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Si2018 PDF
Si2018 PDF
Yu Si, Yu Bin Chen, Yu Guo Chu, Sui Jun Chen, Hao Xiong, Xi
Ming Chen, Wu Hui He, Yi Qing Zheng, Zhi Gang Zhang
PII: S0196-0709(18)30362-4
DOI: doi:10.1016/j.amjoto.2018.06.016
Reference: YAJOT 2051
American Journal of Otolaryngology--Head and Neck Medicine and
To appear in:
Surgery
Received
28 April 2018
date:
Please cite this article as: Yu Si, Yu Bin Chen, Yu Guo Chu, Sui Jun Chen, Hao Xiong,
Xi Ming Chen, Wu Hui He, Yi Qing Zheng, Zhi Gang Zhang , Effects of combination of
balloon Eustachian tuboplasty with methylprednisolone irrigation on treatment of chronic
otitis media with effusion in adults. Yajot (2018), doi:10.1016/j.amjoto.2018.06.016
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Yu Si1,2a, Yu Bin Chen3a, Yu Guo Chu4 ,Sui Jun Chen1,2 , Hao Xiong1,2 , Xi Ming
Chen1,2 , Wu Hui He1,2 , Yi Qing Zheng1,2 , Zhi Gang Zhang1,2 *
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1.Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial
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Hospital, Sun Yat-Sen University, Guangzhou, 510120. CHINA.
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2.Institute of Hearing and Speech-Language Science, Sun Yat-sen University,
Guangzhou, 510120. China.
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3. Department of Otolaryngology Head and Neck Surgery, Third Affiliated Hospital
of Sun Yat-sen, Sun Yat-Sen University, Guangzhou, CHINA.
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4. Institution for drug clinical trial, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen
University, Guangzhou, 510120. CHINA.
a: co-first author
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Correspondence:
zhangzz0369@126.com
Fax: 86-20-81332655, E-mail: .
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were in accordance with the ethical standards of the institutional research committee
and with the 1964 Helsinki declaration and its later amendments or comparable
ethical standards.
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Abstract
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Purpose: Adult chronic otitis media with effusion (COME) is characterized by
eustachian tube dysfunction and mucosal inflammation, which management has long
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been a challenge because of high recurrence. This study was to investigate the
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pathological changes of eustachian tube mucosa and optimized treatment.
eustachian tube mucosa were got preoperative and 1 month post. Recurrence ratio and
eustachian tube scores (ETS) were used to evaluate the effect of treatments.
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Results: All patients showed narrowed with edematous and thickened Eustachian
tube mucosa. At 1 month post treatment, BET with methyprednisolone irrigation
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epithelium and cilia. For group II to IV, The recurrence rate was significantly lower in
group IV compared with the other two, but only significantly lower in group IV VS group II at
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3month and 6 month, no significant difference at 12month. The recurrence rate was
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significantly higher in group I during follow-up. The ETS were improved in group II,
III and IV after treatment. At 1 month and 3 months posttreatment, group IV had
significant higher ETS compared with other groups (P<0.05). There was no serious
complications occurred.
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as a good choice for COME in adults, which has less recurrence rate and prompt
recovery of ET function.
Key words: Adult chronic otitis media with effusion, balloon eustachian tuboplasty,
methyprednisolone irrigation
Introduction
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Otitis media with effusion (OME) is a common disease in young children, but it is
still regularly seen in adulthood, particularly in conjunction with cigarette smoking,
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upper respiratory infection and rhino-sinusitis1 . The symptoms of aural fullness and
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hearing loss can significantly affect quality of life. Besides, OME can also cause
tympanic membrane retraction, ossicular erosion and even cholesteatoma formation2 .
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OME is characterized by inflammation of the middle ear mucosa and effusion within
the usually gas-filled middle ear cavity1 . Past clinical and experimental research
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certified a central role for adequate ET function in maintaining middle ear health.
