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American Journal of Gastroenterology ISSN 0002-9270
C 2007 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2007.01333.x
Published by Blackwell Publishing
Comparison of Endoscopic Ultrasonography and Magnetic
Resonance Cholangiopancreatography in the Diagnosis of
Pancreatobiliary Diseases: A Prospective Study
Gl`oria Fern´andez-Esparrach, M.D., Ph.D.,1 `Angels Gin`es, M.D., Ph.D.,1
Marcelo S´anchez, M.D.,2
Mario Pag´es, M.D.,2
Maria Pellis´e, M.D., Ph.D.,1
Laureano Fern´andez-Cruz, M.D., Ph.D.,3
Miguel Angel L´opez-Boado, M.D.,3
Lloren¸c Quint´o, B.Sc, M.P.H.,4
Salvador Navarro, M.D., Ph.D.,1
Oriol Sendino, M.D.,1
Andr´es C´ardenas, M.D.,1
Carmen Ayuso, M.D., Ph.D.,2
Josep M. Bordas, M.D., Ph.D.,1
Josep Llach, M.D., Ph.D.,1
and Antoni Castells, M.D., Ph.D.1
1
Gastroenterology Department, Institut de Malalties Digestives i Metab`oliques, CIBER HEPAD; 2
Radiology
Unit (CCDI); 3
Surgery Department; and 4
Unitat d’Avaluaci´o, Suport i Prevenci´o (UAPS), Hospital Cl´ınic,
University of Barcelona, Barcelona, Spain
OBJECTIVES: To compare the diagnostic value of endoscopic ultrasonography (EUS) and magnetic resonance
cholangiopancreatography (MRCP) in: (a) patients with a dilated biliary tree unexplained by
ultrasonography (US) (group 1), and (b) the diagnosis of choledocholithiasis in patients with
nondilated biliary tree (group 2).
METHODS: Patients were prospectively evaluated with EUS and MRCP. The gold standard used was surgery or
EUS-FNA and ERCP, intraoperative cholangiography, or follow-up when EUS and/or MRCP disclosed
or precluded malignancy, respectively. Likelihood ratios (LR) and pretest and post-test probabilities
for the diagnosis of malignancy and choledocholithiasis were calculated.
RESULTS: A total of 159 patients met one of the inclusion criteria but 24 of them were excluded for different
reasons. Thus, 135 patients constitute the study population. The most frequent diagnosis was
choledocholithiasis (49% in group 1 and 42% in group 2, P = 0.380) and malignancy was more
frequent in group 1 (35% vs 7%, respectively, P < 0.001). When EUS and MRCP diagnosed
malignancy, its prevalence in our series (35%) increased up to 98% and 96%, respectively, whereas
it decreased to 0% and 2.6% when EUS and MRCP precluded this diagnosis. In patients in group 2,
when EUS and MRCP made a positive diagnosis of choledocholithiasis, its prevalence (42%)
increased up to 78% and 92%, respectively, whereas it decreased to 6% and 9% when any
pathologic finding was ruled out.
CONCLUSIONS: EUS and MRCP are extremely useful in diagnosing or excluding malignancy and choledocholithiasis
in patients with dilated and nondilated biliary tree. Therefore, they are critical in the approach to the
management of these patients.
(Am J Gastroenterol 2007;102:1632–1639)
INTRODUCTION
The diagnosis of pancreatobiliary diseases is a common prob-
lem in clinical practice. It is known that ultrasonography (US)
is not accurate enough in the diagnosis of the etiology of bil-
iar obstruction due to the presence of air preventing a cor-
rect ultrasound transmission (1–3). On the other hand, the
presence of stones in the main bile duct may be difficult
to demonstrate particularly when the biliary tree is not di-
lated (4). Endoscopic retrograde cholangiopancreatography
(ERCP), that has been classically performed to study pan-
creatobiliary diseases, is associated with a significant risk of
serious complications such as pancreatitis, hemorrhage, per-
foration, cholangitis, and even death (5). Therefore, an effort
to safely and accurately image the pancreatobiliary area has
been made in the last few decades.
Endoscopic ultrasonography (EUS) and magnetic reso-
nance cholangiopancreatography (MRCP) have emerged as
two low-risk diagnostic techniques with good performance
for the diagnosis of biliopancreatic diseases (6–18). Although
both techniques have already been compared in this setting,
the studies published up to now have small sample sizes and
include heterogeneous populations, so it is not possible to ob-
tain from them conclusions definitive enough to be applied
in clinical practice (19–23). There are two common situa-
tions in patients with pancreatobiliary diseases that have not
1632
Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1633
been specifically studied, and so the dilemma of choosing
the most accurate technique frequently arises: common bile
duct dilation with no visible cause on US and suspicion of
choledocholithiasis in patients with nondilated biliary tree.
Therefore, the aims of the present study were to prospec-
tively and blindly compare the diagnostic value of EUS and
MRCP in: (a) the etiologic diagnosis of patients with a di-
lated biliary tree unexplained by US and (b) the diagnosis of
choledocholithiasis in patients with nondilated biliary tree.
PATIENTS AND METHODS
This prospective study was conducted following the STARD
statement for reporting studies of diagnostic accuracy (24). It
was approved by the institutional review board of the Hospital
Cl´ınic,Barcelona,andwritteninformedconsentwasobtained
from all patients.
Study Population
ThestudywasperformedbetweenMarch2001andJuly2004.
To avoid selection bias, all consecutive patients evaluated in
the departments of gastroenterology and surgery were asked
to participate in this prospective investigation if they met one
of the following inclusion criteria: (a) unexplained common
bile duct dilation in standard US, independently of clinical
symptoms (group 1) and (b) a nondilated common bile duct
and a high probability of having choledocholithiasis (cholan-
gitis, jaundice, nonsevere pancreatitis, alkaline phosphatase
[ALP] < twice the upper normal limit [UNL] or increased
gamma glutamyl trasferase [GGT], alanine aminotransferase
[ALT]oraspartateaminotransferase[AST])(3,25)(group2).
Although the indication of EUS and MRCP prior to ERCP in
this latter group could be discussed, we chose these patients
in order to obtain a high prevalence of choledocolithiasis
for our study purposes. For ethical reasons, patients with se-
vere pancreatitis were not included since an early ERCP with
sphincterotomy is indicated.
Exclusion criteria were (a) contraindications to MRCP
(claustrophobia, pacemaker, or any prosthesis contraindicat-
ing MR), (b) predictable impossibility to perform a complete
exploration of the pancreatobiliary area by EUS (i.e., gas-
troenteroanastomosis or stenosis), and (c) refusal or inability
to provide informed consent.
METHODS
EUS and MRCP were performed within a 24-h period after
inclusion in order to minimize the chances of a negative study
due to stone passage, and the sequence of the examinations
wasrandomlyassigned.Toensureblinding,eachexamination
was performed by a different operator unaware of the result
of the other procedure.
The diameter of common bile duct and the site and cause
(stones, tumor, or other) of the obstruction were systemat-
ically investigated. The common bile duct was considered
normal in absence of thickened wall and when the maximum
diameter was less than or equal to 7 mm (10 mm in patients
with previous cholecystectomy).
In the patients in whom EUS and/or MRCP disclosed ma-
lignancy, the gold standard used was the pathological exam-
ination of the resected specimen or the cytology obtained by
EUS-FNA. In patients without suspicion of malignancy, the
final diagnosis was established by means of ERCP or intraop-
erative cholangiography. When ERCP was performed, opaci-
fication of the biliary tree and pancreatic duct was carried out.
