Pancreatic Cancer

Background:
In the United States, approximately 30,000 people
die of pancreatic cancer each year.

Among cancers of the gastrointestinal tract, it is the

third most common malignancy and the fifth
leading cause of cancer-related death.
 Pancreatic Cancer

• Background:
• The disease is difficult to diagnose in its early
stages, and most patients have incurable
disease by the time they present with symptoms.

• The overall 5-year survival rate for this disease

is less than 5%.
 Pancreatic Cancer

• Pathophysiology:
• Pancreatic cancers can arise from both the
exocrine and endocrine portions of the pancreas.

• Of pancreatic tumors, 95% develop from the

exocrine portion of the pancreas.
 Pancreatic Cancer

• Pathophysiology:
• Approximately 75% of all pancreatic carcinomas
occur within the head or neck of the pancreas.

• ► 15-20% occur in the body of the pancreas.

• ► and 5-10% occur in the tail.

 Pancreatic Cancer
• Pathophysiology:
• Typically, pancreatic cancer first metastasizes to
regional lymph nodes, then to the liver

• It can also directly invade surrounding visceral

organs such as the:
• ► duodenum
• ► stomach, and colon.
•
• ► and less commonly, to the lungs.
 Pancreatic Cancer
• Pathophysiology:
• The molecular genetics of pancreatic
adenocarcinoma have been well studied.

• ► Of these tumors, 80-95% have mutations in the

KRAS2 gene.

• ► and 85-98% have mutations, or deletions, in

the CDKN2 gene.
 Pancreatic Cancer

• Pathophysiology:
• 50% have mutations in TP53.
•
• and about 55% have deletions or mutations of
Smad4.
 Pancreatic Cancer

• Pathophysiology:
• Remember
• Although studies are underway, the genetic mutations
associated with pancreatic adenocarcinoma are not
yet clinically useful in screening for or diagnosing the
disease.
 Pancreatic Cancer

• Pathophysiology:
• As in other organs, chronic inflammation is a
predisposing factor in the development of pancreatic
cancer.

• Patients with chronic pancreatitis from alcohol,

especially those with familial forms, have much higher
incidence and an earlier age of onset of pancreatic
carcinoma.
 Pancreatic Cancer

• Frequency:
• Worldwide, pancreatic cancer ranks thirteenth in
incidence but eighth as a cause of cancer death.

•
 Pancreatic Cancer

• Frequency:
• Most other countries have incidence rates of 8-12
cases per 100,000 persons per year.

• ► For example, the incidence in India is less

than 2 cases per 100,000 persons per year.
 Pancreatic Cancer

• Mortality/Morbidity:
• Pancreatic carcinoma is unfortunately usually a fatal
disease.

• Patients eventually succumb to the consequence of :

• ► Local lymph node metastasis
• ► Distant metastasis
 Pancreatic Cancer

• Mortality/Morbidity:
• Remember
• ► Overall survival is less than 5%.
• ► Patients able to undergo surgery 20% of cases.
• ►After surgery:
• Survival time is 12-19 months
• 5 years survival rate 15- 20%
 Pancreatic Cancer
• Mortality/Morbidity:
• The best predictors of long-term survival after
surgery are:

• 1) a tumor diameter of less than 3 cm

• 2) no nodal involvement

• 3) and negative resection margins.

 Pancreatic Cancer

• Sex:
• The male-to-female ratio for pancreatic cancer is 1.2-
1.5:1.

• Age:
• The median age at diagnosis is 69 years in whites and
65 years in blacks.
 Pancreatic Cancer

• Clinical Presentation
• History
• The early clinical diagnosis of pancreatic cancer is
fraught with difficulty.

• Unfortunately, the initial symptoms are often quite

nonspecific and subtle in onset.
 Pancreatic Cancer
• Clinical Presentation
• History
• Patients typically report the gradual onset of
nonspecific symptoms such as:

• Anorexia
• malaise
• nausea
• fatigue
• and midepigastric or back pain.
 Pancreatic Cancer

• Clinical Presentation
• History
• Significant weight loss is a characteristic
feature of pancreatic cancer.
 Pancreatic Cancer

• Clinical Presentation
• History
• These initial symptoms can be easily attributed
to other processes unless a physician has a high
index of suspicion for the possibility of
underlying pancreatic carcinoma.
 Pancreatic Cancer
• Clinical Presentation
• History
• ► Delayed diagnosis is a common problem in
patients with pancreatic cancer.

• ► With fewer than a third of patients being

diagnosed within 2 months of the onset of their
symptoms.
 Pancreatic Cancer

• Clinical Presentation
• History
• Pain is the most common presenting symptom in
patients with pancreatic cancer.

• Typically, it is midepigastric in location, with radiation

of the pain sometimes occurring to the mid - or lower-
back region.
 Pancreatic Cancer
• Clinical Presentation
• History
• Back radiation of the pain is a worrisome sign
indicating retroperitoneal invasion of the splanchnic
nerve plexus by the tumor.
 Pancreatic Cancer
• Clinical Presentation
• History
• Weight loss may be related to:

• ► anorexia

• ► malabsorption from pancreatic exocrine

insufficiency caused by pancreatic duct
obstruction by the cancer.
 Pancreatic Cancer

• Clinical Presentation
• History
• The onset of diabetes mellitus within the previous year
is sometimes associated with pancreatic carcinoma.
 Pancreatic Cancer

• Clinical Presentation
• History
• ► The most characteristic sign of pancreatic
carcinoma of the head of the pancreas is
painless obstructive jaundice.
 Pancreatic Cancer
• Clinical Presentation
• History
• a) Patients with this sign may come to medical
attention before their tumor grows large enough to
cause abdominal pain.

• b) These patients usually notice a darkening of their

urine and lightening of their stools before they or their
families notice the change in skin pigmentation.

• c) Pruritus may accompany obstructive jaundice.

 Pancreatic Cancer

• Clinical Presentation
• History
• Migratory thrombophlebitis (i.e. Trousseau sign) and
venous thrombosis also occur with higher frequency
in patients with pancreatic cancer.
 Pancreatic Cancer
• Clinical Presentation
• Physical
• The physical examination findings in a patient with
pancreatic cancer are usually limited to evidence of:

• ► significant weight loss

•
• ► and some mild-to-moderate midepigastric
tenderness.
 Pancreatic Cancer

• Clinical Presentation
• Physical
• Patients with jaundice may have a palpable
gallbladder (i.e. Courvoisier sign).

• ► and may have evidence of skin excoriations from

pruritus.
 Pancreatic Cancer

• Clinical Presentation
• Physical
• Patients presenting with end-stage disease may have:

• ■ ascites

• ■ a palpable abdominal mass hepatomegaly from liver

metastases

• ■ or splenomegaly from portal vein obstruction.

 Pancreatic Cancer
• Causes:
• Smoking
– Smoking is the most common environmental risk
factor for pancreatic carcinoma.

– People who smoke have at least a 2-fold increased

risk for pancreatic cancer.
• Causes:
• Dietary factors
Alcohol consumption does not appear to be
an independent risk factor for pancreatic
cancer unless it is associated with chronic
pancreatitis.
Causes
► The incidence of pancreatic cancer appears to
be higher in people with increased energy.

► and lower in those with a diet rich in fresh fruits

and vegetables.
 Pancreatic Cancer

Causes
• Diabetes mellitus

► Patients with diabetes mellitus of at least 5-years'

duration have a 2-fold increased risk of developing
pancreatic carcinoma.
 Pancreatic Cancer
• Causes

• ► Chronic pancreatitis.

• ► Genetic factors
 Pancreatic Cancer
• Differential Diagnosis

• Choledocholithiasis
Cholelithiasis
Duodenal Ulcers
Gastric Cancer
Gastric Ulcers
Neoplasms of the Endocrine Pancreas
Pancreatitis, Acute
Pancreatitis, Chronic
 Pancreatic Cancer
• Differential Diagnosis

• Abdominal Aortic Aneurysm

Ampullary Carcinoma
Bile Duct Strictures
Bile Duct Tumors
Cholangitis
Cholecystitis
Choledochal Cysts
• Workup
• Lab studies
• ► General laboratory studies
The laboratory findings in patients with pancreatic
cancer are usually nonspecific.

► As with many chronic diseases, a mild anemia

may be present.

►Thrombocytosis is also sometimes observed in

patients with cancer.
• Workup
• Lab studies
• ►General laboratory studies
• Patients presenting with obstructive jaundice show
significant elevations in:
• bilirubin (conjugated and total)
• alkaline phosphatase (ALP)
• gamma-glutamyl transpeptidase (GGT)
• and
• aspartate aminotransferase (ASP) and alanine
aminotransferase (ALT).
• Workup
• Lab studies
• ►General laboratory studies
• Interestingly, amylase and lipase are infrequently
elevated in pancreatic carcinoma.
• Workup
• Lab studies
• ►General laboratory studies

Patients may also have laboratory evidence of

malnutrition
e.g.
low serum albumin or cholesterol levels.
• Workup
• Lab studies
• ►General laboratory studies
• Tumor markers
– The major useful tumor marker for pancreatic
carcinoma is carbohydrate antigen 19-9 (CA 19-9).
• Workup
• Imaging Studies

• computed tomography (CT) scanning.

ultrasonography (US).

• magnetic resonance imaging (MRI).

• (ERCP).

• and positron emission tomography (PET).

Scanning
• TREATMENT
• Medical Care:
• Chemotherapy
• Palliative therapy
• Surgical Care:
• Pancreaticoduodenectomy (Whipple operation).
• Neoadjuvant chemoradiation.
• Thanks