Surgical management of secondary acquired cholesteatoma depends on its characteristics.

OBJECTIVE: Cholesteatoma secondary to tympanic perforation, known as "secondary acquired cholesteatoma" may progress slower than a retraction pocket cholesteatoma, with less bone destruction and fewer intracranial complications. However, complete surgical removal remains difficult because the pathological epithelium on the marginal side of the extension is not covered by the subepithelial layer of the cholesteatoma matrix, making the boundary with the middle ear mucosa difficult to identify. Therefore, considering the pathophysiology of secondary acquired cholesteatoma, suitable preoperative evaluation and surgical techniques are required. In this study, we aimed to evaluate (i) the extension of secondary acquired cholesteatoma according to the size and location of tympanic membrane perforation; and (ii) the microscopic surgical outcomes, including the rate of residual cholesteatoma, requirement for specialized surgical management, and changes in hearing. METHODS: This retrospective study included data of cases with secondary acquired cholesteatoma (n = 66; 66 ears of 64 patients, 2 patients had bilateral ear involvement), including those who underwent a staged operation (n = 25). RESULTS: The perforation level of the tympanic membrane was associated with the cholesteatoma extension. When the cholesteatoma extended around the stapes, staged operation was chosen. Six cases of spontaneous resolution of stapes lesions at the time of staged surgery were observed. A significant postoperative improvement in hearing was observed; however, five cases experienced sensorineural hearing loss. CONCLUSION: Surgery, including staged surgery of the stapes lesions, along with careful observation of the perforation, is required in secondary acquired cholesteatoma. For lesions that are visible yet challenging to remove, it is imperative to exercise prudent judgment, taking into account the possibility of spontaneous resolution.

Proposal of a Treatment Strategy for Eosinophilic Otitis Media Based on Middle Ear Condition.

OBJECTIVE: We classified eosinophilic otitis media (EOM) into three grades (G1-G3) based on the middle ear mucosal thickness and aimed to establish a treatment strategy for EOM based on these pathological categories. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: We evaluated 136 ears of 68 patients (38 women, 30 men; average age, 56.1 yr; range, 32-80 yr) with bilateral EOM, including 14 surgically treated ears. INTERVENTIONS: Diagnostics and treatment. MAIN OUTCOME MEASURES: Treatment responses to intratympanic instillation of triamcinolone acetonide (TA) and surgery. RESULTS: G1 (mild) cases of EOM responded well to intratympanic TA. G2 (moderate) cases required both TA and systemic glucocorticoids. G3 (severe) cases with granulation were unresponsive to but tolerated the treatment. In 14 ears, granulation tissue was surgically removed and the area was covered with a gelatin sponge containing TA. After the surgery, the severity level of EOM decreased from G3 to G2 in 12 ears, and hearing improved in 4 ears. Three ears showed normalization of the tympanic membrane, and seven ears had less otorrhea. Risk factors for granulation (G3) were the presence of bacterial infection (p = 0.017) and diabetes mellitus (HbA1c of ≥6.5%) (P = 0.039) (odds ratios of 4.55 and 3.95, respectively). CONCLUSIONS: This study showed that G3 EOM was unresponsive to conservative glucocorticoid treatment and required granulation tissue removal. Classification based on the middle ear pathology is useful for determining the most appropriate and successful treatment for EOM.

Clinical Characteristics of Chronic Perforated Otitis Media in Different Age Groups.

