Do the Angle and Length of the Eustachian Tube Influence the Development of Chronic Otitis Media?

Transcription

1 The Laryngoscope VC 2015 The American Laryngological, Rhinological and Otological Society, Inc. Do the Angle and Length of the Eustachian Tube Influence the Development of Chronic Otitis Media? Aykut Erdem Dinç, MD; Murat Damar, MD; Mehmet Birol Ugur, MD; Ibrahim Ilker Oz, MD; Sultan Şevik Eliçora, MD; Sultan Bişkin, MD; Hakan Tutar, MD Objectives/Hypothesis: To compare the eustachian tube (ET) angle (ETa) and length (ETl) of ears with and without chronic otitis media (COM), and to determine the relationship between ET anatomy and the development of COM. Study Design: A retrospective case-control study. Methods: The study group comprised 125 patients (age range, 8 79 years; 64 males and 61 females) with 124 normal ears and 126 diseased ears, including ears with chronic suppurative otitis media (CSOM) with central perforation, intratympanic tympanosclerosis (ITTS), cholesteatoma, and a tympanic membrane with retraction pockets (TMRP). ET angle and length were measured using computed tomography employing the multiplanar reconstruction technique. Results: The ETa was significantly more horizontal in diseased versus normal ears of all study groups (P 5.030), and there was no group difference in ETl (P 5.160). ETl was shorter in CSOM versus ITTS ears and normal ears (P and P 5.003, respectively) and in cholesteatoma versus TMRP ears (P 5.014). In the unilateral COM group, there were no significant differences in the ETa or ETl of diseased versus contralateral normal ears (P and P 5.710, respectively). The ETa was significantly more horizontal in childhood-onset diseased versus normal ears (P 5.027), and there was no group difference in ETl (P 5.732). The ETa (P 5.002) and ETl (P <.001) were significantly greater in males than females. Conclusions: A more horizontal ETa and shorter ETl could be contributory (though not significantly) etiological factors in the development of COM. Key Words: Eustachian tube anatomy, chronic otitis media etiology. Level of Evidence: 3b Laryngoscope, 125: , 2015 From the Department of Otorhinolaryngology Head and Neck Surgery (A.E.D., M.D., S.S.E., S.B.) and Department of Radiology (I.I.O.), B ulent Ecevit University Faculty of Medicine, Zonguldak, Turkey; and the Department of Otorhinolaryngology Head and Neck Surgery (M.B.U., H.T.), Gazi University Faculty of Medicine, Ankara, Turkey. Editor s Note: This Manuscript was accepted for publication February 3, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Aykut Erdem Dinç, B ulent Ecevit University Faculty of Medicine, KBB AD, Kozlu, Zonguldak, Turkey. aykuterdem@yahoo.com DOI: /lary INTRODUCTION The eustachian tube (ET) performs three functions: ventilation, protection, and clearance of the middle ear. The ET also plays an important role in maintaining middle ear physiology and functionality. 1 ET length (ETl) and angle (ETa) determine the likelihood of preventing nasopharyngeal reflux into the middle ear. 2 Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear cleft and mastoid mucosa, in which the tympanic membrane is not intact, and recurrent ear discharge or otorrhea is present. 2,3 The pathogenesis of CSOM is multifactorial; environmental and genetic factors, as well as the anatomical and functional characteristics of the ET, are all involved. 2 Infant ETs are shorter, with a morehorizontal ETa, compared with adult ETs 2,4 ; these anatomic features may underlie the increased susceptibility to otitis media with effusion (OME) and recurrent acute otitis media (AOM) observed in infants and children. CSOM in adults is predicted by recurrent AOM or chronic OME in childhood. 3 Studies linking the anatomical and functional characteristics of the ET with the pathogenesis of chronic otitis media (COM) have examined at risk populations, such as those with Down syndrome and craniofacial anomalies. These patients are at increased risk for developing ear disease as infants and young children due to their short, horizontal, and floppy ETs. 2 We found no histopathological or radiological studies analyzing the relationship between ET anatomy (angle and length in the anatomical position) and the development of COM. Tympanosclerosis (TS) is a disorder of the tympanic membrane and middle ear mucosa characterized by hyalinization and calcification of the submucosal connective tissue layer of the middle ear. 5 Although the exact etiology of TS has not been elucidated fully, it is widely accepted that TS commonly develops secondary to AOM and COM. Tympanic membrane retraction pockets are characterized by partial collapse of the mesotympanic or epitympanic cavities. 6 ET dysfunction and weakening of the tympanic membrane, due to OME, are major contributors to retraction pocket development. 7 Cholesteatoma is a benign, gradually expanding, destructive epithelial lesion of the temporal bone that erodes adjacent bony structures, leading to various complications. ET 2187

