Preliminary investigation of endoscopic surgery for tympanic membrane perforation: Regenerative treatment compared with conventional surgery.

PURPOSE: To compare surgical outcomes of regenerative treatment (RT) including basic fibroblast growth factor (bFGF) (Group-R) with the conventional method (Group-C) for patients with tympanic membrane perforation (TMP), both of whom underwent transcanal endoscopic ear surgery. METHODS: The study population of Group-R included 61 ears of 59 patients treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the TMP. Fibrin glue was then dripped over the sponge. Group-C consisted of 13 patients who underwent conventional surgery before adopting the RT-TMP. Patients' characteristics and outcomes including TMP closure rates, and change in hearing level were evaluated three or more weeks after the surgery. RESULTS: The baseline characteristics including size of TMP were not significantly different between the two groups. Although Group-R had significantly shorter operating time than Group-C, the complete TMP closure rates were 69 % (9/13) and 85 % (52/61), respectively. Air-conduction hearing thresholds showed significant improvements, and analysis of variance showed that Group-R achieved significant interactions other than at 8 kHz, implying better improvement in cases with TMP closure. The air-bone gaps also improved at all frequencies in both groups. Specifically, at 4 kHz, there was a trend showing better improvement in Group-R. CONCLUSION: RT-TMP had a high TMP closure rate and good hearing improvement, with no significant differences compared with those of conventional surgery. This new therapy is simple and safe, and requires less operating time, and it could help improve the quality of life of patients with TMP.

Temporal virtual reality-guided, dual-task, trunk balance training in a sitting position improves persistent postural-perceptual dizziness: proof of concept.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a newly defined disorder characterized by functional dizziness. Due to its recent discovery, definitive treatment for PPPD has not been established; therefore, this study aimed to assess the effectiveness of virtual reality (VR)-guided, dual-task, trunk balance training for the management of PPPD using the mediVR KAGURA system. METHODS: We analyzed data of patients who presented with PPPD from January 1, 2021, to February 28, 2021. The VR group included patients who underwent mediVR KAGURA-guided training for 100 tasks (10 min). Patients with PPPD who received standard treatment and rehabilitation were assigned to the control group. Equilibrium tests were performed at baseline and immediately after mediVR KAGURA-guided training to examine its effectiveness in improving static and dynamic balance. Additionally, clinical questionnaires related to balance disorders were administered at baseline and 1 week after mediVR KAGURA-guided training to examine its effects on balance-related symptoms. The primary outcome was improvements in static and dynamic balance and Niigata PPPD Questionnaire (NPQ) scores. RESULTS: VR-guided training using mediVR KAGURA improved objective outcomes, including static and dynamic postural stability, after a single 10-min training session. Additionally, mediVR KAGURA-guided training improved scores on the Hospital Anxiety and Depression Scale and NPQ 1 week after the 10-min training session. CONCLUSION: VR-guided training using mediVR KAGURA represents a viable method for managing balancing ability, anxiety, and symptoms in patients with PPPD. Such training provides a safe and cost-effective solution for PPPD management. Further studies are required to evaluate the clinical efficacy of this strategy. TRIAL REGISTRATION: Institutional Ethics Committee of Kitano Hospital, approval number: 1911003. Registered 18 December 2019, https://kitano.bvits.com/rinri/publish_document.aspx?ID=426 .

Histopathological evaluation and long-term results of soft tissue preservation technique in cholesteatoma surgery.

