The Impact on Clinical Practice of Endoscopic

Pierre-Edouard Queneau1, Guillaume Sauvé1, Stephane Koch1, Pascal Thibault3, Denis Cléau4,
Bruno Heyd2, Georges Mantion2, Pierre Carayon1
1Gastroenterology Unit and 2Digestive and Vascular Surgery Unit, University Hospital of Besançon.
Besançon Cedex. 3Gastroenterology Unit, General Hospital of Lons-le-Saunier. Lons-le-Saunier.
4Gastroenterology Unit, General Hospital of Vesoul. Vesoul, France
ABSTRACT
Context Endoscopic ultrasonography is
considered a highly accurate procedure for
diagnosing small pancreatic tumors and
assessing their locoregional extension.
Objective To evaluate the impact of
endoscopic
ultrasonography
on
the
management of pancreatic adenocarcinoma in
clinical practice.
Patients Sixty-four consecutive patients (mean
age 70.5±11.9 years) hospitalized for staging or
diagnosis of pancreatic adenocarcinoma were
retrospectively (from January 1995 to
November 1997) or prospectively studied (from
December 1997 to August 1999).
Setting Group 1 consisted of 52 patients with
pancreatic adenocarcinoma which was
discovered using computerized tomography
scanning and/or ultrasound. Endoscopic
ultrasonography was utilized for staging
purposes only in patients who were considered
to be operable and the tumor to be resectable
based on computerized tomography scanning
criteria. Group 2 consisted of 12 patients who
were diagnosed as having a pancreatic
adenocarcinoma
using
endoscopic
ultrasonography
whereas
computerized
tomography scanning and ultrasound was
negative.
Main outcome measures The impact of
endoscopic ultrasonography was analyzed on
the basis of the number of patients requiring
endoscopic ultrasonography as a staging
procedure (Group 1) and by evaluating the
performance of endoscopic ultrasonography in
determining resectability (Groups 1 and 2)
based on the surgical and anatomopathological
results.
Results Endoscopic ultrasonography was
performed in 20 out of 64 patients (31.3%):
8/52 in Group 1 (15.4%) and all 12 patients of
Group 2. Endoscopic ultrasonography correctly
assessed an absolute contraindication to
resection in 11 cases. Resection was confirmed
in 8 of the 9 cases selected by endoscopic
ultrasonography. The positive predictive value,
negative predictive value and overall accuracy
of endoscopic ultrasonography for determining
resection were 89%, 100%, and 95%,
respectively.
Conclusions The impact of endoscopic
ultrasonography seems especially relevant for
the detection of pancreatic tumors after

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99
negative computerized tomography scanning,
and for the prevention of unnecessary
laparotomies as complementary staging after
ultrasonography and computerized tomography
scanning.
INTRODUCTION
With a 0-5% survival at 5 years, the prognosis
of pancreatic adenocarcinoma (PA) remains
dim and is dramatically affected by a delayed
diagnosis and a low resection rate [1, 2]. The
situation has not significantly changed over the
past 20 years despite the improvement of
surgical procedures and the introduction of new
imaging techniques such as computerized
tomography scanning (CT-scan) [3].
Endoscopic ultrasonography (EUS) is
considered the most accurate imaging
procedure for the diagnosis of small tumors of
the pancreatic area [4] and is usually indicated
after ultrasonography (US) and CT-scan to
complete locoregional staging and to confirm
the resectability of PA [5, 6]. However, the role
and influence of EUS in decision-making has
not been clearly elucidated in clinical practice.
The aim of this study was to evaluate the
impact of EUS both as a diagnostic and as a
staging procedure in the management of a
consecutive series of patients with PA.
METHODS
From January 1995 to August 1999, 64
consecutive patients hospitalized in our unit for
PA were retrospectively (from January 1995 to
November 1997: n=37) and then prospectively
(from December 1997 to August 1999: n=27)
evaluated. Retrospectively, the study included
only patients in whom PA had been
demonstrated after surgical biopsy or fine-
needle aspiration. In the prospective part of the
study, the selection was based on the
association of a clinical course consistent with
pancreatic malignancy, elevation of CA19.9
greater than 300 U/mL and the presence of a
hypodense (spiral CT-scan) or hypoechoic (US-
EUS) heterogeneous, poorly delimited
pancreatic tumor where adenocarcinoma was
suspected in the absence of any history of
chronic pancreatitis [6, 7, 8, 9]. Thereafter, only
patients with histologically proven PA, as
defined above, were definitively included.
