Management of invasive intralabyrinthine cholesteatoma: Can one realistically preserve hearing when disease is medial to the otic capsule?

PURPOSE: To report our long-term results in surgical management of invasive intralabyrinthine cholesteatoma. MATERIAL AND METHODS: The study is a case series in a tertiary referral center. Retrospective chart review of all mastoid operations performed for chronic ear disease between 1994 and 2019 at University Health Network, Toronto. The type of surgery, intraoperative findings, hearing outcome, recurrence of disease and the need for revision surgery were evaluated. RESULTS: 10 cases of extensive petrous bone cholesteatoma medial to the otic capsule were identified in 616 mastoid surgeries. All but one patient with extensive petrous bone cholesteatoma who underwent an exteriorizing procedure to preserve cochlear function failed the first surgery. A second procedure was needed in all cases due to complications which included facial palsy, recurrent cholesteatoma or internal auditory canal (IAC) abscess. Hearing was not preserved in any patient. In contrast, 57 ears with cholesteatomatous labyrinthine fistula lateral to the otic capsule had matrix exteriorized and had very good long-term results. CONCLUSION: We were rarely able to preserve hearing in massive petrous bone cholesteatoma. There should be no hesitation to remove the otic capsule to exteriorize diseases even under circumstances where residual cochlear and vestibular function is present if required to provide a safe ear.

[Sanation of petrous bone cholesteatoma in the otosurgical practice]. / Sanatsiia kholesteatomy piramidy visochnoi kosti v otokhirurgicheskoi praktike.

The present article reports the clinical cases of the surgical intervention on 20 patients presenting with petrous bone cholesteatoma. We have identified several clinical variants of petrous bone cholesteatoma based on the results of multispiral computed tomography (MSCT) of the temporal bones and categorized them into the following types in accordance with the classification proposed by Moffat-Smith an M. Sanna for this pathological condition: supralabyrinthine (n=8), supralabyrinthine-apical (n=2), infralabyrinthine (n=3), infralabyrinthine-apical (n=5), massive (n=1), and massive - apical (n=1). The surgical sanation of petrous bone cholesteatoma was performed in all the 20 patients in the absence of the pronounced bone destruction in the walls of the temporal bone pyramid and of the subdural expansion of cholesteatoma. In all the cases, the trepanation cavity remained open till its complete epidermization. The follow up period was around 3 years in duration on the average. The post-surgical analysis of the clinical conditions of each of the 20 patients was performed with special reference to the surgical technique applied for the removal of petrous bone cholesteatoma and the final outcome of the radical treatment.

[Otoscopic pitfall : the congenital cholesteatoma]. / Piège otoscopique : le cholestéatome congénital.

The congenital cholesteatoma is a rare benign tumor whose diagnosis is mainly made during childhood. Otoscopic examination shows a white retrotympanic collection with or without hearing loss. In case of a late diagnosis, the disease will spread to the surrounding structures, leading to ossicules destruction, facial palsy, sensorineural hearing loss and vestibular dysfunction. Surgery is the therapeutic gold-standard, with different techniques chosen based on the cholesteatoma's extension. Patient should benefit from a long term medical and radiological (MRI) follow-up.

Le cholestéatome congénital est une tumeur bénigne rare mais dont la fréquence augmente de par une optimisation du diagnostic, celui-ci étant de plus en plus précoce. Le diagnostic est souvent posé devant une masse blanchâtre rétrotympanique visible en otoscopie associée ou non à un trouble auditif. En cas de diagnostic tardif, l'extension de la maladie peut engendrer de graves complications nerveuses (faciales), auditives et vestibulaires. Sa prise en charge est chirurgicale, le type de technique étant guidé par le stade d'extension du cholestéatome. Le suivi post-thérapeutique va bénéficier de l'apport de l'IRM et se déroulera sur le moyen et long terme.

[The surgical treatment of cholesteatoma of the pyramid of the temporal bone].

