Current role of local ablative treatments for hepatocellular carcinoma.

Due to modern diagnostic imaging and the sensitive alpha-fetoprotein test, small hepatocellular carcinoma can now be detected at an early stage. Studies have shown that surgical resection of the tumors is a valuable treatment. Local treatment under ultrasound guidance was initially considered as an alternative when patients' liver reserves were not good enough for surgical resection; however, this technique has been improved and the results indicate that its survival rate can compete with that of surgical resection. In follow-up studies of patients with small hepatocellular carcinoma, a 5-year survival of 60% has been achieved after percutaneous ethanol injection therapy. Percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation therapy have been shown to have some advantages over percutaneous ethanol injection therapy, although the follow-up durations of these studies were not long enough. Percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation therapy have become the 3 most widely used techniques for the treatment of hepatocellular carcinomas that are less than 5 cm in diameter and have a tumor number less than 3. In general, a tumor size of 3 to 5 cm is a good candidate for radiofrequency ablation and a tumor size of 2 to 3 cm is suitable for radiofrequency ablation or microwave coagulation. If the tumor size is around 2 cm or less, microwave coagulation or ethanol injection is often chosen due to the relatively low cost and similar efficacy. Ethanol injection also has the advantage of needing only a fine needle for injection. Informed selection of the appropriate technique, or combining a technique with transcatheter hepatic arterial embolization according to the tumor size and number, might provide the most effective treatment and achieve better results for hepatocellular carcinoma, even if the liver reserve is not good. However, large-scale, randomized, controlled trials are required before a definitive conclusion can be reached.     

Percutaneous microwave coagulation therapy under ultrasound guidance for small hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Percutaneous microwave coagulation therapy (PMCT) can effectively treat hepatocellular carcinomas (HCCs) smaller than 2 cm. However, for tumors 2 to 3 cm in size, combination of transarterial chemoembolization (TACE) or multiple insertions of electrodes may be more effective. This study investigated the treatment efficacy of PMCT for tumors 2 to 3 cm in size. METHODS: Nineteen HCCs smaller than 3 cm in diameter (< 2 cm in 11, and 2-3 cm in 8) in 18 patients (including 14 previously treated patients) were treated by PMCT under ultrasound guidance. One or 2 PMCT electrodes were consecutively inserted either into the left and right portion, or into the distal and proximal portion of the tumor, according to the size, shape, and margin of tumors and puncture direction. Liver function tests and contrast-enhanced computed tomography were used to examine preoperative status and response to PMCT. RESULTS: After an average of 1.6 emissions of PMCT, 18 tumors (95%) were completely ablated. The only case of treatment failure was due to a tumor location which made the approach of the electrode difficult. Bacteremia developed after the procedure in 1 patient (5%) and local inflammatory reaction of the puncture wound in another (5%). During follow-up ranging from 5 to 19 months, no recurrence was noted at the site of the original tumors. Tumor recurrence was detected at another site 2-9 months after PMCT in 9 of the 14 previously treated patients. CONCLUSION: PMCT can effectively and safely treat HCCs smaller than 3 cm in size without combination of TACE or multiple insertions of electrodes.     

Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice*

The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole‐brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy‐three patients were treated with WBRT for cerebral metastases over a 12‐month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7–4.1), with 6‐ and 12‐month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0–2 (P = 0.015), Medical Research Council neurological functional status 0–1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.     

异一枝蒿酮酸的结构

从新疆一枝蒿(Artemisia rupestris L.)中分得一个新成分,命名为异一枝蒿酮酸(isorupestonic acid),根据光谱(IR,UV,MS.NMR),X-ray晶体衍射及CD谱分析,确定其结构及绝对构型。并经X-ray晶体衍射及CD谱分析修正了一枝蒿酮酸的绝对构型。     

Empagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in routine care in East Asia: Results from the EMPRISE study

Aims/IntroductionThe EMPA‐REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium‐glucose cotransporter‐2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all‐cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries.Materials and MethodsThe study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase‐4 inhibitors (DPP‐4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score‐matched (1:1) ‘as‐treated’ analyses comparing the risk of cardiovascular outcomes and all‐cause mortality between empagliflozin and DPP‐4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta‐analysis models comparing both empagliflozin and SGLT2i with DPP‐4i use, respectively. Intention‐to‐treat and subgroup analyses in patients with/without cardiovascular disease and in patients receiving 10 mg empagliflozin were performed.ResultsThe study included 28,712 and 70,233 matched patient pairs for empagliflozin/DPP‐4i and SGLT2i/DPP‐4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all‐cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67–0.86) and SGLT2i (0.71, 0.65–0.77); (ii) combined myocardial infarction, stroke, and all‐cause mortality was also lower with empagliflozin (0.74, 0.61–0.88) and SGLT2i (0.69, 0.60–0.78) compared to DPP‐4i. The intention‐to‐treat and three subgroup analyses were consistent with results of the main analyses.ConclusionsThe results suggest that both empagliflozin and SGLT2i compared with DPP‐4i are associated with a lower risk of cardiovascular events and all‐cause mortality in routine clinical care in East Asia.     

