Cell Biochem Biophys DOI 10.1007/s12013-014-9970-z

ORIGINAL PAPER

Hepatocellular Carcinoma in Budd-Chiari Syndrome: Enhancement Patterns at Dynamic Gadolinium-Enhanced T1-Weighted MR Imaging Chun Yang • Kai Xu • Junnian Zheng • Ping Ma • Chunfeng Hu • Shaodong Li • Yutao Rong • Xin Lu • Qingqiao Zhang • Maoheng Zu Rong Hua • Ling Zhang



Ó Springer Science+Business Media New York 2014

Abstract The objective of this study was to analyze the enhancement patterns at dynamic gadolinium-enhanced T1-weighted MR imaging in patients of Hepatocellular Carcinoma (HCC) with associated Budd-Chiari syndrome (BCS). The MR imaging findings in 10 patients of HCC with associated BCS were compared to those of 32 other patients of HCC without BCS. During the arterial phase, significantly more lesions with BCS were hyperintense than lesions without BCS; during the equilibrium phase, significantly more lesions with BCS were slightly hyperintense or isointense than lesions without BCS (P \ 0.05 for both). For HCC, contrast enhancement on MRI shows different enhancement patterns between patients of HCC with associated BCS and those without BCS. Keywords Hepatocellular carcinoma  Budd-Chiari syndrome  MR imaging  Liver  Blood supply

C. Yang and K. Xu have contributed equally to this work C. Yang  K. Xu (&)  C. Hu  S. Li  Y. Rong  X. Lu  Q. Zhang  M. Zu  R. Hua Department of Radiology, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou 221002, Jiangsu, People’s Republic of China e-mail: [email protected] C. Yang  J. Zheng Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, People’s Republic of China P. Ma Clinical Laboratory, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People’s Republic of China L. Zhang School of Pharmacy, Xuzhou Medical College, XuZhou, People’s Republic of China

Introduction Budd-Chiari syndrome (BCS) is a heterogeneous group of disorders characterized by hepatic outflow obstruction [1]. In patients with BCS, the liver is known to develop severe congestion, fibrosis, and cirrhosis [2, 3]. The prognosis of patients with BCS has been considered poor for many years. However, recent advances in imaging techniques have enabled early diagnosis, recognition of asymptomatic cases, and surgical treatment (e.g., portacaval anastomosis), which have resulted in better survival rates in these patients [4]. At the same time, the nodules associated with BCS have been described in the literature and include mostly hepatocellular carcinoma (HCC) and benign regenerative nodules, which are also called adenomatous hyperplastic nodules, nodular regenerative hyperplasia, and regenerative nodules [5–7]. It is important to distinguish HCC from benign hepatic nodules because treatment modalities differ radically. On radiologic examination, both HCC and benign nodules have been reported as hypervascular [7, 8]. The objectives of this study were as follows: (a) to describe the imaging features of HCC in patients with BCS, and (b) to compare the enhancement patterns of HCC in patients with and without BCS.

Materials and Methods Patients A study of surgical, pathologic, and radiologic records identified 92 patients presenting with BCS from January 2009 to December 2009. Eighty-two patients were excluded from analysis because no HCC was present. The

123

Cell Biochem Biophys

remaining 10 patients had at least one lesion of HCC detected by histologic examination or clinical and biologic data; this comprised the study population. There were five men and five women ranging in age from 35 to 63 (mean, 44) years. None of the patients had positive markers for viral hepatitis. Diagnosis of BCS was made by means of digital subtraction angiography in all patients. Diagnosis of HCC was made on the basis of histopathologic analysis of specimens obtained after surgical resection in four patients and percutaneous needle biopsy in one patient. Iodized oil accumulation after trans-catheter arterial embolization therapy and elevated blood a-fetoprotein level that dropped immediately after transcatheter arterial embolization was used as criteria for diagnosis of HCC in five patients. Histologic analysis of these specimens was reviewed by an experienced liver pathologist. We also attempted to study radiologic findings of HCC (all displayed chronic hepatitis or liver cirrhosis with viral hepatitis but none had BCS). From January 2009 to December 2009, 32 consecutive patients presenting with HCCs who had undergone MR imaging were included in the analysis. These patients included 24 males and 8 females, ranging in age from 38 to 72 years (mean age, 56 years). All patients displayed chronic hepatitis or liver cirrhosis associated with viral hepatitis (hepatitis B in 30, hepatitis C in 1, and both in one patient). A total of 40 lesions of HCCs were observed. Diagnosis of HCC was confirmed by surgical resection in 22 patients. In 10 patients, the following criteria were used: hypervascularity revealed on any radiologic modality, iodized oil accumulation after trans-catheter arterial embolization therapy, or both; and elevated blood a-fetoprotein level that dropped immediately after transcatheter arterial embolization. MR Imaging All MR imaging examinations were performed using a 3.0T system (Signa; GE Medical Systems). An anteroposterior phased-array surface coil (torso-array coil) for signal reception was placed around the patient and covered the entire liver in all patients. A respiratory belt was placed around the patient’s upper abdomen for the acquisition of respiratory-triggered sequences. The imaging protocol at both sessions included a transverse-unenhanced respiratory-triggered T2-weighted fast spin-echo sequence with fat suppression (echo time, ms, 85; echo train length, 16; two signals acquired; field of view, 40 9 40 cm2; matrix, 320 9 224; section thickness, 8.0 mm; intersection gap, 2.0 mm), as well as transverseunenhanced T1-weighted fast multiplanar-spoiled gradientrecalled echo (GRE) sequences with fat suppression

