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Background: The purpose of this study was to compare the hearing outcomes after surgery with reconstruction of the external auditory canal in combination with tympanoplasty, radiotherapy (RT) alone, and surgery followed by postoperative RT for T1 to 2N0M0 external auditory canal cancer., Methods: We performed a retrospective, single-institution review of consecutive patients with early-stage external auditory canal cancer treated with surgery and/or RT between April 1997 and August 2013. Audiological data included the pretreatment hearing thresholds and those obtained at 12 months after the completion of therapy., Results: When we compared the functional gains for air-conduction pure-tone average thresholds and mean air-bone gaps, those in the surgery group (n = 10) were significantly higher than those in the RT (n = 13) and surgery + RT (n = 5) groups., Conclusion: Adequate techniques for reconstruction of the external auditory canal in combination with tympanoplasty after complete surgical resection is useful for hearing preservation in addition to good survival outcomes. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1110-E1116, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disease that manifests as asthma, recurrent sinusitis and peripheral eosinophilia. In this study, we investigated the clinical features of the ear and nasal manifestations of EGPA in comparison with those of granulomatosis with polyangiitis (GPA)., Materials and Methods: Twenty-one patients diagnosed with EGPA were studied. The frequency of otologic manifestations, the degree of hearing loss and the frequency of nasal symptoms were assessed. The onset of ear symptoms, sinusitis and asthma in patients with EGPA were also examined., Results: Eleven patients (52.4%) with EGPA demonstrated otologic symptoms. The EGPA patients commonly presented mild-to-moderate mixed or sensorineural hearing loss. The pattern of hearing loss was mainly flat, and all but 1 patient achieved complete remission from their hearing impairments. Eighteen patients (85.7%) with EGPA demonstrated nasal symptoms. Patients with EGPA showed a significantly higher incidence of nasal polyps than did those with GPA. The median Lund and Mackey scoring system score was 13.7 for patients with EGPA, and ethmoid sinus shadows were more severe than those of the maxillary sinus. Most ear symptoms associated with EGPA were observed after definitive diagnosis, although sinusitis and asthma tended to manifest themselves before diagnosis. There were significant differences between the onset of ear symptoms and those of asthma and sinusitis., Conclusion: As over 80% of patients with EGPA had nasal symptoms and over half had ear symptoms, otolaryngologists should be aware of this disease. Recognition of the characteristic ear and nasal symptoms are thought to be particularly important to obtain an early diagnosis of EGPA., (© 2016 S. Karger AG, Basel.)

Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses., Objectives: To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers., Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters., Measurements and Main Results: Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later., Conclusions: This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

The symptoms of allergic rhinitis show marked day-night changes that are likely to be under the control of the circadian clock, but the mechanism of this control is poorly understood. Because most peripheral tissues have endogenous circadian clocks, we examined the circadian rhythm of the clock gene product PERIOD2 (PER2) in the nasal mucosa of male mice using a luciferase reporter and demonstrated for the first time the phase-dependent effects of dexamethasone (DEX) on nasal PER2 rhythm in vivo and ex vivo. The phase shifts in PER2 rhythm caused by DEX were observed around the peak phase of serum glucocorticoids, suggesting that the circadian rhythm of endogenous glucocorticoids regulates the peripheral clock of the mouse nasal mucosa. From the viewpoint of circadian physiology, the best time to administer intranasal steroid treatment for allergic rhinitis would be when no phase shift is caused by DEX: in the early evening in diurnal humans.

Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.

Objective: To clarify the characteristics and prognosis of hearing loss associated with Vogt-Koyanagi-Harada (VKH) disease., Methods: We retrospectively examined 85 patients diagnosed with VKH disease between January 1996 and December 2012. The control group included age- and gender-matched individuals without definitive ear disease. The patients with VKH disease were treated with high-dose systemic corticosteroids, which were tapered off gradually over a period of 6 months or more by the treating ophthalmologists according to the severity of the ocular inflammation. The features of hearing loss were analyzed based on pure tone audiometric data obtained at the initial presentation according to diagnostic criteria based on the ISO 7029 standard. The efficacy of corticosteroid therapy was evaluated by audiometry at the initial presentation and during therapy for 3-6 months., Results: In patients with VKH disease, the rate of hearing loss detected by audiometry was significantly higher than that of either subjective hearing loss (p < 0.001) or tinnitus (p < 0.001). Bilateral symmetrical hearing loss was the most common type of auditory disturbance associated with VKH disease. The degree of hearing loss was generally low, with no patients showing profound hearing loss. Hearing thresholds were significantly elevated at high frequencies compared with those at low-to-mid frequencies (p < 0.001). Hearing thresholds at all frequencies after high-dose corticosteroid therapy were significantly better than those at initial presentation (p < 0.001), and the rate of patients who returned to within normal-range pure tone thresholds at all frequencies was 74.8%., Conclusions: As auditory manifestations cannot be detected through history taking alone, audiometry should be performed to evaluate hearing loss associated with VKH disease. Early administration of high-dose systemic corticosteroids is effective for treating the auditory manifestations, which generally show a relatively good short-term prognosis.

Background: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP)., Methodologies: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumors arising from the anterior part of the maxillary sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer`s test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery., Results: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumors. No patients suffered tumor recurrence. There was no difference in lacrimal duct function between the diseased side and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100., Conclusions: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.

Objectives: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors., Design: Retrospective analysis., Participants: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases)., Main Outcome Measures: Perioperative complications and risk factor associated with their incidence., Results: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported., Conclusions: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.

Background: Birch pollen is the major pollen allergen in Hokkaido, Northern Japan. We reported a Betula masting model based on the resource budget model hypothesis. In addition to weather conditions, cumulative hours of sunlight and mean temperature from May to July of the previous year, this model used the amount of annual pollen dispersed in previous and penultimate years as a parameter based on data from 1990 to 2000., Objective: We compared the predicted and observed amount of pollen dispersed for 3 years from 2001 to 2003 and evaluated the usefulness of each parameter in this model., Methods: Birch pollen was measured using the Durham sampler at the Hokkaido University Graduate School of Medicine Research Institute in Sapporo., Results: The difference between predicted and observed amounts of pollen dispersal was about 200-500 grains cm(-2). The annual pollen dispersed in the previous year was found to be the most useful parameter., Conclusion: This model is useful in predicting whether the amount of birch pollen will be less than average, about average, more than average, or much more than average.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine whose expression has been found to be critical to the generation of antigen-specific immune responses. Recent studies suggested that MIF played a role in the initiation and maintenance of allergic diseases. To elucidate MIF's role in the pathogenesis of allergic rhinitis (AR), we sensitized MIF-deficient gene knockout (KO) mice and wild-type (WT) mice intraperitoneally with ovalbumin (OVA) and compared their clinical symptoms and allergic responses after intranasal challenge. Antigen-induced nasal symptoms were significantly reduced in MIF KO mice compared to WT mice. Histological examination of nasal mucosa showed that the number of infiltrating eosinophils in MIF KO mice was significantly lower than that in WT mice (P < 0.05). The concentration of TNF-alpha in nasal mucosa was also significantly lower in MIF KO mice than in WT mice (P < 0.05). We have demonstrated that the absence of MIF affects several aspects of experimental AR. One mechanism by which these effects might be mediated is by down regulating TNF-alpha. The block of allergic inflammation in MIF KO mice suggests that MIF may play a role in the allergic response.