Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series

Tumor thrombus in major vasculature is a frequent finding with a poor long-term prognosis in patients with hepatocellular carcinoma (HCC). The utility of surgical resection is still controversial. This study compared morbidity and survival after resection for HCC with and without tumor thrombus. Data of 108 patients who underwent major hepatic resection for HCC were prospectively recorded. Patients were divided into two groups. The venous thrombectomy (VT) group included 26 patients who had HCC with tumor thrombus in the portal or hepatic veins. The matched control group included 82 patients who had HCC without tumor thrombus. Surgical technique, early outcome, and late survival were analyzed in each group. Multivariate analysis was performed to assess the prognostic value of this feature. Surgical technique was comparable in the VT and control group with regard to extent of hepatectomy, procedure duration, and transfusion requirements. Early postoperative outcome was also comparable. Actuarial survival at 1, 3, and 5 years was 38%, 20%, and 13%, respectively, in the VT group (median: 9 months) versus 74%, 56%, and 33%, respectively, in the control group (median: 41 months). In the subgroup of patients with tumor thrombus limited to the portal vein, actuarial survival at 1, 3, and 5 years was 50%, 26%, and 17%, respectively, (median: 12 months) and two patients lived longer than 5 years. Multivariate analysis showed that incomplete resection, alphafetoprotein level greater than 100 N, more than two tumor nodules, and tumor thrombus in major vasculature were independent factors of poor prognosis. Survival after resection for HCC with tumor thrombus in the major vasculature is poorer than after resection for HCC without tumor thrombus. However, an aggressive surgical strategy can provide significant survival with comparable morbidity in selected cases, that is, tumor thrombus located in the portal vein only and expected complete resection of the lesions.     

Enucleation combined with orbital implants for malignant melanoma of the uvea

Advanced malignant melanomas of the uvea unsuited for an eye salvaging approach require enucleation of the tumor containing eye. A series of 68 patients is reported who underwent enucleation combined with insertion of a spherical dura-encased implant after 30 Gray pre-irridiation therapy of the orbit. Postoperative results with special attention to cosmetic outcome and motility of the prosthesis suggest that the insertion of an orbital implant should be preferred to the enucleation with no implant.     

人表皮角质细胞系培养过程中细胞生物学行为和表型的变化

目的:获得较高比例的已分化表皮细胞,为表皮细胞去分化研究奠定基础.方法:采用常规表皮细胞培养方法对人表皮角质细胞系(HEK)进行培养和传代.每一代细胞均通过免疫细胞化学染色和Western blot 方法进行表皮干细胞和表皮细胞相应标志物的检测,包括β1整合素、角蛋白19(K19)、角蛋白10(K10)等指标.结果:第1代HEK呈克隆样生长,表皮干细胞标志物β1整合素、K19均有高表达,而K10的表达为阴性.经过数次传代,细胞克隆形成数目减少,细胞逐渐呈分散分布,K10的表达逐渐增高,而β1整合素、K19的表达呈下降趋势,比例减少.细胞培养至第5～6代时,为其生长的一个转折点,即此时细胞增殖能力开始明显降低,但形态良好,K10表达阳性细胞比例明显增高,而β1整合素、K19表达阳性细胞比例迅速降低.细胞培养至10～11代时,为其生长的第二个转折点,此时细胞几乎丧失增殖能力,数量显著减少,体积变大,核浆比明显减小,完全见不到β1整合素、K19表达阳性细胞,K10染色均为阳性.结论:可以选取适当代数的HEK用于去分化研究,为增加HEK的新用途提供了实验基础.     

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.     

颈内动脉接近完全闭塞时的处理

目的由于卒中风险随着狭窄严重程度的增加而升高，因此认为颈内动脉（ICA）接近闭塞患者的卒中风险很高。在现有的随机试验中，还没有专门针对这种情况进行探讨，因此其处理尚存在争汶。方法：对相关文献进行系统评价。结果：对ICA接近闭塞患者的处理还存在争议：一些学者支持进行干预，而另一些学者则认为存在风险或没有益处而反对进行干预。在ICA接近闭塞的有症状患者中进行一项比较外科治疗与最佳内科治疗的多中心前瞻性随机试验似乎非常困难，因为这类研究需要大量的患者。尽管如此，基于目前的证据，似乎很难拒绝手术治疗。结论：由于目前对ICA接近闭塞患者的最佳处理方案仍存在着争议，因此需要前瞻性观察性研究以证实其在有症状和无症状人群中的患病率以及相关的卒中风险。基于目前的证据，大多数医疗中心选择手术治疗，但它相对干内科治疗的特粱尚右待证章．     

北京自然人群载脂蛋白E基因多态性频率分布研究

应用聚合酶链反应 限制性片段长度多态性技术 (PCR RFLP) ,以北京自然人群为基础 ,采用分层随机抽样的方法进行横断面研究 ,对 1 0 46人进行apoE基因分型 ,并分析不同特点人群apoE基因频率分布特点。结果表明 :1 )本组人群ε2、ε3、ε4基因频率分别为 9.1 %、81 .2 %和 9.7% ,男女和各年龄组间基因频率无显著差异 ;2 )与欧美国家相比 ,本组人群ε2基因频率增高 ,ε4频率减低 ,与日本人群相比也有相同趋势 ;3 )在空腹血糖受损及糖尿病人群中ε2频率明显增高 ;4)在高胆固醇血症人群中ε2频率减低、ε4基因频率增高