Eustachian tube dysfunction caused middle ear pressure dysregulation and mucosal
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46% of OME cases are caused by Eustachian tube dysfunction (ETD) 3 .. For the OME
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with ETD, its treatment in adults is often less satisfactory. Nasal steroid sprays seemed
dysfunction of eustachian tube, with recurrence rates between 9,1% and 59% of
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cases5,6 . The use of long-term ventilation tubes carries the risk of permanent tympanic
membrane perforation, estimated by one study to occur in 19% of cases 7 .
Recent published papers evidenced that balloon dilation eustachian tuboplasty (BET)
significantly improved ET function and ventilation of the middle ear. The first
long-term results by Schroder et al showed an improvement of the eustachian tube
function after 8 weeks in 62% of the patients, and in 66% of the patients after 1 year 8 .
However, nearly 40% of patients still had no improvement of symptom. Regretfully,
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there are rare reports about the failed reason. Besides, mucosal inflammation is
another typical character of OME, which is also an important prognostic factor.
Mucosa production is the normal reaction of mucosal surfaces to inflammation.
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study aims to explore whether BET with methyprednisolone irrigation of the lumen
could restore the normal mucosal function of ET and further increase the therapeutic
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effects for COME.
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Materials and Methods NU
Ethics Statement: Before the study was initiated, approval was obtained from the
local Ethics Committee of Sun Yat-sen University, and written informed consents
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Study population
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This was a retrospective study. Patients were recruited from May 2013 to May 2016 in
Sun yat-Sen Memorial hospital . Criteria for this procedure included: 1) age: between
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18 years to 65 years old; 2) single-side OME; 3) the duration of disease was more
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Study design
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The treatment protocols included: tympanic paracentesis group (group I), BET only
group (group II), BET+ tympanic paracentesis (group III) and combination of BET
and tympanic paracentesis with methyprednisolone irrigation(group IV). For group I,
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systerm (Spiggle & Theiss, Overath, Germany) was employed to dilate ET. The
operations were performed with endoscopic assistance (0-degree view angle) via
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ipsilateral nostril. A curved guiding catheter with a tip angle of 45 degrees was
propelled into the ET nasopharyngeal orifice through the nasal cavity. A 3 mm
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(diameter) and 20mm (length) balloon catheter was pushed through the guiding
catheter and atraumatically into the ET orifice until reaching the first mild resistance
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as it approached the narrowest diameter at the bony-cartilaginous isthmus, inflated to
a pressure of 10 bars for 2 minutes using a pressure applicator (Spiggle & Theiss).
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Group III: Tympanic paracentesis was performed firstly, and then followed by BET.
Group IV: Tympanic paracentesis was performed as described in group I, then 1ml
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methyprednisolone ( 20mg/mL) was intratympanic injected via the same hole in the
tympanic membrane, irrigated and sucked the tympanic cavity for three times. The
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other 1ml methyprednisolone was injected to immerse the middle ear. Finally, BET
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were performed as group II. The changes of ET nasopharyngeal orifice were recorded
after methyprednisolone irrigation, during and after dilation under endoscope. Figure
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received nasal spray hormone treatment for 6 weeks after operation. Except Group I,
the other three groups were operated under general anesthesia. All the surgeries and
biopsy were performed by senior author.
As depicted in supplementary Figure1, Six patients from each group were chosen
randomly, biopsies were taken with pediatric up-biting Blaksley forceps from
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two pathologists who were blinded to the clinical information and to whether the
specimens were pre- or postoperative.
