Pancreatic Cancer

Epidemiology and risk factors (to»*« 2004:363 1049)

• 4th leading cause of cancer death in U.S. men and women

• Acquired risk factors: smoking, obesity, chronic pancreatitis.diabetes

• Hereditary risk factors: genetic susceptibility may play a role in 5-10% of cases

Hereditary chronic pancreatitis: mutation in cationic trypsinogen gene Familial cancer syndromes and gene mutations with Í risk: Peutz-Jeghers (LKB1). familial atypical multiple mole melanoma syndrome (p16).and ataxia-telangiectasia (ATM): hereditary colorectal cancer and BRCA2 mutations may also ' risk Pathology

• 95% of malignant pancreatic neoplasms arise from exocrine (ductal or acinar) cells

• 60% arise in head. 15% in body. 5% in tail; in 20% tumor diffusely involves whole gland

Clinical manifestations

• Painless jaundice (w pancreatic head mass), pain (radiating to back), weight loss

• New-onset atypical diabetes mellitus: unexplained malabsorption: unexplained pancreatitis

• Migratory thrombophlebitis (Trousseau's sign)

• Exam: abdominal mass; nontender. palpable gallbladder (Courvoisier's sign, but more often seen with biliary tract cancers); hepatomegaly, ascites; left supraclavicular (Virchow's) node & palpable rectal shelf (both nonspecific signs of carcinomatosis)

• Laboratory tests may show t bilirubin. T Ad>. anemia Diagnostic and staging evaluation

• Pancreatic protocol CT scan (I w arterial & venous phase imaging)

• If no lesion seen — EUS. ERCR MRI MRCP may reveal mass or malignant ductal strictures

• Biopsy pancreatic lesion via EUS-guided FNA (preferred in potential surgical candidates) or

CT-guided (potential risk of seeding) or biopsy metastasis

• Tumor markers: T CA 19-9; may be useful to follow disease postoperatively

Clinical (Radiologic) Staging & Prognosis of Pancreatic Adenocarcinoma

Stage &

Resectable

No extrapancreatic disease 10-20 mo (favorable: tumor 3 Patent SMV & portal vein; celiac cm. @ marg.. well-differen.)

axis & SMA not involved 5-y survival 30% if node S vs. No bulky nodes 10% if node ®

Locally advanced

(unresectable) 40%

Extensive PV. SMV. celiac axis.

or SMA involvement 8-12 mo No distant mets

Metastatic

40%

Typically liver & peritoneum; 3 6 mo occasionally lung

Treatment

• Resectable: surgery • adjuvant (neoadjuvant or postoperative) therapy pancreaticoduodenectomy Whipple procedure resection of pancreatic head.

duodenum, CBD and gallbladder • partial gastrectomy adjuvant therapy: f survival w chemoradiation (eg. postoperative 5-FU radiation • gemcitabine) (NEJM 2004:350.2713:JC0 2005:23 4S32./AMA 2007:297.267)

• Locally advanced: 5-FU chemorad T survival over chemo or XRT alone; ? followed by gemcitabine (/CO 2005:23 4538)

• Metastatic: gemcitabine improves survival over 5-FU (JCO 1997:15:2403). adding erlotinib to gemcitabine provides slight additional benefit {JCO 2005:2316S.1)

• Palliative and supportive care obstructive jaundice or gastric oudet obstruction: endoscopic stenting or surgical bypass pain: opiates, celiac plexus neurolysis, radiation therapy weight loss: pancreatic enzyme replacement for suspected fat malabsorption nutrition consult

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