2 were variously characterized by CSOM (COM with central tympanic membrane perforation), intratympanic tympanosclerosis (ITTS), cholesteatoma, and a tympanic membrane with retraction pockets (TMRP). All patients exhibited otological symptoms such as recurrent purulent otorrhea or hearing loss. The contralateral sides of group 1 were normal. All patients underwent surgery, including tympanoplasty with or without mastoidectomy, with the diagnosis confirmed intraoperatively. The bilateral healthy control group (group 3) consisted of 31 adult patients with aural diseases (i.e., sensorineural hearing loss, tinnitus, or otitis externa) other than middle ear problems (14 males, 17 females; mean age 5 47 years; range: years; median age 5 48 years). Patients in group 3 had no past or current history of otorrhea; otomicroscopic examination revealed that ear drums were normal. All multislice CT images for group 3 indicated normal inner and middle ears. Ears exhibiting ET obstruction (according to intraoperative results), and patients with craniofacial abnormalities, were not included in the study. Fig. 1. Reconstructed computed tomography images of a 36-yearold male. In the symmetrically reformatted image in the axial and coronal plane, the basal turn of the cochlea (black arrows) is the reference structure. The axial image was adjusted in the anterior posterior axis with respect to the Frankfort line. *The upper-most portions of the right and left external auditory canals; the white arrow indicates the inferior-most portion of the infraorbital rim. [Color figure can be viewed in the online issue, which is available at dysfunction represents the pathophysiologic mechanism underlying retraction pocket formation and cholesteatoma. 8 ET anatomy, physiology, and modeling continue to be a focus of research, due to the important role of the ET in maintaining middle ear physiology and functionality. However, that focus has shifted from histopathological to noninvasive imaging studies. 9 The multiplanar reconstruction (MPR) technique is one of several new imaging techniques for computed tomography (CT), providing clearer imaging of the anatomic features of the ET. 4 The present study measured the angle and length of the ET, against the Frankfort horizontal plane, using MPR CT images of patients with and without COM, to investigate the relationship between the anatomical features of the ET and the development of COM. MATERIALS AND METHODS Participants This retrospective, institutional review board-approved study assessed patients who either underwent ear surgery, or received temporal CT scans due to ear problems other than middle ear disease, between August 2012 and January Of 277 Turkish patients operated on during this period, 94 were diagnosed with COM; 31 polyclinic patients not diagnosed with COM received 0.5-mm-thick multislice CT imaging. The unilateral COM group (group 1) consisted of 124 ears (62 patients; 32 males and 30 females; mean age 5 37 years, range: 8 79 years; median age 5 36 years). The bilateral COM group (group 2) comprised 64 ears (32 patients; 18 males and 14 females; mean age 5 34 years; range: years; median age5 30 years). Diagnoses were rendered according to otomicroscopy, audiometry, and multislice CT images; diseased ears 2188 Procedure A multidetector CT system (Activision 16-row CT scanner; Toshiba Medical Systems, Otawara, Japan) was used for CT imaging. Imaging parameters included a slice thickness and reconstruction interval of 0.5 mm, a pitch/helical factor of 1.438/23, and a field of view of cm. ET measurements were performed using the Osirix imaging software package (Pixmeo, Geneva, Switzerland). The MPR technique was used to reconstruct 0.5- mm-thick gapless images parallel and perpendicular to the long ET axis. During the reconstruction of MPR images, the cochlea was used as a reference structure, because it is not influenced by changes in the mastoid bone. To resolve the asymmetry associated with patient positioning, the angle of the reformatted image was adjusted until the basal turns of both cochleae were equally viewable in axial planes and coronal planes. The axial images were also adjusted in the anterior posterior direction with reference to the Frankfort line, which is defined as the plane connecting the