S.

Hollerbach 1, 2
J. Willert 1 Endoscopic Ultrasound-Guided Fine-Needle Aspiration
T. Topalidis 3
M. Reiser 1
Biopsy of Liver Lesions: Histological and Cytological
W. Schmiegel 1 Assessment

Background and Study Aims: EUS-guided fine-needle aspira-
tion biopsy (EUS-FNA) is used increasingly for the diagnosis of
mediastinal, biliopancreatic, and gastric tumors. However, little
is known about EUS-FNA in hepatic lesions and the best method
Original Article
Results: EUS-FNA provided appropriate biopsy specimens in 40/
41 patients. It was not possible to aspirate sufficient material in
one patient. On average, 1.4 needle passes were necessary to ob-
tain sufficient amounts of tissue. With regard to malignancy, the

Downloaded by: University of Pittsburgh. Copyrighted material.

for tissue analysis. We assessed EUS-FNA combined with histo-
logical and cytological evaluation in selected patients.
Patients and Methods: 41 patients (66  7 years) were prospec-
tively studied, 33 of whom had clinical findings suggestive of liv-
er malignancies. Selection for EUS-FNA was based on an in-
creased risk of bleeding from percutaneous biopsy (coagulopa-
thy, cirrhosis, ascites, aspirin intake; n = 15), presence of small
liver tumors < 2 cm (n = 12), or liver lesions found incidentally
(n = 14). Transgastric EUS-FNA of lesions located in accessible
liver segments was performed using the Hitachi FG-34UX long-
itudinal echo endoscope and a 22-G aspiration needle. Speci-
mens were submitted separately for standard cytological and
histological evaluation. In the case of malignancies, findings at
surgery with histological examination, endoscopy, or computed
tomography (CT)-guided biopsy of the primary cancer served as
reference results (n = 33), while in benign disorders, a combina-
tion of imaging studies (Magnetic Resonance Tomography
[MRT], scintigraphy) and the clinical follow-up, as summarized
in the physician's report, was used as reference.
combination of histological and cytological examination had a
sensitivity of 94 %, specificity of 100 %, negative predictive value
(NPV) of 78 %, and positive predictive value (PPV) of 100 %. Tissue
diagnoses were in agreement in 27/41 patients (65 %). In the re-
maining patients, only the cytological examination identified six
lesions correctly, while the histological assessment was correct
in another seven patients. Malignant lesions were correctly
identified by cytology in 24/33 (73 %) patients, while histology
alone was diagnostic for malignancy in 27/33 (82 %) patients.
When both modalities were combined, 31 out of 33-malignan-
cies (94 %) were correctly diagnosed. Minor complications oc- 743
curred in two patients and consisted of self-limiting local bleed-
ing.
Conclusions: EUS-FNA of liver tumors is a powerful, reliable,
and safe procedure for the diagnosis of malignant liver lesions.
Optimal diagnostic results are achieved by combining cytologi-
cal with histological assessment. Hence, EUS-FNA is an alterna-
tive to percutaneous biopsy, particularly in patients at risk of
bleeding or with small lesions of the liver.

Institution
1
Department of Internal Medicine, Ruhr University Bochum, Knappschaftskrankenhaus, Germany
2
Department of Gastroenterology, Allgemeines Krankenhaus Celle, Celle, Germany
3
Institute of Cytology, Hannover, Germany

Corresponding Author
S. Hollerbach ´ Klinik für Gastroenterologie, Allgemeines Krankenhaus Celle ´ Academic Teaching Hospital ´
University of Hannover ´ Siemensplatz 4 ´ 29223 Celle ´ Germany ´ Fax: +49-5141-721209 ´
E-mail: stephan.hollerbach@akh-celle.de

