Application of artificial intelligence using a convolutional neural network for detecting cholesteatoma in endoscopic enhanced images.

OBJECTIVE: We examined whether artificial intelligence (AI) used with the novel digital image enhancement system modalities (CLARA+CHROMA, SPECTRA A, and SPECTRA B) could distinguish the cholesteatoma matrix, cholesteatoma debris, and normal middle ear mucosa, and observe the middle ear cavity during middle ear cholesteatoma surgery. METHODS: A convolutional neural network (CNN) was trained with a set of images chosen by an otologist. To evaluate the diagnostic accuracy of the constructed CNN, an independent test data set of middle ear images was collected from 14 consecutive patients with 26 cholesteatoma matrix lesions, who underwent transcanal endoscopic ear surgery at a single hospital from August 2018 to September 2019. The final test data set included 58 total images, with 1‒5 images from each modality for each case. RESULTS: The CNN required only 10 s to analyze more than 58 test images. Using SPECTRA A and SPECTRA B, the CNN correctly diagnosed 15 and 15 of 26 cholesteatoma matrix lesions, with a sensitivity of 34.6% and 42.3%, and with a specificity of 81.3% and 87.5%, respectively. CONCLUSION: Our preliminary study revealed that AI and novel imaging modalities are potentially useful tools for identifying and visualizing the cholesteatoma matrix during endoscopic ear surgery. The diagnostic ability of the CNN is not yet appropriate for implementation in daily clinical practice, based on our study findings. However, in the future, these techniques and AI tools could help to reduce the burden on surgeons and will facilitate telemedicine in remote and rural areas, as well as in developing countries where the number of surgeons is limited.

Cholesteatoma Imaging Using a Digital Image Enhancement System During Endoscopic Ear Surgery.

Supplemental Digital Content,http://links.lww.com/MAO/B68.

Relationship between clinicopathological characteristics and CYLD expression in patients with cholesteatoma.

Middle ear cholesteatoma is a destructive disease in which inflammation plays an important role in development and progression, and there are currently no biomarkers predicting prognosis or recurrence. Cylindromatosis (CYLD), a tumor suppressor deubiquitinase, serves as a negative regulator of inflammation expressed in tissues including the middle ear. To determine the clinical significance of CYLD in acquired cholesteatoma, we evaluated CYLD expression in acquired cholesteatoma tissue by immunostaining and analyzed its correlation with clinicopathological characteristics. Our immunohistochemical analysis revealed that CYLD expression levels were varied in the tissues of acquired cholesteatoma patients. The relative expression levels of CYLD in cholesteatoma exhibited a significant correlation with the grade of otorrhea (R = 0.532, p = 0.039). Moreover, the period of epithelialization was also significantly associated with the relative expression levels of CYLD (R = 0.720, p = 0.002). In addition, CYLD expression tended to be lower in the group with recurrence. These results suggest that low CYLD expression correlates with postoperative recovery of acquired cholesteatoma, while potentially affecting the induction of recurrence. This is the first report showing that low CYLD expression correlates with accelerated disease recovery, and suggests a new aspect of CYLD as a prognostic predictor of acquired cholesteatoma.

Role of Dach1 revealed using a novel inner ear-specific Dach1-knockdown mouse model.

The Dach1 gene is expressed in the inner ear of normal mouse embryos in the area that differentiates into the cochlear stria vascularis (SV). We hypothesised that Dach1 downregulation in the inner ear would lead to SV dysplasia. However, because Dach1 knockout is embryonic lethal in mice, the role of Dach1 in the inner ear is unclear. Here, we established inner ear-specific Dach1-knockdown mice and showed that Dach1 downregulation resulted in hearing loss, reduced endocochlear potential and secondary outer hair cell loss. There were no abnormalities in marginal cells and basal cells in the SV or spiral ligament in inner ear-specific Dach1-knockdown mature mice. However, intermediate cell dysplasia and thinning of the SV were observed. Moreover, dynamic changes in the expression of key genes related to the epithelial-mesenchymal transition were observed in the lateral wall of the cochlear epithelium, which differentiated into the SV in inner ear-specific Dach1-knockdown mice at embryonic stages. In summary, suppression of Dach1 expression in the inner ear caused the epithelial-mesenchymal transition in the lateral wall of cochlear epithelium, resulting in loss of intermediate cells in the SV and SV dysplasia.This article has an associated First Person interview with the first author of the paper.

Non-microscopic Middle Ear Cholesteatoma Surgery: A Case Report of a Novel Head-Up Approach.