uppermost portions of the right and left external auditory canals and the inferior-most portion of the infraorbital rim of the left eye (Fig. 1). Images were standardized for all patients. The tympanic and pharyngeal orifices of the ET were observed in sections perpendicular to the long ET axis. The various parts of the ET were defined as described in previous studies 4,10 ; the pharyngeal orifice of the ET lumen was the point nearest the pharynx at which a loop-shaped ET lumen appeared, and the tympanic orifice was the nearest point in the ET before the external auditory canal appeared in cross-sectional images. ETl was defined as the distance between the most superior points of the pharyngeal and tympanic orifices. Angle of the ET was defined as the angle of a straight line representing the length of the ET with respect to the Frankfort plane (Fig. 2). The curved length of the ET was defined as the angled distance between the midpoints of the pharyngeal and tympanic orifices, measured using the curved MPR technique (Fig. 3). ET curved length measurements were possible in a total of only 40 ears, and not in others, because the majority of the ET cartilaginous portion could be visualized in only in those 40 ears. Each measurement was obtained on three occasions by the first author at different times. Because the measurement points were clearly described, measurements were consistent. Although the author was blinded to the intraoperative diagnosis and history of the patients, he could observe normal and diseased ears in CT images. Study Groups The straight and curved lengths of the ET were compared in a total of 40 ears in which curved ETl measurements were

3 Fig. 2. The multiplanar reconstruction process of the computed tomography images showing the right (R) diseased side and left (L) healthy side of the same patient in Figure 1. (A) The horizontal plane parallel to the Frankfort plane at the level of eustachian tube (ET) tympanic orifice (TO). (B) The oblique axial image along the course of the ET between the superior point of the tympanic and pharyngeal orifices. (C) Along the long axis of the ET, perpendicular to the Frankfort plane; the purple line is the line parallel to the Frankfort standard plane at the level of the TO. (D) During measurements, the superior point of the TO and superior point (*) of the pharyngeal orifice can be observed in the sagittal plane. The white arrowheads indicate the superior point of the ET TO. The black arrows indicate the ET lumen, and the green line is the line between the superior points of the ETl. ETa 5 angle of the green line against the Frankfort plane; ETC 5 ET cartilage; ETl 5 superior points of the tympanic and pharyngeal orifices; GG 5 geniculate ganglion; IAC 5 internal acoustic canal; LL 5 lateral lamella of the ETC; ML 5 medial lamella of the ETC; PO 5 pharyngeal orifice just before the fusion of the LL and ML; STR 5 supratubal recess; TT 5canal for the tensor tympani muscle; AL 5 Left-Anterior; LP 5 Left-Posterior; PR 5 Right-Posterior; RA 5 Right-Anterior. [Color figure can be viewed in the online issue, which is available at possible. Normal ears (n 5 124) comprised the contralateral normal ears of group 1 and the bilateral normal ears of group 3. Diseased ears (n 5 126) comprised the diseased ears of groups 1 and 2, and were categorized as CSOM (n 5 42), ITTS (n 5 16), cholesteatoma (n 5 43) or TMRP (n 5 25). Diseased ears in group 1 were also grouped according to disease onset time, with 21 childhood-onset (<8 years of age) and 38 later-onset (8 years of age) ears. Diseased ears were compared with 59 contralateral normal ears; three patients with no reliable medical history were excluded. Statistical Analyses Statistical analyses were performed using the SPSS for Windows software package (version 18; SPSS Inc., Chicago, IL). The distribution of the data was determined by either the Kolmogorov-Smirnov or Shapiro-Wilks test. Continuous variables were expressed as means (6 standard deviation) or medians (minimum maximum); categorical variables were expressed as frequencies and percentages. Continuous variables were compared using either the independent-samples t test or Mann-Whitney U test; categorical variables were compared using the Pearson v 2 test. A value of P <.05 was taken to indicate statistical significance. The Kruskal-Wallis test was used to determine group differences. A Bonferroni-adjusted Mann- Whitney U test was used for post hoc testing of the Kruskal- Wallis test. Pearson correlation coefficient determined the relationship between continuous variables. RESULTS There was a strong correlation (r ) between the straight