Submitted 25 March 2003 ´ Accepted after Revision 3 April 2003

Bibliography
Endoscopy 2003; 35 (9): 743±749  Georg Thieme Verlag Stuttgart ´ New York ´ ISSN 0013-726X
 Introduction
Approximately 20 years after the introduction of endoscopic ul-
trasonography (EUS), this technique is used progressively more
often for the locoregional staging of mediastinal, esophageal, bil-
iopancreatic, and gastric tumors, and of suspicious lymphatic
nodules [1, 2]. In addition, EUS has been increasingly used to
guide fine-needle aspiration (FNA) biopsy through the working
channel of echo endoscopes, to obtain a definitive tissue-based
cytological diagnosis. Endosonography-guided FNA (EUS-FNA)
is particularly helpful in areas surrounding the upper and lower
gastrointestinal tract within a distance of 5±7 cm, where lesions
are difficult to approach or inaccessible for minimally invasive
diagnostic procedures, such as the posterior mediastinum and
Original Article
the pancreas, and the biliary, retroperitoneal, and perirectal
space. In recent years, several prospective controlled studies
have shown that EUS-FNA provides a safe way of obtaining rapid
and reliable diagnoses in benign and malignant disease [1 ± 5].
Improved accuracy and cost-effectiveness have been demon-
strated in comparisons with other imaging techniques [1 ± 7].
In some instances, suspicious lesions in the liver may cause a di-
agnostic dilemma since they may develop with a background of
advanced chronic liver disease (e. g. cirrhosis). Advanced cirrho-
sis is frequently associated with complications such as coagulo-
pathies, infections, or infected ascites, or a combination of these
clinical problems. In particular, advanced coagulopathy and large
amounts of ascites can be a relative contraindication for percuta-
neous biopsy, since severe bleeding can occur which may ulti-
mately lead to severe morbidity and even death. Under these cir-
cumstances, alternative techniques such as laparoscopic biopsy
are clearly beneficial. With the advent of more microinvasive
744 techniques such as transgastric EUS-FNA, another potential al-
ternative technique exists that may also be beneficial in these
patients. EUS-guided FNA is even less invasive than laparoscopy
which makes this technique attractive in this clinical setting.
Figure 1 Schematic overview of the anatomical site, showing the
segments of the liver that can be reached using the endoscopic ultra-
sound transducer with fine-needle aspiration biopsy (EUS-FNA). The
yellow lines indicate the area of the liver that can be visualized from
the stomach/proximal duodenum by EUS, while the white circles indi-
cate small accessible lesions in the liver that can easily be biopsied un-
der direct endosonographic vision and guidance (broken white line).
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
EUS-guided biopsy of accessible liver lesions in such patients has
the significant advantage of minimizing the distance between
the imaging transducer and the lesions (Figure 1). Hence, fine-
needle biopsies using thin 22-G needles, which are obtained un-
der full EUS guidance with the transducer only 1.5 ± 3 cm away
from the lesion, should theoretically be safer, though as yet clin-
ical data are lacking regarding this issue.
In another subgroup of patients, liver lesions are not readily ac-
cessible by ultrasound-guided or computed tomography (CT)-
guided percutaneous biopsy, particularly when they are small
(< 2 cm) or when it is difficult to discern the lesions from the tis-
sue background (ªisodenseº lesions). Until now, few studies have
reported data about the potential role of EUS-FNA of liver masses
in these instances [8 ± 10], and little is known about the clinical
potential of EUS-FNA as an alternative route in these and other
patient subgrups. Though it is not possible to visualize all of the
liver by means of transgastric or transduodenal EUS, the entire
left lobe and most central segments of the liver (i. e., segments
I±V) are usually accessible, as schematically outlined in Figure 1.
To evaluate the feasibility, safety, and reliability of EUS-FNA in
Downloaded by: University of Pittsburgh. Copyrighted material.
circumscribed liver lesions, we performed the following pro-
spective and controlled study with particular regard to patients
at high risk, for example because of portal hypertension, coagu-
lopathy, ascites, or aspirin intake. In addition, we compared the
accuracy of standard routine cytological and histological tech-
niques in this patient setting.
Patients and Methods
Patients
Between August 2000 and March 2002, 41 patients (age 66  7
years) who were considered to be fit for evaluation (Karnofsky
index of 70 % or greater) were prospectively enrolled in this study
according to the following clinical criteria:
1. Patients were considered who had a known or suspected ma-
lignancy (esophageal, gastric, pancreatic, or pulmonary), in
whom liver lesions had either been previously detected, or
suspected during standard ultrasound or helical CT scan
(n = 27).
a) Among these patients, selection for EUS-FNA focused on
patients at increased risk with regard to conventional per-
cutaneous biopsy because of, for instance, the presence of
advanced liver cirrhosis with coagulopathy, low platelet
counts (between 30 000 and 50 000), presence of ascitic
infection, or aspirin intake (n = 15). Cirrhosis had been con-
firmed by biopsy in the majority of patients during prior
hospitalizations.
b) Selection for EUS-FNA also focused on patients in whom
the particular location in the liver of the lesion made access
difficult for CT- or ultrasound-guided biopsy, and/or in
whom only a small mass (< 2 cm) was visible (n = 12).
2. Patients were enrolled in whom a liver lesion or tumor was
accidentally found during EUS for other causes, such as be-
nign or malignant biliary, pancreatic, gastric, or esophageal
disease (n = 14).
All patients completed a standard questionnaire regarding the
performance and safety of endoscopy, EUS, and FNA, including a
standard written informed consent sheet.
Endoscopy and Investigational Techniques
Patients fasted overnight. EUS was then carried out with the pa-
tient in a left lateral decubitus position or supine, and by means
of a longitudinal scanner echo endoscope (FG-34 UX; Hitachi Ul-
trasound, Wiesbaden, Germany), equipped with a 7.5-MHz
curved-array linear ultrasound transducer. A standard Hancke±
Vilmann aspiration biopsy needle (22 G), distributed by GIP
MediGlobe, was used in all instances. All patients received seda-
tion with intravenously administered midazolam (0.1 ± 0.25 mg/
kg body weight) and/or disoprivan (60 ± 380 mg) during the in-
vestigation.
Sampling Protocol
Approximately half of the aspirated tissue cylinders were gently
pushed with the needle stylet onto glass slides for cytological a-
nalysis. Subsequently, slide smears were prepared and air-dried.
The remaining half of the aspirated tissue cylinders were poured
in toto directly into a small plastic bottle containing formalin, to
facilitate standard histological analysis of whole-tissue speci-
mens. These procedures were carried out in a randomized fash-
ion to minimize a possible sampling bias. We performed as many
FNA passes as required to obtain a minimum of five slides of as-
pirated tissue for cytological assessment, while five or more ad-
ditional tissue cylinders submerged in formalin were required
for standard histological examination. From our previous studies
it was known that the optimal number of slide smears for ade-
quate tissue analysis was five or more. The number of needle
passes needed to meet these requirements was noted in each pa-
tient. The order in which tissue samples were placed onto slides
or into formalin bottles was changed in a random fashion. Slides
were then submitted to the Institute of Cytology, Hannover, Ger-
many for standard cytological investigations (T.T.), including
Pappenheim dying and application of Papanicolaou criteria,
while the tissue cylinders in formalin were sent separately for
standard microscopic evaluation. The histological examinations
were performed at the Institute of Pathology at the BG Hospital
ªBergmannsheilº, Ruhr University Bochum.
The cytologist and the histopathologists were not present in the
endoscopy suite during the examinations. In addition, they were
fully blinded to one other's interpretations. Only a brief descrip-
tion of the clinical problem accompanied each tissue sample.
The criteria for a positive test finding consisted either of a defini-
tive histopathological diagnosis, a clear cytological and histologi-
cal result, or presence of a positive cytological finding for malig-
nancy, that was later confirmed by the reference methods and
the clinical course of the patients (see below).
Reference Standards
In all patients with malignant disorders, histological findings
from samples obtained from surgery or CT-guided biopsy, in
combination with the final report from the physician served as
the reference. In benign disorders, however, the clinical follow-
up of greater than 6 months and the results of other imaging
techniques such as helical CT, ultrasound, MRT, and/or scintigra-
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
phy, as carefully listed and documented in the final report of the
physician, were used as reference.
Statistical Analysis
A prospective analysis was carried out of the number of needle
passes (mean values) needed to obtain sufficient amounts of tis-
sue for both histological and cytological examinations, and of the
number of any complications.
The sensitivity, specificity, positive predictive value (PPV), and
negative predictive value (NPV) of the histological and cytologi-
cal findings, compared with the results of the reference methods,
were analyzed using appropriate 2 ” 2 tables. The sensitivity and
specificity were calculated in a combined fashion that included
Original Article
both malignant and benign findings.
Results
General Assessment and Safety
The diagnostic procedure (EUS-FNA) was well tolerated by a
