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Pancreatic Neoplasm

Pancreatic Neoplasm. 5/24/06 Brent White Richard Barth. Facts About Brent & Georgia. Born in Durham, NC 4/8/74 My family moved to Columbus, Georgia when I was 6 weeks old Georgia is known as “The Goober State” Goober=Peanut

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Pancreatic Neoplasm

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  1. Pancreatic Neoplasm 5/24/06 Brent White Richard Barth

  2. Facts About Brent & Georgia • Born in Durham, NC 4/8/74 • My family moved to Columbus, Georgia when I was 6 weeks old • Georgia is known as “The Goober State” • Goober=Peanut • Georgia produces quite a few peanuts, growing 42% of peanuts grown in the US

  3. Overview • During 2006, estimated 32,300 people will die in the US of pancreatic cancer • Fourth and fifth most common cause of cancer deaths in men and women in the US respectively • Peak incidence in age 60-80 • African Americans with slightly higher incidence compared with Caucasians

  4. Types of Pancreatic Neoplasms • Broadly speaking, there are three basic types: • Ductal adenocarcinoma >90% of pancreatic cancers with a 4% 5-year survival (worst of any cancer) • Neuroendocrine tumors aka islet-cell tumors, rare • Cystic neoplasms account for <1% of pancreatic cancers

  5. Clinical Scenario #1 – Adenocarcinoma of the Pancreas • 70yo female with PMH of HTN who developed jaundice without significant abdominal pain, no fever • Bilirubin 12 • No significant complaints of abdominal pain

  6. Clinical Scenario #1 – Adenocarcinoma of the Pancreas • What are typical symptoms of pancreatic CA? • Abdominal pain->pain can suggest neural plexus, tail lesion, unresectability, poor prognosis • Anorexia • Weight loss • Jaundice • Pruritis ->biliary obstruction • Steatorrhea->pancreatic duct obstruction

  7. Risk Factors for Pancreatic Cancer? • Firmly linked to cigarette smoking • No clear dietary factors • Increased BMI associated with increased risk • Occupational exposures to amines (chemistry, hairdressing, rubber work) associated with increased risk

  8. Risk Factors for Pancreatic Cancer • Previous epidemiology identified chronic pancreatitis as a risk factor • May actually be EtOH, smoking, and a degree of selection bias instead of pancreatitis • Familial excess of pancreatic cancer, hereditary cancer syndromes, hereditary pancreatitis, BRCA-2 mutations all associated with increased risk of pancreatic cancer

  9. Adenocarcinoma of the Pancreas: Workup • 70yo female with painless jaundice... • What would widely be regarded as the single most useful imaging study in this patient’s workup? • CT

  10. Adenocarcinoma of the Pancreas: CT scan • CT can confirm pancreatic cancer with a sensitivity of 85-95% (sensitivity is limited by smaller tumor size) • Other than the presence of a pancreatic mass, what else can you determine from CT scan? • PRESENCE of METASTASES (along with CXR) • RESECTABILITY

  11. Adenocarcinoma of the Pancreas: CT scan • What makes a pancreatic mass likely resectable? • No evidence of extrapancreatic disease • Evidence of nonobstructive superior mesenteric-portal vein confluence • No evidence of direct tumor extension to the celiac axis and SMA • EUS, laparoscopy are universally regarded as useful adjuncts to CT, not as essential however

  12. Adenocarcinoma of the Pancreas: CT scan • “Borderline” Resectable lesions include: • SMV occlusion of a short segment (open vein proximally and distally) • Body and tail lesions with + celiac, para-aortic nodes in the vicity • Tumors briefly involving the IVC may be borderline

  13. Adenocarcinoma of the Pancreas: CT scan

  14. Adenocarcinoma of the Pancreas: Workup • The mass appears “borderline” resectable per these criteria • Now what? • GI consultation for ERCP and EUS!

  15. Pancreatic Cancer: Endoscopic Adjuncts • ERCP can be utilized to: • detecting small tumors not visualized on CT (irregular solitary duct stenoses >1cm long, abrupt cutoff of main pancreatic duct, or panc and bile duct obstruction) • palliating biliary obstruction • brush cytology of the pancreatic duct has fair sensitivity (70%) but excellent specificity • EUS can be utilized to: • aid in diagnosis and characterization of lesion • obtain tissue biopsy; may be associated with lower risk of peritoneal seeding c/w percutaneous approach

  16. Pancreatic Cancer: Endoscopic Adjuncts • ERCP picture

  17. Pancreatic Cancer: Serum Markers • Is there a role for serum markers? If so, what? • CA 19-9 is a sialylated Lewis A blood group antigen commonly expressed and shed in pancreatic and hepatobiliary disease, not tumor specific • This antigen, when significantly increased, can assist in differentiating between pancreatic adenocarcinoma and inflammatory pancreatic disease • decrease in serial CA 19-9 correlates with survival of pancreatic patients after surgery or chemotherapy • Debatable as to whether this is useful as early treatment of recurrences have not been shown to improve outcomes

  18. Pancreatic Cancer Staging • Though TNM staging exists, we can roughly simplify to: • local/resectable, median survival 17 months • locally advanced and unresectable, median survival 8-9 months • metastatic disease, median survival of 4-6 months

  19. Pancreatic AdenoCA Algorithm

  20. Pancreatic Cancer: Neoadjuvant Therapy • This 70yo female has “borderline” resectable features, has been stented to answer obstructive jaundice via ERCP with EUS demonstrating a positive adenocarcinoma • Is there any role for neoadjuvant therapy for this patient? If so, what sort of regimen and with what objectives?