123

(repetition time ms/echo time ms, 190/Minimum; flip angle, 70°; one signal acquired; field of view, 40 9 40 cm2; matrix, 288 9 160; section thickness, 8.0 mm; intersection gap, 2.0 mm) was performed prior to intravenous contrast material administration. Subsequently, transverse dynamic LAVA MR sequences were performed before and after the administration of the contrast agent (gadopentetate dimeglumine) in the hepatic arterial phase (25–30 s after contrast agent administration), the portal venous phase (60–70 s after contrast agent administration), and the equilibrium phase (150–180 s after contrast agent administration). The parameters for the LAVA sequence were as follows: flip angle, 12°; field of view, 40 9 40 cm2; matrix, 288 9 256; and section thickness, 4.0 mm with no intersection gap. Gadopentetate dimeglumine was administered as an intravenous bolus at a dose of 0.2 mL/kg of body weight (corresponding to 0.1 mmol/kg of body weight) with a flow rate of 3 mL/sec, which was followed by a 20-mL saline flush at the same flow rate using a power injector (XD2050; Ulrich medical, Germany). Image Analysis Images of HCCs in patients with and without BCS were evaluated in conference by two radiologists with no knowledge of the diagnosis of hepatic lesions or underlying liver disease. All MR imaging sequences were evaluated during the same review session. The radiologists reached a consensus regarding the following features: number; size; signal intensity at MR imaging; and enhancement patterns of the lesions. The signal intensity characteristics of the lesion compared to those of the surrounding liver parenchyma were classified on the precontrast T1-weighted images as well as on images obtained from each phase of the postcontrast LAVA sequence separately by using the following classifications: hypointense, isointense, slightly hyperintense, or hyperintense. When lesions showed an inhomogeneous enhancement pattern on any of the postcontrast images, they were categorized as hypointense, isointense, slightly hyperintense, or hyperintense lesions according to the signal intensity characteristics of the predominant parts of the lesions. Statistical Analysis The results of the signal intensity analysis during the different vascular phases at both imaging sessions were compared by the RANKSUM test. P B 0.05 was considered to indicate statistical significance.

Cell Biochem Biophys Table 1 Lesion characteristics in patients at MR Imaging

Phase and HCC patients

Hyperintense

Slightly hyperintense

Isointense

Hypointense

1

11

4

36

Precontrast T1-weighted images HCC lesions with Budd-Chiari syndrome HCC lesions without Budd-Chiari syndrome Precontrast T2-weighted images HCC lesions with Budd-Chiari syndrome HCC lesions without Budd-Chiari syndrome

12 8

32

Hepatic arterial phase HCC lesions with Budd-Chiari syndrome

12

HCC lesions without Budd-Chiari syndrome

25

10

5

4

3

5

4

4

30

4

1

7

2

38

Portal venous phase HCC lesions with Budd-Chiari syndrome HCC lesions without Budd-Chiari syndrome

2

Equilibrium phase HCC lesions with Budd-Chiari syndrome Note Data are numbers of lesions with MR imaging

