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TX, approved the protocol. Informed consent was obtained cytopathologic findings. Follow-up data were gathered 24
for the participation in the study. to 72 hours after the procedure, from clinic visits, collection
Patients with newly diagnosed pancreatic, biliary, of additional radiologic test results, and review of
esophageal, colon, and gastric cancer were prospectively cytopathologic findings. Patients were followed to the time
enrolled for participation in the study from July 2004 to of death or censored at the time of last visit to their
July 2005; and patients with diagnosis of lung cancer were physicians.
prospectively included from March 2004 to July 2005.
Patients with advanced heart or lung disease that precluded Statistics
conscious sedation were excluded. Patients were referred Sample Size Assumptions and Estimates
from the Veterans Affairs inpatient service, gastroenterol- The study was designed to detect a difference of 35%
ogy clinic, primary care clinic, surgery clinic, and subspeci- between the sensitivity of EUS and that of CT scan with a
alty clinics (Oncology, Pulmonary). Patients were evaluated power of 0.80 and a 2-sided a level of 0.05. To identify such
by means of a history taking, physical examination, blood a difference, the study required a minimum of 27 patients
count, measurement of electrolytes, and tests of renal and with liver metastases. Assuming that liver metastases are
liver function. All participants underwent CT scan and present in about 15% of patients with resectable cancer, a
EUS examination of the liver. In majority of the cases, EUS minimum of 170 patients had to be enrolled.
was performed after the CT scan. Endoscopic ultrasound-
guided fine needle aspiration (EUS-FNA) was performed in
subjects with endosonographic evidence of a noncystic liver
Statistical Tests
lesion. After the procedure patients were referred back to Sensitivity, specificity, positive predictive value, nega-
the clinic from which the patient was identified for further tive predictive value, and accuracy of the CT scan, EUS,
management and follow-up. EUS-FNA, and EUS/EUS-FNA as a combined test were
calculated and compared. EUS/EUS-FNA was defined
Outcomes positive when diagnosis of malignancy could be established
The primary outcome of the study was to compare the cytologically. EUS/EUS-FNA was defined as negative
accuracy of EUS/EUS-FNA and CT scan for the detection when lesions were not visualized on EUS and in cases
of liver metastases. The secondary outcome was to when lesions were visualized, the EUS-guided FNA yielded
determine the safety of EUS-FNA. Gold standard for the nonmalignant cells. The results were analyzed on a per-
diagnosis of metastases included cytopathologic confirma- lesion and per-patient basis. McNemar tests were used to
tion of malignant cells. If tissue could not be obtained from assess the differences between accuracies of tests. Nonpara-
liver lesions and there was progression in the size and metric tests (Wilcoxon signed-rank test) were used to
number of lesions in follow-up imaging, lesions were compare the number of lesions among EUS and other
considered to be malignant. tests. A Spearman correlation coefficient was run to assess
the correlation between the CT scan and EUS for the
EUS/EUS-FNA Procedure multiplicity of the lesions. If one lesion in a subject was
EUS and EUS-FNA was performed by a single cytologically established to be malignant, then all other
endoscopist. The curved linear-array echoendoscope (GF- lesions with similar imaging characteristics were also
UCT/P 1140; Olympus America Corp, Melville, NY) was considered to be malignant. Lesions were defined as false
used for all endosonographic examination and fine needle positive when the cytology was negative for malignancy and
aspiration. EUS/EUS-FNA test was called positive if there was no progression on follow-up imaging. False-
EUS–FNA-guided cytology showed malignant cells. EUS/ negative lesion was defined as lesion that was read as benign
EUS-FNA was called negative if EUS-FNA was negative lesion due to negative cytology or due to characteristics of
for malignant cells or EUS did not show lesion in the liver the lesion; however, on follow-up the lesion increased in
that required sampling. The liver was examined at 7.5 MHz size. A ‘‘P’’ value of less than 0.05 was considered to
frequencies. EUS-FNA was performed using a 22-gauge indicate statistical significance. All analyses were carried
needle (Olympus FNA needle, Olympus America Corp). A out using SAS Version 9.1 (SAS Institute, Cary, NC).