large majority of patients. No major complications requiring sur-
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gical or interventional measures were observed. Minor compli-
cations occurred however, in only two patients, and consisted of
self-limiting local bleeding in both cases. These two patients
were closely monitored clinically and a follow-up abdominal ul-
trasound check was performed after 24 hours, which excluded
relevant pathological conditions. No further interventions (e. g.
endoscopic measures) or blood transfusions were necessary in
either case.
EUS provided excellent local resolution of accessible liver lesions,
which facilitated the identification of even small tumor lesions 745
of diameter < 2 cm (Figure 2 a ± c). Such lesions could subse-
quently be biopsied by EUS-FNA under direct ultrasonographic
visualization, which provided an accurate tissue-based tumor di-
agnosis in most of the patients who participated in our study, as
illustrated for two patients in Figure 3 a, b, 4 a ± c. Table 1 pro-
vides an overview of the details regarding the different tumor
types involved, and the individual results from both the histolo-
gical and cytological specimens obtained by EUS-FNA in all pa-
tients.
Number of Needle Passes
On average, 1.4  0.6 needle passes were necessary to obtain the
substantial amount of tissue that was required by the biopsy
protocol for both histological and cytological analysis in this
study. EUS-FNA provided sufficient amounts of tissue in 40 out
of 41 patients, in whom an FNA biopsy was performed. In one pa-
tient (2 %) presenting with a focal nodular hyperplasia (FNH), the
aspirated cellular material was too scanty to permit precise his-
tological examination.
Biopsy Results
The sensitivity of EUS-FNA for malignant disease was 94 % with
an NPV of 78 % when both modalities of tissue analysis were
combined, as outlined in Tables 1 and 2. Hence, an accurate diag-
nosis could be made in 31 out of 33 patients. Table 2 presents a
summary of the statistical analysis for all the patients who
participated in our study. In particular, the sensitivity for correct
Original Article
746
Figure 2 a Endoscopic ultrasound (EUS) appearance of a small 1-cm
nodule (arrow) that was found incidentally during an EUS examination
in the left lobe of the liver (segment II). b Transgastric EUS-FNA biopsy
of the tumor nodule shown in a, under direct ultrasound-guided visual-
ization. The tip of the 22-G puncture needle can clearly be seen as an
echogenic strand within the echo-reduced tumor nodule (arrow). c
Histological examination revealed a single small metastasis of a well-
differentiated neuroendocrine tumor. The primary tumor was later
found to be located in the ileocecal region of the colon.
diagnosis was 92 % over all the patients, while the specificity was
100 % and the NPV of EUS-FNA was 72 % in this setting (Table 2).
Cytological examination alone identified malignant tumors/me-
tastases correctly in 24 out of 33 patients (73 %), while histologi-
cal examination alone was correct in 27 out of 33 patients (82 %).
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
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Figure 3 a Small (1.2 cm) but sonographically distinct tumor nodule
(arrows) at the base of the left lobe of the liver in a patient with a pan-
creatic carcinoma. The FNA needle is clearly visible in the center of the
tumor (yellow triangle). b Cytological examination revealed metastasis
of a poorly differentiated adenocarcinoma of the pancreas that had not
been detected by helical computed tomography (CT) scanning prior to
the EUS investigation.
In only five patients in this study was the correct diagnosis
provided by neither cytological nor histological examination.
Benign tumors (hemangioma, focal nodular hyperplasia (FNH),
benign cyst) were correctly diagnosed in five out of eight pa-
tients, when the morphological EUS examination results were
combined with cytological and histological findings. However,
both histological and cytological investigation failed to establish
the definite diagnosis in the two patients with FNH, in whom the
final diagnosis was based on the scintigraphy findings and clini-
cal follow-up.
Overall, cytological and histological results were in agreement in
27 out of 41 patients (66 %).
In the two patients with benign FNH, the biopsy specimens con-
tained sufficient cellular material; however, both histological
and cytological assessment only revealed ªunspecific abnormal-
itiesº of the tissue without providing a clearly defined diagnosis.
 Original Article
Figure 4 a Transgastric endosonographic image of an echo-bright tu-
mor nodule measuring 2.5 cm in diameter, which was located in seg-
ment II of the left lobe of the liver in a patient with severe coagulopa-
thy due to decompensated cirrhosis. The tumor had previously been
detected by abdominal ultrasound as arising from a cirrhotic liver,
and confirmed by CT scanning. Percutaneous biopsy appeared to be a

