非肌层浸润性膀胱癌的临床特征及复发的相关因素分析
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摘要
研究背景:膀胱癌是最常见的恶性肿瘤之一,近年来发病有增加趋势,大约75%的膀胱癌患者为男性。膀胱癌确定的危险因素是吸烟和与某些致癌物的接触史。约80%的膀胱癌局限于膀胱粘膜内,称之为非肌层浸润性膀胱癌;而另外20%侵犯至膀胱壁肌层。这两种类型膀胱癌的处理和预后不同:非肌层浸润性膀胱癌恶性度很低,但复发几率高,在新发膀胱癌患者中,经彻底电切切除后,若不进一步治疗约有70%的患者可能复发,约35%的患者在复发时分期和分级将会提高。非肌层浸润性膀胱癌的复发与多种因素密切相关,分析和研究这些因素在膀胱癌复发时所起到的作用,对于膀胱癌的临床治疗、随访以及远期预后判断等具有重要意义。为提高膀胱癌的疗效,改善患者的预后,减少复发,长期以来人们一直在研究影响其预后的危险因素,但除了个别指标,大多数指标的预后价值仍存在争议或缺少大规模研究的支持。本研究通过回顾性分析407例非肌层浸润性膀胱癌患者的临床资料,探讨与肿瘤复发和进展相关的危险因素及其作用,同时分析高级别T1期膀胱癌的临床特点及不同治疗方法间的差异,为临床实践工作提供循证医学依据。
目的:探讨影响非肌层浸润性膀胱癌复发的相关因素及其临床意义,分析诸多危险因素在肿瘤预后和转归中的作用,并给出干预措施以及对策。
方法:回顾性分析苏州大学附属第一医院泌尿外科2004年1月至2011年1月收治的407例非肌层浸润性膀胱癌患者的临床资料,包括:性别,年龄,主诉,既往膀胱癌治疗及复发情况,吸烟史,影像学资料,手术方式,肿瘤数目、大小,病理结果,膀胱灌注药物、时间、剂量,是否复发和进展等指标。采用电话及门诊随访方式采集患者随访资料。分析患者临床特征,通过统计学方法对年龄、性别、肿瘤分期、分级、大小、数目及其生长部位、术后维持灌注用药及既往复发情况等影响肿瘤复发的因素进行单因素分析和COX回归分析,筛选影响膀胱癌术后复发的危险因素。分析高级别T_1期膀胱癌(T_1G_3)患者的临床特征及不同治疗方法的结局。
结果:单因素分析结果显示年龄(P=0.022)、性别(P=0.018)、肿瘤分期(P=0.041)、分级(P=0.048)、肿瘤数目(P=0.002)、既往复发病史(P=0.001)以及是否维持膀胱灌注治疗(P=0.014)与肿瘤复发相关;而肿瘤部位、肿瘤大小、既往复发次数以及不同灌注药物等因素对肿瘤复发均无影响(P>0.05)。COX回归分析结果显示性别(P=0.016)、肿瘤分期(P=0.049)、分级(P=0.014)、肿瘤数目(P=0.018)、既往复发病史(P=0.005)以及定期膀胱灌注(P=0.001)是非肌层浸润性膀胱癌复发的影响因素。T_1G_3膀胱癌患者年龄(P=0.024)、男女比例(P=0.013)、肿瘤数目(P=0.036)、一年内复发例数(P=0.043)、复发时间(P=0.032)及进展时间(P=0.039)均较其余类型膀胱癌有显著差异。T_1G_3膀胱癌患者采用静脉化疗+膀胱灌注治疗较单纯膀胱灌注复发率降低(P=0.041)并且复发时间明显延长(P=0.032)。
结论:性别、肿瘤分期、分级、既往复发病史、肿瘤数目以及是否维持膀胱灌注治疗对非肌层浸润性膀胱尿路上皮癌复发影响最大。对于T_1G_3膀胱癌经尿道膀胱肿瘤电切术后全身静脉化疗明显有效,可以显著延长复发时间,降低复发率,并且患者对全身静脉化疗均能耐受,治疗期间不良反应轻微,且可逆,患者易接受并获得了较好的生活质量。
Background: Bladder cancer is the most common malignant tumor, it shows an increasing trend of incidence in recent years and approximately 75% of patients with bladder cancer were male. There were two established risk factors for bladder cancer, one was smoking and the other one was history of exposure to certain carcinogens. About 80% bladder cancer confined to the bladder mucosa, known as non-muscle invasive bladder cancer (NMIBC); while the other 20% was muscle invasion bladder cancer. The two types of bladder cancer were completely different in treatment and prognosis: NMIBC was low grade but high risk of recurrence in the new bladder cancer patients after resection by transurethral resection of bladder tumor (TURBT), if further treatment was absent, the recurrence rate was about 70% and about 35% of patients would face with a increasing stage and grade. Recurrence of bladder cancer are closely related with many factors, analysis and study of these factors in bladder cancer recurrence plays an important role, particularly in further treatment, follow-up and long-term prognosis. To improve the efficacy of bladder cancer and reduce recurrence rate, a considerable number of researches has been done to find out the risk factors affecting the prognosis, however most of them were still controversial or lack of support with large-scale researches. A retrospective study of 407 cases with non-muscle invasive bladder cancer was done to analysis clinical data of patients including age, gender, tumor number and size and other factors which were affected with the recurrence of bladder cancer, we hoped this study would provide a basis for clinical practice.
