Experimental clinical study on the using of adhesive in the obliteration of varicose veins in humans

Introduction. In order to perform endovasal vein lining, the American Rodney D.Raabe developed a system for varicose veins obliteration, consisting of a glue gun and two catheters, called “VenaSeal”. As an occlusant for varicose veins in this system, “Medtronic” company today proposes to use an adhesive compound synthesized on the basis of butyl ether of α-cyanacrylic acid.

Materials and methods. Endovasal catheter obliteration of tributaries and main trunks of the great saphenous vein on the tibia was performed in 15 patients with varicose disease (C2 to CEAR) in order to substantiate the possibility of using the adhesive compound Sulfacrylate. Severity of pain, presence or absence of phlebitis and thrombophlebitis, hyper pigmentation, neurological disorders, allergic reaction were clinically evaluated.

Results and discussion. All patients after the introduction of the glue Sulfakrilat had a clinic of moderate phlebitis, without the formation of blood clots in the lumen of the vein. No local or general allergic reaction was observed. From day 7 occluded venous segments were palpated in the form of moderate density bands, without infiltration to surrounding tissues. In the absence of blood flow ultrasound examination showed gradual biodegradation of the adhesive strip inside the vein with the development of complete obliteration of the lumen starting from the 4th month. Starting with the 7th day gradually stopped aseptic inflammation in the wall of the vein was observed on histological examination. Monocytic infiltration of the venous wall with the formation of multinucleated cells of foreign bodies was present until the time of complete biodegradation of the glue. The process of diffuse growth of connective tissue with the presence of fibroblasts from the subendothelium and in the middle shell was most actively observed in histological material from 90 to 120 days after occlusion. Within 180 days, the lumen of the veins occluded by “Sulfacrylate” was completely obliterated by mature connective tissue, in the absence of glue particles, which indicated its complete biodegradation.

Conclusion. The experimental studies conducted with the assessment of clinical symptoms, ultrasound examination and histological study of morphogenesis in the lumen of blood vessels in different periods up to 6 months allow us to conclude the potential use of the adhesive compound “Sulfacrylate” (produced in Russia) for endovasal obliteration of varicose veins in humans.

1. Min R.J., Almeida J.I., McLean D.J., Madsen M., Raabe R. Novel vein closure procedure using a proprietary cyanoacrylate adhesive: 30-day swine model results. Phlebology. 2012;27(8):398–403. doi: 10.1258/phleb.2011.011084.

2. Almeida J.I., Min R.J., Raabe R., McLean D.J., Madsen M. Cyanocrylate Adhesive for the Closure of Truncal Veins: 60-Days Swine Model Results. Vasc Endovascular Surg. 2011;45(7):631–635. doi: 10.1177/1538574411413938.

3. Almeida J.I., Javier J.J., Mackay E., Bautista C., Proebstle T.M. First human use of cyanocrylate adhesive for treatment of saphenous vein incompetence. J Vasc Surg Venous Lymphat Disord. 2013;1(2):174–180. doi: 10.1016/j.jvsv.2012.09.010.

4. Shaydakov E.V., Meltsova A.Zh., Porembskaya O.Ya., Kudinova E.A., Korzhevskiy D.E., Kirik O.V., Sukhorukova E.G. Experience with using cyanoacrylate glue in endovascular treatment of varicose veins. Angiologiya i sosudistaya khirurgiya = Angiology and Vascular Surgery. 2017;23(4):62–66. (In Russ.) Available at: http://angiologia.ru/journals/angiolsurgery/2017/4/9.php.

5. Sannikov B.A., Emeliyanenko V.M. Retrospective analysis of results of using cyanoacrylate compositions for varicose veins ablation. Angiologiya i sosudistaya khirurgiya = Angiology and Vascular Surgery. 2019;25(1):93–98. (In Russ.) Available at: http://www.angiolsurgery.org/magazine/2019/1/13.htm.

6. Marchenko V.T., Shkurupii V.A. Morphology of reparative regeneration of organs and tissues during treatment with new generation Sulfacrylate. Bulletin of Experimental Biology and Medicine. 2004;137:206–210. doi: 10.1023/B:BEBM.0000028141.56565.99.