Patients with ampullary carcinoma or those
referred for palliative management of the PA
were excluded. No significant differences were
noted in clinical characteristics between the
retrospectively (n=37) and the prospectively
(n=27) studied cases (Table 1). Patients were
followed for a minimum of 6 months or until
death.
EUS was indicated in our unit either for staging
PA (Group 1) or for screening for pancreatic
tumors (Group 2). EUS was performed as a
complementary staging procedure (Group 1)
Table 1. Comparison of retrospectively and prospectively studied patients with pancreatic adenocarcinoma with regard to of
the different clinical parameters. No significant statistical difference was observed for the different parameters.
Retrospective
Prospective
P value
(n=37)
(n=27)
Age (mean±SD)
70.9 ± 12.0
69.9 ± 12.1
0.744
Gender
0.545
Males
22 (59.5%)
14 (51.9%)
Females
15 (40.5%)
13 (48.1%)
Tumor localization
0.118
Head
27 (73.0%)
24 (88.9%)
Other
10 (27.0%)
3 (11.1%)
Resection rate
3 (8.6%)
5 (18.5%)
0.247
Median survival time (months)
2.5
2.5
-
1-year survival (%)
7.1
4.6
0.930

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100
only in operable patients and in the case of a
resectable tumor as defined by US-color
Doppler and enhanced spiral CT-scan
examinations [10]. EUS was performed as a
screening procedure for pancreatic tumors
(Group 2) in all patients with symptoms
compatible with a pancreatic tumor, after US
and spiral CT-scan examinations were
interpreted as normal.
All EUS procedures (Olympus EUM 20) were
performed under general anesthesia
(midazolam, propofol) by the same operator.
During examination, the following items were
carefully described: location and size of the
tumor, invasion of locoregional organs and
vascular axis, existence and location of lymph
nodes suspected to be malignant, existence of
left liver metastasis and signs of peritoneal
carcinomatosis, based on recognized criteria [6,
11].
Surgical resection was judged inappropriate in
the case of visceral metastasis, distant lymph
node metastasis, arterial involvement (celiac
trunk, common hepatic artery, superior
mesenteric artery and splenic artery) or visible
neoplastic thrombus of the venous axis (portal
vein, superior mesenteric vein, splenic vein).
Suspicion of parietal invasion of the venous
axis constituted a relative contraindication to
resection and was discussed with the surgeon.
We analyzed the number of tumors which were
considered unresectable according to EUS
criteria and which were then confirmed at
laparotomy. These cases were defined as
potentially unnecessary laparotomies (i.e.
laparotomies that could have been avoided)
except in the situation of duodenal involvement
in which palliative surgery was indicated.
Definitive staging of the tumor was assessed
histologically (curative resection), cytologically
(US-guided needle biopsy of a liver metastasis
or peritoneal carcinomatosis) or operatively
(palliative surgery) according to the AJCC 1997
classification (Table 2) [12]. Resection was
considered complete when tumor margins were
free of neoplasia and no lymphatic or
perivenous
invasion
was
visualized
histologically.
The impact of EUS on the management of PA
was determined by the following criteria: the
percentage of all patients with PA requiring
EUS, the percentage of patients with PA
requiring EUS as a staging procedure, the
number of tumors diagnosed by EUS only and
the number of unnecessary laparotomies.
Furthermore, a possible benefit of EUS in
diagnosing small tumors was evaluated by
comparing the proportion of curative resections
and number of survivors in Group 2 to Group 1
patients.
ETHICS
Data were collected by the usual methods used
in clinical practice.
Table 2. UICC-TNM classification of pancreatic adenocarcinoma.
T1
Tumor limited to the pancreas, less than or equal to 2 cm at its maximum diameter
T2
Tumor limited to the pancreas, greater than 2 cm at its maximum diameter
T3
Tumor extending directly into the duodenum, bile duct, or peripancreatic tissue
T4
Tumor extending directly into the stomach, spleen, colon or adjacent large blood vessels
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
M0
No distant metastasis
M1
Distant metastasis-hepatic metastasis or peritoneal dissemination
Stage I
T1-2
N0
M0
Stage II
T3
N0
M0
Stage III
T1-3
N1
M0
Stage IVA
T4
N0-1
M0
Stage IVB
T1-4
N0-1
M1

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101
STATISTICAL ANALYSIS
Data are reported as mean±SD. Survival
analysis was performed by the Kaplan-Meier
method and the groups were compared using
the log-rank test. The chi-squared and the
Student’s t-tests were applied to compare
proportions and age, respectively. Two-tailed P
values less than 0.05 were considered
significant. Statistical analysis was performed
by means of the SPSS/PC+ statistical package.