distance between the pharyngeal and tympanic orifices and the angled ET length. The ETa and ETl in normal ears of all study groups are listed in Table I. The ETa was significantly more horizontal (P 5.002), and the ETl was significantly shorter (P <.001) in females than in males. In group 3, TABLE I. Angle and Length of the ET in Females and Males in Normal Ears of Group 1 and 3. Normal Ears of All Study Groups Fig. 3. Reconstructed computed tomography images of a 58-yearold male. The angled length of the eustachian tube (red dotted line) was measured using the curved multiplanar reconstruction technique. [Color figure can be viewed in the online issue, which is available at Female (64 Ears) Male (60 Ears) P ETa ( ) ETl (mm) 38.5 ( ) 40.0 ( ) <.001 ET 5eustachian tube; ETa 5 ET angle; ETl 5 ET length. 2189

4 TABLE II. Angle and Length of the ET in Normal and Diseased Ears of All Study Groups. No. ETa P Value ETl P Value Normal ears ( ) Diseased ears ( ).160 CSOM ( ).003 ITTS ( ).207 TMRP ( ).156 Cholesteatoma ( ).088 Gender distribution did not differ between normal versus diseased ears (P 5.528) and among the types of the diseased ears (P 5.335) CSOM 5 chronic suppurative otitis media; ET 5eustachian tube; ETa 5 ET angle; ETl 5 ET length; ITTS 5 intratympanic tympanosclerosis; TMRP 5 tympanic membrane with retraction pockets. there were no differences in the ETa or ETl of the right versus left side (P 5.477, P 5.822). There were no differences in the ETa or ETl of the contralateral normal ears of group 1 versus bilateral normal ears of group 3 (P and P 5.380, respectively). The ETa and ETl of normal and diseased ears of all study groups are listed in Table II. The ETa was significantly more horizontal in diseased versus normal ears (P 5.030), but there was no group difference in ETl (P 5.160). Analysis of ETa and ETl in the context of specific types of the COM indicated a significant decrease, compared with normal ears, in the ETa of ITTS ears (P 5.010) and in the ETl of CSOM ears (P 5.003). ETl was shorter in CSOM versus ITTS ears (P 5.007), and there was no group difference in ETa (P 5.092). ETl was shorter in cholesteatoma versus TMRP (P 5.014) ears, and ETa was not different between the groups (P 5.916). The ETa and ETl values of normal and diseased ears in group 1 are listed in Table III. There were no differences in the ETa or ETl of contralateral normal versus diseased ears (P and P 5.710, respectively). ETa and ETl values of group 1, for both ears in which otological symptoms appeared in childhood and normal ears, are listed in Table IV. The ETa was significantly more horizontal in childhood-onset diseased ears versus normal ears (P 5.027), but there was no group difference in ETl (P 5.732). There were no significant differences in the ETa and ETl of normal versus those in which disease appeared after childhood (P and P 5.416, respectively). Patients in group 3 were characterized by a significantly higher mean age compared with those in groups 1 and 2 (P <.001). There were no correlations between age and ETa (r , P 5.057) or ETl (r , P 5.906). DISCUSSION Previous studies measured ETl and ETa using cross-sectional histologic analysis, which is subject to tissue processing and sectioning errors. The ETa is 45 in adults and 10 in infants; ETl ranges between 31 and 38 mm in gross anatomy studies. 11 The angle and length of the ET can be precisely measured using CT with the MPR technique. 4,10 Takasaki et al. studied the anatomical features of the ET of normal adults, infants, and children, with and without OME, using CT with MPR. In normal adult ears, ETa and ETl were and mm, respectively, for the right ear, compared with and mm, respectively, for the left ear. 4 Ishijima et al. evaluated postnatal ET development by three-dimensionally reconstructing temporal bones; mean ETl in a 3-month-old infant increased from 21 mm to 37 mm in the adult. 12 In the present study, ETa and ETl in normal ears were and 40.0 ( ) mm, respectively, in males and and 38.5 ( ) mm, respectively, in females. The ETa or ETl of the right versus left side were statistically not significant. The bony and cartilaginous portions of the ET of a child are arranged in a straight line between the pharyngeal and tympanic orifices; in contrast, the TABLE III. Angle and Length of the ET in Normal and Diseased Ears of Group 1. Group 1 No. ETa ( ) P Value ETl (mm) P Value Contralateral normal ears Unilateral diseased ears CSOM ITTS ( ) ( ).956 TMRP ( ).027 Cholesteatoma Gender distribution did not differ among the types of the diseased ears (P 5.662) CSOM 5 chronic suppurative otitis media; ET 5eustachian tube; ETa 5 ET angle; ETl 5 ET length; ITTS 5 intratympanic tympanosclerosis; TMRP 5 tympanic membrane with retraction pockets. 2190

