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Table of Contents
ORGINAL ARTICLE
Year : 2013  |  Volume : 15  |  Issue : 2  |  Page : 23-26

Effect of use of mitomycin C in two different concentrations in laryngeal surgery


Department of Otolaryngology, Head and Neck Surgery, King Abdulaziz University Hospital, King Saud University, Riyadh, Saudi Arabia

Date of Web Publication21-Jul-2020

Correspondence Address:
MD, FKSU Ahmed Y Al-Ammar
Department of Otolaryngology, Head and Neck Surgery, King Abdulaziz University Hospital, King Saud University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-8491.290344

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  Abstract 


Objective: To study the effect of topical mitomycin C 2 mg/ml in cases of laryngeal stenosis [subglottic stenosis and laryngeal web] and whether there is any difference in the outcome between the two different concentrations 2 mg/ml for 4 minutes and 0.4mg/ml for 4 minutes. By reviewing the literature there was no study found comparing the outcome of different concentrations of mitomycin C.
Patients and Methods: This is a retrospective study of fifteen patients with laryngeal stenosis that were managed at King Abdulaziz University Hospital, King Saud University between June 2008 and February 2010. All patients underwent microlaryngoscopy and laser dilation followed by topical mitomycin C. The outcome of the single use of topical mitomycin C in two concentrations (2 mg/ ml and 0-4 me/ml) for 4 minutes was compared.
Results: Twelve (80%) out of 15 with laryngeal stenosis improved after microlaiyngoscopy, laser dilation and the application of mitomycin C 2mg/mi, compared to 5 (42%) out of 12 patients who underwent the same procedures but with the application of mitomycin C 0.4mg/ml.
Conclusion: According to our data, there was more benefit of the use of mitomycin C in higher concentration (2mg/ml for 4 minutes) and the observed difference was statistically significant p=0.025.

Keywords: mitomycin C, subglottic stenosis and laryngeal web


How to cite this article:
Al-Ammar AY, Al-Amro MS. Effect of use of mitomycin C in two different concentrations in laryngeal surgery. Saudi J Otorhinolaryngol Head Neck Surg 2013;15:23-6

How to cite this URL:
Al-Ammar AY, Al-Amro MS. Effect of use of mitomycin C in two different concentrations in laryngeal surgery. Saudi J Otorhinolaryngol Head Neck Surg [serial online] 2013 [cited 2022 Nov 28];15:23-6. Available from: https://www.sjohns.org/text.asp?2013/15/2/23/290344




  Introduction Top


Scar formation and re-stenosis remain the main causes of failure in the surgical management of airway stenosis [1]. Numerous randomized prospective animal studies [2],[3] have shown convincing results for the use of mitomycin C in the prevention of glottic and subglottic stenosis (SGS) in the post-operative period. Human studies have also demonstrated the efficacy and safety of topical mitomycin C (0.4 mg/ml) in the treatment of airway stenosis [4],[5].

Mitomycin C has been recommended as an adjunct to choanal atresia surgery after observing improved patency and a decreased need for dilatation, stenting and revision surgery [6]. Bradford ct al [7] showed a statistically significant outcome with the use of mitomycin C compared to control for choanal atresia surgeries. On the other hand, according to our previous study on use of mitomycin C for choanal atresia cases; there was no statistically significant improvement with the use of mitomycin C (0.4 mg/ml) [8].

Mitomycin C is an anti-metabolite produced by Streptomyces cacspitosus [4]. It possesses both antineoplastic and anti-proliferative properties. Its antineoplastic property is derived from its ability to crosslink DNA and inhibit RNA and protein synthesis which is used for this purpose primarily in the treatment of gastrointestinal malignancies. Furthermore, mitomycin C has been shown to inhibit fibroblast proliferation both in vivo and vitro [9],[10]. Hence its clinical use as a modulator of wound healing response. The exact mechanism by which it exerts its anti-fibroblastic activity is unknown, though there is evidence to suggest that it may be mediated by apoptosis which is a gene directed process causing cell death. It has successfully been used by ophthalmologists to prevent re-stenosis in glaucoma surgery, dacrocystorhinostomy, optic nerve sheath fenestration and pterygium recurrence [11],[12]. The rationale of the use of mitomycin C is to inhibit fibroblast proliferation during the post-operative phase without damaging mucosa and epithelial growth [13]. In this study an attempt was made to study the effect of the use of mitomycin C 2mg/ml for 4 minutes on the outcome of endoscopic laryngeal surgery and comparing the outcomc to a lower mitomycin C concentration of 0.4 mg/ml for 4 minutes which we used in a previously reported study [8].


