R Lai, V Stephens, R Bardales
17. Hoffer E, Cosgrove J, Levin D, Herskowittz M, Sclafani S.
Radiologic gastrojejunostomy and percutaneous endoscopic
gastrostomy: a prospective randomized comparison. J Vasc
Interv Radiol 1999;10:413-20.
18. Cosentini E, Sautner T, Gnant M, Winkelbauer F, Teleky B,
Jakesz R. Outcomes of surgical, percutaneous endoscopic and
percutaneous radiologic gastrostomies. Arch Surg 1998;133:
1076-83.
19. Little JL, Rhouton AL Jr, Mellinger JF. Comparison of
ventriculoperitoneal and ventriculoatrial shunts for hydro-
cephalus in children. Mayo Clin Proc 1972;47:396-401.
20. Blount JP, Campbell JA, Haines SJ. Complications in ven-
tricular cerebrospinal shunting. Neurosurg Clin N Am 1993;4:
633-56.
21. O’Brien M, Parent A, Davis B. Management of ventricular
shunt infections. Childs Brain 1979;5:304-9.
22. Hahn YS, Engelhard H, McLorne DG. Abdominal CSF pseudo-
cyst. Clinical features and surgical management. Pediatr
Neurosci 1985;12:75-9.
CASE REPORTS
Diagnosis and staging of hepatocellular
carcinoma by EUS-FNA of a portal vein
thrombus
Rebecca Lai, MD, Valerie Stephens, MD,
Ricardo Bardales, MD
Portal vein thrombosis is a well-known but
relatively rare complication of cirrhosis, with a
prevalence that ranges from 1% to 5.7%.1 However,
it is a much more frequent complication of hepato-
cellular carcinoma (HCC). Tumor invasion into the
portal vein by direct venous extension or metas-
tasis occurs in up to 70% of patients with
HCC.1-3 Vascular invasion is a poor prognostic indi-
cator and is a contraindication to surgery and
liver transplantation. Thus, it is important to
distinguish between benign and malignant portal
vein thrombosis.
Several case series describe the feasibility and
safely of FNA of portal vein thrombus under trans-
cutaneous US guidance.1-7 However, this technique
is not used widely, perhaps because of technical
difficulties, especially in accessing thrombus in the
Current affiliations: Division of Gastroenterology, Division of
Pathology, Hennepin County Medical Center, University of
Minnesota, Minneapolis, Minnesota.
Reprint requests: Rebecca Lai, MD, Division of Gastroenterol-
ogy, Hennepin County Medical Center, 701 Park Ave. South,
Minneapolis, MN 55415.
Copyright Ó 2004 by the American Society for Gastrointestinal
Endoscopy 0016-5107/$30.00
PII: S0016-5107(04)00007-0
574 GASTROINTESTINAL ENDOSCOPY
Diagnosis and staging of hepatocellular carcinoma
23. Dulabon GR, Abrams JE, Rutherford EJ. The incidence and
significance of free air after percutaneous endoscopic gastro-
stomy. Am Surg 2002;68:590-3.
24. Panigrahi H, Shreeve DR, Tan WC, Prudham R, Kaufman R.
Role of antibiotic prophylaxis for wound infection in percu-
taneous endoscopic gastrostomy (PEG): result of a prospective
double-blind randomized trial. J Hosp Infect 2002;50:312-5.
25. Dormann AJ, Wigginghaus B, Risius H, Kleimann F,
Kloppenborg A, Rosemann J, et al. Antibiotic prophylaxis
in percutaneous endoscopic gastrostomy (PEG): results from
a prospective randomized multicenter trial. Z Gastroenterol
2000;38:229-34.
26. Kulling D, Sonnenberg A, Fried M, Bauerfeind P. Cost
analysis of antibiotic prophylaxis for PEG. Gastrointest
Endosc 2000;51:152-6.
27. Chaudhary KA, Smith OJ, Cuddy PG, Clarkston WK. PEG
site infections: the emergence of methicillin resistant Staph-
ylococcus aureus as a major pathogen. Am J Gastroenterol
2002;97:1713-6.
centrally located main portal vein. EUS provides
a unique opportunity to image the portal vein in
close proximity. As such, an EUS approach for FNA
would be relatively simple. The first case of EUS-
FNA of a portal vein thrombus is reported here, in
which the primary tumor was suspected but not
apparent at transabdominal US.
CASE REPORT
A 78-year-old man with a 20-year history of exces-
sive alcohol ingestion was hospitalized for evaluation of
generalized weakness and abdominal pain. He was not
known to have liver disease. Examination revealed no
scleral icterus or sign of chronic liver disease. Examination
of the abdomen revealed no enlarged organ or palpable
mass. Laboratory test results were the following: aspartate
aminotransferase, 88 U/L (normal: 5-40 U/L); alanine
aminotransferase, 54 U/L (0-65 U/L); alkaline phospha-
tase, 514 U/L (40-134 U/L); and total bilirubin, 1.9 mg/dL
(0-1.5 mg/dL). The serum albumin was 2.7 g/dL (3.5-5.3 g/
dL) and platelet count, 86,000/mm3 (130-400/mm3). All
serologic tests for viral hepatitis were negative. An alpha
fetoprotein level was not obtained.
Transabdominal US demonstrated a heterogeneous
liver with compression of the inferior vena cava, an ap-
parent portal vein thrombosis, and splenomegaly. The
patient was referred for EUS to rule out pancreatic cancer
as a cause of the portal vein thrombosis. CT obtained in the
interval initially was interpreted as showing a portal vein
thrombosis and intrahepatic biliary dilatation, along with
a possible soft tissue mass in the region of the head of the
pancreas.
EUS was performed with a linear-array echoendoscope
(FG-3630; Pentax Precision Instruments, Orangeburg,
N.Y.), with the patient under conscious sedation. No
pancreatic mass was found. The liver was diffusely
heterogeneous, but no discrete mass was seen. A filling
defect was noted within the main portal vein, which not
only occluded the lumen but expanded the vessel to
VOLUME 59, NO. 4, 2004
Diagnosis and staging of hepatocellular carcinoma
Figure 1. A, Linear-array EUS image, showing lack of color
Doppler flow in main portal vein. B, EUS image, showing 25-
gauge needle in lumen of portal vein.
Figure 2. Photomicrograph of EUS-FNA specimen, showing
a sheet of pleomorphic liver cells with ample granular
cytoplasm, round nuclei, and prominent irregular nucleoli
(Papanicolaou stain, orig. mag. 3600).
VOLUME 59, NO. 4, 2004
R Lai, V Stephens, R Bardales
Figure 3. CT demonstrating large infiltrating mass in right lobe
of liver.
Figure 4. Contrast enhanced CT, showing thrombus (*) in
main portal vein.
a diameter of 2 cm. By Doppler US, there was no flow over
the entire length of the main portal vein (Fig. 1A). Because
of a suspicion that the filling defect was a tumor thrombus,
a specimen was obtained by EUS-FNA with a 25-gauge
needle (EchoTip Ultrasound Needle, Wilson-Cook Medical
Inc., Winston-Salem, N.C.) (Fig. 1B). Three needle passes
were made into the portal vein at the porta hepatis with the
echoendoscope wedged in the duodenal bulb, taking care
to avoid the adjacent bile duct and hepatic artery. Cyto-
pathologists were present during the procedure. The final
cytopathologic diagnosis was hepatocellular carcinoma
(Fig. 2).
The patient tolerated the procedure well, with no
immediate complication. Given the advanced nature of the
disease, he was referred for hospice care. On review of
the CT by a different radiologist, a large mass was noted
in the right lobe of the liver that had previously been
misinterpreted as a combination of biliary dilatation and
hepatic changes related to the portal vein thrombosis
GASTROINTESTINAL ENDOSCOPY 575
R Lai, V Stephens, R Bardales
(Figs. 3 and 4). The patient died approximately 1 month
later from progression of the HCC.
DISCUSSION
Hepatocellular carcinoma accounts for 90% of all
primary liver cancer and causes at least one million
deaths per year worldwide.8 There is marked geo-
graphic variation in the incidence of HCC. Com-
pared with the Far East, it is relatively uncommon
in Western countries. However, the incidence of
HCC has nearly doubled in the past 15 to 20 years
because of the increasing incidence of hepatitis B
and C.7,9 About 80% of HCCs arise against a back-
ground of cirrhosis secondary to viral hepatitis or
alcohol-induced liver disease.8,9 The prognosis is
poor; median survival for patients with unresectable
HCC is 18 weeks.3 Surgery remains the only possi-
bility for cure, and patient selection is dependent
upon prompt and accurate staging.
Hepatocellular carcinoma has a remarkable pro-
pensity for portal venous invasion, which is corre-
lated with intrahepatic metastasis and recurrence.
Thus, vascular invasion is one of the most important
prognostic features and must be correctly identified
before selection of a treatment modality. Surgical
resection and liver transplantation are contraindi-
cated in the presence of portal vein invasion.4-7,10
Because benign portal vein thrombosis can occur,
albeit rarely, in the presence of cirrhosis alone,
benign and malignant thrombus must be distin-
guished in patients who are good candidates for
resection or transplantation.
The appearance of HCC on US can be highly
variable. Small tumors (<3 cm diameter) usually
are hypoechoic relative to the surrounding liver
parenchyma. A larger tumor may exhibit a mosaic
pattern of complex echogenicity, including hyper-
echogenicity that reflects calcification, necrosis,
hemorrhage, or fatty metamorphosis. The reported
accuracy of transabdominal US for detecting HCC in
cirrhotic liver varies widely, with sensitivity that
ranges from 20% to 96%.8,9,11 Small lesions directly
under the right hemidiaphragm often are difficult to
visualize. Detection is especially difficult in end stage
cirrhosis where the echotexture is coarse and the
background heterogeneous; large regenerative nod-
ules and/or extensive fibrosis can hide both small and
large tumors.2,4 Thus, it was not surprising that
transabdominal US and EUS both failed to demon-
strate the liver mass in the present case, whereas, it
was obvious on CT.
Color Doppler US can demonstrate a peritumoral
network of vessels and can help differentiate HCC
from dysplastic nodules and metastasis. Vascular
invasion can be assessed with transabdominal US as
576 GASTROINTESTINAL ENDOSCOPY
Diagnosis and staging of hepatocellular carcinoma
well.8,11 Thrombosis of the portal vein, hepatic veins,
or inferior vena cava can be detected easily and
characterized. The presence of arterial flow within
the thrombus suggests that it is neoplastic instead
of bland.8,11,12 The detection of intrathrombus neo-
vascularity, venous expansion, and direct invasion
of the portal vein on CT may help to differentiate
benign from malignant thrombi.11,13 However, these
imaging characteristics are not entirely specific, and
the diagnostic sensitivity is low, making histopath-
ologic confirmation by FNA desirable.
Percutaneous sampling of a portal vein thrombus
for the diagnosis of HCC was first reported by Joly
et al.2 in 1993. In that case, both US and CT failed
to demonstrate a liver mass, the HCC being
diagnosed by means of a transabdominal US-guided
biopsy from the left portal vein thrombosis obtained
with an 18-gauge needle. Subsequently, the use of
this technique was reported in several case series
that included as many as 46 patients.1,3-7 In all of
these, FNA of portal vein thrombi was found to be
accurate and safe for the diagnosis and staging of
HCC. No complication of the technique has been
reported. It is particularly useful when focal lesions
are not detectable within the cirrhotic liver.2,4,6
Moreover, even in the presence of focal liver lesions,
it may be advisable to sample the portal vein
thrombus instead of the liver mass itself. As long
as the specimen is exclusively from the lumen of the
portal vein, the presence of hepatocytes is definitive
evidence of vascular invasion. Thus, in addition to
providing staging information, a cytopathologic di-
agnosis obtained in this manner also is considerably
simpler, because it avoids the difficulty in distin-
guishing well-differentiated HCC from hepatic
adenoma. In contrast, a bland portal vein thrombus
contains fibrin with scant connective tissue and no
hepatocytes.
Despite well-established efficacy, percutaneous
sampling of portal vein thrombus is not widely
used. This may be because of conceivable complica-
tions such as bleeding, bile duct injury, formation
of a vascular-biliary or arteriovenous fistula, and
pseudoaneurysm formation.5 In addition, substan-
tial technical difficulty may be encountered in
approaching the thrombus while avoiding the he-
patic mass, especially if the thrombus is centrally
located within the main portal vein, in which case,
maximal needle excursion is required. Should the
needle traverse the parenchyma, the presence of
hepatocytes in the specimen could lead to a false-
positive diagnosis.
In contrast to the percutaneous approach, EUS
provides a unique view and access to the main portal
vein. From the duodenal bulb and second part of the
VOLUME 59, NO. 4, 2004
Diagnosis and staging of hepatocellular carcinoma
duodenum, the portal vein can be visualized from
the confluence of the splenic and superior mesenteric
veins cephalad into the porta hepatis. Periportal
collateral vessels or cavernous transformation of the
portal vein, which commonly are associated with
portal vein thrombosis, are also easily and reliably
detected by EUS instruments with color Doppler
US capability. With a linear-array echoendoscope,
the portal vein can be punctured easily with a fine
needle under direct visualization, while avoiding the
adjacent hepatic artery, bile duct, and collateral
vessels (if present). Because the approach is not
transhepatic, it eliminates any need to avoid the
primary tumor and any possibility of contaminating
the specimen with hepatocytes, as can occur if the
needle tracks through the liver parenchyma. Thus,
the rate of false-positive diagnoses is likely to be
lower with the EUS compared with the percutaneous
approach.
Needle track seeding during percutaneous FNA
of abdominal masses (not specifically portal vein
thrombus) is reported, mostly from pancreatic and
liver malignancies. The estimated frequency is
0.003% to 0.009%.14 However, there is no reported
case of needle track seeding as a result of EUS-FNA.
There is one preliminary report of a study,
published in abstract form, that suggested that peri-
toneal carcinomatosis is much less frequent after
EUS-FNA compared with percutaneous FNA.15 In
our patient, the positive result of the EUS-FNA of
the portal vein thrombus established that the HCC
was metastatic. Thus, the clinical outcome would not
have been significantly affected even if needle track
seeding occurred.
The present case is the first reported of EUS-FNA
of a portal vein thrombus for the diagnosis of HCC.
There was no procedure-related complication. Fur-
ther studies are warranted to establish the efficacy
and safety profile for this technique.
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VOLUME 59, NO. 4, 2004
R Lai, V Stephens, R Bardales
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GASTROINTESTINAL ENDOSCOPY 577