Association of Matrix Metalloproteinase-2 mRNA Expression with Subtypes of Pediatric Cholesteatoma.

OBJECTIVE: Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase-2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed MMP2 mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples. METHODS: Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University's Otolaryngology Department, were analyzed for MMP2 expression level, using RNA-in situ hybridization. RESULTS: There were no significant differences in MMP2 mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type (p < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida (p < 0.001). MMP2 mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium. CONCLUSION: Our study reveals that MMP2 mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of MMP2 mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.

Congenital cholesteatoma assessment based on staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society.

OBJECTIVE: We aimed to assess the clinical characteristics of extent patterns in congenital cholesteatoma, based on the Japan Otological Society (JOS) staging system. METHODS: This was a retrospective chart review that included 80 ears of 80 patients with congenital cholesteatoma who underwent primary surgery at a tertiary academic medical center. The main characteristics and outcomes reviewed were sex, age, clinical background, surgical method, and stage classification according to two staging classifications: the criteria advocated by JOS and Potsic staging system. RESULTS: The age at the time of surgery ranged from 1 to 35 years (average 8.4 years), and there were 54 men and 26 women. According to the JOS staging system, 12 ears were Stage Ia (15%), 7 ears were Stage Ib (9%), 1 ear was Stage Ic (1%), 59 ears were Stage II (74%), and 1 ear was Stage III (1%). In the study of postoperative residual recurrence, there were 4 cases after the primary operation and 3 cases after the staged operation. All 3 ears with residual disease after planned surgery were cholesteatomas that extended to all the tympanomastoid space. CONCLUSION: We consider the JOS staging system to be more suitable, in terms of anatomical classification and surgical procedure selection for comparison between Europe, the United States, and Asia. Specifically, it was advantageous that the PTAM classification and the S classification are associated with surgical procedure selection and postoperative course.

Introducing the "ChOLE" Classification and Its Comparison to the EAONO/JOS Consensus Classification for Cholesteatoma Staging.

: Many previous attempts have been made to classify or categorize cholesteatomas. Recently, the European Academy of Otology and Neurotology and the Japanese Otological Society proposed a classification system based primarily on extension and complications. The European Academy of Otology and Neurotology/Japanese Otological Society consensus statement makes an effort to standardize reporting of surgical techniques. Internet-based multicenter studies are facilitated by increasing connectivity, but a mutually-agreed framework for reporting is necessary for results to be comparable across sites. New technologies compete with established standardized surgical approaches and need to be validated. It is definitively the right time to find a consensus on how to record and report surgical findings in cholesteatoma surgery. To stimulate this interesting discussion, we propose a ChOLE-classification system, which is based on the differentiation into extension (Ch), status of the ossicular chain at the end of surgery (O), complications (L), and degree of pneumatization and ventilation (E). A numeric rule is used to stage these cholesteatomas from I-III.

Staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society.

In order to provide a basis for meaningful exchange of information among those treating cholesteatoma, the Committee on Nomenclature of the Japan Otological Society (JOS) was appointed in 2004 to create a cholesteatoma staging system as simple as possible to use in clinical practice in Japan. Following the announcement of preliminary criteria for the staging of pars flaccida (attic) cholesteatoma in 2008, we proposed the 2010 JOS staging system for two major types of retraction pocket cholesteatoma, pars flaccida and pars tensa cholesteatoma. Since then, the JOS staging system has been widely used in clinical studies of cholesteatoma in Japan, allowing standardization in reporting of surgical outcomes based on the respective stages of cholesteatoma. We have recently expanded the range of cholesteatoma by adding cholesteatoma secondary to a tensa perforation and congenital cholesteatoma as the 2015 JOS staging system for middle ear cholesteatoma. Although further revisions may be required for universal acceptance of these criteria, we hope our staging system will open the way for international consensus on staging and classification of middle ear cholesteatoma in the near future.

