Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

腺性膀胱炎三种治疗方法治疗效果的随访观察

目的　比较腺性膀胱炎三种治疗方法的效果。方法　 86例腺性膀胱炎患者分别行膀胱药物灌注、经尿道电切、经尿道电切加膀胱药物灌注治疗。随访观察症状缓解程度和膀胱镜病检结果 1年。结果　 73例完成了随访调查 ,占 84.9%。三种方法治疗后症状缓解程度 ,差异无显著性意义 (P >0 .0 5 ) ;膀胱镜病检复查 ,灌注治疗效果好于电切治疗效果 ,综合治疗效果好于电切治疗效果 ,差异具有显著性意义 ;比较灌注治疗后膀胱镜病检阴性例数 ( 2 2 /2 8)与综合治疗后膀胱镜病检阴性例数 ( 3 0 /3 4) ,差异无显著性意义 ( χ2 =1.0 60 ,P =0 .3 0 3 )。结论　膀胱药物灌注和经尿道电切加膀胱药物灌注的膀胱镜病检复查 ,效果好于电切治疗的效果。     

BDI-1-MT治疗膀胱癌及预防其术后复发的临床观察

目的　通过临床应用膀胱腔内灌注抗人膀胱癌免疫毒素 (BDI- 1-MT) ,观察治疗膀胱癌和预防膀胱癌术后复发的效果及毒副反应。方法　对 18例术后和 5例未手术的膀胱癌病人 ,膀胱腔内灌注BDI- 1-MT 1个疗程以上 ,观察疗效、复发情况及毒副反应。结果　术后 18例随访 6～ 2 0个月未见复发 ,未手术 5例随访 6～ 2 1个月 ,其中 3例显效 ,2例有效。所有病例均无明显毒副反应。结论　膀胱腔内灌注BDI- 1-MT治疗膀胱癌和预防膀胱癌术后复发有良好效果 ,是一种值得推广的新方法。     

支气管动脉灌注化疗联合直线加速器放射治疗Ⅲa期非小细胞肺癌

目的　研究支气管动脉灌注化疗联合直线加速器放射治疗Ⅲa期非小细胞肺癌 (NSCLC)的可行性及临床价值。方法　 76例NSCLC患者随机分成A、B 2组 ,A组先行 2次支气管动脉灌注化疗 (BAI) ,第 2次BAI 1～ 2周后再行直线加速器放射治疗 (RT) ;B组单纯行 2次BAI (对照组 )。结果　临床疗效 ,A组 (BAI RT)和B组 (BAI)分别为 89.47%和 60 .5 3% (Ρ <0 .0 1) ;1、3年生存率 ,A、B组分别为 81.5 8%、5 0 .0 0 %和 60 .5 3%、2 1.0 5 % ( 0 .0 1<Ρ <0 .0 5 )。结论　支气管动脉灌注化疗联合直线加速器放射治疗Ⅲa期非小细胞肺癌的临床疗效和患者 1、3年生存率均显著提高     

IL-2联合吡柔比星膀胱灌注预防膀胱癌复发

目的：探讨生物制剂联合化疗药物膀胱灌注预防膀胱癌术后复发的机制。方法：对比研究白细胞介素2（IL－2）和吡柔比星联合膀胱灌注与单用吡柔比星膀胱灌注前后患者血、尿肿瘤坏死因子（TNF）和血IL－2受体的动态变化。结果：联合膀胱灌注组的TNF和IL－2受体水平显著高于吡柔比星组（P＜0．01）。结论：联合灌注组机体的细胞免疫功能得到更好改善,IL－2增加肿瘤细胞对免疫反应的应答,两者间有免疫促进及协同作用。     

噻哌腔内灌注预防膀胱癌术后复发41例疗效观察

目的：预防膀胱癌术后复发。方法：对４１例表浅性膀胱肿瘤行膀胱部分切除或肿瘤切除等局限性手术后,用噻口替哌膀胱腔内灌注。结果：４１例均获随访,平均随访时间５年,复发率１４６％（６／４１）。结论：此法是一种较为有效的预防膀胱癌复发的治疗措施。     

