| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Original Research |
Department of Ultrasound, School of Oncology, Peking University, 52 Fu-cheng Rd., Beijing 100036, People's Republic of China.
Received June 3, 2005;
accepted after revision August 22, 2005.
Address correspondence to M.-H. Chen
(minhuachen{at}vip.sina.com).
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
MATERIAL AND METHODS. Of the 318 contrast-enhanced sonographic examinations performed between April and September 2004, 95 patients with 117 lesions confirmed by surgery or biopsy pathology were reviewed in this study. We analyzed the enhancement time and patterns according to the types and degrees of pathologic differentiation.
RESULTS. All 65 moderately to poorly differentiated hepatocellular carcinomas (HCCs) enhanced in the arterial phase, and 96.9% (63 lesions) of them quickly washed out in the portal venous phase. All 32 well-differentiated HCCs enhanced in the arterial phase, and 50.0% (16 lesions) washed out slowly during the late phase. The washout time of the two differentiated types was significantly different (p < 0.05). Seventy-five percent of the clear cell carcinomas (12/16) enhanced in the arterial phase, 25% (4/16) did not enhance until the portal venous phase, and 31.3% (5/16) of the clear cell carcinomas washed out slowly during the late phase. The enhancement and washout times of clear cell carcinomas were significantly different than those of moderately to poorly differentiated HCCs (p < 0.05). All four intrahepatic cholangiocarcinomas presented the same patterns as moderately to poorly differentiated HCCs: enhanced in the arterial phase and quickly washed out in the portal venous phase. Among the 72 lesions enhanced homogeneously, 46 lesions (63.9%) were smaller than 3 cm. Thirty-seven lesions (82.2%) of the 45 lesions that enhanced heterogeneously were larger than 3 cm (including the four cholangiocarcinomas). Larger lesions were mainly less differentiated. There were significant differences in tumor sizes in regard to cellular differentiations and types.
CONCLUSION. Our study showed that the enhancement manifestations of primary malignancies of the liver are related to pathologic types and grades. Contrast-enhanced sonograms may provide the histopathologic information for malignant tumors of the liver.
Keywords: contrast agents • primary malignancies of the liver • sonography
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The pathologic results of 117 primary malignancies of the liver were 65 moderately to poorly differentiated HCCs in 57 patients including one fibrolamellar HCC; 32 well-differentiated HCCs in 23 patients; 16 clear cell carcinomas in 11 patients; and 4 intrahepatic cholangiocarcinomas in 4 patients. Three patients had lesions of different differentiations or types. Twenty-two patients had two lesions.
Two pathologists with more than 20 years of experience made the histopathology diagnosis blind to the results of the contrast-enhanced sonograms. The study was approved by our institutional review board.
Imaging Technique
SonoVue (Bracco Diagnostics), the contrast agent used in this study,
consists of sulfur hexafluoride (SF6) microbubbles surrounded by
phospholipids. The average diameter of a microbubble is 2.5 µm.
Contrast-enhanced sonograms were performed using the Technos MPX DU8 (Esaote)
or Aplio (Toshiba) sonographic system with specific imaging techniques.
First, the liver was scanned with a conventional sonogram to select an appropriate section. The sizes, boundaries, and echogenicity of focal liver lesions were recorded. After adequate fundamental scanning, the specific mode of contrast-enhanced sonogram began. The acoustic power used was lowered to a mechanical index of less than 0.1. SonoVue was injected IV as a bolus of 2.4 mL through the antecubital vein followed by a 5-mL saline flush. The perfusion and echogenicity of the lesions were continuously observed until sufficient dynamic information about the lesions was obtained, and then the entire liver was scanned. The echogenicity of the lesions in three different phases—arterial (< 25 sec), portal (25-90 sec), and late phase (> 90 sec)—was compared. Lesions with higher, similar, or lower echogenicity compared with that of the adjacent liver parenchyma were defined as hyperechoic, isoechoic, or hypoechoic, respectively. When the lesion began to appear hyperechoic after injection, it was defined as enhancing. The enhanced lesion becoming hypoechoic was defined as washout.
For those patients with two lesions, an appropriate section was selected to display both lesions. If not, a second injection was used to observe the other lesion. The interval between the two injections was at least 10 min.
The entire scanning process was recorded onto high-resolution VHS videotapes for later analysis. Three physicians with at least 10 years of sonographic experience evaluated all the cases.
