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Hepatocellular Carcinoma in Cirrhotic Liver Disease

Posted Jun 30, 2008 Updated Apr 7, 2023
By Davide Ippolito MD , Sro Sironi MD , Massimo Pozzi MD , Laura Antolini MD , Laura Ratti MD , Chiara Alberzoni MD , Eugenio Biagio Leone MD , Franca Meloni MD , Maria Grazia Valsecchi MD , Ferruccio Fazio MD
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Rationale and Objectives

Our goal was to prospectively determine the value of perfusion computed tomography (CT) in the quantitative assessment of tumor-related angiogenesis in cirrhotic patients with hepatocellular carcinoma (HCC).

Materials and Methods

Forty-seven patients met all the following inclusion criteria: 1) Child-Pugh class A or B liver cirrhosis; 2) presence of a single lesion suspected as HCC at screening ultrasound examination; and 3) lesion diameter between 1 and 3 cm. All patients underwent contrast-enhanced ultrasound, pre- and post-contrast triple-phase CT, and perfusion computed tomographic study using multidetector 16-slice CT. Six parameters related to the blood microcirculation and tissue perfusion were measured for the focal liver lesion and cirrhotic parenchyma: perfusion (P), tissue blood volume (BV), hepatic perfusion index (HPI), arterial perfusion (AP), portal perfusion (PP), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution; univariate paired and unpaired Wilcoxon signed rank tests were used for statistical analysis.

Results

HCC was diagnosed in 21 of the 47 patients; in the remaining 26, HCC was not found at contrast-enhanced ultrasound and multidetector 16-slice computed tomographic study. The values of perfusion parameters measured within tumor tissue were: P (ml/s/100 g): median = 47.0 (first quartile = 36.0, third quartile = 61.4); BV (ml/100 mg): median = 24.0 (first quartile = 18.7, third quartile = 29.3); HPI (%): median = 78.4 (first quartile = 62.9, third quartile = 100); AP (ml/min): median = 45.9 (first quartile = 39.0, third quartile = 60.1); PP (ml/min): median = 9.0 (first quartile = 0.0, third quartile = 24.5); and TTP (seconds): median = 18.7 (first quartile = 16.3, third quartile = 26.5). The corresponding values calculated in cirrhotic surrounding parenchyma were P (ml/s/100 g): median = 11.5 (first quartile = 9.4, third quartile = 13.9); BV (ml/100 mg): median = 10.7 (first quartile = 7.1, third quartile = 14.2); HPI (%): median = 10.6 (first quartile = 8.7, third quartile = 11.9); AP (ml/min): median = 13.2 (first quartile = 10.1, third quartile = 15.5); PP (ml/min) median = 55.2 (first quartile = 40.1, third quartile = 79.5); and TTP (seconds): median = 41.7 (first quartile = 38.9, third quartile = 44.6). P, BV, HPI, and AP values were higher ( P < .001), whereas PP and TTP were lower ( P < .001) in HCC relative to the surrounding liver. Values of perfusion parameters in the cirrhotic liver of patients with and without HCC were not significantly different ( P > .001).

Conclusion

In cirrhotic patients with HCC, perfusion computed tomographic technique can provide quantitative information about tumor-related angiogenesis.

As many diseases induce early changes in tissue hemodynamic status, quantitative tissue perfusion imaging could have the ability to characterize pathologic states, establish a diagnosis, and map the response to treatment ( ). In patients with liver cirrhosis, a spectrum of focal lesions, including benign regenerative nodules, dysplastic nodules, and hepatocellular carcinoma (HCC) lesions, develop; differences in their respective blood supplies can assist in their detection and characterization ( ). Although regenerative nodules receive the majority of blood supply from the portal vein, the evolution from a low-grade dysplastic nodule to frank HCC is associated with a progression toward increasing arterial blood supply, mainly due to tumor-related arterial neovascularization (angiogenesis) ( ). This is a complex process involving endothelial cell proliferation, capillary formation, coordinated remodeling of extracellular tumor stroma, and anastomosis with the pre-existing host vasculature ( ). Tumor angiogenesis may have important implications in the diagnosis and treatment of liver tumors; therefore, the development of clinically applicable techniques enabling its characterization and quantification would be important in the management of these neoplasms ( ). Functional computed tomography (CT) with perfusion imaging is a new application in which a quantitative map of tissue perfusion is created from dynamic computed tomographic data and displayed using a color scale, allowing quantification of perfusion in absolute units at high spatial resolution ( ). Several earlier studies reporting a correlation between contrast enhancement parameters and histologic measurements of angiogenesis have suggested the possible use of perfusion computed tomographic technique as a marker of tumor angiogenesis ( ).

