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Periampullary and Pancreatic Tumors Rod L. Flynn, M.D. Surgical Oncologist Mary Washington Hospital Fredericksburg, VA Periampullary Tumors • Defined as those that arise within 2 cm of the major papilla in the duodenum • Classified on the basis of their tissue of origin • Often difficult or impossible to differentiate from pancreatic head adenocarcinoma before performing a resection Periampullary Tumors • Encompass tumors of the: – ampulla of Vater – distal common bile duct (intrapancreatic distal common bile duct), – duodenal tumors (usually the second part) involving the papilla – tumors of the pancreatic head involving in close proximity to the ampulla • Pancreatic head adenocarcinoma accounts for most (approximately 80%) tumors in the periampullary region Periampullary Anatomy Periampullary Tumors • In general, the more distal the tumor is along the pancreatobiliary tree, the better the prognosis Non-pancreatic periampullary cancers tend to have a better prognosis than does pancreatic adenocarcinoma because they are often more resectable – i.e. 90% of ampullary cancers vs 15-20% of pancreatic head cancers – Hilar Cholangiocarcinomas (Klatskin Tumors) 1520% 5-year survival – Distal bile duct cancers 20-30% 5-year survival – Ampullary carcinomas 40-60% 5-year survival – Duodenal carcinomas 60% -70% 5-year survival – Pancreatic head adenocarcinoma 15-20% 5-year survival Pancreatic Head Adenocarcinoma Pancreatic Head Adenocarcinoma • • • • • Demographics Treatment poses diagnostic and therapeutic challenge Second most common GI malignancy in U.S. (colorectal is the most common) In 2006, 33,730 new cases were diagnosed in U.S. Accounted for about 32,300 deaths Fourth leading cause of cancer-related deaths (following lung, colon, breast/prostate) Pancreatic Head Adenocarcinoma Demographics • Responsible for 5% of all cancer-related deaths • Surgical resection provides the only chance for cure • 80% of patients present with advanced disease not amenable to resection Pancreatic Cancer Risk Factors • Exact cause is unknown • Environmental exposure – Smoking (main risk factor) • Risk increases with dose and exposure • Other tobacco carcinogens likely involved – Organic and nickel-containing solvents – Chlorinated compounds • High BMI – Diet -- low in vegetables and fruits, high in animal fats and meat products Risk higher in obese individuals – Risk higher in obese individuals – Decreases with weight loss and exercise Pancreatic Cancer Risk Factors (cont’d) • Comorbid conditions – Chronic pancreatitis – Diabetes mellitus, type II • Risk doubles with > 5-year history of diabetes mellitus, type II • Genetic factors – Account for 15% to 20% of cases • 1 family member affected: 18 times risk • 3 family members affected: 57 • Familial syndromes times risk Familial Syndromes Syndrome Hereditary pancreatitis Hereditary nonpolyposis colorectal cancer (Lynch syndrome II) Hereditary breast and ovarian cancer Familial atypical multiple mole melanoma (FAMM) Peutz-Jeghers syndrome Ataxia-telangiectasia (ATM) syndrome Molecular/Genetic Defect 7q35 hMSH2, hMLH1 BRCA2 p16 (9p21) STK11/LKB1 (19p13) 11q22-23 Pancreatic Head Adenocarcinoma Clinical Presentation • Most patients with periampullary cancer present with at least one of the following symptoms: – Weight loss – Jaundice (75% of patients) – Vague epigastric/ back pain (retroperitoneal plexus invasion) – Fatigue – Intestinal malabsorption – New onset diabetes (15%) • Symptom complex is vague, which often delays presentation and diagnosis • As a result about 80% of all patients present with unresectable disease Pancreatic Head Adenocarcinoma Clinical Signs • The presence of clinical signs usually means advanced disease • Courvoisier’s sign – Painless jaundice • Palpable abdominal mass – Large tumor or omental cake • Ascites • Umbillical nodule (Sister Mary Joseph’s node) • Blumer’s shelf (rectovaginal/vescicle mass) • Virchow’s node (left supraclavicular) Pancreatic Cancer Clinical Presentation Component Local Constitutional Biliary obstruction Pancreatic insufficiency Symptom Epigastric/back pain Fatigue Anorexia Weight loss Jaundice Pruritus Pale stools Malabsorption of fat-soluble vitamins Malabsorption AJCC STAGING Pancreatic Cancer TUMOR • Tis: in situ carcinoma • T1: < 2 cm • T2: > 2 cm • T3: beyond pancreas • T4: involves celiac axis or superior mesenteric artery (unresectable) NODE • N0: no lymph node metastases • N1: regional lymph node metastases METASTASES • M0: no distant metastases • M1: distant metastases present Stage 0 Tis, N0, M0 Stage IA T1, N0, M0 Stage IB T2, N0, M0 Stage IIA T3, N0, M0 Stage IIB T1-3, N1, M0 Stage III T4, any N, M0 Stage IV Any T, any N, M1 Pancreatic