HCC lesions without Budd-Chiari syndrome

Results HCC Lesions with Budd-Chiari Syndrome (BCS) These lesions were 1.5–13 cm in diameter (mean, 5.5 cm). Two patients had two lesions each with diameters of 1.5 and 12; and 4.3 and 13 cm, respectively. Eight patients had single lesions with diameter ranging from 2.8 to 8 cm. The characteristics of the lesions are summarized in Table 1. On precontrast T1-weighted images, the majority of lesions were hypointense (11 of 12 lesions, 92 %); only one lesion was isointense (9 %). On precontrast T2-weighted images, all lesions were slightly hyperintense(12 of 12 lesions, 100 %). On hepatic arterial phase images, HCC lesions with BCS (n = 12) were hyperintense in 12 (100 %) lesions; On portal venous phase images, HCC lesions with BCS were slightly hyperintense in 4 (33 %) lesions, isointense 3 (25 %) lesions, hypointense in 5 (42 %) lesions; On hepatic equilibrium phase images, HCC lesions with BCS were slightly hyperintense in 4 (33 %) lesions, isointense 1 (8 %) lesions, hypointense in 7 (58 %) lesions. An enlarged hepatic artery was identified in two of the 10 patients (defined as a main hepatic artery diameter

larger than that of the splenic artery). These two patients had three lesions with diameters of 3.2, 4.3, and 13 cm. On hepatic arterial phase images, three HCC lesions were hyperintense; on portal venous phase and equilibrium phase images, lesions were all slightly hyperintense (Fig. 1). HCC Lesions without Budd-Chiari syndrome These lesions were 1.4–8 cm in diameter (mean 3.3 cm). The characteristics of the lesions are summarized in Table 1. On precontrast T1-weighted images, the majority of lesions were hypointense (36 of 40 lesions, 90 %); 4 lesions were isointense (10 %). On precontrast T2-weighted images, all lesions were slightly hyperintense (32 of 40 lesions, 80 %); only 8 lesions were hyperintense (8 of 40 lesions, 20 %). On hepatic arterial phase images, HCC lesions without BCS (n = 10) were hyperintense in 25 (63 %) lesions, slightly hyperintense in 10 (25 %), and isointense in 5 (13 %). On portal venous phase images, HCC lesions were hyperintense in 2 (5 %) lesions, slightly hyperintense in 4 (10 %), isointense in 4 (10 %) cases, and hypointense in 30 (75 %). On hepatic equilibrium phase images, HCC lesions

123

Cell Biochem Biophys

Fig. 1 HCC with BCS: a The enlarged hepatic attery (arrow) was identified (defined as a main hepatic attery diameter larger than that of the splenic artery). b During hepatic arterial phase, lesion (arrow)

is hyperintense compared with surrounding liver parenchyma. (c–d) During portal venous phase and equilibrium phase, lesion (arrow) is slightly hyperintense compared with surrounding liver parenchyma

were isointense in 2 (5 %) cases, and hypointense in 38 (95 %) (Fig. 2).

hepatic veins or inferior vena cava due to endoluminal invasion by the tumor. This produces an acute or fulminant variant of BCS, which has a poor prognosis [3, 4]. Second, HCC can develop in patients with chronic BCS [5]. The prevalence of HCC in patients with BCS varies in the literature and is found to be high in Japan (41 %), South Africa (48 %), and the United States (25 %) [9]. In other reports from Japan, however, the prevalence is lower [10]. In a clinical study of 157 patients with BCS, only 6.4 % of patients developed HCC during a 15-year follow-up period [10]. This wide variation in the prevalence of HCC in patients with BCS may indicate that other factors, such as chronic viral infection, play a role in the development of malignant tumors. In these series evaluating the prevalence of HCC in BCS, imaging data about the tumors were not extensive; however, most tumors were large and heterogeneous. Tumor invasion in the portal vein was also a common finding [5, 6]. The findings in our 10 patients with HCC and BCS were similar to those from previous studies: tumors were large (mean diameter, 5.5 cm for all lesions). HCC is being detected at an earlier stage due to the implementation of screening programs [11–13]. Biopsy is no longer required prior to treatment, and diagnosis of HCC is heavily dependent on imaging characteristics. The

Enhancement Patterns The results of the RANKSUM test demonstrated that during the portal venous phases, the enhancement patterns were very scattered. Therefore, there was no detectable trend in the signal intensity characteristics of lesions in the patients of HCC with and without BCS. Statistically significant differences in signal intensities existed between arterial phase and equilibrium phase images obtained from HCC with BCS and without BCS: during the arterial phase, significantly more lesions with BCS were hyperintense than lesions without BCS; and during the equilibrium phase, significantly more lesions with BCS were slightly hyperintense or isointense than lesions without BCS (P \ 0.05 for both).

