1. 5/24/06 Brent White Richard Barth
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

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

16. 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

17. Pancreatic Cancer: Endoscopic Adjuncts
ERCP picture

18. 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

19. 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

20. Pancreatic AdenoCA Algorithm

21. 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?

22. 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

23. 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

24. Pipas, Barth et al.

25. 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?

26. 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.

27. 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

28. 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

29. 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, % sensitivity

30. 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

31. 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.

32. 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

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

34. 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

35. 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

36. 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

37. 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