CASE PRESENTATION

2. CASE PRESENTATION CC: Jaundice HPI: 64-yr-old man • 4 wk h/o anorexia & 15 lb wt loss • 2 wk h/o • pruritus • dark urine • abdominal pain, midepigastric, dull, constant with radiation to the back • 2 days earlier a family members notes jaundice

3. CASE PRESENTATION PMH: DM, type 2 (dx’d 6 yrs ago) PSH: None Meds: glyburide ALL: NKDA SH: Married. No EtOH or tobacco FH: No malignancies

4. CASE PRESENTATION Physical Exam Vitals: 120/83 65 12 AF 176 lbs Gen: NAD. Heent: Icteric. OP nl. Neck: Supple. No LAD. Lungs: CTA. Heart: RRR w/o m/r/g. Abd: NABS. Tender MEG. Palpable non- tender gallbladder. Ext: No c/c/e.

5. CASE PRESENTATION Laboratory Data TBili 8.5 Alk phos 350 AST 78 ALT 90 Albumin 3.0 Hgb 10.5

7. Rajeev Jain, M.D. PancreaticobiliaryCancer

8. 2005 Estimated US Cancer Cases Men710,040 Women662,870 Prostate 33% Lung and bronchus 13% Colon and rectum 10% Urinary bladder 7% Melanoma of skin 5% Non-Hodgkin 4% lymphoma Kidney 3% Leukemia 3% Oral Cavity 3% Pancreas 2% All Other Sites 17% 32% Breast 12% Lung and bronchus 11% Colon and rectum 6% Uterine corpus 4% Non-Hodgkin lymphoma 4% Melanoma of skin 3% Ovary 3% Thyroid 2% Urinary bladder 2% Pancreas 21% All Other Sites *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2005.

9. Pancreas • Acinar cells 80% • Ductal cells 10-15% • Endocrine cells 1-2%

10. Pancreatic Cancer • Endocrine • 1 to 2% • Exocrine • > 95% • 85 to 90% ductal origin • Head 60-70% • Body 5-10% • Tail 10-15%

11. Pancreatic CancerWHO Classification - Exocrine • Malignant • Ductal adenocarcinoma • Osteoclast-like giant cell tumor • Serous cystadenocarcinoma • Mucinous cystadenocarcinoma • Intraductal papillary mucinous carcinoma • Acinar cell carcinoma • Pancreatoblastoma • Solid-pseudopapillary carcinoma • Miscellaneous carcinoma

12. Pancreatic CancerACS 2005 Estimates www.cancer.org

13. Pancreatic CancerRisk Factors • Tobacco (RR 1.5 – 3) • Family history (7-10%) • 1st degree relative: RR 3-5 • Familial syndromes • Hereditary pancreatitis (AD, cationic trypsinogen gene) • 40% by age 70, up to 75% if paternal • Peutz-Jeghers • Von Hippel-Lindau • Familial atypical multiple-mole melanoma (FAMMM) • Ataxia-telangiectasia • FAP, HNPCC • Chronic pancreatitis (RR up to 16) • Diabetes mellitus, type II (RR 2 if DM present > 5 yrs) • Others: Obesity, inactivity, diet Michaud DS. Gastrointest Endosc 2002;56:S195-200.

14. Pancreatic Carcinogenesis • Activation of oncogenes • Inactivation of tumor suppressor genes • Defects in DNA mismatch repair genes

15. Pancreatic CancerPresentation • Symptoms & signs • Jaundice, pruritus, acholic stool • Abdominal pain • Back pain • Weight loss, anorexia, nausea & vomiting • Curvoisier’s sign: palpable non-tender gallbladder • Acute pancreatitis • New onset diabetes • Pancreatic exocrine insufficiency

16. Pancreatic CancerDiagnostic Evaluation • Laboratory • Tumor markers • Radiology • Computed Tomography Scan • Magnetic Resonance Imaging (MRI/MRCP) • Positron Emission Tomography • Percutaneous Transhepatic Cholangiography (PTC) • Endoscopy • Endoscopic Retrograde Cholangiopancreatography (ERCP) • Endoscopic Ultrasound (EUS)

17. CA 19-9 Tumor-Associated Antigen • Synthesized by pancreatic and biliary ductal cells • Lewis A blood group • 5% of population is Lewis A-B- and cannot synthesize CA 19-9 • Upper limit of normal 37 U/ml • Sensitivity 81% • Specificity 90% • False elevation: cholangitis • CA 19-9 > 1000 predicts unresectability • Predicts recurrence Steinberg W. Am J Gastroenterol 1990;85:350-5.