Discussion The association of BCS and HCC is favored by two conditions. First, HCC can cause obstruction of the main

123

Cell Biochem Biophys

Fig. 2 HCC without BCS: a During hepatic arterial phase, lesion (arrow) is hyperintense compared with surrounding liver parenchyma. b–c During portal venous phase and equilibrium phase, lesion (arrow) is hypointense compared with surrounding liver parenchyma

most recent recommendations by the American Association for the Study of Liver Diseases (AASLD) state that a diagnosis of HCC can be made if a mass larger than 2 cm shows typical features of HCC (hypervascularity in the arterial phase and washout in the venous phase) at contrast material-enhanced computed tomography or magnetic resonance (MR) imaging; or if a mass measuring 1–2 cm shows these features at both modalities [14]. Radiologic criteria favoring malignancy are as follows: size larger than 2 cm, hyperintensity at T2-weighted imaging, delayed hypointensity, ‘‘washout’’-delayed enhancing tumor capsule, and rapid interval growth. Delayed hypointensity of an arterially enhancing lesion is an important feature that increases the specificity of the diagnosis of HCC, especially for lesions smaller than 2 cm, for which the reported sensitivity and specificity are 80 and 95 %, respectively. Rarely, HCC may remain hyperintense relative to adjacent liver parenchyma on venous and delayed phase images [14]. In this study, we have shown that for HCC, contrast enhancement pattern on T1-weighted gradient-echo MR imaging shows different enhancement patterns between HCC with and without BCS. During the arterial phase, significantly more lesions with BCS were hyperintense than lesions without BCS; and during the equilibrium phase, significantly more lesions with BCS were slightly hyperintense or isointense than lesions without BCS. This phenomenon may be explained by the reasons given below.

BCS is a heterogeneous group of disorders induced by thrombotic or non-thrombotic obstruction of hepatic venous outflow (congenital-web, diaphragm, interruption of the inferior vena cava (IVC), injury and/or inflammation, and liver tumor) located at the level of the hepatic venules, large hepatic veins, and IVC up to the confluence with the right atrium. Idiopathic BCS is present in onethird of the cases. As the hepatic veins constitute the sole efferent vascular drainage of the liver, obstruction, or increased pressure within these vessels or in their radicles results in an increased sinusoidal pressure. Regardless of the etiology, elevation of hepatic sinusoidal pressure leads to delayed or reversed portal venous outflow [6, 15]. The portal venous stasis and congestion cause hemodynamic disturbance in the liver in patients with BCS. The hepatic artery can be the major supplier of blood to the liver when portal vein becomes the draining vein in BCS [7, 16]. The transformation from a predominantly portal blood supply to a predominantly arterial blood supply in the liver induces hypervascularization of these HCC lesions in BCS [7]. In two out of 10 cases, as in the study by Vilgrain [7], the caliber of the main hepatic artery was larger than that of the splenic artery, which suggests that an increase in arterial hepatic outflow might explain the hypervascularization of these lesions. On hepatic arterial phase images, we found that HCC lesions with BCS were hyperintense in all lesions; in hepatic equilibrium phase images, HCC lesions with BCS were slightly hyperintense in 4 (33 %) lesions.

123

Cell Biochem Biophys

The roles of the respective changes in the arterial or portal circulation have not been clarified, but similar findings have been observed that, at multiphasic spiral CT or MRI evaluation, large regenerative nodules are markedly and homogeneously hyperattenuating (hyperintensity) on arterial dominant phase images and remain slightly hyperattenuating (hyperintensity) on portal venous phase images [7, 17, 18]. The cause of enhancement patterns of benign regenerative nodules is probably same reason, i.e., the hemodynamic disturbance in the liver in patients with BCS. In this study, we have shown that HCCs with and without BCS have different enhancement patterns. However, our study has a limitation. The diagnosis was confirmed histopathologically in only half of the patients with HCC.

Conclusion In conclusion, this study has shown that the enhancement patterns of HCC lesions on T1-weighted GRE MR images differ between those with and without BCS. Acknowledgments This study was supported by the grants from the Clinical medical science and technology project of Jiangsu Province (BL2012044), and the Science and Technology project of Xuzhou city (XZZD1154).

