IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18.

NK cells, which are composed of phenotypically and functionally heterogeneous subpopulations, play critical roles in immunity against cancer. The mechanism of generation of distinct subsets such as the effector and regulatory subtypes is unclear. Here, we show that this process comprises several steps, including generation of proliferating, highly cytotoxic cells activated by IL-15/IL-18 and differentiation into distinct cell populations induced with IL-12. Freshly prepared murine splenic NK cells expressed IL-15Rs and IL-18Rs and rapidly began to proliferate following stimulation with IL-15/IL-18. The proliferating NK cells highly expressed various activation markers such as B220, CD49b (DX5), lysosome-associated membrane glycoprotein 1 (LAMP-1), DNAX accessory molecule 1, perforin, and granzyme B and showed reduced expression of natural killer cell p46-related protein (NKp46) and IL-18Rα. These cells exerted strong cytotoxicity against YAC-1 cells, but did not secrete cytokines. IL-12 rapidly activated STAT4 in these cells, induced IFN-γ production, and then upregulated p21 and p27, leading to withdrawal from the cell cycle. In parallel, IL-12-stimulated cells gradually reduced cytotoxicity, decreased expression of activation markers, and instead increased expression of Sca-1, CD25, CD49a, and NKp46. Some IL-15/IL-18-induced cells strongly expressed PD-1, whereas NK cells induced with IL-15/IL-18 and IL-12 expressed high levels of T cell immunoglobulin mucin-3, LAG-3, and natural killer group 2 A. Furthermore, these cells spontaneously secreted IL-10 and TGF-ß following prolonged incubation. Thus, IL-12 regulates expansion of NK cells activated with IL-15/IL-18, influences the population size of highly cytotoxic cells, and induces differentiation to unique cells sharing some phenotypes of ILCs.

Volume-rendered computed tomography images of the surgical field for endolymphatic sac surgery.

PURPOSE: Identification of the endolymphatic sac has failed occasionally. Postoperative complications have also rarely been reported. Given a safer and more reliable surgery, preoperative anatomical assessments are valuable, however, the vestibular aqueduct has seldom been seen with multi-planar reconstruction (MPR) computed tomography (CT) images yet. Our study aimed to determine the significance and utility of volume-rendered (VR) CT images of the surgical field for identifying the vestibular aqueduct, compared with MPR CT images. SUBJECTS AND METHODS: 14 patients with Meniere's disease who underwent endolymphatic sac surgery between 2008 and 2011. Location and size of the vestibular aqueduct were assessed using VR and MPR CT images, independently. RESULTS: Accuracy of identifying the location differed significantly between VR and MPR CT images (rate of total correct evaluations: 100% by VR CT images vs 75% by MPR CT images, p = 0.02). Size was correctly identified in cases with a small endolymphatic sac using VR CT images (rate of total correct evaluations for size of the vestibular aqueduct: 100% by VR CT vs 57% by MPR CT, p = 0.046). VR CT images also demonstrated clearly the relationship between the endolymphatic sac and high jugular bulb. In two cases, the endolymphatic sac was identified by VR images, not by MPR images. CONCLUSION: Accurate information about the location and size of vestibular aqueduct can allow sac surgeons to identify a tiny endolymphatic sac more easily and certainly, and also aids surgical trainees to learn sac surgery safely.

Usefulness of our proposed olfactory scoring system during endoscopic sinus surgery in patients with chronic rhinosinusitis.

