Download Pancreatic Cancer

MINISTRY OF PUBLIC HEALTH OF UKRAINE
KHARKOV NATINAL MEDICAL UNIVERSITY
МИНИСТЕРСТВО ЗДРАВООХРАНЕНИЯ УКРАИНЫ
ХАРЬКОВСКИЙ НАЦИОНАЛЬНЫЙ МЕДИЦИНСКИЙ
УНИВЕРСИТЕТ
Pancreatic cancer
Рак поджелудочной железы
Утверждено
ученым советом ХНМУ
Протокол № 4 от 19.01.2007 г.
Kharov KNMU- 2007
Харьков ХНМУ – 2007
Рак поджелудочной железы: Метод. указ. к практ. занятиям для
студентов V-VI курсов медицинских вузов, обучающихся на
английском языке / Сост. В.И. Стариков, А.Н. Белый.– Харьков: ХНМУ,
2007.– 20 с.
Pancreatic cancer is approved by the Scientific Committee of the Kharkov
state medical university and is recommended for V-th, VI-th year students
of medical faculty / Authors: V.I. Starikov, A.N. Bely.– Kharkov:
KNMU.2007. – 20 p.
Authors: Starikov V.I.
Bely A.N.
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Introduction
The pancreas is the tenth most common site of new cancers, but pancreatic cancer is the
fourth leading cause of cancer deaths among both men and women, comprising 6% of all cancerrelated deaths. Pancreatic cancer is notoriously difficult to diagnose in its early stages. At the time of
diagnosis, 52% of all patients have distant disease and 26% have regional spread. The relative 1-year
survival rate for pancreatic cancer is only 24% and overall 5-year survival is 5%.
Pathophysiology
Pancreatic cancers can arise from both the exocrine and endocrine portions of the pancreas,
but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells,
connective tissue, and lymphatic tissue. 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.
Typically, pancreatic cancer first metastasizes to regional lymph nodes, then to the liver and,
less commonly, to the lungs. It can also directly invade surrounding visceral organs such as the
duodenum, stomach, and colon or metastasize to any surface in the abdominal cavity via peritoneal
spread. Ascites may result, and this has an ominous prognosis. Pancreatic cancer may spread to the
skin as painful nodular metastases. Metastasis to bone is uncommon. Pancreatic cancer rarely
spreads to the brain but can produce meningeal carcinomatosis.
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, deletions, or
hypermethylation in the CDKN2 gene; 50% have mutations in p53 and about 55% have homozygous
deletions or mutations of Smad4. Some of these mutations can also be found in high-risk precursors
of pancreatic cancer. For example, in chronic pancreatitis, 30% of patients have detectable mutations
in p16 and 10% have K-ras mutations.
Families with BRCA-2 mutations, which are associated with a high risk of breast cancer, also
have an excess of pancreatic cancer. Assaying pancreatic juice for the genetic mutations associated
with pancreatic adenocarcinoma is invasive but may be useful for the early diagnosis of the disease;6
this approach is problematic as genetic mutations in the pancreatic juice may be found in patients
with inflammatory pancreatic disease.
Certain precursor lesions have been associated with pancreatic tumors arising from the
ductal epithelium of the pancreas. The main morphologic form associated with ductal
adenocarcinoma of the pancreas is pancreatic intraepithelial neoplasia (PIN). These lesions arise
from specific genetic mutations and cellular alterations that all contribute to the development of
invasive ductal adenocarcinoma. The initial alterations appear to be related to KRAS2 gene
mutations and telomere shortening. Thereafter p16/CDKN2A is inactivated. Finally, the inactivation
of TP53 and MAD4/DPC4 occur. These mutations have been correlated with increasing
development of dysplasia, and thus the development of ductal carcinoma of the exocrine pancreas.
As with cancer in other organs, chronic inflammation appears to be a predisposing factor in
the development of pancreatic cancer. Chronic pancreatitis from alcohol and especially familial
chronic pancreatitis are associated with a much higher incidence and an earlier age of onset of
pancreatic carcinoma.
Frequency
Worldwide, pancreatic cancer ranks 13th in incidence but 8th as a cause of cancer death.The
highest incidence rate is 16.2 cases per 100,000 persons per year in black males in the United States.
Native Hawaiian males and men of Korean, Czech, Latvian, and New Zealand Maori ancestry also
have high incidence rates: 11 cases per 100,000 persons per year. Most other countries have
incidence rates of 8-12 cases per 100,000 persons per year. In some areas of the world, pancreatic
cancer is quite infrequent; for example, the incidence in India is less than 2 cases per 100,000
persons per year.
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Mortality/Morbidity
Pancreatic cancer is the fourth leading cause of death among both men and women,
comprising 6% of all cancer-related deaths. The death rate has risen from 5 per 100,000 population
in 1930 to more than 10 per 100,000 in 2003. The disease is notoriously difficult to diagnose in its
early stages. At the time of diagnosis, 52% of all patients have distant disease and 26% have regional
spread.
The relative 1-year survival is only 24%, and the overall 5-year survival rate is 5%, having
increased from 3% in 1975 – 77. A 5-year survival in pancreatic cancer is no guarantee of cure;
patients who survive for 5 years after successful surgery may still die of recurrent disease years after
the 5-year survival point. The occasional patient with metastatic disease or locally advanced disease
who survives beyond 2-3 years may die of complications of local spread, such as bleeding
esophageal varices.
Pancreatic carcinoma is unfortunately usually a fatal disease. The collective median survival
time of all patients is 4-6 months. Most patients eventually succumb to the consequences of local
invasion and metastatic cancer, and true long-term cures are rare. However, neuroendocrine and
cystic neoplasms of the pancreas such as mucinous cystadenocarcinomas or intraductal papillary
mucinous neoplasms (IPMN) have much better survival rates than pancreatic adenocarcinoma.
In patients able to undergo a successful curative resection (only about 20% of patients),
median survival time ranges from 12-19 months, and the 5-year survival rate is 15-20%. The best
predictors of long-term survival after surgery are a tumor diameter of less than 3 cm, no nodal
involvement, negative resection margins, and diploid tumor DNA content.
Race
 The incidence rate of pancreatic cancer for black males in the United States from 2001 to
2005 was 15.4 cases per 100,000 persons per year; the incidence for black females was 12.4 cases
per 100,000 persons per year.
 For white males in the United States from 2001 to 2005, the incidence was 12.1 cases per
100,000 persons per year, and for white females the incidence was 9.1 cases per 100,000 persons per
year.
 The reasons for the higher incidence of pancreatic cancer in African Americans are
unclear. Certainly, differences in risk factors for pancreatic cancer, such as dietary habits, obesity,
and the frequency of cigarette smoking, are recognized among different population groups and may
contribute to the higher incidence of this disease among blacks. However, Arnold et al found that
excess pancreatic cancer in blacks cannot be attributed to currently known risk factors, suggesting
that as-yet undetermined factors that play a role in the disease process. One possibility is a difference
in the underlying frequency of predisposing genetic mutations for pancreatic cancer.
