肾移植术后尿路上皮癌诊断及治疗研究
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摘要
目的探讨肾移植患者并发尿路上皮癌的诊断及治疗要点。
方法回顾性分析1977-2009年8月间接受免疫抑制治疗(至少半年)的2159例肾移植患者中发生尿路上皮癌的共42例病例。所有42例病例均采用手术治疗,9例行开放的肾根治性切除联合经尿道膀胱袖套状切除,11例行后腹腔镜肾根治性切除联合经尿道膀胱袖套状切除术,22例患者行膀胱肿瘤电切。术后常规膀胱灌注化疗药物如吡柔比星或丝裂霉素等防止复发,并定期随访。根据患者是否服用马兜铃酸成分中药,移植前透析时间等因素行相关性卡方检验。
结果在2159例肾移植患者中,发生尿路上皮癌42例,发病率为1.9%。全部42例患者病例资料完整,所有患者均经术后病理证实为尿路上皮癌。35例(83.3%)患者因血尿就诊；7例(16.7%)患者体检时发现病情,其中包括2例无尿的患者。所有患者均接受手术治疗,术后辅以化疗及放疗。9例患者行开放的肾根治性切除联合经尿道膀胱袖套状切除,其中2例术后行床旁血滤；11例行后腹腔镜肾根治性切除联合经尿道膀胱袖套状切除术,住院时间13-19天;22例行经尿道膀胱肿瘤电切,住院天数0-10天。4例患者术后因广泛转移死亡。病理结果：均为泌尿系统尿路上皮癌,纯膀胱癌22例,肾盂癌12例,’肾盂输尿管膀胱癌2例,输尿管癌6例。病理结果均为泌尿系统尿路上皮癌,病理分级：Ⅰ级4例,Ⅱ级34例,Ⅲ级4例。其中有2例并存肾盂腺癌与输尿管癌及膀胱尿路上皮癌。切口愈合时间7-15天,围手术期均未见切口感染、出血、腹腔积液、肠梗阻、肠麻痹、淋巴屡、褥疮或坠积性肺炎等并发症。术后均应用丝裂霉素膀胧灌注化疗。目前随访时间为1-45个月(17.3±11.65),其中4例死亡。复发肾盂癌2人4例次,均行根治性切除术；膀胱尿路上皮癌行TURBt术后的膀胱癌患者,1例于7个月后转移至肾盂、输尿管,行肾、输尿管根治性切除术,另有7人13例次复发,复发后病理为输尿管尿路上皮癌Ⅲ级为3人,恶性程度增加死亡病例中3例为马兜铃酸肾病,最长慢性肾功能衰竭病史11年,平均5.6年。
结论对于肾移植术后患者,特别是存在马兜铃酸类似中药成份服药史及马兜铃酸致间质性肾炎的患者,于复查时应加强泌尿系统的常规检查,如尿常规、尿脱落细胞病理检查以及泌尿系B超等；对于出现血尿、腰痛等症状的患者必要时可行膀胱镜、MRI等检查,争取尽早发现病情,以便及时治疗。对具备手术条件的肾移植术后的尿路上皮癌患者尽量选择微创治疗。及时监测患者肾功能及血药浓度,力争不影响移植肾脏功能的情况下,尽量减少免疫抑制药物用量。
Objective To analyse the characters of clinical pathology of urinary malignancies in patients with renal transplantation.
Methods A retrospective study was performed on 2159 renal allografts under at least 0.5 year immunosuppression from 1978-2009. All of the cases were operated.
Results 42 cases of uroepithelial tumors were found in 2159 cases undergoing renal transplantation with the incidence being 1.9%.42 cases had intact medical history and all of the cases were demonstrated pathologically.35 cases(83.3%) were diagnosed on account of hematuria,7 cases (16.7%)were diagnosed by medical examination including 2 anuric patients. all of the patients accepted operations, additional therapies including chemical or radiological.9 cases accepted patent operation of radical nephrectomy and transurethral cuffing cystectomy, length of stay was 17-25 days; 11 cases accepted retroperitoneoscopic radical nephrectomy and transurethral cuffing cystectomy, length of stay was 13-19 days;22 cases haved TURBT, length of stay was 0-10 days;4 cases died of wide metastasis.
Conclusions Patients with renal transplantation should pay more attention on urological routine examinations,the operations with less trauma should be choosed, at the same time, the dosage of immunosuppressants was reduced to maintain normal function of the graft.
方法回顾性分析1977-2009年8月间接受免疫抑制治疗(至少半年)的2159例肾移植患者中发生尿路上皮癌的共42例病例。所有42例病例均采用手术治疗,9例行开放的肾根治性切除联合经尿道膀胱袖套状切除,11例行后腹腔镜肾根治性切除联合经尿道膀胱袖套状切除术,22例患者行膀胱肿瘤电切。术后常规膀胱灌注化疗药物如吡柔比星或丝裂霉素等防止复发,并定期随访。根据患者是否服用马兜铃酸成分中药,移植前透析时间等因素行相关性卡方检验。
结果在2159例肾移植患者中,发生尿路上皮癌42例,发病率为1.9%。全部42例患者病例资料完整,所有患者均经术后病理证实为尿路上皮癌。35例(83.3%)患者因血尿就诊；7例(16.7%)患者体检时发现病情,其中包括2例无尿的患者。所有患者均接受手术治疗,术后辅以化疗及放疗。9例患者行开放的肾根治性切除联合经尿道膀胱袖套状切除,其中2例术后行床旁血滤；11例行后腹腔镜肾根治性切除联合经尿道膀胱袖套状切除术,住院时间13-19天;22例行经尿道膀胱肿瘤电切,住院天数0-10天。4例患者术后因广泛转移死亡。病理结果：均为泌尿系统尿路上皮癌,纯膀胱癌22例,肾盂癌12例,’肾盂输尿管膀胱癌2例,输尿管癌6例。病理结果均为泌尿系统尿路上皮癌,病理分级：Ⅰ级4例,Ⅱ级34例,Ⅲ级4例。其中有2例并存肾盂腺癌与输尿管癌及膀胱尿路上皮癌。切口愈合时间7-15天,围手术期均未见切口感染、出血、腹腔积液、肠梗阻、肠麻痹、淋巴屡、褥疮或坠积性肺炎等并发症。术后均应用丝裂霉素膀胧灌注化疗。目前随访时间为1-45个月(17.3±11.65),其中4例死亡。复发肾盂癌2人4例次,均行根治性切除术；膀胱尿路上皮癌行TURBt术后的膀胱癌患者,1例于7个月后转移至肾盂、输尿管,行肾、输尿管根治性切除术,另有7人13例次复发,复发后病理为输尿管尿路上皮癌Ⅲ级为3人,恶性程度增加死亡病例中3例为马兜铃酸肾病,最长慢性肾功能衰竭病史11年,平均5.6年。
结论对于肾移植术后患者,特别是存在马兜铃酸类似中药成份服药史及马兜铃酸致间质性肾炎的患者,于复查时应加强泌尿系统的常规检查,如尿常规、尿脱落细胞病理检查以及泌尿系B超等；对于出现血尿、腰痛等症状的患者必要时可行膀胱镜、MRI等检查,争取尽早发现病情,以便及时治疗。对具备手术条件的肾移植术后的尿路上皮癌患者尽量选择微创治疗。及时监测患者肾功能及血药浓度,力争不影响移植肾脏功能的情况下,尽量减少免疫抑制药物用量。
Objective To analyse the characters of clinical pathology of urinary malignancies in patients with renal transplantation.
Methods A retrospective study was performed on 2159 renal allografts under at least 0.5 year immunosuppression from 1978-2009. All of the cases were operated.
Results 42 cases of uroepithelial tumors were found in 2159 cases undergoing renal transplantation with the incidence being 1.9%.42 cases had intact medical history and all of the cases were demonstrated pathologically.35 cases(83.3%) were diagnosed on account of hematuria,7 cases (16.7%)were diagnosed by medical examination including 2 anuric patients. all of the patients accepted operations, additional therapies including chemical or radiological.9 cases accepted patent operation of radical nephrectomy and transurethral cuffing cystectomy, length of stay was 17-25 days; 11 cases accepted retroperitoneoscopic radical nephrectomy and transurethral cuffing cystectomy, length of stay was 13-19 days;22 cases haved TURBT, length of stay was 0-10 days;4 cases died of wide metastasis.
Conclusions Patients with renal transplantation should pay more attention on urological routine examinations,the operations with less trauma should be choosed, at the same time, the dosage of immunosuppressants was reduced to maintain normal function of the graft.
引文
[1]Briggs JD.Causes of death after renal transplantation-Nephrol Dial Transplant, 2001,16(8):1545.
[2]Arend SM, Mallat MJ, Westendorp RJ, et al-Patient survival after renal transplantation; more than 25 years follow-up-Nephrol Dial Transplant,1997, 12(8):1672.
[3]Aaron D, Berger, Benr ard M, etal. Transitionalcellcarcinom a of the bladder two years after suecessful lung transplantation:case reportandreview oftheliterature. Urology,2002,59:296.
[4]LiaoCH, Chueh SCJ, ChenJ. Transitionalcell carcinomain renaltransplantrecipients. Transplant Proc,2004,36:2152-2153.
[5]彭明强,杨志豪,方自林.国内公开报道的肾移植后并发恶性肿瘤病例的总结分析.中华器官移植杂志,2005,26：269-271.
[6]瞿立辉,李群,陈江华,等.肾移植患者并发恶性肿瘤临床分析.中华泌尿外科杂志,2004,25：445-447.
[7]PennI.CancersaftereyclosPorinetheraPy[J].TransPlantProe,1988,20(3):885 - 892.
[8]Gaya SB, Rees AJ, Leehler RI, et al.Malignant disease in patients with Long-termrenaltransPlants[J].TransPlantation,1995,59 (12):1705-1709.
[9]范昱,包尔敦,刘志宏,等.肾移植术后恶性肿瘤47例分析[J].中华器官移植杂志,2003,2(2)：115-116.)
[10]李文刚,方强,金锡御等.肾移植后膀肤恶性肿瘤的临床特征(附2例报并文献复习)[J].1启床泌尿外科杂志,2005,20(4)：202-204.
[14]Blohlnel, Brynger H.Malignani disease inrenal transplant Patients[J]. Transp lantation,1985,39(1):23-25.
