The American Journal of Surgery 194 (Suppl to October 2007) S87S90

Endoscopic ultrasound and early diagnosis of pancreatic cancer

Lars Helmstaedter, M.D., Juergen Ferdinand Riemann, M.D.*
Department of Medicine C, Klinikum Ludwigshafen, Academic Hospital of the Johannes Gutenberg-University of Mainz, Medical Department C,
Klinikum Ludwigshafen gGmbH, Bremserstrasse 79, D-67063 Ludwigshafen, Germany

Abstract
Incidence of pancreatic cancer has increased, but prognosis remains poor. Curative treatment is
dependent on early diagnosis. Endoscopic ultrasound (EUS) has been described as highly sensitive and
accurate in staging, superior to other imaging modalities in early publications. With rapid advances in
technology, other imaging techniques have reached better results. EUS still has the highest accuracy in
assessing tumor size and lymph node involvement. For assessment of tumor respectability, a combination
of a computed tomography (CT) scan and EUS seems to be the procedure with the highest accuracy.
Promising new techniques might improve the diagnostic yield of EUS. But there are several reasons for
failure, and EUS shows a high interobserver variety. Nevertheless, EUS proved to have a high negative
predictive value. Screening for pancreatic cancer and its precursor lesions in the general population is not
feasible, but high-risk subpopulations could be suitable targets for screening, preferably with an EUS- and
CT-based protocol. 2007 Excerpta Medica Inc. All rights reserved.
Keywords: Pancreatic cancer; Early detection; Endoscopic ultrasound

The incidence of pancreatic cancer has increased continuously over the last decades. Despite rapid improvements in
imaging technologies and therapeutic modalities, the prognosis remains poor. The overall 5-year relative survival rate
for 1996 to 2002 is estimated at 5.0% [1]. If data are
critically reviewed, it seems to be even less. CarpelanHolmstrm et al [2] found a 5-year survival rate for pancreatic ductal adenocarcinoma of 0.2%. At the time of
diagnosis, only 7% of pancreatic cancers are found to be
localized to the organ without locoregional spreading or
distant metastases (American Joint Committee on Cancer
stage I) and therefore resectable in a curative intention.
Even if they are found to be in stage I, the prognosis remains
poor with a 5-year survival rate of 19.6% [1]. These data
underline the importance of early diagnosis of pancreatic
cancer, but pain, jaundice, weight loss, and obstruction
usually are late symptoms.
Endoscopic Ultrasound
One of the most promising imaging techniques to detect
early pancreatic cancers is endoscopic ultrasound (EUS).
This method is able to detect focal lesions as small as 2 to
3 mm with the possibility to get tissue samples by fineneedle aspiration (FNA) or true-cut needle biopsy for his* Corresponding author. Tel.: 49-0621-503-4100; fax: 49-0621503-4114.
E-mail address: ToddMc@baylorhealth.edu

topathological examination. At present, there are 3 fundamental different techniques of EUS available: (1)
electronic or mechanical radial scanning scopes, in which
the electronic scanning scopes seem to produce better
B-mode image quality with no apparent difference in
maneuverability, endurance, and endoscopic images [3];
(2) linear scanning scopes; and (3) radial or linear scanning probes for use with standard scopes or alone. Frequencies range from 5 to 20 MHz for scopes up to 30
MHz for probes. The accuracy in staging of pancreatic
cancer is equivalent for radial and linear scanners [4], in
which radial scanners offer a better overview of surrounding structures (Fig. 1), whereas linear scanners allow the safe execution of tissue sampling. In relation to
pancreatic cancer, indications for EUS are persistent epigastric and/or back pain, acute onset of diabetes in the
elderly, unclarified weight loss, and suspect results in
ultrasonography, especially in individuals over 45 years
of age and in high-risk individuals (eg, persons with a
strong family history of pancreatic cancers, with PeutzJeghers syndrome, or multiple endocrine neoplasia). EUS
is a highly sensitive method, but results for accuracy
differ. Whereas initial studies showed excellent accuracy,
results in later publications declined (Table 1 [511]). If
tissue diagnosis is necessary before therapy, EUS-guided
FNA should be the method of choice. EUS-FNA is highly
sensitive (84%), specific (97%), and accurate (84%) and
has a high positive predictive value (99%) with rare