Sex
In the United States, slightly more women than men are diagnosed each year with pancreatic
cancer; slightly more men than women die of the disease.
Age
 Age is the most significant risk factor for pancreatic cancer.
 In the absence of predisposing conditions, such as familial pancreatic cancer and chronic
pancreatitis, pancreatic cancer is unusual in persons younger than 45 years. After age 50 years, the
frequency of pancreatic cancer increases linearly. At age 70, the pancreatic cancer mortality rate is
approximately 60 deaths per 100,000 persons per year.
 The median age at diagnosis is 69 years in whites and 65 years in blacks; some singleinstitution data reported from large cancer centers suggest that the median age at diagnosis in both
sexes has fallen to 63 years of age.
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Clinical
History
The early clinical diagnosis of pancreatic cancer is fraught with difficulty. Unfortunately, the
initial symptoms are often quite nonspecific and subtle in onset.
 Patients typically report the gradual onset of nonspecific symptoms such as anorexia,
malaise, nausea, fatigue, and mid-epigastric or back pain.
 Significant weight loss is a characteristic feature of pancreatic cancer.
 These initial symptoms can be easily attributed to other processes unless the physician has
a high index of suspicion for the possibility of underlying pancreatic carcinoma. Delayed diagnosis
is a common problem in patients with pancreatic cancer, with fewer than a third of patients in the
past being diagnosed within 2 months of the onset of their symptoms. The availability of CT scans
has shortened that interval.
 Pain is the most common presenting symptom in patients with pancreatic cancer.
Typically, it is mid epigastric in location, with radiation of the pain sometimes occurring to the midor lower-back region. Radiation of the pain to the back is worrisome, as it indicates retroperitoneal
invasion of the splanchnic nerve plexus by the tumor. Often, the pain is unrelenting in nature with
night-time pain often being a predominant complaint. Some patients may note increased discomfort
after eating. The pain may be worse when the patient is lying flat. At the time of initial presentation,
about one third of patients may not have pain, one third have moderate pain, and one third have
severe pain. All patients experience pain at some point in their clinical course.
 Weight loss may be related to cancer-associated anorexia and/or subclinical malabsorption
from pancreatic exocrine insufficiency caused by pancreatic duct obstruction by the cancer. Patients
with malabsorption usually complain about diarrhea and malodorous, greasy stools. Nausea and
early satiety from gastric outlet obstruction and delayed gastric emptying from the tumor may also
contribute to weight loss.
 The onset of diabetes mellitus within the previous year is sometimes associated with
pancreatic carcinoma. However, only about 1% of cases of new-onset diabetes mellitus in adults are
related to occult pancreatic cancer. Nevertheless, pancreatic cancer should be at least thought of in a
patient older than 70 years with a new diagnosis of diabetes and without any other diabetic risk
factors.
 The most characteristic sign of pancreatic carcinoma of the head of the pancreas is painless
obstructive jaundice.
o Patients with this sign may come to medical attention before their tumor grows large
enough to cause abdominal pain.
o 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. Physicians can usually
recognize clinical jaundice when the total bilirubin reaches 2.5-3 mg%. Patients and their families do
not usually notice clinical jaundice until the total bilirubin reaches 6-8 mg%. Urine darkening, stool
changes, and pruritus are often noticed by patients before clinical jaundice.
o Pruritus may accompany and often precedes clinical obstructive jaundice. Pruritus can
often be the patient's most distressing symptom.
 Depression is reported to be more common in patients with pancreatic cancer than in
patients with other abdominal tumors. In some patients, depression may be the most prominent
presenting symptom. This may be, in part, secondary to the high frequency of delayed diagnosis
with this disease. In addition, although patients may not communicate it to their families, they are
often aware that a serious illness of some kind is occurring in them.
 Migratory thrombophlebitis (ie, Trousseau sign) and venous thrombosis also occur with
higher frequency in patients with pancreatic cancer and may be the first presentation. Marantic
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endocarditis may develop in pancreatic cancer, occasionally being confused with subacute bacterial
endocarditis.
Physical
The physical examination findings in a patient with pancreatic cancer usually involve
evidence of significant weight loss and some mild-to-moderate midepigastric tenderness together
with other more specific signs.
 Patients with clinical jaundice may also have a palpable gallbladder (ie, Courvoisier sign)
and may have skin excoriations from unrelenting pruritus.
 Patients presenting with or developing advanced intra-abdominal disease may have ascites,
a palpable abdominal mass, hepatomegaly from liver metastases, or splenomegaly from portal vein
obstruction.
 Subcutaneous metastases (referred to as a Sister Mary Joseph nodule or nodules) in the
paraumbilical area signify advanced disease.
 A metastatic mass in the rectal pouch may be palpable on rectal examination (Blumer's
shelf).
 A metastatic node may be palpable behind the medial end of the left clavicle (Virchow's
node). However, other nodes in the cervical area may also be involved. Indeed, prior to the advent of
CT scanners to assess intra-abdominal disease, pancreatic cancer accounted for some 25% of
adenocarcinoma of the cervical nodes, primary site unknown.
Causes
Overall, estimates indicate that 40% of pancreatic cancer cases are sporadic in nature.
Another 30% are related to smoking, and 20% may be associated with dietary factors. Only 5-10%
are hereditary in nature. Fewer than 5% of all pancreatic cancers are related to underlying chronic
pancreatitis.
 Smoking
o Smoking is the most common environmental risk factor for pancreatic carcinoma.
o People who smoke have at least a 2-fold increased risk for pancreatic cancer. Current
smokers with over a 40 pack-year history of smoking may have up to a 5-fold increase risk of the
disease. Smokeless tobacco also increases the risk of pancreatic cancer. It takes 5-10 years of
discontinued smoking to reduce the increased risk of smoking to approximately that of nonsmokers.
 Dietary factors
o Alcohol consumption does not appear to be an independent risk factor for pancreatic
cancer unless it is associated with chronic pancreatitis.
o In a number of studies, obesity, especially central, has been associated with a higher
incidence of pancreatic cancer. For example, Li et al found that being overweight or obese during
early adulthood was associated with a greater risk of pancreatic cancer and a younger age of disease
onset, while obesity at an older age was associated with a lower overall survival.
o The incidence is lower in those with a diet rich in fresh fruits and vegetables. Fruits and
vegetables rich in folate and lycopenes (such as tomatoes) may be especially good at reducing the
risk of developing pancreatic cancer. Red meat consumption, especially processed, is associated with
a higher risk of pancreatic cancer. Poultry and dairy product consumption does not increase the risk
of this disease. Supplemental antioxidants such as vitamin C or E do not appear to decrease the risk
of pancreatic cancer or other gastrointestinal cancers and may actually be associated with excess
mortality.
o Despite early reports to the contrary, coffee consumption is not associated with an
increased risk of pancreatic cancer.