The goal of cholesteatoma surgery is total removal of the cholesteatoma matrix and prevention of recurrence. Preservation of soft tissue in the attic is reported to improve post-operative middle ear aeration, and thus prevents recurrence. However, the histology and nature of the preserved tissue have rarely been reported. The aim of this study is to clarify the histology of the preserved soft tissue in cholesteatoma surgery, and to show its relationship to the clinical course. Surgical specimens were obtained from ten patients with pars flaccida-type cholesteatoma. In these patients, cholesteatoma occupied the attic and the mastoid cavity. The cholesteatoma was removed so as not to expose the bone in the attic. After the removal of the lesions, soft tissue was harvested from the floor of the attic, using cupped forceps. The specimens were fixed with 10 % formalin, and stained with hematoxylin-eosin. The patients were followed-up for 8 years after the surgery. No patients showed post-operative inner ear disturbance or facial nerve palsy. In one patient, residual lesion was found during the revision surgery. The area of residual lesion was not explored during the first operation. Two other patients showed recurrent cholesteatoma in the pars tensa; one of these patients had accompanying otorrhea. The other seven patients showed no residual or recurrent cholesteatoma 8 years after the surgery. The histological examination showed that the harvested tissue was mainly composed of collagen fiber and fibroblasts. Ciliary epithelial cells were found in one patient. In three patients, cysts of mucosal remnants (glandular cysts), were embedded in the connective tissue. Two of these three patients experienced recurrent cholesteatoma, while the other seven patients were without recurrence at follow-up. Preservation of soft tissue behind the cholesteatoma matrix is a safe technique if the surgical field is fully visible. In most cases, the preserved tissue was fibrous connective tissue and lacked the characteristics of mucosa. The glandular cysts in the preserved soft tissue seem to be related to the recurrence of cholesteatoma.

Biocompatibility and efficacy of collagen/gelatin sponge scaffold with sustained release of basic fibroblast growth factor on vocal fold fibroblasts in 3-dimensional culture.

OBJECTIVE: Treatment of vocal fold scarring remains challenging. We have previously reported the therapeutic effects of local injection of basic fibroblast growth factor (bFGF) in animal models and humans. A novel collagen/gelatin sponge (CGS) is capable of sustained release of bFGF, which compensates for its quick absorption in vivo, avoiding multiple injections. This study aimed to evaluate the biocompatibility and efficacy of the CGS in rat vocal fold fibroblasts prior to human trials. METHODS: Fibroblasts extracted from Sprague-Dawley rat vocal folds were seeded onto a CGS and then cultivated with bFGF at concentrations of 0, 10, and 100 ng/mL. Vocal fold fibroblast morphology, adhesion, proliferation, and gene expression were measured under these 3-dimensional conditions. RESULTS: Cells adhered to the CGS from day 1. Although no significant differences in cell morphology were detected, cell proliferation was accelerated by bFGF administration. Expression of endogenous bFGF and hepatocyte growth factor was significantly up-regulated at 10 ng/mL bFGF. The expression of procollagen I and procollagen III was significantly suppressed, whereas HAS-1 and HAS-2 were up-regulated at 10 and 100 ng/mL bFGF. CONCLUSION: The collagen/gelatin sponge is biocompatible with vocal fold fibroblasts and may be useful as a bFGF drug delivery system for the treatment of scarred vocal folds.

Outcomes of regenerative treatment for over 200 patients with tympanic membrane perforation.

OBJECTIVE: To evaluate outcomes of a regenerative treatment (RT) for over 200 patients with tympanic membrane perforation (TMP). The RT-TMP method involves a gelatin sponge, basic fibroblast growth factor (bFGF) and fibrin glue. METHODS: The study population included 216 patients and 234 ears (male: female =100:116; age 1-93 years). All enrolled patients were treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the perforation. Fibrin glue was then dripped over the sponge. Patient outcomes including TMP closure rates, change in hearing level, and complications were obtained from retrospective medical chart reviews. The TMP was examined three or more weeks after surgery. The treatment was repeated up to 4 times until complete TMP closure was achieved. RESULTS: After mechanical disruption, the perforation size was Grade I, ≤1/3 of entire TM area in 22 ears (9.4 %), Grade II, 1/3-2/3 of entire TM in 77 ears (32.9 %) and Grade III, ≥2/3 of entire TM area in 135 ears (57.7 %). The overall TMP closure rates were 97.0 % (227/234). Complete TMP closure was achieved in 68.8 % (161/234), 22.6 % (53/234), 4.7 % (11/234) and 0.9 % (2/234) of ears after 1, 2, 3 and 4 treatments, respectively. In 7 of 234 ears (3.0 %), the TMPs were not closed completely after 4 treatments. There was no correlation between TMP size after mechanical disruption and number of treatments required to achieve complete closure (Fisher's exact test p = 0.70). The mean air-conduction hearing threshold at low frequency improved from 57.3 ± 16.7 dB before treatment to 37.3 ± 16.0 dB (p < 0.0001) after closure of TMPs. For middle and high frequencies, the improvement was 49.0 ± 19.3 dB to 36.9 ± 17.9 dB (p < 0.0001) and 57.7 ± 22.9 dB to 49.2 ± 23.3 dB (p < 0.0001), respectively. The mean air-bone gaps also improved significantly, and were within 10 dB at 250 Hz, 500 Hz and 1 kHz, and 11 dB at 2 kHz. One or more complications occurred in 32 patients (32/216; 14.8 %). The most common complication was formation of an epithelial pearl (16 ears; 6.8 %), followed by severe TM retraction (9 ears; 3.8 %) and otitis media with effusion (6 ears; 2.6 %). There were no serious complications that caused deterioration of the patient's general condition. CONCLUSION: Our results showed that RT-TMP had high success rates for TMP closure and good hearing improvement and produced no severe complications that could affect general health status. This novel therapy is simple, safe and minimally invasive, and could help improve the quality of life in patients with TMP.