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Histological profiles of the eustachian tube mucosa were analyzed according to
Kivekas study9 , but simplified to the overall quality of epithelium, cilia
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quality/quantity and intraepithelial inflammation. The overall quality of epithelium
was rated epithelium uniform as excellent, variable as good, squamous metaplasia as
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fair, and squamous absent as poor, on a scale of 3 to 0; Presence, fair or absence of
To quantify the function of ET, we used a summation point score for ET function that
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Ockermann’s study10 ,which developed to ETDQ-7 later. The ETDQ-7 score is a valid
and reliable symptom score for adult patients with ET dysfunction11 . TMM was used
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pressure values are tested subsequently (30, 40, and 50 mbar). The time of opening in
relation to pressure applied is measured. The opening latency is calculated and named
index R. The TMM results are weighted as follows: no R with 0 points, R >1with 1
point, and R <1 with 2 points for the measurements at 30, 40, and 50 mbar,
respectively.The patients were questioned if they noticed a clicking noise during
swallowing and Valsalva maneuver. No notice of clicking is judged as 0 points,
infrequently with 1 point, and all times noticing of clicking is appraised with 2 points
for swallowing and Valsalva maneuver each. The points of these five tests were
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plused. Therefore, the ET score (ETS) ranges from 0 to 10. A score of 10 corresponds
to optimum eustachian tube function, and a score of 0 refects a strongly obstructive
eustachian tube dysfunction. The ET score (ETS) were collected by the study nurse
blindly.
Follow up
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months and 1 year post -operation. Recurrence was defined by a type B tympanogram,
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or the otic endoscopy findings were air-fluid level air bubbles or completed effusion.
The associated risks of complications, such as otorrhea, persistent perforation of the
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eardrum, patulous eustachian tube,subcutaneous emphysema, haemotympanum,
mucosal laceration and internal carotid artery injury, were observed during follow-up.
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Statistical Analyses:
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Statistical analysis were performed using SPSS for Windows version 16.0 (SPSS,
Chicago, IL, USA). Pared T test was used to compare the histopathological scores
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before and after treatment. One-way ANOVA was used to evaluate the differences of
histopathological scores, and eustachian tube function scores in the four groups. Data
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found, a Bonferroni test was used to assess the difference between each of the two
groups. Chi-square was chosen to analyze the difference of recurrence rate in different
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groups.
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Results
Study Population
All the nasopharyngeal orifice of eustachian tube showed narrowed with edematous
and thickened mucosa. No liquid came out after methyprednisolone irrigation of
middle ear in 46 patients.(Supplementary Fig1A). During dilation, bubbles with water
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Pathologic profile of eustachian tube nasopharyngeal orifice
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There were no complications after the biopsies. All biopsy sites healed well, leaving a
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showed in Figure 1. A summary of the histopathological results was showed in Figure
2. There were significant changes in the quality of epithelium and cilia in group II,III
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and IV before and after BET(paired t tests, all p<0,05), and the scores were the
highest in group IV. The postoperative quality of epithelium and cilia changes were
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the recurrence rate is 92% in group I, which is the highest recurrence rate among the
four groups (Table 3). BET can reduce the recurrence rate to 46% and tympanic
paracentesis can enhance the effect of BET since the recurrence rate is 38% in group
III. Combination of BET and intratympanic injection with methyprednisolone gained
the lowest recurrence rate (20%) among 4 groups ( all P<0.01). At 3 months and 6
months postoperation, the recurrence rate in group IV was significanty lower than
group I and II(all P<0.05). However, no significant difference was observed between
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group II and group III. At 12 months postoperation, the recurrence rates were much
lower in group II, III and IV than group I. However, there were no significant
differences among group II, III and IV (all P>0.5).
The preoperative ETS in four groups were 1.53±3.2, 1.67±2.8, 1.39±1.9 and 1.57±2.1,
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respectively(Table 4 and figure 3). The ETS were much higher in group II, III and IV
compared with group I during follow-up (all p<0,05). At 1 month and 3 months
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postopeartion, group IV got higher ET scores than group II and group III( all P<0.05).
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group II, III and IV. The ETS are higher in group III than group II during follow-up,
but not statistical different.
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Complications and Adverse Effects
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In group II, one patient developed temporary patulous eustachian tube after operation,
but the symptoms disappeared automatically one month later. There was no tympanic
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laceration and internal carotid artery injury occurred in all the four groups.
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Discussion
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The management of adult COME has long been a challenge for ENT clinician.