  Materials and Methods Top


We identified sixteen patients who underwent microlaryngoscopic treatment along with topical application of mitomycin C for their diagnosis of laryngeal airway obstruction at the King Abdulaziz University Hospital, King Saud University in Riyadh, Saudi Arabia from June 2008 to February 2010. Use of mitomycin C consisted of topical application of the drug after microscopic laser dilatation of subglottic stenosis (SGS), or division of laryngeal web (LW).

Mitomycin C was used in a concentration of 2 mg/ml for a period of 4 minutes, followed by irrigation of the application site with 15cc of saline.

Myer and Cotton [14] grading of subglottic stenosis was used to indicate the sev erity of the stenosis; grade I (up to 50%) stenosis, grade II (51-70%), grade III (71- 99%) and grade IVwith no detectable lumen. Cohen’s classification [15] of laryngeal webs was used: type I (comprises >35% of the air way), type 2 (comprises 35-50% of the airway),type 3 (comprises 50-75% of the airway) and type 4 (comprises 75-90% of the airway). For each patient we reviewed the medical records and recorded clinical details such as age, sex, diagnosis, history of past surgery for their complaints, date of first surgery with mitomycin C, outcome of this first surgery (whether improved or not improved), type of revision surgery done (with or without topical application of mitomycin C), the follow up duration in months, final outcome of surgery and complications of the surgery or mitomycin C.

We defined improvement following surgery, as patient having satisfactory airway with no further symptoms of airway obstruction, satisfactory voice production and patent airway on endoscopy.

In this study we compared the outcome of the single use of mitomycin C 2 mg/ml for 4 minutes to the outcome of the single use of mitomycin C 0.4 mg/ml for 4 minutes which was previously reported in one study [8].

Chi-square test was used to compare categorical variables. A p-value less than 0.05 indicates statistical significance. For all statistical tests wc used the Statistical Package for Social Sciences version 17 software.


  Results Top


The study consisted of30 patients with laryngeal stenosis from this study and the previous one [13]. Thirteen patients (43.33%) with laryngeal web (LW), 12 patients (40%) with subglottic stenosis (SGS), 3 patients (10%) with sub-glottic stenosis and laryngeal web (SGS+LW), 1 patient (3.33%) with trans-glottic stenosis, and 1 patient (3.33%) with posterior commissure scar [Table 1] and [Table 2].
Table 1: From the previous study and shows the laryngeal cases, their diagnosis, H/O past surgery (N-NO, Y-Yes),Preoperative grade of narrowing, outcome after surgery (I-Improved, NI-Not improved), revision surgery (WM-With mitomycin, WOM-Without mitomycin), follow-up duration in months and complication PC: posterior commissure

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Table 2: Shows the cases of the study, their diagnosis, previous MMC application (N-NO,Y-Yes), pre and post- operative grade, outcome after surgery (I-Improved, NI-Not improved) follow-up duration in months and complications

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Age in this group ranged between 7 months and 43 years (Mean age = 118.19 months). In this group there were 20 male patient and 10 female patients (M: F = 2:1). These patients were followed up after surgery for a duration ranging from I month to 48 months (Mean = 9.57 months). Of these 30 patients, 3 patients were lost to follow up and will be excluded from our study. In the previous study, 5 patients (42%) improved following the first mitomycin C application of 0.4mg/ml and 7 patients (58%) did not improve. Six of those who failed the first intervention had revision microlaryngoscopic surgery without mitomycin C and 1 had revision microlaryngoscopic surgery with mitomycin C application. At the end of follow-up 5 patients with revision surgery improved, 1 patient did not improve and 1 patient was lost to follow-up. There were no complications seen in this group. [Table 1]

In this study, 11 patients (73.33%) improved after the first mitomycin C application of 2mg’ml, 4 patients did not improve (26.67%) [Table 2].

One patient still hav ing adhesions and scarring and there is no communication between subglottic region and rest of trachea; revision surgeries and stenting were done. The second patient was planned for tracheostomy. The third patient is still having symptoms and there is edema of the vocal cords and scarring; the plan is for revision surgery with possible tracheostomy. The fourth patient was considered as no improvement because there was change in the grade of SGS. Regarding complications; they were seen in 3 patients and included: mild posterior glottis scar, stridor with deep breathing and TC fistula with leaking [Table 2].

Comparing the improvement rate with the use of mitomycin C 2 mg/ml for 4 minutes (73.33%) [Table 2] to that of 0.4 mg/ml for 4 minutes (42%) [Table 1] showed that the concentration of 2mg/ml was associated with better outcome, and this difference was statistically significant p= 0.025.


  Discussion Top


Laryngotracheal stenosis remains a challenge to any otorhinolaryngologist due to scar formation and restenosis. Modulation of wound healing process to prevent excess scar formation can play a major role in improving the success rate and decreasing the need for further surgery. The goal of any treatment is the restoration of adequate airway, provision of competent larynx for protection against aspiration and the achievement of a satisfactory voicc.

Kunimoto and Mori (II) in 1963 presented the first clinical use of mitomycin C in the prevention and treatment of scar formation in pterygium surgery. Since then there have been many studies about the efficacy of mitomycin C and others on its complications on the airway [16]. Perepclitsyn et al [5] study showed a statistically significant difference when comparing the outcome of laryngeal and tracheal stenosis surgery of the mitomycin C with C02 group with those of C02 laser and with the C02 laser with steroid injection group . The percentages of successful outcomes in the study groups were 15%, 18.2%, and 75% with the C02 laser, C02 laser with steroid injection, and C02 laser with mitomycin C, respectively. Rahbar et al [1] demonstrated that topical application of mitomycin C can be beneficial in modulation of wound healing and in decreasing scar formation in treatment of airway stenosis.

Our primary aim of this study was to study the difference in the outcome of using two different concentrations of mitomycin C on the result of laryngeal surgery as such study never been addressed before.

By comparing the two different concentrations we can see that higher concentration of mitomycin C of 2mg/ml can result in better outcome (improvement is 73.33%) than the lower concentration 0.4mg/‘ml (improvement is 42%) [Table 1] and [Table 2]. This difference was statistically significant p= 0.025.

Endoscopic management of laryngeal and tracheal lesions has undergone tremendous advancement in the past 2 decades. The development of microlaryngoscopy, adaptation of the microscope, use of C02 laser, balloon dilatation as well as use of tnicrodebrider has significantly changed the outcome [17],[18].

Despite the advancement in endoscopic surgical techniques and the better understanding of the wound healing process as well as with ihc introduction of mucosa preserving laser surgery such as the micro-trap door flap technique [19] and radial incision and dilation [20], there is still a high degree of scar formation and re- stenosis. The review of literature shows a wide range of success by many authors ranging from 44% to 66% [8],[9] in endoscopic treatment of airway stenosis.

Regardless of the surgical technique used, there is always further injury to the airway mucosa which causes release of plasma proteins, blood cells and platelets, which react with tissue factors to form a fibrin-fibronectin clot [21]. This serves as a matrix for the migration of capillaries, fibroblasts and inflammatory cells. Fibroblasts synthesize collagen, glycosaminoglycans and fibroncctin to form granulation tissue. Over time there are collagen maturation, capillary resorption and myofibroblast contraction causing scar formation.

Use of mitomycin C in higher concentration may serve as an adjuvant tool in endoscopic laryngeal surgery that may help to reduce the need for open surgical technique.

We understand the limitation of this study as being retrospective study with limited number of patients; however, this can pave the way for future prospective studies to come up with more objective conclusions.


  Summary Top


The effect of mitomycin C in laryngeal cases has been proven in many studies before and one of them is our previous study 13. In this study we were interested to study the effect of mitomycin C in two different concentrations (0.4 mg/ml and 2 mg/ml) and our results were statically significant.


  Conclusion Top


In this retrospective study we compared the outcome of topical mitomycin C of 2mg/ml and mitomycin C of 0.4mg/ml on outcome of endoscopic dilatation of laryngeal stenosis. Our data suggest that using mitomycin C on higher concentration can improve the outcome of our surgery and the observed difference was statistically significant p=0.025.



 
  References Top

1.
Rehbar R, Stanley MS. Gerald BH. Mitomycin: Effect on laryngeal and tracheal stenosis, benefits and complications. Ann. Oto- Rhino-Laryngol. 2001; 110 (1): 1-6.  Back to cited text no. 1
    
2.
Eliashar R, Eliachar I. Escalamado R, Gramlich T, Storme M.Can topical mitomycin prevent laryngotracheal stenosis? Laryngoscope. 1999; 109:1594-1600.  Back to cited text no. 2
    
3.
Spector JE, Werkhaven J A, Spector NC, Huang S, Page RN, Baranowski B. Preservation of function and histologic apperarance in the injured glottis with topical mitomycin C. Laryngoscope. 1999; 109:1125-1129.  Back to cited text no. 3
    
4.
Ward RF, April MM. Mitomycin C in the treatment of tracheal cicatrix after tracheal reconstruction. Int J Peds Otorhinolaryngol. 1998; 44:221-226.  Back to cited text no. 4
    
5.
Perepelitsyn I, M.Shapshay S. Endoscpic treatment of laryngeal and tracheal stenosis - has mitomycin C improved the outcome? Otolaryngol Head Neck Surg. 2004 ; 131:16-20.  Back to cited text no. 5
    
6.
Mukesh P, Robert FW, Max MA, Bent JP, Froehlich P. Topical mitomycin as an adjunct to choanal atresia repair. Arch Otolaryngol Head Neck Surg. 2002;128: 398-400.  Back to cited text no. 6
    
7.
Bradford WH, Willam FM. Surgical outcome of choanal atresia. Arch Otolaryngol Head Neck Surg. 2001; 127:1375-1380.  Back to cited text no. 7
    
8.
Al-Ammar AY, Yassin S S. Effect of use of mitomycin C in laryngeal surgery. Saudi Journal Oto-Rhino-laryngol Head Neck Surg. 2008 ; 10:1-5.  Back to cited text no. 8
    
9.
Andrews AA, Horowitz SL. Bronchoscopic C02 laser surgery, Laser Surg Med.1980; 1:35-39.  Back to cited text no. 9
    
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Simpson GT, Strong MS, Healy GB, Shapshay SM, Vaughan CW. Predictive factors of success or failure in the Endoscopic management of laryngeal and tracheal stenosis. Ann Oto- Rhino-Laryngol 1982; 191:384-388.  Back to cited text no. 10
    
11.
Kunitomo N, Mori S. Studies on the pterigium. Part IV-A treatment of pterigium with mitomycin C instillation. Acta Soc Ophthal Jpn. 1963;67:601-607.  Back to cited text no. 11
    
12.
Chen C. Enhanced intra ocular pressure controlling effectiveness of trabeculectomy by local application of mitomycin C. Trans Asia-Pacific Acad Opthalmol. 1983;9:172-177.  Back to cited text no. 12
    
13.
Lee.D.A. Antifibrosis agents in glacucoma surgery. Invest Ophthalmol Vis Sci.1994; 35: 3789-91.  Back to cited text no. 13
    
14.
Myer CM 3rd, O’Connor DM, Cotton RT. Proposed grading system for subglottic steno is based on endotracheal tube sizes. Ann Oto-Laryngol.l994;103:319-23.  Back to cited text no. 14
    
15.
Cohen, S R.: congenital glottis webs in children. A retrospective study of 51 patients. Ann Otol. Rhinol. Laryngol. Suppl. 1985; 121:2-16.  Back to cited text no. 15
    
16.
Hueman E, Simpson B. Airway complication from topical mitomycin. Otolaryngol Head Neck Surg. 2005; 133(6):831-5.  Back to cited text no. 16
    
17.
Potanyi TG. Bredemeier HC, Davis TW. AC02 laser for surgical research. Med Bio- Eng Comput. 1970; 8:514- 518.  Back to cited text no. 17
    
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Shapshay SM, Simpson GT. Laser in broncology. Otolaryngol Clin N Am. 1983; 16:879-886.  Back to cited text no. 18
    
19.
Dedo HH, Soot CD. Endoscopic laser repair of posterior glottic, subglottic and tracheal stenosis by division or trapdoor flap. Lary ngoscope. 1984; 94:445-450.  Back to cited text no. 19
    
20.
Strong MS, Jajo GJ, Palanyi TG, Laser surgery in aerodigestive tract. Am J Surg. 1973; 126:529-533.  Back to cited text no. 20
    
21.
Tahery MM, Lee DA. Review: Pharmacologic control of wound healing inglaucoma filtration surgery. J Ocul Pharmacol. 1989;5:155-179.  Back to cited text no. 21
    



 
 
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