Microarray analysis and functional prediction of differentially expressed circular RNAs in acquired middle ear cholesteatoma

Background Middle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes. Circular RNA (circRNA) plays an essential role in the pathogenesis of many proliferative diseases. However, the role of circRNA in the etiopathogenesis of middle ear cholesteatoma is rarely investigated so far. We aimed to investigate the differential expression profiling of circRNAs between acquired middle ear cholesteatoma and normal skin, and to identify potential circRNAs contributing to the etiopathogenesis of middle ear cholesteatoma. Microarray analysis and functional prediction were performed to investigate the circRNA expression profiling between middle ear cholesteatoma and normal skin. Validation of differentially expressed circRNAs was conducted by qRT-PCR. Prediction of m6A modification was also carried out. Results Microarray analysis displayed that totally 93 up-regulated and 85 down-regulated circRNAs were identified in middle ear cholesteatoma. Through validation, expressions of hsa_circRNA_104327 and hsa_circRNA_404655 were significantly higher, while hsa_circRNA_000319 was significantly down-regulated in cholesteatoma. GO classification, KEGG pathway, and ceRNA network analyses suggested that these differentially expressed circRNAs might play important roles in the etiopathogenesis of middle ear cholesteatoma. Prediction of m6A modification exhibited that hsa_circRNA_000319 possessed 4 m6A sites with very high confidence, and hsa_circRNA_404655 had 3 m6A sites with high confidence. Conclusions Our study revealed that these differentially expressed circRNAs might contribute to the etiopathogenesis of middle ear cholesteatoma. Further researches should be conducted to investigate the exact mechanism of these differentially expressed circRNAs in the etiopathogenesis of middle ear cholesteatoma. Targeting on these circRNAs may provide a new strategy for middle ear cholesteatoma therapy in the future.

Early non-EPI DW-MRI after cholesteatoma surgery

Objective Middle ear cholesteatoma may lead to the erosion of the bony structures of the temporal bone, possibly causing intra- and extracranial complications. Surgical treatment is mandatory, and due to possible residual/recurrent disease, the use of reliable diagnostic methods is essential. Our study aimed to evaluate the reliability of non-EPI DW-MRI for the follow-up of cholesteatoma after surgery. Methods In a study group including 53 consecutive patients who underwent surgery for cholesteatoma at a tertiary university hospital, an imaging protocol was applied, including non-echo planar diffusion-weighted imaging magnetic resonance (MR) at 1 month after surgery and then at 6 and 12 months after surgery. Based on the combination of preoperative assessment and intraoperative findings, the study group was divided into 3 subgroups: petrous bone (PB) cholesteatoma, complicated cholesteatoma and uncomplicated cholesteatoma. PB cholesteatoma patients were treated by a subtotal petrosectomy, whereas complicated and uncomplicated cholesteatoma patients were treated either by a canal wall up procedure or a retrograde (inside-out) canal wall down technique with bone obliteration technique (BOT). Results The results show that patients who had positive findings on non-EPI DW-MRI scans 1 month after surgery consequently underwent revision surgery during which residual cholesteatoma was noted. All the patients who displayed negative findings on non-EPI DWI-MRI scan at 1 month after surgery did not show the presence of a lesion at the 6- and 12-month evaluations. The 6 patients who displayed residual cholesteatoma at the 1-month follow-up presented dehiscence/exposure of the facial nerve canal at the primary surgery, mostly at the level of the labyrinthine segment. Conclusion Non-EPI DW-MRI is a useful and reliable tool for follow-up cholesteatoma surgery, and when applied early, as was done in the protocol proposed in the present study, this tool may be used to detect the presence of residual cholesteatoma in some patients, prompting the planning of early revision surgery.

Transcanal endoscopic treatment for congenital middle ear cholesteatoma in children

