Transcript Pancreatic Cancer - Sheba Hungary Student

Pancreatic Cancer
Incidence and Epidemiology
• 25,000-30,000 diagnosed annually in the
US
• or fifth leading cause of cancer-related
death
• Prevalent in men and African Americans
• 80% of cases occur between the ages 60
and 80
Anatomy
Risk Factors
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Family History of Pancreatic Cancer
Chronic or Hereditary Pancreatitis
Smoking
Exposure to occupational carcinogens
Relation to DM is controversial
Pathology
• Ductal adenocarcinoma account for 80%
to 90% of all pancreatic neoplasms
• 70% of ductal cancers arise in the
pancreatic head or uncinate process
• At diagnosis - both nodal and distant
metastases are frequently present
Pathology
• Areas of vascular and
lymphatic invasion
within and around the
tumor are commonly
seen
• perineural growth of
the tumor is highly
characteristic and
causes upper
abdominal and back
pain
Different Variants of
Adenocarcinoma
• Mucinous Noncystic Carcinoma (Colloid
Carcinoma)
• Signet Ring Cell Carcinoma
• Adenosquamous Carcinoma
• Anaplastic Carcinoma
• Giant Cell Carcinoma
• Sarcomatoid Carcinoma
Molecular Biology
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K-Ras
Early events in tumorogenesis
EGFR, HER2/3/4
p53
Late events in tumorogenesis
BRCA2
Less common : Retinoblastoma, APC
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Hereditary Pancreatic Cancer
Syndromes
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HNPCC
BRCA2 mutation carriers
Peutz-Jeghers Syndrome
AT
Familial Atypical Multiple Mole Melanoma
(FAMMM)
Ataxia Telangectasia
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Peutz Jegher Syndrome
jejunojejunal proximal
intussusceptions
Symptoms and Signs
• insidious tumors that can be present for
long periods and grow extensively before
they produce symptoms.
• The symptoms, once they develop, are
determined by the location of the tumor in
the pancreas
Sings and Symptoms – Pancreatic
Head Cancer
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Weight Loss (92%)
Pain (72%)
Jaundice (82%)
Anorexia (64%)
Dark urine (63%)
Light Stool (625)
Sings and Symptoms – Pancreatic
Body or Tail Cancer
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Weight Loss (100%)
Pain (87%)
Weakness (43%)
Nausea (45%)
Vomiting (37%)
Anorexia (33%)
Physical Examination
• Dependent on location and size of the
pancreatic tumor
• Metastatic subumbilical noudle (“Sister Mary
Joseph node”)
• left supraclavicular lymphadenopathy (“Virchow's
node”)
• pelvic peritoneal (“Blumer's shelf”) deposits
• Portal HTN, Ascits, Caput Medusae, GE Varices
Sister Mary Joseph’s Noudle
Courvoisier’s Sign
• Painless Jaundice
• Distended
Gallbladder
Lab Tests
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Head Lesions
Bilirubin
ALP
Tumor markers : CEA, CA19-9
• Normal Serum levels on early disease
• Increased Serum levels on Cholangitis,
Obstructive Jaundice
Imaging Studies
• For most patients, the initial imaging study
is a transcutaneous US.
• Usually followed by helical contrastenhanced CT
• hypodense mass with poorly demarcated edges. It
may have a more hypodense center, indicating
central necrosis or cystic change
• Sensitivity up to 95% for diameter >2 cm
Imaging Studies
• MRI - sensitivity and specificity of MRI
appear to equal those of CT
• PET - diagnosing small pancreatic tumors
that escaped CT or MRI detection
• ERCP - helpful in evaluating patients with
obstructive jaundice without a detectable
mass on CT or MRI
Double Duct Sign
• superimposable bile duct
and pancreatic duct
strictures (i.e., the doubleduct sign) on ERCP is highly
suggestive of a pancreatic
head
• DD: Chronic pancreatitis,
Autoimmune pancreatitis
Role of Biopsy
• required before chemoradiation therapy of
unrsectable tumor or neoadjuvant
treatment of resectable tumors
• Transcutaneous: CT/US Guided
• Transduodenal : EUS
• Drawbacks of Biopsy:
• May yield FN Results, doesn’t affect management
• Theoretical possibility of peritoneal spread
TNM Staging
• T0 – Tis/PAN-IN3
• T1/2 – Below/Above 2 cm in diameter
• T3/4 – Local extension beyond pancreas
• T3 lesions are considered to be potentially
resectable because they do not involve the celiac
axis or superior mesenteric artery.