INTRODUCTION: The primary aim of the current study was to examine the usefulness of our proposed olfactory scoring system in chronic rhinosinusitis (CRS) patients with olfactory disorders (n = 213) receiving endoscopic sinus surgery (ESS). MATERIALS AND METHODS: Analyzed patients were divided into two groups: an eosinophilic CRS (ECRS) group (n = 153); and a non-ECRS group (n = 60). The T&T recognition threshold test was used to evaluate olfaction at baseline and at 3 and 12 months after ESS. Patients with mean recognition threshold < 2.0 at 3 or 12 months or with a decrease of ≥ 1.0 as compared with baseline were defined as showing clinical improvement. We scored mucosal conditions as normal (0 points), edema (1 point), and polyp (2 points) at the canopy of olfactory cleft (OC), middle and superior turbinates, superior nasal meatus, and sphenoethmoidal recess during ESS. The total score of OCs (SOCs) was calculated (range 0-20 points). We compared SOCs between ECRS and non-ECRS groups. Factors related to olfactory improvement were also investigated using uni- and multivariate analyses. RESULTS: SOCs in the ECRS and non-ECRS groups showed significant correlations with mean recognition thresholds at baseline and at 3 and 12 months. In the multivariate analysis for predicting improvement of mean recognition threshold, lower SOCs were significantly associated with olfactory improvement factors at 3 and 12 months postoperatively in the ECRS group. CONCLUSION: SOCs appears promising for estimating olfactory prognosis after ESS in CRS patients.

Nasal Symptom Questionnaire: Our Proposed Scoring System and Prognostic Factors in Chronic Rhinosinusitis.

OBJECTIVES: We aimed to verify the usefulness of our proposed nasal symptom questionnaire (NSQ) scoring system and to determine predictors linked to the improvement in nasal symptoms in chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). PATIENTS AND METHODS: Ninety-one CRS patients undergoing ESS and 144 volunteers with results of NSQ available were enrolled. The NSQ consists of 10 items. Receiver-operating-characteristic (ROC) curve, area under the ROC curve (AUC), internal consistency, and test-retest reproducibility of the NSQ were analyzed. The relationship of the NSQ score with the visual analogue scale (VAS) was examined. After classifying into two groups, i.e., (i) "improvement group" and (ii) "no-improvement group," factors linked to the improvement in NSQ after ESS were investigated. RESULTS: ROC-AUC (0.9318), the Cronbach α coefficient (0.8696), and the test-retest coefficient (0.8131) showed high reliability. NSQ score significantly correlated with VAS in both pre- (p < 0.0001, rs = 0.6007) and postoperative stages (p < 0.0001, rs = 0.5975). The postoperative NSQ scores significantly decreased compared with baseline levels (p < 0.0001). In multivariate analysis, the computed tomography (CT) score by the Lund-Mackay scoring system revealed to be significant (p = 0.0481). CONCLUSION: Our proposed NSQ scoring system was well verified. The CT score can be helpful for predicting the improvement in nasal symptoms after ESS in CRS patients.

Clinical Study of 1,515 Patients Presenting with Epistaxis Over the Last 6 Years.

AIM: This study reviews our clinical experience of patients with epistaxis and discusses proper management. PATIENTS AND METHODS: We retrospectively investigated 1,515 patients with epistaxis treated in our department between 2005 and 2010. RESULTS: Men over 50 years old predominated. More than half of the patients (n = 828) first visited after consultation hours, and 40% (n = 606) were brought by ambulance. The most common underlying diseases were circulatory diseases (69%, n = 1,047). Antithrombotics were being administered to 23% (n = 345). Kiesselbach's plexus was the most commonly observed bleeding site (51%, n = 769). In 20% (n = 297), no bleeding point was confirmed because hemostasis had been achieved on arrival. Anterior packing was the most common primary treatment, followed by electrocauterization. Hospitalization was required in 2% (n = 30). Re-bleeding occurred within 14 days after primary treatment in 14% (n = 206). Surgical treatment was performed for 5% (n = 11). CONCLUSIONS: Patients showing repeated pulsatile arterial bleeding require hospitalization for surgical therapy, although outpatient therapy is sufficient in most cases. A risk of re-bleeding should be considered if patients show unclarified bleeding points and circulatory diseases.

RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain.

