Computer-tomography features of hemodynamics in hepatocellular carcinoma foci depend on the stage of histological differentiation

Aim of investigation. To define computer-tomography (CT) densitometry features of hepatocellular carcinoma (HCC) at different stages of histological differentiation and to correlate CT vascularisation degree to morphological features.

Material and methods. The study was based on the clinical and morphological data of 19 patients (12 men and 7 women, aged 18–72 years), with hepatocellular carcinoma (HCC) without coexistent liver cirrhosis. At a preoperative stage all patients underwent helical CT with bolus contrast enhancement (four phases study), with estimation of arterial and venous density gain of
the lesion and CT-vascularization index. The morphometric analysis of HCC blood vessels was carried out in immunehistochemical specimens stained for CD34 and CD105.

Results. According to CT and immunohistochemistry data highly differentiated carcinomas were the most vascularized (hypervascular), while poorly differentiated HCC were the least vascularized. Hemodynamic functionality in moderately-differentiated tumor nodes was significantly higher as compared to well differentiated tumor. The poorly differentiated tumor was characterized by decrease in both total number of blood vessels, and the quantity of neovasculatures that underlies transition of cells to anaerobic way of metabolism.

Conclusion. Decrease in histological differentiation grade and concomitant gain of malignant potential of neoplasm is associated to reduction of the total area ofbarterial blood vessels. Computer tomography scores should be applied as additional criteria of the tumor malignant potential and for estimation of treatment efficacy as well.

1. Yang J.D., Roberts L.R. Epidemiology and management of hepatocellular carcinoma. Infect Dis Clin N Am 2010; 24:899-919.

2. Silva A.C., Evans J.M., McCullough A.E., et al. MR Imaging of hypervascular liver masses: A review of current techniques. RadioGraphics 2009; 29:385-402.

3. Nojiri K., Tanaka K., Takeda K., et al. The efficacy of liver resection for multinodular hepatocellular carcinoma. Anticancer Res 2014; 34:2421-6.

4. Pancoska P., Carr B.I. Macroand micro-environmental factors in clinical hepatocellular cancer. Semin Oncol 2014; 41:185-94.

5. Щеголев А.И., Мишнев О.Д., Тинькова И.О. Онкоморфология печени. М.: Изд-во РГМУ, 2006. 252 с.

6. Gaddikeri S., McNeeley M.F., Wang C.L., et al.

7. Hepatocellular carcinoma in the noncirrhotic liver. Am J Roentgenol 2014; 203:34-47.

8. Tarhan N.C., Hatipoglu T., Ercan E., et al. Correlation of dynamic multidetector CT findings with pathological grades of hepatocellular carcinoma. Diagn Interv Radiol 2011; 17:328-33.

9. Туманова У.Н., Дубова Е.А., Кармазановский Г.Г., Щёголев А.И. Компьютерная томография в оценке кровоснабжения гепатоцеллюлярного рака. Анн хир гепатол 2013; 18(4):53-60.

10. Tumanova U.N., Dubova Ye.A., Karmazanovsky G.G., Schegolev A.I. CT characteristics of the vasculature and blood supply of hepatocellular carcinoma. Ann khir gepatol 2013; 18(4):53-60.

11. Theise N.D., Curado M.P., Franceschi S., et al. (Eds.) WHO classification of tumours of the digestive system. Lyon: IARC, 2010. 205-16.

12. Iavarone M., Sangiovanni A., Forzenigo L.V., et al.

13. Diagnosis of hepatocellular carcinoma in cirrhosis by dynamic contrast imaging: the importance of tumor cell differentiation. Hepatology 2010; 52:1723-30.

14. Matsui O., Kadoya M., Kameyama T., et al. Benign and malignant nodules in cirrhotic livers. Distinction based on blood supply. Radiology 1991; 178:493-7.

15. Kim C.K., Lim J.H., Park C.K., et al. Neoangiogenesis and sinusoidal capillarization in hepatocellular carcinoma: correlation between dynamic CT and density of tumor microvessels. Radiology 2005; 237:529-34.

16. Asayama Y., Yoshimitsu K., Nishihara Y., et al.

17. Arterial blood supply of hepatocellular carcinoma and histologic grading: radiologic-pathologic correlation. Am J Roentgenol 2008; 190:28-34.

18. Kudo M., Tomita S., Tochio H., et al. Sonography with intraarterial infusion of carbon dioxide microbubbles

19. (sonographic angiography): Value in differential diagnosis of hepatic tumors. Am J Roentgenol 1992; 158:65-74.

20. Kudo M., Tomita S., Kashida H., et al. Tumor hemodynamics in hepatic nodules associated with liver cirrhosis. Relationship between cancer progression and tumor hemodynamic change. Jpn J Gastroenterol 1991; 88:1554-65.

21. Sharma S., Sharma M.C., Sarkar C. Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology 2005; 46:481-9.

22. Tanaka F., Otake Y., Yanagihara K., et al. Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 2001; 7:3410-5.

23. Ho J.W., Poon R.T., Sun C.K., et al. Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver. World J Gastroenterol 2005; 11:17681.

24. Vermeulen P.B., Gasparini G., Fox S.B., et al. Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumors. Eur J Cancer 2002; 38:1564-79.

25. Zeng W., Gouw A.S.H., van den Heuvel M.C., et al.

26. Hepatocellular carcinomas in cirrhotic and noncirrhotic human livers share angiogenic characteristics. Ann Surg Oncol 2010; 17:1564-71.

27. Туманова У.Н., Дубова Е.А., Кармазановский Г.Г., Щеголев А.И. Компьютерно-томографические и морфологические сопоставления степени васкуляризации очаговой узловой гиперплазии печени. Мол мед 2013; 4:31-6.

28. El-Assal O.N., Yamanoi A., Soda Y., et al. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology 1998; 27:1554-62.

29. Jang H.J., Kim T.K., Burns P.N., Wilson S.R. Enhancement patterns of hepatocellular carcinoma at contrast-enhanced US: comparison with histologic differentiation. Radiology 2007; 244:898-906.

30. Туманова У.Н., Кармазановский Г.Г., Щеголев А.И. Денситометрические характеристики гепатоцеллюлярного рака при спиральной компьютерной томографии. Мед визуализация 2012; 6:42-50