Impact of malpractice caps on use and outcomes of radical cystectomy for bladder cancer: data from the surveillance, epidemiology, and end results program

PURPOSE: The impact of malpractice awards on insurance premiums and health care delivery generates much concern. To our knowledge no data exist regarding the impact of caps, or upper limits, on awards for noneconomic damages (also termed pain and suffering) on health care delivery patterns or outcomes. We investigated the effect of caps on the use of and outcomes following aggressive surgical treatment (radical cystectomy) in patients with bladder cancer. MATERIALS AND METHODS: We performed a retrospective cohort study of patients with bladder cancer who underwent radical cystectomy, identified from the Surveillance, Epidemiology, and End Results (SEER) Program database. Cystectomy rates and post-cystectomy disease specific survival were compared between SEER regions with and without a cap, while controlling for other variables. RESULTS: A significantly greater proportion of patients with stages III and IV bladder cancer underwent cystectomy in SEER regions with a cap. Cap status was a significant predictor of survival from bladder cancer. CONCLUSIONS: Radical cystectomy for bladder cancer is performed more often even for advanced bladder cancer in geographic regions with a cap with a positive impact on survival. The institution of caps may have beneficial effects on patterns of health care beyond that of merely decreasing insurance premium costs.     

Independent validation of the 2002 American Joint Committee on cancer primary tumor classification for renal cell carcinoma using a large, single institution cohort

PURPOSE: The primary tumor classification for renal cell carcinoma (RCC) was updated by the American Joint Committee on Cancer in 2002. To date the new classification has not been validated using an independent group of patients and, therefore, its accuracy for predicting patient outcome is unknown. In the current study we evaluated the 2002 primary tumor classification and compared its predictive ability with that of the 1997 classification. MATERIALS AND METHODS: We studied 2,746 patients treated with radical nephrectomy or nephron sparing surgery for unilateral, sporadic RCC between 1970 and 2000. Cancer specific survival was estimated using the Kaplan-Meier method. The predictive abilities of the 1997 and 2002 classifications were compared using the concordance index. RESULTS: There were 812 deaths from RCC a mean of 3.3 years following nephrectomy. Median followup in patients still alive at last followup was 9 years. Estimated 5-year cancer specific survival rates by the 2002 tumor classification were 97%, 87%, 71%, 53%, 44%, 37% and 20% in patients with pT1a, pT1b, pT2, pT3a, pT3b, pT3c and pT4 RCC, respectively. The concordance index for the association between the 2002 classification and death from RCC was 0.752 compared with 0.737 for the 1997 classification, indicating that the 2002 version contained more predictive ability. CONCLUSIONS: Our data suggest that the 2002 primary tumor classification with pT1 cancers subclassified into pT1a and pT1b provides excellent stratification of patients according to cancer specific survival and it has a predictive ability that is superior to that of the 1997 classification.     

DOES THE MANAGEMENT OF BLADDER PERFORATION DURING TRANSURETHRAL RESECTION OF SUPERFICIAL BLADDER TUMORS PREDISPOSE TO EXTRAVESICAL TUMOR RECURRENCE?

PURPOSE: We evaluated the impact of a bladder perforation during transurethral resection of superficial bladder tumor on extravesical tumor recurrence and patient prognosis. We also defined potential risk factors for extravesical recurrence prospectively giving emphasis to the management of the perforation. MATERIALS AND METHODS: The medical records of 3,410 patients were reviewed. Parameters recorded included patient age and sex, tumor stage, grade, number, size and location at the time of perforation, the type of bladder perforation (extraperitoneal vs intraperitoneal) and the way the perforation was managed (open surgical repair vs conservative treatment). Logistic regression analysis was used to identify risk factors for extravesical recurrence. Cox regression analysis was used to compare cancer specific survival. RESULTS: A total of 34 cases of bladder perforation were recorded, 4 patients were treated with open surgery and 30 treated conservatively. The 4 patients who underwent open surgery presented with extravesical recurrence after a mean followup of 7.5 months. The remaining 30 patients had no evidence of extravesical recurrence after a mean followup of 60 months (p <0.001). Of the patients with extravesical relapse 3 died of disease. The surgical management of bladder perforation was the best predictor of extravesical recurrence (p <0.001, r = 1.13), followed by an intraperitoneal localization of the perforation (p =0.0003, r = 0.67) and tumor size (p =0.01, r = 0.42). CONCLUSIONS: Surgical repair of a bladder perforation during transurethral resection of bladder tumor increases the risk of extravesical tumor cell recurrence and negatively affects patient prognosis.     

高住低练对大鼠骨骼肌PI3K/PKB/mTOR信号通路基因表达的影响

目的:探讨高住低练对大鼠骨骼肌PI3K/PKB/mTOR信号通路基因表达的影响。方法:40只8周龄SD大鼠适应训练后,随机分为低住安静组(LC)、低住低练组(LoLo)、高住安静组(HC)和高住低练组(HiLo)。高住组每天低氧暴露12 h(氧浓度13.6%,相当于海拔3500 m),低练组进行35 m/min、1 h/d、5 d/周、共4周的跑台训练。采用实时荧光定量PCR检测大鼠腓肠肌PI3K、PKB、mTOR mRNA表达,以双因素方差分析进行统计。结果:低氧和运动均显著提高大鼠骨骼肌PI3K和PKB mRNA表达(P<0.01),但低氧和运动无显著交互作用(P>0.05);运动显著提高大鼠骨骼肌mTOR mRNA表达(P<0.01),低氧却显著降低mTOR mRNA表达(P<0.01),且低氧和运动有交互作用,显著降低mTOR mRNA表达(P<0.01)。结论:低氧和运动促进PI3K和PKB基因表达,低氧抑制而运动促进mTOR基因表达;HiLo训练促进PI3K和PKB基因表达,却抑制mTOR基因表达。不同条件下PI3K/PKB/mTOR信号通路基因表达水平不一致。     

