Department of Pediatric Urology, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Pediatric Urology Unit, 'Bambino Gesù' Children's Hospital, Rome, Italy.
J Pediatr Urol. 2018 Dec;14(6):538.e1-538.e7. doi: 10.1016/j.jpurol.2018.04.021. Epub 2018 May 25.
It is extremely important to not only address the short-term success following endoscopic correction of vesicoureteral reflux (VUR) but also the long-term efficacy and safety of the tissue augmenting substance utilized for endoscopic correction.
This study retrospectively evaluated all cases of ureterovesical junction (UVJ) obstruction following endoscopic treatment of VUR over the last 5 years utilizing two tissue augmenting substances, with special emphasis on the safety of Vantris, and performed clinical and histological review of these patients.
The study population comprised 2495 patients who underwent endoscopic correction of VUR utilizing Deflux (1790) and Vantris (705). Tissue sections were stained with hematoxylin & eosin and trichrome, and examined under a light microscope. Nine primary obstructive megaureters after ureteral re-implantation served as controls.
Nine (0.5%) children (three female and six male) in the Deflux group and nine (1.3%) (five females and four males) in the Vantris group developed UVJ obstruction and required ureteral re-implantation. Obstruction developed during the period ranging 2-49 months (average 16 months) following endoscopic correction. The primary reflux grade was III in seven, IV in six, and V in six children. The mean volume of the injected material in all obstructed patients was 1.2 ± 0.6 cc (mean ± SD). Histopathological analysis revealed a pseudocapsule composed of fibrous tissue and foreign-body giant cells surrounding the Vantris implant in all patients. The distal part of the ureters demonstrated significant ureteral dilatation without ureteral fibrosis. In all patients, additional biopsies from the muscularis propria adjacent to the injection site were examined and showed no significant abnormalities. There was an increased collagen deposition in the juxtavesical segment of the obstructive ureters following Deflux and Vantris injections, and of primary obstructive megaureter. No significant difference was found in the tissue response between Deflux and Vantris patients and controls. Statistical analysis of the nonhomogeneous population demonstrated higher obstruction rates in patients from the Vantris group. However, no statistical difference was demonstrated regarding the obstruction rate in the homogenous group with relation to gender, age and reflux grade group of patients. Moreover, univariate analysis revealed that Grade V reflux, the presence of beak sign on the reviewed pretreatment, and inflamed bladder mucosa upon injection were significant independent risk factors leading to obstruction.
This study suggested that the underlining ureteral pathology lead to UVJ obstruction following Vantris injection. There was increased collagen deposition in the juxtavesical segment of the obstructive ureters following Vantris injection. Furthermore, these findings were similar to those discovered in patients who underwent endoscopic correction with Deflux, and in patients who required ureteral reimplantation due to primary obstructive megaureter. Additional biopsies from the muscularis propria adjacent to the injection site showed no significant abnormalities, ironing out the fact that Vantris did not led to adverse tissue reaction following injection. Univariate analysis further ironed out the hypothesis that underlying ureteral pathology was responsible for the increased incidence of UVJ obstruction and demonstrated that Grade V reflux, the presence of beak sign on the reviewed pretreatment VCUG, and inflamed bladder mucosa upon injection were significant independent risk factors leading to obstruction.
Data showed that Vantris injection did not lead to any different ureteral fibrosis or inflammatory changes to the tissue augmenting substances utilized in past and present clinical practice, and therefore did not seem to increase the incidence of UVJ obstruction. High reflux grade, presence of obstructive/refluxing megaureter and inflamed bladder mucosa were the only statistically significant and independent predictive factors for UVJ obstruction following endoscopic correction of VUR.
不仅要关注内镜治疗后膀胱输尿管反流(VUR)的短期成功率,还要关注用于内镜治疗的组织增强物质的长期疗效和安全性,这一点非常重要。
本研究回顾性评估了过去 5 年中使用两种组织增强物质治疗 VUR 后发生输尿管膀胱连接部(UVJ)梗阻的所有病例,特别强调了 Vantris 的安全性,并对这些患者进行了临床和组织学评估。
研究人群包括 2495 例接受 Deflux(1790 例)和 Vantris(705 例)内镜治疗 VUR 的患者。组织切片用苏木精和伊红、三色染色,在光学显微镜下检查。9 例原发性梗阻性巨输尿管(因输尿管再植入术)作为对照。
Deflux 组 9 例(3 例女性,6 例男性)和 Vantris 组 9 例(5 例女性,4 例男性)的 9 例儿童发生 UVJ 梗阻,需要再次行输尿管植入术。梗阻发生在内镜治疗后 2-49 个月(平均 16 个月)。主要反流等级在 7 例为 III 级,6 例为 IV 级,6 例为 V 级。所有梗阻患者的注射材料平均体积为 1.2±0.6cc(平均值±标准差)。组织病理学分析显示,所有患者的 Vantris 植入物周围均有纤维组织和异物巨细胞组成的假包膜。远端输尿管明显扩张,但无输尿管纤维化。所有患者均对注射部位附近的肌肉固有层进行了额外的活检,结果显示无明显异常。Deflux 和 Vantris 注射后,梗阻性输尿管的膀胱下段胶原沉积增加,原发性梗阻性巨输尿管也是如此。Deflux 和 Vantris 患者与对照组之间的组织反应无显著差异。对非同质人群的统计学分析表明,Vantris 组患者的梗阻率较高。然而,在同质性组中,性别、年龄和反流等级组的患者,梗阻率无统计学差异。此外,单因素分析显示,V 级反流、预处理 VCUG 上存在喙状征以及注射时膀胱黏膜炎症是导致梗阻的独立危险因素。
本研究表明,Vantris 注射后输尿管潜在的病理学导致了 UVJ 梗阻。Vantris 注射后,梗阻性输尿管的膀胱下段胶原沉积增加。此外,这些发现与接受 Deflux 内镜治疗的患者以及因原发性梗阻性巨输尿管而需要再次行输尿管植入术的患者相似。对注射部位附近肌肉固有层的进一步活检未显示出明显异常,排除了 Vantris 注射后导致组织不良反应的可能性。单因素分析进一步排除了输尿管潜在病理学是导致 UVJ 梗阻发生率增加的假说,并表明 V 级反流、预处理 VCUG 上存在喙状征以及注射时膀胱黏膜炎症是导致梗阻的独立危险因素。
数据表明,Vantris 注射不会导致组织增强物质发生任何不同的输尿管纤维化或炎症改变,因此似乎不会增加 UVJ 梗阻的发生率。高反流等级、存在梗阻/反流性巨输尿管和炎症性膀胱黏膜是内镜治疗 VUR 后发生 UVJ 梗阻的唯一具有统计学意义和独立的预测因素。