Sanna Classification and Prognosis of Cholesteatoma of the Petrous Part of the Temporal Bone: A Retrospective Series of 81 Patients.

OBJECTIVE: To determine how classification of petrous bone cholesteatomas (PBCs) using the 5-point Sanna classification can predict major structural involvement, facial nerve outcomes, hearing outcomes, postoperative complications, and disease recurrence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center in Bergamo, Italy. PATIENTS: Eighty-one sequential patients with radiologic and surgically confirmed diagnoses of PBC treated at a single tertiary referral center during a 20-year period. MAIN OUTCOME MEASURES: Major structural involvement, facial nerve outcomes, hearing outcomes, postoperative cerebrospinal fluid leak, and disease recurrence were evaluated on the basis of Sanna classification. RESULTS: Using the Sanna classification, 70% (57) were supralabyrinthine, 12% (10) infralabyrinthine, 7% (6) infralabyrinthine-apical, 5% (4) apical, and 5% (4) massive. Massive classification was statistically significantly associated with cochlear involvement (p = 0.009) and internal auditory canal involvement (p = 0.02). The infralabyrinthine-apical class was associated with carotid canal involvement (p = 0.03). Facial nerve interruption was observed in 35% of patients and most frequently in the apical group (75%). Neither hearing nor facial nerve outcomes were associated with Sanna classification. House-Brackmann score improved or was maintained postoperatively in 89% of patients. CONCLUSION: The Sanna classification provides anatomic detail on location of PBCs and is predictive of IAC, cochlear, and carotid artery involvement. However, classification systems for this rare condition continue to pose a challenge in being able to accurately predict facial nerve and hearing outcomes in surgical obliteration of PBC.

Consensus-Based Recommendations on the Definition and Classification of Cholesteatoma.

Development of a consensus on the definitions and classification of cholesteatoma is essential for scientific community to exchange information on clinical studies and compare their outcomes. The aim of the study is to reach a consensus among members of the European Academy of Otology and Neurotology (EAONO) regarding the definitions and classification related to cholesteatoma. A set of statements was developed by the authors utilizing the literature on the definition and classification of cholesteatoma. A questionnaire was sent to the members of the EAONO, inviting them to state if they are in agreement with each of the statements and if not, then to provide comments or suggestions for revision. Responses were evaluated and modified using online questionnaire and survey software based on the Delphi technique, a cyclical process of gathering information, summarizing, and re-submitting the revised statements to the same target population until a consensus is reached. Target agreement among the responders was set at a minimum of 80%, and the cycle of revision and re-submission of the statements were repeated until a consensus was reached on a majority of the statements. A steering group has been established to evaluate the results of the survey and worked via the process of cognitive debriefing. Out of 364 EAONO members, 123 responded to the first consensus cycle, 77 to the second cycle, and 53 to the third cycle. After three cycles, all statements concerning cholesteatoma definitions reached the target of 80% consensus. However, a consensus on the classification of cholesteatoma could not be achieved. The steering group excluded four statements of cholesteatoma definition and established a consensus on cholesteatoma classification. A consensus on cholesteatoma definitions was reached among the members of the EAONO. The final revision on consensus statements for cholesteatoma definition and classification has been made via the process of cognitive debriefing of the steering group.

[Congenital cholesteatoma of middle ear: 20 patients' clinical symptoms and imaging features].

