Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma: Prevalence and Causative Factors of Extrahepatic Collateral Arteries in 479 Patients

OBJECTIVE: We wanted to investigate the prevalence and causative factors of extrahepatic arterial blood supply to hepatocellular carcinoma (HCC) at its initial presentation and during chemoembolization. MATERIALS AND METHODS: Between February 1998 and April 2000, consecutive 479 patients with newly diagnosed HCC were prospectively enrolled into this study. A total of 1629 sessions of transcatheter arterial chemoembolization (TACE) were performed in these patients (range: 1-15 sessions; mean: 3.4 sessions) until April 2004. For each TACE procedure, we determined the potential extrahepatic collateral arteries (ExCAs) depending on the location of the tumor, and we performed selective angiography of all suspected collaterals that could supply the tumor. The prevalence of ExCAs and the causative factors were analyzed. RESULTS: At initial presentation, 82 (17%) of these 479 patients showed 108 ExCAs supplying tumors. Univariate analysis showed that tumor size (p or = 5 cm) was significantly higher than that for those patients with a small tumor (< 5 cm) (p < 0.01). CONCLUSION: The presence of ExCAs supplying HCC is rather common, and the tumor size is a significant causative factor for the development of these collateral arteries.

Correlation of VEGF with contrast enhancement on dual-phase dynamic helical CT in liver tumors: preliminary study

The purpose of this preliminary study is to elucidate that vascular endothelial growth factor (VEGF) influences contrast enhancement of hepatic tumors on computed tomography (CT). Fourteen patients with hepatic tumors (11 hepatocellular carcinomas; 3 metastatic cancers) underwent a dual-phase dynamic helical CT or computed tomographic hepatic arteriography. The attenuation of each mass was determined as hyperattenuation, isoattenuation or hypoattenuation with respect to the adjacent nontumorous parenchyma. Gun-needle biopsy was done for each tumor, and paraffin sections were immunostained with anti- VEGF antibody by the avidin-biotin-peroxidase complex method. The pathologic grade was made by intensity (1 +, 2+, 3+) and area (+/-, 1 +, 2+). The tumor ranged 2.0-14.0 cm in size (mean, 5.8 cm). In arterial phase, the intensity was not correlated with the degree of enhancement (p=0.086). However, the correlation between the attenuation value of hepatic arterial phase and the area of positive tumor cells was statistically significant (p=0.002). VEGF may be the factor that enhances the hepatic mass with water-soluble iodinated contrast agent in CT.

Hemodynamic changes of liver carcinoma after radiofrequency ablation evaluated by color doppler ultrasonography / 中国普通外科杂志

Objective To evaluate the results of liver carcinoma treated by radiofrequency ablation(RFA) with color Doppler ultrasonography(CDU). Methods Hemodynamic changes of the interior and periphery of 212 nodules of liver carcinoma in 152 patients were investigated by CDU one week before and one month after RFA. Results Blood flow signals were found in 187 cancerous nodules before RFA, and were chiefly from mixed arterio-venous blood supply. After RFA, the blood flow signals of these 187 cancerous nodules completely disappeared in 133, were reduced in 40 and did not change in 14. Peripherar blood flow did not change in 51.2% of the tumors. Conclusions CDU is useful in evaluating the therapeutic effect of RFA in patients with liver carcinoma and may provide information for further treatment.

Dynamic Images for Prediction of Therapeutic Efficacy of Hepatocellular Carcinoma Treated with Transcatheter Oily Chemoembolization

PURPOSE: To predict the therapeutic efficacy of transcatheter oily chemoembolization(TOCE) in the treatment. MATERIALS AND METHODS: We reviewed the findings of 24 dynamic CT or MR scans examined for the purpose of diagnosis before TOCE, and follow-up CT scans obtained after this procedure. In 24 patients (M:F=20:4) with a mean age of 52.2 years, 43 nodular HCCs with a diameter of 5 cm or less were present. The patients underwent double dynamic CT or MR imaging as one arterial phase 30 seconds after the intravenous injection of contrast media, and this was followed by a delayed phase 5 minutes fter injection. HCCs were then classified as one of four types: Type I, high and low attenuation or intensity during the arterial and delayed phase, respectively; Type II, iso- and low; Type III, iso- and high; and Type IV, high and iso-. In addition, we classified the degree of lipiodol accumulation by HCC nodules as either Grade 5 (fullmoon-like lipiodolization), Grade 2 (about 40%), or Grade 1 (about 20%), as seen on follow-up CT scans after TOCE. RESULTS: Type I provided an accuracy of 72.1% considering to more than 50% lipiodol accumulation. However, a single finding demonstrating high atenuation or intensity during the arterial phase gave an accuracy of 79.1% better than that of Type I. CONCLUSION: A finding of high attenuation or intensity during the arterial phase, as seen on dynamic CT or MR images, provides the best information about the therapeutic efficacy of HCCs treated by means of with TOCE.