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high-risk procedure in this patient who had already had a history of se-
vere bleeding from another percutaneous procedure elsewhere. b
EUS-guided fine-needle biopsy was performed transgastrically by
using a 22-G fine needle, without any visible and relevant complica-
tion. c Cytological assessment (and also histological assessment) dis-
closed the presence of a well-differentiated hepatocellular carcinoma
in this patient, which was subsequently treated in a palliative fashion
by repeated fine-needle injection therapy using absolute alcohol. Dur-
ing the patient's follow-up visits, no significant tumor growth was ob-
served.

747

Table 1 Agreement between histological and/or cytological re- Table 2 Summary of the statistical analysis of the subgroup of pa-
sults and tumor type, in patients with hepatic tumor le- tients with malignancies (n = 33), and of all patients enrol-
sions (n = 41), as proven by reference methods led (n = 41) in the study

Tumor type n EUS-FNA diag- Histological Cytological Sensitivity, % Specificity, % PPV, % NPV, %
nosis correct diagnosis diagnosis
(histological correct correct EUS-FNA in malignant
and cytological) disease 94 100 100 78
EUS-FNA in all conditions,
Colorectal cancer 8 7/8 7 6 including benign lesions 92 100 100 72
Lung cancer 9 9/9 8 9
Pancreatic cancer 6 6/6 4 5 EUS, endoscopic ultrasonography; FNA, fine-needle aspiration cytology; PPV, pos-
itive predictive value; NPV, negative predictive value.
Breast cancer 4 4/4 4 2
HCC 3 3/3 2 2
CCC 2 1/2 1 0
NHL 1 1/1 1 0
Hemangioma 3 2/3 2 0 Hence, we considered the FNA diagnosis to be incorrect in both
Benign cyst 3 3/3 0 3 cases (Table 1).
Focal nodular
hyperplasia 2 0/2 0 0 In the 15 patients with lesions arising within a cirrhotic liver, the
HCC, hepatocellular carcinoma; CCC, cholangiocellular carcinoma; NHL, Non- biopsy results did not substantially differ from those obtained in
Hodgkin's lymphoma. patients without chronic liver disease.

Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
 Discussion
This prospective controlled study shows that EUS-FNA is a feasi-
ble, safe, and powerful technique for obtaining a definite tissue-
based diagnosis in patients with focal liver lesions, particularly
those of cancerous origin. In addition, it can be performed as an
alternative method in patients who present with an enhanced
risk for complications during percutaneous biopsy, and even in
very small accessible lesions in the liver (< 1 cm). The best diag-
nostic results are achieved when tissue analysis is performed
both by histological and cytological assessment of specimens.
Negative FNA results, however, do not rule out malignant disease
and the procedure should be repeated, if clinically feasible. To
the best of our knowledge, this is the first study that assesses in
Original Article
a prospective fashion the diagnostic performance of EUS-FNA to-
gether with an optimization of tissue sampling from liver le-
sions. From our data we conclude that EUS-FNA has certain ad-
vantages in selected patients, if performed by an expert, but we
acknowledge that we certainly need more data on this subject
before EUS-FNA can be recommended to a broad readership as a
ªstandardº procedure in this clinical setting. Hence, our data
open a new avenue of investigational endoscopy. Comparative
studies are clearly needed, particularly those that compare EUS-
FNA prospectively with various percutaneous techniques in
high-risk patients, before use on a larger scale can be re-
commended.
Besides the literature on the established clinical indications for
EUS-FNA, such as gastrointestinal and pancreatic cancer staging
and the differential diagnosis of submucosal tumors, only a few
studies have yet been published that deal with new applications
of EUS-FNA, such as the diagnosis of liver tumors by using EUS-
748 guided FNA biopsy [8 ± 10]. Recently, a large but retrospective
multicenter study was performed by ten Berge et al. This group
[10] reported a relatively high level of safety and a high sensitiv-
ity of EUS-FNA (> 90 %) in the diagnosis of liver masses, which
was superior to percutaneous biopsy attempts in the same pa-
tient selection. The rate of minor complications was 4 % in ten
Berge's study, while major complications were observed in 1 %
of patients, including one death from biliary sepsis. These results
are in some respects in keeping with ours, particularly with re-
gard to the diagnostic sensitivity and to the rate of minor compli-
cations, which reached 2.5 % in our present prospective study.
However, no major complication occurred in our setting. Such
differences in the complication rate are likely attributable to dif-
ferences in patient selection, since the study of ten Berge and co-
workers seemed to include very sick patients, such as an individ-
ual with an occluded biliary stent and subsequent biliary sepsis.
In addition, the results of Berge et al. were obtained in the condi-
tions of a large multicenter study. Considering the notable pro-
portion of patients in our study who were at a relatively high
risk of bleeding from percutaneous biopsy (15 patients with as-
cites, cirrhosis, aspirin intake, low platelet count, or coagulopa-
thy), the procedure was surprisingly safe and no procedure-relat-
ed infection was seen in our study. This result is well in keeping
with the study of Barawi and co-workers [11], who reported no
adverse events such as bacteremia or any other infectious com-
plications that were attributable to EUS-FNA, in their large sur-
vey on the potential infectious complications that may be asso-
ciated with EUS-FNA.
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
Taking the previous and present study together [8 ± 10], EUS-FNA
of liver lesions compares favourably with the diagnostic accuracy
of EUS-FNA in other diseases, particularly with respect to pan-
creatic malignancies [2,12]. In a large international multicenter
trial, Wiersema et al. report similar results for EUS-FNA in the di-
agnosis of other accessible extraluminal masses [1], suggesting
that EUS-FNA of liver lesions can now be considered to be an in-
tegral part of the EUS repertoire in selected patients, which has
already emerged as routine procedure in specialized EUS centers.
One of the major advantages of EUS-FNA is the ability to simulta-
neously offer diagnostic ultrasound assessment and interven-
tional procedures, such as tissue sampling, and even therapeutic
procedures such as celiac plexus neurolysis. Hence, EUS-guided
FNA of liver lesions should be used particularly in those patients
in whom an endoscopic ªone-stop shopº procedure, including si-
multaneous diagnosis, staging, and sometimes even palliative
therapy [13], is desirable. In the future, it seems possible that
EUS-guided fine-needle injection therapy (EUS-FNI) for pallia-
tive therapy of malignant diseases such as liver metastasis may
play an important role if integrated into a multimodal therapeu-
tic concept, as described recently [13].
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On average, 1.4 needle passes were necessary to provide suffi-
cient tissue in our study. Approximately the same rate was re-
ported in a study by Nguyen et al. [9], suggesting that fine-needle
biopsy of liver lesions is a very reliable technique for obtaining
sufficient amounts of tissue for laboratory analysis in most of
the clinical diseases studied. These results are also in the range
of those reported in previous studies with regard to other acces-
sible organs [1 ± 3, 5, 6]. We used the opportunity to combine his-
tological and cytological examination to achieve the best possi-
ble results from EUS-FNA. This approach apparently optimizes
the results of tissue analysis, since the combined approach en-
hances the sensitivity and, particularly, the specificity of find-
ings. It remains to be demonstrated whether the application of
immunohistochemistry and molecular markers (e. g., oncogenes
or tumor suppressor genes such as SMAD4, p53, k-ras) can fur-
ther enhance diagnostic accuracy from tissue biopsies.
The question of whether EUS-guided biopsy of accessible liver le-
sions in patients with advanced cirrhosis and coagulopathy and/
or thrombocytopenia is really safer than percutaneous biopsy
techniques cannot be resolved from our data. Though EUS-FNA
has the significant advantage of minimizing the distance be-
tween the imaging transducer and the lesions (see Figure 1), we
did not compare the techniques with each other. Theoretically,
fine-needle biopsies using thin 22-G needles, which are obtained
under full EUS guidance with the transducer only 1.5 ± 3 cm away
from the lesion, should be safer than long-distance percutaneous
needle procedures; this is clearly supported by the relatively low
bleeding rate in our patients. However, data regarding these is-
sues are still lacking.
In summary, EUS-FNA of liver tumors is a powerful, accurate,
minimally invasive, and safe alternative tool for the diagnosis of
malignant liver lesions. It can be particularly useful in patients
with small liver lesions that are difficult to reach with percuta-
neous biopsy techniques, and in patients in whom unclear find-
ings are first detected during EUS staging examinations. The best
diagnostic results are achieved by combining standard cytologi-
cal with histological assessment. Negative results do not rule out
malignant disease and the procedures should be repeated, as
clinically required. EUS-FNA can also be simultaneously used for
the diagnosis and staging of malignancies (ªone-stopº proce-
dures). Further investigations are needed to evaluate the thera-
peutic potential of EUS-guided therapy in some of these instan-
ces.
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749