OBJECTIVE: We aimed to analyze preoperative and intraoperative clinical characteristics of chronic perforated otitis media by patient age. MATERIALS AND METHODS: We analyzed 137 tympanoplasties for chronic perforated otitis media in 133 patients. Exclusion criteria were ear adhesions, cholesteatoma, and a history of tympanoplasty. Patients were divided into a younger group (aged 15-39 years), a middle group (40-64 years), and an elderly group (≥65 years). We compared tympanoplasty technique (using Wullstein classification), mastoid air-cell area measured by temporal bone computed tomography, preoperative aeration of the temporal bone, mean preoperative hearing (at 500 Hz, 1000 Hz, and 2000 Hz), and patch effect calculated by the pre- and post-patch air-bone gap at frequencies of 250 Hz and 500 Hz among the three age groups. RESULTS: Although type I tympanoplasty was performed most frequently in all age groups, it was performed significantly less often in the elderly group (p<0.05). The mean mastoid pneumatization index was significantly lower in the elderly group (p<0.05). Preoperative air-conduction hearing and bone-conduction hearing differed significantly among age groups (p<0.05 for both). There were no significant differences in the air-bone gap among the three groups. The mean patch effect was significantly better in the younger group than in middle or elderly groups (p<0.05). CONCLUSION: The less pneumatized mastoid and ossicular diseases in elderly patients with chronic perforated otitis media suggest that they had longer lasting and more severe childhood middle ear pathologies than did younger patients.

Attic cholesteatoma with closure of the entrance to pars flaccida retraction pocket.

We report three patients with pars flaccida-type cholesteatoma (attic cholesteatoma) with closure of the entrance to the cholesteatoma at the time of surgery. These patients were diagnosed with attic cholesteatoma requiring surgery on the basis of abnormal findings of the pars flaccida, audiometry, and temporal bone computed tomography during the clinical course. Intraoperatively, cholesteatoma matrix and granulation tissue were observed behind the intact pars flaccida epithelium, which suggested that the entrance had apparently closed and the continuity with the cholesteatoma matrix disappeared after resolution of inflammation at the pars flaccida. In such patients, a normal pars flaccida may cause cholesteatoma to be initially overlooked, or misdiagnosed as congenital cholesteatoma. The diagnosis should be carefully made on the basis of the clinical course and the results of various examinations.

Predicting postoperative fever and bacterial colonization on packing material following endoscopic endonasal surgery.

Postoperative fever following endoscopic endonasal surgery is a rare occurrence of concern to surgeons. To elucidate preoperative and operative predictors of postoperative fever, we analyzed the characteristics of patients and their perioperative background in association with postoperative fever. A retrospective review of 371 patients who had undergone endoscopic endonasal surgery was conducted. Predictors, including intake of antibiotics, steroids, history of asthma, preoperative nasal bacterial culture, duration of operation, duration of packing and intraoperative intravenous antibiotics on the occurrence of postoperative fever, and bacterial colonization on the packing material, were analyzed retrospectively. Fever (≥38 °C) occurred in 63 (17 %) patients. Most incidences of fever occurred on postoperative day one. In majority of these cases, the fever subsided after removal of the packing material without further antibiotic administration. However, one patient who experienced persistent fever after the removal of packing material developed meningitis. History of asthma, prolonged operation time (≥108 min), and intravenous cefazolin administration instead of cefmetazole were associated with postoperative fever. Odds ratios (ORs) for each were 2.3, 4.6, and 2.0, respectively. Positive preoperative bacterial colonization was associated with postoperative bacterial colonization on the packing material (OR 2.3). Postoperative fever subsided in most patients after removal of the packing material. When this postoperative fever persists, its underlying cause should be examined.

New Insights into Eosinophilic Otitis Media.

Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM.

Contribution of the distal pocket residue to the acyl-chain-length specificity of (R)-specific enoyl-coenzyme A hydratases from Pseudomonas spp.

