Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy

Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.     

预测非肌层浸润性膀胱尿路上皮癌患者复发的炎症反应标志物评分系统构建

目的探讨采用4种炎症反应标志物构建预测非肌层浸润性膀胱尿路上皮癌(NMIBC)患者复发的炎症评分系统。方法选取海南医学院第一附属医院在2012-01-01-2016-02-27收治的271例NMIBC患者。术前1周收集患者中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、白蛋白与球蛋白比值(AGR)、淋巴细胞与单核细胞比值(LMR)。基于NLR、PLR、AGR和LMR最佳截断值构建中性粒细胞与淋巴细胞比值-血小板和淋巴细胞比值-白蛋白球蛋白比值-淋巴细胞和单核细胞比值(NPAL)评分系统(NPALSS),并结合多因素Cox风险比例模型分析NPALSS的临床价值。结果所有患者均获得随访,随访时间18~89个月,平均时间为(55.84±22.68)个月。随访末期64例患者复发,复发率为23.6%,中位无复发生存时间41个月。NLR、PLR、AGR和LMR 4种炎症反应标志物的曲线下面积(AUC)分别为0.785、0.694、0.866和0.750,最佳截断值分别为2.37、136、1.71和3.64。NLR≤2.37、PLR<136、AGR≥1.71、LMR≤3.64患者的无复发生存率高于NLR>2.37、PLR≥136、AGR<1.71、LMR>3.64患者,均Log-rank P<0.001。NPALSS不同等级的生存曲线比较差异有统计学意义,均Log-rank P<0.001。肿瘤数量(HR多发=1.026,95%CI为1.002~1.051)、T分期(HRT1=1.031,95%CI为1.009~1.054)、NPALSS(HR_1级=1.017,95%CI为1.001~1.034;HR_2级=1.935,95%CI为1.438~2.605;HR_3级=2.213,95%CI为1.646~2.977;HR_4级=2.518,95%CI为1.810~3.503)是NMIBC患者复发的独立危险因素,均P<0.05。结论结合NLR、PLR、AGR和LMR最佳截断值所构建的NPALSS可以有效预测高复发风险的NMIBC患者。     

尿液外泌体lncRNA PCAT-1评估非浸润性膀胱癌患者复发的价值

目的探究尿液外泌体长链非编码RNA前列腺癌相关转录本1（lncRNA PCAT-1）评估非浸润性膀胱癌患者复发的价值。方法随机选取2015年1月—2016年3月进行治疗的非浸润性膀胱癌患者50例作为非浸润性膀胱癌组，选取同期在进行健康体检的健康受检者50例作为对照组。测定两组尿液外泌体中lncRNA PCAT-1表达情况。分析尿液外泌体lncRNA PCAT-1表达与临床病理参数的相关性、尿液外泌体lncRNA PCAT-1与尿液脱落细胞学对非浸润性膀胱癌的诊断价值、影响非浸润性膀胱癌患者复发的相关因素，评估非浸润性膀胱癌复发的价值及尿液外泌体lncRNA PCAT-1表达与非浸润性膀胱癌患者预后的关系。结果与对照组比较，非浸润性膀胱癌组患者尿液外泌体lncRNA PCAT-1表达水平明显升高（P<0.01）。尿液外泌体lncRNA PCAT-1表达与病理分期具有明显相关性（P<0.01）。尿液外泌体lncRNA PCAT-1诊断非浸润性膀胱癌的曲线下面积明显高于尿液脱落细胞学。采用Cox比例风险因素回归模型分析，病理分期及lncRNA PCAT-1均为影响非浸润性膀胱癌患者复发的独立危险因素。以尿液外泌体lncRNA PCAT-1相对表达量5.14±1.04分为高表达组（23例）与低表达组（27例），Kaplan-Meier生存曲线分析结果显示，lncRNA PCAT-1低表达量组生存期明显高于lncRNA PCAT-1高表达组。结论外泌体lncRNA PCAT-1在非浸润性膀胱癌患者尿液中的表达水平较健康受检者明显升高，且其表达水平与患者病理分期明显相关。尿液外泌体lncRNA PCAT-1对评估非浸润性膀胱癌患者的复发具有重要作用。     

Efficacy of percutaneous and transcutaneous tibial nerve stimulation in women with idiopathic overactive bladder: A prospective randomised controlled trial

BackgroundDifferent studies have reported the efficacy of percutaneous tibial nerve stimulation (PTNS) and transcutaneous tibial nerve stimulation (TTNS) in treating idiopathic overactive bladder (OAB). However, no study has compared the effectiveness of PTNS and TTNS added to bladder training (BT) in idiopathic OAB.ObjectiveTo compare the efficacy of PTNS and TTNS added to BT in women with idiopathic OAB.MethodsWe randomised 60 women with idiopathic OAB into 3 groups. Group 1 (n = 19) received BT, Group 2 (n = 19) received PTNS in addition to BT, and Group 3 (n = 20) received TTNS in addition to BT. PTNS and TTNS were performed 2 days a week, for 30 min a day, for a total of 12 sessions for 6 weeks. Patients were evaluated by incontinence severity (pad test), a 3-day voiding diary (frequency of voiding, incontinence episodes, nocturia and number of pads used), symptom severity, quality of life, treatment success (positive response rate), treatment satisfaction (Likert scale), discomfort level and preparation time for stimulation (sec).ResultsAt the end of treatment; severity of incontinence, frequency of voiding, incontinence episodes, nocturia, number of pads used, symptom severity and quality of life were significantly improved in Groups 2 and 3 versus Group 1 (P < 0.0167). Treatment success and treatment satisfaction were higher in Groups 2 and 3 than Group 1 (P < 0.001 and P < 0.0167, respectively). Level of discomfort was lower, treatment satisfaction was higher and preparation time for stimulation was shorter in Group 3 than Group 2 (P < 0.05).ConclusionBoth the PTNS plus BT and TTNS plus BT were more effective than BT alone in women with idiopathic OAB. These 2 tibial nerve stimulation methods had similar clinical efficacy but with slight differences: TTNS had shorter preparation time, less discomfort level and higher patient satisfaction than PTNS.     

Síntomas de tramo urinario inferior y síndrome de apnea obstructiva del sueño: evolución urodinámica antes y después de un año de tratamiento con presión continua positiva de la vía aérea

ObjectiveTo report the clinical evolution and the urodynamic behaviour of several lower tract urinary symptoms in patients with obstructive sleep apnea syndrome before and after the treatment with continuous positive airway pressure (CPAP) devices.MethodsA prospective study was performed; patients with recent diagnosis of sleep apnea confirmed by nocturnal sleep polygraphy and absence of medical urological past history. In order to discard important lower urinary tract conditions, urological examinations were previously performed. Urinary symptoms were evaluated using the IPSS and OAB-V8 validated questionnaires, three-day Bladder Diary and invasive urodynamic examinations with a gap of one year before and one year after using the CPAP.Results84 urodynamic studies were carried out in 43 patients. The IPSS score decreased by 3.58 points. The OAB-V8 score decreased by 2.87 points. Nocturia episodes decreased to one per night. The percentage of patients with nocturnal polyuria went down to 26%. The bladder compliance significantly increased (97.39 vs 200.40 ml/cm H2O). The presence of detrusor overactivity decreased from 11 (before CPAP) to 5 patients (after CPAP).ConclusionThe proper treatment with CPAP showed a statistical and clinical improvement of several LUTS with limited urodynamic modifications.