OBJECTIVE: To assess the feasibility of a postauricular transcortical mastoidectomy utilizing an exoscope, which offers 3D stereoscopic visualization. STUDY DESIGN: Clinical capsule report. PATIENTS: Two consecutive patients with cholesteatoma involvement in the mastoid cavity were included in the study. INTERVENTION: After transcanal endoscopic surgery, postauricular mastoidectomy utilizing a surgical 3D exoscope was performed. Then, the cholesteatoma in the mastoid cavity was removed through the mastoidectomy opening with endoscopes. RESULTS: The postauricular transcortical mastoidectomy utilizing a 3D exoscope was not only feasible, but importantly, the exoscope took little time to switch to and resulted in a smooth workflow. There was no cholesteatoma recurrence at 9 months. CONCLUSION: During endoscope-based surgery, in patients with cholesteatoma mastoid involvement, we can continue to perform the surgical procedure in a heads-up position utilizing a surgical 3D exoscope. The combination of transcanal endoscopic ear surgery and the postauricular transcortical mastoidectomy utilizing a surgical 3D exoscope is a very novel treatment strategy for cholesteatoma, and it gives us a comfortable and consistent working environment in endoscope-based ear surgery.

Pharyngocutaneous fistula caused by dried 'Kombu' (edible seaweed) after total laryngectomy.

The most common early complication after total laryngectomy is pharyngocutaneous fistula (PCF). However, there are no reports of PCF after total laryngectomy caused by 'Kombu' (edible seaweed) as a foreign body in the digestive tract. A 68-year-old Japanese man had undergone total laryngectomy 5 years previously. He presented with PCF, neck swelling and pain. Video endoscopy showed that a dark green foreign body obstructed the digestive tract. PCF was successfully treated via emergency surgery comprising abscess drainage, foreign body removal and fistula closure. The foreign body was kombu. Clinicians who perform total laryngectomy should know the potential dangers of consuming hygroscopic food items that can cause bolus obstruction of the upper digestive tract and pharyngeal abscess and perforation.

The effect of cochlear implants on vestibular-evoked myogenic potential responses and postural stability.

OBJECTIVE: Current spread by electrical stimulation via inserted cochlear implant (CI) electrodes and the consequential increase in sound input can affect the equilibrium of patients. The aim of the present study was to clarify the effect of CIs on the equilibrium of patients through cervical vestibular-evoked myogenic potential (cVEMP) testing and static stabilometry performed with the CIs turned on (CI-on) and off (CI-off). METHODS: This prospective study included nine adult patients who underwent unilateral cochlear implantation surgery at our institution. cVEMP testing and stabilometry were performed before surgery and repeated after surgery in the CI-on and CI-off modes. RESULTS: Before surgery, cVEMP responses were diminished in five of the nine patients (55.6%), while the results of stabilometry were poor in six patients (66.7%). After surgery, both cVEMP responses and stabilometry findings in the CI-off mode exhibited significant deterioration relative to the preoperative results (cVEMP: 7/9, 77.8%; stabilometry: 7/9, 77.8%). However, in the CI-on mode, there were significant improvements in both test results relative to the findings in the CI-off mode for all patients. CONCLUSION: CIs compensated for the surgical trauma-induced deterioration in static postural stability when turned on, resulting in a considerable improvement. Our findings suggest that postoperative cVEMP testing in the CI-on and CI-off modes will enable more accurate assessment of the saccule-inferior vestibular nerve system function after cochlear implant surgery.

Long-term changes in vocal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer.

BACKGROUND: The purpose of this study was to assess changes in vocal function over time following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP). METHODS: A total of 17 patients who underwent SCL-CHEP for laryngeal squamous cell carcinoma between 2007 and 2015 were reviewed. We examined maximum phonation time (MPT), mean airflow rate (MFR), voice intensity, the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, Voice Handicap Index-10 (VHI-10), and voice-related quality of life (V-RQOL) scores. To assess changes over time in these parameters, we set 3 evaluation periods after surgery: within the first 12 months (term A), 13-36 months (term B), and after 37 months (term C). RESULTS: The mean MPT, MFR, G and B GRBAS subscale, VHI-10, and V-RQOL scores improved significantly over time postoperatively. CONCLUSION: Multiple vocal function parameters improved significantly with time due to self-adaptation to a newly created glottis after surgery.

Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.

There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

Five-year postoperative outcomes of modified staged canal wall up tympanoplasty for primary acquired cholesteatoma.

