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Objective@#To detect the expression level of YES-associated protein 1 (YAP) in hepatocellular carcinoma (HCC) cell lines and investigate its effects on the proliferation activity and the sensitivity to sorafenib in HCC cells.@*Methods@#Western blot was used to detect the protein expression levels of YAP in SMMC-7721, SK-Hep-1, HepG-2, Huh7 and the normal liver cell line L-O2. YAP specific small interfering RNA (si-YAP) or YAP expression plasmid were transfected in SK-Hep-1 or Huh7 cells, respectively. Cell counting kit-8 (CCK-8) test was used to detect the cell proliferation activity and the cell cycle test was conducted by flow cytometry. SK-Hep-1 and SK-Hep-1 si-YAP cells were subcutaneously injected into the nude mice which were sequentially treated by intragastric administration of sorafenib, and the tumor growth in vivo were observed and compared.@*Results@#The expression of YAP was upregulated in HCC cell lines. Deletion of YAP expression significantly decreased the survival rate of SK-Hep-1 cells [(78.5±0.3)% vs (92.3±0.2)%, P=0.025]. Knockdown of YAP significantly increased the percentage of G0/G1-phase cells [ (65.4±3.3) % vs (55.7±3.4) %, P=0.039]. On the contrary, upregulation of the YAP expression in Huh7 cells significantly increased the cell survival rate [(81.2±1.3)% vs (62.5±1.1)%, P=0.013] and reduced the percentage of G0/G1-phase cells [(38.2±3.8)% vs (48.8±2.9)%, P=0.019]. The survival rate of SK-Hep-1 cells treated by si-YAP combined with sorafenib was (31.13±1.79)%, significantly lower than (48.87±0.58) % of SK-Hep-1 cells treated by sorafenib alone (P=0.001), while overexpression of YAP attenuated the inhibitory effect of sorafenib on the survival of Huh7 cells [(69.98±2.94) % vs (53.53±1.93)%, P=0.001]. The tumor weights of SK-Hep-1 group, sorafenib alone group, SK-Hep-1 si-YAP group and SK-Hep-1 si-YAP combined with sorafenib group were (0.96±0.08) g, (0.62±0.08) g, (0.70±0.06) g and (0.27±0.02) g, respectively. The tumor weights of sorafenib alone group and SK-Hep-1 si-YAP group were significantly lower than that of SK-Hep-1 group (P=0.012 and P=0.031, respectively). The tumor weight of SK-Hep-1 si-YAP combined with sorafenib group was significantly lower than that of SK-Hep-1 si-YAP group (P=0.001).@*Conclusions@#The expression of YAP is upregulated in HCC cell lines, which regulates the proliferation, cell cycle, and sensitivity to sorafenib of HCC cells. YAP is a potential molecular target for HCC treatment.
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Objective@#To explore the factors affecting the prognosis of patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT), and to analyze the clinical value of transcatheter arterial chemoembolization (TACE) combined with iodine-125 seed implantation in such patients.@*Methods@#A retrospective analysis of 53 patients with HCC combined with PVTT was performed. In the study group, 32 cases were treated with TACE combined with iodine-125 seed implantation, and 21 cases in the control group were treated with TACE combined with sorafenib. Survival analysis was carried out on eight factors such as gender, age, Child-Pugh classification, alpha fetoprotein level, portal vein tumor thrombosis (PVTT) type, forms of liver tumor, extra-hepatic metastasis and treatment modalities. The efficacy of TACE combined with iodine-125 seed implantation and TACE combined with sorafenib was further compared. The χ 2 test was used to evaluate the efficacy of the two groups. A single factor survival analysis was calculated by Kaplan-Meier estimator and multifactor survival analysis by Cox proportional hazards model.@*Results@#All 53 patients were successfully treated. The median tumor progression time (mTTP) and median overall survival (mOS) were 8 months and 11 months, respectively. The disease control rate (DCR) of the study group for PVTT was 93.8%, which was significantly higher than that of the control group (61.9%, χ 2 = 6.448, P = 0.011). The difference was statistically significant; the objective remission rate of the study group for PVTT was 75.0%. Significantly higher than 9.5% in the control group, P < 0.05, the difference was statistically significant; the DCR of the primary tumor in the study group was 50.0%, which was lower than the 70.0% of the PVTT in the control group, P = 0.231, the difference was not statistically significant. The progression of primary HCC lesions in patients with multivariate survival analysis: Child-Pugh grade A patients were compared to grade B [Hazard ratio (HR) = 0.236, P = 0.003]; no extra-hepatic metastasis (HR = 0.258, P = 0.002); and TACE combined with iodine-125 seed implantation group compared with TACE combined sorafenib group (HR = 0.372, P = 0.002), the differences were statistically significant. Multivariate survival analysis of patients with overall survival: AFP < 400 ng/mL vs. AFP≥400 ng/mL (HR = 0.389, P = 0.030); Child-Pugh grade A vs. B (HR = 0.263, P = 0.006); and no extra-hepatic metastasis (HR = 0.306, P = 0.006), the differences were statistically significant.@*Conclusion@#TACE combined with iodine-125 seed implantation for the treatment of HCC with PVTT can effectively control the progression of PVTT and intrahepatic lesions and improve the prognosis of patients.