Tympanic Membrane Regeneration Therapy for Pediatric Tympanic Membrane Perforation.

OBJECTIVE: To evaluate tympanic membrane regeneration therapy (TMRT) for pediatric tympanic membrane perforations (TMPs). STUDY DESIGN: Intervention study. SETTING: Research institute hospital. PATIENTS: In this study, 20 patients with chronic TMP (M/F: 13/7, 13/8 ears, age 0-15 years) treated with TMRT were evaluated. As comparison, 20 pediatric patients with chronic TMP who underwent myringoplasty/tympanoplasty were included. INTERVENTIONS: For the TM repair procedure, the edge of the TMP was disrupted mechanically, and gelatin sponge immersed in basic fibroblast growth factor was placed inside and outside the tympanic cavity and covered with fibrin glue. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. MAIN OUTCOME MEASURES: Closure of the TMP and hearing improvement were evaluated at 16 weeks after the final regenerative procedure. Adverse events were monitored. RESULTS: The mean follow-up period was 427.1 days. The TM regenerated in all cases, but pinhole reperforation occurred in two cases, and the final closure rate was 90.5% (19 of 21). Hearing improved to 24.9 ± 7.6 dB on average before surgery and to 13.8 ± 5.4 dB after surgery. The AB gap improved from 12.9 ± 8.0 to 5.2 ± 3.5 dB.The myringoplasty/tympanoplasty group had significantly lower AB gap improvement compared with the TMRT group. There were no adverse events. CONCLUSIONS: TMRT can be expected to regenerate near-normal TMs with a high closure ratio, resulting in better-hearing improvement compared with the myringoplasty/tympanoplasty group, and is an effective treatment for children with long life expectancy.

Long-term exposure to high-concentration dexamethasone in the inner ear via intratympanic administration.

The first-line treatment for inner ear disorders is usually oral/systemic steroids. Intratympanic steroid therapy is an alternative option; however, it requires multiple office visits owing to the short residence time of steroids in the inner ear (systemic: 24 h, intratympanic: 2-3 h). Therefore, intratympanic injections of higher steroid concentrations could result in longer drug exposure, providing better treatment outcomes. This study aimed to develop a prototype for high-concentration steroids and examine their safety and feasibility in vivo. Using wild-type Institute for Cancer Research mice, high-concentration steroids (50 mg/mL dexamethasone), typical steroid concentrations (3.3 mg/mL dexamethasone), and sterile saline were administrated into the middle ear cavity via tympanic membrane injection. Auditory brainstem response analysis, vestibular function tests, and morphological analyses were performed to examine the safety and utility of High-conc Dex. One month post-injection, the frequency-averaged auditory brainstem response thresholds of high-dose dexamethasone-treated mice were not significantly different from those of low-dose dexamethasone- and saline-treated mice at all tested frequencies. Furthermore, the total points on vestibular function tests were similar between the three groups. Morphologically, no damage to the inner ear/middle ear mucosa was observed in all groups. Two months post-injection, dexamethasone could still be detected in the high-dose dexamethasone group. Altogether, our data successfully demonstrates the feasibility and safety of high-dose dexamethasone for in vivo use in the middle ear and ensure that the drug localizes to the inner ear. Further research is warranted to develop this new treatment strategy and further characterize its effects in vivo.

Diagnosing Middle Ear Malformation by Pure-Tone Audiometry Using a Three-Dimensional Finite Element Model: A Case-Control Study.

BACKGROUND: Hearing loss caused by middle ear malformations is treated by tympanoplasty to reconstruct the acoustic conduction system. The mobility of the ossicles plays a crucial role in postoperative success. However, identifying the location of ossicular malformation based solely on preoperative audiograms is challenging due to the complex relationship between fixation location, deformity levels, and ossicular mobility. METHODS: Middle ear finite element models for simulating ossicular malformations were created, and the results were compared with the actual preoperative audiograms. RESULTS: This approach objectively diagnosed ossicular fixation and disarticulation, bypassing traditional criteria reliant on physician examination or imaging. CONCLUSION: This study suggests that future research should focus on developing a diagnostic framework utilizing large-scale data.

Expression of reactive oxygen species during wound healing of vocal folds in a rat model.

OBJECTIVES: Previous studies have indicated that although normal wound healing requires low levels of reactive oxygen species (ROS), excessive amounts of ROS impair wound healing. In injured vocal folds, this excess may result in dysphonia due to scarring that is difficult to treat. However, the expression of ROS during vocal fold wound healing has yet to be investigated. In this study, we assessed the expression and localization of ROS in injured vocal folds by immunohistochemical analysis. METHODS: Vocal folds of Sprague-Dawley rats were unilaterally injured by stripping the mucosa under transoral endoscopy. The larynges were harvested at specific time points after injury and were immunohistochemically examined for 4-hydroxy-2-nonenal (4-HNE), an ROS marker, and for the presence of inflammatory cells. RESULTS: We found that 4-HNE-immunopositive cells were significantly increased in the lamina propria of the injured vocal folds as compared to the normal vocal folds on postinjury days 1 and 3. More than half of the 4-HNE-immunopositive cells were also immunopositive for a macrophage- and granulocyte-specific antibody. CONCLUSIONS: This study suggests that a large amount of ROS is produced during early-phase wound healing, until postinjury day 3, and that this period may be crucial for regulating ROS levels. The results also suggest that inflammatory cells may contribute to ROS generation.

Effects of Kampo medicine hangebyakujutsutemmato on persistent postural-perceptual dizziness: A retrospective pilot study.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a functional disorder, typically preceded by acute vestibular disorders. It is characterized by a shift in processing spatial orientation information, to favor visual over vestibular and somatosensory inputs, and a failure of higher cortical mechanisms. To date, no therapies for PPPD have been approved. Kampo medicine hangebyakujutsutemmato (HBT) has been reported to alleviate disturbances of equilibrium. We hypothesized that HBT would be a beneficial treatment for PPPD. AIM: To examine the efficacy of HBT for the treatment of PPPD. METHODS: Patients with PPPD were enrolled and divided into two groups: The HBT group (n = 24) and the non-HBT group (n = 14). The participants completed questionnaire surveys [Niigata PPPD questionnaire (NPQ), dizziness handicap inventory, hospital anxiety and depression scale (HADS), orthostatic dysregulation questionnaire, pittsburg sleep quality index (PSQI), and motion sickness scores] before and after HBT treatment. Additionally, to identify HBT responders, multivariate regression analysis was performed using the results of the questionnaire surveys and equilibrium tests; including stabilometry, and caloric, vestibular evoked myogenic response, and head-up tilt tests. RESULTS: Thirty-eight outpatients were included in this study, of which 14 patients (3 men, 11 women; mean age, 63.5 ± 15.9 years) received treatment without HBT, and 24 (1 man, 23 women; mean age, 58.2 ± 18.7 years) received combination treatment with HBT. Following HBT treatment, NPQ scores decreased significantly (baseline 40.1 ± 10.0 vs 2 mo 24.6 ± 17.7, P < 0.001). No statistically significant changes were observed in the NPQ scores in the non-HBT group (baseline 38.6 ± 12.2 vs 2 mo 39.4 ± 14.4, P = 0.92). Multivariable regression analysis revealed that the results of stabilometry (P = 0.02) and the caloric (P = 0.03), and head-up tilt tests (P < 0.001), HADS (P = 0.003), and PSQI (P = 0.01) were associated with HBT responsiveness in PPPD patients. CONCLUSION: HBT may be an effective adjunct therapy for PPPD. Patients with autonomic dysfunction, unstable balance, semicircular canal paresis, anxiety, and poor sleep quality may be high responders to HBT.