This paper presents in brief the data on epidemiology, classification, diagnostics, and current tendencies in the surgical treatment of cholesteatoma of the pyramid of the temporal bone. A clinical case of diagnostics and the surgical treatment ofpetrous apex cholesteatomainthe temporal bone is described.

Hearing and vertigo outcomes after congenital labyrinthine cholesteatoma resection.

Congenital labyrinthine cholesteatoma can cause varying degrees of hearing loss and vertigo. Hearing preservation is not always possible when treatment involves total labyrinthectomy. Since 1969, there have been several case reports and case series documenting hearing preservation following surgical treatment of congenital labyrinthine cholesteatoma. However, none of the case reports or case series documents the patients' vestibular complaints after surgery. Herein, we report a case series of four patients who were treated with the goal of hearing preservation and resolution of vertigo after partial or complete removal of the bony labyrinth for congenital inner ear cholesteatoma. We will also discuss possible explanations for the mechanisms of preservation of hearing and vestibular function with a review of the current literature.

Clinical characteristics of spontaneous cholesteatoma of the external auditory canal in children comparing with cholesteatoma in adults.

The purpose of this study was to investigate the characteristics of external auditory canal cholesteatoma (EACC) in children through evaluation of the clinical and radiologic features as well as treatment outcomes. The clinical records were retrospectively reviewed for children under 15 years of age diagnosed with spontaneous EACC between March 2004 and December 2011. The clinical data of adults diagnosed with spontaneous EACC during the same period were evaluated to compare with EACC in children. Eight patients (3 males and 5 females) with pediatric EACC and 18 patients (7 males and 11 females, 20 ears) with adult EACC were included within the boundary of the study. The mean ages were 12.4 years (age range 9-15) for pediatric EACC and 49.8 years (age range 29-79) for adult EACC patients. Follow-up periods ranged from 8 to 86 months (mean 32.5 ± 8.62) in pediatric EACC and from 6 to 72 months (mean 22.2 ± 5.36) in adult EACC. Pediatric EACC, showed involvement most commonly in the posterior wall, while the inferior wall was most commonly involved in adult EACC. Pediatric EACC tended to show a more focal involvement and was not as extensive as adult EACC. Extension into the adjacent structures was similar in both groups, but bony destruction was more common in the adult group. Two children and eight adult patients were treated with surgery, but four adult cases needed more extensive surgical treatment because their disease was widely spread to included areas such as the mastoid segment of facial nerve and the temporomandibular joint. Six pediatric cases treated with conservative management showed no progression of disease on physical examination at the last visit, but two cases of adults progressed and required canaloplasty. Pediatric EACC shows less aggressive behavior compared to adult EACC. Adequate management may work better in pediatric than in adult EACC, even though the treatment modality is conservative management.

[A middle to long-term clinical study on pars flaccida and pars tensa cholesteatoma using survival analysis].

The current clinical study was performed on 311 cases of pars flaccida and 89 cases of pars tensa cholesteatoma which were treated with canal wall reconstructed tympanoplasty between 1991 and 2012. The average follow-up time of these patients was 5.3 years. Since follow-up periods were different in each case and some censored patients were involved, we used survival analysis on this study to discuss the cumulative rates of disease-free successful cases and the rates of recurrent cholesteatoma throughout the postoperative course. The disease-free successful cases were defined as those cases in which patients were both out of re-operation with recurrent and residual cholesteatoma and out of revision operation with another problem, furthermore, maintained good hearing outcome. Based on the criteria set by the Japan Otological Society (2010), the cases that satisfied the following were evaluated as good hearing results; (a) a successful case in which preoperative bone conduction was used, and (b) a case in which the postoperative air-bone gap was within 20dB after tympanoplasty for chronic otitis media. The analysis results were shown for each of (a) and (b). 1. In pars flaccida cholesteatoma, the 5-year survival rate of successful case was (a) 76.1% and (b) 83.9%, the 10-year survival rate was (a) 58.9% and (b) 73.0%. In pars tensa cholesteatoma, the 5-year survival rate of successful cases was (a) 57.7% and (b) 63.5%, the 10-year rate was (a) 42.1% and (b) 56.9%. A significant difference was seen between pars flaccida and pars tensa cholesteatoma (p < 0.001). 2. In pars flaccida cholesteatoma, the 5-year recurrence rate was 7.6% and the 10-year rate was 15.3%, and the recurrence rate increased gradually throughout the follow-up period. On the other hand, in pars tensa cholesteatoma, the increase in the recurrence rate reached a peak 15.8% at 5.5 years after the surgery. A long-term follow-up is necessary when evaluating the clinical results after tympanoplasty.