pathologist and the cytotechnologist were present in the
room to provide immediate interpretation as to whether RESULTS
adequate material was obtained for diagnosis. One hundred thirty-two patients with newly diagnosed
pancreatic, biliary, esophageal, colon, gastric, or lung
CT Scan cancer were prospectively enrolled in the study. Mean age
All CT examinations were performed with the use of a of the subjects was 67 years (SD ± 9.7; range: 45 to 86).
helical CT scanner (model PQ-5000, Picker International, EUS and CT scan were performed in 132 and 131 cases,
Cleveland). Images were acquired with the use of 10-mm respectively. Intravenous contrast for CT scan was used in
collimation, a table speed of 6.25 mm/s at 175 mA and 85% (112) of the cases. Twenty-six subjects were identified
120 kV, and a pitch of 1.50. Images were obtained during a with metastases of the liver. One patient was excluded from
single breath-holding session when possible. Omnipaque the analysis as pancreatic mass was diagnosed as non-
300 (100 mL) was administered intravenously to the Hodgkin lymphoma (Table 1).
patients. Injection rate of 3 mL/s and scan delay
of 60 to 70 seconds was used. EUS/EUS-FNA
EUS was performed in 132 cases of which 35 were
Follow-up for Complications identified with definite liver lesions. EUS-FNA was
Follow-up consisted of a patient interview by a nurse performed in 32 cases. EUS-FNA was not performed in 3
or a physician, communication with the primary physician, cases with EUS findings characteristics of cystic lesions in
collection of additional radiologic test results, and review of the liver. FNA established the tissue diagnosis of metastases
FIGURE 1. A, EUS image showing hypoechoic metastatic lesions. B, EUS-FNA of the hypoechoic metastatic lesion in the liver.
C, EUS image showing isoechoic metastatic lesion in the left lobe of the liver. D, EUS image showing hyperechoic metastatic lesions in
the left lobe of liver. EUS indicates endoscopic ultrasound; EUS-FNA, endoscopic ultrasound-guided fine needle aspiration.
TABLE 2. Comparison of Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Accuracy of the CT Scan, EUS
and EUS-FNA for the Diagnosis of Liver Tumors
Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%)
CT scan 96 (91-98) 92 (85-96) 73 (64-80) 99 (95-100) 92 (86-96)
EUS 100 (96-100) 96 (91-99) 87 (80-92) 100 (96-100) 97 (92-99)
EUS/EUS-FNA 92 (86-96) 99 (95-100) 96 (91-99) 98 (94-100) 98 (93-99)
CT indicates computed tomography; EUS endoscopic ultrasound; EUS-FNA, endoscopic ultrasound-guided fine needle aspiration; NPV, negative
predictive value; PPV, positive predictive value.
months did not show lesions in these 3 cases, it was Content 1, which demonstrates EUS of the liver showing
assumed that these patients developed metastases later. three hypoechoic lesions, http://links.lww.com/A867)].
Two of the five cases had very small (2 to 3 mm)
indeterminate lesions detected at 6 and 15 months. These Interobserver Variation for the Identification
patients are currently under follow-up. Follow-up radi- of the Lesions
ologic imaging of the liver is not available in 42 cases. Radiologist with an expertise in abdominal imaging
Reason for not having follow-up imaging are as follows: 7 performed the blinded review of CT and EUS photographs
of the 42 cases had cytologically proven liver metastases by at a remote time. There was a high degree of reliability
EUS-FNA; and 23 subjects died within 3 to 4 months. between the 2 raters (endoscopist and radiologist). A
There were 12 cases with survival more than 5 months and radiologist was in agreement with endoscopist for the
did not have a follow-up imaging. identification of liver lesions in 96% of cases.
Comparison of EUS With CT Scan for Safety of the EUS/EUS-FNA
Number of Lesions Follow-up of patients is categorized as immediate (24
Of 26 patients with malignant lesions in the liver, 13 to 72 h after the procedure), intermediate (4 to 14 d after the
subjects had numerous (>6) lesions in the liver. The range procedure), and long term (15 d onwards). Immediate
of numerous lesions was from 6 to 20. Eleven subjects had follow-up was available in 68% (90 of the 132) cases.
numerous lesions on EUS and 11 subjects had numerous Intermediate follow-up was available in 37 of the 42 cases
lesions on CT scan. EUS and CT scan were found to be with no immediate follow-up. Five cases in whom neither
significantly positively correlated (P =0.0002) for numer- short nor intermediate follow-up was available, had long-
ous lesions. Patients with numerous lesions were excluded term follow-up. Overall, 116/132 (88%) had long-term
when comparing the EUS and CT scan. follow-up. Six of the 132 cases died within a period of 1
month due to advanced metastatic disease and comorbid-
Total Lesions (Benign and Malignant) ities (median survival 18 d, range: 4 to 25).
Compared with CT scan, EUS detected significantly Thirty-two patients underwent EUS-FNA. In total, 66
higher number of total lesions (51 vs. 27; P = 0.005). needle passes were made in 34 lesions. No complications
Stratifying the lesions to left and right lobes of the liver were observed as a result of EUS-FNA of the liver.
showed that EUS detected significantly higher number
of lesions than CT scan in the left lobe (32 vs. 12; DISCUSSION
P = 0.002). There was no significant difference between This prospective controlled study showed that EUS/
EUS and CT for the number of lesions in right lobe EUS-FNA is a safe and an accurate test for the detection
(19 vs. 15; P = 0.79) (Table 3).
Malignant Lesions
For malignant lesions, EUS detected significantly TABLE 3. Comparison of EUS and CT Scan for Detection of
higher number of lesions than the CT scan (40 vs. Hepatic Lesions
19; P = 0.008). EUS detected more lesions than CT scan CT Scan EUS P
in left lobe of the liver (25 vs. 8; P = 0.005). EUS detected
more lesions in the right lobe as compared with the CT scan Lesions (benign)
(15 vs. 11; P = 0.59); however, the difference was not Both lobes 8 11 1.0
Left lobe 4 7 0.50
statistically significant (Table 3; Figs. 2, 3). Right lobe 4 4 1.0
Lesions (malignant)
Both lobes 19 40 0.008
Small Lesions on CT Scan Left lobe 8 25 0.005
CT scan detected lesions in liver that were too small to Right lobe 11 15 0.59
be characterized (<1 cm) in 8 patients of which 3 were Lesions (benign+malignant)
malignant and 5 were benign. EUS visualized these small Both lobes 27 51 0.005
lesions in 7 (88%) cases. Of these, EUS-FNA correctly Left lobe 12 32 0.002
characterized the lesion to be malignant in 3 cases and benign Right lobe 15 19 0.79
in 4 cases. In one case with benign lesion, the lesion was not CT indicates computed tomography; EUS endoscopic ultrasound.
identified by EUS [Fig. 2, (see Video, Supplement Digital
FIGURE 2. A, CT scan with contrast showing 1 lesion in the right lobe of the liver that was too small to be characterized.
B, Transcutaneous ultrasound showed 2 lesions. C, Magnetic resonance imaging showed 2 lesions, a small single enhancing nodule in
the right lobe of the liver measuring 1.2 cm and another small nodule (not shown in the figure) in the left lobe measuring 6 mm. D,
EUS image showing one of the 3 hypoechoic lesions detected during endosonographic examination of the left and right lobe of the
liver. EUS-FNA of the lesion confirmed the lesion to be malignant. CT indicates computed tomography; EUS, endoscopic ultrasound;
EUS-FNA, endoscopic ultrasound-guided fine needle aspiration.
of the metastases of the liver. In comparison to CT scan, lesions has potential implications on the management as
there was a trend in favor of EUS/EUS-FNA for the higher patients with single lesion are potential candidates for liver
diagnostic accuracy. EUS detected significantly higher resection in some GI cancers (eg, colon).6
number of malignant lesions in the liver as compared with Contrary to popular belief, lesions in the right lobe of
CT scan. EUS-FNA was highly accurate (88%) in the liver could be visualized and successfully sampled
establishing the exact nature of the liver lesions that were during EUS examination (Fig. 3). In comparison with CT
too small to be characterized on the CT scan. scan, the ability of the EUS for the detection of the lesions
Dewitt et al5 in a large retrospective study showed the in the left lobe was significantly higher (25 vs. 8, P = 0.005)
sensitivity of the EUS to be in the range of 82% to 94%. than in the right lobe (15 vs. 11, P = 0.59).
EUS/EUS-FNA detected 17 malignant hepatic lesions in The plausible reason seems to be the relative ease in the
patients with a previously normal CT scan. Prasad et al4 complete examination of the left lobe as there is large
showed cytologically positive malignant lesions in 2.3% (5 endosonographic window of anterior gastric wall and
of the 222 patients) who underwent EUS examination. antrum. The right lobe is examined from the duodenum,
Nguyen et al3 found occult liver metastases in 2.4% of 574 which is technically difficult because of small endosono-
patients with suspected GI or lung malignancy. The graphic window (duodenal bulb and second portion of the
findings of this prospective study are in agreement with duodenum) and is possibly further compounded by
the hypothesis that the accuracy of the EUS is superior to the limited depth of penetration. Particularly, lesions
the CT scan. The reason for the high accuracy was as a in subdiaphragmatic region of right lobe of liver (right
result of high sensitivity of the EUS for the visualization of anterior superior and right posterior superior anatomic
the hepatic lesions and high specificity of the EUS-FNA for segments) may not be accessible to EUS. In addition,
establishing the cytologic nature of the lesions. Though the acoustic shadows as a result of the gallstones poses
sensitivity of the EUS and CT was similar, EUS was significant problem in complete examination of the right
significantly superior to the CT scan in detection of the lobe of liver (see Video, Supplemental Digital Content 2,
number of malignant lesions. The ability to detect more which demonstrates EUS showing the limitation of
metastatic lesions that were missed by both EUS and 4. Prasad P, Schmulewitz N, Patel A, et al. Detection of occult
CT scan. liver metastases during EUS for staging of malignancies.
In conclusion, EUS examination of the liver should be Gastrointest Endosc. 2004;59:49–53.
considered an integral aspect of the staging of the 5. DeWitt J, LeBlanc J, McHenry L, et al. Endoscopic
ultrasound-guided fine needle aspiration cytology of solid liver
esophageal, gastric, pancreatic, biliary, and lung cancer. lesions: a large single-center experience. Am J Gastroenterol.
As EUS detects significantly more lesions than CT, 2003;98:1976–1981.
it should be considered for the preoperative evaluation of 6. Petrelli NJ, Nambisan RN, Herrera L, et al. Hepatic resection
tumors before consideration of liver resection of metastatic for isolated metastasis from colorectal carcinoma. Am J Surg.
lesions. In patients with cancer, EUS/EUS-FNA should be 1985;149:205–209.
considered as the next test after CT scan to identify the 7. Jones EC, Chezmar JL, Nelson RC, et al. The frequency and
nature of lesions that are too small to be characterized on significance of small hepatic lesions (<15 mm) detected by CT.
the CT scan. AJR. 1992;158:535–539.
8. Lawrence H, Schwartz MD, Eric J, et al. Prevalence and
importance of small hepatic lesions found at CT in patients
with cancer. Radiology. 1999;210:71–74.
9. Eberhardt SC, Choi PH, Bach AM, et al. Utility of sonography
REFERENCES for small hepatic lesions found on computed tomography in
1. Glover C, Douse P, Kane P, et al. Accuracy of investigations patients with cancer. J Ultrasound Med. 2003;22:335–343.
for asymptomatic colorectal liver metastases. Dis Colon 10. ten Berge J, Hoffman BJ, Hawes RH, et al. EUS-guided fine
Rectum. 2002;45:476–484. needle aspiration of the liver: indications, yield, and safety
2. Stark DD, Wittenberg J, Butch RJ, et al. Hepatic metastases: based on an international survey of 167 cases. Gastrointest
randomized, controlled comparison of detection with MR Endosc. 2002;55:859–862.
imaging and CT. Radiology. 1987;165:399–406. 11. Haider MA, Amitai MM, Rappaport DC, et al. Multi-detector
3. Nguyen P, Feng JC, Chang KJ. Endoscopic ultrasound (EUS) row helical CT in preoperative assessment of small (< or
and EUS-guided fine-needle aspiration (FNA) of liver lesions. 1.5 cm) liver metastases: is thinner collimation better? Radi-
Gastrointest Endosc. 1999;50:357–361. ology. 2002;225:137–142.