This recent symposium featured speakers from several clinical and research disciplines. Among the findings:
peptic ulcer disease is a significant predisposing risk factor (odds ratio = 3.9) for
pancreatic cancer; as many as 50% of all intraductal papillary
mucinous neoplasms are associated with invasive
adenocarcinomas; alteration of gene expression via methylation of a gene promotor region constitutes a potentially reversible method of tumor suppressor gene inactivation; > 400 transcriptional alterations of gene expression have been identified for
pancreatic cancer; some common molecular markers such as p53 and HER-2/neu may be related to morphologic alterations of in situ
neoplasia and to transcriptional alterations of gene expression rather than mutational events;
epidermal growth factor (
EGF),
transforming growth factor beta (
TGF-beta), and related molecules may modulate gene transcription via "autocrine" or "paracrine" mechanisms; several
cytokines,
amylin (
islet amyloid polypeptide), and other
cachexia factors are responsible for paraneoplastic peripheral
insulin resistance, ineffective utilization of
glucose, and profound
cachexia. In the clinical diagnostic arena: the World Health Organization established a standard nomenclature for intraductal papillary
mucinous neoplasms, mucinous cystic
tumors, intraductal mucinous
hyperplasias, and solid pseudopapillary
tumors; focal glandular differentiation may be commonly identified within pancreatic endocrine
neoplasms (
islet cell tumors) while not necessarily implying an unfavorable prognosis typical of ductal
adenocarcinomas; positron emission tomography scanning may be used for evaluation of early
tumor response to novel chemotherapeutic regimens; helical computed tomography (CT) is the state of the art in preoperative imaging for
pancreatic cancer; neoadjuvant
5-fluorouracil (5-FU)-based chemoradiation in 39 "resectable" patients provided a median survival of 19 months, actuarial 4-year survival of 19%, and improved local
tumor control;
gemcitabine has shown promise in alleviating
tumor-related symptoms with a significantly better "clinical benefit response" than single agent
5-FU (23.8 vs. 4.8%, p = 0.0022) based on change in
pain intensity, daily
analgesic consumption, performance status, and weight; a significant survival advantage was demonstrated in patients treated with conventional
therapies whose
tumors expressed p21WAF-1, an important inhibitor of cell cycle progression and downstream molecule of p53 and
TGF-beta; a p21-adenovirus (rAD-p21) gene therapy resulted in significant growth inhibition of
pancreatic cancer cell lines in tissue culture, and development of a successful SCID mouse-human pancreatic
adenocarcinoma xenograft model provided an animal model for preclinical trials of rAD-p21.