Primer Vezikoüreteral Reflülü (VUR) ve Dx/HA ile Başarısız Enjeksiyon Tedavisi Sonrası Primer VUR'lu Çocukların Üreterovezikal Bileşkesinde Sitokin Profillerinin ve Ultrayapısal Değişikliklerinin Karşılaştırılması.

Year 2020, Volume: 3 Issue: Özel Sayı 1, 33 - 45, 22.06.2020

Mutlu Deger , Volkan İzol , Yurdun Kuyucu , Arbil Açıkalın , İbrahim Atilla Arıdoğan Sait Polat , Nihat Satar

https://doi.org/10.36516/jocass.2020.38

Abstract

Amaç: İmmünohistokimyasal yöntemler ve transmisyon elektron mikroskopisi (TEM) kullanılarak primer vezikoüreteral reflülü (VUR) ve dekstranomer / hyaluronik asit (Dx/HA) ile başarısız enjeksiyon tedavisi sonrası primer VUR'lu çocukların üreterovezikal bileşkesinde sitokin profillerinin ve ultrayapısal değişikliklerinin karşılaştırılması.

Materyal ve Method: Aralık 2011 ve Ağustos 2014 tarihleri arasında, Uluslararası Reflü Çalışmasına göre grade I-V VUR olarak değerlendirilen 41 çocuğa üreteroneosistostomi uygulandı. Dx / HA ile başarısız enjeksiyon tedavisinin ardından 18 çocuğa primer VUR için üreteroneosistostomi uygulandı. Histopatolojik ve ultrayapısal değerlendirmeler için ameliyat sırasında altmış yedi distal intravezikal üreter elde edildi. Üreter duvarı düz kas organizasyonu ve transforme edici büyüme faktörü-β1 (TGF-β1), vasküler endotelyal büyüme faktörü (VEGF) ve CD34 immünohistokimyasal olarak değerlendirildi. Ultrayapısal değerlendirmeler ve morfolojik tanımlar yarı kantitatif olarak yapıldı.

Bulgular: Hastaların 10'u (% 24,3) erkek, 31'i (% 75,7) kadındı. 28 üreterde başarısız Dx/HA enjeksiyon öyküsü mevcuttu. Histopatolojisi; Dx/HA ile başarısız enjeksiyon tedavisini takiben primer VUR hastalarında ve primer VUR hastalarında TGF-β1 ve VEGF ve CD34 düzeyleri aynıydı ancak kontrol grubu ile karşılaştırıldığında farklı idi (sırasıyla p=0.001,p<0.001 ve p<0.001). Ancak farklar reflü derecesi ile ilişkili değildi (sırasıyla p = 0.42, p = 0.26 ve p = 0.94). Tüm VUR örneklerinde kas hücrelerinde ultrayapısal değişiklikler gözlendi.

Sonuç: Çalışmamız, tüm VUR örneklerinde kas hücrelerinin ultra apısal değişikliklerinin gözlendiğini göstermiştir. Primer VUR ve başarısız Dx/HA tedavisi olan primer VUR hastalar arasında sitokin miktarında anlamlı bir fark yoktu. VEGF, CD34 ve TGF-21 düzeyleri her iki primer VUR grubunda da karşılaştırılabilirdi.

Keywords

dekstranomer/hiyalüronik asit, transmisyon elektron mikroskopisi, üreterovezikal bileşke, vezikoüreteral reflü

Comparison Of The Cytokine Profiles And Ultrastructural Changes In The Ureterovesical Junctions Of Children With Primary Vesicoureteral Reflux And Children With Primary VUR Following Failed Injection Therapy With Dx/HA.

Abstract

Purpose: To compare the cytokine profiles and ultrastructural changes in the ureterovesical junctions of children with primary vesicoureteral reflux(VUR) and children with primary VUR following failed injection therapy with dextranomer/hyaluronic-acid (Dx/HA) using immunohistochemical methods and transmission electron microscopy (TEM).

Materials and Methods: 41 children underwent ureteroneocystostomy for VUR and 18 children underwent ureteroneocystostomy for primary VUR following failed injection therapy with Dx/HA. Sixty-seven distal intravesical ureters were obtained during surgery for histopathological and ultrastructural evaluations. The ureteral wall smooth-muscle organization and transforming growth factor-β1(TGF-β1), vascular endothelial growth factor(VEGF), and CD34 were evaluated immunohistochemically. The ultrastructural evaluations and morphological descriptions were performed semi-quantitatively.

Results: Of the patients, 10(24,3%) were male and 31(75,7%) were female. 28 ureter had a history of failed Dx/HA injections. Histopathology; the amount of TGF-β1, and the VEGF and CD34 levels were same in the patients with primary VUR and patients with primary VUR following failed injection therapy with Dx/HA but different compared with the control group(p=0.001,p<0.001, and p<0.001, respectively), but the differences were not correlated with the grade of reflux(p=0.42, p=0.26 and p=0.94 respectively). Ultrastructural changes in the muscle cells were observed in all the VUR specimens.

Conclusions: Our study demonstrated that ultra-structural changes in the muscle cells were observed in all VUR specimens. There was no significant difference in the quantification of cytokine assays between the patients with primary VUR and primary VUR with failed Dx/HA therapy. The quantification of VEGF, CD34, and, TGF-β1 levels was comparable in both primary VUR groups.

Keywords

dextranomer/hyaluronic acid, transmission electron microscopy, ureterovesical junctions, vesicoureteral reflux