[Criteria for the objective assessment of the dynamic state of the retraction pockets in the children presenting with excudative otitis media].

This publication continues the preceding paper entitled "Early diagnostics of the retraction pockets in the tympanic membrane of the children". The objective of the present work was to develop the criteria for the objective estimation of the dynamic state of the retraction pockets (RP) in the children at different stages of excudative otitis media. The secondary objective was to develop an approach to the early diagnostics of cholesteatoma of the middle ear. A group of 138 children at the age varying from 1 to 17 years was placed under dynamic observation for the purpose of drawing up the individual "photo-roentgenological passport of the retraction pockets". Special attention was given to RP-semiotics of different forms of the syndrome and its severity in accordance with the classification universally accepted by foreign researchers. The results of the dynamic observations were used to develop the indications for the early preserving surgical treatment. It was given to 16 children six of which presented with cholesteatoma. The original illustrative materials for all variants of the retraction pockets are presented.

Predictive Role of Ki-67 and Proliferative-Cell Nuclear Antigen (PCNA) in Recurrent Cholesteatoma.

OBJECTIVES: To investigate the potential use of Ki-67 and pronuclear cell antigen (PCNA) as indicators of recurrent cholesteatoma. MATERIAL AND METHODS: Patients who had been diagnosed with cholesteatoma and who had undergone canal wall-down mastoidectomy were included in this study. Subjects were divided into two groups: recurrent and non-recurrent (i.e., cases without recurrence for at least 2 years). Ossicular pathologies were recorded. Histopathologic specimens were stained for Ki-67 and PCNA and the percentages of stained cells were calculated. RESULTS: Neither group demonstrated a significant difference in terms of total Ki-67 per cell, Ki-67-stained cell counts, Ki-67-staining percentages, total PCNA per cell, PCNA-stained cell counts, or PCNA-staining percentages (p>0.05). No significant relationship was noted between the staining percentages for either Ki-67 or PCNA and the incudostapedial involvement (p>0.05); however, a significant relationship was noted between Ki-67 staining and malleus involvement (p<0.05). CONCLUSION: Although the recurrent and non-recurrent cholesteatoma groups showed no significant differences in terms of the percentages of stained cells for either Ki-67 or PCNA, we detected high Ki-67 staining in the malleus involvement group. We concluded that cell-proliferation markers could not be defined as indicators of recurrence of cholesteatoma, but they could be defined as indicators of destructive patterns of this disease.

Endoscope-Assisted Surgery for Petrous Bone Cholesteatoma with Hearing Preservation.