7. Marchenko V.T., Prutovykh N.N., Tolstikov G.A., Tolstikov A.G. Medical glue “Sulfacrylate”. Antibacterial anti-inflammatory adhesive composition. A Guide for use in surgical industries. Novosibirsk; 2005. 80 p. (In Russ.) Available at: http://www.medrk.ru/uploads/doc/sulfakrilat_ins.pdf.

8. Duffy C., Zetterlund Per B., Aldabbagh F. Radical polymerization of Alkyl 2-Cyanoacrylates. Molecules. 2018;23(2):465. doi: 10.3390/molecules23020465.

9. Sannikov A.B., Emelyanenko V.M. Cyanacrylate glue compositions in phlebology. Flebologiya = Flebologiya. Journal of Venous Disorders. 2019;13(1):36–41. (In Russ.) doi: 10.17116/flebo20191301136.

10. Korshak V.V., Polyakov A.M., Shapiro M.S. Cyanoacrylate adhesive and its application. Rossiyskiy khimicheskiy zhurnal = Russian Chemical Journal. 1969;14(1):52–55. (In Russ.).

11. Galperin E.I. Use of cyanacrylate glue MK-7 in surgery of liver and biliary tract. Khirurgiya = Surgery. 1978;(7):41. (In Russ.).

12. Danilov M.V., Blagovidov D.F., Daurova T.T. Filling of pancreatic ducts is a new direction in pancreatic surgery. Klinicheskaya khirurgiya = Clinical Surgery. 1981;(4):63–66. (In Russ.).

13. Shalimov A.A., Zemskov V.S., Shalimov S.A. Application of pancreatic duct occlusion. Vestnik khirurgii im. I.I. Grecova = Grekov’s Bulletin of Surgery. 1984;(1):42–46. (In Russ.).

14. Savelev V.S., Visaitov V.A., Stupin I.V. Using of “Sulfacrylate” glue in gastrointestinal surgery. Khirurgiya = Surgery. 1982;(10):89–93. (In Russ).

15. Wang Y.M., Cheng L.F., Li N. Histopathological study of vascular changes after intra-arterial and intravenous injection of N-butil-2-cyanoacrylate. Chin J Dig Dis. 2006;7(3):175–179. doi: 10.1111/j.1443-9573.2006.00264.x.

16. Almeida J.I., Javier J.J., Mackay E.G., Bautista C., Cher D.J., Proebstle T.M. Two-year follow-up of first human use of cyanocrylate adhesive for treatment of saphenous vein incompetence. Phlebology. 2015;30(6):397–404. doi: 10.1177/0268355514532455.

17. Bozkurt A.K., Yilmaz M.F. A prospective comparison of a new cyanoacrylate glue and laser ablation for the treatment of venous insufficiency. Phlebology. 2016;31(1S):106–113. doi: 10.1177/0268355516632652.

18. Yasim A., Eroglu E., Bozoglan O., Mese B., Acipayam M., Kara H. A new non-tumescent endovenous ablation method for varicose vein treatment: Early results of N-butyl cyanoacrylate (VariClose®). Phlebology. 2017;32(3):194–199. doi: 10.1177/0268355516638577.

19. Eroglu E., Yasim A., Ari M., Ekerbicer H., Kocarslan A., Kabalci M., Acipayam M. Mid-term results in the treatment of varicose veins with N-butil cyanoacrylate. Phlebology. 2017;32(10):665–669. doi: 10/1177/0268355517718761.

20. Srinath S.R., Sharma G. Review of non-thermal non-tumescent endovenous ablation using cyanoacrylate. Journal of Surgery. 2018;14(2):91–95. doi: 10.7438/1584-9341-14-2-10.

21. Zielinski A., Sweircz P. Are non-thermal, non-tumescent techniques more recommended? Endovenous treatment of saphenous veins reflux – methods and results overview and discussion. Phlebological Review. 2018;26(1):4–9. doi: 10.5114/pr.2018.76383.

22. Morrison N., Gibson K., McEnroe S., Goldman M., King T., Weiss R. et al. Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous veins (VeClose). J Vasc Surg. 2015;61(4):985–994. doi: 10.1016/j.jvs.2014.11.071.

23. Proebstle T.M., Alm J., Dimitri S., Rasmussen L., Whitley M., Lawson J. et al. The European multicenter cohort study on cyanoacrylate embolization of refluxing great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2015;3(1):2–7. doi: 10.1016/j.jvsv.2014.09.001.