OBJECTIVE: For successful canal wall up tympanoplasty (CWUT) for the treatment of cholesteatoma, the restoration of stable middle ear aeration is also important; however, little is known about the dynamics of such aeration or the optimal surgical procedure. In this study, alternative additional surgical procedure was selected based on the grade of middle ear aeration during the second-stage operation. SUBJECTS AND METHODS: Patients included in this study underwent staged CWUT surgeries with mastoid cortex plasty (MCP) for well-aerated ears (grade 3) and bony mastoid obliteration (BMO) for poorly aerated ears (grade 2-0). Of the 115 ears included in this study, 62 were followed for more than 5 years. Recurrence rates with deep retraction pocket formation were assessed using the Kaplan-Meier survival analysis. The aeration was graded as: 0, no aeration; 1, aeration of only the mesotympanum; 2, aeration of the entire tympanic cavity; and 3, aeration of both the tympanic and mastoid cavities. RESULTS: No recurrence was observed in ears associated with grade 3 aeration that underwent MCP or in ears with grade 2 aeration that underwent BMO during second-stage surgery. For grades 0 and 1 aeration ears, the recurrence rates were 8.1% after 5 years and 12.5% after 10 years (p < 0.05), and the aeration of recurrent ears deteriorated to grade 0. CONCLUSION: Aeration during second-stage surgery predicts the final outcome.

Transplanting mouse induced pluripotent stem cells into mouse otocysts in vivo.

The otocyst is an attractive target for studying treatment strategies for genetic hearing loss and for understanding inner ear development. We have previously reported that trans-uterine supplemental gene therapy in vivo into the otocysts of mice, which had a loss of function mutation in a causative gene of deafness, was able to prevent putative hearing loss. We herein set out to clarify the feasibility of allogenic cell transplantation into the mouse otocysts in vivo. We transplanted naive mouse-derived induced pluripotent stem cells (miPSCs) into the otocysts of wild type mice or connexin (Cx) 30 deficient mice, at embryonic day 11.5 (E11.5). The transplanted m-iPSCs survived in the lumens of the inner ears at E13.5 and E15.5 in wild type mice. In the Cx30 deficient mouse, the transplanted cells survived similarly, with some of the transplanted cells migrating into the lining cells of the lumens of the inner ears at E13.5 and showing tumorigenic cell proliferation at E15.5. In addition, engrafted cells appear to be able to differentiate after the cell transplantation. Our results suggest that otocyst transplanted cells survived and differentiated. A Cx30 deficiency may facilitate cell migration. These findings may offer some hope for cell transplantation therapy for profound genetic hearing loss caused by a Cxs deficiency.

A Case of Periodontal Necrosis following Embolization of Maxillary Artery for Epistaxis.

Embolization of the maxillary artery (MA) is a common treatment modality for refractory epistaxis. Tissue necrosis after embolization of the MA is a rare complication. Here, we reported the first case of the development of necrosis of soft tissue and alveolar bone in the periodontium after embolization. A 48-year-old man with poor oral hygiene and a heavy smoking habit was referred to our clinic due to intractable epistaxis. After treatment with anterior-posterior nasal packing (AP nasal packing), the epistaxis relapsed. Therefore, he underwent embolization of the MA. Although he did not experience epistaxis after embolization, periodontal necrosis developed gradually. The wound healed with necrotomy, administration of antibiotics and prostaglandin, and hyperbaric oxygen therapy. We speculated that the periodontal necrosis was provoked by reduction of blood supply due to embolization and AP nasal packing based on this preexisting morbid state in the periodontium. Poor condition of the oral cavity and smoking may increase the risk of periodontal necrosis after embolization.

Laryngeal reinnervation featuring refined nerve-muscle pedicle implantation evaluated via electromyography and use of coronal images.

