CURRENT CONCEPTS IN PANCREATIC-CANCER - SYMPOSIUM SUMMARY

This recent symposium featured speakers from several clinical and rese arch disciplines. Among the findings: peptic ulcer disease is a signif icant predisposing risk factor (odds ratio = 3.9) for pancreatic cance r; as many as 50% of all intraductal papillary mucinous neoplasms are associated with invasive adenocarcinomas; alteration of gene expressio n via methylation of a gene promotor region constitutes a potentially reversible method of tumor suppressor gene inactivation; >400 transcri ptional alterations of gene expression have been identified for pancre atic cancer; some common molecular markers such as p53 and HER-2/neu m ay be related to morphologic alterations of in situ neoplasia and to t ranscriptional alterations of gene expression rather than mutational e vents; 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 utiliza tion of glucose, and profound cachexia. In the clinical diagnostic are na: the World Health Organization established a standard nomenclature for intraductal papillary mucinous neoplasms, mucinous cystic tumors, intraductal mucinous hyperplasias, and solid pseudopapillary tumors; f ocal glandular differentiation may be commonly identified within pancr eatic endocrine neoplasms (islet cell tumors) while not necessarily im plying an unfavorable prognosis typical of ductal adenocarcinomas; pos itron emission tomography scanning may be used for evaluation of early tumor response to novel chemotherapeutic regimens, helical computed t omography (CT) is the state of the art in preoperative imaging for pan creatic 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 wi th a significantly better ''clinical benefit response'' than single ag ent 5-FU (23.8 vs. 4.8%, p = 0.0022) based on change in pain intensity , daily analgesic consumption, performance status, and weight; a signi ficant survival advantage was demonstrated in patients treated with co nventional therapies whose tumors expressed p21WAF-1, an important inh ibitor of cell cycle progression and downstream molecule of p53 and TG F-beta; a p21-adenovirus (rAD-p21) gene therapy resulted in significan t growth inhibition of pancreatic cancer cell lines in tissue culture, and development of a successful SCID mouse-human pancreatic adenocarc inoma xenograft model provided an animal model for preclinical trials of rAD-p21.