Moreover, an endoscopic sphincterotomy was systematically
conducted after opacification of the common bile duct and
the observation of a calculi or biliar sludge emerging through
the papilla was considered as gold standard. ERCP was done
without knowledge of the results of EUS and MRCP, pre-
venting an overestimation of the tests’ accuracy. In patients
in whom surgery or ERCP was not performed because of the
disappearance of clinical symptoms, normalization of labo-
ratory abnormalities, and lack of abnormalities on EUS and
MRCP, clinical follow-up for at least 6 months was used as
the gold standard.
EUS Imaging
EUS was performed with a 360◦
radial echoendoscope,
Olympus GF UM20 or GF UM160 (Olympus Optical Co.,
Hamburg, Germany). All the procedures were performed un-
der conscious sedation, as previously described (26). Briefly,
patients were lying in a left lateral position, with the trans-
ducer placed in the distal portion of the second portion of the
duodenum and gradually drawn back to the stomach.
The balloon at the tip of the instrument was filled with
deaerated water to improve visualization, and water was also
instilled in the duodenal lumen to assist coupling. This pro-
vides clear visualization of the papilla, common bile duct,
hepatic duct, cystic duct, gallbladder, portal vein, hepatic
artery, and pancreatic head. EUS was performed by three ex-
perienced endosonographers (G.F., A.G., and M.P.) unaware
of the results of MRCP if already done.
EUS diagnostic criteria for choledocholithiasis was the vi-
sualization of one or more hyperechoic images inside the
common bile duct with or without acoustic shadow (Fig. 1).
Biliary sludge was diagnosed if small echos not associated
with shadowing were seen in the lumen of the bile duct. Hy-
poechoic masses located in the pancreas, in the wall of the
biliary tree, or close to the papilla were considered as tumors
(Fig. 2).
MR Imaging
The MRCP examination was performed with a 1.5-T MRI
scanner (Signa CVi, General Electric Medical Systems, Mil-
waukee, WI) with a body phased-array coil. Investigations
were performed on fasting patients who were lying supine.
A set of axial breath-hold FSPGRE T1-weighted images
with fat-saturation and SSFSE T2-weighted images through
the liver and pancreas were obtained. Cholangiographic se-
quences included SSFSE T2-weighted images with thick col-
limation (single section) in the oblique coronal plane, and thin
1634 Fern´andez-Esparrach et al.
Figure 1. Typical image of choledocholithiasis: (A) EUS: hyper-
echoic spot inside the papilla with acoustic shadow. (B) MRCP:
round area of hypointensity inside the lumen of the hyperintense
bile duct.
collimation (multisection) in the coronal and axial plane. MR
studies were assessed in consensus by two abdominal radiol-
ogists (M.S., M.P.) unaware of the results of EUS if done.
Common bile duct stone was diagnosed at MRCP when a
round, oval, or multifaceted area of signal void (hypointen-
sity) was present inside the lumen of the hyperintense bile
duct (Fig. 1). Sludge was considered to be present if low-
intensity sediments without signal voids equal to or larger
than 2 mm were observed (27). When a neoplasm was sus-
pected in the MRCP examination, an additional dynamic
FSPGRE T1-weighted image was acquired after IV adminis-
tration of 0.2 mL/kg gadopentate dimeglumine. Tumors ap-
peared as a pancreatic hypointense mass on fat-saturated T1-
weighted sequences (Fig. 2), a thickened choledochal wall,
or an enlarged papilla.
Figure 2. Adenocarcinoma in the pancreatic head: (A) EUS image:
hypoechoic mass located in the pancreas that contacts with mesen-
teric vein. (B) MRCP: pancreatic hypointense mass with a dilated
biliary tree and pancreatic duct.
Statistical Analysis
The sample size was calculated for achieving 80% power to
detect an odds ratio of 8 using a two-sided McNemar test
with a significance level of 0.05. The mentioned odds ratio
is equivalent to a difference between two paired proportions
of 15% (which has been considered the smallest clinically
significant difference between the two techniques under in-
vestigation) (28) that occurs when the proportions in the dis-
crepant cells of the 2 × 2 table (EUS vs MRCP) are 16% and
2%, respectively. This calculation was performed using the
program PASS 2002 (29). Continuous variables are expressed
as mean ± standard deviation. Comparisons between them
were done by Student’s t-test. Comparisons between quali-
tative variables were performed using the χ2
test with the
Yates’ correction when needed.
Sensitivity, specificity, positive and negative predictive val-
ues, and accuracy for EUS and MRCP with their 95% con-
fidence interval (CI) were calculated using the standard for-
mulas according to the corresponding gold standard for the
two study groups, using the following end points: detection
of any cause of obstruction, diagnosis of malignancy, or di-
agnosis of choledocolithiasis in group 1 and diagnosis of
choledocholithiasis in group 2. Concordance between EUS
and MRCP was assessed using the McNemar test that evalu-
ates if the discrepancies between both techniques are higher
than those observed by chance alone.
To evaluate the clinical impact of EUS and MRCP in the
two study groups, likelihood ratios (LR) and pre and post-test
positive and negative probabilities of diagnosing either ma-
lignancy or choledocholithiasis were calculated. The positive
likelihood ratio (positive LR) is used to assess how much the
probability of disease increases if the test is positive, while
the negative likelihood ratio (negative LR) informs on how
much it decreases if the test is negative. Due to the lack of
published data on the prevalence of disease (tumor or lithia-
sis) in patients with common bile duct dilation unexplained
by standard US, the pretest probability for group 1 was con-
sidered to be the prevalence of tumor or lithiasis in our series,
as determined by the gold standard. For the same reason, the
pretest probability of having choledocholithiasis in group 2
was considered to be the prevalence of this condition as as-
sessed by the gold standard.
All calculations were made using the SPSS statistical pack-
age (SPSS Inc., Chicago, IL).
RESULTS
Between March 2001 and July 2004, one hundred seventy-
two patients were considered for inclusion, of whom 13 were
excluded because of the presence of one of the exclusion
criteria (claustrophobia N = 4, pacemaker N = 3, gastroen-
teroanastomosis N = 2, lack of informed consent, N = 4).
Therefore, one hundred fifty-nine patients (70 men and 89
women) met one of the inclusion criteria during the study pe-
riod (group 1 N = 75, group 2 N = 84). Twenty-four patients
(15%) were excluded from the analysis for different reasons:
Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1635
Patients screened
172
Patients included
159
Group 1
75
Group 2
84
Patients analyzed
63
Patients analyzed
72
13 exclusions
12 exclusions 12 exclusions
Figure 3. Flow chart of the study.
lack of gold standard (N = 8), no EUS (N = 6), no MRCP
(N = 7), and no EUS nor MRCP (N = 3). Thus, 135 patients
(group 1 N = 63, group 2 N = 72) constitute the final sample
of this study (Fig. 3). Mean age was 68 ± 15 yr (mean ± SD).
EUS was performed before MRCP in 70 cases.
The gold standard was ERCP with sphincterotomy in 80
patients, surgery in 19, EUS-FNA in 7, and intraoperative
cholangiography in 3 patients. In 26 patients in group 2 an
ERCP was not performed because of disappearance of clin-
ical symptoms, normalization of laboratory abnormalities,
and lack of abnormalities on EUS and MRCP. All these pa-
tients were followed up for at least 6 months and none of
them developed biliary complications or laboratory abnor-
malities. When follow-up was used as gold standard, mean
time was 5.8 ± 3.9 months. Mean time between EUS/MRCP
and ERCP was 11 ± 13 days (range 1–73 days) and
30 ± 31 days (range 1–106 days) between EUS/ERCP and
surgery.
