Transcript Pancreatic Neoplasms - Dartmouth

Pancreatic Neoplasm
5/24/06
Brent White
Richard Barth
Facts About Brent & Georgia
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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
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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
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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
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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 Pancreas
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What are typical symptoms of pancreatic CA?
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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?
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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 Cancer
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Previous epidemiology identified chronic
pancreatitis as a risk factor
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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
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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
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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?
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PRESENCE of METASTASES (along with CXR)
 RESECTABILITY
Adenocarcinoma of the Pancreas:
CT scan
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What makes a pancreatic mass likely resectable?
No evidence of extrapancreatic disease
 Evidence of nonobstructive superior mesentericportal 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
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Adenocarcinoma of the Pancreas:
CT scan
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“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:
CT scan
Adenocarcinoma of the Pancreas:
Workup
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The mass appears “borderline” resectable per
these criteria
Now what?
GI
consultation for ERCP and
EUS!
Pancreatic Cancer: Endoscopic
Adjuncts
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ERCP can be utilized to:
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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:
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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: Endoscopic
Adjuncts
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ERCP picture
Pancreatic Cancer: Serum
Markers
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Is there a role for serum markers? If so, what?
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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
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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
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Pancreatic AdenoCA Algorithm
Pancreatic Cancer: Neoadjuvant
Therapy
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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.
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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
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Pipas, Barth et al.
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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
Pipas, Barth et al.
Adenocarcinoma
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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?
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Case #2
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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?
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Whipple’s Triad:
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Definitive test is 72-hour fast with measurement of
insulin and glucose
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symptoms of hypoglycemia during fasting or exercise
serum glucose <45mg/dL during symptoms
relief of symptoms with administration of 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?
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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?
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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?
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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
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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?
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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
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How would you control gastric
acid secretion?
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Proton pump inhibitor titrated to achieve nonacidic gastric pH
Where are gastrinomas? How
would you localize it?
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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?
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Metastatic tumor to liver is found in 5-14% of
cases, nodal metastases in 50% of patients
Where are most gastrinomas
found?
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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
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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 MEN1 gastrinomas only when 2.5-3cm in size in order to
reduce possibility of metastases
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