OBJECTIVE: To investigate the location, staging, clinical symptoms, imaging features, and surgical treatment of the congenital cholesteatoma of middle ear (CCME). METHOD: This was a retrospective review of 20 CCME cases. RESULT: Of 20 cases with CCME, 2 cases were classified as Postic stage I, 0 as stage II, 13 as stage III, 5 as stage IV. Conductive hearing loss was the most common clinical symptom. The mean preoperative PTA was 54.1 dB, and the mean ABG was 41.7 dB. One case underwent a modified mastoidectomy and a second-stage ossicular reconstruction; 2 cases experienced a radical mastoidectomy without ossicular reconsturction for extensive cholesteatoma; 5 cases underwent modified mastoidectomy and a one-stage tympanoplasty, with one case diagnosed as congenital malformation of ossicular chain (stapes hypoplasia); other 12 cases underwent a one-stage tympanoplasty. The cholesteatoma localized to the posterior-epitympanum or mesotympanum in all patients, mainly located in the incudostapedial joint. The mean postoperative PTA from 16 cases was 35.3 dB, and A-B gap was 20.2 dB. All patients were followed-up for at least 1 year after operation and recurrence was found in 2 cases. Three cases were accompanied with congenital malformation of ossicular chain. CONCLUSION: CCME is a rare entity and diagnosis is usually delayed in clinical practice due to the silent nature of disease in its early stage. The prognosis of CCME mainly depended on the stage of the lesions.

[Clinical characteristics and surgical management of extensive cholesteatoma of external auditory canal].

OBJECTIVE: To classify the external auditory canal cholesteatoma(EACC) by high-resolution temporal bone CT scans and the clinical findings of the patients, and to discuss the clinical and imaging characteristics and the surgical management of the extensive EACC. METHOD: A retrospective study was carried out among 56 patients (58 ears) with EACC and their clinical data were carefully analyzed. We classified EACC as the extensive type and the localized type. The operation strategy depended on the extent of lesion. All cases were followed up for 1 to 6 years after surgery. RESULT: There were 31 patients with localized EACC, 2 with no bone erosion and 29 (31 ears) with bone erosion within external auditory canal, and 25 patients with extensive EACC, 16 with bone erosion of intra temporal bone and 9 with bone erosion of extra temporal bone. Among all the 25 patients with the extensive type, the most common symptoms were otorrhea, otalgia and hearing loss, with 25, 23, 22 cases, respectively. The tympanic membrane (TM) was intact in 23 patients and perforated in two. The mastoid air cells in 23 patients were involved by the lesion, as well as tympanic antrum in eight, tympanic cavity in two, sigmoid sinus bony wall in five, mastoid segment of facial canal in four, and temporomandibular joint in two patients. Twenty patients underwent modified radical mastoidectomy, only one underwent reconstruction of ossicular chain, and four underwent canaloplasty. The average time of ear dry after surgery was 29 days. The postoperative hearing was improved by an average of 15 dB. No recurrence except for one patient was found during the follow-up period. CONCLUSION: It was of important clinical significance to classify EACC as the extensive type and the localized type. The extensive EACC was misdiagnosed easily because of the complicated clinical manifestations. The classification was helpful for the diagnosis and the selection of surgery strategy of EACC.

Congenital middle ear cholesteatoma: experience from 26 surgical cases.

OBJECTIVES: We analyzed the clinical features and surgical techniques used in cases of childhood congenital cholesteatoma of the middle ear. METHODS: We studied 26 patients (26 ears) who underwent surgery for congenital cholesteatoma between January 1998 and December 2009, focusing on the location and type of cholesteatoma, the surgical procedures involved, and the results obtained. Patients with prior otologic procedures were excluded. A 4-stage system was used to grade the cholesteatomas. RESULTS: The frequency of posterior-quadrant involvement and open-type cholesteatomas increased in the more advanced stages. Second-look operations were performed in 60% of stage III and 75% of stage IV cases; and residual cholesteatomas were found in 20% of stage III and 75% of stage IV cases. Of the cases evaluated both before and after the operation, 100% of stage I and II cases, 86% of stage III cases, and 50% of stage IV cases showed improvement in hearing function. CONCLUSIONS: The staging system is relatively simple, while accurately reflecting clinical results. However, there are many differences between the anterior and posterior types of congenital cholesteatomas in surgical approach and postoperative progression that are not reflected in the classification systems and require further study. In addition, we reviewed the surgical procedures involved in anterior-quadrant cases, and propose a modified surgical procedure.