  21. Pipas, Barth et al. • 24 patients with pancreatic adenocarcinoma • Inclusion criteria: biopsy-proven adenocarcinoma of pancreas (Stage I-III), age>18yo, Karnofsky of >70%, Creatinine<2, WBC >3000, Hgb >10g/dL, Plts >100,000 • No history of chemo/XRT or malignancy • Treatment consisted of docetaxel 65mg/m2 IV over 1 hour and gemcitabine 4000mg/m2 IV over 30 minutes on days 1, 15, 29. On Day 43, XRT at 50.4 Gray with gemcitabine 50mg/m2 IV over 30 minutes biweekly for 12 doses

  22. Pipas, Barth et al. • All but one of 24 patients completed 12 week course of therapy • Grade 3 and 4 toxicities common, but manageable • No tumor progression, 12 responded to therapy with one radiographic CR • 50% of patients had radiographic response, 17/24 patients underwent resection after therapy • Of 17 resection patients, 13 (76%) with negative margins

  23. Pipas, Barth et al.

  24. Adenocarcinoma • 70yo female undergoes docetaxel/gemcitabine followed by gemcitabine with XRT and appreciable response is seen on repeat CT • Whipple Operation • Utility to pylorus preservation? • Extended lymphadenectomy? • Does type of pancreatic anastamosis matter? • Do stents decrease pancreatic fistulas?

  25. Case #2 • 28yo surgical resident was golfing, badly. Suddenly, according to his partners, he began acting “crazy” and drove the golf cart wildly around the green, through a sandtrap and into a small creek. He was incoherent when he was brought to the ER and found to have a serum glucose of 32.

  26. How is insulinoma diagnosed? • Whipple’s Triad: • symptoms of hypoglycemia during fasting or exercise • serum glucose <45mg/dL during symptoms • relief of symptoms with administration of glucose • Definitive test is 72-hour fast with measurement of insulin and glucose • 75% of patients develop symptoms and GB<40 within 24 hours • insulin:glucose ratio >0.4 is indicative of insulinoma • Elevated c-peptide proinsulin levels are confirmatory along with screening for antiinsulin antibodies, sulfonylureas

  27. What percent are malignant? • 10% are malignant, indicated by metastases • Metastases usually to regional peripancreatic lymph nodes, liver • generally sporadic, solitary, benign, <2cm occurring in equal distribution throughout the pancreas

  28. How are insulinomas localized? • Non-invasive preoperative imaging studies fail to localize 30-35% of insulinomas • CT/MRI, etc. generally reserved by most endocrine surgeons to r/o hepatic metastases • Intraoperative U/S and palpation are the GOLD standard for finding an insulinoma, 96-100% sensitivity

  29. What is proper operation for insulinoma? • Generally wide Kocher maneuver, superior and inferior pancreatic border mobilization, medial reflection of the spleen • Bimanual palpation with U/S • Enucleation of the lesion • Secretin can assist in identifying pancreatic duct leak after enucleation completed • What about lesion in pancreatic head? • Need to monitor glucose levels q15 minutes until lesion out

  30. Case #3 • A patient has a gastric ulcer diagnosed endoscopically and is treated with Cimetidine. One month later, the ulcer is still present despite treatment.

  31. How is ZE diagnosis made? • Elevated serum gastrin level, elevated basal acid secretory rate both only suggest possible gastrinoma • Secretin stimulation test • discontinue acid-inhibitory medication • basal serum gastrin levels • 2 U/kg of secretin IV bolus, then serum gastrin measured at 2, 5, 10, and 20 minutes later • Positive response is gastrin >200pg/mL above basal level

  32. How would you control gastric acid secretion? • Proton pump inhibitor titrated to achieve non-acidic gastric pH

  33. Where are gastrinomas? How would you localize it? • Most are found in the duodenum, pancreas, or lymph nodes near the head of the pancreas, 10% of the time they are heart, liver, bile ducts, ovary, etc. • Localization with somatostatin receptor scintigraphy (SRS) (only 30% of gastrinomas <1.1cm) • SRS and EUS can, in tandem, improve detection of small gastrinomas within the wall of the duodenum

  34. At operation, what is the likelihood of finding metastatic tumor? • Metastatic tumor to liver is found in 5-14% of cases, nodal metastases in 50% of patients

  35. Where are most gastrinomas found? • Gastrinoma triangle is where most tumors are found (70-90%) • Tumor detection can be improved via palpation, IOUS, extended Kocher maneuver, transillumination of the duodenum, and duodenotomy

  36. Hypercalcemia and Gastrinoma • If patient has MEN-1 (hyperparathyroidism, pituitary adenoma, islet-cell tumor), can they be cured with surgery for gastrinoma? • Seldom can biochemical cure be achieved due to multicentric nature of disease in MEN-1 • 93% of patient with MEN-1 alive 15 years after diagnosis, if they are on PPI’s and have no liver mets • some advocate surgical treatment only in sporadic form of disease; others propose operating on MEN-1 gastrinomas only when 2.5-3cm in size in order to reduce possibility of metastases

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