Quantitative results:
The tympanic bulla mucosa and tympanic membrane thicknesses of the
experiment group and the control group were measured. These histological
parameters are given in Table 1 and 2. The decrease in the minimum
mucosal thickness of the tympanic bulla was evaluated as statistically
significant (p=0.019). When the maximum and average thicknesses of the
tympanic membrane were evaluated, the decrease in the experiment group
was statistically significant (p=0.008, p=0.011).
Discussion
In the recent years, Mesna is being used in surgical procedures for
tissue dissection because of its chemical
properties.12 It is being used in the practice of
otolaryngology, especially to open the thickness between the tympanic
membrane and the middle ear mucosa that occurs in the adhesive otitis
media and atelectatic tympanic membranes.8,13 Yılmaz
et al conducted a study where they applied Mesna to the 42 ears of 39
patients diagnosed with retraction pockets fixed to the incudo stapedial
joint, stapes or promontorium and adhesive otitis
media.8 As a result they reported that the use of
Mesna is safe and eases the surgery, increasing surgical success.
Kalcioğlu et al reported in a retrospective study that the use of Mesna
increases surgical success, decreasing the need for second-look
surgery.13 We, in our clinic, usually use %20 Mesna
in the surgery of adhesive otitis media. We administer Mesna from the
non retracted region of the tympanic membrane or the antrum to the
middle ear cavity. We usually use dental injectors and administer one
dose. We wait approximately 4-6 minutes after administration.
When the studies in the literature are considered, it can be seen that
different agents have been used to prevent the development of
experimental cholesteatoma. In these studies, it has been reported that
cyclophospamide, isotretinoin, hyaluronic acid and mitomicin – C have
no inhibiting effect on the development of cholesteatoma, prednisolon,
transretinoic acid, 5- fluorouracilin have been reported to stop the
increase of cholesteatoma.6,14-18 In our study we
administered Mesna to provide the inhibition of the development
cholesteatoma that occurred with the intratympanic injection of
propylene glycol. According to the histopathological evaluation we
observed that Mesna decreases the development of cholesteatoma.
According to the theory of epithelial migration, propylene glycol causes
the formation of cholesteatoma.4,17 However there is
diversity amongs the studies regarding the prevalence of cholesteatoma
formation and histopathological properties. In experimental studies it
has been shown that proliferation of the epithelial basal layer of the
tympanic membrane starts in the third week.19,20 In
the sixth week, the prevalence of the cholesteatoma caused by %90
propylene glycol (%90) is %87.5.21 It has been shown
in the tympanic bullas of the chinchilla type rats that a single
application of %50 propylene glycol (%50) can form cholesteatoma after
three weeks.4 According to the information in the
literature, the concentration of the mucosal irritant used to form
experimental cholesteatoma and the duration of use are important.
Therefore diversity is observed between the studies. We used %50
propylene glycol in our study and sacrificed the rats 45 days after the
first administration. The cholesteatoma prevalence seen in the control
group of our study, %50, was evaluated to be in concordance with the
studies in the literature (%33–90).5
In our animal model study the decreases of the tympanic membrane
thickness and the tympanic bulla mucosal thickness seen in the
histopathological images between the control group and the experiment
group were evaluated to be statistically significant. It was observed in
the histopathological images that the cholesteatoma were mainly located
at the tympanic bulla. Melo et al showed in their experimental study
that epidermal invasion occurred from the tympanic membrane to the
tympanic bulla in the control group and study group.5
In a study conducted on Winstar rats in which the effect of
intratympanic single dose Mesna on cholestatoma was investigated, it was
emphasized that single dose intratympanic Mesna prevented the formation
of cholestatoma.22 In our study, despite the
intratympanic Mesna application applied for 4 times, no statistical
significance was found, indicating that the formation of cholestatoma
was completely prevented. However, in microscopic examination, it was
determined that Mesna reduced the occurrence prevalence of cholesteatoma
and fibrosis.
Conclusion
According to the histopahtological results of our study on the
experimental cholesteatoma model created on rats, the intratympanic
administration of Mesna had a decreasing effect on the prevalence of
cholesteatoma.
Acknowledgments: We thank Dr. Pınar Ergen for performing
histopathological examination.
Conflicts of Interest: The authors declare no conflict of
interest
Funding: This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit sectors.
Table 1. Statistical analysis of groups according to the
thickness of the tympanic membrane