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DOI:10.2214/AJR.05.0535
AJR 2006; 187:752-761
© American Roentgen Ray Society

Original Research

The Role of Contrast-Enhanced Sonography of Focal Liver Lesions Before Percutaneous Biopsy

Wei Wu1, Min-Hua Chen1, Shan-Shan Yin1, Kun Yan1, Zhi-Hui Fan1, Wei Yang1, Ying Dai1, Ling Huo1 and Ji-You Li2

1 Department of Ultrasound, School of Oncology, Peking University, 52 Fu-cheng Rd., Beijing 100036, People's Republic of China.
2 Department of Pathology, School of Oncology, Peking University, Beijing 100036, People's Republic of China.

Received April 2, 2005; accepted after revision August 8, 2005.

 
Address correspondence to M.-H. Chen (minhuachen{at}vip.sina.com).


Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The objective of our study was to evaluate the clinical utility of performing contrast-enhanced sonography before percutaneous biopsy of focal liver lesions.

SUBJECTS AND METHODS. One hundred eighty-six patients with focal liver lesions detected on either sonography or contrast-enhanced CT were randomly divided into two groups: a group who underwent contrast-enhanced sonography and another who underwent unenhanced sonography. The contrast-enhanced sonography group (79 patients, 129 lesions) underwent SonoVue-enhanced sonography before biopsy, and the unenhanced sonography group (107 patients, 143 lesions) did not undergo contrast-enhanced sonography before biopsy. Conventional sonography was used in all patients to guide the biopsy procedures. The pathologic diagnosis was considered definitive and final if the biopsy result was malignant. If the initial biopsy result was benign or negative for malignancy, then the result was either confirmed or denied on the basis of contrast-enhanced CT, MRI, angiography, serum {alpha}-fetoprotein level, or clinical follow-up over a period of 6 months. In some patients with suspected malignancy, biopsy was repeated when considered necessary during the follow-up. The diagnostic accuracy of the initial biopsy was defined as the percentage of the total number of lesions that were correctly diagnosed at the initial biopsy. The difference in diagnostic accuracy between the two groups was analyzed to evaluate the value of performing contrast-enhanced sonography before biopsy.

RESULTS. Of the 129 lesions in the contrast-enhanced sonography group, 28 (21.7%) were benign and 101 (78.3%) were malignant. Of the 143 lesions in the unenhanced sonography group, 36 (25.2%) were benign and 107 (74.8%) were malignant. There was no significant difference in the distribution of malignant and benign lesions in these two groups (p > 0.05). There was no statistically significant difference in the distribution of lesions by size between the contrast-enhanced and unenhanced sonography groups ({chi}2 = 0.619, p > 0.05). The diagnostic accuracy of the initial biopsy was significantly higher in the contrast-enhanced sonography group than in the unenhanced sonography group (95.3% vs 87.4%, respectively; p < 0.05). The diagnostic accuracy of the initial biopsy for malignant lesions ≤ 2.0 cm was also significantly higher in the contrast-enhanced sonography group than in the unenhanced sonography group (97.1% vs 78.8%, respectively; p < 0.05). No major complications occurred in our study except one case of pneumothorax in the unenhanced sonography group.

CONCLUSION. Contrast-enhanced sonography before percutaneous focal liver lesion biopsy improved the diagnostic accuracy of the procedure by providing important intralesional information for differentiating viable, denaturalized, or necrotic tissue; consequently, by providing more accurate information about the site of biopsy even in lesions ≤ 2.0 cm, contrast-enhanced sonography before biopsy reduced the number of puncture attempts.

