オスラー病患者のほとんどが症状として持つ鼻出血であるが，耳鼻咽喉科医ですら適切な対処が取られていない。厄介な鼻出血の原因にオスラー病があると知識には持っていても，治療に懸命になっている最中に本疾患を思いつく耳鼻咽喉科医は少ないのが実情である。そこで，耳鼻咽喉科医がオスラー病だと判定するためのコツと，鼻出血への対処法の要諦を述べる。オスラー病が見過ごされてしまう理由は，診断基準の理解不足，病歴聴取の不足，局所所見のとり方の不徹底に尽きる。診断にはキュラソー診断基準が用いられる。鼻出血患者においては，鼻出血以外の3項目中2項目を満たせば確定例となる。鼻出血を反復している患者さんの鼻の中を見て，血管拡張があると分かった時点でもう臨床診断の疑い例に該当する。あとは問診で，鼻出血の家族歴があったり，肺の血管塞栓や脳梗塞の既往歴があれば確定になるので，そう診断は難しくない。肉眼上血管病変は千差万別で，変化もするので，病歴に比して病変が軽度の時は時期を変えて観察するのがよい。出血のほとんどは鼻腔最前部粘膜からなので，出血時には母指で鼻翼を数分間圧迫させる。止まらないときにはカルトスタット®などを緩めに多めに，血液が染みてこなくなるまで挿入していけば止血する。現状では確実な治療法は存在しないので，出血を予防し，症状を軽減するのが治療目標で，血管壁やその周囲の結合織の強化，それに刺激の減少を図る。

外鼻孔閉鎖術をオスラー病患者の鼻出血に対して施行したところ術後に出血の完全停止がもたらされたという報告が15年ほど前にあり,画期的治療法として期待されたが,その後症例数が増えるにしたがい,完璧な出血制御手段ではないことが判明してきた。しかし,オスラー病の鼻出血に対する手術の中では,止血の観点からは最も優れているものであることは間違いない。2004年から2019年の間に外鼻孔閉鎖術を施行した20例(男性11例,女性9例)を対象とし,術式別にみた外鼻孔閉鎖成功率と術後の出血停止状況についてretrospectiveな検討を行った。大多数は両側に施行し,平均手術時間は74.8分,平均出血量は28.5mlであった。施行した術式は2層縫合によるもの,それに同部の減張を図る縫合を追加するもの,lateral nasolabial crease flapを用いるものなどである。初回手術では37側中12側しか外鼻孔の完全閉鎖はできず,2回目以後でも28側中成功例は8側しかなかった。特にrotation flapを用いた例の結果が悪かった。解剖学的視点を加えたさらなるアプローチ法の改良が必要である。小穿孔があっても出血頻度や程度は術前よりは改善するが,出血停止例はない。完全閉鎖した例でも血圧の急激な変化による出血は予防できないので注意が必要である。

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

オスラー病患者の中等症以上の鼻出血に対して施行される鼻粘膜皮膚置換術は有効な治療法であるが, 出血部位の大半を占める鼻腔前部のみを皮膚置換範囲とするため, 出血の完全制御は期待できない. 術後に出血があっても頻度も量も著減するため, 患者の QOL は改善されるが, 再び出血量が増加する例も存在し, その中には再手術に至る症例もある. 本手術の術後出血についての詳細な分析は従来見られていないため, 再出血症例の出血部位を検討した. 対象は1991年8月～2017年12月までの26年間に鼻粘膜皮膚置換術を施行した患者100名中, 術後経過の追えなかった9例を除く91例である. 再出血の多くは移植した皮膚片が生着しなかった部位からのものであるが, 中には置換した皮膚に新生した怒張血管や, 移植部より前方の鼻前庭皮膚の血管からの例も見られた. 術式の変遷による再出血部位の特徴についてみると, 初期に鼻中隔から下鼻甲介下半にのみ皮膚移植していた時期には, いわゆる縫い代とした鼻中隔前上部からの出血が多く, 移植を全周性にしてからは,出血の多くは移植皮膚の脱落部, 特に前上部, 前下部, 下鼻甲介前方付着部であったが, 出血の頻度は減少した. 置換範囲を鼻前庭皮膚深部に伸ばしてからは脱落部が著減したため, 結果として再出血も著減した. 全症例のうち, 21例 (23.1%) に再手術がなされていたが, 術式の変更に伴いその率は減少した.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