References

• Referans1. Skoog SJ, Peters CA, ArantJr BS, et al: Pediatric Vesicoureteral Reflux Guidelines Panel summary report: clinical practice guidelines for screening siblings of children with vesicoureteral reflux and neonates/infants with prenatal hydronephrosis. J Urol 184: 1145, 2010.
• Referans2. Drzewiecki BA, Thomas JC, Pope JC 4th, et al: Observation of patients with vesicoureteral reflux off antibiotic prophylaxis: physician bias on patient selection and risk factors for recurrent febrile urinary tract infection. J Urol 188:1480, 2012.
• Referans3. Tekgül S, Riedmiller H, Hoebeke P, et al: EAU Guidelines on vesicoureteral reflux in children.EurUrol 62(3): 534, 2012.
• Referans4. Peters C, Rushton HG: Vesicoureteral reflux associated renal damage: congenital reflux nephropathy and acquired renal scarring. J Urol 184: 265, 2010.
• Referans5. Normand IC, Smellie JM. Prolonged maintenance chemotherapy in the management of urinary infection in childhood. Br Med J. 1965;1:1023–1026.
• Referans6. Politano VA, Leadbetter WF. An operative technique for the correction of vesicoureteral reflux. J Urol. 1958;79:932–941.
• Referans7. Glenn JF, Anderson EE. Distal tunnel ureteral reimplantation. J Urol. 1967;97:623–626.
• Referans8. Matouschek E. New concept for the treatment of vesico-ureteral reflux. Endoscopic application of teflon. Arch Esp Urol. 1981; 34:385-388.
• Referans9. Dixon JS, Jen PY, Yeung CK, et al: The structure and autonomic innervation of the vesico-ureteric junction in cases of primary ureteric reflux. Br J Urol 81(1): 146, 1998.
• 1Referans10. Hanna MK, Jeffs RD, Sturgess JM, et al: Ureteral structure and the ultrastructure. Part 1. The normal human ureter.JUrol116: 718, 1976.
• Referans11. Sofikerim M, Sargon M, Oruc O, et al: An electron microscopic examination of the intravesical ureter in children with primary vesico-ureteric reflux. BJU Int99: 1127, 2007.
• Referans12. Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Möbius TE. International Reflux Study in Children: international system of radiographic grading of vesicoureteric reflux. Pediatr Radiol. 1985; 15: 105–109.
• Referans13. Oswald J, Brenner E, Schwentner C, Deibl M, Bartsch G, Fritsch H and Radmayr C. The intravesical ureter in children with vesicoureteral reflux: a morphological and immunohistochemical characterization. J Urol 2003; 170: 2423-2427.
• Referans14. Puri P, Pirker M, Mohanan N, Dawrant M, Dass L and Colhoun E (2006) Subureteral dextranomer/hyaluronic acid injection as first line treatment in the management of high grade vesicoureteral reflux. J Urol176:1856-1860.
• Referans15. Stenberg A, Hensle TW and Lackgren G (2002) Vesicoureteral reflux: a new treatment algorithm. Cur Urol Rep 3:107-114.
• Referans16. Kirsch AJ, Perez-Brayfield M, Smith EA and Scherz HC (2004) The modified sting procedure to correct vesicoureteral reflux: improved results with submucosal implantation within the intramural ureter. J Urol171:2413-2416.
• Referans17. Stenberg A, Läckgren G (1995) A new bioimplant for the endoscopic treatment of vesicoureteral reflux: experimental and short-term clinical results. J Urol 154:800-803.
• Referans18. Lackgren G, Wahlin N, Skoldenberg E and Stenberg A (2001) Long term follow up of children treated with dextranomer/hyaluronic acid copolymer for vesicoureteral reflux. J Urol166:1887-1892
• Referans19. Routh JC, Vandersteen DR, Pfefferle H, Wolpert JJ and Reinberg Y (2006) Single center experience with endoscopic management of vesicoureteral reflux in children. J Urol175:1889-1892.
• Referans20. Lavelle MT, Conlin MJ, Skoog SJ (2005) Subureteral injection of Deflux for correction of reflux: analysis of factors predicting success. Urology 65(3):564-567
• Referans21. Hanna MK, Jeffs RD, Sturgess JM and Barkin M. Ureteral structure and the ultrastructure. Part 1. The normal human ureter. J Urol1976; 116: 718–724.
• Referans22. Sofikerim M, Sargon M, Oruc O, Dogan HS and Tekgul S. An electron microscopic examination of the intravesical ureter in children with primary vesico-ureteric reflux. BJU Int 2007; 99: 1127-1131.
• Referans23. Routh JC, Ashley RA, Sebo TJ, Vandersteen DR, Slezak J and Reinberg Y. Histopathological changes associated with dextranomer/hyaluronic acid injection for pediatric vesicoureteral reflux. J Urol 2007; 178: 1707-1710.
• Referans24. Ben-Meir D, Morgenstern S, Sivan B, Efrat R and Livne PM. Histology proved malpositioning of dextranomer/hyaluronic acid in submucosal ureter in patients after failed endoscopic treatment of vesicoureteral reflux. J Urol 2012; 188: 258-261.
• Referans25. Schwentner C, Oswald J, Lunacek A, et al. Extracellular microenvironment and cytokine profile of the ureterovesical junction in children with vesicoureteral reflux. J Urol. 2008;180:694-700.
• Referans26. Stehr M, Estrada CR, Khoury J et al: Caveolae are negative regulators of transforming growth factor-beta1 signaling in ureteral smooth muscle cells. J Urol 2004; 172: 2451.
• Referans27. Tokunaka S, Gotoh T, Koyanagi T et al: Muscle dysplasia in megaureters. J Urol 1984; 131: 383.
• Referans28. Schwentner C, Oswald J, Lunacek A, et al: Structural changes of the intravesicalureterin children with vesicoureteral reflux—does ischemia have a role? J Urol176: 2212, 2006.
• Referans29. Schwentner C, Oswald J, Lunacek A, et al: Loss of interstitial cells of Cajal and gap junction protein connexin 43 at the vesicoureteral junction in children with vesicoureteral reflux. J Urol174:1981, 2005.