 Diabetes mellitus
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o Numerous studies have examined the relative risk of pancreatic cancer in persons with
diabetes mellitus.
o Meta-analysis of 30 studies concluded that patients with diabetes mellitus of at least 5years' duration have a 2-fold increased risk of developing pancreatic carcinoma. Pancreatic cancer
may follow 18-36 months after a diagnosis of diabetes mellitus in elderly patients with no family
history of diabetes mellitus.
 Chronic pancreatitis
o Long-standing chronic pancreatitis is a substantial risk factor for the development of
pancreatic cancer. A multicenter study of more than 2000 patients with chronic pancreatitis showed
a 26-fold increase in the risk of developing pancreatic cancer. This risk increased linearly with time,
with 4% of patients who had chronic pancreatitis for 20 years' duration developing pancreatic
cancer.13
o The risk of pancreatic cancer is even higher in patients with hereditary pancreatitis. The
mean age of development of pancreatic cancer in these patients is approximately 57 years. The
relative risk of pancreatic cancer in hereditary pancreatitis is increased more than 50-fold, and the
cumulative risk rate of pancreatic cancer by age 70 years is 40%. This cumulative risk increases to
75% in those families with a paternal inheritance pattern.
 Genetic factors
o Approximately 5-10% of patients with pancreatic carcinoma have some genetic
predisposition to developing the disease.
o The inherited disorders that increase the risk of pancreatic cancer include hereditary
pancreatitis, multiple endocrine neoplasia (MEN), hereditary nonpolyposis rectal cancer (HNPCC),
familial adenomatous polyposis (FAP) and Gardner syndrome, familial atypical multiple mole
melanoma (FAMMM) syndrome, von Hippel-Lindau syndrome (VHL), and germline mutations in
the BRCA1 and BRCA2 genes. Hereditary pancreatitis has been associated with a cumulative risk of
developing pancreatic cancer at 40%. MEN-1 and VHL are other genetic syndromes associated with
pancreatic endocrine tumor development.
 Patients with MEN-1 develop symptomatic pancreatic endocrine tumors about 50% of the
time, and these pancreatic tumors are noted to be the leading cause of disease-specific mortality.16
von Hippel-Lindau syndrome has been associated with malignancy in 17% of masses found in the
pancreas in people with this syndrome.
 Syndromes associated with increased risk of the development of colon cancer such as
HNPCC and FAP (and Gardner syndrome) have also shown an increased correlation with existence
of pancreatic cancer but the statistics unfortunately have not been impressive. One cohort study of
1391 patients with FAP only showed 4 to develop pancreatic adenocarcinoma, and in patients with
HNPCC, no statistics are currently available to show incidence of pancreatic cancer in these patients.
FAMMM has been shown to increase relative risk of developing pancreatic cancer by 13- to 22-fold
and incidence in sporadic cases to be 98%. Germline mutations in BRCA1 and BRCA2 have only
been shown to moderately increase risk of developing pancreatic cancer by 2.3- to 3.6-fold, but
BRCA2 has been associated more commonly with pancreatic cancer at an incidence of 7%.
o The above disorders have specific genetic abnormalities associated with the noted
increased risk of pancreatic cancer. Pancreatic cancer in hereditary pancreatitis is associated with a
mutation in the PRSS1 gene. Pancreatic cancer appearing in FAP and HNPCC has been associated
with a mutation in the APC gene and MSH2 and MLH1 genes respectively. FAMMM and pancreatic
cancer has been associated with a mutation in CDKN2A. Endocrine tumors of the pancreas
associated with VHL are thought to develop by way of the inactivation of the VHL tumor suppressor
gene.
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Workup
Laboratory Studies
General laboratory studies
The laboratory findings in patients with pancreatic cancer are usually nonspecific. As with
many chronic diseases, a mild normochromic anemia may be present.
Thrombocytosis is also sometimes observed in patients with cancer.
Patients presenting with obstructive jaundice show significant elevations in bilirubin
(conjugated and total), alkaline phosphatase, gamma-glutamyl transpeptidase, and to a lesser extent,
aspartate aminotransferase and alanine aminotransferase.
Serum amylase and/or lipase levels are elevated in less than half of patients with resectable
pancreatic cancers and are elevated in only one quarter of patients with unresectable tumors.
However, about 5% of patients with pancreatic cancer present initially with acute pancreatitis, in
which case amylase and lipase will be uniformly elevated. Thus, pancreatic cancer should be in the
differential diagnosis of an elderly patient presenting for the first time with acute pancreatitis
without any known precipitating factors.
Liver metastases alone are not associated with clinical jaundice but may result in relatively
low-grade elevations of serum alkaline phosphatase and transaminase levels.
Patients with advanced pancreatic cancers and weight loss may also have general laboratory
evidence of malnutrition (eg, low serum albumin or cholesterol level).
Tumor markers
The major useful tumor marker for pancreatic carcinoma is carbohydrate antigen 19-9 (CA
19-9).
 CA 19-9 is a murine monoclonal antibody originally made against colorectal cancer cells.
The CA 19-9 antigen is a sialylated oligosaccharide that is most commonly found on circulating
mucins in cancer patients. It is also normally present within the cells of the biliary tract and can be
elevated in acute or chronic biliary disease. Some 5-10% of patients lack the enzyme necessary to
produce CA 19-9; in these patients with low or absent titer of CA 19-9, monitoring disease with this
tumor marker will not be possible.
 The reference range of CA 19-9 is less than 33-37 U/mL in most laboratories. Of patients
with pancreatic carcinoma, 75-85% have elevated CA 19-9 levels. In the absence of biliary
obstruction, intrinsic liver disease or benign pancreatic disease, a CA 19-9 value greater than 100
U/mL is highly specific for malignancy, usually pancreatic.
 Evaluation of CA 19-9 levels has been used as an adjunct to imaging studies for helping
determine the resectability potential of pancreatic carcinoma. Fewer than 4% of patients with a CA
19-9 level of more than 300 U/mL have been found to have resectable tumors.
 Unfortunately, CA 19-9 is least sensitive for small early-stage pancreatic carcinomas and
thus has not proven to be effective for the early detection of pancreatic cancer or as a screening tool.
 An elevated CA 19-9 level is found in 0.2% of an asymptomatic population older than 40
years. Of these elevations, 80% are false-positive results. If only symptomatic patients are studied,
4.3% have elevated CA 19-9 levels. Two thirds of these results are false positive.
 Although no standardized role has been set for CA 19-9 in the diagnosis of pancreatic
carcinoma, it has growing importance in the staging and follow-up of patients with this disease.
Patients presenting with low levels of CA 19-9 (<100 IU) are unlikely to have occult metastatic
disease and therefore may not need a staging laparoscopy prior to resection if other imaging shows
no advanced disease. Additionally, during surgical, chemotherapeutic, and/or radiotherapeutic
treatment for pancreatic cancer, a falling CA 19-9 seems to be a useful surrogate finding for clinical
response to the therapy. If biliary obstruction is not present, a rising CA 19-9 suggests progressive
disease.