[Staging-based surgical results in chronic otitis media with cholesteatoma].

Discussions of surgical results in chronic otitis media involving cholesteatoma usually include hearing improvement, side effects, and cholesteatoma recurrence, although such talks could easily involve the influence on surgical results of the intraoperative extension of the cholesteatoma-affected area around the tympanomastoid cavity. Based on intraoperative chronic otitis media staging involving cholesteatoma proposed by the Japan Otological Society in 2010, we studied our tympanoplasty results between April 1997 and March 2010. Hearing improvement in all subjects with pars flaccida cholesteatoma was 79.0% (n= 100) and that with pars tensa 73.3% (n = 30)--results not significantly influenced by intraoperative staging grade but significantly dependent on stapes presence (tympanoplasty type I and III) or absence (type IV). Nine cases of recurrence were seen in pars flaccida and four in pars tensa. Intraoperative side effects and postoperative recurrence often occurred in advanced cases. These findings suggest that intraoperative chronic otitis media staging involving cholesteatoma may make it important to be aware of the need for more careful procedures during surgery and in follow-up.

Ear canal cholesteatoma: meta-analysis of clinical characteristics with update on classification, staging and treatment.

PURPOSE OF REVIEW: We present an update on clinical evaluation, staging, classification and treatment of canal cholesteatoma, including a meta-analysis of clinical data of the last 30 years. RECENT FINDINGS: Ear canal cholesteatoma is frequently associated secondarily to other canal pathologies. The cause for the rare idiopathic form of the disease remains enigmatic. Epidemiologic and experimental studies of its pathogenesis have increased; however, the main explanatory theory of a deficient migratory capacity of the canal epithelium affected has been falsified only recently. Therefore, the debate on the pathogenesis has gained additional impetus and more data is needed. SUMMARY: Canal cholesteatoma is a rarity in otologic pathology, often leading to misdiagnosis as external otitis or otomycosis by physicians unfamiliar with the disease. It presents typically with otorrhea, focal erosion and keratin accumulation in the osseous ear canal and has to be distinguished from keratosis obturans, which leads to otalgia and bilateral conductive hearing loss by ceruminal plugs, with circumferential distention of the ear canal. Treatment by canaloplasty is curative and highly successful. Alternative conservative treatment is feasible, however, requiring long-term follow up, with often painful cleaning of the lesion.

External auditory canal cholesteatoma: reassessment of and amendments to its categorization, pathogenesis, and treatment in 34 patients.

OBJECTIVE: External auditory canal cholesteatoma (EACC) is a rarity. Although there have been numerous case reports, there are only few systematic analyses of case series, and the pathogenesis of idiopathic EACC remains enigmatic. STUDY DESIGN: In a tertiary referral center for a population of 1.5 million inhabitants, 34 patients with 35 EACC (13 idiopathic [1 bilateral] and 22 secondary) who were treated between 1994 and 2006 were included in the study. RESULTS: EACC cardinal symptoms were longstanding otorrhea (65%) and dull otalgia (12%). Focal bone destruction in the external auditory canal with retained squamous debris and an intact tympanic membrane were characteristic. Only 27% of the patients showed conductive hearing loss exceeding 20 dB. Patients with idiopathic EACC had lesions typically located on the floor of the external auditory canal and were older, and the mean smoking intensity was also greater (p < 0.05) compared with patients with secondary EACC. The secondary lesions were assigned to categories (poststenotic [n = 6], postoperative [n = 6], and posttraumatic EACC [n = 4]) and rare categories (radiogenic [n = 2], postinflammatory [n = 1], and postobstructive EACC [n = 1]). In addition, we describe 2 patients with EACC secondary to the complete remission of a Langerhans cell histiocytosis of the external auditory canal. Thirty of 34 patients were treated surgically and became all free of recurrence, even after extensive disease. DISCUSSION: For the development of idiopathic EACC, repeated microtrauma (e.g., microtrauma resulting from cotton-tipped applicator abuse or from hearing aids) and diminished microcirculation (e.g., from smoking) might be risk factors. A location other than in the inferior portion of the external auditory canal indicates a secondary form of the disease, as in the case of 2 patients with atypically located EACC after years of complete remission of Langerhans cell histiocytosis, which we consider as a new posttumorous category and specific late complication of this rare disease.