Diagnosis of Spontaneous Cerebrospinal Fluid Rhinorrhea Using Thin-Slice Computed Tomographic Images With Multiplanar Reconstruction and Three-Dimensional Virtual View Endoscopy.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea represents an important clinical entity, which is associated with elevated intracranial pressure and is rarely treated successfully without surgical intervention. Here we report a case of spontaneous CSF rhinorrhea. The patient was a 54-year-old male, who presented with bacterial meningitis and was referred to the Department of Otorhinolaryngology for a detailed examination of the nose and sinuses. Reconstructed thin-slice computed tomography (CT) revealed multiple fistulae on the clivus. The defect was successfully repaired by transnasal endoscopic surgery, with the assistance of virtual endoscopic images, which were created by the surgical planning and navigation system from thin-slice CT images. This incremental improvement in the imaging technique helped with the diagnosis and surgical treatment of CSF rhinorrhea.

Predictive factors of acute sensorineural hearing loss in adult Japanese patients for clinical application by primary care doctors: a cross-sectional study.

BACKGROUND: Several methods are used for hearing loss screening; however, their benefits are uncertain. In this study, we aimed to determine the predictive factors of acute sensorineural hearing loss for clinical application by primary care doctors. METHODS: This retrospective, cross-sectional study included 365 patients with acute sensorineural hearing loss without prior therapy. The patients' clinical data, demographic information, and medical histories were obtained, and they were asked about comorbidities. In addition, we assessed lifestyle factors such as stress level, alcohol consumption, marital status, and socioeconomic level. Logistic regression analysis was performed to investigate the diagnostic predictive ability of the selected factors associated with acute sensorineural hearing loss. The hearing levels of all patients were evaluated using pure tone audiometry. RESULTS: We identified significant predictive factors for acute sensorineural hearing loss. The absence of hyperacusis was a predictive factor for sudden sensorineural hearing loss. Younger age, female sex, and marital status were predictive factors for acute low-tone hearing loss. High body mass index, high socioeconomic level, low alcohol consumption, high stress level, hyperacusis, and vertigo/dizziness were predictive factors for Ménière's disease. High body mass index and ear fullness were predictive factors for perilymph fistula. Low stress level was a predictive factor for acoustic tumours. CONCLUSIONS: Our findings can be used to distinguish between the types of acute sensorineural hearing loss. Symptoms, physical status, and lifestyle factors identified during this study are useful markers for predicting acute sensorineural hearing loss occurrence.

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.

Laryngeal regeneration using tissue engineering techniques in a canine model.

OBJECTIVES: We previously reported that polypropylene mesh covered with collagen sponge is a useful material for the regeneration of the trachea and the cricoid cartilage. The aim of this study was to regenerate larynges after partial hemilaryngectomy with this new biomaterial. METHODS: A left partial hemilaryngectomy was performed on 12 adult beagles. The defect size was about 1.8 x 1.0 cm. Both sides of polypropylene mesh were coated with either 1% or 3% collagen sponge. This scaffold was wrapped in fascia lata harvested from the left thigh and then fixed in place over the defect. Endoscopic examinations were performed periodically. Six months after treatment, 3-dimensional computed tomographic scanning was performed. Vibratory examinations were also performed with excised larynges. RESULTS: In the 1% collagen group, exposure or dislocation of the mesh was found in 3 of 6 cases, but in the 3% group, no exposure of the mesh was seen. The morphological findings in the vocal fold were better in the 3% group than in the 1% group, but a difference in the vertical levels of the vocal folds was found in both groups. CONCLUSIONS: This study suggests that 3% collagen-coated polypropylene mesh wrapped with autologous fascia is a useful material for laryngeal regeneration.

