Pancreatic Neoplasm

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Pancreatic Neoplasm

• 5/24/06
• Brent White
• Richard Barth

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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
• GooberPeanut
• Georgia produces quite a few peanuts, growing 42
  of peanuts grown in the US

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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

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Types of Pancreatic Neoplasms

• Broadly speaking, there are three basic types
• Ductal adenocarcinoma gt90 of pancreatic cancers
  with a 4 5-year survival (worst of any cancer)
• Neuroendocrine tumors aka islet-cell tumors, rare
• Cystic neoplasms account for lt1 of pancreatic
  cancers

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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

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Clinical Scenario 1 Adenocarcinoma of the
Pancreas

• What are typical symptoms of pancreatic CA?
• Abdominal pain-gtpain can suggest neural plexus,
  tail lesion, unresectability, poor prognosis
• Anorexia
• Weight loss
• Jaundice
• Pruritis -gtbiliary obstruction
• Steatorrhea-gtpancreatic duct obstruction

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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

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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

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Adenocarcinoma of the Pancreas Workup

• 70yo female with painless jaundice...
• What would widely be regarded as the single most
  useful imaging study in this patients workup?
• CT

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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

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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

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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

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Adenocarcinoma of the Pancreas CT scan
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Adenocarcinoma of the Pancreas Workup

• The mass appears borderline resectable per
  these criteria
• Now what?
• GI consultation for ERCP and EUS!

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Pancreatic Cancer Endoscopic Adjuncts

• ERCP can be utilized to
• detecting small tumors not visualized on CT
  (irregular solitary duct stenoses gt1cm 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

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Pancreatic Cancer Endoscopic Adjuncts

• ERCP picture

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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

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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

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Pancreatic AdenoCA Algorithm
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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?

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Pipas, Barth et al.

• 24 patients with pancreatic adenocarcinoma
• Inclusion criteria biopsy-proven adenocarcinoma
  of pancreas (Stage I-III), agegt18yo, Karnofsky of
  gt70, Creatininelt2, WBC gt3000, Hgb gt10g/dL, Plts
  gt100,000
• 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.

• 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

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Pipas, Barth et al.
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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?

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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.

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How is insulinoma diagnosed?

• Whipples Triad
• symptoms of hypoglycemia during fasting or
  exercise
• serum glucose lt45mg/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 GBlt40 within
  24 hours
• insulinglucose ratio gt0.4 is indicative of
  insulinoma
• Elevated c-peptide proinsulin levels are
  confirmatory along with screening for antiinsulin
  antibodies, sulfonylureas

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What percent are malignant?

• 10 are malignant, indicated by metastases
• Metastases usually to regional peripancreatic
  lymph nodes, liver
• generally sporadic, solitary, benign, lt2cm
  occurring in equal distribution throughout the
  pancreas

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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

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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

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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.

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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 gt200pg/mL above
  basal level

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How would you control gastric acid secretion?

• Proton pump inhibitor titrated to achieve
  non-acidic gastric pH

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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
  lt1.1cm)
• SRS and EUS can, in tandem, improve detection of
  small gastrinomas within the wall of the duodenum

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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

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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

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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 PPIs 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