non-TACE Group Research Articles

Effect of preoperative transcatheter arterial chemoembolization on angiogenesis of hepatocellular carcinoma cells

To evaluate the effects of four types of preoperative transcatheter arterial chemoembolization (TACE) on angiogenesis of hepatocellular carcinoma (HCC) cells. A total of 136 patients with HCC underwent liver resection. One to five courses of TACE prior to liver resection were performed in 79 patients (TACE group), in which one to four courses of chemotherapy alone were performed in 11 patients (group A); one to five courses of chemotherapy combined with iodized oil were performed in 33 patients (group B); one to three courses of chemotherapy combined with iodized oil and gelatin sponge were performed in 23 patients (group C); one to three courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge were performed in 12 patients (group D). The other 57 patients only received liver resection (non-TACE group). The microvessels were marked by CD31. The expression of CD31 and vascular endothelial growth factor (VEGF) protein were detected by immunohistochemical methods. The mean microvessel density (MVD) in HCC cells was significantly higher in groups A, B, C and D than in the non-TACE group (P < 0.05). The expression of VEGF protein in HCC cells were significantly higher in groups A, B, C and D than in the non-TACE group (P < 0.05). MVD and the expression of VEGF protein were positively correlated. Mean MVD and the expression of VEGF protein were closely related to the number of courses of TACE and the interval of TACE. Four different types of preoperative TACE regimens enhanced angiogenesis in HCC cells by up-regulating the expression of VEGF protein. It is necessary to repress angiogenesis of liver cancer after TACE.

Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization

Transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for non-curative hepatocellular carcinoma (HCC), and hoped to have chemotherapeutic and ischemic effects; however, the histopathological changes of HCC caused by TACE have not been sufficiently discussed so far. We aimed to assess the morphological and immunohistochemical features of HCC treated with TACE by immunostaining cytokeratin (CK) 7, CK14, CK19 and vimentin, and to correlate these data with observed clinicopathological characteristics. Eighty cases of surgically resected HCC with preoperative TACE and 146 cases of HCC resected without TACE as a control were analyzed. The incidences of intrahepatic metastasis, poorly differentiated histology, multinucleated giant cells, mitotic figures and cytoplasmic inclusion bodies in the TACE group were significantly higher than those in the non-TACE group. The TACE group showed reactivity for CK7 in 56.3% (45/80) of patients, CK14 in 12.5% (10/80), CK19 in 23.8% (19/80) and vimentin in 6.3% (5/80) of patients. CK19 expression in the TACE group was significantly higher than in the non-TACE group (P = 0.0423). There was no correlation between immunoreactivity and the number of times TACE was carried out, but the expression of CK19 and vimentin in the massive necrotic group was higher than that in the mild necrotic group (P = 0.0197, P = 0.0229, respectively). Only TACE was an independent determinant of CK19 expression in all cases by multivariate analysis. These results suggest that preoperative TACE may have an impact on the biliary phenotype of HCC. Some post-therapeutic HCC patients might develop HCC with a biliary phenotype indicating more aggressive malignancies.

Is Preoperative Transarterial Chemoembolization Needed for a Resectable Hepatocellular Carcinoma?

Whether preoperative transarterial chemoembolization (TACE) has the therapeutic benefits in patients with resectable hepatocellular carcinoma (HCC) remains uncertain. We retrospectively investigated the influence of preoperative TACE on both disease-free survival and the pattern of recurrence after curative resection. From March 1998 to January 2005, a series of 273 patients who underwent curative resection for HCC were reviewed. Altogether, 120 patients underwent preoperative TACE, and 153 patients did not. We compared disease-free survival and the recurrence patterns between TACE and non-TACE groups, as well as between subgroups, stratified with regard to initial tumor size (< or =3 cm, 3-5 cm, >5 cm) and pathologic tumor stage (stage I-II and stage III-IVa). We also compared disease-free survival and the pattern of recurrence among the three groups: complete necrosis, incomplete necrosis, non-TACE groups. The 1-, 3-, and 5-year disease-free survival rates were 76.0%, 57.7%, and 51.3%, respectively, in the TACE group and 70.9%, 53.8%, and 46.8%, respectively, in the non-TACE group. No significant difference was observed in disease-free survival or the pattern of recurrence between the TACE and non-TACE groups. Further analysis of disease-free survival and the pattern of recurrence between subgroups according to initial tumor size and tumor stage showed no significant differences. Complete necrosis of tumor was recognized in only 33 patients of the TACE group (p = 0.001). Among the three complete necrosis, incomplete necrosis, and non-TACE groups, no significant difference was observed in disease-free survival or the pattern of recurrence. Preoperative TACE did not significantly improve the disease-free survival or the pattern of recurrence after curative resection of HCC. Even though this study is a retrospective analysis, preoperative TACE cannot be recommended as a routine procedure before hepatectomy for a resectable HCC.

