Downregulation of the adenosine a2b receptor by RNA interference inhibits hepatocellular carcinoma cell growth.

To investigate the biological effect of adenosine A2b receptor (A2bR) on the human hepatocellular carcinoma cell line HepG2, three A2bR siRNA constructs were transiently transfected into HepG2 cells. The results showed that A2bR siRNA reduced the levels of A2bR mRNA and protein. In order to further detect the function of A2bR, we established a stable hepatocellular carcinoma cell line (HepG2) expressing siRNA targeting the adenosine A2b receptor. Targeted RNAi significantly inhibited tumor cell growth in vitro, and flow cytometry (FCM) showed that significantly more cells expressing A2bR siRNA were in the G0/G1 phase compared to the untransfected group ((89.56% ± 3.15%) versus (56.19% ± 1.58%), P < 0.01). These results indicated that silencing the expression of adenosine A2b receptor in HepG2 cells can suppress cell growth effectively by blocking the cell cycle. Downregulation of adenosine A2b receptor gene expression with RNA interference could be a new approach to hepatocellular carcinoma therapy.

[Radiofrequency ablation therapy combined with suture and ligation surgery for patients with giant cavernous hemangiomas of the liver].

OBJECTIVE: To evaluate the feasibility and efficacy of radiofrequency ablation (RFA) therapy combined with suture and ligation surgery for patients with giant hepatic cavernous hemangioma (HCH). METHODS: Between June 2004 and June 2005, a total of 30 patients were treated by RFA therapy after suture and ligation surgery (SL group, n = 15, with 18 liver lesions) or RFA therapy without suture and ligation surgery (non-SL group, n = 15, with 17 liver lesions) under general anesthesia. All patients had obvious symptoms such as abdominal discomfort, pain and swelling. Preoperative diagnosis of HCH was established by means of ultrasonography, helical computed tomography (CT) scans, and magnetic resonance imaging (MRI). The mean maximum diameter of the lesions was 8.8 cm +/- 1.4 cm. All of the 35 lesions were located on the liver surface, in the caudate lobe of the liver, or adjacent to the gallbladder. Seven patients had chronic calculous cholecystitis, 6 common duct stones, 5 thrombocytopenias, and one posthepatitic cirrhosis. Thirteen of the 30 patients had previous laparotomy. Therapeutic efficacy and clinical data of RFA therapy were compared between these two groups. RESULTS: RFA therapy under ultrasound guidance was performed successfully in all the patients. Cholecystectomy was performed simultaneously for gallstones in 7 patients and for abutting of gallbladder from hemangioma in 2 patients. Choledochotomy with T-tube drainage was performed in 6 patients. The mean blood loss, the mean RFA time per lesion and reduction rate of maximum diameter of the lesions 6 months after RFA in the SL group and non-SL group were 88.0 ml +/- 22.4 ml vs. 255.0 ml +/- 71.7 ml (P < 0.001), 23.0 min +/- 7.5 min vs. 53.3 min +/- 16.0 min (P < 0.001), and 61.8% vs. 44.8% (P < 0.001) respectively. No severe complication related to RFA was observed in all patients. At a median follow-up of 12 months (6 approximately 17 months), a complete lesion necrosis was achieved on the contrast-enhanced helical CT scans in both groups. During the follow-up, all of the 15 patients were free of upper abdominal pain in the SL group, and 12 patients were symptom-free and 3 obtained significant amelioration of symptoms in the non-SL group. CONCLUSION: RFA therapy combined with suture and ligation surgery is a feasible, safe, and effective treatment modality for patients with giant HCHs. It can reduce blood loss, shorten RFA therapy time, and increase therapeutic efficacy of RFA. Intraoperative ultrasonography is a useful adjunct for increasing the therapeutic efficacy of RFA and reducing the complications related to RFA.

[Clinical evaluation of radiofrequency ablation therapy in patients with hepatic cavernous hemangiomas].

OBJECTIVE: To evaluate the feasibility, safety and efficacy of radiofrequency ablation (RFA) therapy in patients with hepatic cavernous hemangioma (HCH) and investigate its optimal operative approach. METHODS: Between March 2001 and June 2004, a total of 68 patients, 18 males and 50 females, age 43.1 (30-64), with 104 HCHs 2.5-11 cm in diameter with the mean size of 5.6 cm, were treated by ultrasound-guided RFA, via percutaneous (n = 19), laparoscopic (n = 29), or open surgical (n = 20) approach. In 7 patients with hepatic lesions larger than 7 cm in diameter, Pringle maneuver was used to occlude the hepatic blood flow during the laparoscopic and open RFA therapy. All patients were followed up with helical computed tomographic (CT) scans and ultrasonography for 19 months (6-36 months). RESULTS: Additional intrahepatic lesions not detected preoperatively were found in 2 patients (with 2 new lesions) via laparoscopy and 3 patients (with 4 new lesions) via celiotomy. All patients were treated with RFA successfully. The mean blood loss in the Pringle group (90.0 ml +/- 22.4 ml) was significantly fewer than that in the non-Pringle group (249 ml +/- 56 ml) (P < 0.01). The mean RFA time per lesion in the Pringle group (29.0 min +/- 7.5 min) was shorter markedly compared to the non-Pringle group (55.4 min +/- 12.4 min) (P < 0.01). In the laparoscopic RFA group, laparoscopic cholecystectomy was performed simultaneously in 15 patients with chronic calculous cholecystitis and in another 2 patients because of tumors abutting the gallbladders, and laparoscopic fenestration with intraperitoneal drainage was performed in 3 patients with simple hepatic cysts. In the open RFA group, cholecystectomy was performed in 5 patients with gallbladder diseases, partial cystectomy was performed in one patient with a hepatic cyst, and choledochotomy was performed in 3 patients with common bile duct stones. Postoperative fever and abnormal serum transaminase (ALT and AST) levels were observed in 29 patients (42.6%). A transient hematuria occurred in one patient after open RFA. No specific complications developed during or after RFA. The follow-up showed a complete lesion necrosis rate of 99% (103/104). One patient showed an incomplete lesion necrosis in the margin of RFA site 6 months after percutaneous RFA therapy and obtained retreatment with percutaneous RFA. CONCLUSION: RFA therapy is a safe, feasible and effective treatment options for patients with HCHs. This procedure can be performed via percutaneous, laparoscopic, or open approach. To prevent the RFA-related complications and to increase the therapeutic efficacy of RFA, the choice of optimal operative approach should be based on the lesion size, number, and location and on the patient's clinical status. Hepatic inflow occlusion by Pringle maneuver during laparoscopic or open RFA therapy can reduce the blood loss and increase the therapeutic efficacy significantly.