(R)-Specific enoyl-coenzyme A (enoyl-CoA) hydratases (PhaJs) are capable of supplying monomers from fatty acid ß-oxidation to polyhydroxyalkanoate (PHA) biosynthesis. PhaJ1Pp from Pseudomonas putida showed broader substrate specificity than did PhaJ1Pa from Pseudomonas aeruginosa, despite sharing 67% amino acid sequence identity. In this study, the substrate specificity characteristics of two Pseudomonas PhaJ1 enzymes were investigated by site-directed mutagenesis, chimeragenesis, X-ray crystallographic analysis, and homology modeling. In PhaJ1Pp, the replacement of valine with isoleucine at position 72 resulted in an increased preference for enoyl-coenzyme A (CoA) elements with shorter chain lengths. Conversely, at the same position in PhaJ1Pa, the replacement of isoleucine with valine resulted in an increased preference for enoyl-CoAs with longer chain lengths. These changes suggest a narrowing and broadening in the substrate specificity range of the PhaJ1Pp and PhaJ1Pa mutants, respectively. However, the substrate specificity remains broader in PhaJ1Pp than in PhaJ1Pa. Additionally, three chimeric PhaJ1 enzymes, composed from PhaJ1Pp and PhaJ1Pa, all showed significant hydratase activity, and their substrate preferences were within the range exhibited by the parental PhaJ1 enzymes. The crystal structure of PhaJ1Pa was determined at a resolution of 1.7 Å, and subsequent homology modeling of PhaJ1Pp revealed that in the acyl-chain binding pocket, the amino acid at position 72 was the only difference between the two structures. These results indicate that the chain-length specificity of PhaJ1 is determined mainly by the bulkiness of the amino acid residue at position 72, but that other factors, such as structural fluctuations, also affect specificity.

Risk factors associated with severity of eosinophilic otitis media.

OBJECTIVE: Eosinophilic otitis media (EOM) is an intractable otitis media associated with bronchial asthma. Clinical characteristics of EOM are apparent, but severe EOM, which is unresponsive to ongoing treatments, can occur. The present study aimed to investigate potential risk factors associated with the severity of EOM. METHODS: We scored the EOM severity of 26 patients according to quantity of middle ear effusion (MEE), thickness of the middle ear mucosa, use of topical and oral corticosteroids, and use of antibiotics, all measured over a 3-month period. The scores for four 3-month periods (1 year) were averaged. We analyzed the prevalence of clinical variables by partial regression: sex, age, body mass index (BMI), duration of bronchial asthma, association of aspirin-intolerant asthma, Lund-Mackay score for sinusitis, mastoid pneumatization, width of the bony Eustachian tube at the tympanic orifice, percentage of eosinophils and immunoglobulin E in peripheral blood, and association of allergic rhinitis. Duration of bronchial asthma was defined as the period from onset of bronchial asthma to the age of first consultation at our hospital. Samples of MEE were taken for bacterial culture. RESULTS: The average severity score was 6.6 (out of 16). The severity score in the pathogen-positive MEE group was significantly higher than that in the pathogen-negative MEE group (p<0.05). The score was not significantly different between the seasons. Linear multiple regression analysis showed that BMI and the duration of bronchial asthma significantly affected the EOM severity score (p<0.05). The presence of aspirin intolerant asthma tended to be correlated with the severity score. The Lund-Mackay score tended to be negatively correlated with it. CONCLUSIONS: There is a significant association between the severity of EOM and obesity, as well as with the duration of bronchial asthma.

A comparison of preoperative characteristics of chronic otitis media in Down and non-Down syndrome.

OBJECTIVE: To investigate preoperative clinical findings of chronic otitis media (COM) in patients with Down and without (non-Down) syndrome. STUDY DESIGN: Retrospective. SETTING: Referral hospital, otolaryngology department. PATIENTS: Patients with COM who underwent tympanoplasty were included. There were 10 ears of 8 patients (mean age, 14.9 yr) in the Down group and 44 ears of 41 patients (mean age, 14.7 yr) in the non-Down group. MAIN OUTCOME MEASURES: Clinical characteristics, including the frequency of preoperative persistent otorrhea, cause of COM, and mastoid pneumatization (maturation), were compared between the 2 groups using clinical records and temporal bone computed tomography (CT). RESULTS: Preoperative persistent otorrhea was more frequent in the Down group (60%) than in the non-Down group (27.2%; p < 0.05). Perforation due to tympanostomy tube insertion also occurred more frequently in the Down group (100%) than in the non-Down group (53.3%; p < 0.05). Mastoid pneumatization occurred significantly less in the Down group than in the non-Down group (p < 0.01). There was no significant difference in mastoid pneumatization regardless of the presence or absence of a past history of tympanostomy tube insertion in the Down group (p = 0.3, t test) unlike that in the non-Down group (p < 0.05, t test). All ears attained a dry condition with no perforated eardrums. CONCLUSION: Frequent draining ear and extremely immature mastoid pneumatization, regardless of the presence or absence of a past history of tympanostomy tube insertion, were clinically important characteristics of COM in patients with Down syndrome.

