Melatonin Attenuates Cisplatin-Induced Ototoxicity via Regulating the Cell Apoptosis of the Inner Ear.

Objective: The mechanism of ototoxicity caused by cisplatin is currently unclear, and the induced apoptosis may play an important role in inner ear injury. Melatonin has high antioxidant and antiapoptotic effects. This study is aimed at clarifying the protective effect on the inner ear and the underlying mechanism of melatonin. Design: The mice and HEI-OC1 cells were randomly separated into four groups: control group, cisplatin group, melatonin group, and cisplatin exposure after melatonin pretreatment group. Place and Duration of the Study. From September 2018 to September 2021, all experiments were completed at the Second Hospital of Shandong University. And the study was approved by the Ethics Committee of the Second Hospital of Shandong University (KYLL-2020 (KJ) A-0191). Methodology. Mice were pretreated with peritoneal injection of melatonin prior to the application of cisplatin. Auditory Brainstem Response (ABR) test was performed before and after treatment, then the temporal bones were collected for histology investigation. HEI-OC1 cells were pretreated with melatonin before adding cisplatin. The apoptosis of HEI-OC1 cells was observed by MTS, TUNEL, and flow cytometry, respectively. Moreover, the mRNA expression of apoptosis-related factors was detected by qRT-PCR. Results: ABR and morphological analysis showed that cisplatin caused damage to the function and structure of the inner ear. MTS, TUNEL, and flow cytometry showed that the application of cisplatin caused a significant increase in the apoptosis level of HEI-OC1 cells, and melatonin pretreatment reduced this damage. Moreover, melatonin pretreatment reversed the mRNA expression changes of apoptosis-related factors induced by cisplatin. Conclusions: Apoptosis is involved in the inner ear dysfunction caused by cisplatin. Melatonin reduces the ototoxicity of cisplatin by regulating the induced apoptosis response.

MiR-142-5p directly targets cyclin-dependent kinase 5-mediated upregulation of the inflammatory process in acquired middle ear cholesteatoma.

MicroRNAs (miRNAs) play important roles in the regulation of cell proliferation, differentiation, apoptosis, and inflammatory responses. MiR-142-5p is an important inflammation-associated miRNA, whose abnormal expression has been associated with a variety of inflammation-related diseases. However, the role and signaling pathways targeted by miR-142-5p in acquired middle ear cholesteatoma (AMEC) have not been fully elucidated. Cyclin-dependent kinase 5 (CDK5), a special member of the CDK family compared with classic cyclins that plays a critical role in the inflammatory response. In this study, we investigated the roles of miR-142-5p and CDK5 in inflammatory responses in AMEC. Our results revealed that the expression of miR-142-5p was significantly reduced in AMEC, and was negatively correlated with the expression of CDK5 (r=-0.5451). We also found that miR-142-5p can inhibit CDK5 expression by directly target 3' untranslated region (UTR) of CDK5. Additionally, our findings indicated that the increased expression of CDK5 induces the secretion of inflammatory cytokines. In order to further confirm the involvement of miR-142-5p in the regulation of the inflammatory response in AMEC through its inhibitory effect on CDK5 expression, we studied the inflammatory response in HaCaT cells transfected with small interfering RNA against CDK5 (si-CDK5) and a miR-142-5p inhibitor. The results confirmed that miR-142-5p regulates the inflammatory response in AMEC by downregulating CDK5. In summary, miR-142-5p directly inhibits the CDK5-mediated upregulation of inflammatory cytokines in AMEC, which makes it a potential therapeutic target in this disease.

TFIIB-related factor 2 regulates glucose-regulated protein 78 expression in acquired middle ear cholesteatoma.

Acquired middle ear cholesteatoma leads to hearing loss, ear discharge, ear pain, and more serious intracranial complications. However, there is still no effective treatment other than surgery. TFIIB-related factor 2 (BRF2) acted as a redox sensor overexpressing in oxidative stress which linked endoplasmic reticulum (ER) stress, while glucose-regulated protein 78 (GRP78) was a biomarker of ER stress in cancer, atherosclerosis and inflammation. In our study, we investigated the roles of BRF2 and GRP78 in acquired middle ear cholesteatoma. Our results revealed that the expression of BRF2 was significant increased in acquired middle ear cholesteatoma, and which was positively correlated with the expression of GRP78. In addition, BRF2 and GRP78 showed colocalization in epithelium of acquired middle ear cholesteatomas and HaCaT cells. Prolongation of LPS stimulation in HaCaT cells escalated the expression of BRF2 and GRP78. To confirm the role of BRF2 and GRP78, we transfected si-BRF2 into HaCaT cells. All results indicated that BRF2 expression positively regulates the expression of GRP78 and may participate in the pathogenesis of acquire middle ear cholesteatoma.

