Screening Tests for Pancreatic Cancer

Raffaele Pezzilli
Department of Internal Medicine, Sant'Orsola-Malpighi Hospital. Bologna, Italy
In the past four decades, the incidence of
pancreatic cancer has increased steadily in
most of the world and now this type of tumor
ranks as the fifth or sixth most frequent cause
of death due to cancer in many western
countries [1]. For example, in 2000,
worldwide figures for pancreatic cancer were
projected at 216,400 new cases and 213,500
deaths [2]; the data coming from the United
States in 2004, estimated that 31,860 patients
would be diagnosed with pancreatic cancer
and 31,270 would die of the disease [3]. The
5-year survival rate estimated by the
Surveillance Epidemiology and End Results
program is 4% and this figure is the lowest for
all types of cancer [4]. Late diagnosis and the
subsequently low resection rate is the major
reason for the poor survival of these patients.
Despite technological advances, the diagnosis
of pancreatic cancer continues to be made
very late and the prognosis remains extremely
poor. This delay in diagnosis is, for the most
part, due to the fact that abdominal pain and
jaundice, which are the main symptoms of
pancreatic cancer, appear late when the tumor
is already in an advanced stage [5]. Moreover,
if we consider that the many epidemiological
studies performed so far have failed to
identify significant risk factors for pancreatic
cancer which might facilitate its early
diagnosis or prevention [6], the resulting
picture is extremely poor.
At present, the only source of hope of
reaching a more rapid diagnosis of this type
of cancer would seem to come from the
clinical history and, in particular, from the
presence of earlier symptoms which could
induce patients to seek medical advice at a
time when the tumor might be smaller and
treatment more feasible. Surprisingly, despite
the large number of studies on pancreatic
cancer, very little is known on this topic.
Early studies reported the existence of early
symptoms such as sudden onset of diabetes
mellitus, weight loss tiredness and malaise,
change in bowel habits, and upper abdominal
discomfort of pancreatic cancer; however,
either the time of onset [7] or the symptoms
themselves [8] were not specified.
Three years ago, a study carried-out in Italy
involving a large series of patients with
pancreatic cancer was published. Its objective
was to investigate whether symptoms exist
before the pain and/or jaundice that could
suggest the possibility of pancreatic cancer
and thus help earlier recognition of the tumor
[9]. The authors found that of the 305
pancreatic cancer patients, 49.5% had some
disturbances shortly before diagnosis, 35.4%
had problems 6 months or less before
diagnosis (pain or jaundice) and 14.1% had
problems more than 6 months before
diagnosis. Among the latter, 14 (4.6% of all
patients) had had anorexia and/or early satiety
and/or asthenia (7-20 months before pain or
jaundice), 11 (3.6%) had disgust for coffee
and/or smoking and/or wine (7-20 months
before), 14 (4.6%) had diabetes (7-24 months
before), and four (1.3%) had acute
pancreatitis (8-26 months before). Among the

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241
controls, the only reports of these symptoms
were two (0.7%) cases of asthenia (4 and 6
years earlier), 22 (7.2%) cases of diabetes (of
which only two were diagnosed 7-24 months
before the interview), and one (0.33%) case of
acute pancreatitis (10 years earlier). Apart
from acute pancreatitis, all the differences
between patients and controls were
statistically significant. In approximately 15%
of the patients, disturbances which, although
not specific, could have raised suspicion of
the possibility of pancreatic cancer had
existed for more than 6 months before pain or
jaundice. However, in this study, no
information on the so-called early symptoms
and the possible survival rate was reported.
A possible aid is that of the study coming
from the U.S. [10]. In this population-based
study, data coming from 120 consecutive
patients with pancreatic cancer and control
participants of the San Francisco Bay Area
enrolled between 1994 and 2001 were
collected and analyzed.
Patients with pancreatic cancer 21-85 years of
age were identified by the Northern California
Cancer Center’s rapid case ascertainment
within 1 month of diagnosis in hospitals in 6
Bay Area counties. To confirm diagnoses, the
Surveillance Epidemiology and End Results
abstracts were obtained from the Northern
California Cancer Center which identified all
pancreatic cancer cases in the Bay Area about
18 to 24 months after diagnosis.
Control participants were identified by using
random digit dial and Health Care Financing
Administration files to supplement the
recruitment of those equal to or greater than
65 years of age. All control participants were
matched to patients with pancreatic cancer
according to sex and age within 5 years.
In addition to interviews administered in
person, a questionnaire was designed to
collect clinical data pertaining to the 5 years
before diagnosis or interview. It included
signs and symptoms of pancreatic cancer
previously reported in the literature, and the
diagnostic tests and procedures conducted in
order to evaluate the cause of the reported
symptoms. The rule used to set the symptom-
specific minimum duration for controls was
one half the median duration reported by
patients for each symptom, except for fatigue
and altered sleep.
The clinical questionnaire was carried out as a
telephone interview to 180 age- and sex-
matched
population-based
control
participants. Most signs and symptoms
occurred within 3 years before diagnosis with
pancreatic cancer in the cases and interview in
the controls; many signs and symptoms were
more likely to have been reported by patients
as compared to control participants and
included appetite loss, pale stools, abdominal
pain, jaundice, unusual bloating, unusual
belching, weight loss, dark urine,
constipation, diarrhea, itching, fatigue, altered
ability to sleep, and unusual heartburn.
As expected, the tumor extent was
significantly associated with symptoms of bile
duct obstruction and abdominal pain, and
surgical resection was associated with
symptoms of bile duct obstruction, abdominal
pain, and unusual bloating. In hierarchical
modeling which used factors identified in the
initial analyses of symptoms taken singly, the
model that best differentiated resected tumors
from non-resected tumors based on the model
score chi-square statistic included tumor
extent, jaundice, and dark urine.
Diabetes mellitus was diagnosed in 18 of 120
patients with pancreatic cancer (15%); in 4 of
these patients (3%), diabetes was diagnosed
within the 3 years before their pancreatic
cancer diagnosis. Of the 4 patients with recent
diabetes, 1 patient had a tumor confined to the
pancreas, 2 patients had tumors with regional
spread, and 1 patient had a tumor with distant
metastasis; none of these 4 patients had
undergone surgical resection, thus confirming
the results of a previous Italian study [11].
This study further confirm that pancreatic
cancer is typically diagnosed at a relatively
advanced stage. Most patients are diagnosed
when
pancreatic
cancer
becomes
symptomatic; abdominal pain and jaundice as
primary symptoms often appear late when the
tumor is advanced; some of the common
presenting symptoms such as dyspepsia and

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242
weight loss have an insidious onset and are
easily mistaken for other diseases or
functional disorders.
A prompt diagnosis of pancreatic cancer
comes from a careful clinical history and
appropriate tests and our hope is that, in the
near future, we will able to identify a larger
risk population than that known at present,
such as members of families with a history of
pancreatic cancer, as well as those of families
with distinct hereditary cancer syndromes
such as Peutz-Jeghers syndrome, hereditary
pancreatitis, familial atypical multiple mole
melanoma syndrome, hereditary breast and
ovarian cancer syndrome and hereditary non-
polyposis colorectal cancer.
The identification of germline mutations in
genes predisposing to pancreatic cancer,
together with the analysis of exogenous risk
factors, could be used for a more precise risk
assessment for the development of this
neoplasm. This may allow the application of
non-invasive or invasive screening methods
for the identification of early pancreatic
cancer or, even better, its precursor lesions in
high-risk individuals, providing the option of
timely curative pancreatectomy.
Keywords Diabetes Mellitus; Diagnostic
Tests, Routine; Genetic Screening; Pancreatic
Neoplasms; Pathology, Clinical
Correspondence
Raffaele Pezzilli
Dipartimento di Medicina Interna
Ospedale Sant'Orsola-Malpighi
Via G. Massarenti, 9
40138 Bologna
Italy
Phone: +39-051.636.4148
Fax: +39-051.549.653
E-mail: pezzilli@orsola-malpighi.med.unibo.it
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