[15]Perml.CaneersaftercyclosPorinetherapy[J].TransPlantProe,1988,20(3):885-892.
[16]Fomara P, Doehn C, Fricke L, et al.Laparoseo Picbilateral nephrectomy: resuitsinll renal transPlantPatients[J].JUrol,1997,157(2):445-449.
[18]Wkota K, Fukumitsu M, Kuzuhara K, et al.Development of cancer in renal allograftreeiPients [J].TransPlantProe,1994,26(4):1977-1978.
[19]孟慧林,杨德安,李香铁等.肾移植术后恶性肿瘤12例分析[J]、中华器官移植杂志,2002,23(3)：146-148.
[20]VirajAM, MaxwellV, Gary D, et al.Treatment and outcome of invasive Bladder cancer in Patients after renaltransPlantation[J].J Urol,2004, 171(3):1085 - 1088.
[21]Novitsky YW, Litwin, DEM, Callery Mp.The net immunologic advantage of laparoseoPiesurgery[J].SurgEndosc,2004,18(10):1411-1419.
[22]Desai MM, Gilll S.La Parosco Picsurgery in renal transplant Recipienis [J].UrolClinNorthAm,2001,28(4):759 - 767.
[23]谢立平,王支彬,秦杰.腹腔镜技术治疗泌尿系统肿瘤的现状与问题[J].现代泌尿外科杂志,2007,12(6)：351-354.
[24]马潞林,赵磊,罗康平等.肾移植术后并发自体泌尿系统移行细胞癌九例的诊治体会[J].中华器官移植杂志,2006,27(1)：14-15.
[25]Stein JP, ieskosky G,Cote R, et al.Radical cysteetomy in the treatment of Invasive bladder cancer:long-term results in1054 Patients[J]. J Clin Oncol,2001,19(3):666-675.
[26]Chatterjee SJ, DatarR, Youssef Zadeh D, et al.Combine defects of P53, P21, and PRbex Pression in the Progression of bladder transitional cell carcinoma[J].JClinOncol,2004,22(6):1007-1013.
[27]HojoM, MorimotoT, MalueeioM, et al.CyelosPorine induces caneer Progression by a cell-autonomous mechanism [J]. Nature,1999,397(6619):530-534.
[28]Liao CH, Chueh SCJ, Lai MK et al. Transitional Cell carcinoma in renal transplantrecipients[J].TransPlant Proc,2004,36(7):2152 - 2153.
[29]Nortier JL, MartinezMC, Schmeiserl HH, et al-Urothelial carcinoma associated with the use of a Chineseherb (Aristolochiafangehi) [J]. N Engl J Med,2000, 342(23):1686- 1692.33
[30]Cosyns JP, Jadoul M, Squiffiet JP, et al.Urothelial malignancy in nephropathy due to Chineseherbs[J].Laneet,1994,344(8916):188.
[31]Vanherweghem JL, Tielemans C, Simon J et al. Chinese herbs nephropathy and renal pelvic carcinoma[J]. Nephrol Dial Ttransplant,1995,10(2):270 - 273.
[1]Penn I.Cancers after cyclosporine etherapy[J]. Transplant Proe,1988,20(3):885-892.
[2]Gaya SB, Rees AJ, Lechler RI, et al.Malignant disease in patients with Long-termrenaltransPlants[J].TransPlantation,1995,59(12):1705-1709.
[3]PennI.The changing Pattern of Post transplant malignancies[J].Transplant Proc 1991,23(1PtZ):1101-1103.
[4]Jin DC, Yoon YS, Y oou SA et al.Ten cases of malignancies in kidney allografts[J].TransPlantProe,1994,26(4):1975-1976.
[5]Yokot aK, Fukumitsu M, Kuzuhara K, et al.Development of cancer inr enal allograftreeiPients[J].TransPlantProc,1994,26(4):1977-1978.
[6]VirajAM, MaxwellVM, Gary D get al.Treatment and outcome of invasive bl-addercancer in patients after renal transplantation[J], JUrol,2004, 171(3):1085-1088.
[7]董隽,敖建华,肖序仁等.肾移植受者术后发生恶性肿瘤的分析(附19例报道)[J].中华器官移植杂志,2001.22(4)：214-215.
[8]Geetha, Duvuru, Tong, et al. Bladder carcinoma in a transplant recipient evidence to implicate the BK human polyomavirus as a causal transforming agent[J].TransPlantation,2002,73(12):1933 1936.
[9]Berg, Daniel, Otly Clark C.Skin caneer in organ antransplant recipients EPidemiology, Pathogenesis andmanagement[J].JAmAcadDermatol,2002 47(1):1-17.
[10]lchaso N, Dilworth SM. Cell transformation by the middle T-antigen of Polyomavirus[J].Oneogene,2001,20(54):7908-7916.
[11]MullerM,WilderS,BannaschD, etal.P53 activates the CD95(APO-1/Fas) gene in response to DNA damage by anticancer drugs[J].J ExP Med,1998, 188(11):2033-2045.
[12]Hanahan D,WeinbergRA.The hallmarks of cancer[J].Cell,2000,100(1):57-70.