Objective: To investigate the recurrence-related factors of non-muscle invasive bladder cancer and its clinical characteristics, and analysis the role of various risk factors in prognosis and outcome, meanwhile to give interventions and countermeasures.
Methods: A retrospective study was done to analysis 407 cases that were diagnosed with non-muscle invasive bladder cancer in urology department, the First Affiliated Hospital of Soochow University from January, 2004 to January, 2011. All clinical information were collected, including: gender, age, chief complaint, past treatment and recurrence of bladder cancer, smoking history, imaging data, surgical type, tumor number, size, pathology, tumor grade, bladder instillation, time, dose, recurrence and progress. Follow-up data were collected in outpatient department or by telephone. Univariate and COX multivariate analysis were done for screening the significant indicators that affect the recurrence of bladder cancer risk factors and patient survival curves was draw. Analysis the clinical characters of T1 high grade (T_1G_3) bladder cancer and compare the outcomes of different treatment method.
Results: Univariate analysis showed that gender (P=0.018), tumor stage (P=0.021), grade (P=0.048), tumor number (P=0.002), previous recurrence (P=0.001) and intravesical instillation treatment (P=0.004) were associated with tumor recurrence; age, tumor location, tumor size, previous recurrence times, and infusion drugs had no effect in tumor recurrence (P>0.05). Characters of T_1G_3 were significantly different with other types of bladder cancer including age (P=0.024), gender (P=0.013), tumor number (P=0.036), number of patients recurrence within one year (P=0.043), recurrence time (P=0.032) and progress time (P=0.039). T_1G_3 bladder cancer treated with intravenous chemotherapy had significantly longer recurrence time compared with intravesical instillation treatment (P=0.032).
Conclusion: Gender, tumor stage and grade,previous recurrence, tumor number, and whether routine intravesical instillation treatment play the most important role in recurrence of non-muscle invasive bladder cancer. Combine with transurethral resection of bladder tumor and intravenous chemotherapy can significantly prolong recurrence time in high-risk T_1G_3 non-muscle invasive bladder cancer, and intravenous chemotherapy is well tolerated in patients.
目的:探讨影响非肌层浸润性膀胱癌复发的相关因素及其临床意义,分析诸多危险因素在肿瘤预后和转归中的作用,并给出干预措施以及对策。
方法:回顾性分析苏州大学附属第一医院泌尿外科2004年1月至2011年1月收治的407例非肌层浸润性膀胱癌患者的临床资料,包括:性别,年龄,主诉,既往膀胱癌治疗及复发情况,吸烟史,影像学资料,手术方式,肿瘤数目、大小,病理结果,膀胱灌注药物、时间、剂量,是否复发和进展等指标。采用电话及门诊随访方式采集患者随访资料。分析患者临床特征,通过统计学方法对年龄、性别、肿瘤分期、分级、大小、数目及其生长部位、术后维持灌注用药及既往复发情况等影响肿瘤复发的因素进行单因素分析和COX回归分析,筛选影响膀胱癌术后复发的危险因素。分析高级别T_1期膀胱癌(T_1G_3)患者的临床特征及不同治疗方法的结局。
结果:单因素分析结果显示年龄(P=0.022)、性别(P=0.018)、肿瘤分期(P=0.041)、分级(P=0.048)、肿瘤数目(P=0.002)、既往复发病史(P=0.001)以及是否维持膀胱灌注治疗(P=0.014)与肿瘤复发相关;而肿瘤部位、肿瘤大小、既往复发次数以及不同灌注药物等因素对肿瘤复发均无影响(P>0.05)。COX回归分析结果显示性别(P=0.016)、肿瘤分期(P=0.049)、分级(P=0.014)、肿瘤数目(P=0.018)、既往复发病史(P=0.005)以及定期膀胱灌注(P=0.001)是非肌层浸润性膀胱癌复发的影响因素。T_1G_3膀胱癌患者年龄(P=0.024)、男女比例(P=0.013)、肿瘤数目(P=0.036)、一年内复发例数(P=0.043)、复发时间(P=0.032)及进展时间(P=0.039)均较其余类型膀胱癌有显著差异。T_1G_3膀胱癌患者采用静脉化疗+膀胱灌注治疗较单纯膀胱灌注复发率降低(P=0.041)并且复发时间明显延长(P=0.032)。
结论:性别、肿瘤分期、分级、既往复发病史、肿瘤数目以及是否维持膀胱灌注治疗对非肌层浸润性膀胱尿路上皮癌复发影响最大。对于T_1G_3膀胱癌经尿道膀胱肿瘤电切术后全身静脉化疗明显有效,可以显著延长复发时间,降低复发率,并且患者对全身静脉化疗均能耐受,治疗期间不良反应轻微,且可逆,患者易接受并获得了较好的生活质量。
Background: Bladder cancer is the most common malignant tumor, it shows an increasing trend of incidence in recent years and approximately 75% of patients with bladder cancer were male. There were two established risk factors for bladder cancer, one was smoking and the other one was history of exposure to certain carcinogens. About 80% bladder cancer confined to the bladder mucosa, known as non-muscle invasive bladder cancer (NMIBC); while the other 20% was muscle invasion bladder cancer. The two types of bladder cancer were completely different in treatment and prognosis: NMIBC was low grade but high risk of recurrence in the new bladder cancer patients after resection by transurethral resection of bladder tumor (TURBT), if further treatment was absent, the recurrence rate was about 70% and about 35% of patients would face with a increasing stage and grade. Recurrence of bladder cancer are closely related with many factors, analysis and study of these factors in bladder cancer recurrence plays an important role, particularly in further treatment, follow-up and long-term prognosis. To improve the efficacy of bladder cancer and reduce recurrence rate, a considerable number of researches has been done to find out the risk factors affecting the prognosis, however most of them were still controversial or lack of support with large-scale researches. A retrospective study of 407 cases with non-muscle invasive bladder cancer was done to analysis clinical data of patients including age, gender, tumor number and size and other factors which were affected with the recurrence of bladder cancer, we hoped this study would provide a basis for clinical practice.