[Immunohistochemical discrimination of aggressivity between the cholesteatoma from different positions].

OBJECTIVE: To investigate whether the cholesteatoma from different positions have different biological characteristics. METHODS: The expression of the Ki-67 and collagen IV in 19 specimens of cholesteatoma were stained immunohistochemically using the SP method, according to the origin of the specimens, include 7 cases from the epitympanum, 8 cases from tympanic sinus and 4 cases from the out acoustic canal. According to the severity of the inflammation in the perimatrix, the inflammation group included 7 cases, the non-inflammation group included 8 cases. RESULTS: The average count was the same between the cholesteatoma from epitympanum and tympanic sinus. And the count of the cholesteatoma in the middle ear was also the same to the cholesteatoma from the out acoustic canal. But even from the same sample, the cholesteatoma from the positions with severe inflammation in the perimatrix count much higher, and the difference was statistically significant. Collagen IV had been found to localized in the basic membrane. In some specimens the staining of the collagen IV was not continuous. CONCLUSIONS: The results suggested that it was the severity of inflammation in the perimatrix influenced the differences, but not the origins of the cholesteatoma.

Classification of the external auditory canal cholesteatoma.

OBJECTIVES/HYPOTHESIS: The external auditory canal cholesteatoma (EACC) is a rare disease in the field of otolaryngology. Only 1 in 1,000 new otologic patients present with this entity, which was first described by Toynbee. The aim of this article is to classify EACC by different histopathologic and clinical findings of patients presenting to the Department of Otolaryngology at the University of Mannheim, Germany. METHODS: From 2000 to 2004, 17 patients presented to our clinic with EACC. The cholesteatoma were treated surgically, and the specimens were investigated histologically. Clinical findings were also recorded. We classified four stages: stage I with hyperplasia of the canal epithelium, stage II including periosteitis, Stage III including a defective bony canal, and stage IV showing an erosion of adjacent anatomic structure. RESULTS: Eight patients presented with stage II, five patients with stage III, three with stage I, and only one patient presented with erosion of the mastoid cells, which was determined as stage IV. CONCLUSION: In summary, our classification serves to describe the different histopathologic and clinical stages of EACC.

Congenital cholesteatoma: classification, management, and outcome.

OBJECTIVES: To assess whether a classification system for congenital cholesteatoma (CC) can be derived from analysis of a large clinical sample of cases and to assess whether such a classification system is a reliable guide for surgical intervention, reexploration, and hearing outcome. DESIGN: A retrospective review of clinical and surgical records of 119 patients with CC. SETTING: Four tertiary care children's hospitals. PATIENTS: One hundred nineteen children with CC (age range, 2-14 years). RESULTS: Congenital cholesteatomas in the anterior mesotympanum were treated successfully with exploratory tympanotomy. Congenital cholesteatomas involving the posterior superior quadrant and the attic usually had concurrent involvement of the incus and stapes and often required a canal wall up tympanomastoidectomy and a second look for its control. Congenital cholesteatoma involving the mastoid usually involved all of the ossicles, was inconsistently controlled with canal wall up tympanomastoidectomy, and had a poor prognosis for restoration of conductive hearing loss. The mean +/- SD age of children with CC was 5.6 +/- 2.8 years, while that of children with acquired cholesteatoma was 9.7 +/- 3.3 years. CONCLUSIONS: The sequence of spread of CC, involving 3 sites, suggests a natural classification system. The CC usually originates in the anterior superior quadrant, but does not consistently remain there, and may variably occupy the middle ear and mastoid and result in ossicular destruction and conductive hearing loss. The location of CC and the involvement of the ossicles is an accurate predictor of the type of surgery necessary for its control and for the success of hearing restoration.