RESULTS
Patients
During the study period, PA was diagnosed in
sixty-four patients (mean age 70.5±11.9 years;
36 men and 28 women). The tumor was located
in the pancreatic head in 51 cases (79.7%), in
the body in 6 patients (9.4%) and in the tail in 7
patients (10.9%). PA was diagnosed by US or
CT-scan in 52 cases (Group 1, 81.3%), and by
EUS alone in 12 cases (Group 2, 18.8%). Eight
patients (12.5%) underwent curative surgery.
The median survival time and the one-year
survival rate in all patients were 2.5 months and
6%, respectively.
Endoscopic ultrasonography
EUS was indicated in 30 cases (46.9%), but
was carried out in only 20 cases (31.3%) due to
the poor general condition of the patient (n=8,
Group 1), patient refusal (n=1, Group 1), or
duodenal stenosis (n=1, Group 1).
The 20 EUSs were performed in 8 out of the 52
patients of Group 1 (15.4%) and in all 12
patients of Group 2.
Figure 1 shows the management of the 52
Group 1 patients and the number of EUS
carried out as a staging procedure. After US
and CT-scan, the tumors were classified as
follows: stage I (none), stage II (n=16, 30.8%),
stage III (n=3, 5.8%), stage IVA (n=10, 19.2%),
and stage IVB (n=23, 44.2%). The 8 EUS
examinations (15.4% of Group 1 cases) were
performed in 5 patients with stage II tumors and
3 patients with stage III tumors on initial
US/CT-scan. Celiac involvement was
visualized by EUS in the 3 tumors initially
classified as stage III and in 1 tumor initially
classified as stage II (n=4, 7.7% of Group 1
patients, and 50.0% of EUS performed in this
group), and this was confirmed upon surgical
exploration thus determining the non-
resectability of the tumor. EUS confirmed the
staging of the 4 remaining cases (stage II).
Resection was considered feasible in these 4
patients and this was confirmed at laparotomy
and anatomopathology.
Figure 2 shows the management of the 12
patients with PA diagnosed only by EUS
(Group 2). The procedures were motivated by
the following circumstances: unexplained
abdominal pain (n=2, 16.7%), acute pancreatitis
of unknown origin (n=1, 8.3%), unexplained
Figure 1. Management of patients with pancreatic
adenocarcinoma in Group 1 (tumor visualized on US and
CT-scan).
Figure 2. Management of patients with pancreatic
adenocarcinoma in Group 2 (tumor diagnosed by EUS
only).

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102
jaundice (n=5, 41.7%), increasing pain or
deterioration of general status in patients with
known chronic pancreatitis (n=4, 33.3%). In
these 12 patients, the tumor size on EUS was
2.3±0.8 cm and tumor staging was the
following: 4 EUS stage II, 1 EUS stage III, 4
EUS stage IVA, and 3 EUS stage IVB tumors
(signs of peritoneal carcinomatosis: n=3; left
liver metastasis not visualized at US or with
CT-scan: n=1). At laparotomy, 4 patients were
found to be resectable (33.3% of the patients in
Group 2; 3 EUS stage II and the EUS stage III
tumors) and this was confirmed histologically.
Seven patients were found to be unresectable
(the 4 EUS stage IVA at laparotomy and the 3
EUS stage IVB after US-guided cytology). The
last patient (EUS stage II tumor) died of
myocardial infarction before laparotomy, but
was finally classified as stage IVB at autopsy
(liver metastasis).
On the whole, EUS correctly assessed an
absolute contraindication to resection in 11
cases (17.2% of all patients, 55.0% of all EUS
examinations), 4 cases in Group 1 and 7 cases
in Group 2. Resectability was confirmed in 8 of
the 9 cases selected by EUS. The sensitivity,
specificity, positive predictive value, negative
predictive value, and overall accuracy of EUS
in determining resection were 88.9%, 100%,
100%, 91.7%, and 95.0%, respectively. PA
management could have been modified by EUS
in 16 patients (25.0% of all patients, 80.0% of
all endoscopic ultrasonography examinations).