References 1. Menon, K. V., Shah, V., & Kamath, P. S. (2004). The BuddChiari syndrome. New England Journal of Medicine, 350, 578–585. 2. Lupescu, I. G., Dobromir, C., Popa, G. A., Gheorghe, L., & Georgescu, S. A. (2008). Spiral computed tomography and magnetic resonance angiography evaluation in Budd-Chiari syndrome. Journal of Gastrointestinal and Liver Diseases, 17, 223–226. 3. Erden, A. (2007). Budd-Chiari syndrome: A review of imaging findings. European Journal of Radiology, 61, 44–56. 4. Buckley, O., O’ Brien, J., Snow, A., Stunell, H., Lyburn, I., Munk, P. L., et al. (2007). Imaging of Budd-Chiari syndrome. European Radiology, 17, 2071–2078. 5. Gwon, D, 2nd, Ko, G. Y., Yoon, H. K., Sung, K. B., Kim, J. H., Lee, S. S., et al. (2010). Hepatocellular carcinoma associated with membranous obstruction of the inferior vena cava: Incidence, characteristics, and risk factors and clinical efficacy of TACE. Radiology, 254, 617–626.

123

6. Moucari, R., Rautou, P. E., Cazals-Hatem, D., Geara, A., Bureau, C., Consigny, Y., et al. (2008). Hepatocellular carcinoma in Budd-Chiari syndrome: Characteristics and risk factors. Gut, 57, 828–835. 7. Vilgrain, V., Lewin, M., Vons, C., Denys, A., Valla, D., Flejou, J. F., et al. (1999). Hepatic nodules in Budd-Chiari syndrome: Imaging features. Radiology, 210, 443–450. 8. Maetani, Y., Itoh, K., Egawa, H., Haga, H., Sakurai, T., Nishida, N., et al. (2002). Benign hepatic nodules in Budd-Chiari syndrome: Radiologic-pathologic correlation with emphasis on the central scar. AJR American Journal of Roentgenology, 178, 869–875. 9. Dilawari, J. B., Bambery, P., Chawla, Y., Kaur, U., Bhusnurmath, S. R., Malhotra, H. S., et al. (1994). Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature. Medicine (Baltimore), 73, 21–36. 10. Okuda, H., Yamagata, H., Obata, H., Iwata, H., Sasaki, R., Imai, F., et al. (1995). Epidemiological and clinical features of BuddChiari syndrome in Japan. Journal of Hepatology, 22, 1–9. 11. Hecht, E. M., Holland, A. E., Israel, G. M., Hahn, W. Y., Kim, D. C., West, A. B., et al. (2006). Hepatocellular carcinoma in the cirrhotic liver: Gadolinium-enhanced 3D T1-weighted MR imaging as a stand-alone sequence for diagnosis. Radiology, 239, 438–447. 12. Lutz, A. M., Willmann, J. K., Goepfert, K., Marincek, B., & Weishaupt, D. (2005). Hepatocellular carcinoma in cirrhosis: Enhancement patterns at dynamic gadolinium- and superparamagnetic iron oxide-enhanced T1-weighted MR imaging. Radiology, 237, 520–528. 13. Lewin, M., Handra-Luca, A., Arrive´, L., Wendum, D., Paradis, V., Bridel, E., et al. (2006). Liver adenomatosis: Classification of MR imaging features and comparison with pathologic findings. Radiology, 241, 433–440. 14. Willatt, J. M., Hussain, H. K., Adusumilli, S., & Marrero, J. A. (2008). MR Imaging of hepatocellular carcinoma in the cirrhotic liver: Challenges and controversies. Radiology, 247, 311–330. 15. Cura, M., Haskal, Z., & Lopera, J. (2009). Diagnostic and interventional radiology for Budd-Chiari syndrome. Radiographics, 29, 669–681. 16. Erden, A., Erden, I., Karayalcin, S., & Yurdaydin, C. (2002). Budd-Chiari syndrome: Evaluation with multiphase contrastenhanced three-dimensional MR angiography. AJR American Journal of Roentgenology, 179, 1287–1292. 17. Brancatelli, G., Federle, M. P., Grazioli, L., Golfieri, R., & Lencioni, R. (2002). Large regenerative nodules in Budd-Chiari syndrome and other vascular disorders of the liver: CT and MR imaging findings with clinicopathologic correlation. AJR American Journal of Roentgenology, 178, 877–883. 18. Brancatelli, G., Federle, M. P., Grazioli, L., Golfieri, R., & Lencioni, R. (2002). Benign regenerative nodules in Budd-Chiari syndrome and other vascular disorders of the liver: Radiologicpathologic and clinical correlation. Radiographics, 22, 847–862.

Hepatocellular carcinoma in Budd-Chiari syndrome: enhancement patterns at dynamic gadolinium-enhanced T1-weighted MR imaging.

The objective of this study was to analyze the enhancement patterns at dynamic gadolinium-enhanced T1-weighted MR imaging in patients of Hepatocellula...
530KB Sizes 0 Downloads 3 Views