Apostolidis Apostolos, Jacques Thomas S, Freeman Alex, Kalsi Vinay, Popat Roshni, Gonzales Gwendoline, Datta Soumendra N, Ghazi-Noori Shabnam, Elneil Sohier, Dasgupta Prokar, Fowler Clare J
Institute of Neurology, UCL, London, United Kingdom.
Eur Urol. 2008 Jun;53(6):1245-53. doi: 10.1016/j.eururo.2008.02.037. Epub 2008 Mar 7.
We examined, for the first time in a prospective study, the histological changes in the urothelium and suburothelium of patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat treatments with intradetrusor BoNTA.
Flexible cystoscopic bladder biopsies were obtained from patients with urodynamically proven intractable spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis, hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical comparisons were significant at p values less than 0.05.
Signs of chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs. 50% of IDO, p=0.049), 67.6% of post-first biopsies and 86.4% after repeat injections. The two groups were comparable for degree of baseline inflammation, which did not change significantly after first injection and up to 16 wk after a third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally before and after treatment, but not after repeat injections. No dysplasia or hyperplasia was identified. Eosinophils were identified more frequently in biopsies taken after repeat injections compared with the post-first injection and baseline biopsies (chi2=8.23, p=0.018). No difference existed between NDO and IDO bladders.
BoNTA injections do not appear to be producing significant inflammatory changes, fibrosis, or dysplastic changes in human bladder urothelium/suburothelium after a single injection and in a limited number of repeat treatment biopsies. The presence of eosinophils might be treatment-related, because they were mostly found in post-treatment biopsies.
在一项前瞻性研究中,我们首次检查了神经源性(NDO)或特发性逼尿肌过度活动症(IDO)患者在接受一次或重复膀胱内注射肉毒杆菌毒素A(BoNTA)治疗后膀胱上皮和上皮下组织的组织学变化。
对经尿动力学证实为顽固性脊髓性NDO或IDO的患者,在膀胱内注射保妥适1(NDO 300 U,IDO 200 U)一次或重复治疗前、治疗后4周和16周,通过软性膀胱镜获取膀胱活检组织。标本进行苏木精-伊红染色,并对膀胱上皮和上皮下组织的炎症变化、纤维化、增生和发育异常进行盲法分析。p值小于0.05时,统计比较具有显著性。
59.1%的基线活检组织发现慢性炎症迹象(NDO为65.6%,IDO为50%,p = 0.049),首次活检后为67.6%,重复注射后为86.4%。两组基线炎症程度相当,首次注射后及第三次注射后长达16周炎症程度无显著变化。在所检查的活检组织中,2.2%发现轻度纤维化,治疗前后相同,但重复注射后未发现。未发现发育异常或增生。与首次注射后及基线活检组织相比,重复注射后活检组织中嗜酸性粒细胞更常见(χ2 = 8.23,p = 0.018)。NDO和IDO膀胱之间无差异。
单次注射及有限次数的重复治疗活检后,BoNTA注射似乎不会在人膀胱上皮/上皮下组织中产生显著的炎症变化、纤维化或发育异常变化。嗜酸性粒细胞的存在可能与治疗有关,因为它们大多在治疗后的活检组织中发现。