Pancreatic cancer is the fifth leading cause of cancer death in the United States.
In the year 2005, an estimated 32,180 new cases will be diagnosed, and 31,800
deaths will be ascribed to this cancer.
Incidence and epidemiology
The incidence of pancreatic cancer is slightly higher in males than in
females. These gender differences are most prominent among younger
The peak incidence of pancreatic carcinoma occurs in the seventh decade
of life. Two-thirds of new cases occur in people > 65 years old.
The incidence is higher in the black population, with an excess risk of 40%-
50% over whites. Perhaps more importantly, black males probably have the
highest risk of pancreatic cancer worldwide.
Cancer of the pancreas is a highly lethal disease historically, with few
reports of 5-year survivors. However, more recent series have shown a decrease
in both operative mortality and overall morbidity. There has also been a
significant increase in 5-year survival after curative resection (21%-25%). Factors
that appear to be important in predicting long-term survival after resection
include clear surgical margins, negative lymph nodes, and reduced perioperative
Adenocarcinoma of the pancreas, the most common histologic type, has a median
survival of 9-12 months and an overall 5-year survival rate of 3% for all
stages. At the time of diagnosis, over 50% of patients with pancreatic adenocarcinoma
have clinically apparent metastatic disease. Among patients whose
disease is considered to be resectable, 50% will die of recurrent tumor within
Etiology and risk factors
The specific risk factors for pancreatic cancer are not as striking as those for
other GI malignancies, such as esophageal and gastric carcinomas. There does,
however, appear to be a significant relationship between pancreatic cancer and
Cigarette smoke is one of the carcinogens directly linked
to the causation of pancreatic malignancies. Heavy cigarette smokers have at
least a twofold greater risk of developing pancreatic carcinoma than nonsmokers.
In Japan, cigarette smoking carries an even greater risk, which can be as
much as 10-fold in men smoking one to two packs of cigarettes daily.
found particularly in processed meat products, reliably
induce pancreatic cancer in a variety of laboratory animals. No study has
directly linked dietary carcinogens to pancreatic cancers in humans.
The contribution of caffeine(Drug information on caffeine)
consumption to the development of pancreatic
carcinoma is controversial. A case-controlled study showed a correlation
between caffeine consumption and pancreatic cancer. However, other studies
have been unable to confirm this relationship.
A clear-cut relationship between alcohol(Drug information on alcohol)
use and pancreatic carcinoma
has not been shown.
does not seem to be a risk factor for pancreatic cancer. However,
10% of all patients with pancreatic carcinoma present with new-onset diabetes.
Cancer of the pancreas is a genetic disease. To date, more
than 80% of resected pancreatic cancers have been found to harbor activating
point mutations in K-ras
. In addition, the tumor-suppressor genes p16, p53,
are all frequently inactivated in this cancer.
Familial pancreatic carcinoma has been associated with the following genetic
syndromes: hereditary pancreatitis, ataxia-telangiectasia, hereditary
nonpolyposis colorectal cancer (HNPCC), familial atypical mole melanoma
(FAMM) syndrome, Peutz-Jeghers syndrome, and familial breast cancer. Families
germline mutations may be at higher risk of developing pancreatic
cancer than those without these mutations.
Signs and symptoms
The initial clinical features of pancreatic carcinoma include anorexia, weight
loss, abdominal discomfort or pain, and new-onset diabetes mellitus or thrombophlebitis.
The vague nature of these complaints may delay diagnosis for
Specific symptoms usually relate to localized invasion of peripancreatic
structures. The most common symptom is back pain, which stems from tumor
invasion of the splanchnic plexus and retroperitoneum or pancreatitis. This
pain is described as severe, gnawing, and radiating to the middle of the back.
Pain can also be epigastric or in the right upper quadrant if bile duct obstruction
In a majority of cases, patients with pancreatic cancer present with
epigastric or back pain and/or jaundice. Painless or sometimes painless jaundice
occurs with early lesions near the intrapancreatic bile duct.
Tumor invasion of the duodenum or gastric outlet may give rise
to nausea or vomiting as a presenting symptom. This symptom is rare early in
the course of the disease. Changes in bowel habits related to pancreatic insufficiency
may also be present, along with associated steatorrhea.
Recent onset of glucose intolerance in an elderly patient
associated with GI symptoms should alert physicians to the possibility of pancreatic
A palpable gallbladder
occurring in the absence of cholecystitis or cholangitis
suggests malignant obstruction of the common bile duct until proven
otherwise. This so-called Courvoisier's sign is present in about 25% of all pancreatic
Other physical findings
include Trousseau's syndrome (migratory superficial
phlebitis), ascites, Virchow's node (left supraclavicular lymph node), or a periumbilical
mass (Sister Mary Joseph's node).
Screening and diagnosis
Early diagnosis of pancreatic carcinoma is difficult but essential if surgical resection
and cure are to be improved. Defining early lesions at a resectable stage
remains a diagnostic challenge. To date, leading medical organizations have
not recommended routine screening of asymptomatic individuals for pancreatic
The use of serologic tumor markers for pancreatic carcinoma,
such as CA19-9, was originally thought to be appropriate as a screening tool.