Keywords: biopsy • contrast-enhanced sonography • hepatocellular carcinoma • liver disease • liver neoplasms


Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Percutaneous liver biopsy is being used regularly for histopathologic diagnosis of benign and malignant focal liver lesions in current clinical practice. Histopathologic diagnosis is regarded as the gold standard for the clinical diagnosis of focal liver lesions [1-4]. Percutaneous liver biopsy performed using conventional sonography for guidance has been performed for more than 20 years in our institution, and its diagnostic accuracy was as high as 88.8% in our earlier experience. However, after more than 10,000 biopsies, we discovered that false-negative biopsy results still existed and were sometimes contradictory to results from CT or clinical diagnosis. These false-negative biopsy results were believed to be due to tumor necrosis or denaturalization and inappropriate localization of the site for biopsy. Recently, contrast-enhanced sonography has been used in the diagnosis and characterization of focal liver lesions and has been shown to increase detection of and diagnostic accuracy for focal liver lesions, but there have been few reports about the use of contrast-enhanced sonography before percutaneous liver biopsy [5, 6]. Therefore, the aim of our study was to investigate the role of contrast-enhanced sonography in improving the localization of the target biopsy site and the diagnostic accuracy of percutaneous biopsy of focal liver lesions.


Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
This clinical study was approved by the institutional review board. All patients gave informed consent before contrast-enhanced sonography and biopsy procedures.

Patient Population
From July 2002 to August 2004, 186 patients with 272 uncertain focal liver lesions detected on either conventional sonography or contrast-enhanced CT were enrolled in this study. Among them, there were 112 males and 74 females who ranged in age from 16 to 78 years (mean, 52 years). All patients were randomly divided into two groups: a group who underwent contrast-enhanced sonography and another who underwent unenhanced sonography. The contrast-enhanced sonography group included 79 patients with 129 lesions for biopsy. All these patients underwent real-time gray-scale contrast-enhanced sonography before conventional sonographically guided biopsy. The unenhanced sonography group included 107 patients with 143 lesions who did not undergo contrast-enhanced sonography before conventional sonographically guided biopsy. In the contrast-enhanced sonography group, biopsy of one lesion was performed in 45 patients, two lesions in 19 patients, three lesions in 14 patients, and four lesions in one patient. In the unenhanced sonography group, biopsy of one lesion was performed in 79 patients, two lesions in 20 patients, and three lesions in eight patients.

Contrast Agent and Sonography Procedures
For the contrast-enhanced sonography group patients who underwent contrast-enhanced sonography before biopsy, the sonography contrast agent used was SonoVue (Bracco SpA), supplied as a lyophilized powder and reconstituted with 5 mL of saline to form a homogeneous microbubble suspension that contains 8 µL/mL of sulfur hexafluoride stabilized by a phospholipid shell. The mean microbubble diameter is 2.5 µm with a pH value of 4.5-7.5. SonoVue was administered IV as 2.4-mL boluses through the antecubital vein in 2-3 seconds. Contrast-enhanced sonography was performed using the Technos DU6 or DU8 sonography system (Esaote) with real-time gray-scale contrast-tuned imaging and a 2.5- to 5.0-MHz CA431 or CA430E probe (Esaote).

The liver was first scanned with conventional sonography (fundamental linear imaging), and the location, number, size, and sonographic features of the focal liver lesions were recorded. Contrast-tuned imaging was then initiated, and the acoustic power output was adjusted to about 0.05 mechanical index on the basis of the lesion depth and body habitus of the patient. On contrast agent administration, the perfusion and enhancement patterns of the target lesions were continuously observed throughout all phases of contrast-enhanced sonography.

After all diagnostic images in the parenchymal phase had been obtained, the entire liver was quickly scanned to detect new hypoechoic lesions. The entire scanning process was recorded on high-resolution sVHS videotapes, and digital still images were captured and saved to diskettes. Finally, the location, size, and areas of enhancement (or areas lacking enhancement) of the lesions and vessels adjacent to the lesions were recorded to provide references for the biopsy procedures.

Biopsy Techniques
For the biopsy procedures in this study, another sonography system (SSD-2000, 4000, or 5500, Aloka) with 3.5- to 5.0-MHz small-sector convex probes accessorized for biopsy was used to provide sonography guidance. Color Doppler imaging was routinely used to delineate large vessels and abnormal arteries so the operator could avoid puncturing them during biopsy.