OBJECTIVES: Petrous bone cholesteatoma is a rare pathologic entity and may be a difficult surgical challenge because of potential involvement of the facial nerve, carotid artery, dura mater, otic capsule and superior petrosal or lateral sinus. The objective of this article is to present the endoscope-assisted surgery for petrous bone cholesteatoma. MATERIALS AND METHODS: Eight patients (nine ears) who underwent endoscope-assisted petrous bone surgery for cholesteatoma. Pure tone audiogram, magnetic resonance imaging were performed at preoperatively, and at approximately 12 months postoperatively. RESULTS: Endoscope assisted surgery was performed in 8 patients and 9 ears. Of these patients, 6 were male and 2 were females. Median age was 19,5 (range 7-52) years. Hearing was able to preserved in 8 ears (8/9). Recurrence disease was observed one ear in long term follow up (1/9). In another one patient, cholesteatoma pearl was removed in the office. CONCLUSION: Endoscope-assisted surgery can allow removal of cholesteatoma of petrous apex with preserving hearing. It also provides to remove the cholesteatoma via transmastoid approach for perilabyrinthine space as "minimally invasive surgery" instead of middle fossa approach that is standard surgical procedure. In apical and peri-labyrinthine cholesteatomas, endoscopes allow to preserve hearing with middle fossa approach instead of trans-otic/ trans-labyrinthine/trans-cochlear approach.

Nationwide survey of congenital cholesteatoma using staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society.

OBJECTIVE: This study was undertaken to determine the characteristics of congenital cholesteatoma (CC) in Japan, via a nationwide survey using staging and classification criteria for middle ear cholesteatoma, as proposed by the Japan Otological Society (JOS). METHODS: A nationwide survey regarding middle ear cholesteatoma treated in 2015 was performed. There were 1787 registrations from 74 facilities, among which, CC accounted for 12.9% (231 cases) of all middle ear cholesteatoma cases. The extent of the disease was classified according to the classification and staging of cholesteatoma proposed by JOS in 2015. RESULTS: The age of the patients ranged from 1 to 55 years (mean, 8.2 years; median, 6 years; 149 ears of males; 82 ears of females). Among these cases, 105 (45.5%) were classified as stage I, 121 (52.4%) as stage II, and 5 (2.1%) as stage III, with no cases in stage IV. In the sub classification of stage I, 35 (33%), 43 (41%) and 27 (26%) ears were classified as stages I-a, I-b and I-c, respectively. Stage I-b (cholesteatoma confined to the posterior half of the tympanic cavity) was more frequent than stage I-a (the anterior half of tympanic cavity). Pre-operative hearing level of air-conduction was 20.5dB for stage I-a, 34.5dB for stage I-b, 30.5dB for stage I-c, 38.6dB for stage II, and 59.0dB for stage III. The rate of missing stapes superstructure increased as the disease progressed. In the same way, the mastoid development lowered as the stage of the disease progressed. There were significant differences in the age at operation, pre-operative hearing level, status of stapes, and major ossiculoplasty, between stage l-a and l-b. CONCLUSIONS: The current condition of CC in Japan was been evaluated; in particular, it was observed that the cases limited to the posterior part of tympanic cavity were not rare. The JOS stage classification based on the progression of the disease seemed simple and efficient.

Bilateral Ear Canal Cholesteatoma with Underlying Type I First Branchial Cleft Anomalies.

OBJECTIVES:: To describe a case of bilateral ear canal cholesteatomas in the setting of underlying first branchial cleft cyst anomalies and to review the pathophysiology underlying the development of external auditory canal cholesteatomas from branchial cleft cyst abnormalities. METHODS AND RESULTS:: We present a case study of a 61-year-old man who presented with chronic right-sided hearing loss and left-sided postauricular drainage. Clinical evaluation, radiographic work-up, and pathologic analysis confirmed a diagnosis of bilateral ear canal cholesteatoma in the setting of underlying first branchial cleft cyst anomalies. The patient's clinical course, surgical treatment, and management considerations are discussed here. CONCLUSION:: Ear canal cholesteatoma represents a rare clinical disease entity deserving a thorough initial assessment. Careful consideration of underlying diseases that result in chronic inflammation, such as branchial cleft lesions, should be included in the differential diagnosis of idiopathic canal cholesteatoma in the absence of prior otologic surgery or trauma.

Spontaneous Resolution of Cholesteatoma in a Patient on Long-Term Infliximab.

