EUS-guided fine needle aspiration of the liver: indications,

yield, and safety based on an international survey of 167

cases
Jorgen tenBerge, Brenda J. Hoffman, MD, Robert H. Hawes, MD, Conny van Enckevort, Marc Giovannini, MD,
Richard A. Erickson, MD, Marc F. Catalano, MD, Roberto Fogel, MD, Shawn Mallery, MD, Douglas O. Faigel, MD,
Angelo P. Ferrari, MD, Irving Waxman, MD, Larent Palazzo, MD, Tamir Ben-Menachem, MD, Paul S. Jowell, MD,
Kevin M. McGrath, MD, Thomas E. Kowalski, MD, Cuong C. Nguyen, Wahid Y. Wassef, MD, Keiji Yamao, MD,
Amitabh Chak, MD, Bruce D. Greenwald, MD, Timothy A. Woodward, MD, Peter Vilmann, MD, Luis Sabbagh, MD,
Michael B. Wallace, MD, MPH
Charleston, South Carolina

Background: The liver is a common site of metastases for various malignancies. EUS-guided fine nee-
dle aspiration (EUS-FNA) of liver masses has only been reported in small series from single centers.
Methods: A retrospective questionnaire was sent by e-mail to 130 EUS-FNA centers around the
world regarding indications, complications, and findings of EUS-FNA of the liver.
Results: Twenty-one centers reported 167 cases of EUS-FNA of the liver. A complication was report-
ed in 6 (4%) of 167 cases including the following: death in 1 patient with an occluding biliary stent
and biliary sepsis, bleeding (1), fever (2), and pain (2). EUS-FNA diagnosed malignancy in 23 of 26
(89%) cases after nondiagnostic fine needle aspiration under transabdominal US guidance. EUS
localized an unrecognized primary tumor in 17 of 33 (52%) cases in which CT had demonstrated only
liver metastases. EUS image characteristics were not predictive of malignant versus benign lesions.
Conclusion: EUS-guided FNA of the liver appears to be a safe procedure with a major complica-
tion rate of approximately 1%. EUS-FNA should be considered when a liver lesion is poorly acces-
sible to US-, or CT-guided FNA should be considered when US- or CT-guided FNA fail to make a
diagnosis, when a liver lesion(s) is detected (de novo) by EUS, and for investigation of possible
upper GI primary tumors in the setting of liver metastases. (Gastrointest Endosc 2002;55:859-62.)

The diagnosis of liver metastases is important for
clinical management. With the exception of isolated
metastases from colon cancer, the presence of liver
metastases generally implies that the malignancy is
Received July 6, 2001. For revision October 5, 2001. Accepted
November 2, 2001.
Current affiliations: Medical University of South Carolina,
Charleston, South Carolina, Institut Paoli-Calmettes, Marseilles,
France, Scoff and White Clinic, Temple, Texas, GI Consultants
Ltd., Milwaukee, Wisconsin, Clinica Caracas, Caracas, Venezuela,
Hennepin County Medical Center, Minneapolis, Minnesota,
Portland Veterans Administration Hospital, Portland, Oregon,
Universidade Federal de São Paulo, São Paulo, Brazil, University
of Chicago, Illinois, Beaujen Hospital, Paris VII University, Clichy,
France, Henry Ford Hospital, Detroit, Michigan, Duke University
School of Medicine, Durham, North Carolina, Thomas Jefferson
University Hospital, Philadelphia, Pennsylvania, Mayo Clinic,
Scottsdale, Arizona, University of Massachusetts Medical Center,
Worcester, Massachusetts, Aichi Cancer Center Hospital, Aichi,
Japan, University Hospitals of Cleveland, Cleveland, Ohio,
University of Maryland Medical Center, Baltimore, Maryland,
Mayo Clinic, Jacksonville, Florida, Gentofte University Hospital,
Hellerup, Denmark, Clinica Reina Sofia, Bogota, Columbia.
Reprint requests: Michael B. Wallace MD, MPH, Medical
University of South Carolina, 96 Jonathan Lucas St., Suite 922
CSB, PO Box 250623, Charleston, SC 29425.