18. Pancreatic CancerCT Scan Pancreas protocol • Thin cuts • PO/IV contrast • First (pancreas) phase • 40s after IV contrast • Max. enhancement of normal pancreas • Second (portal vein) phase • 70s after IV contrast • Liver metastases • Tumor involvement of portal & mesenteric veins

19. Pancreatic CancerERCP • Diagnostic • Pancreatic ductal abnormalities • Tissue (brushings) • Sens 18-60%, Spec 99% • Therapeutic • Biliary drainage • Plastic stent • Metal stent

20. Pancreatic CancerERCP

21. Endoscopic Ultrasound • Developed to overcome limitations of transabdominal ultrasound • intervening structures • limited resolution • Transducer placed at distal end of side-viewing endoscope

22. Endoscopic Ultrasound Radial Linear 100° 360°

23. Pancreatic Mass with Vascular Involvement

24. Pancreatic CancerEndoscopic Ultrasound • Tumor staging • more accurate than helical CT in small lesions and assessing local extent, lymph nodes, & vascular invasion • CT better for distant metastases • better than angiography • ? MRI, MRCP, PET scan • Diagnostic – Fine Needle Aspiration (FNA) • Sensitivity 85% • Specificity 99%

25. Percutaneous Transhepatic Cholangiography (PTC)

26. Pancreatic Cancer SUSPICION OF PANCREATIC CANCER Helical CT Scan Pancreatic head tumor < 2 cm Pancreatic head tumor > 2 cm Tumor of body or tail of the pancreas No tumor ERCP EUS Laparoscopy with cytology of washings if + if - Surgical exploration for resection

27. Pancreaticoduodenectomy

28. Pancreatic CancerPalliative Issues • Jaundice • ERCP, PTC, or surgery • Pain • Radiation therapy • Celiac axis neurolysis • Surgical, fluoroscopic- or EUS-guided • Duodenal obstruction • Surgery or metal stent

29. Endoscopic Stents • Plastic stents: polyethylene • Drainage prior to surgery • Up to 11.5 Fr • Life span < 3 months • $100 • Metal stents: self-expanding metal stents (SEMS) • Palliative • 10 mm or 30 Fr • Longer patency • Life span > 3 months • $1,000

30. ERCP Stent v Surgical Bypass Palliation of Biliary Obstruction in Pancreatic Cancer Flamm CR et al. Gastrointest Endosc 2002;56(6):S218-25.

31. Plastic v Metal Stent Palliation of Biliary Obstruction in Pancreatic Cancer Levy MJ et al. Clin Gastroenterol Hepatol. 2004 Apr;2(4):273-85.

32. Duodenal Obstruction

33. Duodenal Obstruction

34. Screening for Pancreatic Cancer No guidelines or recommendations Studies in progress – Univ. Washington & Johns Hopkins • Who • High-risk individuals • When • Age 40 yrs or 10 yrs younger than the youngest family member with PC • How • Serology: Genetic and protein markers • Radiology: CT, MRI/MRCP • Endoscopy: EUS, ERCP

35. Pancreatic CancerAJCC Staging Primary Tumor (T) T1 Limited to pancreas, < 2 cm T2 Limited to pancreas, > 2 cm T3 Extension into duodenum, CBD T4 Extension into vessels (not splenic), stomach, spleen, or colon Regional Lymph Nodes (N) N0 None N1 Regional nodal metastases Distant Metastases (M) M0 None M1 Distant metastases

36. Pancreatic CancerAJCC Staging

37. Biliary Tract Cancer • Gallbladder • Extrahepatic bile duct • Ampulla of Vater

38. Gallbladder Cancer • 2.5 cases per 100,000 • 5th most common GI cancer • 6,500 deaths/year • M:F 1:3 • Risk factors • Gallstones • Porcelain gallbladder • Chronic typhoidal carrier • Presentation • Pain, jaundice • 1-2% of resected gallbladders • 5 YR Survival: 5% • Highest incidences (7-20/100,000) • Native Americans (North & South) • Poland • Northern India

39. Cholangiocarcinoma • 1 case per 100,000 • Slight M>F • Risk factors • Primary sclerosing cholangitis (PSC) • Choledochal cysts • Clonorchis sinensis • Hepatolithiasis • CBD stones • Thorium dioxide (Thorotrast)

40. Cholangiocarcinoma MRCP of PSC • Presentation • Obstructive jaundice • Diagnosis • Tumor markers • CA 19-9 (85%) • CEA (35%) • CA 125 (30-50%) • ERCP/MRCP • CT scan • Treatment • Surgery • Palliation • Biliary drainage • 5 YR Survival: 5% ERCP

41. Bismuth Classification

42. Ampullary Cancer • 3 cases per 1 million • Risk factors • FAP • Peutz-Jeghers • Presentation • Jaundice • “Silver stool” • Diagnosis/Staging • EGD, CT, EUS, ERCP • Treatment: Surgery • 5 YR Survival: 25 – 40%

43. Outcome of Patients after Pancreaticoduodenectomy Sarmiento JM, et al. Surg Clin North Am 2001.