筆者が鼻出血に悩む遺伝性出血性末梢血管拡張症(オスラー病)患者に鼻粘膜皮膚置換術を始めた1991年か らの25年間におけるその術式の改良経過と今後の展望を述べる。鼻粘膜皮膚置換術を最初に提唱したのは Saunders(1960)であり,病的粘膜を切除し,そこに厚い皮膚を移植して下層の血管を保護することにより出 血の頻度や量を減らすことを目的とした。手術開始以来,当初の8年間は安全性を考え片側ずつ施行していた が,8例目からは両側同時に行うようになった。上部の縫合用母地として残した鼻中隔最上部粘膜の血管が拡 張し,術後の出血源となっていたので,2008年からは植皮範囲を鼻腔前半の全周性とした。術中の出血管理に 大きな貢献をしたのは創傷被覆材であるカルトスタットであり,止血効果が格段に高く,しかも除去する際に もゲル化しているので局所を傷害せず再出血しにくいという利点がある。鼻中隔穿孔のある例では植皮片の脱 落とそれに伴う再出血が多く,この難点を解決するためにMW法を開発した。植皮片後方の固定にはマニセプ ス(セプタムスティッチ)の利用が有用だった。さらに最近の変更点として,鼻中隔粘膜の剥離除去から掻 爬への変更,鼻翼切開の廃止と内視鏡操作の導入がある。しかし本術式の持つ特徴から見て鼻出血の完全制御 は不可能であり,コブレーター による焼灼やチモロールなどの薬物治療を併用し,少しでも完璧な制御に近 づけるべく工夫している。

Objective Hereditary hemorrhagic telangiectasia (HHT) is widely known to cause bleeding that is difficult to control because of the associated vascular wall fragility. Although nasal dermoplasty results in decreased severity and frequency of nasal bleeding in patients with HHT, it does not eradicate epistaxis because this procedure cannot cover the entire nasal cavity. Residual bleeding warrants additional effective therapy. Preliminary reports on the use of β-adrenergic blockers for treating epistaxis in patients with HHT encouraged us to examine their effects in HHT patients who had previously undergone nasal dermoplasty but still complained of epistaxis. Methods We performed a prospective topical timolol, a nonselective beta blocker, application study involving 12 HHT patients who had undergone nasal dermoplasty. The observation period lasted for 3 months. Results There was one improperly enrolled case in which timolol administration was discontinued. The mean score of bleeding intensity and that of bleeding frequency were markedly reduced after treatment. Two patients who had required transfusions before treatment did not need them afterward, and patients were generally satisfied with the treatment. Conclusion Topical timolol application was effective in decreasing epistaxis. Although no adverse effects were observed in the properly selected patients, there are contraindications to timolol application that should be kept in mind when applying this treatment.

Objective: The aim of this study was to reduce misdiagnosis and inappropriate treatment of laryngeal tuberculosis.Methods: Between April 2009 and March 2013, 1660 inpatients with tuberculosis were treated at the Osaka Prefectural Medical Center for Respiratory and Allergic Diseases. Seventeen of these patients were diagnosed with laryngeal tuberculosis. Criteria used for diagnosis were findings of histologic examination of biopsy specimens (2 patients) or clinical response of granuloma to antituberculosis therapy (15 patients). Medical records were used for this retrospective study.Results: Patients' age ranged from 30 to 84 years with an average of 51.4 +/- 14.0 years (mean SE); nine were men and eight were women. The most frequent chief complaint was hoarseness (n = 15). Thirteen patients had persistent cough before they showed otolaryngologic symptoms. Endoscopic findings were categorized into five types of lesions: perichondritic (n = 6), ulcerative (n = 6), granulomatous (n = 6), polypoid (n = 1) and nonspecific inflammatory (n = 1). Laryngeal tuberculosis showed as a single lesion in one patient and as multiple lesions in the other patients. The most commonly involved site was the true vocal cord (n = 16, 94.1%), while 16 patients showed radiographic evidence of active pulmonary tuberculosis. These results indicate that deterioration of the lesions tended to result in the occurrence of multiple lesions.Conclusion: While morbidity in tuberculosis has been decreasing in Japan, a significant number of patients still has laryngeal tuberculosis in association with advanced pulmonary tuberculosis. If a patient has a protracted cough, laryngeal tuberculosis should be taken into consideration for differential diagnosis. Pulmonary imaging study should be performed for early diagnosis and to prevent the infection from spreading. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:Blue nevus is a benign dermal melanocyte tumor that mainly arises from the skin. We report an extremely rare case of blue nevus in a pediatric patient with extensive progression from the middle ear and inner ear to the nasopharynx through the Eustachian tube.CASE REPORT:A 2-year-old girl with blue tympanum was referred to our department. Computed tomography scans and magnetic resonance imaging were performed, followed by a tissue biopsy and histopathologic evaluations. Radiologic examinations revealed that the lesion had progressed beyond the middle ear into the inner ear and the nasopharynx through the Eustachian tube. Subsequent histopathologic examinations indicated dermal dendritic melanocytic proliferations, but no evidence of malignancy. Based on the clinical and histopathologic findings, we concluded that the lesion was consistent with blue nevus.DISCUSSION:Blue nevus is a relatively common skin lesion. However, no prior reports have described the extension of blue nevus from the auditory organ to the nasopharynx in a pediatric patient. Despite the benign nature of the lesion, the patient experienced profound hearing loss in the affected ear, which necessitates continued monitoring as the lesion may expand with patient growth.