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response.

BACKGROUND: In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 (RvE1) has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models. METHODS: A dose of RvE1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response (ABR), relative balance ability, inner ear morphology and the expression levels of inflammatory factors in the inner ear were analyzed on days 7 and 14 after irradiation and compared among different experimental groups. RESULTS: Changes of ABR and relative balance ability showed the inner functions of experimental mice presented severe damage after irradiation, but the damage was significantly alleviated after RvE1 pretreatment compared to irradiation alone. Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the RvE1-pretreated group compared to that in the irradiation alone group. Along with these functional and morphological changes, the mRNA expression level of anti-inflammatory factors interleukin-2 was significantly increased, while those of proinflammatory factors interleukin-6 and tumor necrosis factor-α were significantly decreased in the inner ear of mice after RvE1 pretreatment compared to irradiation alone. CONCLUSIONS: We believe that inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that RvE1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.

Preliminary study on the feasibility of a two-stage screening strategy for otitis media with effusion in children.

AIM: To evaluate the feasibility of a two-stage screening strategy for otitis media with effusion (OME) in pre-school and school children. The risk factors of OME were also studied. METHODS: One hundred and eighty-nine children aged 4-8 years were recruited. The two-stage screening consisted of an on-site screening with a portable otoscopy along with a questionnaire to both diagnose children with OME and identify children at risk, and a standard screening performed at a regional hospital for final diagnosis. The prevalence detected from the two-stage screening approach was compared to the actual prevalence. RESULTS: The detection rate of OME through the two-stage screening approach was not significantly different from the actual prevalence rate (12.7% vs. 13.4%, P = 0.847). Children from the urban area had a lower risk for OME than that from the rural area (P = 0.007, odds ratio (OR) = 0.28, 95% confidence interval (CI): 0.11-0.74). Compared to childcare dining, family dining helped to reduce the chance of OME (P < 0.001, OR = 0.15, 95% CI: 0.06-0.38). CONCLUSIONS: The two-stage screening strategy was effective for screening for OME among pre-school and school children. It can be used in rural areas that have a high prevalence of OME and limited medical resources.

Analysis of the developmental trajectory and influencing factors of auditory and speech functions after cochlear implantation in Mandarin Chinese speaking children.

Background: The auditory and speech development of the children with cochlear implants (CIs) are influenced by many factors.Objective: To study the developmental trajectory and influencing factors of auditory and speech functions for the Mandarin Chinese speaking children with CIs.Material and methods: The children with CIs undergoing rehabilitation in the same institution from June 2016 to June 2019 were followed up. Their closed monosyllables and disyllables recognition rate, closed average language age, categories of auditory performance (CAP) and speech intelligibility rating (SIR) were evaluated at 0, 1, 3, 6, 12 and 24 months of rehabilitation. The results were analyzed by SPSS 23.0.Results: 49 children were followed up for 1 year, 29 children for 2 years. The evaluated indicators of auditory and speech functions were improved with the prolongation of rehabilitation and influenced by the age of cochlear implantation, the use of hearing aids before surgery, guardian's educational degree, the relationship between guardian and child.Conclusions and significance: The auditory and speech functions of the children with CIs were improved significantly with the prolongation of rehabilitation and influenced by many factors, which can help us to predict the effect of CI more accurately and develop an individualized rehabilitation program.