Objective: To investigate the recurrence-related factors of non-muscle invasive bladder cancer and its clinical characteristics, and analysis the role of various risk factors in prognosis and outcome, meanwhile to give interventions and countermeasures.
Methods: A retrospective study was done to analysis 407 cases that were diagnosed with non-muscle invasive bladder cancer in urology department, the First Affiliated Hospital of Soochow University from January, 2004 to January, 2011. All clinical information were collected, including: gender, age, chief complaint, past treatment and recurrence of bladder cancer, smoking history, imaging data, surgical type, tumor number, size, pathology, tumor grade, bladder instillation, time, dose, recurrence and progress. Follow-up data were collected in outpatient department or by telephone. Univariate and COX multivariate analysis were done for screening the significant indicators that affect the recurrence of bladder cancer risk factors and patient survival curves was draw. Analysis the clinical characters of T1 high grade (T_1G_3) bladder cancer and compare the outcomes of different treatment method.
Results: Univariate analysis showed that gender (P=0.018), tumor stage (P=0.021), grade (P=0.048), tumor number (P=0.002), previous recurrence (P=0.001) and intravesical instillation treatment (P=0.004) were associated with tumor recurrence; age, tumor location, tumor size, previous recurrence times, and infusion drugs had no effect in tumor recurrence (P>0.05). Characters of T_1G_3 were significantly different with other types of bladder cancer including age (P=0.024), gender (P=0.013), tumor number (P=0.036), number of patients recurrence within one year (P=0.043), recurrence time (P=0.032) and progress time (P=0.039). T_1G_3 bladder cancer treated with intravenous chemotherapy had significantly longer recurrence time compared with intravesical instillation treatment (P=0.032).
Conclusion: Gender, tumor stage and grade,previous recurrence, tumor number, and whether routine intravesical instillation treatment play the most important role in recurrence of non-muscle invasive bladder cancer. Combine with transurethral resection of bladder tumor and intravenous chemotherapy can significantly prolong recurrence time in high-risk T_1G_3 non-muscle invasive bladder cancer, and intravenous chemotherapy is well tolerated in patients.
引文
[1] Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer [J]. Can Urol Assoc J. 2010; 4(1): 56-64.
[2]那彦群,孙光.中国泌尿外科疾病诊断治疗指南.人民卫生出版社. 2009: 16-18.
[3] Epstein JI, Amin MB, Reuter VR, et al. The World Health Organization/ International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. AmJsurg Pathol, 1998; 22: 1435-1488.
[4] Sobin DH and Witteking. TNM Classification of Malignant tumors. 6th edition. Wiley-Liss: New York, 2002. 199-202.
[5]李建国,浦金贤.经尿道等离子体双极电切术治疗浅表膀胱肿瘤25例报告[J].苏州大学学报(医学版). 2007; 27(6): 931-932.
[6]曾福华,杨土保,江勃年.原发浅表性膀胱癌预后影响因素分析[J].中华泌尿外科学杂志[J], 2004; 10: 171-175.
[7]申文江,郭应禄.膀胱癌的辅助治疗[J].临床肿瘤学杂志, 2003; 3(4): 104-105.
[8] Kanaroglou A, Shayegan B. Management of the urethra in urothelial bladder cancer [J]. Can Urol Assoc J. 2009; 3(6): 211-214.
[9] Sexton WJ, Wiegand LR, Correa JJ. Bladder cancer: a review of non-muscle invasive disease [J]. Cancer Control. 2010 Oct; 17(4): 256-268.
[10]董胜国,纪祥瑞,侯四川.影响膀胱癌患者长期生存的因素分析[J].临床泌尿外科杂志,1999; 14(6): 256-259.
[11]孔良,叶敏.经尿道电汽化术治疗浅表性膀胱癌[J].中华泌尿外科杂志. 2001; 34(3): 326-328.
[12] Bryan RT, Collins SI, Daykin MC. Mechanisms of recurrence of Ta/T1 bladder cancer [J]. Ann R Coll Surg Engl. 2010; 92(6): 519-524.
[13] Kohjimoto Y, Iba A, Shintani Y. Impact of patient age on outcome followingbladder-preserving treatment for non-muscle-invasive bladder cancer [J]. World J Urol. 2010; 28(4): 425-30.
[14] Bryan RT, Collins SI, Daykin MC. Mechanisms of recurrence of Ta/T1 bladder cancer [J]. Ann R Coll Surg Engl. 2010; 92(6): 519-24.
[15] Gofrit ON, Shapiro A. Active surveillance of low grade bladder tumors [J]. Arch Ital Urol Androl. 2008; 80(4): 132-5.
[16] Messing EM, Madeb R, Feng C. Grade and stage at presentation predict mortality in patients with bladder cancer who survive their diseases [J]. J Clin Oncol. 2009; 27(15): 2443-9.