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Objective To investigate the regularity of abdominal pain and its influence factors in patients with primary hepatic carcinoma (PHC) after receiving transcatheter arterial chemoembolization (TACE).Methods A total of 121 patients with PHC were enrolled in this study.All patients were admitted to the Department of Interventional Radiology of Zhejiang Provincial Cancer Hospital from December 2012 to June 2013,and all patients were suffered from PHC.The occurrence,duration and severity of the abdominal pain as well as the used dosage of morphine within 48 hours after TACE were documented.The results were statistically analyzed.Results A total of 96 patients (96/121,78.5％) complained of different degrees of abdominal pain after interventional therapy,and 72 patients (72/121,59.5％) showed moderate to severe pain,with the VAS score being more than 4 points.The average dosage of morphine used each time for one patient was 19.7 mg.Statistical analysis indicated that these patients were more prone to develop abdominal pain after TACE if they carried more than one of the following risk factors:age ≥60 years (when compared with patients ＜60 years,OR:0.307,P=0.008),preoperative ECOG score ＞2 (when compared with a ECOG score of 0-1,OR:0.195,P=0.006),the distance between tumor and liver capsule ＞1 cm (when compared with the distance ≤ 1 cm,OR:0.296,P=0.007),the use of THP in performing chemoembolization (when compared with other chemotherapeutic drugs,OR:0.232,P＜0.003 4).Conclusion After TACE abdominal pain is a high-frequency event.The independent factors affecting the occurrence of abdominal pain are age＜60 years,preoperative ECOG score ＞2,tumor located close to liver capsule,and the use of THP-lipiodol mixture as embolic agent.Therefore,for patients carrying moderate-high risk of abdominal pain,routine use of analgesics before TACE as well as within 12 hours after TACE to prevent the occurrence of abdominal pain is quite necessary.
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Objective To evaluate the safety and clinical efficacy of CT-guided 125I seeds interstitial implantation in treating the refractory liver cancers that show poor response to commonly used therapies. Methods A total of 40 patients with refractory clinically or pathologically-proved liver cancer were enrolled in this study, the diseases included primary liver cancer (n = 27, with coexisting portal vein cancerous thrombus in 2) and metastatic liver cancer (n = 13). CT-guided 125I seeds interstitial implantation was performed in all patients. Preoperative plan of seeds implantation protocol was formulated by using the treatment plan system (TPS); the 125I seed activity was 0.6 -0.8 mCi and the peripheral matching dose (MPD) was 100 -140 Gy. The procedure of 125I seeds interstitial implantation was performed under local anesthesia in all patients. By using percutaneous trans-hepatic puncturing and single-or multiple-needle technique, the 125I seeds were implanted along a line parallel to the long axis of the tumor and/or tumorous thrombus with an interval of 0.5 -1.0 cm. The short-term efficacy was evaluated by modified response evaluation criteria in solid tumors (mRECIST), and the median time to tumor progression (mTTP) and the median overall survival time (mOS) were calculated by Kaplan and Meier method. Results The technical success rate was 100%. The diameter of the tumor was 1.5 -12.0 cm (mean 4.0 cm), and a total of 1 748 125I seeds were implanted in 40 patients (mean 44 seeds per patient). The short-term effective rate was 37.5%(n = 15), including complete remission in 8 cases and partial remission in 7 cases, the stable disease was seen in 15 cases (37.5%), and the disease control rate was 75%. The mTTP was 7.0 months (95%CI:4.524-9.476 months), while mOS was 10 months (95%CI: 6.901 -13.099 months). The procedure-related adverse reactions included small amount of subcapsular hemorrhage (n =2, 5%), intrahepatic migration of 125I seeds (n=2, 5%), pain at liver area (n=1, 2.5%); and no special treatment was needed in these patients. One patient developed high fever with chills 3 hours after the procedure, which was relieved after symptomatic and antipyretic treatment. Conclusion For the treatment of refractory liver cancers, CT-guided 125I seeds permanent interstitial implantation, used as a remedial therapy, is safe and effective. This technique is worth popularizing in clinical practice.
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Objective To investigate the efficacy and safety of CT-guided radiofrequency ablation (RFA) in treating lung tumors. Methods A total of 33 patients with lung cancer (35 lesions in total), who were admitted to authors’ hospital during the period from May 2007 to August 2013 to receive treatment, were enrolled in this study. RFA was carried out in all patients. After RFA the patients were followed up regularly (once every 3 months) to evaluate the therapeutic efficacy and the adverse reaction. The deadline for the following-up was November 2013, or to the time when tumor progression occurred. Results Of the total 34 lesions in 32 patients who had received RFA and had complete follow-up data, the one-year local control rate was 85.3%. The average one-year progression-free survival rate was 75.0%, among them 15 cases with primary lung cancer had a mean one-year progression-free survival rate of 80.0% and 17 cases with metastatic lung cancer had a mean one-year progression-free survival rate of 70.6%. The overall median progression-free survival (PFS) was(18.0±1.3) months. No obvious correlation existed between PFS and age, sex, tumor size, pathological type, clinical stage (P<0.05). The main adverse reactions of RFA were pain, hydrothorax and pneumothorax; no serious life-threatening complications occurred. Conclusion RFA is a safe, effective and minimally-invasive treatment for lung cancer, regardless of early stage or late stage of the tumor.