1. Pancreatic Cancer

2. Incidence and Epidemiology 25,000-30,000 diagnosed annually in the US or fifth leading cause of cancer-related death Prevalent in men and African Americans 80% of cases occur between the ages 60 and 80

3. Anatomy

4. Risk Factors Family History of Pancreatic Cancer Chronic or Hereditary Pancreatitis Smoking Exposure to occupational carcinogens Relation to DM is controversial

5. Pathology Ductal adenocarcinoma account for 80% to 90% of all pancreatic neoplasms 70% of ductal cancers arise in the pancreatic head or uncinate process At diagnosis - both nodal and distant metastases are frequently present

6. Pathology Areas of vascular and lymphatic invasion within and around the tumor are commonly seen perineural growth of the tumor is highly characteristic and causes upper abdominal and back pain

7. Different Variants of Adenocarcinoma Mucinous Noncystic Carcinoma (Colloid Carcinoma) Signet Ring Cell Carcinoma Adenosquamous Carcinoma Anaplastic Carcinoma Giant Cell Carcinoma Sarcomatoid Carcinoma

8. Molecular Biology K-Ras EGFR, HER2/3/4 p53 BRCA2 Less common : Retinoblastoma, APC … Late events in tumorogenesis Early events in tumorogenesis

9. Hereditary Pancreatic Cancer Syndromes HNPCC BRCA2 mutation carriers Peutz-Jeghers Syndrome AT Familial Atypical Multiple Mole Melanoma (FAMMM)

10. Ataxia Telangectasia ?

11. Peutz Jegher Syndrome jejunojejunal proximal intussusceptions

12. Symptoms and Signs insidious tumors that can be present for long periods and grow extensively before they produce symptoms. The symptoms, once they develop, are determined by the location of the tumor in the pancreas

13. Sings and Symptoms – Pancreatic Head Cancer Weight Loss (92%) Pain (72%) Jaundice (82%) Anorexia (64%) Dark urine (63%) Light Stool (625)

14. Sings and Symptoms – Pancreatic Body or Tail Cancer Weight Loss (100%) Pain (87%) Weakness (43%) Nausea (45%) Vomiting (37%) Anorexia (33%)

15. Physical Examination Dependent on location and size of the pancreatic tumor Metastatic subumbilical noudle (“Sister Mary Joseph node”) left supraclavicular lymphadenopathy (“Virchow's node”) pelvic peritoneal (“Blumer's shelf”) deposits Portal HTN, Ascits, Caput Medusae, GE Varices

16. Sister Mary Joseph’s Noudle

17. Courvoisier’s Sign Painless Jaundice Distended Gallbladder

18. Lab Tests Head Lesions Bilirubin ALP Tumor markers : CEA, CA19-9 Normal Serum levels on early disease Increased Serum levels on Cholangitis, Obstructive Jaundice

19. Imaging Studies For most patients, the initial imaging study is a transcutaneous US. Usually followed by helical contrast- enhanced CT hypodense mass with poorly demarcated edges. It may have a more hypodense center, indicating central necrosis or cystic change Sensitivity up to 95% for diameter >2 cm

20. Imaging Studies MRI - sensitivity and specificity of MRI appear to equal those of CT PET - diagnosing small pancreatic tumors that escaped CT or MRI detection ERCP - helpful in evaluating patients with obstructive jaundice without a detectable mass on CT or MRI

21. Double Duct Sign superimposable bile duct and pancreatic duct strictures (i.e., the double- duct sign) on ERCP is highly suggestive of a pancreatic head DD: Chronic pancreatitis, Autoimmune pancreatitis

22. Role of Biopsy required before chemoradiation therapy of unrsectable tumor or neoadjuvant treatment of resectable tumors Transcutaneous: CT/US Guided Transduodenal : EUS Drawbacks of Biopsy: May yield FN Results, doesn’t affect management Theoretical possibility of peritoneal spread

23. TNM Staging T0 – Tis/PAN-IN3 T1/2 – Below/Above 2 cm in diameter T3/4 – Local extension beyond pancreas T3 lesions are considered to be potentially resectable because they do not involve the celiac axis or superior mesenteric artery. T4 lesions are considered to be unresectable because they involve the critical peripancreatic arteries

24. TNM STaging Stage 0 Tis N0 M0 Stage 1A T1 N0 M0 Stage 1B T2 N0 M0 Stage 2A T3 N0 M0 Stage 2B T1/T2/T3 N1 M0 Stage 3 T4 Nx M0 4 Stage Tx Nx M1

25. Staging Stage I and II cancers are amenable to resection Poor prognostic signs aneuploidy large tumor size (T2) positive regional nodes (N1) incomplete resection at the pancreatic or retroperitoneal margin

26. Staging Stages III and IV cancers are considered to be unresectable Stage III due to vascular invasion Stage IV due to distant metastases Mean survival Stage III – 8-12 mo. Stage IV – 3-6 mo.

27. Imaging for Staging High-resolution helical CT, with phased imaging. Signs of unresectibility Circumferential encasement, invasion, or occlusion of the portal vein, SMV, or SMA extension beyond the pancreatic capsule and into the retroperitoneum involvement of neural or nodal structures extension of the tumor along the hepatoduodenal ligament

28. Role of Laparoscopy in Staging Patients believed to have stage I or II disease may have unrecognized small metastases to peritoneal surfaces (e.g., diaphragm, liver) and that those metastases can be laparoscopically detected, thus preventing a needless laparotomy

29. Resectional Surgery for Pancreatic Head and Uncinate Process Tumors Tumors of the head, neck, and uncinate process of the pancreas account for about 70% of pancreatic tumors Resected by pancreaticoduodenectomy Pylorus sparing – faster and easier, same morbidity and mortality but greater chance for delayed gastric emptying.

30. Pancreaticoduodenectomy (Whipple’s procedure) preliminary search for metastases or other reasons to abort resection The gallbladder is usually removed the common bile duct is divided above the duodenum The proximal GI tract is divided at the level of the gastric antrum (standard Whipple) or 1st part of the duodenum (pylorus-preserving) The proximal jejunum is divided, and the neck of the pancreas is transected uncinate process of the pancreas is resected from the retroperitoneum along the lateral surface of the superior mesenteric artery

31. Pancreaticoduodenectomy (Whipple’s procedure) pancreaticojejunostomy (as an end-to-end or end-to-side) end-to-side hepaticojejunostomy gastrojejunostomy (standard Whipple) or duodenojejunostomy (pylorus- preserving Whipple)

32. Comlications of Pacreatoduodenectomy When performed by experienced surgeons mortality rate is 2% to 4% Anastamotic Leaks Intra abdominal abcesses Delayed gastric emtying pancreatic malabsorption and steatorrhea

33. Results of Pancreaticoduodenectomy 10-15% 5-ys. Survival, usually don’t survive additional 5 ys. Tumor free margins – 26% 5-ys. survival Tumor positive margins – 8% 5-ys. survival Other prognostic factors: tumor diameter, diploid or aneuploid DNA content, and lymph node status

34. Resectional Surgery for Pancreatic Body and Tail Tumors Only 10% deemed resectable at diagnosis Resection involves a distal pancreatectomy +/- splenectomy Complications: Subphrenic Abcess (5-10%) Pancreatic duct leak (20%) Outcome – 8-14% 5-ys. survival

35. Palliative Nonsurgical Treatment of Pancreatic Cancer Jaundice – Drainage either percutanously endoscopically, placement of a metal or plastic stent Gastric Outlet obstruction – direct extension of the tumor into the duoudenum. Placement of a stent endoscopically into the duodenum. Pain – Invasion into peripancreatic nerve plexuses. Analgetics, Narcotics, Percutaneous CT/US guided Celiac Plexus Block

36. Palliative Surgical Management of Pancreatic Cancer Jaundice - cholecystojejunostomy or a choledochojejunostomy Gastric Outlet Obstruction - can be managed by creation of a side-to-side gastrojejunostomy pain - can be achieved, intraoperatively, by injecting alcohol into the celiac plexus, and some surgeons routinely perform operative celiac plexus block at the time of surgical palliation

37. Chemoradiation Therapy best results have been achieved using radiation therapy combined with either 5- fluorouracil or gemcitabine Patients undergoing resection may also benefit from adjuvant chemoradiation therapy