Background To investigate the feasibility and efficacy of transcanal endoscopic treatment for congenital middle ear cholesteatoma in children. Methods Eleven children diagnosed with congenital middle ear cholesteatoma were collected at Huazhong University of Science and Technology Union Shenzhen Hospital from January 2016 to December 2020. The retrospective study of their operation process, comparison of pre- and post-operative hearing result, surgical complications through the surgical video. Results Eleven children received total ear endoscopic surgery under general anesthesia. One of them received planned second operation to reconstruct the ossicular chain. At six months after operation, 11 children underwent re-examination. The mean bone conduction hearing threshold had no significant change (P>0.05), the mean air conduction hearing threshold was significantly decreased (P<0.05), and the air-bone conduction difference was significantly reduced (P<0.05). In 11 children, the air-bone conduction difference were all reduced to less than 20 dB, and 7 cases were reduced to less than 10 dB. All the children were followed up so far without sensorineural deafness, facial paralysis and other serious complications, as well as no recurrence. Conclusion Otoendoscope can provide a wide-angle field of vision and advantages in small surgical trauma, quick healing, avoiding repeated dressing changes and high acceptance of secondary surgery. Intraoperative application of 30° and 45° otoendoscope can effectively reduce residuals. Otoendoscope is widely used as a surgical method in the treatment of congenital middle ear cholesteatoma in children.

The Role of Otoscopy in the Diagnosis of Rare Diseases in Pediatrics. Congenital Middle Ear Cholesteatoma in the Child: Clinical Case

The clinical recommendations “Acute respiratory viral infection (ARVI) in children" indicate that otoscopy should be a part of routine pediatric examination of each patient along with auscultation, percussion, etc. Nowadays, there are no legal regulations on which specialists can perform otoscopy. Thus, there is significant pediatricians’ interest in otoscopy, especially in diagnosis of acute otitis media (AOM) during primary examination for timely antibacterial management. Moreover, pediatricians could reveal such rare and very aggressive middle ear disease as cholesteatoma, its early diagnosis can prevent the development of any complications and determines the range and quality of rehabilitation actions.

Expression of Cytokeratin 6 and 16 in Middle Ear Cholesteatoma

BACKGROUND: Cholesteatoma is hyperproliferative because of the response of direct biomechanical trauma, and inflammation processes then lead to temporal bone destruction with some clinical manifestations of complications. The hyperproliferation mechanism occurred because of the activation of intermediate filament protein type I and type II known as cytokeratin (CK). AIM: This study aimed to examine the expression CK 6 and CK 16 in cholesteatoma. METHODS: This is a cross-sectional comparative study. Cholesteatoma specimens obtained from 15 patients who underwent surgery were considered as the case, and 15 normal retro-auricular skins were considered as the control. All samples were examined for expression through immunohistochemistry and scored using the immunoreactivity score. Data were analyzed using SPSS via χ2 test, and the difference was significant (p < 0.05). RESULTS: The expression of CK 6 was high in cholesteatoma (33.3%) and low in retro-auricular skin. The expression of CK 16 was high in all samples of cholesteatoma and mostly high in the retro-auricular skin; both expressions were statistically significant (p < 0.05). CONCLUSION: The expression of CK 6 and CK 16 in cholesteatoma was higher than in normal retro-auricular skin.

Microarray Analysis And Functional Prediction Of Differentially-Expressed Circular RNAs In Acquired Middle Ear Choleateatoma

Background: Middle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes. Circular RNA (circRNA) plays an essential role in the pathogenesis of many proliferative diseases. However, the role of circRNA in the etiopathogenesis of middle ear cholesteatoma is rarely investigated so far. Our aim was to investigate the differential expression profiling of circRNAs between acquired middle ear cholesteatoma and normal skin, and to indentify potential circRNAs contributing to the etiopathogenesis of middle ear cholesteatoma. Microarray analysis and functional prediction were performed to investigate the circRNA expression profiling between middle ear cholesteatoma and normal skin. Validation of differentially expressed circRNAs was conducted by qRT-PCR. Prediction of m6A modification was also carried out. Results: Microarray analysis displayed that totally 93 up-regulated and 85 down-regulated circRNAs were identified in middle ear cholesteatoma. Through validation, expressions of hsa_circRNA_104327 and hsa_circRNA_404655 were significantly higher, while hsa_circRNA_000319 was significantly down-regulated in cholesteatoma. GO classification, KEGG pathway, and ceRNA network analyses suggested that these differentially expressed circRNAs might play importantant roles in the etiopathogenesis of middle ear cholesteatoma. Prediction of m6A modification exhibited that hsa_circRNA_000319 possessed 4 m6A sites with very high confidence, and hsa_circRNA_404655 had 3 m6A sites with high confidence.Conclusions: Our study indicated possible roles of differentially expressed circRNAs in the etiopathogenesis of middle ear cholesteatoma. Targeting on these differentially expressed circRNAs may provide a new and effective treatment for middle ear cholesteatoma in the future.