Copyright © 2002 by the American Society for Gastrointestinal
Endoscopy 0016-5107/2002/$35.00 + 0 37/1/124557
doi:10.1067/mge.2002.124557
incurable. EUS is an important method for the diag-
nosis and staging of malignant GI and lung
tumors.1-5 Numerous studies have found that the
addition of EUS-guided fine needle aspiration
(EUS-FNA) increased diagnostic and staging accu-
racy compared with EUS alone in patients with pan-
creatic cancer.6-10 However, little is known about the
effectiveness and safety of EUS-guided FNA for the
diagnosis of liver lesions. A Medline search revealed
only one single center study and a few case reports
on EUS-FNA of the liver.11-13 An advantage of EUS-
FNA is that detection, staging, and confirmation of
malignancy can usually be accomplished in a single
procedure whereas CT or US typically require 2 ses-
sions to accomplish these tasks, one for detection
and another for FNA. Although CT and US are less
invasive than EUS, liver metastases are occasional-
ly detected de novo during EUS staging of a prima-
ry tumor. This is a report of the results of an inter-
national survey of EUS centers regarding the yield
and safety of EUS-FNA of liver masses.
MATERIALS AND METHODS
A retrospective survey questionnaire was developed
based on experience with EUS-FNA at one center (Medical
University of South Carolina, Charleston, S.C.) and on pub-

VOLUME 55, NO. 7, 2002 GASTROINTESTINAL ENDOSCOPY 859

J tenBerge, B Hoffman, R Hawes, et al.
Table 1. Indication for EUS before FNA (N = 167)
Indication N (%)
Pancreatic mass 62 (37.1)
Liver metastases with unknown primary tumor 33 (19.8)
Esophageal mass 19 (11.4)
Gastric mass 16 (9.6)
Liver mass 8 (4.8)
Other 29 (17.3)
lished information.14-17 A list of EUS centers worldwide
was developed from the membership list of the American
Society for Gastrointestinal Endoscopy (ASGE), the mail-
ing list of the American Endosonography Club, the list of
attendees at the 11th and the 12th International
Symposium on Endoscopic Ultrasound, authors of EUS-
FNA–related studies published in Gastrointestinal
Endoscopy and Endoscopy from 1996 to 2000, and knowl-
edge of recognized EUS-FNA centers. The survey question-
naire was sent by e-mail to all centers. From some centers
more than one expert contributed cases, but each case was
counted only once. When an e-mail address was lacking or
incorrect, a letter was sent by facsimile with an invitation
to participate in the survey and a request for an e-mail
address. In cases in which there was no response, centers
were contacted again by e-mail after 2, 4, and 6 weeks. The
time interval between the first e-mail message and the cut-
off date for inclusion in the survey was 8 weeks. All data
were converted into a digital file and analyzed with a sta-
tistical software package (SPSS Inc., Chicago, Ill.).
Univariate analysis was performed to describe the distri-
butions of indications, complications, and findings.
RESULTS
In total, 130 endosonographers were contacted by
e-mail and 75% responded to the questionnaire.
Twenty-one centers reported results for 167 cases in
which EUS-FNA of the liver was performed. The
indications for EUS before EUS-FNA of the liver are
shown in Table 1. A pancreatic mass was the most
common, followed by a suspicion of liver metastases
with an unknown primary tumor. In order,
esophageal, gastric, and primary liver masses con-
stitute the next 3 most common indications.
For the 167 EUS-FNA procedures, the findings of
the cytopathology was malignancy in 138 (83%),
benign in 22 (13%), and indeterminate in 7 (4%)
(Table 2). Because of the retrospective design of the
study, follow up-data were not consistently available
for patients with a benign diagnosis by EUS-FNA.
The US features of the liver lesions as demonstrat-
ed by EUS including size, shape, echogenicity, and
edge characteristics were not predictive of malig-
nant versus benign disease.
The results of US-guided versus CT-guided FNA
were compared with those for EUS-FNA of the liver.
EUS-FNA diagnosed malignancy in 89% (23/26) of
cases in which the diagnosis was missed by US-
860 GASTROINTESTINAL ENDOSCOPY
EUS-guided fine needle aspiration of the liver: international survey
Table 2. US-guided liver FNA versus EUS-guided
liver FNA (N = 26)
Results of Results of
US-FNA EUS-FNA
N (%) N (%)
Diagnostic for malignancy 0 (0) 23 (88.6)
Raising suspicion for malignancy and/or 0 (0) 1 (3.8)
atypical cells
Nondiagnostic for malignancy with 4 (15.4) 1 (3.8)
adequate cellularity
Nondiagnostic for malignancy with 22 (84.6) 1 (3.8)
scant or inadequate cellularity
guided FNA. EUS-FNA was performed after CT-
guided FNA in 7 cases. In 83% (5/6) EUS-FNA of the
liver diagnosed malignancy when CT-guided liver
FNA failed to do so. EUS was performed to locate a
previously undetected primary tumor in the setting
of liver metastases in 33 of 167 (20%) cases. In 17 of
33 (52%) cases, EUS identified a primary tumor (all
in the pancreas).
