Intravesical Bacillus Calmette-Guérin Treatment Is Inversely Associated With the Risk of Developing Alzheimer Disease or Other Dementia Among Patients With Non–muscle-invasive Bladder Cancer

BackgroundThe immune system plays an important role in the pathogenesis of Alzheimer disease (AD), but it remains unclear whether bacillus Calmette-Guérin (BCG) may affect the risk of AD or not.MethodsUsing retrospective chart review, we collected data regarding demographics, comorbidities, cancer diagnosis, BCG treatment, and subsequent diagnosis of AD or other dementia in a racially/ethnically diverse cohort of patients with non–muscle-invasive bladder cancer (NIMBC) receiving treatment between 1984 and 2020 in the Bronx, New York. We used Cox proportional hazard models to examine association between BCG treatment and risk of incident AD or other dementia, adjusting for age, gender, race/ethnicity, and major comorbidities.ResultsIn our cohort of 1290 patients with NMIBC, a total of 99 (7.7%) patients developed AD or other dementia during follow-up. Patients who received BCG treatment (25%) had a 60% lowered incidence of AD or other dementia (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.80) in comparison to those who did not receive BCG. There was also suggestive evidence that the reduction in risk of AD or other dementia associated with BCG treatment was stronger in men (adjusted HR, 0.34; 95% CI, 0.15-0.81) but not in women (adjusted HR, 0.75; 95% CI 0.25-2.24). When we stratified the patients who received BCG by type of treatments, patients who received both induction and maintenance rounds of BCG had a further lowered incidence of AD or other dementia (HR, 0.23; 95% CI, 0.06-0.96) than patients who did not receive BCG.ConclusionsTo our knowledge, our study is one of the first to suggest that BCG treatment is associated with a reduced risk of developing AD or other dementia in a multiethnic population, independent of significant comorbidities. Larger cohort studies are needed to corroborate our findings.     

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     

BT—BAK细胞和BCG膀胱腔内过继免疫治疗对膀胱癌患者全身免疫功能影响的比较

目的：观察BT-BAK细胞与BCG膀胱腔内灌注治疗对患者全身免疫功能的影响。方法：由手术切除的膀胱瘤标本制备膀胱肿瘤可溶性抗原,以BCG为佐剂,从PBMNC中诱导出抗膀胱肿瘤特异性细胞毒性BT-BAK细胞,临床选择72例浅表性膀胱癌术后患者随机平均分成2组分别进行BT-BAK和BCG的膀胱腔内灌注治疗。于不同阶段采用ELISA法测定患者外周血中IL-2、TNF-α及IFN-γ的含量;观察治疗后患者PBMNC对T24膀胱肿瘤细胞株杀伤活性的变化。结果：BT-BAK组患者血清中IL-2、TNF-α及IFN-γ的水平均较治疗前明显提高（P＜0.01);患者PBMNC对T24膀胱肿瘤细胞株的杀伤活性显著增强（P＜0.01)。BT-BAK组上述指标均高于BCG组（P＜0.05)。平均随访18.16个月,两组的复发率分别为2.7%和11.11%。结论：BT-BAK细胞及其培养上清进行膀胱腔内灌注治疗,能够有效提高膀胱癌术后患者的全身免疫水平,降低膀胱癌的术后复发率。     

Immunolocalization of transitional cell carcinoma of the bladder with intravesically administered technetium-99m labelled HMFG1 monoclonal antibody

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3–6 mCi (111–222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with singlephoton emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12–20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFGI monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using^99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%–9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of^99mTc-HMFGI monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.     

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。     

The best management of superficial bladder tumours: Comparing TUR alone versus TUR combined with intravesical chemotherapy modalities?

To compare retrospectively the recurrence rates of TUR alone versus different intravesical chemotherapy modalities in superficial bladder cancer cases, 187 patients with stage Ta and T₁ bladder tumours were treated with transurethral resection followed by adjuvant intravesical chemotherapy with mitomycin, BCG or epirubicin or by transurethral resection alone. All patients in this study had historically proven transurethrally resectable primary, category Ta and T₁ transitional cell carcinoma (TCC) of the bladder. Group I included transurethral resection alone, and the other groups included intravesical mitomycin-C(Group II), BCG (Group III) and epirubicin (Group IV) therapies after transurethral resection. 146 male and 41 female patients (78% male and 22% female patients) in this study were diagnosed as primary TCC bladder tumours. Only 52 of them were stage Ta and 135 of them were stage T₁ bladder tumours. Examining the histological grade of the bladder tumours, 88 (47%) of the patients had grade I, 53 (28%) had grade IIa, 30 (16%) had grade IIb and remaining 16 (9%) had grade III bladder cancers. The recurrence rates were 25% for Group I, 23.8% for Group II, 26.2% for Group III and 22.7% for Group IV. These values were given with disregarding the grade and volume of the bladder tumours. For solitary, less than 3 cm low grade tumours (grade I, IIa) recurrence rates were 16% for Group I, 15.4% for Group II, 17.8% for Group III, 17.2% for Group IV (p> 0.05). As a result of this retrospective study, for patients with low grade, stage Ta and T₁ tumours TUR alone may be the best treatment modality. Although intravesical chemotherapy is effective in decreasing short-term incidences of tumour recurrence, it has not decreased long-term incidences of tumour recurrence. The high cost and adverse side effects of intravesical chemotherapy should also be taken into consideration in superficial, single, low grade tumours of bladder. This revised version was published online in August 2006 with corrections to the Cover Date.     

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。