OBJECTIVE:: To describe an observed case of spontaneous regression of cholesteatoma in a patient on chronic anti-tumor necrosis factor-alpha (TNF-a) therapy and inspire further research into the role of TNF-a in cholesteatoma. METHODS:: Clinical assessment of disease in a single-patient case report. RESULTS:: A 49-year-old woman suffered a severe case of Stevens-Johnson syndrome when she was 12 years old, leaving her with bilateral corneal opacification and tympanic membrane perforations with extensive cholesteatoma. For her corneal opacification, a corneal prosthesis was placed, which was complicated by a foreign body reaction necessitating long-term therapy with infliximab, a monoclonal antibody against TNF-a that is therapeutic in some chronic inflammatory diseases. She was otherwise healthy and took no other medications. While on infliximab, the patient had spontaneous and complete resolution of her cholesteatoma without any surgical intervention. CONCLUSIONS:: This surprising case suggests that there may be a prominent role of TNF-a in cholesteatoma pathophysiology and that TNF-a may be an effective target for nonsurgical therapy.

Assessment of nasal functions and their relationship with cholesteatoma formation in patients with unilateral chronic otitis media.

OBJECTIVES: To evaluate the nasal functions of patients with unilateral chronic otitis media using rhinomanometry, comparing chronic otitis media sides with healthy sides, chronic otitis media patients with cholesteatoma and without cholesteatoma, and patients with healthy individuals. METHODS: This prospective study included 102 patients with unilateral chronic otitis media (48 with and 54 without cholesteatoma). The control group comprised 40 individuals without any ear or nasal pathologies. All patients underwent active anterior rhinomanometry to measure nasal airway resistance and a saccharin test to measure mucociliary transport times. RESULTS: There were no significant differences in nasal airway resistance and mucociliary transport time between the chronic otitis media sides and unaffected sides in the 102 patients (p = 0.72 and p = 0.28, respectively), between the non-suppurative chronic otitis media patients (without cholesteatoma) and chronic otitis media with cholesteatoma patients (p > 0.05), or between the study and control groups (p > 0.05). CONCLUSION: The present study, with a larger sample size compared to previously published literature, supports the conclusion that unilateral nasal obstruction is unlikely to lead to chronic otitis media on the same side. The results also suggest that nasal functions do not contribute to the development of cholesteatoma.

External auditory canal cholesteatoma and benign necrotising otitis externa: clinical study of 95 cases in the Capital Region of Denmark.

OBJECTIVE: To identify epidemiological and pathophysiological factors, and treatment strategies, in external auditory canal cholesteatoma and benign necrotising otitis externa. METHODS: A retrospective case study was conducted of patients suffering from external auditory canal cholesteatoma and benign necrotising otitis externa admitted to tertiary hospitals, in the Capital Region of Denmark, over a five-year period. RESULTS: Eighty-three patients (95 ears) with external auditory canal cholesteatoma or benign necrotising otitis externa were identified. A minimum incidence rate of 0.97 per 100 000 inhabitants per year was demonstrated. Sixty-eight per cent of cases had a history of smoking. Most lesions (74 per cent) were localised in the floor of the ear canal. Treatment time was 3.2 months for patients who had surgery and 6.0 months for those who received conservative treatment. CONCLUSION: It is suggested that external auditory canal cholesteatoma and benign necrotising otitis externa are in fact the same disease, and therefore the diagnosis of external auditory canal cholesteatoma should be changed to benign necrotising otitis externa. Microangiopathy has a leading role in the aetiology. Surgery should be conducted in most cases.

Modeling the cholesteatoma microenvironment: coculture of HaCaT keratinocytes with WS1 fibroblasts induces MMP-2 activation, invasive phenotype, and proteolysis of the extracellular matrix.