EUS, including EUS-FNA of the liver, was gener-
ally performed by highly experienced endosonogra-
phers. Endosonographers responding to the survey
had performed a median of 2990 EUS examinations
(range 250-30,000), 500 EUS-FNA procedures
(range 30-1570), and 11 EUS-guided fine needle
aspirations of liver lesions (range 0-41).
Complications and safety
Complications were reported in 6 (4%) cases and
included death, bleeding, fever, and abdominal pain.
One patient (0.6%) died 36 hours after EUS-FNA.
The indication for EUS was a pancreatic mass, and
a liver lesion was identified incidentally. The patient
was suspected to have an occluded biliary stent at
the time of EUS based on a rising bilirubin.
Cholangitis developed and the patient died. One
case was complicated by bleeding. The indication for
EUS was a gastric submucosal lesion. The patient
was hospitalized for 2 days of observation but did
not receive a blood transfusion. Two patients from
different centers had postprocedure abdominal pain
develop. Both were observed as outpatients for 6
hours with no intervention. Six hours was the nor-
mal observation period after FNA of the liver at
both centers. In both cases the indication for EUS
was a pancreatic lesion.
Fever was reported in 2 cases. In one the indica-
tion for EUS was liver metastases from an unknown
primary tumor. The patient was hospitalized and
the fever resolved spontaneously without prophylac-
tic treatment with antibiotics. In the second case,
the indication for EUS was a pancreatic lesion. This
patient was also hospitalized for observation but
VOLUME 55, NO. 7, 2002
EUS-guided fine needle aspiration of the liver: international survey
there was no therapeutic intervention including pro-
phylactic administration of antibiotics.
Impact of EUS-FNA on patient management
The endosonographer responding to the survey
questionnaire was asked to characterize the impact
of the EUS-FNA of the liver on the management of
each patient (Table 3). For one case, data on the
effect of EUS-FNA on clinical management were
missing. Overall, EUS-FNA provided a diagnosis in
70% (118/166) of cases, obviated the need for
surgery in 32% (53/166), and upstaged the tumor in
30% (50/166). Of the 118 cases in which EUS-FNA
made the diagnosis, 94% (111/118) were liver metas-
tasis and 6% (7/118) a primary liver tumor. In 1 case
of pancreatic carcinoma, EUS with EUS-FNA of the
liver negative for malignancy downstaged the tumor
to T4N0M0.
DISCUSSION
This international survey of experience with
EUS-FNA of the liver demonstrates that, in expert
hands, this procedure is relatively safe. The compli-
cation rate was 4%, although this includes one
major complication (death) and several minor com-
plications (bleeding, infection, abdominal pain). The
death after EUS-FNA is of concern and likely result-
ed from introduction of bacteria into an obstructed
bile duct by the needle. For this reason it is recom-
mended that antibiotics be administered prophylac-
tically and biliary drainage be established rapidly
(preferably pre-EUS) if fine needle aspiration of the
liver by any method is to be performed in the setting
of obstructive jaundice.
This study demonstrates that EUS-FNA can pro-
vide a cytopathologic diagnosis of liver metastases
and primary liver malignancies. Additionally, the
findings in this survey show that EUS can identify
a pancreatic primary tumor in a large proportion of
cases in which US, CT, and magnetic resonance
imaging fail to do so. A possible reason for this is
that the resolution of EUS is higher than CT.18-21
One disadvantage of EUS-FNA of the liver is the
limited depth of penetration of high frequency (7.5-
12 MHz) echoendoscopes. Although image resolution
is increased at these higher frequencies, the depth of
examination is limited to 5 to 6 cm, and thus the lat-
eral aspect of the right lobe of the liver cannot be
routinely visualized. Complete hepatic examination
may be possible with newer instruments with lower
frequencies.
The need to identify a primary malignancy in the
setting of liver metastasis is controversial. The iden-
tification of primary pancreatic cancer may be ben-
eficial because pancreatic specific chemotherapy
VOLUME 55, NO. 7, 2002
J tenBerge, B Hoffman, R Hawes, et al.
