Joseph David B, Borer Joseph G, De Filippo Roger E, Hodges Steve J, McLorie Gordon A
University of Alabama at Birmingham, Birmingham, Alabama.
Boston Children's Hospital, Boston, Massachusetts.
J Urol. 2014 May;191(5):1389-95. doi: 10.1016/j.juro.2013.10.103. Epub 2013 Oct 29.
Augmentation cystoplasty using gastrointestinal segments in children/adolescents with medically refractory neurogenic bladder is associated with significant complications. We evaluated an autologous cell seeded biodegradable scaffold (Tengion®) for bladder augmentation as an alternative to traditional enterocystoplasty in this population.
A phase II prospective study was performed in children with neurogenic bladder due to spina bifida requiring enterocystoplasty for detrusor pressure 40 cm H2O or greater despite maximum antimuscarinic medication. Following open bladder biopsy, urothelial and smooth muscle cells were grown ex vivo and seeded onto a biodegradable scaffold to form a regenerative augment as the foundation for bladder tissue regeneration. Bladder neck sling was the only concomitant surgical procedure permitted. Bladders were cycled postoperatively to promote regeneration. Primary and secondary outcomes at 12 months included change in bladder compliance, bladder capacity and safety. Long-term assessment was done with similar outcomes at 36 months.
Compliance improved in 4 patients at 12 months and in 5 patients at 36 months, although the difference was not clinically or statistically significant. There was no clinical or statistical improvement in bladder capacity at 12 or 36 months in any patient. Adverse events occurred in all patients, and most were easily treated. Two patients had low cell growth following bladder biopsy, of whom 1 withdrew from the study and 1 underwent a second biopsy. Serious adverse events of bowel obstruction and/or bladder rupture occurred in 4 patients.
Our autologous cell seeded biodegradable scaffold did not improve bladder compliance or capacity, and our serious adverse events surpassed an acceptable safety standard.
在患有药物难治性神经源性膀胱的儿童/青少年中，使用胃肠道段进行膀胱扩大术会伴有严重并发症。我们评估了一种自体细胞接种的可生物降解支架（Tengion®）用于膀胱扩大术，作为该人群传统肠膀胱扩大术的替代方法。
对因脊柱裂导致神经源性膀胱且尽管使用了最大剂量抗毒蕈碱药物但逼尿肌压力仍达40 cm H2O或更高而需要进行肠膀胱扩大术的儿童进行了一项II期前瞻性研究。在进行开放性膀胱活检后，将尿路上皮细胞和平滑肌细胞在体外培养并接种到可生物降解支架上，形成再生扩大物作为膀胱组织再生的基础。膀胱颈悬吊术是唯一允许的同期手术。术后对膀胱进行循环以促进再生。12个月时的主要和次要结局包括膀胱顺应性、膀胱容量的变化及安全性。在36个月时进行了类似结局的长期评估。
12个月时4例患者的顺应性有所改善，36个月时5例患者顺应性改善，尽管差异在临床或统计学上均无显著性。在12个月或36个月时，任何患者的膀胱容量均无临床或统计学上的改善。所有患者均发生了不良事件，且大多数易于治疗。2例患者在膀胱活检后细胞生长不良，其中1例退出研究，1例接受了第二次活检。4例患者发生了肠梗阻和/或膀胱破裂的严重不良事件。
我们的自体细胞接种可生物降解支架未改善膀胱顺应性或容量，且我们的严重不良事件超过了可接受的安全标准。