Identification of Key Modules, Hub Genes, and Noncoding RNAs in Chronic Rhinosinusitis with Nasal Polyps by Weighted Gene Coexpression Network Analysis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with relatively easy recurrence. However, the precise molecular mechanisms of this disease are poorly known. Based on gene sequencing data obtained from the Gene Expression Omnibus (GEO) database, we constructed coexpression networks by weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core gene of pathogenesis, CRSwNP, was screened by protein-protein interaction data (PPI) from the HPRD database. Unsupervised clustering was applied to screen hub genes related to the phenotype of CRSwNP. Blue and turquoise modules were found to be most significantly related to the pathogenicity of CRSwNP. Functional enrichment analysis showed that cell proliferation in the blue modules, the apoptotic process in the turquoise module, and the cancer pathway in both modules were mostly significantly correlated with the development of CRSwNP. The noncoding RNAs (long noncoding RNA and microRNA) and the top 10 core genes in each module were found to be associated with the pathogenesis of CRSwNP. A total of nine hub genes were identified to be related to the CRSwNP phenotype. By qRT-PCR analysis, AKT1, CDH1, PIK3R1, CBL, LRP1, MALAT1, and XIST were proven to be associated with the pathogenesis of CRSwNP. AGR2, FAM3D, PIP, DSE, and TMC were identified to be related to the CRSwNP phenotype. Further exploration of these genes will reveal more important information about the mechanisms of CRSwNP.

Cmah deficiency may lead to age-related hearing loss by influencing miRNA-PPAR mediated signaling pathway.

BACKGROUND: Previous evidence has indicated CMP-Neu5Ac hydroxylase (Cmah) disruption inducesaging-related hearing loss (AHL). However, its function mechanisms remain unclear. This study was to explore the mechanisms of AHL by using microarray analysis in the Cmah deficiency animal model. METHODS: Microarray dataset GSE70659 was available from the Gene Expression Omnibus database, including cochlear tissues from wild-type and Cmah-null C57BL/6J mice with old age (12 months, n = 3). Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes database followed by module analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. The upstream miRNAs and potential small-molecule drugs were predicted by miRwalk2.0 and Connectivity Map, respectively. RESULTS: A total of 799 DEGs (449 upregulated and 350 downregulated) were identified. Upregulated DEGs were involved in Cell adhesion molecules (ICAM1, intercellular adhesion molecule 1) and tumor necrosis factor (TNF) signaling pathway (FOS, FBJ osteosarcoma oncogene; ICAM1), while downregulated DEGs participated in PPAR signaling pathway (PPARG, peroxisome proliferator-activated receptor gamma). A PPI network was constructed, in which FOS, ICAM1 and PPARG were ranked as hub genes and PPARG was a transcription factor to regulate other target genes (ICAM1, FOS). Function analysis of two significant modules further demonstrated PPAR signaling pathway was especially important. Furthermore, mmu-miR-130b-3p, mmu-miR-27a-3p, mmu-miR-27b-3p and mmu-miR-721 were predicted to regulate PPARG. Topiramate were speculated to be a potential small-molecule drug to reverse DEGs in AHL. CONCLUSIONS: PPAR mediated signaling pathway may be an important mechanism for AHL. Downregulation of the above miRNAs and use of topiramate may be potential treatment strategies for ALH by upregulating PPARG.

Substrate specificity characterization for eight putative nudix hydrolases. Evaluation of criteria for substrate identification within the Nudix family.

The nearly 50,000 known Nudix proteins have a diverse array of functions, of which the most extensively studied is the catalyzed hydrolysis of aberrant nucleotide triphosphates. The functions of 171 Nudix proteins have been characterized to some degree, although physiological relevance of the assayed activities has not always been conclusively demonstrated. We investigated substrate specificity for eight structurally characterized Nudix proteins, whose functions were unknown. These proteins were screened for hydrolase activity against a 74-compound library of known Nudix enzyme substrates. We found substrates for four enzymes with kcat /Km values >10,000 M-1  s-1 : Q92EH0_LISIN of Listeria innocua serovar 6a against ADP-ribose, Q5LBB1_BACFN of Bacillus fragilis against 5-Me-CTP, and Q0TTC5_CLOP1 and Q0TS82_CLOP1 of Clostridium perfringens against 8-oxo-dATP and 3'-dGTP, respectively. To ascertain whether these identified substrates were physiologically relevant, we surveyed all reported Nudix hydrolytic activities against NTPs. Twenty-two Nudix enzymes are reported to have activity against canonical NTPs. With a single exception, we find that the reported kcat /Km values exhibited against these canonical substrates are well under 105 M-1  s-1 . By contrast, several Nudix enzymes show much larger kcat /Km values (in the range of 105 to >107 M-1  s-1 ) against noncanonical NTPs. We therefore conclude that hydrolytic activities exhibited by these enzymes against canonical NTPs are not likely their physiological function, but rather the result of unavoidable collateral damage occasioned by the enzymes' inability to distinguish completely between similar substrate structures. Proteins 2016; 84:1810-1822. © 2016 Wiley Periodicals, Inc.