Galanin and its receptors, GALR 1 and GALR 2, are known tumor suppressors and potential therapeutic targets in head and neck squamous cell carcinoma ( HNSCC ). Previously, we demonstrated that, in GALR 1‐expressing HNSCC cells, the addition of galanin suppressed tumor proliferation via upregulation of ERK 1/2 and cyclin‐dependent kinase inhibitors, whereas, in GALR 2‐expressing cells, the addition of galanin not only suppressed proliferation, but also induced apoptosis. In this study, we first transduced HEp ‐2 and KB cell lines using a recombinant adeno‐associated virus ( rAAV )‐green fluorescent protein ( GFP ) vector and confirmed a high GFP expression rate (>90%) in both cell lines at the standard vector dose. Next, we demonstrated that GALR 2 expression in the presence of galanin suppressed cell viability to 40–60% after 72 h in both cell lines. Additionally, the annexin V‐positive rate and sub‐G0/G1 phase population were significantly elevated in HEp ‐2 cells (mock vs GALR 2: 12.3 vs 25.0% ( P < 0.01) and 9.1 vs 32.0% ( P < 0.05), respectively) after 48 h. These changes were also observed in KB cells, although to a lesser extent. Furthermore, in HEp ‐2 cells, GALR 2‐mediated apoptosis was caspase‐independent, involving downregulation of ERK 1/2, followed by induction of the pro‐apoptotic Bcl‐2 protein, Bim. These results illustrate that transient GALR 2 expression in the presence of galanin induces apoptosis via diverse pathways and serves as a platform for suicide gene therapy against HNSCC .

Galanin and its receptors, GALR1 and GALR2, are tumor suppressors and represent therapeutic targets in head and neck squamous cell carcinoma (HNSCC). In the present study, it was demonstrated that the re‑expression of GALR1 in GALR1 and GALR2‑negative HNSCC cells suppresses tumor cell proliferation. This is mediated via extracellular‑regulated protein kinase‑1/2 (ERK1/2)‑dependent effects on the cyclin‑dependent kinase inhibitors (CKI) and cyclin D1. In combination with galanin, GALR2 also suppressed proliferation by increasing CKI and decreasing cyclin D1 levels. In contrast to GALR1, overexpression of GALR2 also induced caspase‑3‑dependent apoptosis. It was identified that in GALR2‑transfected cells, galanin induced activation of ERK1/2 and suppressed cell proliferation. Galanin stimulation also decreased the expression of cyclin D1 and induced apoptotic DNA ladder formation in GALR2‑transfected cells. Pretreatment with the ERK1/2‑specific inhibitor U0126 and pertussis toxin prevented the suppression of cyclin D1 expression, however did not affect DNA ladder formation. In conclusion, GALR2 expression in the presence of galanin exerts antitumor effects via cell cycle arrest and apoptotic pathways, and reactivation of these pathways may have therapeutic benefits in HNSCC.