Antigen-specific IgE in middle ear effusion of patients with eosinophilic otitis media.

BACKGROUND: Eosinophilic otitis media (EOM) is an intractable otitis media characterized by a highly viscous effusion that contains eosinophils. We previously reported that high levels of IgE were detected in middle ear effusion (MEE) of patients with EOM. OBJECTIVE: To examine antigen-specific IgE in MEE of patients with EOM to clarify the pathogenesis of EOM. METHODS: Twenty-six patients with EOM associated with bronchial asthma were included in this study. Antigen-specific IgE against inhalant and bacterial antigens were measured in the serum and MEE of these patients. RESULTS: In patients with EOM, 1 or more antigen-specific IgEs were detected from the MEE of 16 of 26 patients (62%), whereas 1 of 9 control patients (11%) had antigen-specific IgE (P < .01). Total serum IgE concentrations were not different between the groups who tested positive (16 patients) and negative (10 patients) for antigen-specific IgE. None of the fungi-specific IgEs were detected in serum even though 11 patients tested positive for 1 or more fungal antigens detected in MEE. The severity score of EOM in the antigen-specific IgE-positive group was significantly higher than that in the antigen-specific IgE-negative group (P < .05). CONCLUSION: Antigen-specific IgE against inhalant and bacterial antigens may be locally produced in the middle ear mucosa in patients with EOM. In particular, local sensitization against fungi together with Staphylococcus aureus could result in local IgE production in the middle ear and may be responsible for the severity of EOM.

Effect of omalizumab on biomarkers in middle ear effusion in patients with eosinophilic otitis media.

CONCLUSIONS: Eosinophil cationic protein (ECP) concentrations in middle ear effusion (MEE) in patients with eosinophilic otitis media (EOM) were significantly decreased at 3 months after the administration of omalizumab from the baseline level (p < 0.05). This study provides new evidence that omalizumab reduces eosinophilic inflammation in the middle ear and that the reduction of ECP may not be caused by suppression of interleukin (IL)-5 production in the middle ear mucosa. OBJECTIVE: EOM is an intractable otitis media characterized by a highly viscous effusion containing eosinophils. We recently reported that anti-IgE therapy using omalizumab was efficacious in the treatment of EOM. To clarify the underlying mechanism, we determined changes in biomarkers in MEE related to eosinophilic inflammation after therapy. METHODS: Nine patients with EOM received the anti-IgE agent omalizumab for 3 months. Among them, five patients continued anti-IgE therapy for longer than 1 year. Eight EOM patients without administration of omalizumab were also included in the study as controls. The concentrations of eosinophilic inflammatory markers such as ECP, IgE, IL-4, and IL-5 in MEE were measured before and after the administration of omalizumab. RESULTS: After 3 months of omalizumab therapy, the ECP concentration in MEE was significantly reduced from the baseline level (p < 0.05), while no significant change of ECP in the serum was observed. The concentrations of IL-4 and IL-5 in MEE showed no significant change before and after the therapy in EOM patients treated with omalizumab.

Fallopian canal dehiscence at pediatric cholesteatoma surgery.