Radiation‐induced hepatic toxicity after radiotherapy combined with chemotherapy for hepatocellular carcinoma

The purpose of the present study was to analyze hepatic toxicity following radiotherapy combined with regional chemotherapy for hepatocellular carcinoma (HCC). From 2001 to 2003, a total of 132 patients with HCC received 3-D conformal radiation therapy (3D-CRT) combined with chemotherapy. Patients were divided into two groups based on drug localization: the transcatheter arterial chemoembolization (TACE) group, where the chemotherapeutic drug (adriamycin) was localized within the tumor, and the non-TACE group, where the drugs (adriamycin, cisplatin, 5-fluorouracil) were diffusely spread over the entire liver. Patients were evaluated by biochemical parameters for any hepatic toxicity prior to, during, and until 12 months after 3D-CRT. Hepatic toxicity was defined as radiation-induced liver disease (RILD) or combined modality-induced liver disease (CMILD), which is defined as RILD with abnormal elevation of total bilirubin levels. In the TACE group, three patients developed RILD (5.6%) and none developed CMILD. In the non-TACE group, three patients (3.7%) and seven patients (8.8%) developed RILD and CMILD, respectively. Hepatic toxicity following radiotherapy combined with regional chemotherapy for HCC might be influenced by the distribution of the chemotherapeutic drugs. A more precise understanding of hepatic toxicity from chemoradiotherapy will help design optimal treatments for HCC.

Effect of preoperative transcatheter arterial chemoembolization on proliferation of hepatocellular carcinoma cells

To evaluate the effect of preoperative transcatheter arterial chemoembolization (TACE) on proliferation of hepatocellular carcinoma (HCC) cells. A total of 136 patients with HCC underwent liver resection. Of 136 patients, 79 patients received 1 to 5 courses of TACE prior to liver resection (TACE group), who were further subdivided into four groups: Group A (n = 11) who received 1 to 4 courses of chemotherapy alone; Group B (n = 33) who received 1 to 5 courses of chemotherapy combined with iodized oil; Group C (n = 23) who received 1 to 3 courses of chemotherapy combined with iodized oil and gelatin sponge; and Group D (n = 12) who received 1 to 3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge. The other 57 patients only received liver resection (non-TACE group). The expressions of Ki-67 and proliferating cell nuclear antigen (PCNA) protein were detected in the liver cancer tissues by immunohistochemical method. The Ki-67 protein expression was significantly lower in Groups C and D as compared with non-TACE group (31.35% +/- 10.85% vs 44.43% +/- 20.70%, 30.93% +/- 18.10% vs 44.43% +/- 20.70%, respectively, P < 0.05). The PCNA protein expression was significantly lower in Groups C and D as compared with non-TACE group (49.61% +/- 15.11% vs 62.92% +/- 17.21%, 41.16% +/- 11.83% vs 62.92% +/- 17.21%, respectively, P < 0.05). The Ki-67 protein expression was significantly higher in Group A as compared with non-TACE group (55.44% +/- 13.72% vs 44.43% +/- 20.70%, P < 0.05). The PCNA protein expression was significantly higher in Groups A and B as compared with non-TACE group (72.22% +/- 8.71% vs 62.92% +/- 17.21%, 69.91% +/- 13.38% vs 62.92% +/- 17.21%, respectively, P < 0.05). Preoperative multi-material TACE suppresses the proliferation of HCC cells, while a single material embolization and chemotherapy alone enhance the proliferation of HCC cells.

Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma

Aims To study the effect of preoperative transcatheter arterial chemoembolization (TACE) on long-term survival after hepatic resection for hepatocellular carcinoma (HCC), we conducted a comparative analysis in 235 HCC patients who underwent hepatic resection with a curative intent. Methods We compared clinicopathologic background, mortality, and survival rates after hepatic resection between those who underwent preoperative TACE ( n = 109) and those who did not ( n = 126). Results One hundred and two patients in the TACE group (93.6%) received TACE only once. The mean interval between TACE and hepatic resection was 33.1 days. Patients in the TACE group were younger than those in the non-TACE group, and liver cirrhosis and non-anatomical hepatic resection were more prevalent in this group. The 5-year overall survival rate after hepatic resection was significantly lower in the TACE group (28.6%) than in the non-TACE group (50.6%), especially in patients without cirrhosis or with stage I or II tumor. There was no difference between the two groups in mortality or disease-free survival after hepatic resection. Multivariate analysis showed preoperative TACE, preoperative aspartate aminotransferase elevation, and microscopic portal invasion to be independent risk factors for a poor outcome after hepatic resection. Conclusions Preoperative TACE should be avoided for patients with resectable HCC, especially for those without cirrhosis or with an early stage tumor.