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Medicine and physical training usually show poor efficacy in the treatment of COME.
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Tympanostomy tube placement can equalize middle ear pressure and improve patients’
symptoms, but it would increases risks of complications such as perforation, otorrhea,
Recently, BET has emerged as a potential therapeutic option for ETD and shown
promising results. A five-year result of BET has proved that BET is a feasible and safe
therapeutic procedure with few side effects. Eustachian tube function is improved
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that BET leads to micro-fractures within the cartilage of the eustachian tube and
persistent extension of the lumen. Moreover, the inflammatory infiltration and
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lymphoid follicles are crushed by BET and could be replaced by a thinner layer of
healthy fibrous tissue, with a wider lumen for the ET. The effect seemed like a
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mucosal-preserving adenoidectomy within the lumen of the ET, thereby reducing the
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inflammatory burden and giving the tissues a “fresh start.” . Although high
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successful ratios of improvement of ET function after BET were reported, there are
still some patients presented ETD symptoms again after BET treatment. In our study,
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the recurrence rate in BET group is up to 46% one month after treatment. Even in
patients treated with BET and tympanic paracentesis, the recurrence rate is still more
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than one third one month after treatment. We proposed this phenomenon is attributed
to the crush injury of the mucosa by the dilation. The immediate post dilation
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histopathology showed crush injury to the epithelium and submucosa, 9 . Though BET
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could extend the lumen of the ET, it also leads to the damage of mucosa during
dilation, which would aggravate the inflammation and edema of the mucosa. That
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significantly decreased the recurrence rate to 20% at the same time point. Similarly,
combination of BET and tympanic paracentesis with methyprednisolone irrigation
promptly improved ETD symptoms compared to other three groups one month after
treatment. One month post dilation histopathology also showed best mucosal recovery
in BET and tympanic paracentesis with methyprednisolone irrigation group. These
data suggest that methyprednisolone irrigation can reduce the mucosal crush injury
caused by dilation.
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effusion, and found swelling of the mucosa of eustachian tube and middle ear with
goblet cell hyperplasia, and cilia were irregularly arranged 13 . Histological evaluation
of the ET’s mucosal lumen from patients with ETD also found inflammatory change
of the mucosa with lymphocytic infiltrates and lymphoid follicles 9. Our study also
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found different levels of ET’s mucosal disruption, cilia loss and inflammatory
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infiltrate, even penetrating through to the surface of the epithelium in some cases.
Therefore, it is crucial to regain normal mucosa of middle ear for treatment of COME.
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Methyprednisolone is a classic steroid. Steroids are commonly applied for OME
treatment because of its efficient anti-inflammatory activity. Steroids can also
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promote to remove of fluid in middle ear, decrease mucin production. In addition,
steroid remained in the Eustachian tube could improve the status of mucosa, recover
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the transport function of ciliary epithelium and enhance the secretion function of
Eustachian tube surfactant14 .In our study, one month post dilation histopathology
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can effectively improve the function of ET. We think that combination of BET and
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methyprednisolone could to remove fluid in the middle ear to the greatest extent, and
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steroid could exert its anti-inflammatory and anti-edema effects in the middle ear.
Limitations of the study: Our study design is deficient. Because the patients enrolled in
cohort were the recurrent COME patients, most of them refused to go to the wait-list
control group. It is our limitation that we could not have an important comparison
between the natural course of the disease and provide for a more robust interpretation
of what the findings may mean clinically. We lack tympanic methylprednisolone
injection with paracentesis group, If we can have a tympanic methylprednisolone injection
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with paracentesis group, it will be a perfect design. We might be able to answer the question:
necessary? But without BET, can methylprednisolone be deliver to ET lumen as effect as with
BET. We only enrolled patients with single side of COME, because we plan to analyze
the effects by patients not by ears. In the further study, we may research on bilateral
patients. Besides, we did do the biopsy at 3month, 6month and 1year follow-up, we
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could not know the histopathological changes in the late stage.
