Molecular pathogenesis of pancreatic ductal adenocarcinoma and clinical implications.

University of Liverpool, Department of Surgery, 5th Floor UCD Building, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, UK.
Surgical Oncology (Impact Factor: 2.37). 07/2001; 10(1-2):1-23. DOI: 10.1016/S0960-7404(01)00016-0
Source: PubMed

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer death worldwide. PDAC is also one of the best-studied cancers with regard to molecular pathogenesis. The chief risk factors associated with PDAC are smoking and pancreatitis, in addition genetic predisposition seems to play a major role. This genetic predisposition may in some cases be indirect, for example via the elevated risk of pancreatitis seen in patients with hereditary pancreatitis (HP). The elucidation of the molecular causes of PDAC has enabled the provision of secondary screening for PDAC in conditions such as HP. This review is concerned with the molecular pathogenesis of PDAC and the application of this basic scientific understanding into state-of-the-art clinical practice.

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: High-resolution, multiphase, computed tomography (CT) is a standard preoperative test prior to pancreatectomy, yet the clinical significance of routinely reported findings remains unknown. METHODS: We identified patients who underwent a pancreaticoduodenectomy for a periampullary adenocarcinoma (PA) over the previous 5 years and had a pancreas protocol CT at our institution. Clinicopathologic implications of reported CT findings were evaluated. RESULTS: There were 155 pancreatic ductal adenocarcinomas (PDA) and 47 non-pancreatic PAs. No mass was visualized on CT in 6 % of PDAs and 23 % of non-pancreatic PA. A size discrepancy of ≥1 cm between radiographic and pathologic tumor diameters was observed in 40 % of PAs, with CT underestimating the size in most instances (75 %). Radiographically enlarged lymph nodes were not associated with true lymph node metastases in PDAs (70 % lymph node positive cases were enlarged on CT vs 74 % lymph node negative, p = 0.5), but were associated with a preoperatively placed biliary endoprosthesis (63 % with endoprosthesis were enlarged vs 37 % no endoprosthesis, p = 0.013). Major visceral vessel involvement on CT was not associated with a vascular resection (3 % with CT vessel involvement vs 2 % without, p = 0.8) or a positive uncinate resection margin (24 vs 20 %, respectively, p = 0.6). DISCUSSION: While dedicated pancreas protocol CT provides unprecedented detail, the test may lead to overinterpretation of the extent of disease in some instances. A radiographic suggestion of enlarged lymph nodes and vascular involvement does not necessarily preclude exploration with curative intent. CTs with local disease should be reported in an objective template and carefully reviewed by a multidisciplinary group of surgeons, radiologists, and oncologists to avoid missing an opportunity for neoadjuvant therapy or cure by resection.
    Journal of Gastrointestinal Surgery 04/2013; · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic Ductal Adenocarcinoma (PDAC) is a malignant neoplasm and is the fourth leading cause of cancer-related deaths in US with a 5-year survival rate less than 5%. Surgery is the only potentially curative treatment even though the result is a palliation in the majority of cases and the majority of lesions are lately diagnosed. Progression from normal pancreatic epithelium to metastatic disease is now a well-characterized sequence of events. Research has shown that pancreatic cancer is fundamentally a genetic disease with several biological pathway implied in apoptosis, cell proliferation and self-sufficiency in growth signaling, but how those findings could be applied in daily clinical practice remain unknown. Several studies tried to characterize diagnostic and prognostic biomarkers in PDAC to make it possible an earlier diagnosis, guarantee a more effective treatment and reach a better prognosis even though the results remain contrasting. The main limit of the published researches is the small number of patients studied, but even the heterogeneity of the used methods of analysis. Examining critically the research of the last years future trials may be addressed toward a translational models integrating "the bench and the bed" with the clinical experience and drive the basic research toward the clinical applications.
    Surgical Oncology 09/2012; 21(4):e171-82. · 2.37 Impact Factor
  • Onkologe. 01/2010; 16(6):453-463.