HEPATOCELLULAR CARCINOMA AND LIVER TRANSPLANTATION: AN ANALYSIS OF PROGNOSTIC FACTORS

O368 Aims: Orthotopic liver transplantation (OLT) is the only curative treatment of inoperable hepatocellular carcinoma (HCC). The prognosis after OLT depends on the characteristics of the primary tumor such as size, grading and vascular invasion and it is still controversial which patient to transplant. We performed an uni- and multivariate analysis of prognostic factors in 64 HCC patients undergoing OLT. Methods: Between 1998 and 12/2003 64 patients suffering from HCC were transplanted. 34 received a neoadjuvant treatment by transarterial chemoembolisation (TACE) with Mitomycin C and Lipiodol at intervalls of 6 weeks (mean 4.9 sessions) while waiting for OLT (male 27, female 7; age 58,5±7.3 years; liver function Child A 76%, Child B 18%, Child C 6%; Milan Criteria (MC) fulfilled 32%, beyond MC 68%). The control group consisted of 30 patients without (19/30) or other (11/30) pretreatment (male 20, female 10; age 56.1±6.4 years; liver function Child A 33%, Child B 20%, Child C 47%; Milan Criteria (MC) fulfilled 60%, beyond MC 40%). The median follow up was 672 days. Univariate and multivariate analyses of several prognostic factors for recurrence-free survival after OLT were performed using Kaplan Meier method and Cox regression, respectively. Results: Recurrence-free survival (5 years) of all patients was 45%, 84% (TACE group) and 23% (non TACE group), respectively. 16/64 patients died after OLT, 6/16 (37%) due to HCC recurrence, 10/16 (63%) due to HCC unrelated causes. 1/34 (3%) patient with TACE pretreatment, but 9/30 (30%) without TACE died due to HCC unrelated causes. HCC recurrence after OLT occurred in 3/34 (9%) patients in the TACE group (2 patients are still alive), and 5/30 (17%) patients in the non-TACE group. In the TACE group MC were fulfilled in 11/34 patients, 23/34 patients were beyond the MC, survival was comparable: 86% vs. 83%. 25/34 TACE patients had stable disease during pretreatment, all of them are recurrence-free after 3 years. 9/34 had progressive tumor under TACE, only 51% are recurrence-free (p=0.001). In the multivariate analysis only TACE vs. non TACE showed an influence on survival (p=0.008). The influence of tumor stage, MC, grading, solitary vs. multifocal growth or waiting time was not significant. The univariate analysis of prognostic factors proved statistical influence on recurrence-free survival for TACE vs. non-TACE (p=0.004) and waiting time >150 days (p=0.028). Vascular invasion (p=0.093), grading (p=0.138), tumor size (p=0.621), MC (p=0.433), and solitary vs. multifocal growth (p=0.967) had no significant influence on survival. Conclusions: Neoadjuvant treatment of HCC patients awaiting OLT influences recurrence-free survival, whereas tumor characteristics as stage, grading and MC do not. Sequential TACE without tumor progress is a strong predictor for recurrence-free survival. Even in patients with large tumors OLT may be justified if the tumor is stable during TACE pretreatment and if TACE is performed in close intervalls.

Effects of p53 on apoptosis and proliferation of hepatocellular carcinoma cells treated with transcatheter arterial chemoembolization.

To evaluate the effects of p53 on apoptosis and proliferation of hepatocellular carcinoma (HCC) cells treated with transcatheter arterial chemoembolization (TACE). A total of 136 patients with HCC received TACE and other management before surgery were divided into TACE group and non-TACE group. TACE group included 79 patients who had 1-5 courses of TACE before surgery, of them, 11 patients had 1-4 courses of chemotherapy (group A), 33 patients had 1-5 courses of chemotherapy combined with iodized oil (group B), 23 patients had 1-3 courses of chemotherapy, iodized oil and gelatin sponge (group C), 12 patients had 1-3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge (group D). Non-TACE group included the remaining 57 patients who had surgery only. The extent of apoptosis was analyzed by transferase mediated dUTP nick end labeling (TUNEL) staining. The expressions of p53, Bcl-2, Bax, Ki-67 and PCNA protein were detected by immunohistochemical method. P53 protein expressions in trabecular and clear cells in HCC specimens were significantly lower than that in pseudoglandular, solid, poorly differentiated or undifferentiated and sclerosis HCC (P<0.05). Expression of p53 protein in HCC cells increased with the increase of pathological grades (P<0.05), and correlated positively with expressions of Ki-67 and PCNA protein, and negatively with Bcl-2 to Bax protein expression rate and AI (P<0.05). Expression of p53 protein was significantly higher in group A than in groups B, C, D and the non-TACE group, and was higher in group B than in groups C and D, and lower in group D than in the non-TACE group (P<0.05). Expression of p53 protein can enhance proliferation of HCC cells and suppress apoptosis of HCC cells after TACE.