Color Doppler Ultrasound of Hepatocellular Carcinoma: Evaluation of Recurrence after Transcatheter Arterial Chemoembolization

PURPOSE: To evaluate the efficacy of color and pulsed Doppler ultrasound (US) for the detection of arterial revascularization of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: One hundred and four histologically proven HCCs (0.7-12.5 cm, mean 4.14 cm) of 87 consecutive patients who had undergone TACE using a Lipiodol-chemoagent suspension were examined using color Doppler equipment. The criteria for diagnosing arterial revascularization of HCC were detection of inward blood vessels within HCC and demonstration by spectral Doppler US of pulsatile arterial flow within the vessel. Color Doppler US was prospectively performed using a multi-Hertz probe (2.5-5 Hz), and was followed by digital subtraction angiography (DSA). RESULTS: In 37 of 104 HCCs in 87 patients treated with TACE, color and spectral Doppler US demonstrated intratumoral arterial flows, with peak systolic velocity of 4.2-220 (mean, 59) cm/sec. DSA revealed neovascularity or tumor stains in 38 HCCs (3.4-12.5 cm, mean 5.9 cm in size) including 37 which on Doppler US showed arterial flow. The remaining 66 of 104 HCCs (0.7-6.3 cm, mean 3.2 cm) did not stain during DSA. Doppler US showed a false negative result in only one HCC (4.6 cm, located at segment VII of the Couinaud classification), which stained faintly during DSA. The sensitivity, specificity, and accuracy of color and spectral Doppler US used for the detection of recurrent HCC were 97.4%, 100%, and 99%, respectively. CONCLUSIONS: Color and spectral Doppler US is an effective method for the evaluation of arterial revascularization of HCC after TACE.

Use of Epinephrine Infusion During CT Hepatic Arteriography (Pharmaco-CTHA):Clinical Application in Patients with Hepatocellular Carcinoma

PURPOSE: To evaluate the usefulness of epinephrine infusion (Pharmaco-CTHA) prior to liver to liver spiral CT during hepatic arteriography in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Twenty-two patients in whom hepatocellular carcinoma had been diagnosed underwent three types of liver spiral CT during hepatic arteriography. In the first method, spiral CT scanning was started 5 seconds after injecting 8cc of contrast media at a rate of 0.3cc/sec. In the second, 10 microgram of epinephrine was slowly injected for 1 minute via the catheter and subsequent spiral CT scanning began 11 seconds after injecting 8cc of contrast media at a rate of 0.3cc/sec. In the third method, spiral CT scanning was started 5 seconds after injecting 25cc of contrast media at a rate of 1cc/sec. The following were evaluated and compared with the results of follow-up lipiodol CT: 1) the incidence of false positive lesions; 2) the incidence of false negative lesions; 3) portal enhancement; and 4) lesion conspicuity. RESULTS: Follow-up lipiodol CT of 22 patients showed 16 masses. In 12 patients there was no lipiodol uptake, and in five, four and one patient(s), uptake occurred once, twice, and three times, respectively. With method 1there were nine false-positive lesions, with method 2 there were 13, and with method 3, there were 49. The use of method 2(Pharmaco-CTNA) led to less false-positives than did method 3 (conventional CTHA)(p=0.000). Method 1 showed the lowest false positive rate (nine lesions), but its false-negative rate was two and four times higher than with method 2 (four lesions) and with method 3 (two lesions), respectively. Portal enhancement was observed four times using method 3 and once with method 1, but was absent with method 2. As regards the conspicuity of 16 masses, "good" and "excellent" lesions were seen four times with method 1(25%), ten times with method 2 (62.5%) and thirteen times with method 3 (81.3%). CONCLUSION: The infusion of epinephrine (Pharmaco-CTHA) prior to spiral CT during hepatic arteriography has the advantage of reducing the amount of contrast media required as well as the number of cases which are false positive and show no portal enhancement.

