CAJ | 학술논문

目的观察二次TURBt联合膀胱灌注化疗及肿瘤细胞抗原负载的树突状细胞(DC)治疗非肌层浸润性膀胱癌的安全性及疗效. 方法 T1期膀胱尿路上皮癌患者80例.男59例,女21例.年龄30～ 85岁,平均65岁.入组患者均在第一次TURBt术后4～6周行二次TURBt,术后常规膀胱灌注化疗.分为2组:DC组40例,对照组40例.DC组自外周血分离出单核细胞,体外诱导分化为DC,加入该患者的肿瘤抗原共培养,获取负载肿瘤细胞抗原的DC；在二次TURBt术后6～8周将肿瘤细胞抗原负载的DC回输,每周1次,共4次,每次腹股沟皮下注射细胞数不低于1×106个,每疗程回输细胞总数＞4×106个.观察DC组免疫指标改变及不良反应,比较2组患者肿瘤复发比例.结果 80例患者第一次TURBt病理分级G117例(21.3％)、G254例(67.5％)、G39例(11.2％)；二次TURBt病理检查发现残存肿瘤27例,总阳性率33.7％；Ta期8例(29.6％)、T1期19例(70.4％)；G13例(11.1％)、G2 19例(70.4％)、G3 5例(18.5％).二次TURBt时Ta期8例中分级同第一次TURBt 6例,分级升高2例；T1期19例中分级同第一次TURBt 12例,分级升高5例,降级2例.单发16例,均位于原电切处；多发11例,其中原电切处可见菜花样肿瘤7例.DC回输治疗时出现寒战、发热5例,给予地塞米松10 mg静脉推注治疗后缓解.治疗前、治疗后1年及2年患者血中白细胞、SCr、ALT值比较差异无统计学意义(P＞0.05).与治疗前比较,治疗后1年及2年CD4、CD8、CD4/CD8等指标比较差异均有统计学意义(P＜0.05),而治疗后1年后及2年各指标比较差异无统计学意义.DC组1年内复发1例(2％),2年内复发3例(6％)；对照组中1年内复发6例(20％)；2年内复发9例(30％),2组复发率比较差异有统计学意义(P＜0.05). 结论二次TURBt联合膀胱灌注及肿瘤细胞抗原负载的DC回输治疗是降低非肌层浸润性膀胱癌复发率较有效的方法.
목적 관찰이차TURBt연합방광관주화료급종류세포항원부재적수돌상세포(DC)치료비기층침윤성방광암적안전성급료효. 방법 T1기방광뇨로상피암환자80례.남59례,녀21례.년령30～ 85세,평균65세.입조환자균재제일차TURBt술후4～6주행이차TURBt,술후상규방광관주화료.분위2조:DC조40례,대조조40례.DC조자외주혈분리출단핵세포,체외유도분화위DC,가입해환자적종류항원공배양,획취부재종류세포항원적DC；재이차TURBt술후6～8주장종류세포항원부재적DC회수,매주1차,공4차,매차복고구피하주사세포수불저우1×106개,매료정회수세포총수＞4×106개.관찰DC조면역지표개변급불량반응,비교2조환자종류복발비례.결과 80례환자제일차TURBt병리분급G117례(21.3％)、G254례(67.5％)、G39례(11.2％)；이차TURBt병리검사발현잔존종류27례,총양성솔33.7％；Ta기8례(29.6％)、T1기19례(70.4％)；G13례(11.1％)、G2 19례(70.4％)、G3 5례(18.5％).이차TURBt시Ta기8례중분급동제일차TURBt 6례,분급승고2례；T1기19례중분급동제일차TURBt 12례,분급승고5례,강급2례.단발16례,균위우원전절처；다발11례,기중원전절처가견채화양종류7례.DC회수치료시출현한전、발열5례,급여지새미송10 mg정맥추주치료후완해.치료전、치료후1년급2년환자혈중백세포、SCr、ALT치비교차이무통계학의의(P＞0.05).여치료전비교,치료후1년급2년CD4、CD8、CD4/CD8등지표비교차이균유통계학의의(P＜0.05),이치료후1년후급2년각지표비교차이무통계학의의.DC조1년내복발1례(2％),2년내복발3례(6％)；대조조중1년내복발6례(20％)；2년내복발9례(30％),2조복발솔비교차이유통계학의의(P＜0.05). 결론 이차TURBt연합방광관주급종류세포항원부재적DC회수치료시강저비기층침윤성방광암복발솔교유효적방법.
Objective To observe the clinical efficacy and safety of second transurethral resection combined with instillation therapy and transfusion therapy of dendritic cells pulsed with tumor cells on non muscle-invasive bladder cancer.Methods Eighty patients with stage T1 non muscle-invasive bladder cancer were included in this protocol in which all patients prospectively received second transurethral resection within 4 to 6 weeks following initial resection.All 80 cases were divided into a DC group and a control group.In the DC group,dendritic cells pulsed with tumor cells were transfused between 6 -8 weeks.Bladder instillation therapy and follow-up was applied on the control group.The recurrence rate,the clinical efficacy and adverse reactions were observed and compared between the two groups.Results In the initial resection,21.3％,67.5％ and 11.2％ had G1,G2 and G3 transitional cell carcinoma,respectively.Twenty-seven (33.7％) had residual tumors at the second TUR,8 patients had Ta(29.6％ ) and 19 had T1 (70.4％).After the initial TUR-Bt,residual tumors were detected in 11.1％,70.4％ and 18.5％ in G1,G2 and G3,respectively.In the 8 Ta cases,2 cases moved to a higher grade,while the grade was unchanged in 6 cases.In the 19 cases with stage T1,12 had a higher grade,5 had a lower grade and 2 remained the same.In the DC group,5 cases suffered chills and fever when dendritic cells were transfused.The fever was releaved when dexamethasone was administered.The white blood cells count,creatinine and alanine aminotransferase had no statistically significance change at pre-therapy,one year after therapy and two years after therapy (P ＞0.05).The index of CD4 、CD8 、CD4/CD8 had statistically significance change at pre-therapy,one year after therapy and two years after therapy ( P ＜ 0.05 ),while the difference between one year after therapy and two years after therapy was not statistically significance ( P ＞ 0.05 ).The first and second year recurrence rate was 2％ and 6％ in the DC group,while in the control group it was 20％ and 30％.The difference was statistically significant ( P ＜ 0.05 ).Conclusion Second transurethral resection combined with instillation therapy and transfusion therapy of dendritic cells pulsed with tumor cells could be an effective therapeutic approach to lower the recurrence rate on non muscle-invasive bladder cancer.