5 TABLE IV. Angle and Length of the ET in Normal Ears, and Childhood- and Later-Onset Diseased Ears of Group 1.* Normal Ears (n 5 59) Disease Onset in Childhood (n 5 21) P Value Disease Onset After Childhood (n 5 38) P Value ETa ( ) ETl (mm) Gender distribution did not differ among the groups (P 5.772). *Three patients with no reliable medical history were excluded. ET 5eustachian tube; ETa 5 ET angle; ETl 5 ET length. cartilaginous portion is angled in adults. 12 However, Yoshida et al. 13 reported that the entire ET air space of an adult patient with severe, patulous ET was observed on CT to follow an almost straight line. In the present study, ETs were angled for ears in which the course of the cartilaginous portion of the ET could be followed. There was also a very strong correlation between the straight and curved lengths of the ET (r ); thus, measuring the straight distance between the tympanic and pharyngeal orifices, to ascertain ET length, is an appropriate and straightforward method. Several studies have measured ETa according to a longitudinal line through the external auditory canal and longitudinal axis of the ET, to investigate the relationship between ETa and chronic ear diseases. 14,15 The present study is the first to measure ETa against the horizontal plane, giving the ET s angle in anatomical position, in CT images to investigate the relationship between ETa, ETl, and the development of COM. In our study, patient age ranged between 8 and 79 years. Takasaki et al. reported that ETa and ETl increase commensurate with age, and further that the values of the angle and length of the ET in 6 or 7 year olds or older are similar to those in adults. 4 Based on this report, we did not group subjects as being children or adults; rather, we grouped ears according to type of ear disease. We also observed no correlation between age and the ETa and ETl of the ears in subjects with age >8 years old. Although COM is a common problem worldwide, there is no single theory of how or why an ear disease becomes chronic. CSOM generally begins with acuteonset otitis media (either AOM or OME) 1 ; for children with recurrent episodes of AOM or OME, anatomical or physiological abnormality of the ET may also be an important factor. 2,3,16 Populations at greater risk for developing otitis media, such as infants and young children, and patients with craniofacial anomalies, Down syndrome, or of American Indian descent, are also at an increased risk of nasopharyngeal reflux, because the ETs of such individuals are short, horizontal, and floppy. 2,3,7,16 We observed a significant decrease in the ETa of diseased versus normal ears. In the unilateral COM group, the difference of the ETa and the ETl between normal versus diseased ears were not significant, though the ETa was more horizontal in unilateral childhood-onset diseased versus normal ears. These results suggest that a more horizontal ET may be a contributory (but not significant) factor in the pathogenesis of COM. However, this study does not rule out the possible impact of childhood-onset middle ear disease on the development of ET. Analysis of subgroups revealed that ETl in CSOM ears was shorter compared with ITTS, and there was no group difference in ETa. The pathogenesis of tympanosclerosis are still unclear, but it is a well-known sequela of AOM and COM. 5 This anatomic difference in ETl may have a role in progression of some CSOM cases to tympanosclerosis. The ETl in ears with cholesteatoma was shorter compared with TMRP ears, and there was no group difference in ETa. Cholesteatoma may develop from TMRP, 17,18 but certain pockets can remain free from cholesteatoma indefinitely. The reason for this is unclear, but the absence of inflammation may be a significant factor. 18 It is possible to hypothesize that the longer ETl in TMRP versus cholesteatoma ears may be important in preventing nasopharyngeal reflux into the middle ear (and by extension inflammatory conditions) in the context of indifferent ETa, which may attenuate the progression of retraction pockets to cholesteatoma. These results suggest that the length of the ET may be a factor in the pathogenesis of COM. The present study did not assess ET function; several studies have related poor ET function with a shorter ETl, and reduced tensor veli palatini muscle (mtvp)-et vectors to ET angle and mtvp surface area. 19,20 Reconstructing the vector relationships between the mtvp, membrano-cartilaginous ET (mcet), and cranial base or functional anatomy of the mcet, using computer-generated