Table 3. Effect of EUS-FNA on clinical manage-
ment (N = 166, 1 case missing data)
N (%)
Avoided surgery 15 (9.1)
Upstaged tumor 9 (5.4)
Downstaged tumor 1 (0.6)
Made diagnosis 67 (40.5)
Made diagnosis and avoided surgery 15 (9.0)
Made diagnosis and upstaged tumor 18 (10.8)
Made diagnosis, upstaged tumor, and avoided surgery 18 (10.8)
Avoided surgery and upstaged tumor 5 (3.0)
No change 19 (10.8)
offers a survival advantage compared with standard
chemotherapy based on 5-fluoruracil.22 The identifi-
cation of a colorectal primary tumor may allow cura-
tive surgical resection of a liver metastasis or colon
specific chemotherapy, but EUS is not generally
used to detect colon primary tumors. Although this
study suggests that EUS may be useful in the set-
ting of liver metastases from an unknown primary
malignancy, it is premature to conclude that EUS
should be considered for all patients in this setting.
EUS-FNA of the liver can make a diagnosis of
malignancy in cases in which US- or CT-guided fine
needle aspiration do not provide a diagnosis.
Although the present study does not directly com-
pare the accuracy of EUS-FNA with CT- or US-FNA,
the results do suggest that EUS is highly accurate
in cases in which US and CT fail to make a diagno-
sis of malignancy. The reason(s) for this is unclear,
but higher resolution imaging, better access to
lesions in the posterior aspect of the liver, and lack
of interposed bowel and vasculature structures are
possible explanations.
This study has several limitations. It is retro-
spective and was not intended to directly compare
EUS with CT or US for FNA of the liver.
Furthermore, it was not possible to predict the sen-
sitivity and specificity of EUS-FNA of the liver
because definitive follow-up data were not available
for all cases. An attempt was made to minimize
response bias by providing a method of rapid and
convenient communication (e-mail) and by regular
reminders to submit data. The request for responses
from a wide variety of endosonographers also mini-
mized selection bias. The high level of experience of
the endosonographers who participated in the cur-
rent study (median experience 2990 cases) makes it
difficult to extrapolate the results to general clinical
practice. Until further data are available, EUS-FNA
of the liver should be performed by endosonogra-
phers who have considerable experience with EUS
imaging and EUS-FNA of tumors and lymph nodes.
EUS-FNA of the liver is a relatively safe proce-
dure that had a significant impact on the clinical
GASTROINTESTINAL ENDOSCOPY 861
J tenBerge, B Hoffman, R Hawes, et al.
management of the patients included in this survey.
Further prospective data are needed to define the
accuracy of EUS in the detection of liver lesions and
EUS-FNA in comparison to less invasive procedures
such as CT and US. EUS-FNA should be considered
when liver lesions are poorly accessible to CT- or
US-guided FNA but are more accessible to trans-
gastric or transduodenal EUS-FNA. EUS can be
useful in detecting a primary tumor in the setting of
upper abdominal malignancy. Furthermore, the
liver should be carefully imaged during routine EUS
staging of all upper abdominal malignancies.
REFERENCES
1. Rösch T, Lorenz R, Braig C, Gain T, Feuerbach S, Siewert JR,
et al. Staging of pancreatic and ampullary carcinoma by
endoscopic ultrasonography: comparison with conventional
sonography, computed tomography, and angiography. Gastro-
enterology 1992;102:188-99.
2. Rösch T, Lorenz R, Braig C, Classen M. Endoscopic ultra-
sonography in diagnosis and staging of pancreatic and biliary
tumors. Endoscopy 1992;24(Suppl):304-8.
3. Rösch T, Lorenz R, Braig C, Feuerbach S, Siewert JR,
Schusdziarra V, et al. Endoscopic ultrasound in pancreatic
tumor diagnosis. Gastrointest Endosc 1991;37:347-52.
4. Yasuda K, Mukai H, Fujimoto S, Nakajima M, Kawai K. The
diagnosis of pancreatic cancer by endoscopic ultrasonography.
Gastrointest Endosc 1988;34:1-8.
5. Kaufmann AR, Sivak MV Jr. Endoscopic ultrasonography in
the differential diagnosis of pancreatic disease. Gastrointest
Endosc 1989;35:214-9.