Characteristics of the patients in the two study groups and
final diagnosis are described in Table 1. The most frequent
Table 1. Characteristics of Patients With Dilated (Group 1) and
Nondilated (Group 2) Biliary Tree
Group 1 Group 2
N = 63 N = 72 P
Age 70 ± 14 66 ± 16 0.187
Gender (M/F) 27/36 34/38 0.611
Serum bilirubin (mg/dL) 6.9 ± 9.2 4.6 ± 5.1 0.085
Common bile duct size (mm) 11 ± 4 6 ± 2 <0.001
Malignancy (%) 22 (35%) 5 (7%) <0.001
No pathologic findings (%) 6 (9%) 32 (44%) <0.001
Final diagnosis
Choledocholithiasis 31 (49%) 30 (42%) 0.380
Cholelithiasis + NBT 2 (3%) 5 (7%) 0.324
Pancreatic cancer 14 (22%) 2 (3%) <0.001
Other 10 (17%) 3 (4%) <0.05
Table 2. Clinical and Laboratory Characteristics of Patients With
Malignant and Benign Conditions in Patients With Biliary Tree Di-
lation (Group 1, N = 63)
Benign
Malignancy Condition
N = 22 N = 41 P
Age 71 ± 12 69 ± 15 0.527
Gender (M/F) 8 /15 19/21 0.326
Bilirubin 13.7 ± 12 2.9 ± 3 <0.001
ALT 356 ± 232 222 ± 206 <0.05
AST 208 ± 111 153 ± 226 0.361
GGT 969 ± 617 503 ± 411 0.001
APL 1,287 ± 866 679 ± 443 0.001
Common bile 13 ± 4 10 ± 4 0.01
duct size (mm)
Cholecystectomy 2 8 0.237
Cholelithiasis 28 15 0.063
diagnosis in the two groups of patients was choledocholithi-
asis (49% in group 1 and 42% in group 2, P < 0.380). As
expected, the diagnosis of malignancy was more frequent in
group 1 than in group 2 (35% vs 7%, respectively, χ2
= 14.7,
P < 0.001). In group 1, age and the presence of cholelithiasis
did not differ between patients with malignant or benign ob-
struction. By contrast, serum levels of bilirubin, ALT, GGT,
and ALP as well as the diameter of the common bile duct
were significantly higher when a malignancy was the cause
of obstruction (Table 2). No pathologic findings were found
in 9% and 44% of patients in groups 1 and 2, respectively
(χ2
= 18.6, P < 0.001).
The acceptance of EUS and MRCP was good in all cases
and no complications occurred.
Diagnostic Accuracy of EUS and MRCP
GROUP 1. Performance characteristics of EUS and MRCP
in patients with unexplained common bile duct dilation in
standard US are described in Table 3.
EUS was more sensitive and MRCP more specific in iden-
tifying any cause of obstruction, but the differences did not
reach statistical significance. The accuracy was similar in
both techniques. EUS gave false-positive results in 3 cases
(choledocholithiasis in 1 case and choledochal sludge in 2
cases) and had no false-negative results. In the case of MRCP,
there was 1 false-positive diagnosis of ampulloma and 4 false
negative results (1 ampuloma, 1 choledocholithiasis, and 2
choledochal sludge).
To assess whether differences between EUS and MRCP are
of clinical relevance, likelihood ratios and the post-test proba-
bility of disease were also calculated. On the other hand, since
clinically relevant information is whether the cause of ob-
struction is a tumor or stones, we analyzed separately patients
with a final diagnosis of tumor and those with a definitive di-
agnosis of common bile duct stones. In this regard, when EUS
and MRCP diagnosed malignancy, the probability of hav-
ing it increased from 35% (prevalence or pretest probabil-
ity) to 98% and 96%, respectively (positive LR 99 and 47,
1636 Fern´andez-Esparrach et al.
Table 3. Performance Characteristics With Their 95% Confidence Interval of EUS and MRCP in the Diagnosis of the Cause of Obstruction,
Malignancy, and Choledocholithiasis in Patients With Dilated Biliary Tree (group 1)
Se (%) Sp (%) PPV (%) NPV (%) Accuracy (%)
Diagnosis of Cause of Obstruction
EUS 100 (95–100) 62 (24–91) 95 (86–99) 100 (55–100) 95 (87–99)
MRCP 93 (82–98) 87 (47–100) 98 (90–100) 64 (31–89) 92 (82–97)
Diagnosis of Malignancy
EUS 100 (87–100) 100 (93–100) 100 (87–100) 100 (93–100) 95 (95–100)
MRCP 95 (77—100) 98 (87–100) 95 (77–100) 98 (87–100) 97 (89–100)
Diagnosis of Choledocholithiasis
EUS 100 (91–100) 91 (75–98) 91 (76–98) 100 (90–100) 95 (87–100)
MRCP 90 (74–98) 100 (91–100) 100 (90–100) 91 (77–98) 95 (87–99)
∗
P > 0.05 in all cases.
respectively). On the contrary, when EUS and MRCP ruled
out malignancy, the probability of having it decreased from
35% to 0% and 2.6%, respectively (negative LR 0 and 0.05,
respectively). Similarly, if EUS and MRCP diagnosed chole-
docholithiasis, the probability of having it increased from
49% (prevalence or pretest probability) to 84% and 99%,
respectively (positive LR 11 and 90, respectively). On the
contrary, when EUS and MRCP ruled out this diagnosis,
the probability of having choledocholithiasis decreased from
49% to 0% and 9%, respectively (negative LR 0 and 0.1,
respectively) (Table 4).
GROUP 2. Performance characteristics of EUS and MRCP
in patients with clinical suspicion of choledocholithiasis
without common bile duct dilation at standard US are de-
scribed in Table 5. MRCP was more specific and EUS more
sensitive in diagnosing choledocholithiasis in this group of
patients but, again, no statistically significant differences
were found between both techniques. The accuracy of both
techniques was similar. EUS gave a false-positive result in
8 cases (4 with diagnosis of choledocholithiasis and 4 with
choledochalsludge)andwasfalsenegativein3(1patientwith
a pancreatic cancer in the uncinated process and 2 with chole-
docholithiasis). The pancreatic cancer was seen on MRCP but
this technique was also negative in the 2 patients with chole-
docholithiasis. On the other hand, 3 MRCP showed false-
positive results (1 Klatskin tumor, 1 choledocholithiasis, and
1 choledochal sludge), and 4 false-negative results (choledo-
cholithiasis in all cases).
To assess the clinical relevance of these results, the post-
test probability of having choledocholithiasis was calculated.
The prevalence of choledocholithiasis (pretest probability) is
42% in our series (Table 1). When EUS and MRCP made
Table 4. Pre- and Post-test Positive and Negative Probabilities of Diagnosing Malignancy and Choledocholithiasis
(Post-test Probabilities)
Prevalence
(Pretest Probability) EUS + EUS − MRCP + MRCP −
Group 1
Malignancy 35% 98% 0% 96% 2.6%
Choledocholithiasis 49% 84% 0% 99% 9%
Group 2
Choledocholithiasis 42% 78% 6% 92% 9%
a positive diagnosis, the probability of having it increased
from 42% to 78% and 92%, respectively (positive LR 5 and
17, respectively). Conversely, if EUS and MRCP ruled out
any pathologic finding, the probability of choledocholithiasis
decreased from 42% to 6% and 9%, respectively (negative
LR 0.08 and 0.1, respectively) (Table 4).
Concordance EUS/MRCP
EUS and MRCP disagreed in only 16 of the 135 patients
(11.8%: group 1, N = 6 and group 2, N = 10). According
to the gold standard, EUS was correct in 7 patients whereas
MRCP was right in the remaining 8. Final diagnosis in these
16 patients was choledocholithiasis (N = 5: 3 patients in
group 1 and 2 patients in group 2), ampulloma (one patient
in group 1), or no abnormalities (N = 10: 2 patients in group
1 and 8 patients in group 2). No tumor was missed by both
techniques in this set of patients.
DISCUSSION
The present study is a prospective and blind comparison be-
tween EUS and MRCP in pancreatobiliary diseases focused
on two relevant clinical populations that represent a diag-
nostic problem in clinical practice and that have not been
specifically assessed in previous investigations: those with
dilated biliary tree and no etiological diagnosis after stan-
dard US and those suspected of having choledocholithia-
sis without biliary tree dilation. Up to now, both techniques
had been compared in heterogeneous study populations (pa-
tients with and without a visualized cause of obstruction
and with and without common bile duct dilation). More
specifically, patients with unexplained dilated biliary tree
on transabdominal US had never been studied as a group.
Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1637
Table 5. Performance Characteristics of EUS and MRCP in the Diagnosis of Choledocholithiasis in Patients With Nondilated Biliary Tree
(group 2)
Se (%) Sp (%) PPV (%) NPV (%) Accuracy (%)
EUS 93 (78–99) 81 (66–91) 78 (61–90) 94 (81–99) 86 (76–98)
MRCP 87 (69–96) 95 (84–99) 93 (76–99) 91 (78–97) 92 (83–97)
∗
P > 0.05 in all cases.
Similarly, patients with choledocholithiasis had always been
studied without separating them according to the size of the
common bile duct. Therefore, the main issue was discerning
how confident one might be when applying the data existing
in the literature to the patients in clinical practice. Moreover,
likelihood ratios and post-test probabilities had never been
calculated in this setting. These calculations allow for the ap-
plication of the results to a particular case, helping physicians
in caring for their patients.
Our results show that EUS is more sensitive and MRCP
more specific in both study groups, although differences are
not statistically significant. It is important to point out that
only one tumor was missed with each technique (one ampu-
loma and a small tumor in the uncinatus process), which was
diagnosed with the other technique. In contrast, most false-
positive and false-negative results were related to choledo-
cholithiasis and occurred in patients with a nondilated bil-
iary tree (group 2). Reasons for false-positive results are
difficult to ascertain, but intraductal artifacts such as blood
or air (pneumobilia) or image reconstruction artifacts may
have been potential pitfalls (30–33). On the other hand, the
gold standard used was ERCP with sphincterotomy in 86 pa-
tients and intraoperative cholangiography in 23 patients. Al-
though both are accepted reference tests for choledocholithi-
asis in the medical literature, it is obvious that a minilithi-
asis or a small amount of sludge may be missed. Further-
more, the delay between EUS or MRCP and the reference
test may account for some of the false-positive results, since
it is known that spontaneous migration of the lithiasis may
occur.
The results of a recently published review on the compar-
ison of EUS and MRCP for detection of choledocholithiasis
are consistent with those of the present investigation although
the study populations are different (34). The strengths of the
present study are the following: first, reference bias has been
avoided by recruiting patients from emergency care, inpatient
and outpatient clinic who cover all the spectrum of the dis-
ease. Second, the independent and blinded comparison of the
EUS and MRCP results with a reference standard enhances
the internal validity of the study. Finally, the use of follow-up
as gold standard in patients with no pathological findings at
EUS and MRCP overcomes verification bias.
Concerning concordance between the compared tech-
niques, the present study demonstrates that both tests usually
agree and they are correct. These two facts had never been as-
sessed in the two study groups in a prospective, comparative,
and blinded manner.
According to our results, in patients with dilated biliary
tree, EUS and MRCP increase the pretest probability of ac-
curately diagnosing malignancy as the cause of obstruction
from 35% (prevalence of malignancy in our series) to 98%
and 96%, respectively. Contrarily, the probability of hav-
ing a malignancy causing biliary obstruction decreases from
35% to 0% and 2.6% when EUS and MRCP preclude it. Ac-
cording to these results, both EUS and MRCP are extremely
useful to diagnose or exclude malignancy as the cause of
obstruction. The probability that the cause of obstruction is
choledocholithiasis increases from 49% (prevalence in our
series) to 84% and 99% with EUS and MRCP, respectively, if
they disclose this diagnosis. On the contrary, this probability
decreases from 49% to 0% and 9% if they rule out lithiasis
as the cause of obstruction, demonstrating that both tech-
niques under evaluation are also very useful in this setting. In
patients with nondilated biliary tree and suspicion of chole-
docholithiasis, even if the results are not so impressive, both
techniques were also very useful (Table 4). Although post-test
probabilities may change among different study populations
due to variations in the prevalence of tumors and stones, the
performance of EUS and MRCP is good enough to allow the
generalization of the results of the present investigation.
In conclusion, there are no significant differences in the
performance of EUS and MRCP for diagnosing or excluding
malignancy and choledocholithiasis in patients with dilated
and nondilated biliary tree, and both are extremely useful.
Therefore, the use of either one may be based on reasons
other than its performance, such as availability or economical
issues.
STUDY HIGHLIGHTS
What Is Current Knowledge
r Endoscopic ultrasonography (EUS) and magnetic reso-
nance cholangiopancreatography (MRCP) are low-risk
diagnostic techniques with good performance for the
diagnosis of biliopancreatic diseases.
What Is New Here
r EUS and MRCP are extremely useful in diagnosing or
excluding malignancy and choledocholithiasis in pa-
tients with dilated and nondilated biliary tree, and so
they are critical in the approach to patient management.
Therefore the use of EUS or MRCP in this setting may
be based on reasons other than its performance, such
as availability or economical issues.
r Concordance between EUS and MRCP in these pa-
tients is high and they are usually right.
1638 Fern´andez-Esparrach et al.
Reprintrequestsandcorrespondence: `AngelsGin`es,M.D.,Ph.D.,
Endoscopy Unit, Institut de Malalties Digestives, Hospital Cl´ınic,
Villarroel 170, 08036 Barcelona, Spain.
Received December 22, 2006; accepted March 7, 2007.
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Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1639
CONFLICT OF INTEREST
Guarantor of the article: `Angels Gin`es,t M.D., Ph.D.
Specific author contributions: Gl`oria Fern´andez-Esparrach
M.D., Ph.D.: development of the protocol and the study, EUS
performance, statistical calculations and manuscript writing
`Angels Gin`es, M.D., Ph.D.: supervision of the protocol, EUS
performance and manuscript writing
Marcelo S´anchez M.D.: MRCP performance and manuscript
correction
Mario Pag´es M.D.: MRCP performance and manuscript cor-
rection
Maria Pellis´e M.D., Ph.D.: EUS performance, protocol dis-
cussion and manuscript correction
Laureano Fern´andez-Cruz, M.D., Ph.D.: patients’ enrollment
and surgery
Miguel Angel L´opez-Boado M.D.: patients’ enrollment and
surgery
Lloren¸c Quint´o B.Sc. M.P.H.: statistical calculations
Salvador Navarro M.D., Ph.D.: patients enrollement.
Oriol Sendino M.D.: patients’ enrollment and follow-up
Andr´es C´adenas, M.D.: manuscript correction
Carmen Ayuso M.D., Ph.D.: manuscript correction
Josep M. Bordas, M.D., Ph.D.: ERCP performance
Josep Llach M.D., Ph.D.: ERCP performance
Antoni Castells, M.D., Ph.D.: manuscript correction
Financial support: This work was supported by grants from
the Instituto de Salud Carlos III (C03/02, C03/10, G03/156)
Potential competing interests: None.

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Comparison of endoscopic ultrasonography and magnetic resonance cholangiopancreatography in the diagnosis of pancreatobiliary diseases a prospective study

  • 1. American Journal of Gastroenterology ISSN 0002-9270 C 2007 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2007.01333.x Published by Blackwell Publishing Comparison of Endoscopic Ultrasonography and Magnetic Resonance Cholangiopancreatography in the Diagnosis of Pancreatobiliary Diseases: A Prospective Study Gl`oria Fern´andez-Esparrach, M.D., Ph.D.,1 `Angels Gin`es, M.D., Ph.D.,1 Marcelo S´anchez, M.D.,2 Mario Pag´es, M.D.,2 Maria Pellis´e, M.D., Ph.D.,1 Laureano Fern´andez-Cruz, M.D., Ph.D.,3 Miguel Angel L´opez-Boado, M.D.,3 Lloren¸c Quint´o, B.Sc, M.P.H.,4 Salvador Navarro, M.D., Ph.D.,1 Oriol Sendino, M.D.,1 Andr´es C´ardenas, M.D.,1 Carmen Ayuso, M.D., Ph.D.,2 Josep M. Bordas, M.D., Ph.D.,1 Josep Llach, M.D., Ph.D.,1 and Antoni Castells, M.D., Ph.D.1 1 Gastroenterology Department, Institut de Malalties Digestives i Metab`oliques, CIBER HEPAD; 2 Radiology Unit (CCDI); 3 Surgery Department; and 4 Unitat d’Avaluaci´o, Suport i Prevenci´o (UAPS), Hospital Cl´ınic, University of Barcelona, Barcelona, Spain OBJECTIVES: To compare the diagnostic value of endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) in: (a) patients with a dilated biliary tree unexplained by ultrasonography (US) (group 1), and (b) the diagnosis of choledocholithiasis in patients with nondilated biliary tree (group 2). METHODS: Patients were prospectively evaluated with EUS and MRCP. The gold standard used was surgery or EUS-FNA and ERCP, intraoperative cholangiography, or follow-up when EUS and/or MRCP disclosed or precluded malignancy, respectively. Likelihood ratios (LR) and pretest and post-test probabilities for the diagnosis of malignancy and choledocholithiasis were calculated. RESULTS: A total of 159 patients met one of the inclusion criteria but 24 of them were excluded for different reasons. Thus, 135 patients constitute the study population. The most frequent diagnosis was choledocholithiasis (49% in group 1 and 42% in group 2, P = 0.380) and malignancy was more frequent in group 1 (35% vs 7%, respectively, P < 0.001). When EUS and MRCP diagnosed malignancy, its prevalence in our series (35%) increased up to 98% and 96%, respectively, whereas it decreased to 0% and 2.6% when EUS and MRCP precluded this diagnosis. In patients in group 2, when EUS and MRCP made a positive diagnosis of choledocholithiasis, its prevalence (42%) increased up to 78% and 92%, respectively, whereas it decreased to 6% and 9% when any pathologic finding was ruled out. CONCLUSIONS: EUS and MRCP are extremely useful in diagnosing or excluding malignancy and choledocholithiasis in patients with dilated and nondilated biliary tree. Therefore, they are critical in the approach to the management of these patients. (Am J Gastroenterol 2007;102:1632–1639) INTRODUCTION The diagnosis of pancreatobiliary diseases is a common prob- lem in clinical practice. It is known that ultrasonography (US) is not accurate enough in the diagnosis of the etiology of bil- iar obstruction due to the presence of air preventing a cor- rect ultrasound transmission (1–3). On the other hand, the presence of stones in the main bile duct may be difficult to demonstrate particularly when the biliary tree is not di- lated (4). Endoscopic retrograde cholangiopancreatography (ERCP), that has been classically performed to study pan- creatobiliary diseases, is associated with a significant risk of serious complications such as pancreatitis, hemorrhage, per- foration, cholangitis, and even death (5). Therefore, an effort to safely and accurately image the pancreatobiliary area has been made in the last few decades. Endoscopic ultrasonography (EUS) and magnetic reso- nance cholangiopancreatography (MRCP) have emerged as two low-risk diagnostic techniques with good performance for the diagnosis of biliopancreatic diseases (6–18). Although both techniques have already been compared in this setting, the studies published up to now have small sample sizes and include heterogeneous populations, so it is not possible to ob- tain from them conclusions definitive enough to be applied in clinical practice (19–23). There are two common situa- tions in patients with pancreatobiliary diseases that have not 1632
  • 2. Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1633 been specifically studied, and so the dilemma of choosing the most accurate technique frequently arises: common bile duct dilation with no visible cause on US and suspicion of choledocholithiasis in patients with nondilated biliary tree. Therefore, the aims of the present study were to prospec- tively and blindly compare the diagnostic value of EUS and MRCP in: (a) the etiologic diagnosis of patients with a di- lated biliary tree unexplained by US and (b) the diagnosis of choledocholithiasis in patients with nondilated biliary tree. PATIENTS AND METHODS This prospective study was conducted following the STARD statement for reporting studies of diagnostic accuracy (24). It was approved by the institutional review board of the Hospital Cl´ınic,Barcelona,andwritteninformedconsentwasobtained from all patients. Study Population ThestudywasperformedbetweenMarch2001andJuly2004. To avoid selection bias, all consecutive patients evaluated in the departments of gastroenterology and surgery were asked to participate in this prospective investigation if they met one of the following inclusion criteria: (a) unexplained common bile duct dilation in standard US, independently of clinical symptoms (group 1) and (b) a nondilated common bile duct and a high probability of having choledocholithiasis (cholan- gitis, jaundice, nonsevere pancreatitis, alkaline phosphatase [ALP] < twice the upper normal limit [UNL] or increased gamma glutamyl trasferase [GGT], alanine aminotransferase [ALT]oraspartateaminotransferase[AST])(3,25)(group2). Although the indication of EUS and MRCP prior to ERCP in this latter group could be discussed, we chose these patients in order to obtain a high prevalence of choledocolithiasis for our study purposes. For ethical reasons, patients with se- vere pancreatitis were not included since an early ERCP with sphincterotomy is indicated. Exclusion criteria were (a) contraindications to MRCP (claustrophobia, pacemaker, or any prosthesis contraindicat- ing MR), (b) predictable impossibility to perform a complete exploration of the pancreatobiliary area by EUS (i.e., gas- troenteroanastomosis or stenosis), and (c) refusal or inability to provide informed consent. METHODS EUS and MRCP were performed within a 24-h period after inclusion in order to minimize the chances of a negative study due to stone passage, and the sequence of the examinations wasrandomlyassigned.Toensureblinding,eachexamination was performed by a different operator unaware of the result of the other procedure. The diameter of common bile duct and the site and cause (stones, tumor, or other) of the obstruction were systemat- ically investigated. The common bile duct was considered normal in absence of thickened wall and when the maximum diameter was less than or equal to 7 mm (10 mm in patients with previous cholecystectomy). In the patients in whom EUS and/or MRCP disclosed ma- lignancy, the gold standard used was the pathological exam- ination of the resected specimen or the cytology obtained by EUS-FNA. In patients without suspicion of malignancy, the final diagnosis was established by means of ERCP or intraop- erative cholangiography. When ERCP was performed, opaci- fication of the biliary tree and pancreatic duct was carried out. Moreover, an endoscopic sphincterotomy was systematically conducted after opacification of the common