The purpose of this study was to determine the value of functional CT with perfusion imaging in the quantitative assessment of tumor-related arterial angiogenesis in patients with cirrhotic liver disease and HCC, as determined by the European Association for the Study of the Liver (EASL) criteria.

Materials and methods

Patients

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Contrast-Enhanced Ultrasound

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MDCT Imaging and Perfusion Computed Tomographic Protocol

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Image Analysis and Quantification of Perfusion Parameters

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Figure 1, Perfusion computed tomographic study performed in a 57-year-old woman with Child B liver cirrhosis and 14-mm focal lesion of hepatocellular carcinoma in the left hepatic lobe. ( a ) Raw data from multidetector 16-slice computed tomographic scan image shows regions of interest (ROIs) placed on the tumor (T1) and on the surrounding liver parenchyma (T2). ( b ) Arterial perfusion color map; ROIs are also shown at the same position. ( c ) Enhancement curves derived from analyses of ROIs. Pixel values in Hounsfield units; A1 = aorta; V1 = portal vein; S1 = spleen; T1 = tumor; T2 = surrounding liver parenchyma. Use of dual-input single-compartment modeling techniques for derivation of perfusion parameters required enhancement data from both inputs, aorta and portal vein, as well as the spleen.

Figure 2, Perfusion computed tomographic (CT) study performed in a 74-year-old man with Child B liver cirrhosis and 11-mm focal lesion of hepatocellular carcinoma in the eighth segment of the liver. ( a ) Raw data from multidetector 16-slice CT scan image shows regions of interest (ROIs) positioned on the tumor (T1), and on the surrounding liver parenchyma (T2). ( b ) Arterial perfusion color map; ROIs are also shown at the same position.

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Standard of Reference

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Statistical Analysis

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Results

Patients with HCC

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Perfusion Parameters in Patients with HCC

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Table 1

Descriptive Characteristics of Analyzed Perfusion Parameters

Hepatocellular Carcinoma Background Liver in Patients with Hepatocellular Carcinoma Background Liver in Patients without Hepatocellular Carcinoma Parameter Median First Quartile Third Quartile Median First Quartile Third Quartile Median First Quartile Third Quartile XP 47.0 36.0 61.4 10.4 9.3 13.2 11.5 9.4 13.9 BV 24.0 18.7 29.3 11.7 9.5 11.9 10.7 7.1 14.2 HPI 78.4 62.9 100 16.4 13.8 18.3 10.6 8.7 11.9 AP 45.9 39.0 60.1 10.4 9.5 11.9 13.2 10.1 15.5 PP 9.0 0 24.5 55.2 40.1 79.5 72.5 62.8 92.7 TTP 18.7 16.3 26.5 44.6 40.3 51.8 41.7 38.9 44.6

AP, arterial perfusion (ml/min); BV, tissue blood volume (ml/100 g); HPI, hepatic perfusion index (%); PP, portal perfusion (ml/min); TTP, time to peak (TTP, seconds); XP, hepatic perfusion (mL/s/100 g).

Figure 3, Box plots of group perfusion parameters in which boundary of boxes closest to zero indicates 25th percentile, line within boxes marks median, and boundary of boxes farthest from zero indicates 75th percentile. Errors bars below and above boxes indicate minimum and maximum values, respectively. Perfusion (P). Tissue blood volume (BV). Hepatic perfusion index (HPI). Arterial perfusion (AP). Time to peak (TTP). Portal perfusion (PP). P, BV, HPI, and AP values were higher, whereas PP and TTP values were lower, in hepatocellular carcinoma (HCC) relative to the surrounding liver. The values of perfusion parameters as measured in the cirrhotic liver parenchyma of patients with and without hepatocellular carcinoma were not significantly different.

Figure 4, Box plots of difference of perfusion parameters (perfusion [P], tissue blood volume [BV], hepatic perfusion index [HPI], arterial perfusion [AP], portal perfusion [PP], and time to peak [TTP]) between hepatocellular carcinoma and surrounding liver (21 patients). The lower boundary of boxes indicates 25th percentile, line within boxes marks median, and the higher boundary of boxes indicates 75th percentile. Errors bars below and above boxes indicate minimum and maximum values, respectively.

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Patients without HCC

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Perfusion Parameters in Patients without HCC

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Discussion

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Conclusion

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Academic Radiology, Volume 15, Issue 7
Journals General Radiology
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