Current concepts in pancreatic cancer: symposium summary

Area of Science:

• Oncology
• Molecular Biology
• Gastroenterology

Background:

• Pancreatic cancer presents complex challenges, with peptic ulcer disease identified as a significant risk factor (OR=3.9).
• Intraductal papillary mucinous neoplasms (IPMNs) show a high association (up to 50%) with invasive adenocarcinomas.
• Gene expression alterations, particularly promoter methylation leading to tumor suppressor gene inactivation, are key molecular events.

Framework:

• Over 400 transcriptional alterations in gene expression are identified in pancreatic cancer.
• Molecular markers like p53 and HER-2/neu may correlate with morphological changes and transcriptional alterations rather than mutations.
• Growth factors (EGF, TGF-beta) and cytokines influence gene transcription via autocrine/paracrine signaling.

Implementation:

• Standardized nomenclature for pancreatic cystic neoplasms (IPMNs, mucinous cystic tumors) has been established by the WHO.
• Helical CT is the gold standard for preoperative imaging, while PET scanning aids in evaluating treatment response.
• Neoadjuvant 5-FU-based chemoradiation and gemcitabine show efficacy in managing resectable pancreatic cancer and improving clinical benefit.

Implications:

• Focal glandular differentiation in endocrine neoplasms does not necessarily portend a poor prognosis.
• Expression of p21WAF-1 correlates with improved survival in patients receiving conventional therapy.
• Gene therapy with p21-adenovirus (rAD-p21) demonstrates significant inhibition of pancreatic cancer cell lines in vitro and in vivo models.