Recent studies have indicated an important role of ATP receptors in spinal microglia, such as P2Y12 or P2Y13, in the development of chronic pain. However, intracellular signaling cascade of these receptors have not been clearly elucidated. We found that intrathecal injection of 2-(methylthio)adenosine 5'-diphosphate (2Me-SADP) induced mechanical hypersensitivity and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the spinal cord. Intrathecal administration of P2Y12/P2Y13 antagonists and Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor H1152 suppressed not only p38 MAPK phosphorylation, but also mechanical hypersensitivity induced by 2Me-SADP. In the rat peripheral nerve injury model, intrathecal administration of antagonists for the P2Y12/P2Y13 receptor suppressed activation of p38 MAPK in the spinal cord. In addition, subarachnoidal injection of H1152 also attenuated nerve injury-induced spinal p38 MAPK phosphorylation and neuropathic pain behavior, suggesting an essential role of ROCK in nerve injury-induced p38 MAPK activation. We also found that the antagonists of the P2Y12/P2Y13 receptor and H1152 had inhibitory effects on the morphological changes of microglia such as retraction of processes in both 2Me-SADP and nerve injured rats. In contrast these treatments had no effect on the number of Iba1-positive cells in the nerve injury model. Collectively, our results have demonstrated roles of ROCK in the spinal microglia that is involved in p38 MAPK activation and the morphological changes. Inhibition of ROCK signaling may offer a novel target for the development of a neuropathic pain treatment.

Clinical Features of Patients Treated with Endoscopic Sinus Surgery for Posttraumatic Paranasal Sinus Mucocele.

AIM: The purpose of this study was to analyze the clinical features of patients with posttraumatic paranasal sinus mucocele (PSM). SUBJECTS AND METHODS: Between 2009 and 2013, we performed endoscopic sinus surgery (ESS) on 68 patients with PSM at the Department of Otolaryngology - Head and Neck Surgery at Hyogo College of Medicine. Five male patients (age range, 45-76 years) with posttraumatic PSM were analyzed retrospectively. Diagnosis was based on the history of injury and radiological findings. RESULTS: Posttraumatic PSM was found in 7% (5/68) of patients. The mean interval from injury to diagnosis was 28.4 years. All patients had frontal sinus mucocele. Four patients had symptoms of headache, diplopia, visual field defect, and forehead swelling, and 1 patient was asymptomatic. ESS was performed under general anesthesia in all cases, and the symptoms improved postoperatively. Reoperation was required in 1 patient (20%) because headache developed with obstruction of the frontal drainage route 7 months after ESS. CONCLUSIONS: Posttraumatic PSM was the least frequent form of PSM and was located predominantly in the frontal sinus, causing symptoms long after the forehead injury. The important lessons to be learned for treating posttraumatic PSM are to obtain a detailed history and to enlarge the route to the cyst to avoid its recurrence.

[A Clinical Study of 109 Cases of Glottic Squamous Cell Carcinoma].

A total of 109 patients with glottic squamous cell carcinoma were retrospectively evaluated at Hyogo College of Medicine Hospital between 2003 and 2010; 106 patients were male and 3 patients were female, with a median age of 69 years (range, 51-90 years). According to the 7th edition of the Union for International Cancer Control TNM classification, the clinical TN stages were T1aN0 in 47 cases, T1aN1 in 1 case, T1aN2a in 1 case, T1bN0 in 19 cases, T3N0 in 11 cases, T4aN in 5 cases, and T4aN2b in 1 case. No distant metastasis was observed in any cases at initial treatment. Treatments were radiotherapy alone in 75 cases, concurrent chemo-radiotherapy in 20 cases, supra-cricoid laryngectomy in 1 case, and total laryngectomy in 13 cases. Salvage surgery was performed for 14 patients who had undergone radiotherapy or concurrent chemo-radiotherapy. Salvage surgeries included frontolateral partial laryngectomy in 8 cases, supra-cricoid laryngectomy in 2 cases, and total laryngectomy in 4 cases. The 5-year overall survival rate was 77.6%, and the 5-year disease-specific survival rate was 92.5%. The 5-year laryngeal preservation rate was 82.9%. With regard to T-stages, the laryngeal preservation rates were 100% for T1a, 89.5% for T1b, 91.5% for T2, 18.2% for T3, and 16.7% for T4a.

[A Case of Tongue Carcinoma Resection and Reconstruction with Microsurgical Free Flap during Pregnancy].

Malignant tumors during pregnancy are rarely seen by otolaryngologists, and they cause various problems which require special treatment with careful consideration of both the mother and fetus. Cases of tongue carcinoma resection and reconstruction with a microsurgical free flap during pregnancy have not previously been reported in Japan. We report herein on a case, in which the mother and her child made satisfactory progress after surgery. A-33-year-old female at 25 weeks and 4 days of pregnancy was referred to our department for the treatment of a tumor on the right edge of her tongue. Examinations including biopsy revealed SCC (T2N0M0). We performed an operation to remove the tongue carcinoma with the pull-through method and reconstruct the tongue with an ALT flap at just 28 weeks of pregnancy. The postoperative recovery was favorable, and she gave natural birth to a girl safely at 38 weeks and 6 days of pregnancy. She is currently free of disease and her child is growing normally, at 2 years and 10 months after surgery.

[Time course of changes in gustatory function test results and subjective symptoms, and predictive factors for response in patients with taste disorder receiving 24-week zinc replacement treatment].

In a taste disorder, an agreement between patients' complaints and gustatory function test results is not necessarily found both at the initial hospital visit and during the course of treatment; therefore, it is difficult to assess treatment responses and review treatment strategies based on the assessed treatment responses. The present study investigated the time course of changes in disc gustometry results and subjective symptom scores measured at 4-week intervals in 44 patients with a taste disorder who were considered eligible for zinc replacement treatment and who received polaprezinc at a dose of 150 mg/day (equivalent to a 34 mg/day dose of zinc) for up to 24 weeks. The study also examined the potential differences in treatment outcomes according to the predictive factors for response such as patient background and assessed disc gustometry results during the course of treatment. Results indicated that disc gustometry results and subjective symptom scores showed different time courses of changes. The response rate as measured by disc gustometry was 47.7% at week 12 of treatment, and showed a subsequent slow increase to 56.8% at week 24. On the other hand, subjective symptom scores showed a time-proportional improvement up to week 24. Among the patients included in the present study, a clear difference was found according to the presence or absence of an improving trend as determined by disc gustometry at week 12 of treatment, although there were no differences in ultimate treatment responses, including categories of taste disorder, according to patient background. Patients showing a trend toward improvement had significantly better treatment responses in terms of both ultimate response rates and subjective symptom scores, whereas patients showing no trend toward improvement were less likely to respond to the subsequent 12-week continued treatment.

Decreased expression of VE-cadherin and claudin-5 and increased phosphorylation of VE-cadherin in vascular endothelium in nasal polyps.

VE-cadherin and claudin-5 are major components of adherens and tight junctions of vascular endothelial cells and a decrease in their expression and an increase in the tyrosine-phosphorylation of VE-cadherin are associated with an increase in endothelial paracellular permeability. To clarify the mechanism underlying the development of edema in nasal polyps, we studied these molecules in polyp microvessels. Normal inferior turbinate mucosal tissues and nasal polyps from patients treated with or without glucocorticoid were stained for VE-cadherin or claudin-5 and CD31 by a double-immunofluorescence method and the immunofluorescence intensities were graded 1-3 with increasing intensity. To correct for differences in fluorescence intensity attributable to a different endothelial area being exposed in a section or to the thickness of a section, the relative immunofluorescence intensity was estimated by dividing the grade of VE-cadherin or claudin-5 by that of CD31 in each microvessel. Tyrosine-phosphorylation of VE-cadherin was examined by Western blot analysis. The relative intensities of VE-cadherin and claudin-5 in the CD31-positive microvessels significantly decreased in the following order; inferior turbinate mucosa, treated polyps and untreated polyps. The ratio of tyrosine-phosphorylated VE-cadherin to VE-cadherin was significantly higher in untreated polyps than in the inferior turbinate mucosa and treated polyps, between which no significant difference in the ratio was seen. Thus, in nasal polyps, the barrier function of endothelial adherens and tight junctions is weakened, although glucocorticoid treatment improves this weakened barrier function.

Therapeutic evaluation of outpatient submucosal inferior turbinate surgery for patients with severe allergic rhinitis.

BACKGROUND: Surgical treatment for inferior turbinate (IT) is selected to treat severe allergic rhinitis (AR) that is unresponsive to conservative treatment. This study aimed to determine the clinical effects of outpatient submucosal IT surgery (OSITS) on patients with severe AR. METHODS: Between January 2008 and August 2012, 95 patients with severe AR who underwent OSITS at the Department of Otolaryngology, Hyogo College of Medicine, were retrospectively analyzed. There were 53 men and 42 women. Their mean age was 27 years (11-75 years). OSITS was bilaterally performed using a bipolar radiofrequency electrocautery under local anesthesia. Symptoms, QOL, and physical findings were evaluated using scores from both pre- and postoperative periods (average: 12.4 months), according to Practical Guideline for the Management of AR in Japan 2009. RESULTS: In perennial AR, all mean scores of nasal symptoms, QOL, and physical findings significantly improved after OSITS (p < 0.05, n = 83). Nasal obstruction, sleep problems, and IT congestion were the most strongly affected. Eye symptoms were not influenced by OSITS. OSITS also showed significant effects on nasal obstruction and IT congestion in seasonal AR (p < 0.05, n = 12), but not sneezing, nasal discharge, and QOL. In terms of the efficacy, OSITS was beneficial in 90% of perennial AR cases and 75% of seasonal AR cases. Epistaxis (1%), vestibulitis (1%), and IT atrophy (4%) were observed after OSITS. CONCLUSIONS: These data indicate that OSITS using radiofrequency electrocautery could be a beneficial therapeutic option in patients with severe AR.

[The effect of zinc agent in 219 patients with zinc deficiency-inductive/ idiopathic taste disorder: a placebo controlled randomized study].

Diagnosis and treatment of taste disorders are challenging because the disorder can only be determined by the awareness of the patient. Hence, these disorders still require comprehensive evidence. We conducted a randomized, placebo-controlled double-blind study to investigate the effect of polaprezinc, a zinc-containing agent, in 219 patients with either zinc deficiency-inductive or an idiopathic taste, disorder. As a result, the zinc-treated arm experienced a statistically significant improvement against the placebo-treated arm in the perceptible threshold scores of the filter-paper disk method 8 weeks after the administration of the investigational drug. Moreover, the effect lasted for 4 weeks after discontinuation of the drug. However, the effective ratios based on the initial criteria were 55.6% in the treatment group and 43.2% in the placebo, where no statistical significance was recorded. Sex and degree of depression could be two of the potential factors to explain this discrepancy. Furthermore, the effect was not significant among male patients and patients with a high depression score based on the Self-rating Depression Scale (SDS) test. These results indicate that determining the symptom among such patients remains undisclosed. Whereas, in approximately 77%, or 168 patients with "normal" SDS scores and with completely impaired taste qualities, the ratio of effective cases reached 60.9% in the zinc-treated group, the ratio of the placebo-treated group reached 39.5%, resulting in a statistical significance. This may be partly because of a problem in the adaption of male subjects to the gustatory analyses, especially to the identification of saltiness and sourness. Care must also be taken regarding the depressive state of patients when diagnosing and treating taste disorders. Taste disorders caused by depression may not be cured by zinc supplementation due in part to the fact that the symptom is based on a mental issue, and due in part to the conservative responding bias generated by the depression itself, which may inhibit accurate and precise diagnosis of the disorder. In conclusion, administration of a zinc agent is effective for patients with taste disorders, provided selection of appropriate patients is performed, and that proper examination and evaluation are conducted. The present study also indicated that examining depressiveness based on the SDS scores and investigating disturbance of each taste quality using the filter-paper disk method are recommended for the diagnosis and determination of the treatment effect of a taste disorder.

[Clinical analysis of 1059 patients with taste disorders].