BACKGROUND: Increased keratinocyte proliferation, increased keratinocyte migration, elaboration of proteases resulting in proteolysis of the extracellular matrix (ECM), and destruction of surrounding tissues all typify the course of cholesteatoma growth. The contribution of stromal fibroblasts to these behaviors remains relatively unexplored. OBJECTIVES: Our objective for the current studies was to create a simple model with which to study these cholesteatoma behaviors, specifically, cell migration, invasion, and proteolysis of the extracellular matrix as well as the role of fibroblasts in the activated keratinocyte phenotype of cholesteatoma. DESIGN: The authors conducted an in vitro culture model. METHODS: The resulting model consists of activated keratinocytes (HaCaT cells) cocultured with normal dermal fibroblasts (WS1 cells) within a three-dimensional reconstituted ECM. We used a confocal imaging assay and software analysis to quantify total functional proteolysis of the ECM in monotypic and organotypic cocultures. This was accomplished by growing cells on an artificial ECM comprised of Matrigel and DQ-collagen IV. DQ-collagen is a "quenched" fluorescent peptide whose fluorescence is unmasked by proteolytic cleavage. RESULTS: Organotypic cocultures of keratinocytes and fibroblasts exhibited increased cell migration, increased cell invasion, increased matrix metalloproteinase-2 secretion and activation, and increased proteolysis of type IV collagen in three-dimensional ECM. Exposure to NSC27366, inhibitor of the small GTPase, Rac, resulted in reduction in both cell invasion and ECM proteolysis. CONCLUSIONS: Stromal fibroblasts may stimulate the invasive phenotype of keratinocytes, including ECM proteolysis. Increased cell invasion and proteolysis are dependent on the Rac pathway in this model. This simple culture model may help further our understanding of these destructive behaviors in cholesteatoma keratinocytes.

[The comparison of clinical features of 2 cases of intracranial otogenic complications].

Two cases of special intracranial otogenic complications were analyzed in the aspects of clinical characteristics, diagnosis and therapy. We concluded that for patients with huge cholesteatoma which damaged the bone of skull base, or chronic otitis media patients with sharp deterioration in symptoms, accompanied by headache and fever, we should promptly do the enhanced magnetic resonance to avoid the missed diagnosis of intracranial complications.

TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction.

Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1ß. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction, and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1ß expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis.

Keratin particle-induced osteolysis: a mouse model of inflammatory bone remodeling related to cholesteatoma.

We implanted keratin and poly(methyl methacrylate) (PMMA) particles to the surface of mouse calvariae to produce a quantitative, localized, inflammatory bone remodeling similar to that seen in cholesteatoma. Both types of particles resulted in increased osteoclast density compared with controls. Osteoclasts infiltrated from marrow and vascular spaces and were active at the periphery of these spaces leading to significant bone remodeling, as demonstrated by the incorporation of bone-labelling fluorophores. Osteoclasts were rarely found on the surface of the calvariae, and mineral apposition rate at the ventral surface was not altered in keratin-implanted animals compared with nonoperated controls. While not useful for the study of the root cause of cholesteatoma, this model will allow the study ofpathologic bone remodeling related to cholesteatoma in a genetically defined animal.

Tympanic membrane displacement patterns in experimental cholesteatoma.

Tympanic membrane (TM) stiffness changes in the pars tensa in response to experimentally induced ear canal cholesteatoma by obstruction of the ear canal were studied. To this aim TM displacement versus pressure was measured with a high resolution, differential moiré interferometer. The measurements were performed on fresh, isolated gerbil temporal bones after removal of the cholesteatoma bulk. Besides an overall stiffness reduction we found that local stiffness variations were present in nine out of 18 studied ears. The stiffness changes as a function of time after ear canal obstruction had a pattern similar to those previously shown to develop in response to various forms of otitis media, showing that the TM stiffness properties decrease in a similar way in response to different inflammatory middle ear diseases. The stiffness changes correlated with an increased overall TM thickness and increased thickness of the lamina propria in particular as measured in histology sections. The stiffness changes may play an important role in the pathophysiology of cholesteatoma.