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 Preoperative CA19-9 levels may be of prognostic value with high levels indicating poorer
outcome and less chance of resectability. Preoperative values above 50 U/mL have been shown to be
associated with higher chances of recurrence.
Carcinoembryonic antigen (CEA) is a high molecular weight glycoprotein found normally in
fetal tissues. It has commonly been used as a tumor marker in other gastrointestinal malignancies.
 The reference range is less than or equal to 2.5 mg/mL.
 Only 40-45% of patients with pancreatic carcinoma have elevations in CEA levels.
 Multiple other benign and malignant conditions can lead to elevated CEA levels; thus,
CEA is not a sensitive or specific marker for pancreatic cancer.
Many other tumor markers have been studied in pancreatic cancer, but none has yet been
shown to have general clinical utility in this disorder. As with all cancers, there is growing interest in
molecular diagnosis using powerful techniques such as gene expression microarrays and proteomics.
These novel tests are adding to our understanding of the basic defects causing pancreatic neoplasms
and pathobiology. However, these are still research tools at present.
Imaging Studies
General considerations
A number of continually evolving imaging modalities are available to help diagnose
pancreatic carcinoma in patients in whom the disease is suggested clinically. These include
computed tomography (CT) scanning, transcutaneous ultrasonography (TUS), endoscopic
ultrasonography (EUS), magnetic resonance imaging (MRI), endoscopic retrograde
cholangiopancreatography (ERCP), and positron emission tomography (PET) scanning. Which of
these modalities is used at a particular institution may depend largely on the local availability and
expertise with the procedure as well as local cancer protocols.
Additional considerations in the choice of diagnostic modality include the accuracy of the
imaging procedure for providing staging information, its ability to simultaneously obtain tissue
samples for cytologic or histologic confirmation of the diagnosis, and its capacity to facilitate
therapeutic procedures such as biliary stent placement or celiac neurolysis.
Computed tomography scanning
 Because of its ubiquitous availability and ability to image the whole abdomen and pelvis,
abdominal CT scanning continues to be the mainstay of initial diagnostic modalities used for
assessing patients suspected to have pancreatic carcinoma.
 The quality of CT scanners has been rapidly evolving. The speed of image acquisition, 3D
imaging, and slices as thin as 2-3 mm have revolutionized the technology.
 Newer models using spiral (ie, helical) CT scanning with multiple detectors and dual or
triple-phase contrast enhancement have significantly improved the sensitivity and specificity of
abdominal CT findings in patients with pancreatic carcinoma. Triple-phase spiral CT findings are
approximately 90% accurate for helping determine the resectability potential of pancreatic
carcinoma. However, small tumors can still be missed even with the most advanced CT scanning
currently available. Multidetector, pancreas protocol CT is at least as accurate as endoscopic
ultrasound in overall determination of the resectability of pancreatic carcinoma. In fact, CT may be
more accurate than EUS in predicting involvement of the superior mesenteric artery.
 Because of higher rate of enhancement by the normal pancreas, malignant tumors appear
as lower density lesions. These are often associated with obstruction of the pancreatic duct.
 When lesions are visible, CT scanning can also be used to direct fine-needle aspiration of
pancreatic masses.
 Even though it is less expensive and generally more readily available than CT scanning,
TUS has less utility in pancreatic carcinoma than CT scanning because the pancreas is often
obscured by overlying gas from the stomach, duodenum, and colon.
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 Additionally, the depth of the pancreas from the abdominal wall limits transcutaneous
ultrasonic imaging to lower frequency (2-5 MHz), and, thus, a lower-resolution ultrasonographic
image is obtained. Therefore, TUS can help detect only 60-70% of pancreatic carcinomas, and
similar to CT scanning, more than 40% of the lesions smaller than 3 cm are missed.
 TUS is very useful as an initial screening test in evaluating patients who present with
possible obstructive jaundice. By helping to detect intrahepatic or extrahepatic bile duct dilation,
abdominal ultrasonography can rapidly and accurately assess whether or not a patient has biliary
obstruction. However, other studies, such as abdominal CT scanning, EUS, ERCP, or magnetic
resonance cholangiopancreatography (MRCP), usually should then be performed to definitively
diagnose the source of biliary obstruction.
Endoscopic ultrasonography
 EUS obviates the physical limitations of TUS by placing a high-frequency
ultrasonographic transducer on an endoscope, which is then positioned in the stomach or duodenum
endoscopically to help visualize the head, body, and tail of the pancreas. Unlike CT, the patient
requires conscious sedation for this procedure.
 Additionally, because of the proximity of the pancreas to the EUS transducer, highfrequency ultrasonography (7.5-12 MHz) can be used to produce very high-resolution
(submillimeter) images. Where expert EUS is available, it has proven to be the most sensitive and
specific diagnostic test for pancreatic cancer. A negative endoscopic ultrasound is nearly 100%
specific at ruling out the presence of a pancreatic neoplasm.
 In numerous series, EUS has detection rates of 99-100% for all pancreatic carcinomas,
including those smaller than 3 cm. EUS is as accurate as ERCP or MRCP for assessing the etiology
of obstructive jaundice.
 An additional significant diagnostic advantage is EUS-guided fine-needle aspiration,
which allows for the simultaneous cytologic confirmation of pancreatic carcinoma at the time of
EUS diagnosis.
 EUS appears to be equivalent to dual-phase spiral CT scanning for assessing tumor
resectability potential. It is probably superior to CT at assessing the T stage of the tumor, especially
looking for portal vein involvement in pancreatic head lesions. EUS is probably inferior to CT in
assessing arterial involvement and distant metastases. Both EUS and CT are poor at detecting occult
nodal involvement.
Endoscopic retrograde cholangiopancreatography
 ERCP is highly sensitive at detecting pancreatic and/or biliary ductal abnormalities in
pancreatic carcinoma. Of patients with pancreatic adenocarcinoma, 90-95% have abnormalities on
ERCP findings. However, the changes observed on ERCP are not always highly specific for
pancreatic carcinoma and can be difficult to differentiate from changes observed in patients with
chronic pancreatitis.
 ERCP is more invasive than the other diagnostic imaging modalities available for
pancreatic carcinoma. ERCP also carries a 5-10% risk of significant complications with the
procedure. Because of this morbidity, it is usually reserved as a therapeutic procedure for biliary
obstruction or for the diagnosis of unusual pancreatic neoplasms such as intraductal pancreatic
mucinous neoplasms (IPMN).
 Brush cytology and forceps biopsy at the time of ERCP have been used to diagnose
pancreatic carcinoma histologically; however, in most series, the yield of a cytologic diagnosis with
these procedures has been less than 50%.
 ERCP findings provide only limited staging information, but ERCP does have the
advantage of allowing for therapeutic palliation of obstructive jaundice with either a plastic or metal
biliary stent.
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Magnetic resonance imaging
 Interest in using MRI for abdominal imaging continues to grow. The role of MRI in
pancreatic cancer has been less well studied than the role of CT scanning. It does not appear to be
superior to spiral CT scanning. Dynamic gadolinium enhanced 3D gradient echo MRI may offer
enhanced sensitivity at detecting small pancreatic lesions. However, in patients with jaundice,
magnetic resonance cholangiopancreatography (MRCP) can be used as a noninvasive method for
imaging the biliary tree and pancreatic duct.
 Whether MRCP is as sensitive and specific for pancreaticobiliary pathology as other
procedures is still being investigated. Because of the difficulty of working within intense magnetic
fields, MRI is limited in performing MRI-directed needle aspirations; however, this technology is
undergoing rapid change.
Positron emission tomography scanning
 PET scanning uses 18F-fluorodeoxyglucose (FDG) to image both the primary tumor and
metastatic disease.
 PET scanning appears to be especially useful in detecting occult metastatic disease. Its role
in pancreatic cancer evaluation management is still under investigation. False-positive PET scans
have been reported in pancreatitis.
 By itself, PET does not seem to offer additional benefits to high-quality CT scan.
However, recent studies of PET scanning combined with simultaneous CT (PET-CT) suggest that
PET-CT is more sensitive than conventional imaging for detection of pancreatic cancer, and that
PET-CT findings sometimes change clinical management.
Evaluation algorithm
 Most patients suspected of having pancreatic carcinoma are initially studied with
transcutaneous abdominal ultrasonography and/or spiral CT scanning (usually not done initially with
dual-phase contrast thin-cut pancreatic protocols). Patient management thereafter can vary from
institution to institution depending on local expertise, interest, and protocols.
 If patients have obvious hepatic metastatic disease based on initial TUS or CT findings,
they undergo a CT- or TUS-guided biopsy of one of the liver metastases and then proceed to
palliative therapy.
 Patients with a suggested or definite pancreatic mass observed on abdominal CT scanning
or TUS or those who are still considered to have pancreatic cancer but do not have an obvious
pancreatic mass need to have more definitive imaging studies. This can be done using high-quality
thin-cut multidetector CT scanning with dual phase contrast and/or by other procedures such as
endoscopic ultrasonography.
 In the author's institution, where high-quality endoscopic ultrasonography and EUS-guided
fine-needle aspiration are readily available, EUS plays a central role in the definitive diagnosis and
staging of patients with pancreatic carcinoma.
 If a pancreatic mass is observed on EUS images, EUS-guided fine-needle aspiration is
performed to confirm the disease cytologically. At the same time, the condition is staged using EUS
to determine resectability potential. Patients thought to have resectable tumors based on EUS
findings proceed directly to operative intervention. If tumors are deemed unresectable based on EUS
findings and patients have obstructive jaundice, they proceed directly to therapeutic stent placement
with ERCP while under the same endoscopic sedation. Most patients then undergo dedicated
pancreas protocol multidetector CT scanning to complete preoperative staging if the initial CT scan
was not of the highest quality. MRI, MRCP, and PET scanning are rarely used in the authors'
evaluation algorithm unless other procedures are still nondiagnostic in a patient with a high
suspicion of pancreatic cancer or altered gastric anatomy precludes endoscopic ultrasound
examination.
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 Patients with unresectable disease are offered chemotherapy for their disease. In
institutions without EUS and EUS-guided fine-needle aspiration capabilities, spiral CT scanning
with CT-guided pancreatic fine-needle aspiration or biopsy plays the central role in evaluation.
 Abdominal TUS can also be used as an initial diagnostic study, especially in the jaundiced
patient. However, this approach rarely obviates eventually performing abdominal CT scanning or
EUS in patients in whom disease is a strong possibility.
ERCP is also used frequently for evaluating patients with jaundice or patients with possible
pancreatic masses based on findings from imaging modalities if EUS is not available.
The most difficult clinical situation in which to diagnose pancreatic carcinoma is in the
patient with underlying chronic pancreatitis. In this situation, all of the above imaging studies may
show abnormalities that may not help differentiate between pancreatic carcinoma and chronic
pancreatitis. Even tumor markers can be elevated in patients with chronic pancreatitis. In these
patients, one must often combine multiple imaging modalities, close clinical follow-up, serial
imaging studies, and occasionally empiric resection to diagnose an underlying pancreatic carcinoma.
Other Tests
Needle aspiration
The necessity of obtaining a cytologic or tissue diagnosis of pancreatic cancer prior to
operation remains controversial and is highly dependent on the institution.
 Arguments in favor of preoperative biopsy include its ability to provide proof of pathology
prior to surgery, exclude unusual pathology, and provide evidence of disease before initiation of
multidisciplinary treatment such as neoadjuvant chemotherapy.
 Arguments against preoperative biopsy of pancreatic lesions are that the biopsy results will
not alter therapy, biopsy may result in seeding and interfere with definitive surgery, and the
procedure increases the cost of care.
 Studies of the risk of peritoneal contamination with CT-guided biopsy have suggested that
this risk is actually very low. EUS-guided fine-needle aspiration provides the additional advantage
of aspiration through tissue that would ultimately be included in the operative field should the
patient undergo resection.
EUS-guided fine-needle aspiration has proven to be the most effective means for making a
definitive cytologic diagnosis of pancreatic carcinoma.
 Using EUS-guided fine-needle aspirations, a cytologic diagnosis can be made in 85-95%
of patients. For example, a retrospective study by Turner et al found that EUS-guided fine needle
aspiration was 80% accurate for detection of pancreatic carcinoma, and 94% accurate when atypical
and suspicious samples are considered positive.
 A study by Micames et al suggested that percutaneous aspiration may be associated with a
higher risk of peritoneal tumor spread than aspiration with EUS.
 Thus, for potentially resectable tumors, EUS-guided fine-needle aspiration is the preferred
biopsy technique, if it is available and if a biopsy needs to be obtained. Cost-benefit analyses have
also confirmed that it is the most cost-effective mode of tissue acquisition in suspected pancreatic
cancer.
The yield of CT-guided fine-needle aspiration or biopsy findings is approximately 50-85%
in the lesions that are visible on CT scanning.
Preoperative staging laparoscopy
Some centers advocate performing a staging laparoscopy before proceeding to attempted
resection. The purpose of the laparoscopic staging is to avoid subjecting patients with liver or
peritoneal metastases to unnecessary surgery. Some surgeons advocate the use of routine staging
laparoscopy in all patients with pancreatic cancer. Their argument is that up to 20% of attempted
pancreatic resections can be prevented because of the laparoscopic findings. Others advise more a
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selective approach to staging laparoscopy, recommending its use in patients with any one of the
following criteria: CA19-9 above 150 U/mL, low volume ascites, body of pancreas tumors,
borderline resectable tumors, size above 3 cm, and common bile duct lymphadenopathy.