The objectives of the study were to investigate the characteristics of ears with dehiscence of the fallopian canal at the time of cholesteatoma surgery and the relationship between dehiscence and age, and to consider the reasons why the fallopian canal tends to be preserved in pediatric patients. This study included 37 ears with cholesteatoma in pediatric patients (mean age 9.2 years, age range 4-14 years) and 273 ears with cholesteatoma in non-pediatric patients (mean age 45 years, age range 15-84 years). Patients were treated between January 2006 and April 2012. All patients had undergone prior tympanoplasty under general anesthesia at our institution. Facial canal dehiscence was evaluated by inspection and through palpation by blunt picking after the pathological tissues had been removed. The size of fallopian canal dehiscence was not investigated in this study. The frequency of dehiscence of the fallopian canal according to the type of cholesteatoma and coexisting pathological conditions, including destruction of the stapes, presence of a labyrinthine fistula, and dural exposure, were compared between the pediatric and non-pediatric groups. The frequency of dehiscence in cases with destruction of the stapes was also compared between the pediatric and non-pediatric groups. Dehiscence of the fallopian canal occurred in 6 of 37 ears (16.8 %) in the pediatric group and 91 of 273 ears (33.3 %) in the non-pediatric group (p < 0.05). In congenital cholesteatoma, the frequency of dehiscence was lower in the pediatric group than in the non-pediatric group (p < 0.05). However, in other types of cholesteatoma there was no statistically difference between the two types of cholesteatoma. The frequency of the destruction of the stapes was higher in the pediatric group than in the non-pediatric group (43.2 vs. 16.5 %, p < 0.001). In patients with severe destruction of the stapes, the fallopian canal was preserved more frequently in the pediatric group than in the non-pediatric group (p < 0.05). The frequency of dehiscence of the fallopian canal at the time of cholesteatoma surgery was lower in the ears of pediatric patients than in the ears of non-pediatric patients. This is probably due to the difference in types of cholesteatoma between the two groups and other unknown mechanisms.

Reversible cochlear function with ANCA-associated vasculitis initially diagnosed by otologic symptoms.

OBJECTIVE: To present 8 cases with hearing loss as an initial symptom of antineural cytoplasmic antibody (ANCA)-associated vasculitis (AAV) involving granulomatosis with polyangiitis (GPA) and to discuss the treatment and mechanisms of hearing outcomes after immunosuppressive therapy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Eight patients were referred to our university hospital between 2004 and 2012 for intractable otitis media with acute progressive mixed (conductive and sensorineural) hearing loss and facial palsy. INTERVENTION(S): Diagnostics and treatment. MAIN OUTCOME MEASURES: Otologic symptoms as initial manifestations of otitis media with AAV and cochlear function after treatment. RESULTS: Eight cases (6 female and 2 male subjects; aged 54-73 yr; 6 MPO [myeloperoxidase]-ANCA-positive and 2 PR3 [proteinase 3]-ANCA-positive cases) were included. Progressive hearing loss was present in all patients, and facial palsy was present in 5 of 8 patients total. Patients with hearing levels better than 95 dB improved with good speech discrimination after immunosuppressive therapy, but the completely deaf could not be recovered. All patients have been successfully controlled for 1 to 8 years without any systemic disorders. CONCLUSION: This study showed the difficulty of diagnosing localized AAV and the effectiveness of immunosuppressive therapy for hearing loss in the early stage. Based on these results, early-stage AAV would influence the stria vascularis in the cochlea. Otitis media with ANCA-associated vasculitis is a new entity among the causes of intractable otitis media and progressive hearing loss.

Differences in clinical characteristics of fallopian canal dehiscence associated with pars flaccida and pars tensa cholesteatomas.

This study investigated the difference in clinical characteristics of fallopian canal dehiscence associated with pars flaccida and pars tensa cholesteatomas for the purpose of increasing the preoperative detectability of dehiscence. A total of 189 ears of patients 7-80 years of age (mean 42 years) with pars flaccida cholesteatoma and 63 ears of patients 9-84 years of age (mean 50 years) with pars tensa cholesteatoma were studied. All patients had undergone prior surgical management at our institution from January 2006 to April 2012. The incidence of fallopian canal dehiscence and its location were compared between pars flaccida and pars tensa cholesteatomas. Intraoperative findings of coexistent pathologies, including destruction of the stapes superstructure, labyrinthine fistula, and dural exposure, were compared between the dehiscence and no-dehiscence groups for the two types of cholesteatomas. The incidence of dehiscence was significantly higher in patients with pars tensa cholesteatoma (55.6 %) than in patients with pars flaccida cholesteatoma (26.5 %). Dehiscence located posterior to the cochleariform process occurred slightly more frequently in patients with pars tensa cholesteatoma than in those with pars flaccida cholesteatoma. In patients with pars flaccida cholesteatoma, labyrinthine fistulas and dural exposure were significantly more frequent in the dehiscence group than in the no-dehiscence group. Fallopian canal dehiscence is more frequent in patients with pars tensa cholesteatoma than in those with pars flaccida cholesteatoma. Especially in patients with pars flaccida cholesteatoma, paying special attention to these coexisting pathologies is important to increase preoperative detectability of dehiscence.

Large carcinoma ex pleomorphic adenoma of the parotid gland: a case report and review of literature.

Pleomorphic adenoma (PA) is one of the most common benign tumors of the parotid gland. PA usually grows slowly and is painless. Surgery is necessary for treating PA. Facial palsy, salivary fistula, and Frey syndrome have been reported as complications of tumor resection. PA can transform into a carcinoma ex pleomorphic adenoma (CXPA) over time and as it enlarges. This report describes a case of a large CXPA that transformed from a PA that had developed over 17 years and caused withdrawal from social contact because fear of surgery made the patient refuse treatment. The tumor gradually enlarged without any pain for a decade, but rapid growth and bleeding began a year before admission. Postoperative facial function and local control of the tumor were excellent, but the patient required adjuvant chemotherapy for lung and mediastinum lymph node metastasis leading to dyspnea from tracheal stenosis. This case indicates the importance of adequate explanation and advice when choosing therapy for PA, especially given the risk of a PA transforming to a CXPA.

Powered endoscopic dacryocystorhinostomy with radiowave instruments: surgical outcome according to obstruction level.

Endoscopic endonasal dacryocystorhinostomy (EDCR) is an accepted alternative to external dacryocystorhinostomy (DCR) for relieving obstruction of the lacrimal drainage system. Powered and radiowave instruments are useful for the control of bleeding and for wide exposure of the lacrimal sac and canaliculus. In this study, we evaluated the surgical outcome of powered EDCR with radiowave instruments at five obstruction levels: (1) upper and/or lower canaliculi (obstruction was located less than 8 mm from puncta); (2) common canaliculus (obstruction was less than 10 mm from puncta); (3) lacrimal sac; (4) duct-sac junction; and (5) nasolacrimal duct. The overall success rate was 93.6 % (104/111), with 60.0 % (3/5) success for upper and lower canalicular stenosis, 85.0 % (17/20) for common canalicular stenosis, 92.0 % (23/25) for obstruction at the lacrimal sac, 100 % (41/41) for obstruction at the duct-sac junction, and 100 % (20/20) for nasolacrimal duct obstruction. EDCR resulted in a good overall surgical outcome for any obstruction of the lacrimal drainage pathway compared with external DCR. Powered EDCR using radiowave instruments is useful for not only obstruction of the lacrimal sac and duct-sac junction, but also for that of the upper/lower and common canaliculi.

A comparison of patterns of disease extension in keratosis obturans and external auditory canal cholesteatoma.

OBJECTIVE: To investigate the different pathways of progression to the middle ear in keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). STUDY DESIGN: Retrospective case review. SETTING: Referral hospital otolaryngology department. PATIENTS: Patients with KO or EACC and middle ear disease who underwent surgical management were included. Four ears of 4 patients (mean age, 41.25 yr) were the KO group, and 5 ears of 4 patients (mean age, 49.5 yr) were the EACC group. MAIN OUTCOME MEASURES: Intraoperative findings of the middle ear cavity were investigated in KO and EACC groups. RESULTS: In the KO group, 3 patients had a perforated tympanic membrane and cholesteatoma in the tympanic cavity. The other patient had preoperative right facial palsy. Removal of the keratin plug revealed an adherent tympanic membrane. In intraoperative findings, the tympanic segment of the fallopian canal was found to be eroded because of inflammation. No case initially progressed to the mastoid cavity. Four patients had external auditory canal cholesteatoma with middle ear disease. In EACC group, all patients had initial progression to the mastoid cavity. CONCLUSION: KO tends to progress initially to the tympanic cavity via a diseased tympanic membrane. EACC tends to progress to the mastoid cavity via destruction of the posterior bony canal. This is the first report to investigate differences in pathway of progression to the middle ear cavity in these 2 diseases.