Pathogenesis of attic retraction pocket and cholesteatoma as studied by computed tomography.

It is hypothesized that blockade of the tympanic isthmus causes isolation of the attic and the adjacent middle ear spaces and that subsequent building up of the negative pressure in these spaces results in retraction of the pars flaccida, leading to formation of attic retraction pockets and cholesteatomas. To examine this theory, computerized tomographic (CT) findings of these conditions were evaluated in a series of 53 ears with retractions of the pars flaccida (attic retractions of Tos type II or deeper), including both retraction pockets and cholesteatomas. In 26 of 28 ears with attic retraction pockets, at least a portion of attic was aerated, and in 22 of these 26 ears, the mastoid antrum was also aerated. In contrast, in the 25 cases with attic cholesteatomas, these numbers decreased to 10 and 5, respectively, and the lack of aeration of the attic was demonstrated in 15 of 25 (60%) of the cases. In three cases of cholesteatoma, follow-up CT revealed either growth of a cholesteatoma from a retraction pocket or development of a small cholesteatoma into a large one. In these ears it was seen that the well-pneumatized attic and mastoid antrum seen in the initial CT was depleted by the growth of cholesteatoma that took place over a period of 4 months to 2 years. These results, showing good patency of the aditus and a pneumatized antrum in early stages of most cases of retraction pockets and cholesteatomas, are not in agreement with the hypothesis that the blockade of the tympanic isthmus is responsible for the pathogenesis of retraction pockets and cholesteatomas originating in the pars flaccida.

Treatment of cholesteatoma and retraction pockets.

Treatment of retraction pockets (RP) and cholesteatomas depends on their nature and evolvement and the size of mastoid pneumatization. RP are secondary to vacillating middle ear negative pressure. Treatment when necessary consists of placing a ventilating tube, excision of the RP or both. In most children and adults, cholesteatoma is derived from RP (or "atelectasis") of the tympanic membrane, where it can be termed "retraction pocket" cholesteatoma or "secondary" cholesteatoma. This type of cholesteatoma is associated with a non-pneumatized mastoid coupled by negative pressure. Approximately one-third of children's cholesteatomas present clinically behind an intact drum despite a pneumatized mastoid. Pathogenetically this type may be "congenital" or "metaplastic" and should be best termed "primary" cholesteatoma. Central perforations associated with cholesteatoma are probably derived from continuous tympanic membrane destruction by infection in cases of RP cholesteatomas or due to a primary cholesteatoma bursting out from the tympanic cavity. Canal-up surgery of cholesteatoma fails in 60% of cases at Tel Aviv University because of the inherent tendency of the tympanic membrane to retract once again. Residual disease was found in our cases to be a lesser cause for failure. Treatment depends on the type of cholesteatoma, emphasizing small "radicals" in sclerotic mastoids. When a pneumatized mastoid is encountered, a posterior tympanotomy should be considered.

O colesteatoma - classificaçäo, histopatologia, e tratamento / cholesteatomas - classsification, histophatology and therapy

Após fazerem consideraçöes sobre o conceito de colesteatoma, os autores dissertam sobre seu mecanismo de formaçäo e várias teorias existentes, ao mesmo tempo que o classifica. Descrevem seu padräo histólogico o relacionado com sua agressividade ao osso temporal. Comentam sobre as principais técnicas operatórias, discutindo as vantagens e desvantagens dos vários procedimentos cirúrgicos

My current cholesteatoma techniques.

Correct treatment of cholesteatoma should always be based on a good knowledge of its pathogenesis. The basic process consists of the ectopic presence of a basal malpighian-like epithelium in the middle ear. Different types of cholesteatoma exist, ranging from the cystic to the invasive form. The most appropriate surgical techniques for each type will be discussed by the author.