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异嗜性小鼠白血病病毒相关病毒(XMRV)与我国前列腺癌发病的相关性研究
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摘要
目的
     建立中国人前列腺肿瘤病理组织标本库,计划目标标本数1000例;研究XMRV在我国前列腺癌患者中感染情况,了解我国前列腺癌患者中XMRV感染的流行病学特点,明确XMRV在前列腺癌中的致病性;分析XMRV感染与我国前列腺癌疾病临床及病理分级的相关性。
     方法
     采集患者静脉血,利用生物化学方法提取收集患者血液DNA、RNA标本,建立前列腺癌及良性前列腺增生症患者的血液标本库。利用经会阴前列腺穿刺活检系统收集患者前列腺组织标本,建立前列腺病理组织标本库;
     应用巢式PCR和免疫生化技术检测124例前列腺疾病患者的组织标本,检测XMRV病毒DNA及组织中感染的病毒特异性抗原。统计分析XMRV感染与前列腺癌临床分期及病理分级之间的相关性。
     结果
     初步建立中国人前列腺肿瘤疾病病理组织标本库,收集病理标本300余例;巢式PCR检测结果为:68.5%的患者感染XMRV,其中前列腺癌患者组的感染率为73.4%:良性前列腺增生组的感染率为60.0%。免疫组化法检测.XMRV抗体在前列腺组织内的表达总阳性反应率为:32.35%:其中前列腺癌患者组感染率为43.04%:良性前列腺增生组感染率为13.33%。表达主要位于前列腺腺体细胞胞质中。不同恶性程度的前列腺癌组织在XMRV感染率上有显著差异。
     结论
     成功建立中国人前列腺肿瘤疾病病理组织标本库体系,不断完善管理,标本量稳步增加,为后续前列腺疾病的各项研究打下基础;中国前列腺癌患者人群中约有43.04%的患者感染XMRV,高于良性前列腺增生症患者的13.33%感染率。提示XMRV的感染与我国前列腺癌的发生可能存在相关关系。XMRV的感染与肿瘤的恶性程度有相关性。
     目的
     分析应用2μm激光膀胱部分切除术治疗膀胱非尿路上皮肿瘤的方法特点,观察分析本法治疗膀胱嗜铬细胞瘤的手术特点、术中术后并发症及手术治疗效果;应用经尿道2μm激光膀胱部分切除术治疗膀胱尿路上皮肿瘤、观察一组膀胱尿路上皮癌患者术后3年的随诊特点。
     方法
     选取2009年8月至2011年12月间,解放军总医院泌尿外科收治的膀胱非尿路上皮肿瘤患者共9例。采用经尿道2μm激光膀胱部分切除术治疗,术中用2μm激光沿肿瘤周围全层切开膀胱壁,在肌层与外层结缔组织之间剥离整块膀胱壁,完整切除肿块及其基底部膀胱全肌层标本送病理检查。观察手术实施过程,术中出血情况,术中及术后并发症,术后病理诊断结果及临床随诊。特别观察和研究了经尿道2μm激光膀胱部分切除术诊断和治疗膀胱嗜铬细胞瘤的诊治特点,手术方式及术中术后并发症特点。
     在2009年4月至2012年4月间,根据已制定的入组标准,通过术前检查,继续选取我科门诊和住院的膀胱尿路上皮癌患者107例,采用经尿道2μm激光膀胱部分切除术进行治疗。观察临床疗效,随访总结患者3年远期的治疗结果,分析膀胱肿瘤患者术后的随诊特点。
     结果
     9例膀胱非尿路上皮肿瘤的患者,手术过程顺利,手术时间25-47分钟,平均36.4分钟;术中出血量极少或几乎不出血,无闭孔神经反射,术后亦无继发出血,术后获得明确病理诊断:平滑肌瘤3例、嗜铬细胞瘤3例、子宫内膜异位症1例、肺癌膀胱转移瘤2例。嗜铬细胞瘤患者,术中血压平稳,波动小,病理诊断明确。
     所观察的107例膀胱尿路上皮癌的患者耐受经尿道2μm激光膀胱部分切除术良好。术中及术后无明显并发症,病理诊断明确;术后随访6~49个月,中位时间35个月,无原位复发。本组107例尿路上皮癌患者随访近3年生存率100%,生活质量较好,随诊配合率高。
     结论
     经尿道2μm激光膀胱部分切除术治疗膀胱肿瘤是一种安全有效的新方法。由于2μm激光可以做到对膀胱壁全层进行精细的分层解剖,手术可以完成肌层与疏松结缔组织之间进行剥离,因此可以达到膀胱部分切除的目的。2μm激光膀胱部分切除术不仅可以有效地治疗膀胱尿路上皮肿瘤,也可以用于治疗非尿路上皮肿瘤。这样可能为治疗膀胱非尿路上皮肿瘤开辟了新途径。
     经尿道2μm激光膀胱部分切除术所获得的标本,肿瘤及其附着的膀胱壁全层组织完整,所得标本可准确判定肿瘤性质,有效地指导后续治疗,为部分非尿路上皮肿瘤如:嗜铬细胞瘤、血管瘤、转移瘤等的微创诊断提供了安全有效的新方法。
     通过三年的长期随访观察,应用经尿道2μm激光膀胱部分切除术治疗膀胱尿路上皮肿瘤安全可靠,疗效明确,可以很好的制定患者个性化治疗方案,减少不必要的手术并发症。患者术后疗效满意,生活质量较好,随诊配合率高。在实施前宜将疗效及预后客观地告知患者及家属以期理解和积极配合,患者选择保留膀胱及正常排尿功能的意愿得到尊重,参与治疗决策的过程,符合循证医学的原则。
Objective
     To establish a pathology tissue library of prostate disease of Chinese people the target in1000cases; To survey the epidemiological situation of XMRV infection in Chinese prostate cancer patients, To analyze the relationship between XMRV infection and pathogenesy of prostate cancer. Analyze the correlation of the XMRV and prostate disease.