6. Williams D, Sahai A, Aabakken L, Penman I, Velse van A, Webb
J, et at. Endoscopic ultrasound guided fine needle aspiration
biopsy: a large single center experience. Gut 1999;44:720-6.
7. Chang K, Nguyen P, Erickson R, Durbin T, Katz K. The clini-
cal utility of endoscopic ultrasound guided fine-needle aspi-
ration in the diagnosis and staging of pancreatic carcinoma.
Gastrointest Endosc 1997;45:387-93.
8. Binmoeller K, Brand B, Thul R, Rathod V, Soehendra N. EUS-
guided, fine-needle aspiration biopsy using a new mechanical
scanning puncture echoendoscope. Gastrointest Endosc 1998;
47:335-40.
9. Erickson R, Sayage-Rabie L, Beissner S. Factors predicting the
number of EUS-guided fine-needle passes for diagnosis of pan-
creatic malignancies. Gastrointest Endosc 2000;51:184-90.
10. Gress F, Hawes R, Savides T, Ikenberry S, Lehman G.
862 GASTROINTESTINAL ENDOSCOPY
EUS-guided fine needle aspiration of the liver: international survey
Endoscopic ultrasound-guided fine-needle aspiration biopsy
using linear array and radial scanning endosonography.
Gastrointest Endosc 1997;45:243-50.
11. Nguyen P, Feng J, Chang K. Endoscopic ultrasound (EUS)
and EUS guided fine-needle aspiration (FNA) of liver lesions.
Gastrointest Endosc 1999;50:357-62.
12. Bentz J, Kochmann M, Faigel D, Ginsberg G, Smith D, Gupta
P. Endoscopic ultrasound-guided real-time fine-needle aspira-
tion: clinicopathologic features of 60 patients. Diagnostic
Cytopathology 1998;18:98-100.
13. Fritscher-Ravens A, Schirror L, Atay Z, Petrasch S, Brand B,
Bohnack S, et al. Endosonographically controlled fine needle
aspiration cytology-indications and results in routine diagno-
sis. Zeitschrift fur Gastroenterologie 1999;37:343-51.
14. Sahai AV, Schembre D, Stevens PD, Chak A, Isenberg G,
Lightdale CJ, et al. A multicenter U.S. experience with EUS-
guided fine-needle aspiration using the Olympus GF-UM30P
echoendoscope: safety and effectiveness. Gastrointest Endosc
1999;50:792-6.
15. Allescher HD, Rösch T, Willkomm G, Lorenz R, Meining A,
Classen M. Performance, patient acceptance, appropriateness
of indications and potential influence on outcome of EUS: a
prospective study in 397 consecutive patients. Gastrointest
Endosc 1999;50:737-45.
16. Williams DB, Sahai AV, Aabakken L, Penman ID, Van Velse A,
Webb J, et al. Endoscopic ultrasound guided fine needle aspira-
tion biopsy: a large single centre experience. Gut 1999;44:720-6.
17. Nickl NJ, Bhutani MS, Catalano M, Hoffman B, Hawes R,
Chak A, et al. Clinical Implications of endoscopic ultrasound:
the American Endosonography Club Study. Gastrointest
Endosc 1996;44:371-7.
18. Hünerbein M, Totkas S, Balanou P, Handke T, Schlag PM. EUS-
guided fine needle biopsy: minimally invasive access to metasta-
tic or recurrent cancer. Eur J Ultrasound 1999;10:151-7.
19. Rösch T. Endoscopic ultrasonography in pancreatic cancer.
Endoscopy 1994;26:806-7.
20. Tio L, Sie H, Kallimanis G, Luiken GJ, Kimmings MN,
Huibregste K, et al. Staging of ampullary and pancreatic car-
cinoma: comparison between endosonography and surgery.
Gastrointest Endosc 1996;44:706-13.
21. Buscail L, Paghs P, Berthilemy P, Fourtanier O, Frexnos J,
Escourrou J. Role of EUS in the management of pancreatic and
ampullary carcinoma: a prospective study assessing resectabil-
ity and prognosis. Gastrointest Endosc 1999;50:34-40.
22. Burns H, Moore M, Andersen J, Green MR, Rotbenberg ML,
Modiano MR, et al. Improvements in survival and clinical
benefit with gemcitabine as first-line therapy for patients
with advanced pancreas cancer: a randomized trial. J Clin
Oncol 1997;15:2403-13.
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