Guofeng Zhou

The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor.

Transarterial chemo-embolization (TACE), which combined embolization therapy and chemotherapy, has become the most widely used treatment for unresectable liver cancer. Blood-vessel-embolic materials play key role on TACE. In the present work, doxorubicin-loaded p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels-iohexol dispersions (IBi-D) were reported firstly for TACE therapy to liver cancer. Using inverting-vial method, IBi-D dispersions showed three phases (swollen gel, flowable sol and shrunken gel) as temperature increased. Although Dox had little effect on the CGTs between flowable and shrunken gel, the rheological properties of IBi-D dispersions could greatly improved by Dox. A sustained Dox-release, which was necessary in TACE therapy, was found from IBi-D dispersions in the eluting medium of PBS buffers. The studies about renal artery embolization of normal rabbits indicated that IBi-D dispersions showed good properties in embolizing all kinds of renal arteries (including peripheral, small and large arteries) by controlling their injecting dosages. Angiography and medical evaluation indicated that TACE therapy of IBi-D dispersions has better efficacy on rabbit VX2 liver tumors than TAC treatment of free Dox and TAE treatment of IBi dispersions.

Effect of Transcatheter Intraarterial Therapies on the Distribution of Doxorubicin in Liver Cancer in a Rabbit Model

Background and Aims Transcatheter intraarterial techniques can effectively deliver chemotherapeutic agents to tumor and improve the efficacy of chemotherapy. The present study is designed to evaluate the effect of transcatheter intraarterial techniques on the distribution of doxorubicin in relation to blood vessels in liver cancer. Methods VX2 tumors were implanted in the livers of 32 rabbits. The animals were divided into 4 groups of 8 animals each. Group 1 (doxo iv) animals received doxorubicin intravenous injection; group 2 (doxo ia) received doxorubicin hepatic intraarterial infusion; group 3 (doxo ia + E) received doxorubicin hepatic intraarterial infusion followed by embolization; group 4 (doxo + L ia + E) received hepatic intraarterial infusion of doxorubicin mixed with Lipiodol followed by embolization. Ten minutes or 4 hours after treatment, the animals were sacrificed and tumors were sampled. Immunofluorescence techniques were used to evaluate the distribution of doxorubicin in relation to blood vessels. Results Doxorubicin fluorescence was distributed around tumor blood vessels and decreased with distance from the blood vessels. Tumor cells in avascular and adjacent regions were not exposed to detectable concentrations of doxorubicin. Tumors in the group 2, 3 and 4 had a significant increase in doxorubicin penetration compared with the group 1 tumors (P<0.05). Among the three groups of transcatheter therapies, doxorubicin penetration distance in group 3 was significantly larger than that in group 2 and 4 (P<0.05), and no significant difference was found between group 2 and 4 tumors (P>0.05) at 10 minutes. In contrast, at 4 hours and in total, both group 3 and 4 tumors had significant increases in drug penetration compared with group 2 (P<0.05), and no significant difference was noted between group 3 and 4 tumors (P>0.05). Conclusion Transcatheter intraarterial therapies improve doxorubicin penetration in liver cancer; nevertheless their effect on drug distribution is somewhat limited.

Intra-arterial interleukin-12 gene delivery combined with chemoembolization: anti-tumor effect in a rabbit hepatocellular carcinoma (HCC) model.

Background Interleukin-12 (IL-12), a cytokine naturally secreted by activated dendritic cells and monocytes/macrophages, is known as a key anti-tumor agent in many tumor models, including hepatocellular carcinoma (HCC) models. Purpose To evaluate the anti-tumor effect of intra-arterial IL-12 gene delivery alone and in combination with transcatheter arterial chemoembolization (TACE) in rabbit VX2 liver cancer model. Material and Methods Rabbits with VX2 liver tumors were randomized into four groups, eight in each group. After laparotomy and insertion of a 30-gauge needle into the proper hepatic artery, the following interventional procedure protocols were applied: 0.9% saline solution (group A, control), TACE (group B, TACE alone, lipiodol + mitomycin), intra-arterial interleukin-12 gene infusion (group C, IL-12 alone), and intra-arterial interleukin-12 gene infusion in combination with TACE (group D, IL-12 plus TACE). Growth ratio was estimated by computed tomography. To analyze apoptotic index, tumor tissues were explanted for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining, 14 days after therapy. Results Significant differences of the relative tumor growth ratio were observed in TACE alone group and IL-12 plus TACE group in comparison with control (P < 0.05, ANOVA, Tukeys HSD correction) but not between IL-12 alone and control, or IL-12 plus TACE group and TACE alone group (P > 0.05). Significant changes of the apoptotic index were observed in group D in comparison with remaining three groups (P < 0.05). The difference between group C and group A was not significant statistically (P > 0.05). Conclusion Intra-arterial interleukin-12 gene therapy combined with TACE has a potent anti-tumor effect in rabbit VX2 liver cancer in comparison with TACE alone.