Implantation of an atelocollagen sponge with autologous bone marrow-derived mesenchymal stromal cells for treatment of vocal fold scarring in a canine model.

OBJECTIVES: Vocal fold scarring remains a therapeutic challenge. A new regenerative approach is needed to restore disorganized extracellular matrix. Tissue regeneration requires appropriate cells and a scaffold. Bone marrow-derived mesenchymal stromal cells (BMSCs) are multipotent and secrete many kinds of growth factors to regenerate tissues. Atelocollagen sponges have many large pores that permit cell entry. The present study was performed to evaluate whether implantation of an atelocollagen sponge plus BMSCs is effective for the treatment of vocal fold scarring. METHODS: Twelve beagles underwent implantation of an atelocollagen sponge or of an atelocollagen sponge with autologous BMSCs (1.0 x 10(6) cells) in the subepithelial pockets of scarred vocal folds. Six months after the operation, vibratory examinations and histologic examinations were performed. RESULTS: Mucosal vibrations improved significantly for the atelocollagen sponge-implanted vocal folds. Histologic analyses revealed favorable restoration of the extracellular matrix in the lamina propria. Increased distribution of hyaluronic acid and decreased dense collagen deposition were also noted. These improvements were enhanced by implantation of BMSCs. CONCLUSIONS: Implantation of atelocollagen sponges with autologous BMSCs into scarred vocal folds significantly increased hyaluronic acid distribution and decreased dense collagen deposition in the lamina propria, leading to better mucosal vibration.

Hearing Outcomes and Complications of Cochlear Implantation in Elderly Patients over 75 Years of Age.

OBJECTIVE: Populations are aging in many countries, and the proportion of elderly people with severe to profound hearing loss is increasing in parallel with the increasing average life span. The objective of this study was to investigate the outcomes of cochlear implant (CI) surgery in elderly patients compared to those in younger patients. METHODS: The outcomes of CI surgery were retrospectively investigated for 81 adults (32 men and 49 women) who underwent CI surgery at our hospital. They were divided according to age at the time of implantation into the younger group (<75 years of age; n = 49) or elderly group (≥75 years of age; n = 32). RESULTS: The mean sentence recognition score on the CI-2004 Japanese open-set test battery (±standard deviation) was 82.9% ± 24.1 in the younger group and 81.9% ± 23.2 in the elderly group, with no significant difference between the groups (Mann-Whitney U test). The incidence of major complications that required surgical treatment was not significantly different between the groups (4.1% vs. 6.2%, respectively). Thus, there were no severe complications that could affect general health status in either group. Three patients in each group died for reasons unrelated to CI surgery during follow-up. The proportion of patients who were alive and continued to use the CI five years after surgery was 92.8% and 91.5%, respectively. CONCLUSION: Our results show good speech recognition and a low incidence of major complications in elderly patients. This comprehensive report on the outcomes of CI surgery in elderly patients will be helpful to the elderly with severe to profound hearing loss when deciding whether to undergo CI surgery.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Glottal reconstruction with a tissue engineering technique using polypropylene mesh: a canine experiment.