Statistical Analysis
SPSS 10.0 was used for statistical analysis. One-way analysis of variance
and the Kruskal-Wallis test were used to compare the enhancement and washout
time of the four groups. The chi-square test or Fisher's exact test was used
to analyze the relationship between the tumor echogenicity in three phases and
the pathologic grade and type, enhanced manifestation and lesion size, and
histopathology and lesion size, respectively. The level of statistical
significance was set at p <0.05.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
|
Table 2 shows the results of the comparison of tumor echogenicity in the three different phases and the cellular differentiation and type. In the arterial phase, all HCCs except four clear cell carcinomas enhanced quickly and appeared hyperechoic. In the portal venous phase, 96.9% of moderately to poorly differentiated HCCs (Figs. 2A, 2B, 2C and 2D), 50% of well-differentiated HCCs, 68.7% of clear cell carcinomas, and 100% of intrahepatic cholangiocarcinomas washed out quickly and became hypoechoic with respect to the surrounding liver. Significant differences were found in tumor echogenicity according to differentiation in the portal venous phase (p < 0.05). Appearing isoechoic in the portal venous phase were 16/32 (50%) of well-differentiated HCCs (Figs. 3A, 3B, 3C and 3D) and 2/65 (3.1%) of moderately to poorly differentiated HCCs. For the clear cell carcinomas, 31.3% slowly washed out in the late phase (Figs. 4A, 4B, 4C and 4D).
|
|
|
|
|
|
|
|
|
|
|
|
|
The enhancement patterns had a correlation to tumor sizes
(
2 = 21.87, p = 0.00). Among the 117 lesions, 72
lesions enhanced homogeneously with 46 lesions (63.9%) smaller than 3 cm.
Forty-five lesions enhanced heterogeneously with 37 lesions (82.2%) larger
than 3 cm (including the four intrahepatic cholangiocarcinomas).
Table 3 shows the result of
tumor size and histopathology. There were significant differences in tumor
size in regard to pathologic types and cellular differentiations
(2 =9.657, p = 0.0348): 64.6% (42/65) of moderately
to poorly differentiated HCCs were larger than 3 cm, 56.3% (18/32) of
well-differentiated HCCs were smaller than 3 cm, and 75% (12/16) of clear cell
carcinomas were smaller than 3 cm.
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Until now, fine-needle biopsy and core-needle biopsy were the most commonly used methods to obtain a pathologic diagnosis before treatment. However, with the new sonographic contrast agents that enter directly into the tumor capillary [14] together with specific imaging technologies, we are now able to visualize enhancement characteristics of the tumor microcirculation dynamically with sonography. Our study showed that the perfusion patterns of HCCs were not only useful for definitive diagnosis but also made it possible to provide histopathologic information noninvasively.
The characteristic manifestation of moderately to poorly differentiated HCCs in contrast-enhanced sonography is quick enhancement in the arterial phase and fast washout in the portal venous phase, which is similar to enhanced CT and MRI [15, 16]. Moderately to poorly differentiated HCCs are nourished mainly by the hepatic artery, and the contrast agent quickly enters the tumor. Conversely, the liver parenchyma is supplied mainly by the portal vein and enhances relatively late. Because the contrast agent in a tumor quickly washes out, liver parenchyma just begins to enhance, so the tumor appears hypoechoic with respect to the surrounding liver. This is observed from the portal to the late phase. There were two moderately to poorly differentiated lesions that did not wash out until the late phase in our study. Sugihara et al. [17] reported that the proportion of the moderately differentiated lesions in the tumor tends to increase as the tumor increases in size. The two lesions may contain well-differentiated tissues that cause the contrast agents to wash out slowly.
Half of the well-differentiated HCCs washed out slowly during the late phase. The average washout time was significantly different than that of the moderately to poorly differentiated HCCs. This was in accordance with a previous report [18]. Well-differentiated HCCs are mainly fed by the portal vein or by both the hepatic artery and the portal vein [19]. Microbubbles continuously infusing the tumor through the portal vein may be the pathologic basis of "slow washout." Furthermore, well-differentiated HCCs consist of a trabecular pattern of cell cords and abundant sinusoids that may cause stagnation and slow clearing of microbubbles. Conversely, less differentiated HCCs contain fewer sinusoids and are mainly fed by the hepatic artery, which could cause the different washout time compared with well-differentiated HCCs.
Clear cell carcinoma, accounting for 10% of HCCs, is characterized by a lot of glycogen and/or fat in cellular plasm. Approximately 37% of minute early-stage HCCs are accompanied by fat or clear cell degeneration [20], so most tumor cells of this type are better differentiated. There are few studies on clear cell carcinoma in the field of imaging. Tu and Zhou [21] reported that approximately 52.9% of clear cell carcinomas smaller than 3 cm displayed hypodensity, whereas the others displayed heterogeneous enhancement in the arterial phase on CT. The cause of nonenhancement was not clear. In our study, four clear cell carcinomas enhanced in the portal venous phase and not in the arterial phase. Two of them enhanced heterogeneously. A small amount of portal vein blood signals were detected only on one lesion before contrast-enhanced sonography. The results suggested that this kind of primary malignancy of the liver might have less of a blood supply than the well-differentiated HCCs. Five clear cell carcinomas that were seen to wash out slowly in the late phase were diagnosed as well differentiated pathologically. This may result in different perfusion patterns during contrast-enhanced sonography.