Conclosion
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The main findings of the study provided evidence that combination of BET and
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tympanic paracentesis with methyprednisolone irrigation is a good choice for chronic
OME, which has less recurrence rateand prompt recovery of ET function.
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References
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dysfunction in adults and children. Acta Otolaryngol Suppl;500:66–9.
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4. Gluth M.B., McDonald D.R., Weaver A.L. et al. (2011) ‘Manage ment of eustachian tube dysfunction
with nasal steroid spray: a prospective, randomized, placebo -controlled trial.’. Arch. Otolar- yngol.
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Head Neck Surg. 137, 449–455.
6. Huseyin Yaman *, Suleyman Yilmaz, Ender Guclu2010). Otitis media with effusion: Recurrence after
7. Van H.N., De S.G. & Mulder J.J. (2002) ‘Long-term ventilation tubes: results of 726 insertions’. Clin.
8. Schroder, S., Reineke, U., Lehmann, M., Ebmeyer, J. & Sudhoff, H. (2013) Chronic obstructive
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10. Ockermann T1 , Reineke U, Upile T. Balloon dilatation eustachian tuboplasty: a clinical study.
11. Edward D. McCoul, MD, MPH, Vijay K. Anand. (2012). Validating the Clinical Assessment of
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12. Miller, B.J. & Elhassan, H.A(2013). Balloon dilatation of the Eustachian tube: an evidence-based
review of case series for those considering its use. Clin. Otolaryngol. 38, 525–532.
13. Zhu, Z. H., Shan, Y. J., Han, Y., Zhu, L. W. & Ma, Z. X(2013). Pathological study of otitis media with
effusion after treatment with intranasal pulmonary surfactant. Laryngoscope 123, 3148-3155,
doi:10.1002/ lary.24166.
14. Fengling Yang, Yu Zhao, Ping An, Yongbo Zheng, Rong Yu, Deying Gu, and Hong Zheng.( 2014)
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Longitudinal Results of Intratympanic Injection of Budesonide for Otitis Media With Effusion
in
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Figure legend
A: Preballoon biopsy, the mucosa was infiltrated with lymphocytes, cilia loss.
B:One month postballoon biopsy from patients without methyprednisolone irrigation,
Less lymphocytic infiltrated compared to the preballoon biopsy. Fibrous tissue
formed.
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C: One month postballoon biopsy from patients with methyprednisolone irrigation.
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Healthy ciliated pseudo-columnar epithelium appeared. No inflammation infiltrated.
(magnification 20x ,hematoxylin and eosin stain).
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Figure 2.Quantitively analysis of histological profile of eustachian tube mucosa
A, B: Epithelium scores and cillia scores were significantly increased in group II,III
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and IV one month postoperative.
C: Intraepithelial inflammation scores were significantly decreased in group IV
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NO.of Female 23 27 27 25
Allergic rhinitis 5 6 7 8
Adenoid hypertrophy 0 0 0 0
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ET mucosal inflammation 50 50 50 50
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Scores of ET function 1.53±3.2 1.67±2.8 1.39±1.9 1.57±2.1
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nasal spray hormone 47 42 43 41
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*some patients droped out during follow-up. recurrence rates were analyzed by “intention
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to treat principle” % recurrence= NO. of recurrence/ 50 at each follow-up time
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Scores
Epithelium quality
Excellent(uniform) 3
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Good(variable) 2
Fair(Squamous metaplasia) 1
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Poor(absent) 0
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Cilia quality/quantity NU
Present 2
fragmented 1
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absent 0
Intraepithelial inflammation
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present 0
absent 1
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M onth 6 4.61±2.95 3.79;5.46 7.26±2.58 6.48;7.94 7.46±2.10 6.85;8.09 8.54±1.85 8.01;9.07
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M onth12 3.73±2.08 3.11;4.27 7.22±1.34 6.75;7,69 7.39±1.98 6.81;7.99 8.05±1.67 7.53;8.57
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Figure 1
Figure 2
Figure 3
Figure 4