Before biopsy, all patients were tested for coagulation function (platelet count, bleeding time, prothrombin time, and partial thromboplastin time); if results were abnormal, the patient was either treated or referred for other diagnostic methods. All patients fasted for at least 8 hours before the procedure. The ultrasound probe was sterilized with gaseous formaldehyde for at least 24 hours. In the contrast-enhanced sonography group patients, contrast-enhanced sonography was performed 30-60 minutes before the biopsy and the areas showing contrast enhancement within the tumors were recorded.

Biopsy was performed using a 21-gauge manual aspiration needle (Sonopsy, Hakko Medical Co.) or a 20-gauge automatic cutting needle (Bard Magnum, Bard). The number of puncture attempts was decided by the quantity and color of the specimen obtained. If the biopsy was unsatisfactory with the small-gauged needles or if repeat biopsy was needed, an 18-gauge automatic cutting needle was used. The skin was sterilized, and local anesthetic was applied using 2% lidocaine. After the probe was fixed and the guiding needle was inserted into the abdominal wall, the biopsy needle was inserted for biopsy. Patients were told to hold their breath when the needle was advanced into or when it was withdrawn from the liver. Care was taken to insert the needle through normal liver tissue to reduce tumor seeding. The shortest pathway was used for deep lesions. For superficial ones, effort was always made to traverse some normal liver parenchyma if possible. Otherwise, a 21-gauge needle was used and the number of attempts minimized. The whole biopsy procedure was continuously monitored using conventional sonography, and the biopsy needle was kept away from the gallbladder, the costophrenic angle, the lungs, and the stomach to prevent them from being damaged. The specimens obtained during the biopsy were fixed in 10% formalin.

After biopsy, the puncture site was routinely checked for bleeding or other complications. The patient was kept in the hospital for at least 1 hour after the procedure and was told to continue fasting for 4 hours after the biopsy. The specimens were sent to the pathology department for histologic and cytologic examinations by two experienced pathologists.

Final Lesion Diagnosis
Diagnosis of the biopsy sample was considered definitive and final if the pathology result was positive for malignancy, and that diagnosis was considered to be a true-positive. However, if the pathology result was benign or negative for malignancy, then the biopsy result was further validated using contrast-enhanced CT, MRI, angiography, serum {alpha}-fetoprotein level, or clinical follow-up over a period of 6 months before a final diagnosis was established. If no malignancy was found, then the final diagnosis would be confirmed to be benign and the biopsy result would be a true-negative. Otherwise, if malignancy was later confirmed, the final diagnosis would be revised to malignancy and the initial biopsy result would be a false-negative (Fig. 1). In some patients, biopsy was repeated during the follow-up period when considered necessary.


Figure 1
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  		Fig. 1 —Flow chart shows algorithm for diagnosis of liver tumor.

 
Statistical Analysis
The diagnostic accuracy in this study was defined as the percentage of the total number of lesions that had true-positive and true-negative biopsy results as described in Figure 1 and can be expressed as follows:

Formula

The difference in the diagnostic accuracy between the two groups was analyzed to evaluate the value of performing contrast-enhanced sonography before biopsy for correct localization of the biopsy site. Statistical analysis was performed using statistics software (SPSS version 10.0, SPSS). The study results in enumeration data were analyzed with the chi-square test. A p value of less than 0.05 was considered statistically significant.


Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The size of the lesions ranged from 0.8 to 12.6 cm (mean, 3.1 cm) in the contrast-enhanced sonography group and from 0.8 to 13.6 cm (mean, 3.2 cm) in the unenhanced sonography group. Of all the lesions, 48 (37.2%) were ≤ 2.0 cm in diameter among the 129 lesions in the contrast-enhanced sonography group and 48 (33.6%) were ≤ 2.0 cm among the 143 lesions in the unenhanced sonography group (Table 1). There was no statistically significant difference between the two groups in the size ranges of the focal liver lesions ({chi}2 = 0.619, p > 0.05).