Taste disorders are caused by several factors, and there have been few reports concerning the clinical course of taste disorders. In this study, patients with taste disorders were classified into 10 groups according to causes, and they were retrospectively studied in terms of therapeutic effects. In total, 1059 patients (412 men and 647 women, mean age: 60.0 years) who complained of taste disorders were reviewed in our clinic. The patients were asked detailed questions about their history of symptoms, and their emotional status was assessed using a self-rating depression scale. In all subjects, taste functions were measured by electrogustometry (EGM) and filter paper disks (FPD). The grades of their symptoms were assessed with a visual analogue scale (VAS). In addition, the levels of serum iron, copper, and zinc were examined. The patients were treated with zinc sulfate, polaprezinc, iron preparation, herbal medicine, and minor tranquilizers according to the factors causing the taste disorders. The most frequent cause was idiopathic taste disorder (192 cases, 18.2%), the second was psychogenic (186 cases, 17.6%), and the third was drug-induced (179 cases, 16.9%). The recovery rate of the symptoms was 64/92 (70.2%) in post-common cold, 31/35 (88.6%) in iron deficiency, and 85/116 (73.3%) in zinc deficiency. In these groups, the rates of recoveries were better than in the other groups. The recovery period in drug-induced taste disorders was approximately twice as long as the recovery period in the other groups. In the patients who were able to start treatment within 6 months from the onset of taste disorder, the recovery rate was significantly higher and the therapeutic period was significantly shorter than in those who had the disorders for more than 6 months (p<0.05, respectively).

Microglia Negatively Regulate the Proliferation and Neuronal Differentiation of Neural Stem/Progenitor Cells Isolated from Poststroke Mouse Brains.

We previously demonstrated that neural stem/progenitor cells (NSPCs) were induced within and around the ischemic areas in a mouse model of ischemic stroke. These injury/ischemia-induced NSPCs (iNSPCs) differentiated to electrophysiologically functional neurons in vitro, indicating the presence of a self-repair system following injury. However, during the healing process after stroke, ischemic areas were gradually occupied by inflammatory cells, mainly microglial cells/macrophages (MGs/MΦs), and neurogenesis rarely occurred within and around the ischemic areas. Therefore, to achieve neural regeneration by utilizing endogenous iNSPCs, regulation of MGs/MΦs after an ischemic stroke might be necessary. To test this hypothesis, we used iNSPCs isolated from the ischemic areas after a stroke in our mouse model to investigate the role of MGs/MΦs in iNSPC regulation. In coculture experiments, we show that the presence of MGs/MΦs significantly reduces not only the proliferation but also the differentiation of iNSPCs toward neuronal cells, thereby preventing neurogenesis. These effects, however, are mitigated by MG/MΦ depletion using clodronate encapsulated in liposomes. Additionally, gene ontology analysis reveals that proliferation and neuronal differentiation are negatively regulated in iNSPCs cocultured with MGs/MΦs. These results indicate that MGs/MΦs negatively impact neurogenesis via iNSPCs, suggesting that the regulation of MGs/MΦs is essential to achieve iNSPC-based neural regeneration following an ischemic stroke.

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

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

Change in chorda tympani nerve function after two-stage tympanoplasty for cholesteatoma.

Objectives: Chorda tympani nerve (CTN) function may be damaged more by two-stage than by one-stage surgery for middle ear cholesteatoma. However, few studies have reported the relationship between two-stage cholesteatoma surgery and CTN function. This study aimed to investigate CTN function after two-stage surgery for cholesteatoma. Methods: In this prospective study, 35 patients underwent two-stage canal wall up tympanoplasty (CWUT). Perioperative CTN function was assessed using questionnaires and electrogustometry (EGM). Participants were categorized into minor, major, and section groups, based on the degree of CTN manipulation during surgery. Results: In the first-stage surgery, posterior tympanotomy with an intact canal wall reduced the degree of CTN manipulation. The incidence of taste disorder after the first-stage surgery was 71.4%. Postoperative taste disorder and the EGM threshold improved early in the minor manipulation group. In the second-stage surgery, no new CTN damage occurred, even if this surgery involved removal of residual cholesteatoma. The incidence of taste disorder after second-stage surgery was less than that after first-stage surgery, independent of CTN preservation. However, the recovery rate of the EGM threshold after second-stage surgery was significantly lower in the section group than in those with CTN preservation. Conclusion: CTN function, including symptoms and EGM threshold, can be preserved during two-stage cholesteatoma surgery if care is taken to preserve the CTN in both the first- and second-stage surgeries. A two-stage CWUT, ensuring an intact bony annulus, may be effective to facilitate CTN preservation. Level of Evidence: 2b.