Another argument for selective versus routine staging laparoscopy is the fact that in many
cases where the tumor is deemed unresectable, laparoscopy would not have shown the vascular
invasion or retroperitoneal invasion that ultimately leads to unresectability of tumor.
Histologic Findings
Of all pancreatic cancers, 80% are adenocarcinomas of the ductal epithelium. Only 2% of
tumors of the exocrine pancreas are benign. Less common histologic appearances of exocrine
pancreatic cancers include giant cell carcinoma, adenosquamous carcinoma, microglandular
adenocarcinoma, mucinous carcinoma, cystadenocarcinoma, papillary cystic carcinoma, acinar
cystadenocarcinoma, and acinar cell cystadenocarcinoma. Very rarely, primary connective tissue
cancers of the pancreas can occur. The most common of these is primary pancreatic lymphoma.
Cystic neoplasms of the pancreas account for fewer than 5% of all pancreatic tumors. These
consist of benign serous cystadenomas, premalignant mucinous cystadenomas, and
cystadenocarcinomas. Intraductal mucinous pancreatic neoplasms can be benign or malignant and
usually manifest as a cystic dilation of the pancreatic ductal system.
Patients can also develop tumors of the islet cells of the pancreas. These can be functionally
inactive islet cell carcinomas or benign or malignant functioning tumors such as insulinomas,
glucagonomas, and gastrinomas.
Staging
Once an imaging modality has helped establish a probable diagnosis of pancreatic cancer,
the next issue is whether the lesion is amenable to surgical resection. Only 20% of all patients
presenting with pancreatic cancer are ultimately found to have easily resectable tumors with no
evidence of local advancement. Noncurative resections for pancreatic carcinoma provide no survival
benefit. Thus, to avoid operating on patients who cannot benefit from the operation, accurate
preoperative staging is very important.
Cancer of the exocrine pancreas is classified by the tumor, node, metastasis (TNM) staging
system. The staging for pancreatic cancer was most recently modified by the American Joint
Committee on Cancer (AJCC) in 2002.
AJCC staging of pancreatic tumors is as follows :
 Tumor (T)
o TX - Primary tumor cannot be assessed
o T0 - No evidence of primary tumor
o Tis - Carcinoma in situ
o T1 - Tumor limited to the pancreas, 2 cm or smaller in greatest dimension
o T2 - Tumor limited to the pancreas, larger than 2 cm in greatest dimension
o T3 - Tumor extension beyond the pancreas (eg, duodenum, bile duct, portal or superior
mesenteric vein) but not involving the celiac axis or superior mesenteric artery
o T4 - Tumor involves the celiac axis or superior mesenteric arteries
 Regional lymph nodes (N)
o NX - Regional lymph nodes cannot be assessed
o N0 - No regional lymph node metastasis
o N1 - Regional lymph node metastasis
 Distant metastasis (M)
o MX - Distant metastasis cannot be assessed
o M0 - No distant metastasis
o M1 - Distant metastasis
Stage grouping for pancreatic cancer is as follows:
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 Stage 0 - Tis, N0, M0
 Stage IA - T1, N0, M0
 Stage IB - T2, N0, M0
 Stage IIA - T3, N0, M0
 Stage IIB - T1-3, N1, M0
 Stage III - T4, Any N, M0
 Stage IV - Any T, Any N, M1
At initial presentation, only 20% of patients present with stage I disease, 40% present with
locally advanced disease, and 40% present with disease metastatic to nodes or distant sites.
To date, studies show that EUS is approximately 70-80% accurate for correctly staging
pancreatic carcinoma. EUS appears to better assess involvement of the portal vein/superior
mesenteric vein. Multidetector CT scanning with dual-phase contrast probably has similar or better
overall accuracy and is especially good at assessing major arterial involvement or distant metastases.
EUS is better than CT scanning to help detect abnormal lymph nodes around the pancreas and celiac
axis. Furthermore, with the addition of EUS-guided fine-needle aspiration, EUS can help
cytologically document metastatic disease in suggestive lymph nodes.
Medical Care
There is consensus on the fact that surgery is the primary mode of treatment for pancreatic
cancer. However, an important role exists for the use of chemotherapy and/or radiation therapy in an
adjuvant setting, neoadjuvant setting, and in the treatment of patients with unresectable disease.
Chemotherapy
 The 2 most active agents have been 5-fluorouracil (5-FU) and, more recently, gemcitabine.
The addition of targeted therapy in the form of epidermal growth factor receptor antagonists (ie,
erlotinib) has had a synergistic effect.
 In patients with metastatic disease, the combination of gemcitabine and erlotinib has led to
a significantly higher median survival and 1-year survival than the use of gemcitabine alone. This
has led to FDA approval of erlotinib to be used in combination with gemcitabine in advanced
unresectable pancreatic cancer. The recommendation that this combination should now constitute
standard therapy for metastatic or unresectable local disease is premature and problematic. The
improvements in response rates seen, although significant, were not great and were obtained with no
small amount of patient toxicity.
o The combination should be used with considerable care, and the use of gemcitabine alone
should still be considered as appropriate therapy for patients with metastatic disease. Gemcitabine
alone should also be considered as appropriate therapy for patients with unresectable disease; there
is no meaningful significant benefit obtained to adding radiotherapy in this situation. Such an
addition simply increases toxicity.
o The addition of bevacizumab to the combination of gemcitabine and erlotinib does not
improve the response rate of the combination alone.
o The combination of gemcitabine and capecitabine in advanced pancreatic cancer has been
investigated by several groups.
 A randomized multicenter phase III clinical trial in 319 patients by the Central European
Cooperative Oncology Group found that clinical response or quality of life was no better with the
combination than with gemcitabine alone.
 This finding contrasts with the results of the phase III United Kingdom National Cancer
Research Institute GEMCAP trial, an open-label randomized study of gemcitabine alone versus
gemcitabine combined with capecitabine in 533 patients. Compared with gemcitabine alone,
treatment with the gemcitabine-capecitabine combination produced a significantly higher objective
response rate (19.1% vs 12.4%; P=.034) and progression-free survival (hazard ratio [HR], 0.78; 95%
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confidence interval [CI], 0.66-0.93; P=.004) and was associated with a trend toward improved
overall survival (HR, 0.86; 95% CI, 0.72-1.02; P=.08).
 In addition, a meta-analysis of two additional studies involving 935 patients showed a
significant survival benefit in favor of the gemcitabine-capecitabine combination -CAP (HR, 0.86;
95% CI, 0.75-0.98; P=.02). Accordingly, these researchers recommend considering gemcitabinecapecitabine as one of the standard first-line options in locally advanced and metastatic pancreatic
cancer.
o Capecitabine alone or capecitabine plus erlotinib may provide second-line therapy benefit
in patients refractory to gemcitabine. There is no advantage to giving gemcitabine in any dose or
time of infusion other than 1000 mg/m² over one half hour intravenously.
o Combinations of gemcitabine with any of cisplatin, oxaliplatin, irinotecan, or docetaxel
have in phase III trials not been of superior benefit to gemcitabine alone.