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  		TABLE 1: Size Ranges of 272 Liver Lesions in Two Patient Groups

 

Biopsy was performed on all 272 lesions (129 lesions in the contrast-enhanced sonography group, 143 in the unenhanced sonography group). The average number of puncture attempts per lesion during the biopsy procedures was similar in the two groups. There were 256 puncture attempts for the 129 lesions in the contrast-enhanced sonography group (slightly fewer than two punctures per lesion) and 296 attempts for the 143 lesions in the unenhanced sonography group (slightly more than two punctures per lesion). However, the rate of successful single-puncture attempts in the contrast-enhanced sonography group (14.0% or 18/129) was higher than that in the unenhanced sonography group (4.9% or 7/143) ({chi}2 = 5.626, p < 0.05). The rest of the lesions required two or more punctures (Table 2).


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  		TABLE 2: The Number of Puncture Attempts of all 272 Lesions in Two Groups

 

There were no statistically significant differences in the number of lesions using needles of different gauges between the contrast-enhanced sonography group and unenhanced sonography group (p > 0.05) (Table 3).


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  		TABLE 3: The Number of Lesions Using Different Gauge Needles in Two Groups

 

Of the 129 lesions in the contrast-enhanced sonography group, 28 (21.7%) were benign and 101 (78.3%) were malignant. Of the 143 lesions in the unenhanced sonography group, 36 (25.2%) were benign and 107 (74.8%) were malignant. Among the malignant lesions, 35 were ≤ 2.0 cm in diameter in the contrast-enhanced sonography group and 33 were ≤ 2.0 cm in the unenhanced sonography group. There was no significant difference in the distribution of malignant and benign lesions in these two groups ({chi}2 = 0.281, p = 0.5965).

In the contrast-enhanced sonography group, the initial biopsy led to the correct diagnosis of 27 (96.4%) of 28 benign lesions and 96 (95.0%) of 101 malignant lesions, with an overall diagnostic accuracy of 95.3%. In the unenhanced sonography group, the initial biopsy led to the correct diagnosis of 33 (91.7%) of 36 benign lesions and 92 (86.0%) of 107 malignant lesions, with an overall diagnostic accuracy of 87.4%. The difference between the contrast-enhanced sonography group and the unenhanced sonography group in the overall diagnostic accuracy was statistically significant (p < 0.05) (Table 4). The diagnostic accuracy of malignant lesions in the contrast-enhanced sonography group was significantly higher than in the unenhanced sonography group (p < 0.05). The accuracy of the initial biopsy in the diagnosis of malignant lesions ≤ 2.0 cm was also higher in the contrast-enhanced sonography group (97.1% or 34/35) than in the unenhanced sonography group (78.8% or 26/33) (p < 0.05) (Fig. 2). However, there was no statistically significant difference in the diagnostic accuracy of benign lesions between the contrast-enhanced sonography group and the unenhanced sonography group (p > 0.05).


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  		TABLE 4: Diagnostic Accuracy of Benign and Malignant Lesions in Two Groups

 

Figure 2
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  		Fig. 2 —Bar graph shows accuracy for contrast-enhanced sonography group (light gray) and unenhanced sonography group (black) in diagnosis of malignant lesions by lesion size. There was statistically significant difference between contrast-enhanced sonography group and unenhanced sonography group in accuracy for diagnosis of malignant lesions ≤ 2.0 cm (97.1% [n = 34/35] vs 78.8% [n = 26/33], respectively; {chi}2 = 3.886, p = 0.0490).

 

The color of the specimen from most of the malignant lesions in both groups was white or pink (87.0%, 181/208), whereas most of the benign lesions were reddish brown (54.7%, 35/64) (Table 5). There was a statistically significant difference in the color of specimens between malignant and benign lesions ({chi}2 = 46.033, p = 0.000).


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  		TABLE 5: Pathologic Diagnoses of Biopsy and Color of Specimens for Both Patient Groups

 

No major complications occurred in patients in the contrast-enhanced sonography group. One case of pneumothorax occurred in a patient in the unenhanced sonography group because the lesion was located near the diaphragm. Minor complications (pain in the region of the liver or right shoulder) developed in 8.9% of cases (7/79) in the contrast-enhanced sonography group and 21.5% of cases (23/107) in the unenhanced sonography group. Only one case of pain in the unenhanced sonography group required analgesic therapy; all the others resolved spontaneously. Neither intraperitoneal bleeding nor needle tract seeding was observed on sonography, CT, or clinical follow-up. No death related to biopsy occurred in this study.