OBJECTIVES: The larynx must be resected in some cases of cancer or stenosis, and various techniques are generally employed to fill the resulting defect. No ideal way, however, has been established to restore vocal function after this form of insult. The aim of this preliminary feasibility study in a canine model was to investigate the effectiveness of a polypropylene-based tissue engineering approach to repair a partial glottal defect. METHODS: Eight dogs were used in this study. A laryngeal defect involving resection of the left vocal fold was created through a thyroid cartilage window. A scaffold made of polypropylene and collagen was preclotted and wrapped with autologous fascia lata, inserted through the window, and sutured to the laryngeal defect in 5 dogs. The defect was reconstructed with an adjacent sternohyoid muscle flap in 3 control dogs. The surgical site was evaluated 3 months after operation by fiberscopic examination, computed tomographic imaging, histologic evaluation, and study of excised larynges. RESULTS: On fiberscopic examination, the experimental group implants were completely covered with regenerated mucosa in all cases, and a favorable vocal fold contour was found in 4 of the 5 cases. One case was characterized by a concave vocal fold shape and red granulation. In the control group, the muscle flap was replaced by scarred mucosa with a concave vocal fold contour in 2 cases, and there was soft white granulation at the anterior resected edge in the third case. The histologic data revealed the regeneration of lined epithelium, subepithelial tissue, and muscle structure in both groups. The excised larynx phonatory data revealed reduced vibratory amplitude in the experimental group compared with the control group; however, excised phonation was not achieved in 2 of the 3 cases in the control group. CONCLUSIONS: This polypropylene-based tissue engineering technique appears to be a viable tool for glottal reconstruction; however, additional refinement is required to maximize long-term phonatory function.

Implantation of an atelocollagen sheet for the treatment of vocal fold scarring and sulcus vocalis.

OBJECTIVES: The management of vocal fold scarring and sulcus vocalis is challenging. These disorders are thought to be fibroplastic anomalies in the cover portion of the vocal fold that cause deterioration of the vibratory properties of the vocal fold mucosa. Histologic studies have revealed disorganization of extracellular matrix that needs to be addressed in the treatment of scarred vocal folds. Replacement of scar tissues with an appropriate implant may lead to regeneration of the vocal fold mucosa and its tissue properties. This retrospective case study examined the feasibility of using an atelocollagen sheet as a regenerative implant. METHODS: Six patients with a post-cordectomy scar or sulcus vocalis underwent implantation of an atelocollagen sheet into the lamina propria of the vocal folds. The procedure consisted of elevation of a microflap, dissection and removal of scar tissue, implantation of the material, and wound closure. Vocal function was evaluated before and after surgery by stroboscopic examination and by aerodynamic and acoustic analyses. RESULTS: The postoperative changes of aerodynamic and acoustic parameters varied among patients; however, gradual improvement was seen in most cases over a year. Stroboscopic findings also revealed gradual improvement of vibratory properties in most cases. CONCLUSIONS: Implantation of an atelocollagen sheet may have restorative effects on vocal fold scarring and sulcus vocalis in terms of tissue properties and function of the mucosa.

Effect of exogenous hepatocyte growth factor on vocal fold fibroblasts.

OBJECTIVES: We have previously demonstrated the therapeutic potential of hepatocyte growth factor (HGF) in the treatment of vocal fold scarring, although how exogenous HGF affects gene expression of endogenous HGF or extracellular matrix components in the vocal fold fibroblasts remains unclear. In this in vitro study, we aimed to clarify this aspect in order to better understand the effects of HGF on the vocal folds. METHODS: Fibroblasts were obtained from the lamina propria of the vocal folds of 5 Sprague-Dawley rats and were cultured with HGF at concentrations of 100, 10, 1, and 0 ng/mL. The cells were collected on days 1, 3, and 7, and the expression of endogenous HGF, its receptor c-Met, transforming growth factor-beta1 (TGF-beta1), procollagen types I and III, and hyaluronic acid synthase (HAS)-1 and HAS-2 messenger RNAs (mRNAs) was examined by real-time reverse transcription-polymerase chain reaction. RESULTS: The expression of endogenous HGF and HAS-1 mRNAs increased significantly when exogenous HGF was administered at a concentration of 1 ng/mL. On day 1, the expression of TGF-beta1 and HAS-2 mRNAs increased significantly in response to 1 ng/mL HGF. CONCLUSIONS: Exogenous HGF triggered the up-regulation of endogenous HGF, TGF-beta1, HAS-1, and HAS-2 mRNAs in vocal fold fibroblasts.