However, since the prevalence of pancreatic carcinoma in the general population
is extremely low (0.01%), many false-positive screening results are generated.
Also, the sensitivity of CA19-9 is not high (20%) in stage I cancers. Nevertheless,
CA19-9 may be a useful marker for diagnosing patients at high risk
with the appropriate symptoms, such as smokers, recent-onset diabetics, those
with familial pancreatic cancer, or those with unexplained weight loss or diarrhea.
This marker also is useful in following disease and in assessing the adequacy
of resection or therapy.
No currently available serum marker is sufficiently accurate to be considered
reliable for screening asymptomatic patients.
is useful for staging patients with pancreatic carcinoma and for
formulating treatment plans. Approximately 10%-15% of patients thought to
have resectable disease are found to have distant metastases at laparoscopy.
The false-negative rate of laparoscopy is < 10%. The strongest indications for
laparoscopy are locally advanced disease and tumors of the body and tail of
also is being explored for the diagnosis of pancreatic carcinoma.
Cytology is positive in 5%-10% of patients who are thought to have
localized disease. There are anecdotal cases of long-term survival after resection
where positive cytology of peritoneal washings was noted. However, the
clinical/prognostic value of this test is not yet known.
Imaging for pancreatic carcinoma is best performed with conventional ultrasonography
The limit of sonographic resolution for early pancreatic carcinoma
is a diameter on the order of 1.0-1.5 cm. A mass located in the pancreatic
head will produce dilatation of the common bile duct and pancreatic duct. The
actual sensitivity of ultrasonography in the diagnosis of pancreatic carcinoma is
provides better definition of the tumor and surrounding structures than
does ultrasonography and is operator-independent. CT correctly predicts
unresectable tumors in 85% of patients and resectable tumors in 70% of patients.
Findings of tumor unresectability on CT scanning include distant lymphadenopathy,
encasement or occlusion of the superior mesenteric artery (SMA) or
celiac artery, occlusion of the portal vein or superior mesenteric vein (SMV),
and distant metastases.
More recently, spiral CT has emerged as a preferred technique for
increasing the accuracy of detecting pancreatic carcinoma in general and vessel
encasement in particular. This technique permits rapid data acquisition and computer-
generated three-dimensional (3D) images of the mesenteric arterial and
venous tributaries in any plane. Spiral CT is quicker and less expensive and uses
less contrast medium than angiography.
The use of positron emission tomography with 18
in the evaluation of patients with pancreatic cancer is expanding. A recent
study of 126 patients with focal, malignant, or benign pancreatic lesions
showed high sensitivity of FDG-PET for detection of small pancreatic neoplasms.
Lack of focal glucose uptake excludes pancreatic neoplasms (sensitivity
85.4%, specificity 60.9%).
At present, MRI is not as accurate as CT in diagnosing and staging
pancreatic carcinoma. MRI may be as useful as CT in staging and can provide
magnetic resonance angiography and magnetic resonance cholangiopancreatography
(MRC) images if needed. As yet, MRC is not a standard test
for the diagnosis of pancreatic carcinoma, but it may become helpful in
Endoscopic ultrasonography (EUS)
is a newer modality for the diagnosis
of pancreatic carcinoma, with an overall diagnostic accuracy rate of approximately
85%-90%. For the assessment of regional lymph node metastases, the
accuracy of EUS is 50%-70%. This technique is also important in the evaluation
of portal vein/SMV involvement by tumor. In addition, EUS-guided
fine-needle cytology of periampullary tumors may yield new information
with respect to the diagnosis of pancreatic cancer and may be less risky in
spreading cells by needle tracking than percutaneous biopsies.
In a comparison of EUS and spiral CT, both techniques showed comparable
efficacy in detecting tumor involvement of lymph nodes and the SMVs and
portal veins. However, EUS is less helpful in the evaluation of the SMA.
Endoscopic retrograde cholangiopancreatography (ERCP)
be supplanted as a diagnostic tool by EUS, although, at present, ERCP is used
in many clinics. Also, if a patient presents with jaundice and the CT scan reveals
dilatation of the common bile duct without an obvious mass, ERCP may
be complementary to spiral CT. ERCP findings of pancreatic cancer include
an abrupt or tapered cutoff of either or both the main pancreatic and common
arising from the exocrine gland ductal system is the most
common type of pancreatic cancer, accounting for 95% of all cases. Two-thirds
of these cancers originate in the pancreatic head, and the remainder arise in the
body or tail. Most ductal carcinomas are mucin-producing tumors and usually
are associated with a dense desmoplastic reaction.
Although most pancreatic adenocarcinomas arise from the ductal epithelium,
pancreatic acinar carcinomas and cancers arising from mucinous cystic neoplasms
are also found.
which is usually microscopic, is not unusual.
Perineural invasion occurs in the majority of patients with
pancreatic carcinoma. In addition, pancreatitis distal to and surrounding the
tumor is usually present. Most patients present with lymph node metastases in
the region of the pancreaticoduodenal drainage basins. Subpyloric and inferior
pancreatic head, SMA, and para-aortic lymph node groups also may be involved.