In additional analysis to confirm the value of contrast-enhanced sonography before sonographically guided biopsy, we performed a post-hoc analysis on a subgroup of 15 patients in the unenhanced sonography group who showed a negative diagnosis for malignancy from the initial biopsy but malignancy could not be excluded clinically due to results from tumor markers ({alpha}-fetoprotein, carcino-embryonic antigen [CEA], cancer antigen [CA] 199, and so on), CT, MRI, or angiography. Repeat biopsy was considered necessary in these patients to confirm the diagnosis. We also performed contrast-enhanced sonography before the repeat biopsy to better localize the biopsy site (Figs. 3A, 3B, 3C, 3D, 3E, 4A, 4B, 4C, 4D, 4E, 4F, 4G, 5A, and 5B). Fourteen of the 15 lesions were diagnosed as malignant at the second biopsy including seven lesions that were ≤ 2.0 cm (Table 6).


Figure 3
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  		Fig. 3A —32-year-old man with focal liver lesion in left lobe in unenhanced sonography group. First and second biopsy procedures were performed with 21-gauge manual aspiration needle guided by conventional sonography. Pathologic diagnosis of both biopsy samples was hepatocellular fatty degeneration. Contrast-enhanced sonograms show lesion (arrow) to exhibit slight inhomogeneous enhancement in arterial phase (A). Area of enhancement washed out quickly in parenchymal phase (B).

 

Figure 4
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  		Fig. 3B —32-year-old man with focal liver lesion in left lobe in unenhanced sonography group. First and second biopsy procedures were performed with 21-gauge manual aspiration needle guided by conventional sonography. Pathologic diagnosis of both biopsy samples was hepatocellular fatty degeneration. Contrast-enhanced sonograms show lesion (arrow) to exhibit slight inhomogeneous enhancement in arterial phase (A). Area of enhancement washed out quickly in parenchymal phase (B).

 

Figure 5
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  		Fig. 3C —32-year-old man with focal liver lesion in left lobe in unenhanced sonography group. First and second biopsy procedures were performed with 21-gauge manual aspiration needle guided by conventional sonography. Pathologic diagnosis of both biopsy samples was hepatocellular fatty degeneration. Sonogram shows lesion (arrow), which was biopsied using 18-gauge automated cutting needle.

 

Figure 6
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  		Fig. 3D —32-year-old man with focal liver lesion in left lobe in unenhanced sonography group. First and second biopsy procedures were performed with 21-gauge manual aspiration needle guided by conventional sonography. Pathologic diagnosis of both biopsy samples was hepatocellular fatty degeneration. Photomicrograph of biopsy specimen shows tumor cells to exhibit glandular structures and form into multilayer in some areas. Pathologic diagnosis of biopsy sample was cholangiocarcinoma.

 

Figure 7
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  		Fig. 3E —32-year-old man with focal liver lesion in left lobe in unenhanced sonography group. First and second biopsy procedures were performed with 21-gauge manual aspiration needle guided by conventional sonography. Pathologic diagnosis of both biopsy samples was hepatocellular fatty degeneration. Photograph of sample of tumor shows hepatocellular fatty degeneration (star) and cholangiocarcinoma (arrowhead).

 

Figure 8
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  		Fig. 4A —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. Contrast-enhanced sonogram shows large area of ringlike enhancement (long arrow) and small area of ringlike enhancement (short arrow) in early arterial phase.

 

Figure 9
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  		Fig. 4B —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. Sonogram obtained later in arterial phase than A shows central area of large ringlike area (long arrow) as being enhanced, but central area of small ringlike area (short arrow) is not enhanced at all.

 

Figure 10
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  		Fig. 4C —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. Enhanced area (arrowhead) was washed out in late parenchymal phase.

