1. Pilot study of a resorbable
poly-l-lactide Eustachian Tube stent;
feasibility and tolerability in two
animal models
JA Litner M.D., CJ Linstrom M.D.,
P Presti, MD, CA Silverman Ph.D.,
S McCormick M.D.,
GP Yu M.D., J Arigo M.D.

2. Middle Ear Disease
Susceptibility is clearly multifactorial
Hypoventilation is regarded as the root cause
ET dysfunction is the principal culprit

3. Background:
The Eustachian tube:
*Adam Images and Content under license from adam.com, Inc., ©
2002 adam.com, Inc.

4. Theories of Causality
Eustachian tubes are mechanically obstructed
Tubal stenosis noted in nearly half of chronic ears1
No significant post-mortem alteration in tube caliber2
Eustachian tubes are functionally obstructed
Tubal hypercompliance, The Floppy Tube3
Alteration in tubal surface tension dynamics4-8
1Tos M. Journal of Laryngology and Otology 1980;94:25-30
2Sade et al. American Journal of Otology 1986;7(6)
3Bluestone CD. Head and Neck Surgery- Otolaryngology. Ch. 111; 1993
4Miura M et al. Acta Otolaryngologica. 1996;116:840-44
5Fornadley JA et al. Otolaryngology- Head and Neck Surgery. 1994;110:110-4
6Nemechek AJ et al. Otolaryngology- Head and Neck Surgery. 1997;117:475-9
7Passali D et al. Respiration. 1987;51 supp.1:52-9
8Sujana S et al. Laryngoscope. 2004:114 ; 472-485

5. Significance
 Most Common Reason For Sick visits to PMD’s for Children <3
 5 Billion spent annually1
 One Million children undergo myringotomy annually 1
 Morbidity associated with MT
 Frequent returns to the OR
 Over prescription of Abx and rising resistance
 No Modality that specifically addresses the underlying
pathophysiology: Eustachian Tube Dysfunction
1Gates GA. Otolaryngology Head Neck Surg. 1996;114:525-530
Bluestone CD. Head and Neck Surgery- Otolaryngology. Ch. 111; 1993

6. Historical Interventions
ET insufflation prior to 19501
Elaborate surgical shunts, ET irradiation in
1960’s2-4
Armstrong tube invented in 19545
―Permanent‖ vent tubes
Silverstein tube6
Jahn Hydroxylvent tube7
1Shapiro SL. Eye Ear Nose and Throat Monthly. 1969;48:72-7
2Drettner B et al. Archives of Otolaryngology. 1969;90:122-8
3Goode RL et al. Laryngoscope. 1975;85:100-12
4House WF et al. Laryngoscope. 1969;79:1765-82
5Armstrong BW. Archives of Otolaryngology. 1954;59:653-4
6Silverstein H. Archives of Otolaryngology. 1970;91:313-8
7Jahn AF. Otolaryngology- Head and Neck Surgery. 1991;105(5):758-60

7. Problems with Current Approach
Medical
Increased antibiotic resistance
Surgical
Extrusion
Scarring/Perforation
Infection
Cholesteatoma
Disruption of graft healing
Failure to alter natural course
About 25% of procedures are repeat

8. ET Stenting
Wright Jr., 1976 –
Silastic Eustachian Tube
Prosthesis (SETP)
 Series of 138 patients with
average 26 month follow-
up
 80% had an aerated ME
behind intact TM after 6
months
 Poor results after 6 months
 No serious complications
Wright Jr. JW et al. Laryngoscope. 1977;87:207-14
Wright Jr. JW et al. ORL. 1978;86:834-7

9. Hypothesis
 Functional restoration most physiologically sensible
approach
 ET Stenting should augment function and restore
ventilation
 Success achievable through advances in biomaterials
science & capacity to elute drugs
 Successful applications to other hollow viscera1-6
1Korpela A et al. Chest. 1999;115:490-95
2Tamai H et al. Circulation. 2000;102:399-404
3Lumiaho J et al. Journal of Urology. 2000;164:1360-3
4Middleton JC et al. Medical Plastics and Biomaterials. 1998;March
5van Berkel A et al. Gastrointestinal Endoscopy. 2000;51:19-22
6Sung JJY. Journal of Industrial Microbiology. 1995;15:152-5

10. Stent Design Issues
 Stent Deployment
 Stent Retrieval
 Indwelling Effects
 Perforation
 Migration
 Occlusion
 Extrusion
 Ascending infection
 Reflux
 Autophony/Patulous
symptoms
 Longevity

11. Specific Aims
Aim 1– Explore technical ease
Aim 2– Establish safety profile
Aim 3– Determine tissue response
Aim 4– Assess extent of stent resorption

12. Stent Prototype
Manufactured by
PPD Méditech
Waterville, QC

13. Stent Location

14. Methodology- Study 1
 Adult Chinchilla ear
model
 NYMC Dept. Comp. Med.
facility—IACUC approved
 Sample size of 5 animals
 Baseline tympanograms
& otomicroscopy
 Stent implanted randomly
via transbullar approach
 Remaining ear matched
control