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doi:10.1016/j.amjsurg.2007.05.009

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L. Helmstaedter and J.F. Riemann / The American Journal of Surgery 194 (Suppl to October 2007) S87S90

single technique. With regard to cost minimization, the

combination of CT and EUS seems to increase the price
compared with each single method. However, if the cost of
unnecessary explorative laparotomies were taken into account, the cost minimization analysis favored a sequential
strategy in which EUS was used as a confirmatory technique
in those patients in whom helical CT suggested resectability
of the tumor [11].

Fig. 1. Endoscopic ultrasound of an adenocarcinoma in the pancreatic head

with a maximum diameter of 4.2 cm.
Table 1
Results for accuracy of EUS in literature
Accuracy (%)
Legmann et al [6], AJR Am J Roentgenol 1998
Akahoshi et al [7], Br J Radiol 1998
Cannon et al [8], Gastrointest Endosc 1999
Ahmad et al [9], Gastrointest Endosc 2000
Meining et al [10], Gut 2002
Soriano et al [11], Am J Gastroenterol 2004

93
94
78
69
72
63

major complications but with a low negative predictive

value of only 64% [12]. If pancreatic cancer is suspected
and if EUS-FNA is negative, cancer cannot be excluded
and operation will be the next step despite positive or
negative FNA.
Comparing EUS
As mentioned earlier, early studies showed high sensitivity and accuracy for EUS. In most studies, EUS was
superior or at least equal to other imaging modalities regarding sensitivity, determining tumor size and extent,
lymph node involvement and vascular infiltration [6,13].
With rapid advances in technology, first of all, computed
tomography (CT) and magnetic resonance imaging (MRI)
have reached better results. Compared with helical CT, MRI
(Fig. 2), and angiography in a prospective study with histopathological or surgical confirmation of results, helical
CT had the highest accuracy in assessing extend of primary
tumor, locoregional extension, vascular invasion, distant
metastasis, tumor TNM stage and tumor resectability,
whereas EUS reached the highest accuracy in assessing
tumor size and lymph node involvement. To predict tumor
resectability, the combination of CT and EUS proved to be
the method with the highest accuracy compared with each

Improving EUS
One of the major problems in diagnosing pancreatic
cancer is the discrimination between focal pancreatitis and
pancreatic cancer. A promising technique seems to be the
contrast-enhanced EUS using perfusion characteristics to
differentiate between focal inflammation and pancreatic
carcinoma. The sensitivity and specificity of conventional EUS were 73.2% and 83.3% for pancreatic carcinoma, increasing to 91.1% and 93.3% with the contrastenhanced power mode [14].
Another major problem for EUS is the assessment of
vascular invasion. Sensitivity and specificity of EUS are
63% and 64% for vascular adherence and 50% and 58% for
vascular invasion [15]. In a pilot study of 22 patients, the
additional 3-dimensional reconstructions appeared to improve the evaluation of vesseltumor relationships, but the
acquisition system needs to be improved [16]. These promising new techniques to improve EUS may enrich the armamentarium for staging pancreatic cancer correctly, but
they need to be evaluated in further studies.
Reasons for failure
EUS is not a foolproof method for detecting pancreatic
neoplasm. It has a high interobserver variety even among
experienced endosonographers [17,18]. In addition, accuracy of EUS seems to be dependent on further clinical and
imaging information [10]. Chronic pancreatitis, diffusely
infiltrating carcinoma, a prominent ventral/ dorsal split, and
a recent episode of acute pancreatitis are also possible
associated factors that may increase the likelihood of a
false-negative EUS examination [19].
Negative predictive value
Normal EUS examination findings seem to have a high
negative predictive value (NPV). In 2 studies with 76 and
135 patients and a mean follow-up period of 23.9 and 25
months, respectively, none of the patients with clinically
indeterminate suspicion of pancreatic cancer and a normal
EUS developed pancreatic cancer [20,21], which means an
NPV of 100%. In contrast, Soriano et al [11] found an NPV
for locoregional extension, lymph node involvement, and
vascular invasion of merely 44%, 65%, and 74% confirmed
by intraoperative or histopathological findings.
Screening for pancreatic cancer
Pancreatic cancer is a disease with a poor overall 5-year
survival rate of 5% [1]. There are reports of a 4-year survival rate of 78% in resected stage 1 ductal adenocarcinomas of the pancreas 2 cm in size, in which 42% were not
associated with symptoms [22]. These data suggest that
screening and early detection of pancreatic neoplasia might

