ABSTRACT: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, significant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation.
A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology.
Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local infiltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor.
Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.
Hepatobiliary & pancreatic diseases international: HBPD INT 09/2008; 7(4):345-56. · 1.08 Impact Factor
ABSTRACT: The aim of our study was to evaluate the clinical significance of prolonged organ failure during the first week of severe acute pancreatitis and the potential correlation with final outcome.
Of 234 patients with acute pancreatitis admitted to our department between January 2002 and December 2006, 64 patients with predicted severe acute pancreatitis were studied according to the presence and also the duration of organ failure early in the course of the disease.
Transient (<48 h duration) or persistent (>48 h duration) early organ failure (EOF) was present in 33 of 64 patients (51.5%). All 9 deaths (9/55 patients; 16.5% mortality) were recorded among patients who developed pancreatic necrosis, and the combination ofEOF and necrosis was present in most (8/9) patients with fatal outcome (P = 0.009). Persistent EOF was significantly associated with development of infected necrosis (P = 0.037) and worse outcome (P=0.028) as well. Multivariate analysis with backward elimination identified the duration of EOF as an independent factor affecting outcome.
Persistent organ failure early in the course of acute pancreatitis is a major determinant of outcome. In combination with pancreatic necrosis, survival rate is strongly compromised.
Pancreas 04/2008; 36(3):249-54. · 2.39 Impact Factor
Gastrointestinal Endoscopy 05/2006; 63(4):705-6, discussion 706. · 4.88 Impact Factor