[Cochlear implantation in bilateral traumatic severe to profound sensorineural deafness].

OBJECTIVE: To analyze the audiologic results of cochlear implantation in bilateral severe to profound sensorineural hearing loss following head trauma. METHODS: A retrospective study of our cochlear implantation cases in bilateral severe to profound sensorineural hearing loss following head trauma (with or without temporal bone fractures). Four patients in second hospital of Shandong university were analyzed in this study. RESULTS: All the patients received unilateral cochlear implantation and gained open-set speech perception ranging from 92% to 100%. The aided hearing threshold ranged from 30 dBHL to 35 dBHL. None of them experienced a decrease in the hearing performance in the follow-up (1-2 years). CONCLUSION: With sufficient preoperative assessment, cochlear implantation is an effective management for hearing rehabilitation in bilateral severe to profound sensorineural hearing loss following head trauma.

Antiproliferative effects of celecoxib in Hep-2 cells through telomerase inhibition and induction of apoptosis.

BACKGROUND: To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). MATERIALS AND METHODS: The growth inhibition rate of Hep-2 cells in vitro was measured by MTT assay, and apoptosis by TUNEL assay and flow cytometry (FCM). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. The mRNA expression of human telomerase RNA component(hTR), human telomerase reverse transcriptase (hTERT) and human telomerase-associated protein(hTEP1) was determined by RT-PCR assay. Expression of Bax and Bcl-2 proteins was assessed by Western blotting. RESULTS: Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. CONCLUSIONS: Celecoxib had the antiproliferative and pro-apoptotic effect in Hep-2 cells. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may thus play an important role in telomerase activity as well as apoptosis.

[Efficacy of high-resolution CT in differential diagnosis of chronic suppurative otitis media and cholesteatoma otitis media by soft-tissue shadows].

OBJECTIVE: To evalute the efficacy of high-resolution CT(HRCT) in differential diagnosis and treatment of chronic suppurative otitis media and cholesteatoma otitis media by soft-tissue shadows. METHODS: HRCT scanning was performed in 120 cases, 153 ears, with chronic otitis suppurative media and cholesteatoma otitis media, of which original data were processed with multi-planar reconstruction (MPR) and maximum intensity projection (MIP), the characteristics of the soft-tissue shadows' growth, window width or window leveling and bony destruction were respectively observed, as well as compared with the surgery findings. RESULTS: In 120 patients (153 ears), 109 ears were diagnosed as cholesteatoma otitis media, and 44 ears were diagnosed as chronic suppurative otitis media, among which 33 ears had granulation tissue and 11 ears had secretion. One hundred and seven ears were postoperatively diagnosed as cholesteatoma otitis media, among which 25 ears had granulation tissue. Among 46 ears of chronic suppurative otitis media, 35 ears had granulation tissue, and only 11 ears had secretion. A 98.6% diagnostic accuracy can be reached with HRCT in diagnosing cholesteatoma otitis media and chronic suppurative otitis media. The Youden's index was 0.98, 0.98 and 1.00 respectively with HRCT in diagnosing cholesteatoma, granulation tissue and secretion. CONCLUSIONS: Combination of the three different imaging methods, axial images, coronal MPR images and MIP images, can improve the efficacy of the HRCT diagnosis and definite chronic otitis media, which can be routinely used for surgery plan.

Down-regulation of toll-like receptor 4 in the granulation tissues of postoperative mastoid cavities with otorrhea.

CONCLUSIONS: The expression of toll-like receptor (TLR) 4 and associated downstream events, such as the activation of signal pathway proteins and inflammatory cytokine production, were down-regulated in the granulation tissues of postoperative mastoid cavity with otorrhea, possibly leading to endotoxin tolerance. OBJECTIVE: The postoperative mastoid cavity is exposed to a high density and diversity of bacteria, but very little is known about how the immune environment is maintained in these regions with otorrhea. In this study, we investigated the changes in the TLR2 and TLR4 signaling pathways and inflammatory cytokine production in the granulation tissues of mastoid cavities with otorrhea and in normal auditory canal skin. MATERIALS AND METHODS: We investigated the expression of TLR2 and TLR4, as well as downstream signal pathway proteins, nuclear factor-kappaB (NF-kappaB) DNA binding, and secretion of tumor necrosis factor-alpha (TNF-alpha) in 28 samples of granulation tissue obtained from the postoperative mastoid cavity with otorrhea and 10 normal external auditory canal skin samples. RESULTS: We found that the frequency of TLR2- and TLR4-positive cells was not increased in granulation tissues relative to normal skin, but the TLR4 mRNA and protein were down-regulated. In this pathophysiological process, there was also a lack of downstream signal pathway protein activation and secretion of TNF-alpha.

[The diagnostic value of multi-planar reconstruction in semicircular canals disease by HRCT].

OBJECTIVE: To study the diagnostic value of high-resolution computed tomography (HRCT) and multiplanar reconstruction (MPR) in assessment of semicircular canals disease. METHOD: Eighty-three patients were scanned with HRCT and the original data were processed with MPR. The semicircular canals full length was respectively observed in one image of MPR in the normal ears. The abnormal location of the canal were observed. RESULT: In one image the full length of the horizontal, superior and posterior semicircular canal can be respectively displayed in one image of MPR in normal ears. By this way ,1 superior semicircular canal dehiscence (SSCD)was found in precaution group, 1 superior and 2 horizontal semicircular canal blocked, 1 vestibular aqueduct (VA) joined into superior semicircular canal and 2 VAs joined into posterior semicircular canal and abnormity of the three semicircular canals were found in SNHL. CONCLUSION: MPR canould display the three canals full length in one picture and have a high specificity in the diagnosis of the semicircular canal abnormity.

Expression of VEGF, iNOS, and eNOS is increased in cochlea of diabetic rat.

CONCLUSION: The results of this study indicate that diabetes causes up-regulation of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS), which may be involved in the pathogenesis of cochlea functional loss. OBJECTIVE: To investigate the underlying mechanisms that may be responsible for diabetic microangiopathy in the inner ear, we studied the expression of VEGF, iNOS, and eNOS in the streptozotocin (STZ)-induced diabetic rat cochlea. MATERIALS AND METHODS: The immunofluorescence studies were performed by using FITC-labelled specific antibodies to VEGF, iNOS, and eNOS on paraffin sections of the cochlea. The expression levels of VEGF, iNOS, and eNOS were quantified by means of Western blot analysis of cochlea protein extracts. Evans blue (EB) was used to investigate blood-labyrinth barrier (BLB) permeability in the cochlea. RESULTS: Increased cochlear expression of VEGF, iNOS, and eNOS was detected in the diabetic rat. Furthermore, increased permeability of BLB was evidenced by increased cochlear EB extravasation in the diabetic rat.

[Expression and significance of nuclear factor-kappa B ligand and correlation factor in the tissue of otitis media with cholesteatoma].

OBJECTIVE: To investigate the expressions of nuclear factor-kappa B ligand (RANKL), receptor activator of nuclear factor-kappa B(RANK)and osteoprotegerin (OPG) and the relation of RANKL with bone- erosion in human cholesteatoma tissue. METHOD: Thirty cholesteatoma and twenty normal auditory canal skin specimens were investigated. The expressions of RANKL, RANK and OPG were examined by immunohistochemistry. RESULT: The overexpressions of the cytokine RANKL and RANK were found in infiltrated lymphocytes in the cholesteatoma tissue comparing with normal external meatal skin( t = 7. 758,6. 482, P <0. 05); While, the expression of OPG was significantly higher in cholesteatoma tissue comparing with normal external meatal skin. the OPG/ RANKL was decreased in cholesteatoma tissue comparing with normal external meatal skin( t = 8. 183, P < 0. 05). CONCLUSION: This study revealed that the expressions level of RANKL and RANK were markedly increased in the perimatrix of cholesteatoma, which is closely related to the bone- erosion induced by cholesteatoma.

[Diagnostic value of high-resolution computed tomography imaging in congenital inner ear malformations].