OBJECTIVE: To evaluate the long-term efficacy of laryngeal reinnervation via refined nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction to treat unilateral vocal fold paralysis (UVFP), employing laryngeal electromyography (LEMG), coronal imaging, and phonatory function assessment. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: We retrospectively reviewed 12 UVFP patients who underwent refined NMP implantation with arytenoid adduction. Videostroboscopy, phonatory functional analysis, LEMG, and coronal imaging were performed before and 2 years after surgery. In LEMG analysis, a 4-point scale was employed to grade motor unit (MU) recruitment: 4+ reflected no recruitment, 3+ greatly decreased recruitment, 2+ moderately decreased recruitment, and 1+ mildly decreased activity, associated with less than the full interference pattern. Coronal images were assessed in terms of differences in thickness and the vertical positions of the vocal folds. RESULTS: Phonatory function improved significantly after operation in all patients. In terms of LEMG findings, the preoperative MU recruitment scores were 1+ in no patients, 2+ in 4 patients, 3+ in 1 patient, and 4+ in 7 patients. Postoperative MU recruitment results were 1+ in 6 patients, 2+ in 5 patients, 3+ in 1 patient, and 4+ in no patients. Thinning of the affected fold during phonation was evident preoperatively in 9 of 10 patients. The affected and healthy folds were equal in volume in 4 of 9 patients postoperatively. CONCLUSION: The LEMG findings and coronal imaging suggest that NMP implantation may have enabled successful reinnervation of the laryngeal muscles of UVFP patients.

Neurogenesis of the spiral ganglion cells in the cochlea requires the transcriptional cofactor TIS21.

The molecular mechanisms controlling the proliferation and differentiation of spiral ganglion cells (SGCs) in the inner ear are still largely unknown. TIS21 is a transcriptional cofactor that shows antiproliferative, antiapoptotic, and prodifferentiative effects on neural progenitor cells. To investigate the function of TIS21 during SGC development, we analyzed SGC neurogenesis from embryonic day 13.5 (E13.5) to postnatal day 4 (P4) in Tis21-GFP knock-in mice, in which the protein-encoding exon of the Tis21 gene was replaced by EGFP. Through E13.5 to P4, we found fewer SGCs in homozygous Tis21-GFP knock-in mice than in wild-type mice. Our results suggest that TIS21 is required for development of SGCs. Deleting Tis21 may affect progenitor cells or neuroblasts at the beginning of cochlear-vestibular ganglion formation and would consequently lead to a decrease in the number of SGCs.

Laryngeal muscle activity in unilateral vocal fold paralysis patients using electromyography and coronal reconstructed images.

OBJECTIVE: To assess laryngeal muscle activity in unilateral vocal fold paralysis (UVFP) patients using laryngeal electromyography (LEMG) and coronal images. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: Twenty-one patients diagnosed with UVFP of at least 6 months in duration with paralytic dysphonia, underwent LEMG, phonatory function tests, and coronal imaging. A 4-point scale was used to grade motor unit (MU) recruitment: absent = 4+, greatly decreased = 3+, moderately decreased = 2+, and mildly decreased = 1+. Maximum phonation time (MPT) and mean flow rate (MFR) were employed. Coronal images were assessed for differences in thickness and vertical position of the vocal folds during phonation and inhalation. RESULTS: MU recruitment in thyroarytenoid/lateral cricoarytenoid (TA/LCA) muscle complex results were 1+ for 4 patients, 2+ for 5, 3+ for 6, and 4+ for 6. MPT was positively correlated with MU recruitment. Thinning of the affected fold was evident during phonation in 19 of the 21 subjects. The affected fold was at an equal level with the healthy fold in all 9 subjects with MU recruitment of 1+ and 2+. Eleven of 12 subjects with MU recruitments of 3+ and 4+ showed the affected fold at a higher level than the healthy fold. There was a significant difference between MU recruitment and the vertical position of the affected fold. CONCLUSIONS: Synkinetic reinnervation may occur in some cases with UVFP. MU recruitments of TA/LCA muscle complex in UVFP patients may be related to phonatory function and the vertical position of the affected fold.

Retrospective analysis of the clinical course for intubation vs. unspecified laryngeal granulomas.

Intubation laryngeal granulomas (ILGs) are a well-known complication of endotracheal intubation. Cases other than ILGs can be categorized as unspecified laryngeal granulomas (ULGs) since their etiologies are often difficult to confirm. We intended to clarify clinical features of both ILGs and ULGs and that anticoagulant medication could cause the formation and delayed healing of ILGs in terms of wound-healing delay. We compared the results of our treatment of ILGs (n = 16) and ULGs (n = 47) treated between 1998 and 2009 to characterize these patients. The clinical course, treatment (medical vs. surgical), indications for surgical resection, treatment outcome, and use of anticoagulants for preexisting disease were reviewed and compared between these two groups. The resolution rate was significantly better in ILGs (p < .05). Five ILGs and seven ULGs were surgically resected. The main reason for resection was airway obstruction and the need for histological assessment, respectively. The use of anticoagulants was significantly higher in ILGs than ULGs (8/16 vs. 4/47, p < .01). The resolution period was significantly longer in the ILGs patients with anticoagulant medication compared to that in the ILGs patients without anticoagulant medication (152 ± 101 days vs. 76 ± 44 days, p < .05). ILGs may have different clinical course from ULGs, especially in terms of the resolution period. Moreover, administration of anticoagulants may deter healing of small injury due to intubation. Patients taking anticoagulants should be managed carefully during the perioperative period to prevent the occurrence of ILGs.