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improve the dismal outcome of pancreatic cancer. There are

morphologically well-defined noninvasive precursor lesions
for invasive pancreatic cancer, including pancreatic intraductal neoplasia and intraductal papillary mucinous neoplasms (IPMNs). The treatment of these precursor lesions
might prevent their progression to invasive cancer, as it is
well experienced in other organs. Because of the low incidence of pancreatic cancer and the lack of accurate, inexpensive, and noninvasive diagnostic tests for early disease,
screening for pancreatic cancer and its precursor lesions in
the entire population is not reasonable. But there are some
known high-risk subpopulations, such as members of families with a strong history of pancreatic cancer or with
hereditary pancreatitis and with distinct hereditary cancer
syndromes, such as Peutz-Jeghers syndrome, hereditary
breast or ovarian cancer syndrome, familial atypical multiple mole melanoma syndrome, and hereditary nonpolyposis
colorectal cancer. Canto et al [23] screened for early pancreatic neoplasia with an EUS-based and an EUS- and
CT-based [24] protocol. In the latter, pancreatic abnormalities were compared in high-risk individuals and control
subjects. The EUS- and CT-based approach found 8 patients
among 78 high-risk individuals with pancreatic neoplasms
confirmed by surgery or FNA (6 patients with 8 benign
IPMNs, 1 patient with an IPMN with progression to invasive ductal adenocarcinoma, and 1 patient with pancreatic
intraepithelial neoplasia) and no pancreatic neoplasia
among 149 control subjects. Abnormalities suggestive of
chronic pancreatitis were more common in high-risk individuals.
Conclusions
The incidence of pancreatic cancer has increased over the
last decades. Despite rapid improvements in imaging techniques and therapeutic modalities, prognosis remains poor.
One of the most promising techniques for early diagnosis
seemed to be endoscopic ultrasound. EUS with or without
fine-needle aspiration has a high sensitivity, whereas accuracy in TNM staging differs. Optimistic results in early
studies yielded to a more critical view. Compared with CT
scan, MRI, and angiography, EUS showed the highest accuracy in assessing tumor size and lymph node involvement, whereas helical CT had the highest accuracy in assessing extend of primary tumor, locoregional extension,
vascular invasion, distant metastasis, tumor TNM stage, and
tumor resectability. The evaluation of tumor resectability
should be done by a minimum of 2 imaging techniques, in
which the combination of CT scan and EUS proved to be
the method with highest accuracy at lowest cost or if needed
intraoperatively. A detection of distand metastases with
EUS is not possible. A normal EUS examination excludes a
pancreatic tumor with a high probability. The quality of
EUS shows a high interobserver variance; additional reasons for failure are a chronic or recent episode of acute
pancreatitis, diffusely infiltrating carcinoma, and a prominent ventral/ dorsal split. New techniques such as contrastenhanced EUS or additional 3-dimensional reconstructions
look promising for improving EUS. Screening for pancreatic cancer or its noninvasive precursor lesions in the general population is not feasible because of its low incidence,

Fig. 2. (A) Endoscopic ultrasound of a carcinoma in the pancreatic head

and (B) corresponding MRI.

but high-risk subpopulations, such as families with a strong

history of pancreatic cancer, hereditary cancer syndromes,
or pancreatitis, seem to be suitable targets for screening
programs.
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