Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
Pediatr Surg Int. 2024 Aug 13;40(1):222. doi: 10.1007/s00383-024-05803-z.
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).
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.
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).
Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.
我们研究了神经源性膀胱尿路上皮的炎症细胞浸润（ICI）、纤维化和线粒体活力是否参与了乙状结肠直肠膀胱成形术后持续性膀胱输尿管反流（VUR）的机制。
对 1994 年至 2023 年间的 62 名神经源性膀胱患者的膀胱活检标本进行苏木精-伊红染色以评估 ICI，马松三色染色评估纤维化，免疫荧光染色评估尿路上皮生长分化因子 15（GDF15；一种线粒体应激反应细胞因子）（阳性/阴性）和热休克蛋白 60（HSP60；一种线粒体基质标志物）（强≥50%/弱≤50%）的表达。GDF15+弱 HSP60 表示线粒体活力受损。膀胱测压评估新膀胱顺应性/容量。
乙状结肠直肠膀胱成形术时的平均年龄（岁）为 9.4±4.6，膀胱活检时的平均年龄为 14.2±7.1。乙状结肠直肠膀胱成形术时，38 名患者中有 38 名（51 个输尿管）存在 VUR，其中 4 名患者单独通过乙状结肠直肠膀胱成形术治愈，17 名患者通过乙状结肠直肠膀胱成形术联合输尿管肠吻合术治愈，17 名患者 VUR 持续存在。GDF15+（n=24）弱 HSP60 组的纤维化密度明显高于 GDF15-（n=38）强 HSP60 组（p<0.001 和 p<0.01）。GDF15+与 GDF15-相比，ICI 差异有统计学意义（p<0.05），但 HSP60 无差异。乙状结肠直肠膀胱成形术后存在 VUR 的患者中，GDF15+弱 HSP60 的发生率高于无 VUR 的患者（p<0.05 和 p<0.001）。
线粒体活力似乎受损，这可能对乙状结肠直肠膀胱成形术后持续性 VUR 有病因学意义。