 

Figure 11
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  		Fig. 4D —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. After contrast-enhanced sonography was performed, repeat biopsy of enhanced area was performed. Arrow points to needle tip.

 

Figure 12
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  		Fig. 4E —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. Photomicrograph shows biopsy sample from enhanced area obtained during repeat biopsy (D). Pathologic diagnosis was well-differentiated hepatocellular carcinoma.

 

Figure 13
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  		Fig. 4F —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. Sonogram obtained during biopsy of unenhanced area shows needle tip (arrow).

 

Figure 14
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  		Fig. 4G —79-year-old woman with history of hepatitis B-related cirrhosis for 1 year in unenhanced sonography group. Serum {alpha}-fetoprotein level was 800 ng/mL. Hypoechoic lesion was found in hepatic segments V-VIII during routine sonography examination. Initial biopsy guided by conventional sonography was negative. Photomicrograph shows biopsy sample from unenhanced area. Pathologic diagnosis was hepatocellular degeneration.

 

Figure 15
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  		Fig. 5A —71-year-old man with radiofrequency-treated hepatocellular carcinoma in unenhanced sonography group. After ablation, tumor was enlarged with suspected recurrence. Serum {alpha}-fetoprotein value was 0.815 ng/mL. Initial biopsy guided by conventional sonography was negative. Contrast-enhanced sonograms obtained after ablation during arterial phase (A) and parenchymal phase (B) show 3.3 x 2.4 cm abnormal enhancement in lesion (arrow). Area of enhancement (arrow, A) in arterial phase washed out quickly in parenchymal phase (arrow, B). However, postablation lesion was not enhanced and presented as hypoechoic during all phases (arrowhead). Area of enhancement was punctured again, and well-differentiated hepatocellular carcinoma was diagnosed.

 

Figure 16
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  		Fig. 5B —71-year-old man with radiofrequency-treated hepatocellular carcinoma in unenhanced sonography group. After ablation, tumor was enlarged with suspected recurrence. Serum {alpha}-fetoprotein value was 0.815 ng/mL. Initial biopsy guided by conventional sonography was negative. Contrast-enhanced sonograms obtained after ablation during arterial phase (A) and parenchymal phase (B) show 3.3 x 2.4 cm abnormal enhancement in lesion (arrow). Area of enhancement (arrow, A) in arterial phase washed out quickly in parenchymal phase (arrow, B). However, postablation lesion was not enhanced and presented as hypoechoic during all phases (arrowhead). Area of enhancement was punctured again, and well-differentiated hepatocellular carcinoma was diagnosed.

 

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  		TABLE 6: Post-Hoc Analysis of a Subgroup of 15 Patients in the Unenhanced Sonography Group with a False-Negative Diagnosis Based on Initial Biopsy

 


Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Imaging-guided liver biopsy has gained wide acceptance in clinical practice for the histopathologic diagnosis of focal liver lesions because it may provide crucial information for patient management including the selection of therapeutic methods. Besides CT, conventional sonography is routinely used for guiding biopsy procedures [7-10]. Fine-needle aspiration biopsy has a high sensitivity and specificity (90-95%) in experienced hands, but has a high rate for insufficient sampling (≤ 15%) [1]. Repeat biopsy should be performed when necessary [8]. The size and location of the tumor, extent of necrosis, status of the blood supply, and experience of the operators may affect the success of a biopsy procedure and can cause false-negative results.

Schlottmann et al. [5] used contrast-enhanced sonography for detecting hepatic lesions under contrast harmonic imaging conditions with phase inversion at a low mechanical index. They evaluated 12 patients with hepatic tumors or abscesses that could not be analyzed and punctured under fundamental B-mode guidance. In 11 of the 12 interventions under contrast harmonic imaging, the conditions were successful. Bang et al. [6] also proposed that biopsy be performed in areas of tumors with rich vasculature shown on contrast-enhanced sonography. In the current study, we show the importance of contrast-enhanced sonography being performing before conventional sonographically guided biopsy compared with conventional sonographically guided biopsy being performed without knowledge of the findings from contrast-enhanced sonography performed before the procedure.

Comparison of the Diagnostic Accuracy Between the Two Groups With and Without Contrast-Enhanced Sonography Before Biopsy
Results from this study showed that contrast-enhanced sonography can provide the biopsy operators with important information about malignant lesions including lesions < 1 cm. Our results also indicated that operators' knowledge of the information from contrast-enhanced sonography before biopsy resulted in a reduced number of puncture attempts during the procedure. A single puncture attempt was successful in 14.0% of the patients in the contrast-enhanced sonography group compared with a successful single puncture in 4.9% of the patients who did not undergo contrast-enhanced sonography.

Reasons for False-Negative Diagnosis
In the course of tumor development or after chemotherapy, necrosis or denaturalization often occurs in the center of the tumor and that may affect the pathologic diagnosis if the biopsy site is not localized correctly. Therefore, biopsy is often performed in the peripheral zone or a hypervascular area of the tumors [11]. Necrotic tissue cannot be identified on conventional sonography, especially before liquefaction has occurred [12], possibly leading to an unsuccessful biopsy or a false-negative diagnosis. Contrast-enhanced sonography, on the contrary, allows clinicians to differentiate viable from necrotic tumor regions by depicting ringlike enhancement or bolus enhancement in the arterial phase and contrast material washout in the portal or parenchymal phase. The necrotic regions usually present with no enhancement in all vascular phases of contrast-enhanced sonography and may appear echo-free or slightly hypoechoic in the background of enhanced liver parenchyma [13]. Moreover, contrast-enhanced sonography can be used to detect metastatic lesions as small as 3 mm that cannot be detected with conventional sonography [14-16].

Radiofrequency ablation has been shown to be an effective treatment for malignant liver tumors, even in cases in which the tumor is unresectable [17-19]. After radiofrequency ablation, it can be difficult to differentiate active tumor from coagulation necrosis under sonographic guidance [20]; even negative biopsy results cannot be used to exclude residual viable tumor [7]. In practice, contrast-enhanced CT or MRI can be performed immediately after ablation when either is being used for guidance and can quickly provide information about whether residual tumors for further ablation are present. Contrast-enhanced sonography, as well as CT and MRI, has shown high sensitivity and accuracy for the detection of residual tumor and for the evaluation of treatment outcome. Throughout all phases of contrast-enhanced sonography, residual viable areas may present with intratumor enhancement, whereas ablated areas present with no enhancement [21-25]; thus, contrast-enhanced sonography may be able to replace contrast-enhanced CT or MRI in this regard.

At present, most liver biopsies are performed using conventional sonography for imaging guidance. Although other contrast-enhanced imaging techniques, such as CT and MRI, can also provide similar information, contrast-enhanced sonography is capable of providing images obtained in the same plane as conventional sonography, which are used to guide biopsy; therefore, the information from contrast-enhanced sonography can be used more directly during biopsy to guide the procedure more accurately than that from CT and MRI.

Precautions and Complications
Bleeding after biopsy is rare and is reported to occur in 0-1% of patients [26]. To further decrease the risk of bleeding, operators should keep away from large and abnormal vessels, especially superficial vessels, in the liver. Damage to other organs and structures such as the bile duct, lungs, and diaphragm should also be avoided. Seeding of malignant tumors in the needle tract may happen after biopsy; its rate after percutaneous biopsy of hepatocellular carcinoma was reported to be 2.66% and did not seem to influence survival [27]. The number of puncture attempts should be limited to one or two when an 18-gauge needle is used. In our study, no major complications occurred except for one patient who developed pneumothorax.

In conclusion, having the information yielded by contrast-enhanced sonography performed before biopsy procedures using conventional sonography guidance can significantly decrease the false-negative rate for malignant lesions. Contrast-enhanced sonography can be used to localize the site for biopsy more accurately by differentiating areas of viable tumor from denaturalization or necrosis. In addition, contrast-enhanced sonography can be used to detect tumors ≤ 2.0 cm, and its use in this setting reduces the number of puncture attempts and significantly increases the success rate of biopsy.


References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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