ABSTRACT
PURPOSE: Anorectoplasty and pull-through procedure can be performed with extensive mobilization or tension anastomosis, which can compromise bowel blood perfusion. We aimed to analyze the hypoxia biomarker values and histopathological findings in both conditions to correlate the occurrence of anal stenosis and defecation disorders in experimental models. METHODS: We created anorectal reconstruction models with impaired vascularization of the anorectum (group I) and tension anastomosis (group II) in rats. A third group of animals underwent sham operation (group III) and another as controls (group IV). Hypoxia biomarker values were assessed in all groups. The histopathological changes on the postoperative days 3 and 35, anal stenosis and defecation disorders on day 35 were compared. RESULTS: Hypoxia biomarker values confirmed postoperative ischemia in groups I-III compared to control. Group I and II rats had a similarly pronounced ischemia with histopathologic changes in the anorectum on the postoperative day 3 and accompanied by severe fibrosis on day 35. Compared to the sham operation, both groups showed defecation disorders with significant anal stenoses. CONCLUSION: Extensive rectal mobilization to about the same extent as tension anastomosis has a major impact on postoperative rectal ischemia, resulting in severe fibrotic changes in the anorectum and defecation disorders in the long term.
Subject(s)
Anorectal Malformations , Intestine, Large , Animals , Rats , Constriction, Pathologic , Anastomosis, Surgical , Anorectal Malformations/surgery , HypoxiaABSTRACT
PURPOSE: To investigate the urinary levels of TGF-ß1, VEGF, and MCP-1 as potential biomarkers of latent inflammation and fibrosis in the kidney before and 6 months after correction of vesicoureteral reflux (VUR) in children. METHODS: A total of 88 patients (mean age 26 months) with VUR were divided into three groups: group A-patients with grades II-III VUR, conservative treatment; group B-patients with grades III-V VUR, endoscopic correction of VUR; group C-patients with grades III-V VUR, ureteral reimplantation after failed endoscopic correction. Control group included 20 healthy children. Biomarker levels were measured by ELISA. 99mTc-DMSA scintigraphy and renal histology were performed if possible. RESULTS: At admission, TGF-ß1 was close to control in all study groups, VEGF increased with severity of the disease, and MCP-1 increased in group C. Six months after correction of VUR, despite clinical and laboratory improvement, TGF-ß1 and MCP-1 increased while VEGF decreased compared to the admission values in all groups; no amelioration of renal scarring was detected either by 99mTc-DMSA scintigraphy or renal histology. CONCLUSION: The results support our hypothesis that successful correction of VUR is not sufficient to stop or reduce the latent inflammatory and fibrotic processes that have already started in the kidney regardless of the reflux grade and treatment option. Measuring the urinary levels of TGF-ß1, VEGF, and MCP-1 may aid in the development of non-invasive, pathophysiologically relevant approach to diagnosis and monitoring of kidney injury and fibrosis in children with VUR.
Subject(s)
Chemokine CCL2/urine , Inflammation/urine , Kidney/pathology , Transforming Growth Factor beta1/urine , Vascular Endothelial Growth Factor A/urine , Vesico-Ureteral Reflux/complications , Biomarkers/urine , Case-Control Studies , Child , Child, Preschool , Conservative Treatment , Endoscopy , Female , Fibrosis , Follow-Up Studies , Humans , Infant , Inflammation/etiology , Kidney/diagnostic imaging , Male , Radionuclide Imaging , Vesico-Ureteral Reflux/pathology , Vesico-Ureteral Reflux/therapyABSTRACT
BackgroundSurgical treatment for gastroschisis and congenital diaphragmatic hernia (CDH) commonly leads to abdominal compartment syndrome (ACS) associated with hypoxic renal injury. We hypothesized that measurement of urinary and serum concentrations of vascular endothelial growth factor (VEGF), π-glutathione S-transferase (π-GST), and monocyte chemoattractant protein-1 (MCP-1) may serve for noninvasive detection of hypoxic renal injury in such patients.MethodsIntra-abdominal pressure (IAP), renal excretory function, and the biomarker levels were analyzed before, 4, and 10 days after surgery. Association between the biomarker levels and renal histology was investigated using an original model of ACS in newborn rats.ResultsFour days after surgery, IAP increased, renal excretory function decreased, and the levels of VEGF, π-GST, and MCP-1 increased, indicating renal injury. Ten days after surgery, IAP partially decreased, renal excretory function completely restored, but the biomarker levels remained elevated, suggesting the ongoing kidney injury. In the model of ACS, increase in the biomarker levels was associated with progressing kidney morphological alteration.ConclusionSurgical treatment for gastroschisis and CDH is associated with prolonged hypoxic kidney injury despite complete restoration of renal excretory function. Follow-up measurement of VEGF, π-GST, and MCP-1 levels may provide a better tool for noninvasive assessment of renal parenchyma in newborns with ACS.