吡柔比星膀胱灌注预防浅表性膀胱肿瘤术后复发的初步临床观察

目的：探讨吡柔比星膀胱灌注对浅表性膀胱肿瘤术后复发的预防效果和毒副作用。方法：选择浅表性膀胱肿瘤患者，在行经尿道电切或行膀胱部分切除术后定期经导尿管给予膀胱内灌注吡柔比星30mg／40mL，每周1次，每次膀胱内保留30min--40min，共8次。术后3月进行1次膀胱镜检，如无复发，则进行第2个疗程的吡柔比星膀胱内灌注，方法同第1个疗程。如发现复发，立即安排进行手术。结果：46例共完成90个疗程的预防灌注。随访4月--27月，平均12．1月。共有5例复发。18例患者有尿频、尿急和膀胱区疼痛不适，程度较重者6例，但均可耐受继续灌注。结论：吡柔比星膀胱内灌注预防肿瘤术后复发具有较显著的疗效。吡柔比星的副作用主要表现在局部反应，未发现全身性毒性反应。     

羟基喜树碱灌注预防膀胱癌术后复发的疗效观察

目的 观察羟基喜树碱灌注预防膀胱癌术后复发的疗效。方法 术后3年内用羟基喜树碱15～20 mg定期行膀胱灌注。结果 189例患者随访2.4～5年,复发24例,3年内总复发率为12.7％。结论 羟基喜树碱膀胱灌注预防膀胱癌术后复发疗效显著,无明显副作用,对预防切口种植的作用尚待进一步探讨。     

Allergic rhinitis induced by intranasal sensitization and challenge with trimellitic anhydride but not with dinitrochlorobenzene or oxazolone in A/J mice.

Allergic airway diseases induced by low molecular weight (LMW) chemicals, including trimellitic anhydride (TMA), are characterized by airway mucus hypersecretion and an infiltration of eosinophils and lymphocytes. Many experimental models have linked LMW chemical-induced allergic airway disease to Th2 cytokines. Most murine models, however, use dermal exposure to sensitize mice. The present study was designed to test the hypothesis that intranasal sensitization and challenge with the known chemical respiratory allergen TMA, but not the nonrespiratory sensitizers dinitrochlorobenzene (DNCB) and oxazolone (OXA), will induce characteristic features of LMW chemical-induced allergic airway disease in the nasal and pulmonary airways. A/J mice were intranasally sensitized and challenged with TMA, DNCB, or OXA. Only mice that were intranasally sensitized and challenged with TMA had a marked allergic rhinitis with an influx of eosinophils, lymphocytes, and plasma cells, increased intraepithelial mucusubstances, and a regenerative hyperplasia. Cytokine mRNA levels in the nasal airway of TMA treated mice also revealed an increase in the mRNA levels of the Th2 cytokines IL-4, IL-5, and IL-13, but no change in the level of the Th1 cytokine IFN-gamma. No lesions were found in the nasal airways of mice exposed to DNCB or OXA. TMA increased lung-derived IL-5 mRNA while DNCB and OXA caused no change in lung-derived cytokine mRNA levels. Both TMA and DNCB caused increases in total serum IgE, unlike OXA-exposed mice. However, no adverse alterations were found microscopically in the lungs of mice treated with TMA, DNCB, or OXA. This study is the first to demonstrate that intranasal administration of a known chemical respiratory allergen is an effective method of sensitization resulting in the hallmark features of allergic rhinitis after challenge with a concomitant increase in nasal airway-derived Th2 cytokine mRNA, lung-derived IL-5 mRNA, and total serum IgE. In contrast, DNCB and OXA failed to elicit the pathologic changes in the nasal airways and cytokine changes in the lung. This model may be useful for identifying other chemical respiratory allergens.     

A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer

Purpose: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). Materials and methods: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80?mg in 50?mL) delivered with the novel Combat BRS® system at a temperature of 43?°C for 60?min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. Results: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. Conclusions: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy.