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.

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.

Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data.

Zinc intake is recommended for zinc deficiency. In clinical practice, polaprezinc has been used as a zinc replacement therapy for zinc deficiency. However, the efficacy of polaprezinc has not been established. To confirm the efficacy on zinc deficiency of polaprezinc and provide additional information on an appropriate regimen, we conducted a systematic review using individual patient data (IPD). We searched PubMed, the Japanese database Ichushi, and the database owned by the marketing authorization holder of polaprezinc. Randomized placebo-controlled trials that reported the serum zinc concentration were eligible. The mean difference of the change from baseline in serum zinc concentration was estimated using a fixed-effects model. The linear dose-response relationship and the subgroup effects were also assessed. Out of 54 unique randomized clinical trials (RCTs), four studies met the eligibility criteria, and we could access IPD for all of them. All three doses of polaprezinc (75 mg, 150 mg, and 300 mg) and the placebo group were examined. The dose-combined overall polaprezinc increased the change from baseline by a mean of 9.08 µg/dL (95% confidence interval: 5.46, 12.70; heterogeneity: I2 = 0.61%) compared to the placebo. A significant dose-response relationship was confirmed (p < 0.001). Baseline serum zinc concentration was considered an effect modifier in polaprezinc 300 mg. All doses of polaprezinc were tolerable, but a dose-response relationship with adverse events (AEs) was observed in gastrointestinal disorders. The dose of 300 mg may be useful among patients with baseline serum zinc concentration of less than 70 µg/dL, and 150 mg for 70 µg/dL or more.

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.

Earlier recovery of lingual dysfunction after middle ear surgery in pediatric versus adult patients.

OBJECTIVES: It is generally thought that the recovery of damaged chorda tympani nerve (CTN) function after middle ear surgery is different in pediatric patients from that in adult patients. The purpose of this study was to investigate the changes and the progress of taste and somatosensory functions of the tongue after middle ear surgery in pediatric patients compared with those of adult patients. STUDY DESIGN: Prospective study. METHODS: Fifty-nine pediatric patients and 106 adult patients underwent middle ear surgery. Taste and somatosensory functions of the anterior tongue, the so-called CTN functions, were assessed using electrogustometry (EGM), a 2-point discriminator, an electrostimulator, and a questionnaire before and 2 weeks and 6 months after surgery. RESULTS: Two weeks after surgery, there was no significant difference in the incidence of dysgeusia and abnormal EGM thresholds between the patient groups. The incidence of tongue numbness was significantly lower in pediatric patients than in adult patients regardless of CTN manipulation. Although the lingual somatosensory thresholds of adult patients were significantly increased, those of pediatric patients were not increased. Six months after surgery, the incidences of dysgeusia and an abnormal EGM threshold were lower in pediatric patients than in adult patients. Tongue numbness disappeared, and the thresholds of lingual somatosensory tests returned to normal in most pediatric patients. CONCLUSION: Not only taste function but also lingual somatosensory function was damaged after middle ear surgery even in pediatric patients. Pediatric patients complained of tongue numbness less frequently and showed earlier recovery than adult patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:1016-1022, 2020.

International Collaborative Assessment of the Validity of the EAONO-JOS Cholesteatoma Staging System.

OBJECTIVE: Assessment of validity of the Japanese Otological Society and the European Academy of Otology and Neurotology (EAONO-JOS) cholesteatoma staging system (EJS) through international collaboration to investigate: (a) feasibility of retrospectively staging previously acquired data, (b) strengths and weaknesses of the staging system. METHOD: Nine centers with prospective cholesteatoma databases were recruited. Cases were allocated to EJS Stage at each center using details from time of initial surgery. An independent rater also staged the cases and noted any discrepancies. At one center results from database staging were compared with staging based on contemporaneous operative records. Inter and intrarater reliabilities were calculated, and recidivism rates calculated according to Stage. RESULTS: Of 1482 cases of cholesteatoma, 320 (22%) were Stage 1, 977 (67%) Stage 2, 153 (11%) Stage 3 and 4 (0.3%) Stage 4. No database contained details of all parameters required for accurate staging. Staging discrepancies occurred in >10% cases but inter and intrarater reliability of staging were high (Kappa 0.8; 95% confidence interval between 0.7-0.9). At 5 years, 11% had residual and 8% had recurrent cholesteatoma: rates increased with Stage but generally not significantly (Kaplan-Meier Log Rank analysis). CONCLUSION: The EJS Staging system provides an internationally agreed standard for collecting data to classify cholesteatoma severity. Although data can be applied retrospectively with reasonable reliability, prospective data collection would prevent inaccuracies that arise from missing data fields. To enhance validity of the EJS system, we propose clearer definitions of some categories. Refinements to definitions of stage may improve prognostic utility of the EJS but should be made using evidence powered by large-scale collaboration.

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.

Nationwide survey of congenital cholesteatoma using staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society.

OBJECTIVE: This study was undertaken to determine the characteristics of congenital cholesteatoma (CC) in Japan, via a nationwide survey using staging and classification criteria for middle ear cholesteatoma, as proposed by the Japan Otological Society (JOS). METHODS: A nationwide survey regarding middle ear cholesteatoma treated in 2015 was performed. There were 1787 registrations from 74 facilities, among which, CC accounted for 12.9% (231 cases) of all middle ear cholesteatoma cases. The extent of the disease was classified according to the classification and staging of cholesteatoma proposed by JOS in 2015. RESULTS: The age of the patients ranged from 1 to 55 years (mean, 8.2 years; median, 6 years; 149 ears of males; 82 ears of females). Among these cases, 105 (45.5%) were classified as stage I, 121 (52.4%) as stage II, and 5 (2.1%) as stage III, with no cases in stage IV. In the sub classification of stage I, 35 (33%), 43 (41%) and 27 (26%) ears were classified as stages I-a, I-b and I-c, respectively. Stage I-b (cholesteatoma confined to the posterior half of the tympanic cavity) was more frequent than stage I-a (the anterior half of tympanic cavity). Pre-operative hearing level of air-conduction was 20.5dB for stage I-a, 34.5dB for stage I-b, 30.5dB for stage I-c, 38.6dB for stage II, and 59.0dB for stage III. The rate of missing stapes superstructure increased as the disease progressed. In the same way, the mastoid development lowered as the stage of the disease progressed. There were significant differences in the age at operation, pre-operative hearing level, status of stapes, and major ossiculoplasty, between stage l-a and l-b. CONCLUSIONS: The current condition of CC in Japan was been evaluated; in particular, it was observed that the cases limited to the posterior part of tympanic cavity were not rare. The JOS stage classification based on the progression of the disease seemed simple and efficient.

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.

Relationship Between p16 Expression and Prognosis in Patients with Oropharyngeal Cancer Undergoing Surgery.

BACKGROUND/AIM: Prognostic impact of p16 expression in patients with oropharyngeal squamous cell carcinoma (OSCC) undergoing surgery is not fully examined. The aim of this study was to clarify these issues. PATIENTS AND METHODS: Sixty-four OSCC subjects were analyzed. Immuno-histochemical staining of p16, a surrogate marker for human papillomavirus (HPV), was performed histopathologically. Data were retrospectively analyzed according to p16 positivity and factors linked to prognosis were also analyzed. RESULTS: No significant difference was observed in the prognosis between the p16-positive group (n=28) and the p16-negative group (n=36). In patients undergoing post-operative radiation, the p16-positive group (n=18) had a significantly better prognosis than the p16-negative group (n=6). On multivariate analysis, transoral surgery was a significant predictor of overall survival (p=0.0173). CONCLUSION: Prognostic impact of p16 can be emphasized in a subgroup of OSCC patients undergoing surgery. Surgery with sufficient surgical margin may be chosen as the first treatment for HPV-negative OSCC in some cases.

Bone-conducted Vestibular-evoked Myogenic Potentials Before and After Stapes Surgery.

OBJECTIVE: To identify whether stapes surgery causes otolith dysfunction using bone-conducted vestibular-evoked myogenic potentials (VEMPs). STUDY DESIGN: Prospective study. SETTING: Hyogo College of Medicine Hospital. PATIENTS: Twenty primary ears (19 otosclerosis, 1 congenital stapes fixation) in 17 patients (2 men, 15 women; mean age 51 yr, range 20-68 yr) who had normal cervical VEMP (cVEMP) and ocular VEMP (oVEMP) results with bone-conducted stimulation were included. INTERVENTION: Stapes surgery. MAIN OUTCOME MEASURE: Both VEMP tests with bone-conducted stimulation were performed before and after stapes surgery. The normalized p13-n23 amplitude of cVEMPs and the nI-pI amplitude of oVEMPs were measured within 3 months after stapes surgery. Then, the asymmetry ratio (AR) was calculated to examine the effect of surgery on otolith function. RESULTS: Seven patients complained of temporary dizziness postoperatively, but their symptoms disappeared within approximately a week. Deterioration of VEMPs of the operated ear was not seen in any ears. Significantly greater amplitude compared with the opposite ear was found for cVEMP in one ear and oVEMP in two ears after the surgery. Their VEMP results recovered to the normal range at 6 months postoperatively. CONCLUSIONS: These findings suggest that stapes surgery causes no or undetectably small otolith dysfunction from the perspective of VEMP evaluation.

Practicality analysis of the staging system proposed by the Japan Otological Society for acquired middle ear cholesteatoma: A multicenter study of 446 surgical cases in Japan.

OBJECTIVE: The Objective of this study was to assess the practicality of the cholesteatoma staging system proposed by the Japan Otological Society (JOS) for acquired middle ear cholesteatoma (the 2010 JOS staging system). METHODS: Between 2009 and 2010, 446 ears with retraction pocket cholesteatoma underwent primary surgery at 6 institutions in Japan. The extent of cholesteatoma was surgically confirmed, and classified into three stages. RESULTS: The cholesteatoma affected the pars flaccida in 325 ears (73%), the pars tensa in 100 ears (22%), and both regions combined in 21 ears (5%). The hearing outcome (postoperative air-bone gaps dB) worsened as follows (Stage I, II, III): 84%, 68%, 53% in pars flaccida; 71%, 62%, 30% in pars tensa, and 42% at Stage II, and 50% at Stage III in the combined group. The incidence of residual cholesteatoma increased as follows (Stage I, II, III): 2%, 12%, 23% in pars flaccida; 7%, 30%, 21% in the pars tensa group. The severity of disease was reflected in postoperative hearing and increasing incidence of recurrence rate. CONCLUSION: The 2010 JOS staging system is suitable for evaluating initial pathology. It is particularly practical for standardizing reporting of retraction pocket cholesteatoma and for adjusting for the severity of the condition during outcome evaluations. It may also provide information that is useful for counseling patients.

Change of somatosensory function of the tongue caused by chorda tympani nerve disorder after stapes surgery.

OBJECTIVES: Patients after middle ear surgery often complain of taste disturbance and a lingual numbness. The purpose of this study was to objectively assess changes in the somatosensation of the tongue and taste function in patients undergoing stapes surgery. STUDY DESIGN: Prospective study. METHODS: Symptoms of taste disturbance and tongue numbness after surgery were investigated before and after surgery in 41 patients (13 males, 28 females; mean age 41.8 years) who underwent stapes surgery. Twenty-eight patients (9 males, 19 females; mean age 43.1 years) underwent sensory and taste function tests before and after surgery. Sensory function of the tongue was measured at the operated side and the nonoperated side using the 2-point discrimination test and an electrostimulator test. Taste function was assessed with electrogustometry (EGM). RESULTS: The chorda tympani nerve (CTN) was gently touched or stretched in all patients. Postoperative thresholds on the operated side were significantly higher than preoperative thresholds in all tests in the patients who underwent all three kinds of tests. Tongue somatosensory symptoms improved significantly earlier than the taste disturbance postoperatively, and the sensory thresholds returned to the baseline along with recovery of symptoms. CONCLUSION: These findings suggest that dysfunction of the CTN occurred following surgery even when the CTN was preserved, and that the sensory nerve threshold of the tongue correlated with the symptom of lingual numbness. The CTN may play a role not only in taste function but also in the somatosensory function of the tongue. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:701-706, 2018.

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.

EAONO/JOS Joint Consensus Statements on the Definitions, Classification and Staging of Middle Ear Cholesteatoma.

The European Academy of Otology and Neurotology (EAONO) has previously published a consensus document on the definitions and classification of cholesteatoma. It was based on the Delphi consensus methodology involving the broad EAONO membership. At the same time, the Japanese Otological Society (JOS) had been working independently on the "Classification and Staging of Cholesteatoma." EAONO and JOS then decided to collaborate and produce a joint consensus document. The EAONO/JOS joint consensus on "Definitions, Classification and Staging of Middle Ear Cholesteatoma" was formally presented at the 10th International Conference on Cholesteatoma and Ear Surgery in Edinburgh, June 5-8, 2016. The international otology community who attended the consensus session was given the chance to debate and give their support or disapproval. The statements on the "Definitions of Cholesteatoma" received 89% approval. The "Classification of Cholesteatoma" received almost universal approval (98%). The "EAONO/JOS Staging System on Middle Ear Cholesteatoma" had a majority of approval (75%). Some international otologists wanted to see more prognostic factors being incorporated in the staging system. In response to this, the EAONO/JOS steering group plans to set up an "International Otology Outcome Working Group" to work on a minimum common otology data set that the international otology community can use to evaluate their surgical outcome. This will generate a large database and help identify relevant prognostic factors that can be incorporated into the staging system in future revisions.

An unexpected skin ulcer and soft tissue necrosis after the nonconcurrent combination of proton beam therapy and pazopanib: A case of myxofibrosarcoma.

We herein report the case of a patient presenting with myxofibrosarcoma (MFS) who underwent treatment with surgery, proton beam therapy (PBT), and pazopanib. A 64-year-old male was diagnosed with MFS, which ranged from the posterior neck to the shoulder. Surgery was performed as an initial treatment; however, the primary tumor recurred 83 months after the initial treatment. We, therefore, administered PBT. Although most of the recurrent tumor disappeared after PBT, multiple lung metastases were identified 3 months after the completion of PBT. We initiated antiangiogenic treatment with pazopanib. Although long-term survival was achieved with the treatments, the patient suffered from a skin ulcer and soft tissue necrosis and eventually died of general prostration caused by infection, and complicated by pneumonia. Although PBT and pazopanib were effective for treating the local recurrence and lung metastases of MFS, respectively, clinicians must be cognizant of the fact that the combination of high-dose irradiation and angiogenesis inhibitors, even in nonconcurrent cases, can result in a severe skin ulcer and soft tissue necrosis.

Staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society.

In order to provide a basis for meaningful exchange of information among those treating cholesteatoma, the Committee on Nomenclature of the Japan Otological Society (JOS) was appointed in 2004 to create a cholesteatoma staging system as simple as possible to use in clinical practice in Japan. Following the announcement of preliminary criteria for the staging of pars flaccida (attic) cholesteatoma in 2008, we proposed the 2010 JOS staging system for two major types of retraction pocket cholesteatoma, pars flaccida and pars tensa cholesteatoma. Since then, the JOS staging system has been widely used in clinical studies of cholesteatoma in Japan, allowing standardization in reporting of surgical outcomes based on the respective stages of cholesteatoma. We have recently expanded the range of cholesteatoma by adding cholesteatoma secondary to a tensa perforation and congenital cholesteatoma as the 2015 JOS staging system for middle ear cholesteatoma. Although further revisions may be required for universal acceptance of these criteria, we hope our staging system will open the way for international consensus on staging and classification of middle ear cholesteatoma in the near future.

Usefulness of the Saccharin Test for Assessment of Eustachian Tube Function in Patients With Chronic Otitis Media With Perforation.

OBJECTIVE: The eustachian tube (ET) has two important functions, ventilation and clearance of the middle ear. We evaluated the ET ventilator function by the sonotubometry and the inflation-deflation test that are widely used today, and the ET clearance function by the saccharin test. Results of both tests were compared with surgical outcomes, and assessed which test was more closely related to the surgical outcomes. STUDY DESIGN: Prospective case series. SETTING: A single university hospital. PATIENTS AND INTERVENTION: One hundred four ears of 95 patients with chronic otitis media with perforation underwent type I tympanoplasty. MAIN OUTCOMES AND MEASURES: Based on sonotubometry and the inflation-deflation test, the patients were divided into normal, stenosis, and patulous types. Based on the saccharin test, they were divided into a normal function group and a partial/gross dysfunction group. Surgical outcomes about the hearing results and the condition of the eardrum were assessed 1 year postoperatively. Preoperative evaluation of ET function was compared with the surgical outcome. RESULTS: Sonotubometry and inflation-deflation tests showed there was no significant difference among the groups about the hearing improvement and the surgical success rate. The saccharin test showed that the rate of the hearing improvement was significantly lower in the gross dysfunction group and that the success rate of Type I tympanoplasty was significantly higher in the normal group than in the dysfunction group. CONCLUSION: There is a relationship between the saccharin test results and surgical outcomes.

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.