补充计量学研究可视化分析

本文对来自于中国知识基础设施工程（China National Knowledge Infrastructure,CNKI）数据库中研究补充计量学的相关文献进行收集整理,并使用CiteSpace软件进行可视化分析,分析方法有关键词聚类、作者聚类、作者合作网络等。分析结果显示中文补充计量学相关研究主要聚焦在补充计量学、学术影响力研究、科学评价研究、相关性分析研究、社交网络研究这几个方面。同时,分析结果也揭示出理论创新不足、合作研究较少等情况,建议这两方面进一步加强。     

17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。     

MED治疗腰椎间盘突出症91例临床分析

目的　探讨显微内窥镜腰椎间盘切除术 (Micro.Endoscopilc.Discectom y.MED)治疗腰椎间盘突出症的手术操作特点。手术适应症 ,并发症及临床效果 ,旨在正确认识这一新技术 ,提高手术疗效。方法　采用 MED治疗腰椎间盘突出症 91例 ,取后正中切口约 1.6 CM,操作间隙在 C臂 X光机准确定位后 ,按操作程序置入内窥镜 ,镜下行椎板间开窗切除椎间盘组织 ,对于伴有骨化及狭窄者 ,在特殊器械帮助下完成 ,对于进入椎管或止血十分困难者 ,选用自制的器械 ,行内窥镜下有限开窗术。结果　 91例均获得临床随访 ,时间 3个月— 1年 ,按陆裕朴疗效评定标准 ,优 80例 ,良 6例 ,可 3例 ,差 2例 ,优良率 94 .5 %。结论　 MED是一项发展中的技术。在发挥其优势的前提下 ,适应症的选择十分重要 ,预防手术并发症亦不可忽视。MED手术器械亟待改进 ,术者必须具备熟练的常规腰椎管手术技巧     

Rapamycin ameliorates the CTLA4‐Ig–mediated defect in CD8+ T cell immunity during gammaherpesvirus infection

Latent viral infections are a major concern among immunosuppressed transplant patients. During clinical trials with belatacept, a CTLA4‐Ig fusion protein, patients showed an increased risk of Epstein–Barr virus‐associated posttransplant lymphoproliferative disorder, thought to be due to a deficient primary CD8⁺ T cell response to the virus. Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus‐specific CD8⁺ T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4‐Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen‐specific CD8⁺ T cells. However, the addition of rapamycin to the CTLA4‐Ig regimen was able to quantitatively and qualitatively restore the antigen‐specific CD8⁺ T cell response to the virus. This improvement was physiologically relevant, in that CTLA4‐Ig treated animals exhibited a greater viral burden following infection that was reduced to levels observed in untreated immunocompetent animals by the addition of rapamycin. These results reveal that modulation of T cell differentiation though inhibition of mTOR signaling can restore virus‐specific immune competence even in the absence of CD28 costimulation, and have implications for improving protective immunity in transplant recipients.     

纳米粒子包载反义雷帕霉素靶蛋白基因转染对移植静脉内膜增生的影响

目的观察纳米粒子包载的反义雷帕霉素靶蛋白（mTOR）基因局部转染对移植静脉内膜增生的影响。方法应用聚乳酸聚乙醇酸共聚物（PLGA）和聚乙烯醇（PVA）包载mTOR基因。建立自体静脉移植模型，随机分成转基因组、空载体组、对照组。转基因组移植静脉转染纳米粒子包载的反义mTOR基因，空载体组单纯转染纳米粒子包载的空载体，对照组不予特殊处理。分别于移植3、7、14、28d取材，常规苏木素．伊红（HE）、Verhoeff染色，检测mTOR基因的mRNA及蛋白产物表达的变化，TUNEL法观察血管平滑肌细胞（VSMC）凋亡的动态变化。结果转基因组内膜中mTOR基因的mRNA及蛋白产物表达明显减少（P〈0．01）；转基因组内膜增生程度在术后7、14、28d较其他组明显减少（P〈0．01）；转基因组凋亡细胞明显增多（P〈0．01）。结论纳米粒子可以作为基因载体，反义mTOR基因的表达能够抑制移植静脉内膜的增生，促进VSMC凋亡。     

Expression of mTOR signaling pathway markers in prostate cancer progression

BACKGROUND: The PI3K/AKT/mTOR pathway is central to prostate cancer progression. A preliminary investigation of immuno-histochemical expression of mammalian target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of expression in prostate tissue. METHODS: Immunohistochemistry was performed on a custom-made prostate tissue array. Mean long scores and variability of long scores for each marker were recorded for normal lumenal cells, prostate intraepithelial neoplasia (PIN), and cancer. RESULTS: Expression of PTEN decreased and mTOR signaling pathway markers increased in PIN and in cancer as compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression of 4E-BP1 was significantly higher than with any other marker. DISCUSSION: Results suggest that 4E-BP1 overexpression is strongly associated with prostate cancer, especially when combined with PTEN and mTOR expression data. Hierarchical clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer cell populations in most cases.