[17] Chee KG, Cambio A, Lara PN Jr. Recent developments in advanced urothelial cancer [J]. Curr Opin Urol. 2005; 15(5): 342-9.
[18] Koss LG, Emerson RE. Clinical utility of immunohistochemistry in the diagnoses of urinary bladder neoplasia [J]. Appl Immunohistochem Mol Morphol. 2010; 18(5): 401-10.
[19] Lopez Beltran A. Bladder cancer: clinical and pathological profile [J]. Scand J Urol Nephrol Suppl. 2008; (218): 95-109.
[20] Amada T, Tsuchiya K, Kato S. A pretreatment nomogram predicting recurrence- and progression-free survival for nonmuscle invasive bladder cancer in Japanese patients[J]. Int J Clin Oncol. 2010; 15(3): 271-9.
[21] Deterry H. Management of non invasive bladder tumours (NMIBC) [J]. Bull Cancer. 2010; 97: 11-17.
[22]黄玉华,严春寅,浦金贤.膀胱癌合并上尿路上皮癌的诊断与外科治疗[J].山东医药, 2009, 49(22): 13-14.
[23] Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer[J]. Can Urol Assoc J. 2010; 4(1): 56-64
[24] Bowman J, Grossman HB, Dinney CP. The pharmacogenetic impact of inflammatory genes on bladder cancer recurrence [J]. Pharmacogenomics. 2005; 6(6): 575-84.
[25] Maffezzini M, Campodonico F, Capponi G. Prognostic significance of fluorescent insitu hybridisation in the follow-up of non-muscle-invasive bladder cancer[J]. Anticancer Res. 2010; 30(11): 4761-5.
[26] Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer [J]. Can Urol Assoc J. 2010; 4(1): 56-64.
[27] Rhijn BW, Burger M, Lotan Y. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy [J]. Eur Urol. 2009; 56(3): 430-42.
[28] Stein JP.The treatment of patients with bladder cancer: let's not forget the past! [J] J Urol. 2005; 174(3): 814-5.
[29] Smaldone MC, Gayed BA, Tomaszewski JJ. Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer [J]. Minerva Urol Nefrol. 2009; 61(2): 71-89.
[30]贡冰峰,严春寅,浦金贤.膀胱移行细胞癌组织中PCNA、MVD表达及意义[J].山东医药, 2007; 47(21): 48-49.
[31] Malats N, Bustos A, Nascimento CM. P53 as a prognostic marker for bladder cancer: a meta-analysis and review [J]. Lancet Oncol. 2005; 6(9): 678-86.
[32]贡冰峰,严春寅,浦金贤.膀胱移行细胞癌mp53、VEGF表达的相关性及临床意义[J].苏州大学学报(医学版)2007; 27(5): 750-753.
[33] De Berardinis E, Busetto GM, Antonini G. T1G3 high-risk NMIBC (non-muscle invasive bladder cancer): conservative treatment versus immediate cystectomy [J]. Int Urol Nephrol. 2010; 29: 101-105.
[34] Williams SK, Hoenig DM, Ghavamian R. Intravesical therapy for bladder cancer [J]. Expert Opin Pharmacother. 2010; 11(6): 947-958.
[35] Lebret T. Nonmuscle-invasive bladder cancer (NMIBC): when to perform cystectomy [J]. Prog Urol. 2008; 18: 111-114.
[36] Smaldone MC, Gayed BA, Tomaszewski JJ, Gingrich JR. Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer[J]. Urol. 2008; 15(2): 36-39.
[37] Chade DC, Shariat SF, Godoy G. Clinical outcomes of primary bladder carcinoma in situ in a contemporary series [J]. J Urol. 2010; 184(1): 74-80.
[1]黄玉华,严春寅,浦金贤.膀胱癌合并上尿路上皮癌的诊断与外科治疗.山东医药[J]. 2009; 49(22): 13-14.
[2] Pointreau Y, Klotz S. Bladder Cancer [J]. Cancer Radiother, 2010; 14: 89-97.
[3] Thompson DJ, Kramer HC. Late invasive recurrence despite long term surveillance for superficial bladder cancer [J]. J Urol. 2003, 149: 1010-1012.
[4] Calabro F, Sternberg CN. The evolving role of chemotherapy in advanced urothelial cancer [J]. Curr Opin Support Palliat Care. 2007; 1(3): 180-6.
[5] Bartoletti R, Cai T, Mondaini N. New therapeutics in the suppression of superficial bladder carcinoma [J]. Arch Ital Urol Androl. 2006; 78(4): 7-8.
[6] Nakagawa S, Kojima M, TakadaH, et al. Short duration bladder instillation therapy with pirarubicin for superficial bladder tumor based on pharmacodynamic study[J]. Gan To Kagaku Ryoho, 2004, 19(11): 1873-1877.
[7]姚剑.表阿霉素黏膜下浸润注射加单次灌注预防浅表性膀胱癌术后复发的研究[J].中华泌尿外科杂志. 2004; 10: 47-51.
[8] Hashimura T, Shirahase T, Inoue T. A randomized study of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection of superficial bladder cancer[J]. Hinyokika Kiyo. 2005; 51(7): 439-42.
[9]汪朔,余家琦,夏丹.表阿霉素单次膀胱灌注预防浅表性膀胱癌术后复发的前瞻性随机对照研究[J].中华泌尿外科杂志, 2003;15:135-141.