Radiofrequency ablation combined with transcatheter therapy in rabbit VX2 liver tumors: effects and histopathological characteristics

Background Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) treatment (TACE-RFA) has been confirmed superior to TACE or RFA alone in animal liver tumors. TACE before RFA was shown to increase hepatocellular damage. Further optimization of the combination strategy for transcatheter arterial embolization (TAE) or TACE combined with RFA is warranted. Purpose To determine the optimal strategy for radiofrequency ablation combined with transcatheter therapies in VX2 liver tumors in a rabbit model. Material and Methods Twenty-four Japanese White rabbits with VX2 liver tumors were randomly divided into four groups: TACE-RFA (TACE-RFA group), transcatheter arterial embolization (TAE) combined with RFA treatment (TAE-RFA group), RFA only group, and TACE only group. Blood samples were collected 1 day before the operation and at 3 and 7 days postoperatively. Seven days after the operation, maximal diameters of coagulation or infarcted zones in the gross specimens, CT images, histopathological characteristics, tumor necrotic rate, and growth rate were compared. Results Significantly larger mean long-axis (P < 0.05) and short-axis (P < 0.05) diameters of coagulation and infarction were observed in the TACE-RFA group compared with the TAE-RFA, RFA, and TACE groups on day 7; and the TAE-RFA group showed a significant (P < 0.05) increase versus the RFA and TACE groups on day 7. There were no significant differences in tumor growth rate (109.3 ± 37.5 vs. 119.0 ± 43.1%, P = 0.45) and necrotic rate (89.5 ± 12.0 vs. 83.5 ± 9.3%, P = 0.73) between the TACE-RFA and TAE-RFA groups. TACE-RFA was more effective for achieving tumor destruction than the other treatment strategies, but led to increased rabbits discomfort and more severe liver dysfunction compared with TAE-RFA. Conclusion TAE-RFA appears to be a beneficial therapeutic modality for treating VX2 liver tumors in a rabbit model.

The studies on highly concentrated complex dispersions of gold nanoparticles and temperature-sensitive nanogels and their application as new blood-vessel-embolic materials with high-resolution angiography

Recently temperature sensitive polymers have been developed as novel embolization materials. However, their flowability and embolization have been seriously impacted by iodine-based X-ray contrast agents. In order to resolve the drawbacks of these contrast agents, highly concentrated complex (HCC) dispersions of gold nanoparticles (GNPs) with p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogels were developed as new blood-vessel-embolic materials with high-resolution angiography. Although GNPs have better X-ray attenuation than iodinated compounds, their poor dispersion stability limits their application in digital subtraction angiography (DSA). HCC dispersions show excellent X-ray attenuation ability which is 2.6 times higher than Omnipaque at 0.31 mol L-1. This can be attributed to the fact that the sol-gel transition of nanogel dispersions improves the colloid stability of GNPs. In the two sol-gel transition temperatures (Tg-s and Ts-g) of nanogel dispersions, GNPs have no influence on Ts-g, and a great influence on Tg-s. The in vivo experimental data indicate that HCC dispersions show high angiographic ability and good blood-vessel embolization, and can be used for postoperative examination for long periods owing to the entrapment of GNPs into the embolic sites. The HCC dispersions have potential to be developed as new blood-vessel-embolic materials with high-resolution angiography.

Noninvasive diagnosis of cardiac amyloidosis by MRI and echochardiography

This study described the radiological features on echocardiography and MRI specific to cardiac amyloidosis confirmed on biopsy. Eleven cases of biopsy-proven cardiac amyloidosis were retrospectively reviewed in this study. All patients underwent biopsy, cardiac MRI and echocardiography. The main echocardiography and MRI findings were as follows: diffuse ventricular and septum wall thickening, atrial enlargement, pericardial effusion, restricted left ventricular (LV) systolic and diastolic function, characteristic granular sparkling of myocardium. MRI revealed a characteristic pattern of global subendocardial late enhancement, extending in varying degrees into the neighboring myocardium. The findings agreed with the infiltration distribution of amyloid protein. Typical abnormalities seen on echocardiography and MRI should have important diagnostic and prognostic value of cardiac amyloidosis. MRI should be considered in the diagnosis of cardiac amyloidosis if echocardiographic features are suspicious.SummaryThis study described the radiological features on echocardiography and MRI specific to cardiac amyloidosis confirmed on biopsy. Eleven cases of biopsy-proven cardiac amyloidosis were retrospectively reviewed in this study. All patients underwent biopsy, cardiac MRI and echocardiography. The main echocardiography and MRI findings were as follows: diffuse ventricular and septum wall thickening, atrial enlargement, pericardial effusion, restricted left ventricular (LV) systolic and diastolic function, characteristic granular sparkling of myocardium. MRI revealed a characteristic pattern of global subendocardial late enhancement, extending in varying degrees into the neighboring myocardium. The findings agreed with the infiltration distribution of amyloid protein. Typical abnormalities seen on echocardiography and MRI should have important diagnostic and prognostic value of cardiac amyloidosis. MRI should be considered in the diagnosis of cardiac amyloidosis if echocardiographic features are suspicious.

Heat shock protein 70 expression and effect of combined transcatheter arterial embolization and radiofrequency ablation in the rabbit VX2 liver tumour model

AIM To evaluate the effects of a combined therapy using transcatheter arterial embolization (TAE) and radiofrequency ablation (RFA) on heat shock protein 70 (HSP70) expression and treatment effects in a rabbit model of VX2 liver tumours. MATERIALS AND METHODS Tumour growth and necrosis rates were evaluated on day 7. Five rabbits were assigned to each group and were killed on days 1, 3, and 7 after treatment. HSP70 expression was detected and quantified by immunohistochemistry, Western blot, and reverse transcription polymerase chain reaction (RT-PCR). RESULTS Tumour growth rate was significantly decreased and the necrosis rate increased in the TAE + RFA group on day 7 compared with the other groups. HSP70 expression in the TAE group peaked on day 1 and bottomed on days 3 and 7. HSP70 expression in the TAE group was significantly greater than in the control group on days 1, 3, and 7. HSP70 expression was increased on day 1, peaked on day 3, and dropped on day 7 in the RFA and TAE + RFA groups. In the TAE + RFA group, HSP70 expression was significantly greater than in the other groups on days 1, 3, and 7. HSP70 expression in Western blot analysis and HSP70 mRNA peaked on day 3 and dropped on day 7 in the TAE, RFA, and TAE + RFA groups. CONCLUSIONS HSP70 over-expression in residual tumours after TAE + RFA could be attributed to the additive effects of hypoxia and hyperpyrexia generated by TAE combined with RFA.

Clinical Features and Endovascular Treatment of Visceral Artery Pseudoaneurysms

BACKGROUND To analyze our experience with clinical features and endovascular treatment of visceral artery pseudoaneurysms (VAPAs). METHODS We performed endovascular treatments on 52 patients (34 men and 18 women) affected by VAPA. These cases were pseudoaneurysms of the celiac axis, superior mesenteric artery, and their branches. Endovascular treatments of VAPA using isolation techniques were performed after failure of conservative treatments. Follow-up was carried out via assessment of contrast-enhanced computed tomography or computed tomography angiography images. RESULTS The initial technical success rate of endovascular treatment is 100% with only 4 patients rebled during 2-week follow-up. One patient among no rebleeding died of multisystem organ failure 28 days after intervention; thus, 30-day mortality rate was 1.9%. Four patients (7.7%) required secondary interventions because of rebleeding and were successfully treated by reintervention; however, one of the patients died from uncontrolled sepsis 39 days after reintervention. Postembolization syndrome developed in 3 patients (5.8%); one of these patients underwent splenectomy. During follow-up, no change of hepatic function was observed, no bowel ischemia was reported, and VAPA remained absent in all patients. CONCLUSIONS Endovascular management is minimally invasive and highly successful in treating VAPA. It is particularly useful in poor surgical candidates.

Radiofrequency ablation combined with transarterial chemoembolization for liver metastases from gastrointestinal cancers

SummaryTransarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients’ demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients’ demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.

Changes of CD4+ CD25+ regulatory T cells in peripheral blood in patients with hepatocellular carcinoma before and after TACE

SummaryThis study investigated the changes of CD4+ CD25+ regulatory T cells (Tregs) in peripheral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoembolization (TACE). The proportion of CD4+ CD25+ Tregs among CD4+ T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups: 22 in group A, who were in stable condition or getting better; and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4+CD25+ Tregs among CD4+ T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant (P<0.01) between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4+ CD25+ Tregs among CD4+ T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and 1 week after TACE (P<0.01), whereas, that in group B was increased significantly 1 month after TACE (P<0.01). It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4+CD25+ Tregs in peripheral blood. TACE did not significantly affect the level of CD4+ CD25+ Tregs within short time (such as 1 week). The proportion of CD4+CD25+ Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.This study investigated the changes of CD4+ CD25+ regulatory T cells (Tregs) in peripheral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoembolization (TACE). The proportion of CD4+ CD25+ Tregs among CD4+ T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups: 22 in group A, who were in stable condition or getting better; and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4+CD25+ Tregs among CD4+ T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant (P<0.01) between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4+ CD25+ Tregs among CD4+ T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and 1 week after TACE (P<0.01), whereas, that in group B was increased significantly 1 month after TACE (P<0.01). It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4+CD25+ Tregs in peripheral blood. TACE did not significantly affect the level of CD4+ CD25+ Tregs within short time (such as 1 week). The proportion of CD4+CD25+ Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.