EFFECTIVENESS OF MESNA ON THE SUCCESS OF CHOLESTEATOMA SURGERY M.Tayyar KALCIOĞLU, M.D. Professor Inonu University Medical Faculty, Turgut Ozal Medical Center, Malatya, TURKEY “TUZLA ENT SCHOOL” Turkey-Croatia-Bosnia and Herzegowina ENT meeting Tuzla, May 31.- June 1. 2012  

Introduction One of the goals of surgery for chronic otitis media (COM) with cholesteatoma is elimination of disease Residual or recurrent cholesteatoma may happen Residual cholesteatoma develops from a remnant of keratinized epithelium left behind from a previous procedure. The rate of residual cholesteatoma is reported to vary from 5% to 50%* *Kaylie DM, Gardner EK, Jackson CG. Revision chronic ear surgery. Otolaryngol Head Neck Surg 2006;134:443-450. *Syms M, Luxford W. Management of cholesteatoma: status of the canal wall. Laryngoscope 2003;113:443-448 *Stangerup S, Drozdziewicz D, Tos M, Hougaard-Jensen A. Recurrence of attic cholesteatoma: different methods of estimating recurrence rates. Otolaryngol Head Neck Surg 2000;123:283-287 *Corso ED, Marchese MR, Scarano E, Paludetti G. Aural acquired cholesteatoma in children: surgical findings, recurrence and functional results. Int J Ped Otorhinolaryngol 2006;70:1269-1273 *Yung M, Jacobsen NL, Vowler SL. A 5-year observational study of the outcome in pediatric cholesteatoma surgery. Otol Neurotol 2007;28:1038-1040 *Drahy A, De Barros A, Lerosey Y, Choussy O, Dehesdin D, Marie JP. Acquired cholesteatoma in children: strategies and mesium-term results. ORL 2012, In Press

MESNA (Sodium 2-mercaptoethanesulfonate) It is a synthetic sulfur compound and belongs to a class of thiol compounds that produce mucolysis by disrupting disulfide bonds of the mucous polypeptide chains . It has been used in a variety of disorders such as mucolytic agent for pulmonary disorders* and protective agent against the toxicity of some chemotherapotic agents. *Clarke SW, Lopez-Vidriero MT, Pavia D, Thomson D: The effect of sodium 2-mercaptoethane sulphonate and hypertonic saline aerosols on bronchial clearance in chronic bronchitis. Br J Clin Pharmacol 1979; 7: 39–44. *Berrigan MJ, Marinello AJ, Pavelic Z, Williams CJ, Struck RF, Gurtoo HL: Protective role of thiols in cyclophosphamide-induced urotoxicity and depression of hepatic drug metabolism. Cancer Res 1982; 42: 3688–3695

This effect facilitates totally dissection of cholesteatoma matrix. The matrix of cholesteatoma is mainly composed of keratin, which has disulfide bonds MESNA can be used during ear surgeries such as cholesteatoma or athelectatic ears to make simpler the dissection of tissue layers because of its disrupting effect on disulfide bonds* This effect facilitates totally dissection of cholesteatoma matrix. *Yilmaz M, Goksu N, Bayramoglu I, Bayazit YA. Practical use of mesna in atelectatic ears and adhesive otitis media. ORL 2006;68:195-198

Does MESNA has any side effect on hearing? Vincenti et al reported that there was no side effect of Mesna application into the middle ear on hearing Thus let the some surgeons to use Mesna during cholesteatoma surgery Vincenti V, Mondain M, Pasanisi E, Piazza F, Puel JL, Bacciu S, Quaranta N, Uziel A, Zini C. Cochlear effects of Mesna application into the middle ear. Ann N Y Acad Sci 1999;884:425-432

The aim of this study The purpose of this study was to compare the residual cholesteatoma rates between MESNA used and non-used cholesteatoma surgeries performed by the same author

Materials and Methods The research protocol was approved by the Inonu University Clinical Researchs Ethic committee (2011/68) 934 patients, who underwent tympanoplasty and/or mastoidectomy by the same surgeon between September 2000 and March 2012 in the department of Otolaryngology, Inonu University, Turkey, were analysed during this retrospective study

Materials and Methods 224 of 934 patients had cholesteatoma. For these patients, canal wall down (CWD) or canal wall up (CWU) mastoidectomy was performed using standard retroauricular incisions under general anesthesia with or withoud MESNA application.

Materials and Methods MESNA was diluted by saline (20% MESNA and 80% saline) and applied during the surgery After waiting approximately 5 minutes, cholesteatoma matrix was dissected by using dissector or cotton similarly with MESNA non-used group

Materials and Methods 145/224; CWD mastoidectomy 79 / 224; CWU mastoidectomy 63/224; MESNA used 41; CWD mastoidectomy 22; CWU mastoidectomy 161/224; MESNA non-used 104; CWD mastoidectomy 57 ; CWU mastoidectomy

Materials and Methods The patients followed-up at least 1 year. Postoperative follow-up was performed by otoscopic examination If it was necessary magnetic resonans imaging and/or second look tympanoplasty was performed. Residuel cholesteatoma rates for mesna applied and non-applied groups were compared using pearson Chi-square test.

Results MESNA used group; 46/63 patients were routinely followed up at least one year, postoperatively The mean follow-up period was 35.2 months, with a range of 12 to 65 months There were 26 male and 20 female The ages of the patients ranged from 6 to 64 (mean, 27.3) CWD or CWU mastoidectomy was performed for 24 and 22 patients, respectively Residual cholesteatoma developed in 3 patients with a 6.5% ratio Residual cholesteatoma was noted in 1 of 22 patients with CWU and 2 of 24 with CWD mastoidectomy The mean age of residual cholesteatoma’s group was 15,7 (6, 7, and 34 years old) Two children had CWD mastoidectomy while the older had CWU

Results MESNA non-used group; 95/161 patients came to the routine postoperative follow-up at least one year The mean follow-up period for this group was 39.1 months, with a range of 12 to 134 months Fourty-five of the patients were male and 50 female The mean age was 31.4 with a range 11 to 58 years old CWD or CWU mastoidectomy surgery was performed for 56 and 39 patients, respectively Residual cholesteatoma was seen in 17 patients with a 17.9% ratio Residual cholesteatoma was noted in 9 of 56 patients with CWD and 8 of 39 with CWU The mean age for residual cholesteatoma’s group was 29.4 (range, 13-58 years old).

Results The residual cholesteatoma was seen significantly higher in MESNA non-applied group than MESNA applied group (pearson Chi-square test; p=0.045) When we compared demographics of the groups with each other, no statistically significance was found (pearson Chi-square test; p=0.239) There was no statistically significance residual cholesteatoma rate between CWD and CWU mastoidectomy procedures (pearson Chi-square test; p=0.686).

Discussion One of the main goals for successful surgery for COM with cholesteatoma is to completely eradicate the disease After middle ear cholesteatoma surgery high residual rates is one of the main problems, which is reported to vary from 5% to 54 % Residual cholesteatoma is cholesteatoma felt to be left behind from a previous procedure and thence not secondary to a retraction pocket. To solve this problem, surgeons have been discussing on it for a long time

Discussion The surgical treatment of cholesteatoma has been conducted by two methods The choice between canal wall up (CWU) and canal wall down (CWD) tympanoplasty techniques to decrease cholesteatoma recurrence remains controversial Although most studies have revealed lower recurrent/residual cholesteatoma rates after CWD than CWU mastoidectomy*, some others has good results after CWU mastoidektomy** *Drahy A, De Barros A, Lerosey Y, Choussy O, Dehesdin D, Marie JP. Acquired cholesteatoma in children: strategies and mesium-term results. ORL 2012, In Press *Hirsch BE, Kamerer DB, Doshi S. Single stage management of cholesteatoma. Otolaryngol Head Neck Surg. 1992;106:351-354. *Roden D, Hanrubia VF, Wiet R. Outcome of residual cholesteatoma and hearing in mastoid surgery. J Otolaryngol 1996;25:178-181. *Karmarkar S, Bhatia S, Saleh E et al. Choleateatoma surgery: the individualized technique. Ann Otol Rhinol Laryngol. 1995;104:591-595 . **Vartiainen E, Nuutinen J. Long term results of surgical treatment of different cholesteatoma types. Am J Otol. 1993;14:507-511. **Ho SY, Kveton JF. Efficacy of the 2-staged procedure in the management of cholesteatoma. Arch Otolaryngol Head Neck Surg 2003;129:541-545

Discussion Literature Technique Residual Cho. % Hirsch et al CWD 5 CWU 19 Roden et al CWD 5 CWU 20 Karmarkar et al CWD 4 CWU 36 Vartiainen et al CWD 9 CWU 8 Ho and Kveton CWD 5 CWU 4

Discussion In the current study; In 80/141 case with CWD mastoidectomy, 11 residual cholesteatoma (13,75 %) In 61/141 case with CWU mastoidectomy, 9 residual cholesteatoma (14,75 %) There was no statistically significance residual cholesteatoma rate between CWD and CWU mastoidectomy procedures

Discussion MESNA ; no side effect on hearing * make simpler the dissection of tissue layers because of its disrupting effect on disulfide bonds ** is it avert to left epitelium from a previous surgery and decrease residual cholesteatoma rate? *Vincenti V, Mondain M, Pasanisi E, Piazza F, Puel JL, Bacciu S, Quaranta N, Uziel A, Zini C. Cochlear effects of Mesna application into the middle ear. Ann N Y Acad Sci 1999;884:425-432 **Yilmaz M, Goksu N, Bayramoglu I, Beyazit YA. Practical use of mesna in atelectatic ears and adhesive otitis media. ORL 2006;68:195-198.

Discussion MESNA used group; MESNA non-used group; Residual cholesteatoma, 3/46 cases (6,5%) MESNA non-used group; Residual cholesteatoma, 17/95 (17,9%) The residual cholesteatoma was seen significantly higher in mesna non-applied group than mesna applied group (pearson Chi-square test; p=0.045)

Conclusion According to the results of this study, which is the first in the literature; The matrix of cholesteatoma is mainly composed of keratin, which has disulfide bonds, can be disrupted by MESNA. This effect may help totally dissection of cholesteatoma matrix This may decrease residual cholesteatoma rates and increase success rate

Thank You Hvala E-mail: mtkalcioglu@hotmail.com Web: http://www.mahmuttayyarkalcioglu.com/