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Pancreatic Cancer 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 Anatomy Risk Factors • • • • • Family History of Pancreatic Cancer Chronic or Hereditary Pancreatitis Smoking Exposure to occupational carcinogens Relation to DM is controversial 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 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 Different Variants of Adenocarcinoma • Mucinous Noncystic Carcinoma (Colloid Carcinoma) • Signet Ring Cell Carcinoma • Adenosquamous Carcinoma • Anaplastic Carcinoma • Giant Cell Carcinoma • Sarcomatoid Carcinoma Molecular Biology • • • • • • K-Ras Early events in tumorogenesis EGFR, HER2/3/4 p53 Late events in tumorogenesis BRCA2 Less common : Retinoblastoma, APC … Hereditary Pancreatic Cancer Syndromes • • • • • HNPCC BRCA2 mutation carriers Peutz-Jeghers Syndrome AT Familial Atypical Multiple Mole Melanoma (FAMMM) Ataxia Telangectasia ? Peutz Jegher Syndrome jejunojejunal proximal intussusceptions 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 Sings and Symptoms – Pancreatic Head Cancer • • • • • • Weight Loss (92%) Pain (72%) Jaundice (82%) Anorexia (64%) Dark urine (63%) Light Stool (625) Sings and Symptoms – Pancreatic Body or Tail Cancer • • • • • • Weight Loss (100%) Pain (87%) Weakness (43%) Nausea (45%) Vomiting (37%) Anorexia (33%) 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 Sister Mary Joseph’s Noudle Courvoisier’s Sign • Painless Jaundice • Distended Gallbladder Lab Tests • • • • Head Lesions Bilirubin ALP Tumor markers : CEA, CA19-9 • Normal Serum levels on early disease • Increased Serum levels on Cholangitis, Obstructive Jaundice Imaging Studies • For most patients, the initial imaging study is a transcutaneous US. • Usually followed by helical contrastenhanced 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 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 Double Duct Sign • superimposable bile duct and pancreatic duct strictures (i.e., the doubleduct sign) on ERCP is highly suggestive of a pancreatic head • DD: Chronic pancreatitis, Autoimmune pancreatitis 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 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 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 4Stage Tx Nx M1 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 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. 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 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 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. 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 Pancreaticoduodenectomy (Whipple’s procedure) • pancreaticojejunostomy (as an end-to-end or end-to-side) • end-to-side hepaticojejunostomy • gastrojejunostomy (standard Whipple) or duodenojejunostomy (pyloruspreserving Whipple) 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 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 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 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 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 Chemoradiation Therapy • best results have been achieved using radiation therapy combined with either 5fluorouracil or gemcitabine • Patients undergoing resection may also benefit from adjuvant chemoradiation therapy