Cancer Diagnosis • The goals of evaluating patients with periampullary cancers is to obtain diagnosis and clinical stage • Based on these determinations the patient can be triaged into a treatment category • (operative or non-operative) • At time of initial diagnosis, approx 50% of patients will have metastatic disease • 30% will have locally-advanced disease not amenable to surgical resection • The superior mesenteric vein is involved with the large pancreatic head tumor Pancreatic Cancer Diagnostic Tests • Blood tests including CBC, LFTs, amylase/lipase, CEA, CA 19-9 • Abdominal ultrasound – A common initial test to evaluate jaundice • Abdominal CT scan – Gives better anatomical information on the source of the biliary obstruction – Can give information about extrapancreatic sites of spread (liver, peritoneal/omental surfaces, ascites, extensive nodal involvement, adjacent organ involvement) – Can assess involvent of major blood vessels (SMA/portal vein) • Angiography • ? PET scan Pancreatic Cancer Diagnostic Tests • ERCP – Brush cytology – Stenting if necessary – Look for dilated pancreatic duct – Look for filling defect within bile duct Pancreatic Cancer Diagnostic Tests • Endoscopic ultrasound – Can detect very small tumors (<2cm) – Can assist in staging by assessing mesenteric vascular involvement – FNA biopsies are relatively easy to do – Operator dependant Laparoscopy for staging Looking for 1. Local involvement of adjacent organs 2. Loco-regional extension (lymph nodes, soft tissue) 3. Small liver metastases 4. Peritoneal nodules Peritoneal Nodule Treatment Available • Chemotherapy • Radiation therapy • Chemoradiation followed by resection • Resection • Resection + Adjuvant Therapy • Palliation – Stents – Bypass – Feeding tubes Treatment Available • Only 10-20% of patients are eligible for surgery • Most have advanced disease at time of diagnosis • Most common chemo 5-FU & Gemcitabine Whipple Procedure Pancreaticoduodenectomy • The Whipple operation was first described in the 1930’s by Allan Whipple • In the 1960’s and 1970’s the mortality rate for the Whipple operation was very high (Up to 25% of patients died from the surgery) • This experience of the 1970’s is still remembered by some physicians who are reluctant to recommend the Whipple operation • Today the Whipple operation has become an extremely safe operation in the USA - At tertiary care centers where large numbers of these procedures are performed by selected surgeons, the mortality rate is less than 4%. Most common Diagnosis of patients undergoing Whipple • Peripancreatic Cancer (jaundice) – Pancreatic head – Ampulla – Bile duct • • • • • Duodenal wall Pancreatitis Cystic neoplasm Carcinoid Islet cell tumors Surgery 1. Incisions 2. Omentum 3. Resectability (Portal Vein/SMA) 4. Gall Bladder and Porta Hepatis 5. Gastrectomy 6. Pancreas Transection 7. Reconstruction Surgery 1. Incisions 2. Omentum 3. Resectability (Portal Vein/SMA) 4. Gall Bladder and Porta Hepatis 5. Gastrectomy 6. Pancreas Transection 7. Reconstruction Surgery (cont.) 1. Pylorus Preserving 2. Extended Nodal Dissection 3. Gastric Inversion Surgery (cont.) • Exposure of SMV Surgery (cont.) • Portal Triad – Hepatic artery – Portal vein – Common bile duct Surgery (cont.) • Division of pancreas Surgery (cont.) • Resected specimen Surgery (cont.) • Plumbing restored Outcomes Possible complications 44% in modern series out of Johns Hopkins; <5% 30-day mortality; 17day LOS v. 28 for complicated 1. Pancreatic fistula (Leak-8%) 2. Gastro paresis 3. Nutritional deficiencies 1. Malabsorption 2. Early satiety 3. Weight loss 4. Diabetes Outcomes (Johns Hopkins study, con’t) • N= 201 patients • The mean age of the patients was 63 years, with a slight male predominance (108 men and 93 women). • There were no differences in survival based on age, gender, or race. • The actuarial one, three and five-year survival rates for all 201 patients were 57%, 26%, and 21% respectively, with a median survival of 15.5 months. • 11 five-year survivors, • 7 six-year survivors • one fifteen-year survivor. Summary • Periampullary cancers include bile duct, ampulla of vater, duodenal, pancreatic head • Prognoses depend on relative location • Pancreatic head adenocarcinoma carries worst prognosis • Surgery is the only chance of cure, although a majority of patients are unresectable at the time of diagnosis • Better preoperative evaluation can reduce the number of unnecessary operations • Preoperative diagnosis is often very difficult if not impossible to make despite a myriad of diagnostic modalities at our disposal • In this group of patients we surgeons sometime have to tell the patient after a lengthy Whipple operation: “…I have good news, you don’t have cancer…” Bye-bye