Massimo Agresti

Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV).Continuous oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental factors or cellular mitochondrial dysfunction, has recently been associated with hepatocarcinogenesis. On the other hand, a distinctive pathological hallmark of HCC is a dramatic down-regulation of oxido-reductive enzymes that constitute the most important free radical scavenger systems represented by catalase, superoxide dismutase and glutathione peroxidase.The multikinase inhibitor sorafenib represents the most promising target agent that has undergone extensive investigation up to phase III clinical trials in patients with advanced HCC. The combination with other target-based agents could potentiate the clinical benefits obtained by sorafenib alone. In fact, a phase II multicenter study has demonstrated that the combination between sorafenib and octreotide LAR (So.LAR protocol) was active and well tolerated in advanced HCC patients.The detection of molecular factors predictive of response to anti-cancer agents such as sorafenib and the identification of mechanisms of resistance to anti-cancer agents may probably represent the direction to improve the treatment of HCC.

BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy.

Poor data have been previously reported about the mutation rates in K-RAS, BRAF, and PIK3CA genes among patients with hepatocellular carcinoma (HCC). Here we further elucidated the role of these genes in pathogenesis of primary hepatic malignancies. Archival tumour tissue from 65 HCC patients originating from South Italy were screened for mutations in these candidate genes by direct sequencing. Overall, oncogenic mutations were detected in 15 (23%) patients for BRAF gene, 18 (28%) for PIK3CA gene, and 1 (2%) for K-RAS gene. Using statistical analysis, BRAF mutations were significantly correlated with the presence of either multiple HCC nodules (P=0.021) or higher proliferation rates (P=0.034). Although further extensive screenings are awaited in HCC patients among different populations, our findings clearly indicated that mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population.

Additional prognostic factors in right colon cancer staging

Based on the theory—which is now acknowledged—of a clinical difference between proximal and distal colon cancer and on the results of recent genetic and microbiological studies, a minority of authors have assumed that also in the sphere of right-sided colon cancer, tumors at three different locations, namely, the cecum and ascending and transverse colon, can be considered to be biologically different. These studies have provided the basis for a retrospective study carried out on 50 patients admitted to our department from 1996 to 2008 for tumor pathology of the right colon. The tumor was considered to be a unified biological entity and assessed in relation to the three above-mentioned locations. The results verify that the aggressive of the tumor increases from the cecum to the transverse, with a higher percentage of cecal tumors being in I stage, more tumors in the ascending colon being in II stage, and more transverse tumors, with the largest percentage of N+ and M+, in stages III and IV. This difference in biological behavior for the three tumor locations has been also found in terms of sensitiveness, both pre- and post-operation, of tumor markers CEA, TPA, and CA19-9. Clinical data revealed a binary relationship between the transverse, cecum, and ascending tumors, which ultimately affects patient mortality, which increases in a directly proportional way from the cecum to the transverse—in the case of a tumor at one of these locations.

Treating rhinophyma: A case report illustrating decortication/vaporization with an 808-nm diode laser

Abstract Rhinophyma is a skin disease that is not only disfiguring but can also have a negative impact on respiratory function by causing nasal obstruction. There is a wide range of techniques used in the surgical management of rhinophyma, including laser treatment, all of which involve tissue ablation. With regard to the laser therapy, there is no consensus as to which laser is most effective. The authors present a case report to illustrate their method of treating rhinophyma with an 808-nm diode laser, which included the use of exogenous pigment to define the target area and the application of human fibrin glue to obtain good hemostasis and wound healing and prevent infection. Zusammenfassung Das Rhinophym ist eine Hauterkrankung, die nicht nur entstellenden Charakter hat sondern durch die Verengung der Nase auch die Atmung erheblich beeinträchtigen kann. Zu den verschiedenen ablativen chirurgischen Behandlungsmethoden gehört auch die Lasertherapie, wobei es derzeit keinen Konsens darüber gibt, welcher Laser am effektivsten ist. In der vorliegenden Fallstudie wird die Anwendung eines 808 nm-Diodenlasers dokumentiert. Die Operationsgrenzen wurden dabei vor der Laserbehandlung mit “Carbon black“ markiert. Zur Blutungsstillung, Verbesserung der Wundheilung und Vermeidung von Infektionen wurde im Anschluss an die Laserbehandlung Fibrinkleber verabreicht.