[13]Bouwes Bavinck JN, Hardie DR, GreenA,e tal.The risk of skin caneer in renal transplant recipients in Queensland, Anstralia.A follow-up study[J]. Transpla-ntation,1996,61(5):715721.
[14]Hojo M, Morimoto T, Maluceio M, et al.Cyclosporine induces cancer Progression by a cell-autonomous mechanism[J].Nature,1999 397(6619):530-534.
[15]Cherikh WS, Kauffman HM, Delmonico FL.A multivariate analysis of discharge immunosuppression and Post-transplant malignaney[J].Am J transplant,2001(51):353
[16]Schmidtko J, Wang Ruojie, Wu Cl et al.post transplant lymphoproli-ferative DisorderassoeiatedwithanEPstein-Barr-relatedvirusincynomolgus monkeys[J]. monkeys[J].TransPlantation,2002, 73(9):1431-1439.
[17]ChatterjeeSN.OrganTransPlantation[M].Boston:John Wright,1982; 151-268.
[18]HoshidaY, NakanishiH, ShinMetal.Renal neoPlasias in Patients receiving dialysis and renal transplantation:clinieal-pathological features and P53genemutations[J].TransPlantation,1999,68(3):385 - 390.
[19]Cosyns JP,Jadoul M,Squfflet JP, et al.Urothelial malignancy in nephropathy due to Chieseherbs[J].Lancet,1994,344(8916):188
[20]Cosyns JP. Axistolochic acid and Chinese herbs nephropathy:a review of the
evidence to date[J].Drug Saf,2003,26(1):33-48.
[21]NortierJL, MartinezMCM, SehlneiserHH, etal.Urothelial carcinoma A SSociated With the use of a Chiese herb (Aristoloehiafangchi) [J] NEngl J.Med,2000,342(23):1686-1692.
[22]Lord GM, Hollstein M, Allt VM, etal.DNAadduets and P53 mutations in a Patient with aristoloehicacid-associated nephroPathy[J]. AmJ kidney Dis.2004, 43(4):e11-7.
[23]Stiborova M, Hajek M, Frei E etal.Carcinogenic and nephrotoxic alkaloidsaristolochie acids upon activation by NADPH:cytoehromeP450 reduetase form adduets found in DNA of Patients with Chinese herbs nephropathy[J].GenPhysiolBioPhys.ZOOI,20(4):375-392.
[24]GoldfarbDA, NeumannhP, perml et al.Results of renal transplantation in Patienis with renal cell carcinoma and von Hippel-Lindaudisease[J].TransPlantation,1997,64(12):1726-1729.
[25]Penn I.Evaluation of transplant candidates with Pre-existing malignancies[J]. Ann TransPlant,1997,2(4):14-17.
[26]洪宝发,王晓雄,肖序仁,等.肾输尿管全长切除术治疗肾孟输尿管癌(附39例报告)[J].中华泌尿外科杂志,2000,21(6)：334-335
[27]马潞林,赵磊,罗康平等,肾移植术后并发自体泌尿系统尿路上皮癌九例的诊治体会[J],中华器官移植杂志,2006,27(1)：14-15.
[28]MatZkiesFK, TombaehB, DietrichM, etal.MVAC-theraPyforadvaneed urothelialcarcinomainananuricrenaltransplantreeipient[J].NePhrolDiTransPlantati on,2000,15(1):110-112.
[29]Edward M Messing, William Catalona. CamPbell's Urology, Seventh Edition, Harcourt Brace Company,1997.2348-2349.
[30]Chatterjee SJ, Datar R, YoussefZadeh D, e tal.Combinedeffects of P53, P21 and PRb expression in the Progression of bladder transitional cell carcinoma[J].JClinOneol,2004,22(6):1007-1013.
[31]ChaPman JR,Sheil Aq,Disney AP. Recurrence of cancer after renal transplantation[J]. TransPlantProe,2001,33(1- 2):1830 1831.
[32]CamPistol JM, Gutierrez-DalmauA, Torregrosa JV.Conversion to sirolimus:asueeessfultreatmentforPosrtransPlantationKaposi'ssarcomaIJ].TransPl antation,2004,77(5):760-762.
[33]NePotnueeno, Balatoni CE, Natkunam Y et al.Rapamycin inhibitsthe Interleukin 10 signal transduction Pathway and the growth of EPstein-Barrvirus B-cell lymPhomas[J].CancerRes,2003,63(15):4472-4480.
[34]王长希,刘龙山,陈立中等.雷帕霉素治疗肾移植术后肿瘤八例[J1.中华器官移植杂志,2005,26(5)：278-279
[35]LuanFL, DingR, Sharma VK, et al.Rapamycin is an effeetivei nhibitor of human renaleaneermetastasis[J].KidneyInt,2003,63(3):917-926.
[36]KoehlqGubaM, SeeligerH, et al. Rapamycin treatment at immuno-suppressive doses affects tumor blood vessel circulation[J]. TransPlantProe,2003,35(6):2135-2136.
[37]李小毛,肖兰,杨越波,等.SB203580与雷帕霉素联合对人子宫内膜癌Ishikawa细胞的体外抗肿瘤作用[J].广东医学,2009,30(1)：26-28.
[38]Nagaoka Yasuo,Otsuki, etal.Effects of PhosPhorylation of Immunomodulatory agent FTY720(fingolimod) on antiProliferative Activity against breast and colon cancer cells[J].Biol Pharm Bull,2008,31(6):1177-1181.
[39]Shen, Y, Wang, X, Xia, W et al. AntiProliferative and overadditive effects of rapamycin and FTY720 in Pancreatic cancer cells in vitro [J]. Transplant Proc, 2008,40(5):1727-1733.
[1]Cosyns J,Jadoul M,Squifflet J P,et all Urothelial malignancy in ne2phropathy due to Chinese herbsl Lancet,2003,344:188.
[2]Vanherweghem JL,Depierreux M,Tielemans C,et all Rapidly pro2gressive interstitial renal fibrosis in young women:association withslimming regimen including Chinese herbsl Lancet,2005;341:387.
[3]Nortier J,Simon J,Petein M,et all Chinese herbs nephropathy and urinary tract carcinomal J Am Soc Nephrol,2004,9:164.
[4]Vanherweghem JL, Depierreux M, Tielemans C, et al. Rapidly progressive intestitial renal fibrosis in young women:association with slimming regimen including Chinese herbs [J]. The Lancet,1993,341:387391.
[5]Shaoming Zhu, Jiubo Liu, Lin Chen, et al. Chemopreventive Effect of five drugs on renal interstitial fibrosis induced by an aristolochic acidcontaining Chinese herb in rats [J]. AM J Nethrol,2005,25:2329.
[6]郑法雷,张晓明,黄庆元,等.慢性马兜铃酸肾病动物模型的建立及其意义[J].中华医学杂志,2001,81：10951100.
[7]陈文,谌贻璞,李安,等.马兜铃酸肾病的临床与病理表现—附58例报告[J].中华医学杂志,2001,81：11011105.
[8]Cosyns JP, Jadoul M, Squiffiet JP, et al. Urothelial lesions in Chineseherb nephropathy [J]. Am J Kidney Dis,1999,33:10111017.
[9]Nortier JI, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of Chinese herb (Aristolochia fangchi) [J]. N Engl J Med,2000, 342:16861692.
[10]Nortier JL, Schmeiser HH, Martinez MCM, et al. Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristoiochic acid may occur without severe renal failure [J]. Nephrol Dial Transplants,2003, 18:426428.
[11]Lord GM, Cook T, Arlt VM, et al. Urothelial malignant disease and Chinese herbal nephropathy [J]. The Lancet,2001,358:15151516.
[12]林凡,许菲菲,徐玉兰.与甘露消毒丸相关的泌尿系肿瘤10例分析[J].温州医学院学报,2004,34：452454.
[13]李卫华,杨莉,苏涛,等.服用含马兜铃酸成分药物对尿毒症透析患者伴发尿路尿路上皮癌的影响[J].中华医学杂志,2005,85：24872491.
[14]Debelle F, Nortier J, Arlt VM, et al. Efiects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chineseherb nephropathy [J]. Arch Toxico,2003,77:218216.
[15]高艳丽,邹万忠,董鸿瑞,等.关木通对大鼠致癌性的试验研究[J].中华肾脏杂志,2003,19：250253.
[16]Arlt VLM, Wiessler M, Schmeiser HH. Using polymerase arrest to detect DNA binding specificity of aristolochic acid in the mouse Hras gene [J]. Carcinogenesis,2000,21:235242.
[17]Bieler CA, stiborova M, Wiessler M, et al.32Ppostlabeling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy [J]. Carcinogenesis,1997,18:10631067.
[18]Arlt VM, Schmeiser HH, Pfeifer GR. Sequencespecific detection of aristolochic acidDNA adducts in the human P53 gene by terminal transferasedependent PCR [J]. Carcinogenesis,2001,22:133140.
[19]Lord GM, Hollstein M, Arlt VM, et al. DNA adducts and p53 mutations in a patient with aristolochic acidassociated nephropathy [J]. Am J Kidney Dis, 2004,43:1117.
[20]Vanherweghem JL, Abramowicz D, Tiplemans C, et al. Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis:a pilot study in Chinese herbs nephropathy [J]. Am J Kidney Dis,1996,27:209215.
[21]陈俊良,吴宜鸿,邓跃毅,等.丹参对马兜铃酸致肾小管上皮细胞损害的保护作用研究[J].中国中西医结合肾病杂志,2005,6：445448.
[2]Arend SM, Mallat MJ, Westendorp RJ, et al-Patient survival after renal transplantation; more than 25 years follow-up-Nephrol Dial Transplant,1997, 12(8):1672.
[3]Aaron D, Berger, Benr ard M, etal. Transitionalcellcarcinom a of the bladder two years after suecessful lung transplantation:case reportandreview oftheliterature. Urology,2002,59:296.
[4]LiaoCH, Chueh SCJ, ChenJ. Transitionalcell carcinomain renaltransplantrecipients. Transplant Proc,2004,36:2152-2153.
[5]彭明强,杨志豪,方自林.国内公开报道的肾移植后并发恶性肿瘤病例的总结分析.中华器官移植杂志,2005,26：269-271.
[6]瞿立辉,李群,陈江华,等.肾移植患者并发恶性肿瘤临床分析.中华泌尿外科杂志,2004,25：445-447.
[7]PennI.CancersaftereyclosPorinetheraPy[J].TransPlantProe,1988,20(3):885 - 892.
[8]Gaya SB, Rees AJ, Leehler RI, et al.Malignant disease in patients with Long-termrenaltransPlants[J].TransPlantation,1995,59 (12):1705-1709.
[9]范昱,包尔敦,刘志宏,等.肾移植术后恶性肿瘤47例分析[J].中华器官移植杂志,2003,2(2)：115-116.)
[10]李文刚,方强,金锡御等.肾移植后膀肤恶性肿瘤的临床特征(附2例报并文献复习)[J].1启床泌尿外科杂志,2005,20(4)：202-204.
[14]Blohlnel, Brynger H.Malignani disease inrenal transplant Patients[J]. Transp lantation,1985,39(1):23-25.
[15]Perml.CaneersaftercyclosPorinetherapy[J].TransPlantProe,1988,20(3):885-892.
[16]Fomara P, Doehn C, Fricke L, et al.Laparoseo Picbilateral nephrectomy: resuitsinll renal transPlantPatients[J].JUrol,1997,157(2):445-449.
[18]Wkota K, Fukumitsu M, Kuzuhara K, et al.Development of cancer in renal allograftreeiPients [J].TransPlantProe,1994,26(4):1977-1978.
[19]孟慧林,杨德安,李香铁等.肾移植术后恶性肿瘤12例分析[J]、中华器官移植杂志,2002,23(3)：146-148.
[20]VirajAM, MaxwellV, Gary D, et al.Treatment and outcome of invasive Bladder cancer in Patients after renaltransPlantation[J].J Urol,2004, 171(3):1085 - 1088.
[21]Novitsky YW, Litwin, DEM, Callery Mp.The net immunologic advantage of laparoseoPiesurgery[J].SurgEndosc,2004,18(10):1411-1419.
[22]Desai MM, Gilll S.La Parosco Picsurgery in renal transplant Recipienis [J].UrolClinNorthAm,2001,28(4):759 - 767.
[23]谢立平,王支彬,秦杰.腹腔镜技术治疗泌尿系统肿瘤的现状与问题[J].现代泌尿外科杂志,2007,12(6)：351-354.
[24]马潞林,赵磊,罗康平等.肾移植术后并发自体泌尿系统移行细胞癌九例的诊治体会[J].中华器官移植杂志,2006,27(1)：14-15.
[25]Stein JP, ieskosky G,Cote R, et al.Radical cysteetomy in the treatment of Invasive bladder cancer:long-term results in1054 Patients[J]. J Clin Oncol,2001,19(3):666-675.
[26]Chatterjee SJ, DatarR, Youssef Zadeh D, et al.Combine defects of P53, P21, and PRbex Pression in the Progression of bladder transitional cell carcinoma[J].JClinOncol,2004,22(6):1007-1013.
[27]HojoM, MorimotoT, MalueeioM, et al.CyelosPorine induces caneer Progression by a cell-autonomous mechanism [J]. Nature,1999,397(6619):530-534.
[28]Liao CH, Chueh SCJ, Lai MK et al. Transitional Cell carcinoma in renal transplantrecipients[J].TransPlant Proc,2004,36(7):2152 - 2153.
[29]Nortier JL, MartinezMC, Schmeiserl HH, et al-Urothelial carcinoma associated with the use of a Chineseherb (Aristolochiafangehi) [J]. N Engl J Med,2000, 342(23):1686- 1692.33
[30]Cosyns JP, Jadoul M, Squiffiet JP, et al.Urothelial malignancy in nephropathy due to Chineseherbs[J].Laneet,1994,344(8916):188.
[31]Vanherweghem JL, Tielemans C, Simon J et al. Chinese herbs nephropathy and renal pelvic carcinoma[J]. Nephrol Dial Ttransplant,1995,10(2):270 - 273.
[1]Penn I.Cancers after cyclosporine etherapy[J]. Transplant Proe,1988,20(3):885-892.
[2]Gaya SB, Rees AJ, Lechler RI, et al.Malignant disease in patients with Long-termrenaltransPlants[J].TransPlantation,1995,59(12):1705-1709.
[3]PennI.The changing Pattern of Post transplant malignancies[J].Transplant Proc 1991,23(1PtZ):1101-1103.
[4]Jin DC, Yoon YS, Y oou SA et al.Ten cases of malignancies in kidney allografts[J].TransPlantProe,1994,26(4):1975-1976.
[5]Yokot aK, Fukumitsu M, Kuzuhara K, et al.Development of cancer inr enal allograftreeiPients[J].TransPlantProc,1994,26(4):1977-1978.
[6]VirajAM, MaxwellVM, Gary D get al.Treatment and outcome of invasive bl-addercancer in patients after renal transplantation[J], JUrol,2004, 171(3):1085-1088.
[7]董隽,敖建华,肖序仁等.肾移植受者术后发生恶性肿瘤的分析(附19例报道)[J].中华器官移植杂志,2001.22(4)：214-215.
[8]Geetha, Duvuru, Tong, et al. Bladder carcinoma in a transplant recipient evidence to implicate the BK human polyomavirus as a causal transforming agent[J].TransPlantation,2002,73(12):1933 1936.
[9]Berg, Daniel, Otly Clark C.Skin caneer in organ antransplant recipients EPidemiology, Pathogenesis andmanagement[J].JAmAcadDermatol,2002 47(1):1-17.
[10]lchaso N, Dilworth SM. Cell transformation by the middle T-antigen of Polyomavirus[J].Oneogene,2001,20(54):7908-7916.
[11]MullerM,WilderS,BannaschD, etal.P53 activates the CD95(APO-1/Fas) gene in response to DNA damage by anticancer drugs[J].J ExP Med,1998, 188(11):2033-2045.
[12]Hanahan D,WeinbergRA.The hallmarks of cancer[J].Cell,2000,100(1):57-70.
[13]Bouwes Bavinck JN, Hardie DR, GreenA,e tal.The risk of skin caneer in renal transplant recipients in Queensland, Anstralia.A follow-up study[J]. Transpla-ntation,1996,61(5):715721.
[14]Hojo M, Morimoto T, Maluceio M, et al.Cyclosporine induces cancer Progression by a cell-autonomous mechanism[J].Nature,1999 397(6619):530-534.
[15]Cherikh WS, Kauffman HM, Delmonico FL.A multivariate analysis of discharge immunosuppression and Post-transplant malignaney[J].Am J transplant,2001(51):353
[16]Schmidtko J, Wang Ruojie, Wu Cl et al.post transplant lymphoproli-ferative DisorderassoeiatedwithanEPstein-Barr-relatedvirusincynomolgus monkeys[J]. monkeys[J].TransPlantation,2002, 73(9):1431-1439.
[17]ChatterjeeSN.OrganTransPlantation[M].Boston:John Wright,1982; 151-268.
[18]HoshidaY, NakanishiH, ShinMetal.Renal neoPlasias in Patients receiving dialysis and renal transplantation:clinieal-pathological features and P53genemutations[J].TransPlantation,1999,68(3):385 - 390.
[19]Cosyns JP,Jadoul M,Squfflet JP, et al.Urothelial malignancy in nephropathy due to Chieseherbs[J].Lancet,1994,344(8916):188
[20]Cosyns JP. Axistolochic acid and Chinese herbs nephropathy:a review of the
evidence to date[J].Drug Saf,2003,26(1):33-48.
[21]NortierJL, MartinezMCM, SehlneiserHH, etal.Urothelial carcinoma A SSociated With the use of a Chiese herb (Aristoloehiafangchi) [J] NEngl J.Med,2000,342(23):1686-1692.
[22]Lord GM, Hollstein M, Allt VM, etal.DNAadduets and P53 mutations in a Patient with aristoloehicacid-associated nephroPathy[J]. AmJ kidney Dis.2004, 43(4):e11-7.
[23]Stiborova M, Hajek M, Frei E etal.Carcinogenic and nephrotoxic alkaloidsaristolochie acids upon activation by NADPH:cytoehromeP450 reduetase form adduets found in DNA of Patients with Chinese herbs nephropathy[J].GenPhysiolBioPhys.ZOOI,20(4):375-392.
[24]GoldfarbDA, NeumannhP, perml et al.Results of renal transplantation in Patienis with renal cell carcinoma and von Hippel-Lindaudisease[J].TransPlantation,1997,64(12):1726-1729.
[25]Penn I.Evaluation of transplant candidates with Pre-existing malignancies[J]. Ann TransPlant,1997,2(4):14-17.
[26]洪宝发,王晓雄,肖序仁,等.肾输尿管全长切除术治疗肾孟输尿管癌(附39例报告)[J].中华泌尿外科杂志,2000,21(6)：334-335
[27]马潞林,赵磊,罗康平等,肾移植术后并发自体泌尿系统尿路上皮癌九例的诊治体会[J],中华器官移植杂志,2006,27(1)：14-15.
[28]MatZkiesFK, TombaehB, DietrichM, etal.MVAC-theraPyforadvaneed urothelialcarcinomainananuricrenaltransplantreeipient[J].NePhrolDiTransPlantati on,2000,15(1):110-112.
[29]Edward M Messing, William Catalona. CamPbell's Urology, Seventh Edition, Harcourt Brace Company,1997.2348-2349.
[30]Chatterjee SJ, Datar R, YoussefZadeh D, e tal.Combinedeffects of P53, P21 and PRb expression in the Progression of bladder transitional cell carcinoma[J].JClinOneol,2004,22(6):1007-1013.
[31]ChaPman JR,Sheil Aq,Disney AP. Recurrence of cancer after renal transplantation[J]. TransPlantProe,2001,33(1- 2):1830 1831.
[32]CamPistol JM, Gutierrez-DalmauA, Torregrosa JV.Conversion to sirolimus:asueeessfultreatmentforPosrtransPlantationKaposi'ssarcomaIJ].TransPl antation,2004,77(5):760-762.
[33]NePotnueeno, Balatoni CE, Natkunam Y et al.Rapamycin inhibitsthe Interleukin 10 signal transduction Pathway and the growth of EPstein-Barrvirus B-cell lymPhomas[J].CancerRes,2003,63(15):4472-4480.
[34]王长希,刘龙山,陈立中等.雷帕霉素治疗肾移植术后肿瘤八例[J1.中华器官移植杂志,2005,26(5)：278-279
[35]LuanFL, DingR, Sharma VK, et al.Rapamycin is an effeetivei nhibitor of human renaleaneermetastasis[J].KidneyInt,2003,63(3):917-926.
[36]KoehlqGubaM, SeeligerH, et al. Rapamycin treatment at immuno-suppressive doses affects tumor blood vessel circulation[J]. TransPlantProe,2003,35(6):2135-2136.
[37]李小毛,肖兰,杨越波,等.SB203580与雷帕霉素联合对人子宫内膜癌Ishikawa细胞的体外抗肿瘤作用[J].广东医学,2009,30(1)：26-28.
[38]Nagaoka Yasuo,Otsuki, etal.Effects of PhosPhorylation of Immunomodulatory agent FTY720(fingolimod) on antiProliferative Activity against breast and colon cancer cells[J].Biol Pharm Bull,2008,31(6):1177-1181.
[39]Shen, Y, Wang, X, Xia, W et al. AntiProliferative and overadditive effects of rapamycin and FTY720 in Pancreatic cancer cells in vitro [J]. Transplant Proc, 2008,40(5):1727-1733.
[1]Cosyns J,Jadoul M,Squifflet J P,et all Urothelial malignancy in ne2phropathy due to Chinese herbsl Lancet,2003,344:188.
[2]Vanherweghem JL,Depierreux M,Tielemans C,et all Rapidly pro2gressive interstitial renal fibrosis in young women:association withslimming regimen including Chinese herbsl Lancet,2005;341:387.
[3]Nortier J,Simon J,Petein M,et all Chinese herbs nephropathy and urinary tract carcinomal J Am Soc Nephrol,2004,9:164.
[4]Vanherweghem JL, Depierreux M, Tielemans C, et al. Rapidly progressive intestitial renal fibrosis in young women:association with slimming regimen including Chinese herbs [J]. The Lancet,1993,341:387391.
[5]Shaoming Zhu, Jiubo Liu, Lin Chen, et al. Chemopreventive Effect of five drugs on renal interstitial fibrosis induced by an aristolochic acidcontaining Chinese herb in rats [J]. AM J Nethrol,2005,25:2329.
[6]郑法雷,张晓明,黄庆元,等.慢性马兜铃酸肾病动物模型的建立及其意义[J].中华医学杂志,2001,81：10951100.
[7]陈文,谌贻璞,李安,等.马兜铃酸肾病的临床与病理表现—附58例报告[J].中华医学杂志,2001,81：11011105.
[8]Cosyns JP, Jadoul M, Squiffiet JP, et al. Urothelial lesions in Chineseherb nephropathy [J]. Am J Kidney Dis,1999,33:10111017.
[9]Nortier JI, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of Chinese herb (Aristolochia fangchi) [J]. N Engl J Med,2000, 342:16861692.
[10]Nortier JL, Schmeiser HH, Martinez MCM, et al. Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristoiochic acid may occur without severe renal failure [J]. Nephrol Dial Transplants,2003, 18:426428.
[11]Lord GM, Cook T, Arlt VM, et al. Urothelial malignant disease and Chinese herbal nephropathy [J]. The Lancet,2001,358:15151516.
[12]林凡,许菲菲,徐玉兰.与甘露消毒丸相关的泌尿系肿瘤10例分析[J].温州医学院学报,2004,34：452454.
[13]李卫华,杨莉,苏涛,等.服用含马兜铃酸成分药物对尿毒症透析患者伴发尿路尿路上皮癌的影响[J].中华医学杂志,2005,85：24872491.
[14]Debelle F, Nortier J, Arlt VM, et al. Efiects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chineseherb nephropathy [J]. Arch Toxico,2003,77:218216.
[15]高艳丽,邹万忠,董鸿瑞,等.关木通对大鼠致癌性的试验研究[J].中华肾脏杂志,2003,19：250253.
[16]Arlt VLM, Wiessler M, Schmeiser HH. Using polymerase arrest to detect DNA binding specificity of aristolochic acid in the mouse Hras gene [J]. Carcinogenesis,2000,21:235242.
[17]Bieler CA, stiborova M, Wiessler M, et al.32Ppostlabeling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy [J]. Carcinogenesis,1997,18:10631067.
[18]Arlt VM, Schmeiser HH, Pfeifer GR. Sequencespecific detection of aristolochic acidDNA adducts in the human P53 gene by terminal transferasedependent PCR [J]. Carcinogenesis,2001,22:133140.
[19]Lord GM, Hollstein M, Arlt VM, et al. DNA adducts and p53 mutations in a patient with aristolochic acidassociated nephropathy [J]. Am J Kidney Dis, 2004,43:1117.
[20]Vanherweghem JL, Abramowicz D, Tiplemans C, et al. Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis:a pilot study in Chinese herbs nephropathy [J]. Am J Kidney Dis,1996,27:209215.
[21]陈俊良,吴宜鸿,邓跃毅,等.丹参对马兜铃酸致肾小管上皮细胞损害的保护作用研究[J].中国中西医结合肾病杂志,2005,6：445448.