Nationwide survey of middle ear cholesteatoma surgery cases in Japan: Results from the Japan Otological society registry using the JOS staging and classification system.

OBJECTIVE: This study was aimed to determine the characteristics of middle ear cholesteatoma and to investigate short-term outcomes regarding the rates of residual and recurrent cholesteatoma and the postoperative hearing results in Japan, via a nationwide survey using staging and classification criteria for middle ear cholesteatoma, as proposed by the Japan Otological Society (JOS). METHODS: The first-round survey was conducted in 2016. The target was patients with middle ear cholesteatoma who were surgically treated in Japan between January and December 2015. Medical information on the patients was anonymized. The questionnaire entries were age, sex, cholesteatoma classification and stage, preoperative hearing level, mastoid development, status of the stapes, and surgical method. There were a total of 1,787 registered patients from 74 facilities from all over Japan. The second survey was conducted in January 2018 and received 1,456 responses from 49 facilities in Japan. Of the 1,456 cases, 1,060 were conducted in the postoperative hearing survey and 1,084 in the residual recurrence survey. RESULTS: The most common cholesteatoma type was pars flaccida cholesteatoma (63.3%), followed by pars tensa cholesteatoma (13.0%), congenital cholesteatoma (12.9%), and cholesteatoma secondary to chronic tensa perforation (5.6%). Cholesteatoma of uncertain origin accounted for 5.0% (90 cases). Stage II was predominant in pars flaccida and pars tensa cholesteatoma, which frequently involves the mastoid, whereas about half of cases of cholesteatoma secondary to chronic tensa perforation and congenital cholesteatoma were classified as stage I. One hundred fifty-two of 1,084 cases (14.0%) had recurrent cholesteatoma, residual cholesteatoma, or both following first surgeries. The postoperative rates of hearing success rate was 63.3%. CONCLUSION: We were able to clarify not only the current epidemiological status of middle ear cholesteatoma but also the current trends of cholesteatoma surgery in Japan. The development of a staging system by the JOS Committee serving an epidemiological database for international or time-dependent comparison. It is possible to use this staging system with reasonable reliability.

Prognostic factors of long-term outcomes after ossiculoplasty using multivariate analysis.

The objective of the retrospective study is to investigate the prognostic factors of long-term outcomes following ossiculoplasty. The setting was a tertiary referral and academic center. The series consisted of 269 patients, who underwent ossiculoplasty by the same surgeon between 1989 and 2003 and were followed for more than 5 years. Postoperative hearing outcomes were considered successful, if the postoperative air-bone gap was <20 dB. Prognostic factors were analyzed using multivariate analysis with logistic regression. Successful hearing was achieved in 143 patients (53.2%). The presence of the stapes and primary surgery was significantly favorable predictive factors. Better knowledge of these predictive factors may contribute to improve the surgeon's judgement and the information given to the patients preoperatively.

[Voice restoration and long-term progress in voice rehabilitation using the Provox2 voice prosthesis after total laryngectomy].

From January 2000 to December 2008, we conducted voice rehabilitation using the Provox2 voice prosthesis total-laryngectomy subjects. Of these, 36 attained restoration of 90.0%. Mean maximum phonation time (MPT) was 14.5s, ranging from MPT was not influenced by age, radiotherapy use, primary tumor site, or reconstructive surgery use. Voice prosthesis replacement averaged 25 weeks (5.8 months), ranging from 9 to 74 weeks. Complications occurred in 16 caces (40.0%), mainly granulation tissue formation and prosthesis-site infection, also aspiration pneumonia, prosthesis-site salivary leakage, inability to replace the prosthesis, tracheomalacia, bodies in the trachea. Management rather than medical problems included cost, frequent hospital visits, and lack of motivation to use a prosthesis. The Provox2 voice prosthesis speech provides a higher rate of speech restoration, longer phonatory better intelligibility. Management problems, however, require that we work to understand subjects' living environments and family situations better for evaluating Provox2 voice prosthesis indication more effectively.