[10] Mitsumori K, Tsuchiya N, Habuchi T. Early and large-dose intravesical instillation of epirubicin to prevent super-ficial bladder carcinoma recurrence after transurethral resection[J] . BJUInt, 2004, 4 (3): 317-321.
[11] Agarwal PK, Black PC, Mcconkey DJ, et al. Emer-ging drugs for targeted herapy of bladder cancer[J] .Expert OpinEmerg Drugs, 2007, 12(3) :435-548 .
[12] Hendricksen K, Witjes WP, Idema JG. Comparison of three schedules of intravesical epirubicin in patients with non-muscle-invasive bladder cancer [J]. Eur Urol. 2008; 53(5): 984-91.
[13] Naito S, Koga H, Yamaguchi A. Prevention of recurrence with epirubicin and lactobacillus casei after transurethral resection of bladder cancer[J]. J Urol. 2008; 179(2): 485-90.
[14] Hendricksen K, Witjes JA. Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer [J]. Curr Opin Urol. 2007; 17(5): 352-357.
[15] Lamm DL, McGee WR, Hale K. Bladder cancer: current optimal intravesical treatment [J]. Urol Nurs. 2005; 25(5): 323-326.
[16] Hirano MC, Gayed BA, Tomaszewski JJ. Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer [J]. Minerva Urol Nefrol. 2009; 61(2): 71-89.
[17] Herr HW. Perioperative intravesical therapy: effective treatment, unfulfilled promises [J]. Eur Urol. 2009; 55(4): 781-782.
[18] Cai T, Nesi G, Tinacci G. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study [J]. J Urol. 2008; 180(1): 110-5.
[19] Mitsumori K, Tsuchiya N, Habuchi T. Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection[J]. BJU Int. 2004; 94(3): 317-21.
[20] Oddens JR, Van der Meijden AP. One immediate postoperative instillation of chemotherapy in low risk Ta, T1 bladder cancer patients. Is it always safe [J]. Eur Urol. 2007; 46(3): 336-8.
[21]徐涛,王晓峰.上尿路移行细胞癌术后发生膀胱癌的危险因素分析[J].中华泌尿外科杂志. 2004; 12: 103-108.
[22] Slam MA, Bhuiyan ZH, Shameem IA. Intravesical adjuvant therapy using mitomycinC [J]. Mymensingh Med J. 2006; 15(1): 40-4.
[23] Trinchieri A, Bonacina P, Butti A. Conservative treatment of high grade superficial bladder tumours [J]. Arch Ital Urol Androl. 2005; 77(4): 215-8.
[24] Kerigh BF, Bahrami A, Shamsa A. Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin[J]. Urol Ann. 2010; 2(3): 91-95.
[25] Jaiswal F, Tschirdewahn S, Rubben H. Non-muscle-invasive transitional cell carcinoma. Is BCG still a necessary part of treatment? Urology [J]. 2010; 49(10): 1274-1276.
[26] Mostafid H. Editorial comment to Maintenance intravesical bacillus Calmette-Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: randomized controlled trial by the BCG Tokyo Strain Study Group [J]. Int J Urol. 2010; 17(9): 766-767.
[27] Patard AB, Nicholson S, Patel PM. Recent advances in bacillus Calmette-Guerin immunotherapy in bladder cancer[J]. Immunotherapy. 2010; 2(4): 551-60.
[28] Kresowik TP, Griffith TS. Bacillus Calmette-Guerin immunotherapy for urothelial carcinoma of the bladder [J]. Immunotherapy. 2009; 1(2): 281-8..
[29] Chade DC, Shariat SF, Dalbagni G. Intravesical therapy for urothelial carcinoma of the urinary bladder: a critical review [J]. Int Braz J Urol. 2009; 35(6): 640-650
[30] Fiorz P, Bohle A, Malmstrom PU. The role of bacillus Calmette-Guérin in the treatment of non-muscle-invasive bladder cancer [J]. Eur Urol. 2010; 57(3): 410-29
[31] Wallerand H. Intravesical chemotherapy and bladder cancer Prog Urol[J]. 2009; 19(12): 868-71.
[32] Nativ O, Witjes JA, Hendricksen K. Combined thermo-chemotherapy for recurrent bladder cancer after bacillus Calmette-Guerin [J]. J Urol. 2009; 182(4): 1313-1317.
[33] Lamm C, Brown ET, Zaslau S. Use of Bacillus Calmette-Guerin in superficial bladder cancer: a review [J]. W V Med J. 2007; 105(3):17-9.
[34]闫鸣,陈晓,郑志学.卡介苗与羟基喜树碱膀胱灌注预防肿瘤复发Meta分析比较[J].现代泌尿外科杂志, 2008; 6: 98-104.
[35] Esuvaranathan K, Chiong E, Thamboo TP. Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha. Cancer [J]. Mar 15; 109(6):1095-1099..
[36] Giannopoulos A, Constantinides C, Fokaeas E. The immunomodulating effect of interferon-gamma intravesical instillations in preventing bladder cancer recurrence [J]. Clin Cancer Res. 2003; 9(15):5550-5558.
[37] Nicolas MM, Gschwend JE, Retz M. Update on chemotherapy for bladder cancer [J]. Update 2010. Urologe A. 2010; 49(10):1294-300.
[38] Lamm DL, Muller SC. Current and new strategies in immunotherapy for superficial bladder cancer [J]. Urology. 2004; 64(3): 409-21.
[39] Morales A, Chin JL, Ramsey EW. Mycobacterial cell wall extract for treatment of carcinoma in situ of the bladder [J]. J Urol. 2001; 166(5): 1633-1637;
[40] Dietrich HM, Blumenten BA, Crissan JD. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group study [J]. J Urol.2000; 6: 1123-1126.
[41] Sarosdy W, Kamat AM. Current state of immunotherapy for bladder cancer [J]. Expert Rev Anticancer Ther. 2004; 4(6):1037-1046.
[42] Lammers RJ, Witjes JA. Developments in intravesical therapy for non-muscle-invasive bladder cancer [J]. Expert Rev Anticancer Ther. 2010; 10(12): 1903-16.
[43] Sexton WJ, Wiegand LR, Correa JJ. Bladder cancer: a review of non-muscle invasive disease [J]. Cancer Control. 2010; 17(4): 256-68.
[44]樊晓栋,姜庆,王家武.新辅助化疗对肌层浸润性膀胱癌预后影响的Meta分析[J].第三军医大学学报, 2010; 2: 131-135.
[45] Uchio JJ, Streeter E, Jones A. Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma [J]. Br J Cancer. 2005;20(12):2140-7.
[46] Gontero P, Cattel L, Paone TC. Pharmacokinetic study to optimize the intravesical administration of gemcitabine [J]. BJU Int. 2010; 106(11):1652-1656.
[2]那彦群,孙光.中国泌尿外科疾病诊断治疗指南.人民卫生出版社. 2009: 16-18.
[3] Epstein JI, Amin MB, Reuter VR, et al. The World Health Organization/ International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. AmJsurg Pathol, 1998; 22: 1435-1488.
[4] Sobin DH and Witteking. TNM Classification of Malignant tumors. 6th edition. Wiley-Liss: New York, 2002. 199-202.
[5]李建国,浦金贤.经尿道等离子体双极电切术治疗浅表膀胱肿瘤25例报告[J].苏州大学学报(医学版). 2007; 27(6): 931-932.
[6]曾福华,杨土保,江勃年.原发浅表性膀胱癌预后影响因素分析[J].中华泌尿外科学杂志[J], 2004; 10: 171-175.
[7]申文江,郭应禄.膀胱癌的辅助治疗[J].临床肿瘤学杂志, 2003; 3(4): 104-105.
[8] Kanaroglou A, Shayegan B. Management of the urethra in urothelial bladder cancer [J]. Can Urol Assoc J. 2009; 3(6): 211-214.
[9] Sexton WJ, Wiegand LR, Correa JJ. Bladder cancer: a review of non-muscle invasive disease [J]. Cancer Control. 2010 Oct; 17(4): 256-268.
[10]董胜国,纪祥瑞,侯四川.影响膀胱癌患者长期生存的因素分析[J].临床泌尿外科杂志,1999; 14(6): 256-259.
[11]孔良,叶敏.经尿道电汽化术治疗浅表性膀胱癌[J].中华泌尿外科杂志. 2001; 34(3): 326-328.
[12] Bryan RT, Collins SI, Daykin MC. Mechanisms of recurrence of Ta/T1 bladder cancer [J]. Ann R Coll Surg Engl. 2010; 92(6): 519-524.
[13] Kohjimoto Y, Iba A, Shintani Y. Impact of patient age on outcome followingbladder-preserving treatment for non-muscle-invasive bladder cancer [J]. World J Urol. 2010; 28(4): 425-30.
[14] Bryan RT, Collins SI, Daykin MC. Mechanisms of recurrence of Ta/T1 bladder cancer [J]. Ann R Coll Surg Engl. 2010; 92(6): 519-24.
[15] Gofrit ON, Shapiro A. Active surveillance of low grade bladder tumors [J]. Arch Ital Urol Androl. 2008; 80(4): 132-5.
[16] Messing EM, Madeb R, Feng C. Grade and stage at presentation predict mortality in patients with bladder cancer who survive their diseases [J]. J Clin Oncol. 2009; 27(15): 2443-9.
[17] Chee KG, Cambio A, Lara PN Jr. Recent developments in advanced urothelial cancer [J]. Curr Opin Urol. 2005; 15(5): 342-9.
[18] Koss LG, Emerson RE. Clinical utility of immunohistochemistry in the diagnoses of urinary bladder neoplasia [J]. Appl Immunohistochem Mol Morphol. 2010; 18(5): 401-10.
[19] Lopez Beltran A. Bladder cancer: clinical and pathological profile [J]. Scand J Urol Nephrol Suppl. 2008; (218): 95-109.
[20] Amada T, Tsuchiya K, Kato S. A pretreatment nomogram predicting recurrence- and progression-free survival for nonmuscle invasive bladder cancer in Japanese patients[J]. Int J Clin Oncol. 2010; 15(3): 271-9.
[21] Deterry H. Management of non invasive bladder tumours (NMIBC) [J]. Bull Cancer. 2010; 97: 11-17.
[22]黄玉华,严春寅,浦金贤.膀胱癌合并上尿路上皮癌的诊断与外科治疗[J].山东医药, 2009, 49(22): 13-14.
[23] Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer[J]. Can Urol Assoc J. 2010; 4(1): 56-64
[24] Bowman J, Grossman HB, Dinney CP. The pharmacogenetic impact of inflammatory genes on bladder cancer recurrence [J]. Pharmacogenomics. 2005; 6(6): 575-84.
[25] Maffezzini M, Campodonico F, Capponi G. Prognostic significance of fluorescent insitu hybridisation in the follow-up of non-muscle-invasive bladder cancer[J]. Anticancer Res. 2010; 30(11): 4761-5.
[26] Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer [J]. Can Urol Assoc J. 2010; 4(1): 56-64.
[27] Rhijn BW, Burger M, Lotan Y. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy [J]. Eur Urol. 2009; 56(3): 430-42.
[28] Stein JP.The treatment of patients with bladder cancer: let's not forget the past! [J] J Urol. 2005; 174(3): 814-5.
[29] Smaldone MC, Gayed BA, Tomaszewski JJ. Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer [J]. Minerva Urol Nefrol. 2009; 61(2): 71-89.
[30]贡冰峰,严春寅,浦金贤.膀胱移行细胞癌组织中PCNA、MVD表达及意义[J].山东医药, 2007; 47(21): 48-49.
[31] Malats N, Bustos A, Nascimento CM. P53 as a prognostic marker for bladder cancer: a meta-analysis and review [J]. Lancet Oncol. 2005; 6(9): 678-86.
[32]贡冰峰,严春寅,浦金贤.膀胱移行细胞癌mp53、VEGF表达的相关性及临床意义[J].苏州大学学报(医学版)2007; 27(5): 750-753.
[33] De Berardinis E, Busetto GM, Antonini G. T1G3 high-risk NMIBC (non-muscle invasive bladder cancer): conservative treatment versus immediate cystectomy [J]. Int Urol Nephrol. 2010; 29: 101-105.
[34] Williams SK, Hoenig DM, Ghavamian R. Intravesical therapy for bladder cancer [J]. Expert Opin Pharmacother. 2010; 11(6): 947-958.
[35] Lebret T. Nonmuscle-invasive bladder cancer (NMIBC): when to perform cystectomy [J]. Prog Urol. 2008; 18: 111-114.
[36] Smaldone MC, Gayed BA, Tomaszewski JJ, Gingrich JR. Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer[J]. Urol. 2008; 15(2): 36-39.
[37] Chade DC, Shariat SF, Godoy G. Clinical outcomes of primary bladder carcinoma in situ in a contemporary series [J]. J Urol. 2010; 184(1): 74-80.
[1]黄玉华,严春寅,浦金贤.膀胱癌合并上尿路上皮癌的诊断与外科治疗.山东医药[J]. 2009; 49(22): 13-14.
[2] Pointreau Y, Klotz S. Bladder Cancer [J]. Cancer Radiother, 2010; 14: 89-97.
[3] Thompson DJ, Kramer HC. Late invasive recurrence despite long term surveillance for superficial bladder cancer [J]. J Urol. 2003, 149: 1010-1012.
[4] Calabro F, Sternberg CN. The evolving role of chemotherapy in advanced urothelial cancer [J]. Curr Opin Support Palliat Care. 2007; 1(3): 180-6.
[5] Bartoletti R, Cai T, Mondaini N. New therapeutics in the suppression of superficial bladder carcinoma [J]. Arch Ital Urol Androl. 2006; 78(4): 7-8.
[6] Nakagawa S, Kojima M, TakadaH, et al. Short duration bladder instillation therapy with pirarubicin for superficial bladder tumor based on pharmacodynamic study[J]. Gan To Kagaku Ryoho, 2004, 19(11): 1873-1877.
[7]姚剑.表阿霉素黏膜下浸润注射加单次灌注预防浅表性膀胱癌术后复发的研究[J].中华泌尿外科杂志. 2004; 10: 47-51.
[8] Hashimura T, Shirahase T, Inoue T. A randomized study of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection of superficial bladder cancer[J]. Hinyokika Kiyo. 2005; 51(7): 439-42.
[9]汪朔,余家琦,夏丹.表阿霉素单次膀胱灌注预防浅表性膀胱癌术后复发的前瞻性随机对照研究[J].中华泌尿外科杂志, 2003;15:135-141.
[10] Mitsumori K, Tsuchiya N, Habuchi T. Early and large-dose intravesical instillation of epirubicin to prevent super-ficial bladder carcinoma recurrence after transurethral resection[J] . BJUInt, 2004, 4 (3): 317-321.
[11] Agarwal PK, Black PC, Mcconkey DJ, et al. Emer-ging drugs for targeted herapy of bladder cancer[J] .Expert OpinEmerg Drugs, 2007, 12(3) :435-548 .
[12] Hendricksen K, Witjes WP, Idema JG. Comparison of three schedules of intravesical epirubicin in patients with non-muscle-invasive bladder cancer [J]. Eur Urol. 2008; 53(5): 984-91.
[13] Naito S, Koga H, Yamaguchi A. Prevention of recurrence with epirubicin and lactobacillus casei after transurethral resection of bladder cancer[J]. J Urol. 2008; 179(2): 485-90.
[14] Hendricksen K, Witjes JA. Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer [J]. Curr Opin Urol. 2007; 17(5): 352-357.
[15] Lamm DL, McGee WR, Hale K. Bladder cancer: current optimal intravesical treatment [J]. Urol Nurs. 2005; 25(5): 323-326.
[16] Hirano MC, Gayed BA, Tomaszewski JJ. Strategies to enhance the efficacy of intravescical therapy for non-muscle invasive bladder cancer [J]. Minerva Urol Nefrol. 2009; 61(2): 71-89.