models, requires information from histological studies and gross skull dissection. We suggest that measurement of the ET and surrounding structures, using gross anatomy techniques, may not be as accurate as noninvasive imaging techniques. Future studies should evaluate ET function using noninvasive imaging techniques. CONCLUSION ETa and ETl were measured using CT with the MPR technique, to investigate the role of the anatomical features of the ET in the development of COM. The ETa was significantly more horizontal in diseased versus normal ears, and the ETl was statistically not different between the groups. ETl was shorter in CSOM with central perforations compared with ITTS; ETl was shorter in cholesteatoma versus TMRP. The ETa was significantly more horizontal in childhood-onset diseased ears versus contralateral normal ears, and there was no 2191

6 group difference in ETl. A more horizontal ETa and shorter ETl may be a contributory factor in COM development. The straight distance between the tympanic and pharyngeal orifices correlated strongly with angled ET length. ET angle was significantly more horizontal, and ET length was significantly shorter in females compared with males. Acknowledgments The authors thank associate professor Utku Aydil, MD, from the Gazi University Faculty of Medicine for his contributions to the study. The authors also thank assistant professor F ur uzan K okt urk, from the Biostatistics Department of B ulent Ecevit University Faculty of Medicine, who performed the statistical analysis in the study. BIBLIOGRAPHY 1. Bluestone CD, Paradise JL, Beery QC. Physiology of the Eustachian tube in the pathogenesis and management of middle ear effusions. Laryngoscope 1972;82: Verhoeff M, van der Veen EL, Rovers MM, Sanders EA, Schilder AG. Chronic suppurative otitis media: a review. Int J Pediatr Otorhinolaryngol 2006;70: Bluestone CD. Epidemiology and pathogenesis of chronic suppurative otitis media: implications for prevention and treatment. Int J Pediatr Otorhinolaryngol 1998;42: Takasaki K, Takahashi H, Miyamoto I, Yoshida H, Yamamoto-Fukuda T, Enatsu K, Kumagami H. Measurement of angle and length of the Eustachian tube on computed tomography using the multiplanar reconstruction technique. Laryngoscope 2007;117: Sorensen H, True O. Histology of tympanosclerosis. Acta Otolaryngol 1972; 73: Alzahrani M, Saliba I. Tympanic membrane retraction pocket staging: is it worthwhile? Eur Arch Otorhinolaryngol 2014;271: Ramakrishnan Y, Kotecha A, Bowdler DA. A review of retraction pockets: past, present and future management. J Laryngol Otol 2007;121: Soldati D, Mudry A. Knowledge about cholesteatoma, from the first description to the modern histopathology. Otol Neurotol 2001;22: Swarts JD, Alper CM, Luntz M, et al. Panel 2: eustachian tube, middle ear, and mastoid-anatomy, physiology, pathophysiology, and pathogenesis. Otolaryngol Head Neck Surg 2013;148:E26 E Kikuchi T, Oshima T, Ogura M, Hori Y, Kawase T, Kobayashi T. Threedimensional computed tomography imaging in the sitting position for the diagnosis of patulous eustachian tube. Otol Neurotol 2007;28: Seibert JW, Danner CJ. Eustachian tube function and the middle ear. Otolaryngol Clin North Am 2006;39: Ishijima K, Sando I, Balaban CD, Suzuki C, Takasaki K. Length of the eustachian tube and its postnatal development: computer-aided threedimensional reconstruction and measurement study. Ann Otol Rhinol Laryngol 2000;109: Yoshida H, Kobayashi T, Takasaki K, et al. Imaging of the patulous Eustachian tube: high-resolution CT evaluation with multiplanar reconstruction technique. Acta Otolaryngol 2004;124: Habesoglu TE, Habesoglu M, Bolukbasi S, et al. Does auditory tube angle really affect childhood otitis media and size of the mastoid? Int J Pediatr Otorhinolaryngol 2009;73: Sirikci A, Bayazit YA, Bayram M, Kanlikama M. Significance of the auditory tube angle and mastoid size in chronic ear disease. Surg Radiol Anat 2001;23: Licameli GR. The eustachian tube. Update on anatomy, development, and function. Otolaryngol Clin North Am 2002;35: Louw L. Acquired cholesteatoma pathogenesis: stepwise explanations. J Laryngol Otol 2010;124: Persaud R, Hajioff D, Trinidade A, et al. Evidence-based review of aetiopathogenic theories of congenital and acquired cholesteatoma. J Laryngol Otol 2007;121: Doyle WJ, Swarts JD. Eustachian tube-tensor veli palatini muscle-cranial base relationships in children and adults: an osteological study. Int J Pediatr Otorhinolaryngol 2010;74: Takasaki K, Sando I, Balaban CD, Miura M. Functional anatomy of the tensor veli palatini muscle and Ostmann s fatty tissue. Ann Otol Rhinol Laryngol 2002;111: