Trans-arterial p53-Gene-Embolization with Gelatin Sponge Microparticles for Hepatocellular Carcinoma with BCLC Stage B: Single-Center Experience

Abstract

Trans-arterial chemoembolization for hepatic cellular carcinoma (HCC) is a recommended treatment schedule for stage B patients under the Barcelona-Clinic Liver Cancer (BCLC) diagnostic and treatment strategy system. Data from treatments with embolization performed with different embolizing microparticle reagents either alone or in combination with different chemotherapeutic agents showed favorable safety profile and significant efficacy in tumor control. In addition, recombinant adenoviral human p53 gene (rAd-p53) therapy has been shown effective in the treatment of many solid tumors and some pre-cancerous lesions such as oral leukoplakia, while also presenting a favorable safety profile. To date, no data are available regarding the safety and efficacy of trans-catheter treatment of HCC with embolizing microparticles combined with rAd-p53 in the world. In this study, we demonstrated the safety and efficacy of trans-arterial embolization combined with rAd-p53 gene therapy (TAGE) in the treatment of patients with BCLC stage B HCC. In this retrospective study, 15 HCC patients with BCLC stage B were received TAGE. Fifteen males were included with an average age of 65 (53-89) years and with Child-Pugh score A or B (12 or 3, respectively). The embolic agent used in TAE was gelatin sponge microparticles of diameter 350-560 µm, and 3-5 × 10(12) viral of rAd-p53 was diluted with physiological saline into 15 ml suspension. The study endpoints included response rate, 1 year survival, liver function, and adverse effects. With a median follow-up time of 15.5 months, 15 HCC patients received a total number of 64 TAGE treatments without any significant complication. Based on the modified response evaluation criteria in solid tumors, complete response (CR) was observed in four, six, and six patients at 1, 3, and 6 months after the first treatment, respectively. The objective tumor response (CR + PR) rates at 1, 3, and 6 months were 100.0, 93.3, and 80.0%. The total survival rates of 6 and 12 months in 15 patients were 100%, 100% respectively. The median survival time was 32 months in all. Mild or median fever was observed in all 15 patients, which occurred 4-12 h after treatment and lasted for 12-24 h. Transient abdominal pain, nausea, and cholecystitis were the common side effects with a frequency of 46.7, 33.3, and 26.7%, respectively, and three cases (20%) showed decrease in platelet count. However, other severe (grade 3 or 4) adverse events associated with TAGE were not observed. TAGE is a safe and effective treatments for HCC with BCLC stage B HCC patients.

Gelatin sponge microparticles for the treatment of the spontaneous rupture of hepatocellular carcinoma hemorrhage

“…In the current study, 4 cases succumbed to complications, such as tumor progression complicated with multiple organ failure, gastrointestinal bleeding and hepatic encephalopathy; however, patient mortality showed no direct correlation with GSM-TACE. The results of the present study were concordant with those of previous studies with regards to the safety and clinical efficacy of GSMs for the treatment of HCC (19)(20)(21). Pre-operative shock, low hemoglobin and albumin expression levels, prolonged prothrombin time, increased serum creatinine expression levels, hepatic encephalopathy, severe ascites, portal vein tumor thrombus and multinodular tumors in the left and right lobe are the primary factors that affect the treatment of HCC rupture hemorrhage.…”

“…A previous study using animal experimentation, performed at the Affiliated Zhongshan Hospital of Dalian University (Dalian, China), demonstrated the safety of GSMs (18). Clinical application studies have suggested that GSM-TACE in the treatment of HCC results in tumor necrosis and a reduction in tumor size, and has good clinical curative effects (19)(20)(21). The present study aimed to summarize the clinical hemostatic effect of GSM-TACE in the treatment of HCC, and to investigate the safety and efficacy of the clinical application of GSMs.…”

Changes in the Peripheral Blood Treg Cell Proportion in Hepatocellular Carcinoma Patients After Transarterial Chemoembolization With Microparticles

“…TACE procedures are currently widely used for various cases of HCC, mostly patients at BCLC stage B. Gelatin sponge microparticle (GSM) is an effective embolization agent, and a study reported that when compared with the ethiodized oil which is a permanent embolization agent, GSMs had many advantages, such as a higher tumor response rate at 1 month after treatment, especially in large tumors (13). Our previous clinical practices have confirmed the safety and efficacy of GSMs-TACE (5,14,15). It was found that 350-560 mm GSMs combined with single chemotherapy drug TACE procedures was effective and safe in treating elderly HCC without surgical resection, and more elderly patients may have better prognosis (5).…”

“…It was found that 350-560 mm GSMs combined with single chemotherapy drug TACE procedures was effective and safe in treating elderly HCC without surgical resection, and more elderly patients may have better prognosis (5). GSMs combined with trans-arterial p53-gene-embolization also achieved satisfactory efficacy in treating BCLC stage B HCC as evidenced by favorable survival rates (100% for both 6 and 12 months) and no significant complications (14). Therefore, GSMs were adopted in this study, and imaging scan confirmed the efficacy of GSMs-TACE.…”

Transarterial chemoembolization combined with Huaier granule for the treatment of primary hepatic carcinoma

“…Treatment resulted in tumor necrosis and shrinking, rapid recovery of liver function, and good short-term effectiveness. [8] …”