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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

Pancreatic Neoplasm

5/24/06

Brent White

Richard Barth

facts about brent georgia
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
overview
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
types of pancreatic neoplasms
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
clinical scenario 1 adenocarcinoma of the pancreas
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
clinical scenario 1 adenocarcinoma of the pancreas6
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
risk factors for pancreatic cancer
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
risk factors for pancreatic cancer8
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
adenocarcinoma of the pancreas workup
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
adenocarcinoma of the pancreas ct scan
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
adenocarcinoma of the pancreas ct scan11
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
adenocarcinoma of the pancreas ct scan12
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
adenocarcinoma of the pancreas workup15
Adenocarcinoma of the Pancreas: Workup
  • The mass appears “borderline” resectable per these criteria
  • Now what?
    • GI consultation for ERCP and EUS!
pancreatic cancer endoscopic adjuncts
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
pancreatic cancer serum markers
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
pancreatic cancer staging
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
pancreatic cancer neoadjuvant therapy
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?
pipas barth et al
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
pipas barth et al23
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
adenocarcinoma
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?
case 2
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.
how is insulinoma diagnosed
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
what percent are malignant
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
how are insulinomas localized
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
what is proper operation for insulinoma
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
case 3
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.
how is ze diagnosis made
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
how would you control gastric acid secretion
How would you control gastric acid secretion?
  • Proton pump inhibitor titrated to achieve non-acidic gastric pH
where are gastrinomas how would you localize it
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
at operation what is the likelihood of finding metastatic tumor
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
where are most gastrinomas found
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
hypercalcemia and gastrinoma
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