bile duct and the observation of a calculi or biliar sludge emerging through the papilla was considered as gold standard. ERCP was done without knowledge of the results of EUS and MRCP, pre- venting an overestimation of the tests’ accuracy. In patients in whom surgery or ERCP was not performed because of the disappearance of clinical symptoms, normalization of labo- ratory abnormalities, and lack of abnormalities on EUS and MRCP, clinical follow-up for at least 6 months was used as the gold standard. EUS Imaging EUS was performed with a 360◦ radial echoendoscope, Olympus GF UM20 or GF UM160 (Olympus Optical Co., Hamburg, Germany). All the procedures were performed un- der conscious sedation, as previously described (26). Briefly, patients were lying in a left lateral position, with the trans- ducer placed in the distal portion of the second portion of the duodenum and gradually drawn back to the stomach. The balloon at the tip of the instrument was filled with deaerated water to improve visualization, and water was also instilled in the duodenal lumen to assist coupling. This pro- vides clear visualization of the papilla, common bile duct, hepatic duct, cystic duct, gallbladder, portal vein, hepatic artery, and pancreatic head. EUS was performed by three ex- perienced endosonographers (G.F., A.G., and M.P.) unaware of the results of MRCP if already done. EUS diagnostic criteria for choledocholithiasis was the vi- sualization of one or more hyperechoic images inside the common bile duct with or without acoustic shadow (Fig. 1). Biliary sludge was diagnosed if small echos not associated with shadowing were seen in the lumen of the bile duct. Hy- poechoic masses located in the pancreas, in the wall of the biliary tree, or close to the papilla were considered as tumors (Fig. 2). MR Imaging The MRCP examination was performed with a 1.5-T MRI scanner (Signa CVi, General Electric Medical Systems, Mil- waukee, WI) with a body phased-array coil. Investigations were performed on fasting patients who were lying supine. A set of axial breath-hold FSPGRE T1-weighted images with fat-saturation and SSFSE T2-weighted images through the liver and pancreas were obtained. Cholangiographic se- quences included SSFSE T2-weighted images with thick col- limation (single section) in the oblique coronal plane, and thin
  • 3. 1634 Fern´andez-Esparrach et al. Figure 1. Typical image of choledocholithiasis: (A) EUS: hyper- echoic spot inside the papilla with acoustic shadow. (B) MRCP: round area of hypointensity inside the lumen of the hyperintense bile duct. collimation (multisection) in the coronal and axial plane. MR studies were assessed in consensus by two abdominal radiol- ogists (M.S., M.P.) unaware of the results of EUS if done. Common bile duct stone was diagnosed at MRCP when a round, oval, or multifaceted area of signal void (hypointen- sity) was present inside the lumen of the hyperintense bile duct (Fig. 1). Sludge was considered to be present if low- intensity sediments without signal voids equal to or larger than 2 mm were observed (27). When a neoplasm was sus- pected in the MRCP examination, an additional dynamic FSPGRE T1-weighted image was acquired after IV adminis- tration of 0.2 mL/kg gadopentate dimeglumine. Tumors ap- peared as a pancreatic hypointense mass on fat-saturated T1- weighted sequences (Fig. 2), a thickened choledochal wall, or an enlarged papilla. Figure 2. Adenocarcinoma in the pancreatic head: (A) EUS image: hypoechoic mass located in the pancreas that contacts with mesen- teric vein. (B) MRCP: pancreatic hypointense mass with a dilated biliary tree and pancreatic duct. Statistical Analysis The sample size was calculated for achieving 80% power to detect an odds ratio of 8 using a two-sided McNemar test with a significance level of 0.05. The mentioned odds ratio is equivalent to a difference between two paired proportions of 15% (which has been considered the smallest clinically significant difference between the two techniques under in- vestigation) (28) that occurs when the proportions in the dis- crepant cells of the 2 × 2 table (EUS vs MRCP) are 16% and 2%, respectively. This calculation was performed using the program PASS 2002 (29). Continuous variables are expressed as mean ± standard deviation. Comparisons between them were done by Student’s t-test. Comparisons between quali- tative variables were performed using the χ2 test with the Yates’ correction when needed. Sensitivity, specificity, positive and negative predictive val- ues, and accuracy for EUS and MRCP with their 95% con- fidence interval (CI) were calculated using the standard for- mulas according to the corresponding gold standard for the two study groups, using the following end points: detection of any cause of obstruction, diagnosis of malignancy, or di- agnosis of choledocolithiasis in group 1 and diagnosis of choledocholithiasis in group 2. Concordance between EUS and MRCP was assessed using the McNemar test that evalu- ates if the discrepancies between both techniques are higher than those observed by chance alone. To evaluate the clinical impact of EUS and MRCP in the two study groups, likelihood ratios (LR) and pre and post-test positive and negative probabilities of diagnosing either ma- lignancy or choledocholithiasis were calculated. The positive likelihood ratio (positive LR) is used to assess how much the probability of disease increases if the test is positive, while the negative likelihood ratio (negative LR) informs on how much it decreases if the test is negative. Due to the lack of published data on the prevalence of disease (tumor or lithia- sis) in patients with common bile duct dilation unexplained by standard US, the pretest probability for group 1 was con- sidered to be the prevalence of tumor or lithiasis in our series, as determined by the gold standard. For the same reason, the pretest probability of having choledocholithiasis in group 2 was considered to be the prevalence of this condition as as- sessed by the gold standard. All calculations were made using the SPSS statistical pack- age (SPSS Inc., Chicago, IL). RESULTS Between March 2001 and July 2004, one hundred seventy- two patients were considered for inclusion, of whom 13 were excluded because of the presence of one of the exclusion criteria (claustrophobia N = 4, pacemaker N = 3, gastroen- teroanastomosis N = 2, lack of informed consent, N = 4). Therefore, one hundred fifty-nine patients (70 men and 89 women) met one of the inclusion criteria during the study pe- riod (group 1 N = 75, group 2 N = 84). Twenty-four patients (15%) were excluded from the analysis for different reasons:
  • 4. Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1635 Patients screened 172 Patients included 159 Group 1 75 Group 2 84 Patients analyzed 63 Patients analyzed 72 13 exclusions 12 exclusions 12 exclusions Figure 3. Flow chart of the study. lack of gold standard (N = 8), no EUS (N = 6), no MRCP (N = 7), and no EUS nor MRCP (N = 3). Thus, 135 patients (group 1 N = 63, group 2 N = 72) constitute the final sample of this study (Fig. 3). Mean age was 68 ± 15 yr (mean ± SD). EUS was performed before MRCP in 70 cases. The gold standard was ERCP with sphincterotomy in 80 patients, surgery in 19, EUS-FNA in 7, and intraoperative cholangiography in 3 patients. In 26 patients in group 2 an ERCP was not performed because of disappearance of clin- ical symptoms, normalization of laboratory abnormalities, and lack of abnormalities on EUS and MRCP. All these pa- tients were followed up for at least 6 months and none of them developed biliary complications or laboratory abnor- malities. When follow-up was used as gold standard, mean time was 5.8 ± 3.9 months. Mean time between EUS/MRCP and ERCP was 11 ± 13 days (range 1–73 days) and 30 ± 31 days (range 1–106 days) between EUS/ERCP and surgery. Characteristics of the patients in the two study groups and final diagnosis are described in Table 1. The most frequent Table 1. Characteristics of Patients With Dilated (Group 1) and Nondilated (Group 2) Biliary Tree Group 1 Group 2 N = 63 N = 72 P Age 70 ± 14 66 ± 16 0.187 Gender (M/F) 27/36 34/38 0.611 Serum bilirubin (mg/dL) 6.9 ± 9.2 4.6 ± 5.1 0.085 Common bile duct size (mm) 11 ± 4 6 ± 2 <0.001 Malignancy (%) 22 (35%) 5 (7%) <0.001 No pathologic findings (%) 6 (9%) 32 (44%) <0.001 Final diagnosis Choledocholithiasis 31 (49%) 30 (42%) 0.380 Cholelithiasis + NBT 2 (3%) 5 (7%) 0.324 Pancreatic cancer 14 (22%) 2 (3%) <0.001 Other 10 (17%) 3 (4%) <0.05 Table 2. Clinical and Laboratory Characteristics of Patients With Malignant and Benign Conditions in Patients With Biliary Tree Di- lation (Group 1, N = 63) Benign Malignancy Condition N = 22 N = 41 P Age 71 ± 12 69 ± 15 0.527 Gender (M/F) 8 /15 19/21 0.326 Bilirubin 13.7 ± 12 2.9 ± 3 <0.001 ALT 356 ± 232 222 ± 206 <0.05 AST 208 ± 111 153 ± 226 0.361 GGT 969 ± 617 503 ± 411 0.001 APL 1,287 ± 866 679 ± 443 0.001 Common bile 13 ± 4 10 ± 4 0.01 duct size (mm) Cholecystectomy 2 8 0.237 Cholelithiasis 28 15 0.063 diagnosis in the two groups of patients was choledocholithi- asis (49% in group 1 and 42% in group 2, P < 0.380). As expected, the diagnosis of malignancy was more frequent in group 1 than in group 2 (35% vs 7%, respectively, χ2 = 14.7, P < 0.001). In group 1, age and the presence of cholelithiasis did not differ between patients with malignant or benign ob- struction. By contrast, serum levels of bilirubin, ALT, GGT, and ALP as well as the diameter of the common bile duct were significantly higher when a malignancy was the cause of obstruction (Table 2). No pathologic findings were found in 9% and 44% of patients in groups 1 and 2, respectively (χ2 = 18.6, P < 0.001). The acceptance of EUS and MRCP was good in all cases and no complications occurred. Diagnostic Accuracy of EUS and MRCP GROUP 1. Performance characteristics of EUS and MRCP in patients with unexplained common bile duct dilation in standard US are described in Table 3. EUS was more sensitive and MRCP more specific in iden- tifying any cause of obstruction, but the differences did not reach statistical significance. The accuracy was similar in both techniques. EUS gave false-positive results in 3 cases (choledocholithiasis in 1 case and choledochal sludge in 2 cases) and had no false-negative results. In the case of MRCP, there was 1 false-positive diagnosis of ampulloma and 4 false negative results (1 ampuloma, 1 choledocholithiasis, and 2 choledochal sludge). To assess whether differences between EUS and MRCP are of clinical relevance, likelihood ratios and the post-test proba- bility of disease were also calculated. On the other hand, since clinically relevant information is whether the cause of ob- struction is a tumor or stones, we analyzed separately patients with a final diagnosis of tumor and those with a definitive di- agnosis of common bile duct stones. In this regard, when EUS and MRCP diagnosed malignancy, the probability of hav- ing it increased from 35% (prevalence or pretest probabil- ity) to 98% and 96%, respectively (positive LR 99 and 47,
  • 5. 1636 Fern´andez-Esparrach et al. Table 3. Performance Characteristics With Their 95% Confidence Interval of EUS and MRCP in the Diagnosis of the Cause of Obstruction, Malignancy, and Choledocholithiasis in Patients With Dilated Biliary Tree (group 1) Se (%) Sp (%) PPV (%) NPV (%) Accuracy (%) Diagnosis of Cause of Obstruction EUS 100 (95–100) 62 (24–91) 95 (86–99) 100 (55–100) 95 (87–99) MRCP 93 (82–98) 87 (47–100) 98 (90–100) 64 (31–89) 92 (82–97) Diagnosis of Malignancy EUS 100 (87–100) 100 (93–100) 100 (87–100) 100 (93–100) 95 (95–100) MRCP 95 (77—100) 98 (87–100) 95 (77–100) 98 (87–100) 97 (89–100) Diagnosis of Choledocholithiasis EUS 100 (91–100) 91 (75–98) 91 (76–98) 100 (90–100) 95 (87–100) MRCP 90 (74–98) 100 (91–100) 100 (90–100) 91 (77–98) 95 (87–99) ∗ P > 0.05 in all cases. respectively). On the contrary, when EUS and MRCP ruled out malignancy, the probability of having it decreased from 35% to 0% and 2.6%, respectively (negative LR 0 and 0.05, respectively). Similarly, if EUS and MRCP diagnosed chole- docholithiasis, the probability of having it increased from 49% (prevalence or pretest probability) to 84% and 99%, respectively (positive LR 11 and 90, respectively). On the contrary, when EUS and MRCP ruled out this diagnosis, the probability of having choledocholithiasis decreased from 49% to 0% and 9%, respectively (negative LR 0 and 0.1, respectively) (Table 4). GROUP 2. Performance characteristics of EUS and MRCP in patients with clinical suspicion of choledocholithiasis without common bile duct dilation at standard US are de- scribed in Table 5. MRCP was more specific and EUS more sensitive in diagnosing choledocholithiasis in this group of patients but, again, no statistically significant differences were found between both techniques. The accuracy of both techniques was similar. EUS gave a false-positive result in 8 cases (4 with diagnosis of choledocholithiasis and 4 with choledochalsludge)andwasfalsenegativein3(1patientwith a pancreatic cancer in the uncinated process and 2 with chole- docholithiasis). The pancreatic cancer was seen on MRCP but this technique was also negative in the 2 patients with chole- docholithiasis. On the other hand, 3 MRCP showed false- positive results (1 Klatskin tumor, 1 choledocholithiasis, and 1 choledochal sludge), and 4 false-negative results (choledo- cholithiasis in all cases). To assess the clinical relevance of these results, the post- test probability of having choledocholithiasis was calculated. The prevalence of choledocholithiasis (pretest probability) is 42% in our series (Table 1). When EUS and MRCP made Table 4. Pre- and Post-test Positive and Negative Probabilities of Diagnosing Malignancy and Choledocholithiasis (Post-test Probabilities) Prevalence (Pretest Probability) EUS + EUS − MRCP + MRCP − Group 1 Malignancy 35% 98% 0% 96% 2.6% Choledocholithiasis 49% 84% 0% 99% 9% Group 2 Choledocholithiasis 42% 78% 6% 92% 9% a positive diagnosis, the probability of having it increased from 42% to 78% and 92%, respectively (positive LR 5 and 17, respectively). Conversely, if EUS and MRCP ruled out any pathologic finding, the probability of choledocholithiasis decreased from 42% to 6% and 9%, respectively (negative LR 0.08 and 0.1, respectively) (Table 4). Concordance EUS/MRCP EUS and MRCP disagreed in only 16 of the 135 patients (11.8%: group 1, N = 6 and group 2, N = 10). According to the gold standard, EUS was correct in 7 patients whereas MRCP was right in the remaining 8. Final diagnosis in these 16 patients was choledocholithiasis (N = 5: 3 patients in group 1 and 2 patients in group 2), ampulloma (one patient in group 1), or no abnormalities (N = 10: 2 patients in group 1 and 8 patients in group 2). No tumor was missed by both techniques in this set of patients. DISCUSSION The present study is a prospective and blind comparison be- tween EUS and MRCP in pancreatobiliary diseases focused on two relevant clinical populations that represent a diag- nostic problem in clinical practice and that have not been specifically assessed in previous investigations: those with dilated biliary tree and no etiological diagnosis after stan- dard US and those suspected of having choledocholithia- sis without biliary tree dilation. Up to now, both techniques had been compared in heterogeneous study populations (pa- tients with and without a visualized cause of obstruction and with and without common bile duct dilation). More specifically, patients with unexplained dilated biliary tree on transabdominal US had never been studied as a group.