 Adjuvant therapy
o Several studies (including the GITSG, ESPAC, CONKO) had suggested the possibility
that chemotherapy, with or without radiation therapy, would significantly improve median survivals
following surgical resection of operable disease. These studies were not definitive and not widely
accepted as justification for offering either modality for adjuvant therapy.
o A recent large retrospective study supports the use of adjuvant chemoradiotherapy. Yang
et al analyzed a registry of 2,877 patients who underwent surgical resection with curative intent for
pancreatic adenocarcinoma; approximately half received no adjuvant therapy, and approximately a
quarter received postoperative chemoradiotherapy. There was a significant additional survival
benefit for chemoradiotherapy (hazard ratio = 0.69, P = .04). In addition, treatment at high-volume
centers (hazard ratio = 0.85, P < .001) and teaching facilities (hazard ratio = 0.84, P < .001) were
independent predictors of improved survival.
o Gemcitabine alone has been shown to significantly affect survival following resection for
operable disease. A study by Neuhaus et al in 368 patients with resected pancreatic cancer found that
adjuvant gemcitabine prolongs survival when compared with surgery alone.
o The 3-year survival rates were 36.5% and 19.5% for the gemcitabine and surgery only
arms respectively (p<0.001). The 5-year survival rates were 21% and 9% for the gemcitabine and
surgery only arms respectively (p<0.001). Postsurgical adjuvant treatment with gemcitabine doubled
the 5-year survival rate when compared with surgery and observation alone.
o This trial is definitive and transformative. Adjuvant therapy with gemcitabine is now
accepted as standard therapy for surgically resected pancreatic cancer.
 The use of chemotherapy and/or radiation therapy in the neoadjuvant setting has been a
source of controversy. The rationale for neoadjuvant therapy includes the following:
o Pancreatic cancer is a systemic disease and should be treated systemically from the start.
o Patients will be able to tolerate the toxic effects of chemotherapy more readily before
undergoing major pancreatic resection than after.
o The tumor will shrink and the resection will be less cumbersome, leading to an improved
overall survival.
 Several trials conducted at M.D. Anderson Cancer Center have shown median survival as
high as 25 months. No form of neoadjuvant therapy in pancreatic carcinoma should be regarded as a
standard form of therapy; this remains an area for clinical trial study.
Palliative therapy
 Pain
o Patients not undergoing resection for pancreatic cancer should have therapy focused on
palliating their major symptoms. Pain relief is crucial in these patients. Narcotic analgesics should be
used early and in adequate dosages. Combining narcotic analgesics with tricyclic antidepressants or
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antiemetics can sometimes potentiate their analgesic effects. In some patients, narcotics are
insufficient and other approaches must be considered.
o Neurolysis of the celiac ganglia may provide significant long-term pain relief in patients
with refractory abdominal pain. This can be performed either transthoracically or transabdominally
by invasive radiology or anesthesiology, transgastrically using EUS-guided fine-needle injection, or
intraoperatively when assessing the patient's potential for resection.
o Radiation therapy for pancreatic cancer can palliate pain but does not affect the patient's
survival.
o Some patients may be experiencing pain from the obstruction of the pancreatic or biliary
ducts, especially if the pain significantly worsens after eating. These patients may benefit from
endoscopic decompression with stents.
 Jaundice
o Obstructive jaundice warrants palliation if the patient has pruritus or right upper quadrant
pain or has developed cholangitis. Some patient's anorexia also seems to improve after relief of
biliary obstruction. Biliary obstruction from pancreatic cancer is usually best palliated by the
endoscopic placement of plastic or metal stents. The more expensive and permanent metallic stents
appear to have a longer period of patency and are preferable in patients with an estimated lifespan of
more than 3 months. Plastic stents usually need to be replaced every 3-4 months.
o Patients can also undergo operative biliary decompression, either by
choledochojejunostomy or cholecystojejunostomy, at the time of an operation for resectability
assessment.
 Duodenal obstruction: Approximately 5% of patients develop duodenal obstruction
secondary to pancreatic carcinoma. These patients can be palliated operatively with a
gastrojejunostomy or an endoscopic procedure. Endoscopic stenting of duodenal obstruction is
usually reserved for patients who are poor operative candidates. Some surgeons empirically palliate
patients with a gastrojejunostomy at the time of an unsuccessful attempt at pancreatic resection in an
effort to prevent the later need for this operation.
Surgical Care
Prior to any surgical procedures, the resectability of malignant pancreatic tumors needs to be
established. Pancreatic masses are characterized as resectable, unresectable, or borderline resectable.
The latter is usually based on both the experience and technical skill of the surgeon involved in
treatment as well as the overall health of the patient and his or her wishes. Typically, extrapancreatic
disease precludes curative resection, and surgical treatment may be palliative at best.
Historically, vascular involvement has been considered a contraindication to resective cure. The
invasion of the superior mesenteric or portal vein is no longer an absolute contraindication. These
veins can be resected partially with as much as 50% narrowing of the lumen. Also, complete
reconstruction is possible especially using native veins as replacement (ie, internal jugular, greater
saphenous, or splenic). Nonetheless, invasion of the superior mesenteric, celiac, and hepatic arteries
still presents a barrier to resection. No evidence indicates that a vascular reconstruction, which
permits an attempt at surgical resection, improves or contributes to survival.
After a thorough preoperative workup, the surgical approach can be tailored to the location,
size, and locally invasive characteristics of the tumor. Curative resection options include
pancreaticoduodenectomy, with or without sparing of the pylorus, total pancreatectomy, or distal
pancreatectomy. Each procedure is associated with its own set of perioperative complications and
risks, and these points should be taken into consideration by the surgical team and discussed with the
patient when considering the goal of resection.
Pancreaticoduodenectomy (Whipple procedure)
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Patients who will most likely benefit from this procedure have a tumor located in the head of
the pancreas or the periampullary region. The Whipple procedure is not strictly the surgical approach
for pancreatic head tumors. Pancreatic ductal tumors, cholangiocarcinoma (bile duct cancer), and
duodenal masses will all require this resection. The operation traditionally involves the following:
removal of the pancreatic head, duodenum, gallbladder, and the antrum of the stomach with surgical
drainage of the distal pancreatic duct and biliary system, usually accomplished through anastomosis
to the jejunum. The primary reason for removing such a large quantity of intraabdominal structures
is that they all share a common blood supply.
Pancreaticoduodenectomy has been shown to have an overall mortality rate of 6.6%. Many
forms of morbidity are associated with the operation. One of these is delayed gastric emptying. This
occurs in approximately 25% of patients. This condition may require nasogastric decompression and
will lead to a longer hospital stay. Other morbidities include pancreatic anastomotic leak. This can be
treated with adequate drainage. Postoperative abscesses are not uncommon.