     Methods
     To collect patients' blood specimens, to collect the patient's blood DNA, RNA specimens. To establish the blood specimen bank of Prostate cancer and benign prostatic hyperplasia patients. Collect patients' prostate tissues with transperineal prostate biopsy system and establish prostate tissue library. Detection124cases of prostate tissue specimens with Nested PCR and immunohistochemical for XMRV DNA and viral antigens in tissue. Analyze the relationship of XMRV and prostate cancer in clinical stage and pathological grade by statistical methods.
     Results
     We had established initially the prostate disease pathology tissue library in Chinese people. Prostate pathologic specimens were more than300cases. The results of Nested PCR:68.5%patients had infected XMRV in total,73.4%prostate cancer patients had infected XMRV, and60.0%benign prostatic hyperplasia patients had infected XMRV. We detected XMRV antibody expression in prostate tissue by immunohistochemical methods, and the total positive response rate was32.35%in total; the prostate patients group's infection rate was43.04%; benign prostatic hyperplasia group's infection rate was13.33%.
     Conclusions
     We established the Chinese people prostate disease pathology tissue library system successfully and the number of samples has increased steadily. This laied the foundation for the futher studies prostate disease. Approximately43.04%Prostate cancer patients infected XMRV and about13.33%benign prostatic hyperplasia patients infected XMRV. There is some correlation between the XMRV infection and prostate cancer's pathogenesy.
     Objective
     To investigate the characteristics of transurethral partial cystectomy with a2μm laser in diagnosis and treatment for the bladder submucosal lesions in adults; To analyze the clinical characteristics of this method; To observe the efficiency of2μm continuous wave laser on the edge of the surgery field; To summarize and analyze the clinic characteristics of bladder tumor patients in follow-up periods after the surgery.
     Methods
     From August2009to December2011, according to the established standard, we chose patients with bladder submucosal lesions treated by2μm laser via transurethral under sacral block. We overview these following variables: operation characteristics, clinic curative effect, pathologic diagnosis;
     From Apirl2009to Apirl2011, according to the established standard, we chose107patients with bladder carcinoma treated by2μm laser and summarize and analyze the clinic characteristics of bladder tumor patients in follow-up periods after the surgery for3years.
     Results
     All operations were successful. Mean operative time was36.4minutes (range25to47), Perioperative blood loss was minimal. There was no obturator nerve reflection and no hemorrhage was detected after surgery. Postoperative pathological diagnosis:leiomyoma in3cases, pheochromocytoma in3cases, endometriosis in1case and metastatic bladder cancer in2cases. When the entire tumor and the full-thickness bladder wall at the base were freed, blood pressure of the pheochromocytoma patients reverted to stability.
     The follow-up periods of bladder carcinoma patients were between6to49months, and the median period was35months. There was no recurrence in situ. The survival rate is100%.
     Conclusions
     The2μm laser not only can vaporize and cut the wall of bladder finely, but also can dissect the muscular layers from connective tissue efficiently. So it can be partial cystectomy in the treatment of bladder tumor. It can be used in diagnose and treat bladder submucosal lesions. Patients could get accurate pathological diagnosis without further painful and some bladder tumors can be treated by minimally invasive surgery.
     For three yeas follow up periods, minireal influences on the patient's quality of life. It accords with the principle of evidence-based medicine.
引文
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    1. Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, Klein EA, Malathi K, Magi-Galluzzi C, Tubbs RR, Ganem D, Silverman RH, DeRisi JL. Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog.2006;2(3):e25.
    2. Coffin JM, Stoye JP. Virology. A new virus for old diseases? Science. 2009;326(5952):530-1.
    3. Dong B, Silverman RH, Kandel ES. A natural human retrovirus efficiently complements vectors based on murine leukemia virus. PLoS One. 2008;3(9):e3144.
    4. Yan Y, Liu Q, Kozak CA. Six host range variants of the xenotropic/polytropic gammaretroviruses define determinants for entry in the XPR1 cell surface receptor. Retrovirology.2009 Oct 7;6:87.
    5. Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR. XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. Proc Natl Acad Sci U S A.2009; 106(38):16351-6.
    6.Rodriguez JJ, Goff SP. Xenotropic Murine Leukemia Virus-Related Virus Establishes an Efficient Spreading Infection and Exhibits Enhanced Transcriptional Activity In Prostate Carcinoma Cells. J Virol.2009. [Epub ahead of print]
    7. Metzger, M. J., Holguin, C. J., Mendoza, R.& Miller, A. D. The prostate cancer-associated human retrovirus XMRV lacks direct transforming activity but can induce low rates of transformation in cultured cells. J Virol 84,1874-80.
    8. Kim, S. et al. Integration site preference of xenotropic murine leukemia virus-related virus, a new human retrovirus associated with prostate cancer. J Virol 82,9964-77 (2008).
    9. Dong, B.& Silverman, R. H. Androgen stimulates transcription and replication of xenotropic murine leukemia virus-related virus. J Virol 84,1648-51.
    10. Rodriguez, J. J.& Goff, S. P. Xenotropic murine leukemia virus-related virus establishes an efficient spreading infection and exhibits enhanced transcriptional activity in prostate carcinoma cells. J Virol 84,2556-62.
    11. Hong, S. et al. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol 83,6995-7003 (2009).
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