• T4 lesions are considered to be unresectable
because they involve the critical peripancreatic
arteries
TNM STaging
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Stage 0 Tis N0 M0
Stage 1A T1 N0 M0
Stage 1B T2 N0 M0
Stage 2A T3 N0 M0
Stage 2B T1/T2/T3 N1 M0
Stage 3 T4 Nx M0
4Stage Tx Nx M1
Staging
• Stage I and II cancers are amenable to
resection
• Poor prognostic signs
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aneuploidy
large tumor size (T2)
positive regional nodes (N1)
incomplete resection at the pancreatic or
retroperitoneal margin
Staging
• Stages III and IV cancers are considered
to be unresectable
• Stage III due to vascular invasion
• Stage IV due to distant metastases
• Mean survival
• Stage III – 8-12 mo.
• Stage IV – 3-6 mo.
Imaging for Staging
• High-resolution helical CT, with phased
imaging. Signs of unresectibility
• Circumferential encasement, invasion, or occlusion
of the portal vein, SMV, or SMA
• extension beyond the pancreatic capsule and into
the retroperitoneum
• involvement of neural or nodal structures
• extension of the tumor along the hepatoduodenal
ligament
Role of Laparoscopy in Staging
• Patients believed to have stage I or II
disease may have unrecognized small
metastases to peritoneal surfaces (e.g.,
diaphragm, liver) and that those
metastases can be laparoscopically
detected, thus preventing a needless
laparotomy
Resectional Surgery for Pancreatic Head
and Uncinate Process Tumors
• Tumors of the head, neck, and uncinate
process of the pancreas account for about
70% of pancreatic tumors
• Resected by pancreaticoduodenectomy
• Pylorus sparing – faster and easier, same
morbidity and mortality but greater chance for
delayed gastric emptying.
Pancreaticoduodenectomy
(Whipple’s procedure)
• preliminary search for metastases or other reasons to abort
resection
• The gallbladder is usually removed
• the common bile duct is divided above the duodenum
• The proximal GI tract is divided at the level of the gastric antrum
(standard Whipple) or 1st part of the duodenum (pylorus-preserving)
• The proximal jejunum is divided, and the neck of the pancreas is
transected
• uncinate process of the pancreas is resected from the
retroperitoneum along the lateral surface of the superior mesenteric
artery
Pancreaticoduodenectomy
(Whipple’s procedure)
• pancreaticojejunostomy (as an
end-to-end or end-to-side)
• end-to-side
hepaticojejunostomy
• gastrojejunostomy (standard
Whipple) or
duodenojejunostomy (pyloruspreserving Whipple)
Comlications of
Pacreatoduodenectomy
• When performed by experienced surgeons
mortality rate is 2% to 4%
• Anastamotic Leaks
• Intra abdominal abcesses
• Delayed gastric emtying
• pancreatic malabsorption and steatorrhea
Results of Pancreaticoduodenectomy
• 10-15% 5-ys. Survival, usually don’t
survive additional 5 ys.
• Tumor free margins – 26% 5-ys. survival
• Tumor positive margins – 8% 5-ys. survival
• Other prognostic factors: tumor diameter, diploid or
aneuploid DNA content, and lymph node status
Resectional Surgery for Pancreatic
Body and Tail Tumors
• Only 10% deemed resectable at diagnosis
• Resection involves a distal
pancreatectomy +/- splenectomy
• Complications:
• Subphrenic Abcess (5-10%)
• Pancreatic duct leak (20%)
• Outcome – 8-14% 5-ys. survival
Palliative Nonsurgical Treatment of
Pancreatic Cancer
• Jaundice – Drainage either percutanously
endoscopically, placement of a metal or plastic stent
• Gastric Outlet obstruction – direct extension of the tumor
into the duoudenum. Placement of a stent
endoscopically into the duodenum.
• Pain – Invasion into peripancreatic nerve plexuses.
Analgetics, Narcotics, Percutaneous CT/US guided
Celiac Plexus Block
Palliative Surgical Management of
Pancreatic Cancer
• Jaundice - cholecystojejunostomy or a
choledochojejunostomy
• Gastric Outlet Obstruction - can be managed by creation
of a side-to-side gastrojejunostomy
• pain - can be achieved, intraoperatively, by injecting
alcohol into the celiac plexus, and some surgeons
routinely perform operative celiac plexus block at the
time of surgical palliation
Chemoradiation Therapy
• best results have been achieved using
radiation therapy combined with either 5fluorouracil or gemcitabine
• Patients undergoing resection may also
benefit from adjuvant chemoradiation
therapy