Although preoperative biliary drainage was introduced to improve the postoperative outcome
in patients with obstructive jaundice caused by tumors of the pancreatic head, van der Gaag et al
found that routine use of this maneuver increases the rate of complications. In a multicenter
randomized trial, 202 patients with obstructive jaundice and a bilirubin level of 40–250 mmol/L
(2.3-4.6 mg/dL) were assigned to undergo either preoperative biliary drainage for 4-6 weeks,
followed by surgery, or surgery alone within 1 week after diagnosis. The rate of serious
complications was higher in the biliary drainage group than in the early surgery group (74% vs 39%;
relative risk in the early-surgery group, 0.54; 95% CI, 0.41-0.71; P<0.001). No significant difference
was noted in mortality or length of hospital stay between the two groups.
Similarly, Limongelli et al found that preoperative biliary drainage predisposes to a positive
intraoperative biliary culture, which, in turn, is associated with increased risk of postoperative
infectious complications and wound infection.
The standard Whipple operation may be altered in order to include a pylorus-sparing
procedure. This modification was previously incorporated to increased nutritional strength in these
patients as the increased-gastric emptying associated with antrectomy caused nutritional
deficiencies. Although many believe that delayed gastric emptying is worsened by this modification,
studies have proven both resections to be equivalent in that regard. Another source of controversy is
the extent of lymphadenectomy that is necessary in a Whipple operation. In an elegant study, Pawlik
et al found the ratio of positive nodes to total nodes removed was an important prognostic factor. 52
This was even more significant than margin positivity.
Distal pancreatectomy
This procedure possesses a lower mortality rate than the standard Whipple procedure at
3.5%, but its use in curative resection remain limited. Essentially, a distal pancreatectomy may be an
effective procedure for tumors located in the body and tail of the pancreas. Unfortunately, masses
located in this area present later than the periampullary tumors and hence have a higher
unresectability rate. The procedure involves isolation of the distal portion of the pancreas containing
the tumor followed by resection of that segment, with oversewing of the distal pancreatic duct. The
main complications for distal pancreatectomy involve pancreatic stump leak, hemorrhage, or
endocrine insufficiency. Once again, the best treatment for the pancreatic leak is adequate drainage.
Total pancreatectomy
Although this procedure is the least commonly done with the highest associated mortality at
8.3%, it may still remain a valuable instrument in the surgical cure of pancreatic cancer. The
indication is cases in which the tumor involves the neck of the pancreas. This can either be a
situation in which the tumor originates from the neck or is growing into the neck. These patients
obviously get insulin-dependent diabetes. In some cases, the diabetes can be hard to control. Despite
this, the morbidity of a total pancreatectomy is comparable to that of a Whipple procedure.
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Consultations
The management of pancreatic carcinoma is a multidisciplinary process. Most patients
initially present to their primary care practitioner with general symptoms such as abdominal pain,
weight loss, or fatigue. Patients may also be seen initially by a gastroenterologist if they present with
obstructive jaundice. Typically, the management of pancreatic cancer would entail consultations
with a gastroenterologist, medical oncologist, general surgeon or surgical oncologist, and possibly a
radiation oncologist.
 A gastroenterologist would usually be involved either for evaluation of the cause of the
patient's presenting symptoms (eg, abdominal pain, nausea, weight loss, diarrhea) or for definitive
diagnosis of the cause of jaundice by EUS and/or ERCP. Consultation with a gastroenterologist is
needed if an endoscopically placed stent is needed for palliation of obstructive jaundice. If a
gastroenterologist is able to provide EUS-guided fine-needle aspiration, then this is the preferred
biopsy technique for pancreatic neoplasms, especially if resection is considered an option.
Consultation with a gastroenterologist may also be required to place an enteral stent for palliation of
duodenal obstruction by tumor.
 Consultation with a medical oncologist is often needed to select and administer
neoadjuvant, adjuvant, or primary chemotherapy for the disease. Consultation with a medical
oncologist is also useful for management of other common cancer symptoms such as pain and
nausea.
 Consultation with a surgeon is needed when the patient's imaging studies suggest that
operative resection may be feasible. The surgeon may perform diagnostic laparoscopy or even
laparoscopic ultrasonography prior to an attempt at definitive resection. If curative resection is not
possible, consultation with a surgeon may still be useful to consider operative palliation of biliary
and/or duodenal obstruction. Consult with a surgeon or surgical oncologist who is very experienced
in performing pancreaticoduodenectomies.
 Consultation with a radiologist may be needed for special issues such as obstructive
jaundice that is difficult to manage where percutaneous transhepatic cholangiography may be
needed.
 Consultation with a radiation oncologist is usually considered at the discretion of a medical
oncologist when combined chemoradiation may be beneficial. This approach is only indicated when
this combination therapy is the subject of a clinical trial.
Diet
 As with most patients with advanced cancer, patients with pancreatic carcinoma are often
anorexic. Pharmacologic stimulation of appetite is usually unsuccessful, but it may be tried.
 Patients may have some degree of malabsorption secondary to exocrine pancreatic
insufficiency caused by the cancer obstructing the pancreatic duct. Patients with malabsorption
diarrhea and weight loss may benefit from pancreatic enzyme supplementation. Their diarrhea may
also be improved with avoidance of high-fat or high-protein diets.
Medication
The most active single agents for pancreatic cancer have been 5-fluorouracil (5-FU) and
gemcitabine. Gemcitabine appears to be slightly more active than 5-FU. Objective responses,
meaning actual regression of tumor, have been 20% or less.
Antineoplastic agents
These agents inhibit cell growth and proliferation. They are used for chemotherapy.
Follow-up
Deterrence/Prevention
 Smoking is the most significant reversible risk factor for pancreatic cancer. Estimates
indicate that smoking accounts for up to 30% of cases of pancreatic cancer.
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 A diet high in energy intake and low in fresh fruits and vegetables increases the risk of
pancreatic cancer.
 Alcohol consumption does not increase the risk of pancreatic cancer unless it leads to
chronic pancreatitis. A multicenter study of more than 2000 patients with chronic pancreatitis
showed a 26-fold increase in the risk of developing pancreatic cancer.
Prognosis
 The mean survival for patients with unresectable disease remains 4-6 months, with a 5year survival rate of less than 3%.
 The median survival for patients who undergo successful resection (only 20% of patients)
is approximately 12-19 months, with a 5-year survival rate of 15-20%. Although discouraging, these
results are still markedly better than those for patients with unresectable pancreatic carcinoma.
Medicolegal Pitfalls
 Pancreatic cancer in its early stages is a protean disease that can be difficult to distinguish
from other much more common disorders. Early diagnosis is therefore often a problem. Many
patients have sought care for symptoms for weeks to months before a definitive diagnosis of
pancreatic cancer is made.
 Failure to accurately stage patients preoperatively can also be a problem. Patients with
advanced disease should avoid fruitless attempts at resection. However, patients with potentially
resectable disease should be offered this option because complete resection is the only therapy for
pancreatic carcinoma associated with a significant improvement in survival.
 Adequate pain control should be provided for patients with unresectable disease.
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