OBJECTIVE: To observe the inner ear structure with volume rendering (VR) reconstruction and to evaluate the role of high-resolution computed tomography (HRCT) in congenital inner ear malformations. METHOD: HRCT scanning was performed in 10 patients (20 ears) without ear disease (control group) and 7 patients (11 ears) with inner ear malformations (IEM group) and the original data was processed with VR reconstruction. The inner ear osseous labyrinth structure in the images generated by these techniques was observed respectively in the normal ears and malformation ears. RESULT: The inner ear osseous labyrinth structure and the relationship was displayed clearly in VR imaging in the control group,meanwhile, characters and degree of malformed structure were also displayed clearly in the IEA group. Of seven patients (11 ears) with congenital inner ear malformations, the axial, MPR and VR images can display the site and degree in 9 ears. VR images were superior to the axial images in displaying the malformations in 2 ears with the small lateral semicircular canal malformations. The malformations included Mondini deformity (7 ears), vestibular and semicircular canal malformations (3 ears), vestibular aqueduct dilate (7 ears, of which 6 ears accompanied by other malformations) , the internal auditory canal malformation (2 ears, all accompanied by other malformations). CONCLUSION: HRCT can display the normal structure of bone inner ear through high quality VR reconstructions. VR images can also display the site and degree of the malformations three-dimensionally and intuitively. HRCT is valuable in diagnosing the inner ear malformation.

[Surgical approaches of anterior skull base tumors].

OBJECTIVE: Study for surgical approaches on anterior skull base tumors. METHOD: All 37 cases with anterior skull base tumors were surgically treated. Twenty-one cases were treated with anterior craniofacial approaches: Frontal subcranial combined with total maxillectomy in 8 cases or/with orbital exenteration in 5 cases, combined with lateral rhinotomy in 1 cases, combined with naso translocation with medial maxillectomy in 7 cases. Partial or total maxillary swing combined with naso pyramid translocation in 13 cases. Frontonasal, fronto-orbital and midface degloving in one case respectively. RESULT: Of the 27 malignant cases the 3 and 5-year survival rates were 81.9% (22/27) and 62.9% (17/27) respectively, and one tumor free case living well more than 9 years. There were no recurrence in 10 cases with benign tumor. CONCLUSIONS: Various craniofacial approaches except lateral rhinotomy provide directly satisfactory tumor exposure and facilitate enbloc resection of the naso paranasal sinus tumor with intracranial extension. Partial or total maxillary swing combined with naso pyramid translocation is good for tumor involving the skull base without intracranial invasion. The fronto-nasal pyramid translocation is good for removal of the upper part of nasal tumor with intracranial extension on well developed frontal sinus. The fronto orbital approach is proper for removal of fronto-sphenoid tumor and midface degloving may be used in selected cases.

Results of hearing tests after total middle ear reconstruction.

CONCLUSIONS: Patients treated by mastoidectomy in the past often present with hearing loss and cavity problems such as pus discharge. Total middle ear reconstruction (TMER) improves the hearing of these patients by correcting cavity problems and resolution of ear discharge, which facilitates ossicular chain reconstruction such as type III or type IV tympanoplasty. OBJECTIVE: To evaluate the effectiveness of TMER in improving hearing. PATIENTS AND METHODS: We reviewed the audiograms of 56 ears of 48 patients who underwent TMER in combination with either type III or type IV tympanoplasty. Audiometric pure tone thresholds averaged over three frequencies (500, 1000, and 2000, pure tone average) were measured and compared before and after surgery. Successful outcome was defined as improvement of 15 dB or more. The mean follow-up was 5.7 years (range 1.1-12.6). We also analyzed the relations between hearing improvement and factors such as type of tympanoplasty (types III and IV), choice between one-stage and two-stage operation, and the interval between original mastoidectomy and final operation. RESULTS: The mean hearing gain was 13.6 (+/-11.9) dB. Twenty-seven procedures (48.2%) were considered successful, with improvement of 15 dB or more. The results of type III tympanoplasty group were significantly superior to those of type IV (p<0.05, Student's t test). One- and two-stage surgery did not significantly influence outcome. The interval between the initial operation correlated weakly and negatively (r = - 0.266, p<0.05) with hearing gain.