Abstract：
OBJECTIVE: We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP).
METHODS: Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson\'s trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity.
RESULTS: Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively).
CONCLUSIONS: Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.
METHODS: Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson\'s trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity.
RESULTS: Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively).
CONCLUSIONS: Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.
摘要：
目的：我们研究了炎性细胞浸润（ICI）纤维化，神经源性膀胱尿路上皮的线粒体活力参与乙状结肠上皮细胞成形术（SCP）后持续性膀胱输尿管反流（VUR）的机制。
方法：1994-2023年从62例神经源性膀胱患者中获得的膀胱活检通过苏木精和伊红检查ICI，Masson三色检查纤维化，和免疫荧光的尿路上皮生长分化因子15（GDF15；线粒体应激反应细胞因子）（阳性/阴性）和热休克蛋白60（HSP60；线粒体基质标记）（强≥50％/弱≤50％）表达。GDF15+/弱HSP60表明线粒体活力受损。膀胱测压测量新膀胱顺应性/容量。
结果：SCP和膀胱活检的平均年龄分别为9.4±4.6和14.2±7.1。VUR出现在SCP的38/62名患者（51个输尿管）中，并在4/38名患者中单独使用SCP解决，在17/38中使用SCP和输尿管膀胱造口术，并在17/38中持续存在。与GDF15-（n=38）/强HSP60（n=31）相比，GDF15（n=24）/弱HSP60（n=31）的纤维化明显更密集（分别为p<0.001和p<0.01）。ICI的差异对于GDF15+和GDF15-(p<0.05),但对于HSP60不是。与没有VUR的患者相比，SCP后有VUR的患者GDF15+/弱HSP60的发生率更高（分别为p<0.05和p<0.001）。
结论：线粒体的活力似乎受到损害，可能与SCP后VUR持续的病因学意义有关。
方法：1994-2023年从62例神经源性膀胱患者中获得的膀胱活检通过苏木精和伊红检查ICI，Masson三色检查纤维化，和免疫荧光的尿路上皮生长分化因子15（GDF15；线粒体应激反应细胞因子）（阳性/阴性）和热休克蛋白60（HSP60；线粒体基质标记）（强≥50％/弱≤50％）表达。GDF15+/弱HSP60表明线粒体活力受损。膀胱测压测量新膀胱顺应性/容量。
结果：SCP和膀胱活检的平均年龄分别为9.4±4.6和14.2±7.1。VUR出现在SCP的38/62名患者（51个输尿管）中，并在4/38名患者中单独使用SCP解决，在17/38中使用SCP和输尿管膀胱造口术，并在17/38中持续存在。与GDF15-（n=38）/强HSP60（n=31）相比，GDF15（n=24）/弱HSP60（n=31）的纤维化明显更密集（分别为p<0.001和p<0.01）。ICI的差异对于GDF15+和GDF15-(p<0.05),但对于HSP60不是。与没有VUR的患者相比，SCP后有VUR的患者GDF15+/弱HSP60的发生率更高（分别为p<0.05和p<0.001）。
结论：线粒体的活力似乎受到损害，可能与SCP后VUR持续的病因学意义有关。