[17] Herr HW. Perioperative intravesical therapy: effective treatment, unfulfilled promises [J]. Eur Urol. 2009; 55(4): 781-782.
[18] Cai T, Nesi G, Tinacci G. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study [J]. J Urol. 2008; 180(1): 110-5.
[19] Mitsumori K, Tsuchiya N, Habuchi T. Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection[J]. BJU Int. 2004; 94(3): 317-21.
[20] Oddens JR, Van der Meijden AP. One immediate postoperative instillation of chemotherapy in low risk Ta, T1 bladder cancer patients. Is it always safe [J]. Eur Urol. 2007; 46(3): 336-8.
[21]徐涛,王晓峰.上尿路移行细胞癌术后发生膀胱癌的危险因素分析[J].中华泌尿外科杂志. 2004; 12: 103-108.
[22] Slam MA, Bhuiyan ZH, Shameem IA. Intravesical adjuvant therapy using mitomycinC [J]. Mymensingh Med J. 2006; 15(1): 40-4.
[23] Trinchieri A, Bonacina P, Butti A. Conservative treatment of high grade superficial bladder tumours [J]. Arch Ital Urol Androl. 2005; 77(4): 215-8.
[24] Kerigh BF, Bahrami A, Shamsa A. Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin[J]. Urol Ann. 2010; 2(3): 91-95.
[25] Jaiswal F, Tschirdewahn S, Rubben H. Non-muscle-invasive transitional cell carcinoma. Is BCG still a necessary part of treatment? Urology [J]. 2010; 49(10): 1274-1276.
[26] Mostafid H. Editorial comment to Maintenance intravesical bacillus Calmette-Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: randomized controlled trial by the BCG Tokyo Strain Study Group [J]. Int J Urol. 2010; 17(9): 766-767.
[27] Patard AB, Nicholson S, Patel PM. Recent advances in bacillus Calmette-Guerin immunotherapy in bladder cancer[J]. Immunotherapy. 2010; 2(4): 551-60.
[28] Kresowik TP, Griffith TS. Bacillus Calmette-Guerin immunotherapy for urothelial carcinoma of the bladder [J]. Immunotherapy. 2009; 1(2): 281-8..
[29] Chade DC, Shariat SF, Dalbagni G. Intravesical therapy for urothelial carcinoma of the urinary bladder: a critical review [J]. Int Braz J Urol. 2009; 35(6): 640-650
[30] Fiorz P, Bohle A, Malmstrom PU. The role of bacillus Calmette-Guérin in the treatment of non-muscle-invasive bladder cancer [J]. Eur Urol. 2010; 57(3): 410-29
[31] Wallerand H. Intravesical chemotherapy and bladder cancer Prog Urol[J]. 2009; 19(12): 868-71.
[32] Nativ O, Witjes JA, Hendricksen K. Combined thermo-chemotherapy for recurrent bladder cancer after bacillus Calmette-Guerin [J]. J Urol. 2009; 182(4): 1313-1317.
[33] Lamm C, Brown ET, Zaslau S. Use of Bacillus Calmette-Guerin in superficial bladder cancer: a review [J]. W V Med J. 2007; 105(3):17-9.
[34]闫鸣,陈晓,郑志学.卡介苗与羟基喜树碱膀胱灌注预防肿瘤复发Meta分析比较[J].现代泌尿外科杂志, 2008; 6: 98-104.
[35] Esuvaranathan K, Chiong E, Thamboo TP. Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha. Cancer [J]. Mar 15; 109(6):1095-1099..
[36] Giannopoulos A, Constantinides C, Fokaeas E. The immunomodulating effect of interferon-gamma intravesical instillations in preventing bladder cancer recurrence [J]. Clin Cancer Res. 2003; 9(15):5550-5558.
[37] Nicolas MM, Gschwend JE, Retz M. Update on chemotherapy for bladder cancer [J]. Update 2010. Urologe A. 2010; 49(10):1294-300.
[38] Lamm DL, Muller SC. Current and new strategies in immunotherapy for superficial bladder cancer [J]. Urology. 2004; 64(3): 409-21.
[39] Morales A, Chin JL, Ramsey EW. Mycobacterial cell wall extract for treatment of carcinoma in situ of the bladder [J]. J Urol. 2001; 166(5): 1633-1637;
[40] Dietrich HM, Blumenten BA, Crissan JD. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group study [J]. J Urol.2000; 6: 1123-1126.
[41] Sarosdy W, Kamat AM. Current state of immunotherapy for bladder cancer [J]. Expert Rev Anticancer Ther. 2004; 4(6):1037-1046.
[42] Lammers RJ, Witjes JA. Developments in intravesical therapy for non-muscle-invasive bladder cancer [J]. Expert Rev Anticancer Ther. 2010; 10(12): 1903-16.
[43] Sexton WJ, Wiegand LR, Correa JJ. Bladder cancer: a review of non-muscle invasive disease [J]. Cancer Control. 2010; 17(4): 256-68.
[44]樊晓栋,姜庆,王家武.新辅助化疗对肌层浸润性膀胱癌预后影响的Meta分析[J].第三军医大学学报, 2010; 2: 131-135.
[45] Uchio JJ, Streeter E, Jones A. Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma [J]. Br J Cancer. 2005;20(12):2140-7.
[46] Gontero P, Cattel L, Paone TC. Pharmacokinetic study to optimize the intravesical administration of gemcitabine [J]. BJU Int. 2010; 106(11):1652-1656.