Cholangiocarcinoma is hypovascular and is characterized by a large number of fibrous connective tissues forming sclerotic glandular structures. Massive necrosis usually occurs in the center of the tumor because of ischemia. Chen et al. [22] reported that cholangiocarcinomas are predominantly supplied by the hepatic artery, and digital subtraction angiography showed abnormally distributed blood vessels in the lesions, some of them accompanied by an arteriovenous fistula. Enhanced CT showed slight or moderate enhancement in the peripheral area of the tumor, whereas no enhancement was seen in the center in the early arterial phase. In the late phase, central enhancement became gradually obvious [23, 24]. On contrast-enhanced sonography, the four cholangiocarcinomas in our study presented slight enhancement around the periphery of the tumors in the arterial phase, and the center of the tumors did not enhance at all. The enhanced pattern was similar to that of dynamic CT. Compared with the delayed enhancement on CT in the late phase, contrast-enhanced sonography showed quick washout in the portal venous phase. Valls et al. [24] reported that the hyperenhancing pattern of cholangiocarcinomas in the late phase on CT seems to be related to the large amount of interstitial space in the fibrous stroma of the tumor. Slow diffusion of contrast medium from the vascular to the interstitial space may account for the delayed and prolonged enhancement of the tumor on images obtained 10-15 min after injection. SonoVue is a blood pool agent and microbubbles do not enter the interstitial space, which may explain the different manifestation in the late phase between contrast-enhanced sonography and enhanced CT. Moreover, the arteriovenous fistula may have been another reason for the quick washout during contrast-enhanced sonography.
One patient with fibrolamellar HCC participated in our study. Contrast-enhanced sonography showed quick enhancement in the arterial phase and washout in the portal venous phase that was similar to the pattern of moderately to poorly differentiated HCCs. The pathologic characteristics were massive fibrous tissues, hemorrhage, and necrosis within the tumor. Abnormal vessels of septum distribution were seen. The representation of dynamic CT and MRI of fibrolamellar hepatocellular carcinoma is heterogeneous enhancement in the arterial phase. In the portal venous phase, it gradually enhances homogeneously, which is helpful to discriminate it from focal nodular hyperplasia [25, 26]. Because of the small representation of fibrolamellar HCC in our study, further investigation is necessary to evaluate its enhancement characteristics.
Our study showed significant correlation between tumor size and the degree of differentiation. Most large tumors were less-differentiated; small tumors were shown to be well differentiated or clear cell carcinoma. Tumor size is one of the prognostic factors of HCC. DNA analysis suggests that lesions greater than 3 cm in HCC may have different biologic activity than smaller lesions [27]. Most small HCCs at the early stage are well differentiated. As the tumor increases in size, foci of the less-differentiated malignant tissue arise in the well-differentiated tissue and increase until they replace the well-differentiated tumor tissue [17]. Our study also showed that inhomogeneous enhancement mainly occurred in tumors larger than 3 cm, which usually contain more necrosis and liquefaction tissues than tumors smaller than 3 cm.
Our study had its limitations. First, it only included primary hepatic malignancies with a pathologic diagnosis. The sensitivity, specificity, and accuracy of this method in characterizing primary hepatic malignancies were not achieved. Second, there still was overlap in enhancement patterns among the groups. Further study including evaluation of lesion vascularity and other enhancement characteristics may be helpful for differentiation. The small number of cholangiocarcinomas was another limitation. Further investigations including a larger number of lesions combined with surgical pathology are necessary.
In conclusion, our study investigated the enhancement patterns according to histopathologic grades and types of primary malignancies of the liver. It may be useful for the differential diagnosis of primary malignancies of the liver histologically. Fine-needle aspiration biopsy is an imperfect procedure; contrast-enhanced sonography may therefore be helpful in addition to biopsy in some patients.
Acknowledgments
We thank Ji-You Li for invaluable assistance in the preparation of this
article.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L.-P. Liu, B.-W. Dong, X.-L. Yu, P. Liang, D.-K. Zhang, and L.-C. An Focal Hypoechoic Tumors of Fatty Liver: Characterization of Conventional and Contrast-Enhanced Ultrasonography J. Ultrasound Med., September 1, 2009; 28(9): 1133 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Quaia, M. D'Onofrio, P. Cabassa, F. Vecchiato, S. Caffarri, F. Pittiani, K. M. Wittkowski, and M. A. Cova Diagnostic Value of Hepatocellular Nodule Vascularity After Microbubble Injection for Characterizing Malignancy in Patients with Cirrhosis Am. J. Roentgenol., December 1, 2007; 189(6): 1474 - 1483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Jang, T. K. Kim, P. N. Burns, and S. R. Wilson Enhancement Patterns of Hepatocellular Carcinoma at Contrast-enhanced US: Comparison with Histologic Differentiation Radiology, September 1, 2007; 244(3): 898 - 906. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