角质形成细胞的培养及其表皮生长因子受体表达

目的:在成功分离人皮肤角质形成细胞的基础上,观察表皮生长因子受体在人皮肤角质形成细胞中的表达情况。方法:实验于2006-3/10在北京大学深圳医院中心实验室进行。采用dispase Ⅱ-trypsin两步消化法获取表皮基底层细胞,用小鼠皮肤成纤维母细胞滋养层和黄素腺嘌呤二核苷酸培养液进行培养。小鼠皮肤成纤维母细胞的预处理:向对数生长期的小鼠皮肤成纤维母细胞培养液中加入丝裂霉素C至终浓度为4mg/L,37℃下培养4h,弃去培养液,用D-Hank’s液洗3次,加入浓度为0.25g/L的胰蛋白酶消化,分离出细胞,离心(200g,5min),用黄素腺嘌呤二核苷酸培养液悬浮细胞,计数,以5.0×104/cm2的密度种于培养皿内,37℃、体积分数0.05的CO2培养箱下培养。角质形成细胞的培养:将分离的角质形成细胞悬浮在黄素腺嘌呤二核苷酸培养液中,以2.0×104/cm2的密度接种在前1天经丝裂霉素C处理的小鼠皮肤成纤维母细胞滋养层上,37℃、体积分数0.05的CO2培养箱下培养。24h换液,以后每3d换1次液。采用免疫细胞化学的方法检测表皮生长因子受体的表达,采用复合逆转录聚合酶链反应检测角质形成细胞中表皮生长因子受体mRNA的表达。结果:采用dispaseⅡ消化法分离了真皮和表皮,获得较多的角质形成细胞,可以避免真皮成纤维细胞的污染。人皮肤角质形成细胞在黄素腺嘌呤二核苷酸培养液中培养5d可见明显的集落,约10d可长满单层。免疫细胞化学显示表皮生长因子受体在细胞表面有明显的表达,复合逆转录聚合酶链反应显示表皮生长因子受体mRNA有明显的表达。结论:用小鼠皮肤成纤维母细胞滋养层和黄素腺嘌呤二核苷酸培养液可以较好地培养原代人皮肤角质形成细胞,表皮生长因子受体在细胞表面有明显的表达,这些结果为与表皮生长因子受体相关的皮肤病(如银屑病)的研究奠定了基础。     

富血小板血浆对人骨髓间充质干细胞成骨分化的抑制效应

目的:一些理论质疑富血小板血浆对骨前体细胞成骨分化的作用,本实验拟验证富血小板血浆对体外培养的人骨髓间充质干细胞成骨分化的抑制效应。方法:实验于2005-05/11在南方医科大学组织工程试验室(省级)完成。①实验方法:抽取6名健康志愿者髂前上棘骨髓5mL进行体外细胞培养扩增,静脉血10mL以二次离心法制得富血小板血浆。诱导骨髓间充质干细胞时富血小板血浆与骨髓间充质干细胞均来自同一个体。②碱性磷酸酶染色:取第4代骨髓间充质干细胞,分为两组:富血小板血浆组加入富血小板血浆使终浓度为100g/L,单纯血清培养组仅加入等量胎牛血清。培养后第7天进行碱性磷酸酶染色,阳性细胞为胞质中呈现黑色颗粒或块状沉淀。③矿化结节染色:取第4代骨髓间充质干细胞,分组同上。培养后第19天以0.1%茜素红-TrisHcl(pH8.3)37℃下放置30min,矿盐沉积染色阳性为红色。④Cbfa1基因表达:取第4代骨髓间充质干细胞,分组同上。培养后第3,7,12,16天RT-PCR法检测骨髓间充质干细胞Cbfa1基因的表达。⑤形态学观察:实验过程中使用相差显微镜观察各组细胞生长情况及形态学变化。结果:①骨髓间充质干细胞碱性磷酸酶染色结果:培养后第7天,富血小板血浆组碱性磷酸酶阳性细胞数量较单纯血清培养组明显减少,且阳性细胞内灰黑色颗粒也明显减少,为弱阳性。②骨髓间充质干细胞矿化结节染色结果:培养后第19天,单纯血清培养组可见细胞表面有较多的矿盐沉积,但未形成明显的矿化结节。富血小板血浆组细胞表面只有稀少的矿盐沉积。③骨髓间充质干细胞cbfa1mRNA的表达:培养后第3,7,12,16天,随着培养时间的延长单纯血清培养组与富血小板血浆组cbfa1基因表达量均逐渐增高,同一时间点两组间cbfa1基因的表达基本相似。④骨髓间充质干细胞形态学变化:富血小板血浆组骨髓间充质干细胞增殖旺盛,细胞达到单层汇合的时间较单纯血清培养组明显缩短。单纯血清培养组细胞在完全汇合后开始出现聚合现象(14～16d),但趋向性不明显,未完全形成团簇;富血小板血浆组细胞在完全汇合后未出现聚合现象,细胞密集生长。培养初期两组细胞以梭形为主,多角形细胞较少,培养至14～16d单纯血清培养组多角形细胞较富血小板血浆组增多。结论:富血小板血浆可抑制人骨髓间充质干细胞碱性磷酸酶的分泌与矿盐沉积,对人骨髓间充质干细胞成骨分化的直接效应是抑制其分化。     

Comparative Effectiveness of Computed Tomography- Versus Ultrasound-Guided Percutaneous Radiofrequency Ablation Among Medicare Patients 65 Years of Age or Older With Hepatocellular Carcinoma

Background

For patients with hepatocellular carcinoma (HCC) not eligible for surgical resection, radiofrequency ablation (RFA) is a promising technique that reduces the risk of disease progression.