direct sequencing, and promoter hypermethylation of BNIP3 was determined by methylation-specific PCR. Expressions of HIF-2α, CA9, p53, BNIP3 and M30 were analysed immunohistochemically. Poorer survival of HIF-2α and CA9 stromal-positive CRCs was associated with wild-type TP53 (P=0.001 and P=0.0391), but not with BNIP3 methylation. Furthermore, apoptotic levels were independent of the TP53 status, but lower in unmethylated BNIP3 CRCs (P=0.004). It appears that wild-type TP53 in CRC cells favours the progression of tumours expressing markers for hypoxia in their stroma, rather than in the epithelial compartment. Preserved BNIP3 function in CRC cells lowers apoptosis, and may thus be involved in alternative cell death pathways, such as autophagic cell death. However, BNIP3 silencing in tumour cells does not impact on hypoxia-driven poorer prognosis

Intramyocardial navigation and mapping for stem cell delivery

Method for delivery remains a central component of stem cell-based cardiovascular research. Comparative studies have demonstrated the advantages of administering cell therapy directly into the myocardium, as distinct from infusing cells into the systemic or coronary vasculature. Intramyocardial delivery can be achieved either transepicardially or transendocardially. The latter involves percutaneous, femoral arterial access and the retrograde passage of specially designed injection catheters into the left ventricle, making it less invasive and more relevant to wider clinical practice. Imaging-based navigation plays an important role in guiding catheter manipulation and directing endomyocardial injections. The most established strategy for three-dimensional, intracardiac navigation is currently endoventricular, electromechanical mapping, which offers superior spatial orientation compared to simple x-ray fluoroscopy. Its provision of point-by-point, electrophysiologic and motion data also allows characterization of regional myocardial viability, perfusion, and function, especially in the setting of ischemic heart disease. Integrating the mapping catheter with an injection port enables this diagnostic information to facilitate the targeting of intramyocardial stem cell delivery. This review discusses the diagnostic accuracy and expanding therapeutic application of electromechanical navigation in cell-based research and describes exciting developments which will improve the technology’s sensing capabilities, image registration, and delivery precision in the near future.Peter J. Psaltis, Andrew C. W. Zannettino, Stan Gronthos and Stephen G. Worthle