Long-term voice handicap index after type II thyroplasty using titanium bridges for adductor spasmodic dysphonia.

OBJECTIVES: To determine the long-term functional outcomes of type II thyroplasty using titanium bridges for adductor spasmodic dysphonia (AdSD) by perceptual analysis using the Voice Handicap Index-10 (VHI-10) and by acoustic analysis. METHODS: Fifteen patients with AdSD underwent type II thyroplasty using titanium brides between August 2006 and February 2011. VHI-10 scores, a patient-based survey that quantifies a patient's perception of his or her vocal handicap, were determined before and at least 2 years after surgery. Concurrent with the VHI-10 evaluation, acoustic parameters were assessed, including jitter, shimmer, harmonic-to-noise ratio (HNR), standard deviation of F0 (SDF0), and degree of voice breaks (DVB). RESULTS: The average follow-up interval was 30.1 months. No patient had strangulation of the voice, and all were satisfied with the voice postoperatively. In the perceptual analysis, the mean VHI-10 score improved significantly, from 26.7 to 4.1 two years after surgery. All patients had significantly improved each score of three different aspects of VHI-10, representing improved functional, physical, and emotional well-being. All acoustic parameters improved significantly 2 years after surgery. CONCLUSIONS: The treatment of AdSD with type II thyroplasty significantly improved the voice-related quality of life and acoustic parameters 2 years after surgery. The results of the study suggest that type II thyroplasty using titanium bridges provides long-term relief of vocal symptoms in patients with AdSD.

Glottal configuration in unilaterally paralyzed larynx and vocal function.

CONCLUSIONS: Three different types of glottal configuration in unilaterally paralyzed larynx were proposed by utilizing three-dimensional computed tomographic (3DCT) images. This new classification might facilitate understanding of the behavior of the affected vocal fold in terms of vocal function. OBJECTIVES: To develop a classification of glottal configuration in unilateral vocal fold paralysis (UVFP) based on the thickness and location of the vocal folds utilizing 3DCT and to compare each type of configuration with vocal function. METHODS: Thirty-seven consecutive patients with UVFP underwent CT during phonation and inhalation. 3D endoscopic and coronal images on two occasions were produced. Maximum phonation time and mean airflow rate were also measured. RESULTS: Three types of glottal configuration were proposed. The thickness of the affected vocal fold during phonation was equal to or slightly thinner than the healthy fold in 10 patients (type A). The affected fold of the remaining 27 was thin during phonation; they were further classified into types B and C. In type B, the affected fold remained thin during phonation and inhalation (n = 12). Type C was allocated to those showing one or two paradoxical movements of the affected fold (n = 15). Those with type A showed significantly better vocal function.

Nimodipine accelerates reinnervation of denervated rat thyroarytenoid muscle following nerve-muscle pedicle implantation.

OBJECTIVES/HYPOTHESIS: To determine whether nimodipine, an L-type voltage-operated calcium channel antagonist that is an accelerator of axonal regeneration following peripheral nerve injury, can expedite reinnervation of denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle (NMP) flap implantation. STUDY DESIGN: A quantitative histologic and physiologic assessment of the TA muscle following NMP flap implantation, with or without nimodipine treatment. METHODS: Using 72 Wistar rats, we performed a transection on the left recurrent laryngeal nerve, followed by NMP flap implantation. Thirty-six animals received nimodipine treatment (NIMO [+] group), and the remaining 36 animals received no nimodipine treatment (NIMO [-] group). As a control, 18 animals were subjected only to transection of the left recurrent laryngeal nerve. We performed a histologic assessment for muscle area, axon, nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA muscle and electromyography at 2, 4, and 10 weeks after surgery. RESULTS: Muscle area, ratio of the number of NTs to that of AchRs (NT/AchR ratio), and evoked action potential in the TA muscle were significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05) at 4 weeks. At 10 weeks, the NT/AchR ratio was significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05). CONCLUSIONS: We found that nimodipine accelerated reinnervation of the denervated TA muscle following NMP flap implantation.