15. Methodology
All animals treated with peri-operative systemic
antibiotics
Serial testing at 4,6,8,10,14,18,22,26 weeks
Digital otomicro photos taken at each interval
One animal sacrificed at 10, 18, & 26 weeks
Temporal bones sectioned and evaluated blindly
by head and neck pathologist
Statistical comparison of between-group
differences in ME pressures over time

16. Results
2 animals died intra-operatively due to
respiratory arrest
Follow-up available for 3 animals up to time of
sacrifice
One animal developed transient post-operative
otorrhea in implanted ear via existing
myringotomy incision; resolved with ototopical
antibiotics

17. Otomicroscopy
Baseline 4 weeks 12 weeks 26 weeks
Test
Ear
Control
Ear

18. Tympanometry
100 100
Animal #1, Control ear 75 Animal #1, Test ear
75
Peak Compliance
Peak Compliance
50 50
(daPa)
25
(daPa)
25
0 0
-25 -25
-50 -50
-75 -75
-100 -100
Base 4 6 8 10 14 18 22 26 Base 4 6 8 10 14 18 22 26
Time (weeks) Time (weeks)
100
Control
100
Test
Peak Compliance (daPa)
Animal #2, Control ear 75 Animal #2, Test ear
75
50
Peak Compliance
Peak Compliance
50
25 25
(daPa)
(daPa)
Ear 0
-25 -25
0
Ear
-50 -50
-75 -75
-100 -100
-125 -125
Base 4 6 8 10 14 18 22 26 Base 4 6 8 10 14 18 22 26
Time (weeks) Time (weeks)
100 100
75 Animal #3, Control ear 75 Animal #3, Test ear
Peak Compliance
Peak Compliance
50 50
(daPa)
25
(daPa)
25
0 0
Data Points -25 -25
-50
Zero Point -50
-75 -75
-100 -100
Base 4 6 8 10 14 18 22 26 Base 4 6 8 10 14 18 22 26
Time (weeks) Time (weeks)

19. Pathology– Gross

20. Pathology– Micro
N
Control Ear
LP
C
Original Magnification x 60
O
B
TVP

21. Pathology– Micro
N
C
Test Ear
LP
Original Magnification x 60
O
TVP B

22. Pathology– Micro
Control Ear
Test Ear
G
G

23. Pathology– Micro
TZ
C
Test Ear

24. Stent Resorption

25. Data Analysis
Number Mean Standard Z value† P value
Peak Compliance(daPa)
deviation
Animal #1
Left 5 6.0 8.2 0.00 >0.05
Right 5 8.0 26.1
Animal #2
Left 9 -11.7 48.5 2.49 0.013
Right 9 -40.6 58.4
Animal #3
Left 7 8.6 22.7 1.89 0.058
Right 7 -17.9 46.4
† Wilcoxon signed ranks test.

26. Methodology- Study 2
 Adult NZ White Rabbit ear
model
 NYMC Dept. Comp. Med.
facility—IACUC approved
 Sample size of 10 animals
 Similar study protocol-
serial otomicroscopy at 2
week intervals
 All animals sacrificed at 6
months

27. Results Findings on Otomicroscopy in Test Ears
Test Week Week Week Week Week Week Week Week Week Week Week Week
Animal 1-2 3-4 5-6 7-8 9-10 11-12 13-14 15-16 17 –18 19-20 21 –22 23-24
#1 Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
#2 OM OM and Facial Resolved Normal Normal Normal Normal Normal Normal Normal Normal Normal
Cellulitis OM
#3 Normal Normal Normal Normal OM OM Normal Normal Normal Normal Normal Normal
#4 Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
#5 Normal Normal OM Normal Normal Normal Normal Normal Normal Normal Normal Normal
#6 Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
#7 Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
#8 OM Resolved Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
#9 Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
#10 Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal

28. Results
Histologic Findings at 6 months
Specimen Implanted Ear Control Ear
1 No Inflammation No Inflammation
2 No Inflammation No Inflammation
3 No Inflammation No Inflammation /
Cholesteatoma
4 No Inflammation No Inflammation
5 No Inflammation No Inflammation
6 No Inflammation No Inflammation
7 No Inflammation No Inflammation
8 No Inflammation No Inflammation
9 No Inflammation No Inflammation
10 No Inflammation No Inflammation

29. Results
Transient infections in 4 test ears
No chronic inflammatory response in all test
ears after 6-month incubation
No remnants of stents noted at 6 months

30. Conclusions
Stents were easily implanted
Stents were well tolerated with development of
transient otorrhea in few subjects
Stents engendered negligible inflammatory
response
Differential resorption- Stents were minimally
resorbed at 6 months in the Chinchilla model

31. Future Directions
Technology merits further testing for efficacy
Determine appropriate sterilization procedures
Clarify resorption spectrum
Explore use of surface agents or drug elution to
improve biocompatilibity and reduce biofilm

32. Acknowledgments
Dr. Ellen Levee, DVM for supervision of animal
care
New York Medical College DCM Staff
PPD Meditech, 50 Raymond, Waterville, QC
for manufacture and supply of stent prototypes