Effects of angiopioetins/Tie-2 and VEGF expression on hepatocellular carcinoma angiogenesis / 中国普通外科杂志

Objective To investigate the effects of angiopioetins and tyrosine kinase receptor Tie-2 ,vascular endothelial growth factor (VEGF)on the angiogenesis and progression of hepatocellular carcinoma(HCC). Methods With the methods of RT-PCR and immunohistochemistry, the specimens from 28 HCC patients, 10 cirrhotics, and 10 normal livers were analysed, and the relationship between angiopioetins, VEGF (expression) and the clinical pathological characteristics of HCC was studied. Results Ang/Tie-2 and VEGF were significantly up-regulated in HCC compared to cirrhotic tissue and normal liver tissue. (Immunohistochemical) staining also showed increased expression of Ang-2,VEGF,Tie-2 protein in HCC. A high Ang-2/Ang-1mRNA ratio and high VEGF in HCC were closely associated with tumor vascular invasion and microvascular density level which assesssed by CD34. Conclusions Ang /Tie-2 and VEGF may play critical roles in promoting tumor angiogenesis and progression in human HCC.

Hemodynamic Change by Portal Tumor Thrombus in Hepatocellular Carcinoma: Evaluation by Combined Spiral CT Hepatic Arteriography and CT Arterial Portography

PURPOSE: To evaluate the hemodynamic change by portal tumor thrombus in hepatocellular carcinoma(HCC). MATERIALS AND METHODS: We reviewed 35 cases of combined spiral CTHA and CTAP in 25 HCC patients with portal tumorthrombus from April 1993 to October 1994, regarding to portal tumor thrombus, the involved area of arterioportal(AP) shunt and the development of cavernous transformation of portal vein, in comparison with hepaticand superior mesenteric arteriography. RESULTS: Spiral CTHA showed hyperattenuating tumor, portal tumor thrombus and hyperattenuating peritumoral parenchymal area. Spiral CTAP showed perfusion defect area including tumor, portal tumor thrombus and peritumoral area distal to portal vein obstruction. In 15 cases, portal tumor thrombus showed intraluminal and marginal hyperattenuating linear structures on CTHA due to transvasal AP shunt and tumor feeding arteries, which were corresponding to thread and streaks sign on hepatic arteriography. Cavernous transformation of portal vein was demonstrated in 15 cases as irregular periportal hyperattenuating collateral vessels on spiral CTAP. In 32 cases, portal vein was visualized on CTHA due to AP shunt. And according to shunt amount, we classified AP shunt into 4 grades. Grade I means only the presence of portal tumor thrombus without AP shunt, grade II with segmental AP shunt, grade III with one lobar AP shunt, and grade IV with both lobar AP shuntor the presence of cavernous transformation of portal vein. Grade I was seen in 3, grade II in 4, grade III in 13 and grade IV in 15 cases. CONCLUSION: Variable CTHA and CTAP findings were shown in HCC patients with portal tumor thrombus according to the amount of AP shunt and the presence of cavernous transformation of portal vein. Combined CTHA and CTAP are useful to differentiate the tumor thrombus from simple thrombus and are very sensitive method for detecting AP shunt. Understanding these findings related with portal tumor thrombus is important topredict patient}s prognosis and to decide treatment method.

Significance of expression of angiopoietin mRNA in the tissue of in-situ implanted hepatoma / 中国普通外科杂志

Objective To study the relationship of expression of angiopoietin gene and angiogenesis in the in-situ implanted hepatoma in rats. Methods Forty Wistar rats were used to establish the in-situ implanted hepatoma model by implanting Walker256 hepatoma cell line. The number of microvessel density(MVD) in hepatoma was calculated . The expression of angiopoietin mRNA was observed by in-situ hybridization method. Results The MDV in the implanted hepatoma in the first day of 1, 2 and 3 week postimplantatively were (15?4.3)/Hp,(17?3.6)/Hp,(45?7.8)/Hp respectively. The amount of MDV and expression of Ang-1 mRNA were increased significantly and correlated with MDV in the hepatoma tissues and non-hepatoma tissues,and no significant difference between the two types of tissues. Expression of Ang-2 mRNA was not seen in non-hepatoma tissues,but in hepatoma tissues,the expression of Ang-2 was obvious. Conclusions Angiopoietin-2 mRNA may play a role in the angiogenesis of the in-situ implanted hepatoma.

The expression and clinical significance of vascular endothelial growth factor in primary hepatocellular carcinoma / 中国普通外科杂志

Objective To study the relationship between the expression of vascular endothelial growth factor (VEGF) and invasion, metastasis of primary hepatocellular carcinoma (PHCC). Methods Paraffin-embedded specimens from 30 patients with PHCC undergoing radical resection were studied. Agiogenesis was assessed by the expression of VEGF and microvascular density (MVD) using LSAB immunohistochemical staining. Results (1) The level of VEGF and MVD in PHCC was higher than that in the paratumorous tissue (P5*!cm) and small ones (diameter ≤5*!cm). (4) The expression of VEGF was positively correlated with MVD (P