  • 6. Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1637 Table 5. Performance Characteristics of EUS and MRCP in the Diagnosis of Choledocholithiasis in Patients With Nondilated Biliary Tree (group 2) Se (%) Sp (%) PPV (%) NPV (%) Accuracy (%) EUS 93 (78–99) 81 (66–91) 78 (61–90) 94 (81–99) 86 (76–98) MRCP 87 (69–96) 95 (84–99) 93 (76–99) 91 (78–97) 92 (83–97) ∗ P > 0.05 in all cases. Similarly, patients with choledocholithiasis had always been studied without separating them according to the size of the common bile duct. Therefore, the main issue was discerning how confident one might be when applying the data existing in the literature to the patients in clinical practice. Moreover, likelihood ratios and post-test probabilities had never been calculated in this setting. These calculations allow for the ap- plication of the results to a particular case, helping physicians in caring for their patients. Our results show that EUS is more sensitive and MRCP more specific in both study groups, although differences are not statistically significant. It is important to point out that only one tumor was missed with each technique (one ampu- loma and a small tumor in the uncinatus process), which was diagnosed with the other technique. In contrast, most false- positive and false-negative results were related to choledo- cholithiasis and occurred in patients with a nondilated bil- iary tree (group 2). Reasons for false-positive results are difficult to ascertain, but intraductal artifacts such as blood or air (pneumobilia) or image reconstruction artifacts may have been potential pitfalls (30–33). On the other hand, the gold standard used was ERCP with sphincterotomy in 86 pa- tients and intraoperative cholangiography in 23 patients. Al- though both are accepted reference tests for choledocholithi- asis in the medical literature, it is obvious that a minilithi- asis or a small amount of sludge may be missed. Further- more, the delay between EUS or MRCP and the reference test may account for some of the false-positive results, since it is known that spontaneous migration of the lithiasis may occur. The results of a recently published review on the compar- ison of EUS and MRCP for detection of choledocholithiasis are consistent with those of the present investigation although the study populations are different (34). The strengths of the present study are the following: first, reference bias has been avoided by recruiting patients from emergency care, inpatient and outpatient clinic who cover all the spectrum of the dis- ease. Second, the independent and blinded comparison of the EUS and MRCP results with a reference standard enhances the internal validity of the study. Finally, the use of follow-up as gold standard in patients with no pathological findings at EUS and MRCP overcomes verification bias. Concerning concordance between the compared tech- niques, the present study demonstrates that both tests usually agree and they are correct. These two facts had never been as- sessed in the two study groups in a prospective, comparative, and blinded manner. According to our results, in patients with dilated biliary tree, EUS and MRCP increase the pretest probability of ac- curately diagnosing malignancy as the cause of obstruction from 35% (prevalence of malignancy in our series) to 98% and 96%, respectively. Contrarily, the probability of hav- ing a malignancy causing biliary obstruction decreases from 35% to 0% and 2.6% when EUS and MRCP preclude it. Ac- cording to these results, both EUS and MRCP are extremely useful to diagnose or exclude malignancy as the cause of obstruction. The probability that the cause of obstruction is choledocholithiasis increases from 49% (prevalence in our series) to 84% and 99% with EUS and MRCP, respectively, if they disclose this diagnosis. On the contrary, this probability decreases from 49% to 0% and 9% if they rule out lithiasis as the cause of obstruction, demonstrating that both tech- niques under evaluation are also very useful in this setting. In patients with nondilated biliary tree and suspicion of chole- docholithiasis, even if the results are not so impressive, both techniques were also very useful (Table 4). Although post-test probabilities may change among different study populations due to variations in the prevalence of tumors and stones, the performance of EUS and MRCP is good enough to allow the generalization of the results of the present investigation. In conclusion, there are no significant differences in the performance of EUS and MRCP for diagnosing or excluding malignancy and choledocholithiasis in patients with dilated and nondilated biliary tree, and both are extremely useful. Therefore, the use of either one may be based on reasons other than its performance, such as availability or economical issues. STUDY HIGHLIGHTS What Is Current Knowledge r Endoscopic ultrasonography (EUS) and magnetic reso- nance cholangiopancreatography (MRCP) are low-risk diagnostic techniques with good performance for the diagnosis of biliopancreatic diseases. What Is New Here r EUS and MRCP are extremely useful in diagnosing or excluding malignancy and choledocholithiasis in pa- tients with dilated and nondilated biliary tree, and so they are critical in the approach to patient management. Therefore the use of EUS or MRCP in this setting may be based on reasons other than its performance, such as availability or economical issues. r Concordance between EUS and MRCP in these pa- tients is high and they are usually right.
  • 7. 1638 Fern´andez-Esparrach et al. Reprintrequestsandcorrespondence: `AngelsGin`es,M.D.,Ph.D., Endoscopy Unit, Institut de Malalties Digestives, Hospital Cl´ınic, Villarroel 170, 08036 Barcelona, Spain. Received December 22, 2006; accepted March 7, 2007. REFERENCES 1. O’Connor HJ, Hamilton I, Ellis WR, et al. Ultrasound de- tection of choledocholithiasis: Prospective comparison with ERCP in the postcholecystectomy patient. Gastrointest Ra- diol 1986;11:161–4. 2. Sugiyama M, Atomi Y. Endoscopic ultrasonography for diagnosing choledocholithiasis: A prospective comparative study with ultrasonography and computed tomography. Gas- trointest Endosc 1997;45:143–6. 3. Abboud PC, Malet PF, Berlin JA. Predictors of common bile duct stones prior to cholecystectomy: A meta-analysis. Gastrointest Endosc 1996;44:450–9. 4. Guibaud L, Bret PM, Reinhold C, et al. Bile duct obstruction and choledocholithiasis: Diagnosis with MR cholangiogra- phy. Radiology 1995;197:109–15. 5. 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  • 8. Comparison of EUS and MRCP in the Diagnosis of Pancreatobiliary Diseases 1639 CONFLICT OF INTEREST Guarantor of the article: `Angels Gin`es,t M.D., Ph.D. Specific author contributions: Gl`oria Fern´andez-Esparrach M.D., Ph.D.: development of the protocol and the study, EUS performance, statistical calculations and manuscript writing `Angels Gin`es, M.D., Ph.D.: supervision of the protocol, EUS performance and manuscript writing Marcelo S´anchez M.D.: MRCP performance and manuscript correction Mario Pag´es M.D.: MRCP performance and manuscript cor- rection Maria Pellis´e M.D., Ph.D.: EUS performance, protocol dis- cussion and manuscript correction Laureano Fern´andez-Cruz, M.D., Ph.D.: patients’ enrollment and surgery Miguel Angel L´opez-Boado M.D.: patients’ enrollment and surgery Lloren¸c Quint´o B.Sc. M.P.H.: statistical calculations Salvador Navarro M.D., Ph.D.: patients enrollement. Oriol Sendino M.D.: patients’ enrollment and follow-up Andr´es C´adenas, M.D.: manuscript correction Carmen Ayuso M.D., Ph.D.: manuscript correction Josep M. Bordas, M.D., Ph.D.: ERCP performance Josep Llach M.D., Ph.D.: ERCP performance Antoni Castells, M.D., Ph.D.: manuscript correction Financial support: This work was supported by grants from the Instituto de Salud Carlos III (C03/02, C03/10, G03/156) Potential competing interests: None.