The proportion of resectable tumors was
significantly higher (P=0.015) in Group 2 (i.e.,
diagnosed only by EUS: 4/12, 33.3%) than in
Group 1 (i.e., diagnosed by US or CT-scan:
4/52, 7.7 %). In this subgroup of patients, the
one-year survival was superior to that of other
patients, although not reaching statistical
significance (18.1% versus 2.7 %, P=0.17).
DISCUSSION
This study is one of the attempts to evaluate the
impact of EUS on clinical practice in the
management of a homogeneous series of
patients with PA [13, 14, 15]. According to our
criteria, EUS was indicated in nearly half of the
patients either for staging or for making the
diagnosis, and it was eventually performed in
about one-third of the patients. Overall, EUS
influenced decision-making in 80% of these
selected cases. In our study, the impact of EUS
on the management was therefore much higher
than the 26% to 45% found by other authors in
their series [15]. The discrepancy between these
results may be explained by the differences in
the criteria applied for performing EUS. The
study by Nickl et al. [15] pools data from
several centers, where indications for EUS and
PA management may be heterogeneous.
Furthermore, criteria for pancreatic neoplasia
and for confirming EUS results are not clearly
defined. Finally, EUS was only indicated as a
complementary examination after initial US
and CT-scan, which excluded all PAs
diagnosed only by EUS. In our study, we
selected only patients with histologically or
cytologically confirmed PA, including patients
with pancreatic tumors diagnosed only by EUS
and we restricted the use of EUS as a staging
procedure only to those patients having tumors
considered to be resectable after CT-scan
criteria. We therefore believe that the selection
process of our patients more precisely reflects
the clinical reality.
In our study, the major impact of EUS lies in
the detection of pancreatic tumors (more than
50% of all EUS procedures). In fact, EUS is
considered the most sensitive technique for
diagnosing pancreatic tumors, permitting the
detection of tumors smaller than 1 cm [4, 6].
The resection rate (50%) is significantly higher
in patients with PA diagnosed only by EUS as
compared to other patients. The absence of
significant improvement in one-year survival
was probably due to the insufficient number of
patients in our study. However, patients with
non-invasive tumors at presentation represent
only a small minority of all PAs and their life
expectancy remains poor despite favorable
management conditions [16]. An accurate
determination of patients at risk for PA is the
first step in improving early screening by EUS
[17].

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Unlike earlier series [13], our study confirms
that, since the development of spiral CT-scan,
the role of radial EUS as a staging technique of
PA is relatively limited. Recent studies report a
90% prediction of non-resectability by US and
spiral CT-scan used as first intention techniques
[18, 19, 20]. Since locally advanced or
metastatic disease constitutes nearly 80% of
PAs, EUS as a second intention staging
procedure is subsequently indicated in a
minority of patients. However, the impact of
EUS is evident in these highly selected patients
as reflected by the detection of local invasion
and non-resectability criteria in 50 % of cases
deemed resectable by CT-scan. The use of EUS
in the staging of PA could benefit from the
development of EUS-guided fine-needle biopsy
which enhances the diagnostic value of lymph
node staging from 60% (without fine-needle
biopsy) to more than 85% [21, 22].
Our study demonstrates that EUS is performed
in about one-third of all patients with PA in our
clinical practice. Its impact lies essentially in
the detection of pancreatic tumors. As a staging
procedure, EUS may help to prevent
unnecessary laparotomies, but its influence is
limited by the usual invasive presentation of the
disease at diagnosis. These results are likely to
be modified by the development of EUS-guided
fine-needle aspiration which allows tumor
staging and histological confirmation of the
cancer during the same examination. This
procedure appears particularly attractive in neo-
adjuvant therapy since it limits the risk of tumor
dissemination, as seen by means of US- or CT-
scan-guided cytology and restricts the use of
surgical biopsies [21, 22, 23].
Received February 19th, 2001 – Accepted
March 5th, 2001
Key words Carcinoma, Pancreatic Ductal;
Disease Management; Laparotomy, Neoplasm
Staging, Surgical Procedures, Operative
Abbreviations
CT-scan: Computerized
Tomography Scanning; EUS: Endoscopic
Ultrasonography;
PA:
pancreatic
adenocarcinoma; US: Ultrasonography
Correspondence
Pierre-Edouard Queneau
Division of Gastroenterology
Hôpital Cantonal
Rue Micheli-du-Crest 24
1211 Genève 14
Switzerland
Phone: +41-22-372.9340
Fax: +41-22-372.9366
E-mail: pierre-edouard.queneau@huge.ch
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