甲状腺癌は予後良好であるが，進展例もあり，このうち縦隔進展例は気道に関わる致死的な合併症の一方で，胸骨切開による手術侵襲から術後合併症の頻度が高まることが予想され手術適応に関する明確な基準がない。基準設定の一助として，手術施行の時期により適応や術式が大きく異なることに着目し，当科で1980年代に胸骨切開を施行した6症例（初期症例）と最近経験した4症例（後期症例）の背景因子・進展範囲，手術術式，術後合併症，治療成績につき検討した。初期症例では分化癌以外の症例や分化癌でも広範囲進展例に対して積極的に縦隔廓清術を行っており，術式もより根治的であった。後期症例では乳頭癌症例のみに行われており気管や食道の処理も保存的であった。この結果，後期症例では術後合併症もなく全員生存している。以上より，合併切除臓器が少ない甲状腺分化癌の縦隔進展例に対しては，胸骨切開による縦隔廓清術は積極的に検討すべきと思われた。

Background. Pleomorphic adenoma (PA) is a benign tumour that mainly arises from salivary glands, and PA of the external auditory canal (EAC) is very rare. The objective of this study was to clarify the clinical presentation and treatment of PA of the EAC. Method. The authors present a case of PA arising from the EAC together with a literature review. Results. A 40-year-old man complained of hearing loss and foreign-body sensation of the right ear. Clinical and radiological examinations revealed a well-defined tumour limited to the EAC, with no connection to the parotid gland. Preoperative fine-needle aspiration cytology findings were characteristic of PA. The tumour was removed en bloc with the overlying skin. Conclusion. PA of the EAC is very rare, and methods to rule out malignancy before treatment are lacking. Thus, long-term follow-up is necessary, because malignant tumours are common in the EAC and PA has malignant potential.

Abstract Background: Revision laryngeal framework surgery is usually performed for medialisation laryngoplasty failure, rather than for failure after arytenoid adduction. We describe a new method for revision arytenoid adduction surgery, performed by directly pulling the lateral cricoarytenoid muscle (‘lateral cricoarytenoid muscle pull surgery’). Methods: We describe a case of revision laryngeal framework surgery, present a literature review and describe the advantages of lateral cricoarytenoid muscle pull surgery over the original method of arytenoid adduction using a posterior approach. Results: Medialisation laryngoplasty combined with arytenoid adduction was performed following unilateral vocal fold paralysis from mediastinal surgery, resulting in severe glottic insufficiency. The patient's voice improved after the initial surgery, but had deteriorated 18 months later. Revision surgery was performed using lateral cricoarytenoid muscle pull surgery, and her voice recovered normally in terms of perceptual impression. The post-operative course was uneventful for 10 months following revision surgery. Conclusion: To our knowledge, this is the first case of revision arytenoid adduction performed using a lateral cricoarytenoid muscle pull approach. Lateral cricoarytenoid muscle pull surgery should therefore be considered as a new fenestration approach for arytenoid adduction.

CONCLUSIONS:We describe a Japanese family with high-frequency sensorineural hearing loss (SNHL) harboring a c.211delC mutation in the KCNQ4 gene. Families showing progressive high-frequency SNHL should be investigated for mutations in the KCNQ4 gene.OBJECTIVE:To determine the responsible deafness gene in a Japanese family with dominantly inherited high-frequency SNHL of unknown etiology.METHODS:We performed hearing tests for five members of the family, and the three affected with hearing loss underwent further audiological and vestibular examinations. Genetic analysis was performed to identify any possible causative mutations, as well as analysis of detailed clinical findings to determine the phenotype.RESULTS:The three affected subjects showed high-frequency SNHL. Extensive audiologic evaluation suggested cochlear involvement and progressive hearing loss. As for bilateral caloric testing, two of the three affected subjects showed hyporeflexia with recurrent vestibular symptoms. We identified the c.211delC mutation in the KCNQ4 gene and the c.2967C>A (p.H989Q) mutation in the TECTA gene. Based on the genotype-phenotype correlation, the c.211delC mutation in the KCNQ4 gene was associated with high-frequency SNHL in this family.

nasopharyngeal carcinoma Skull base osteoradionecrosis is one of the most serious post-irradiation complications. In spite of localized lesions, patients have symptoms of foul odor and headache, which are very uncomfortable. What is even worse, without appropriate management, is that a mortal complication such as a rupture of the internal carotid artery may occur. We must recognize this disease and take a positive attitude toward this problem. We report on a 61-year-old man with skull base osteoradionecrosis after re-irradiation for a recurrence of nasopharyngeal carcinoma. Based on a few literature reviews, endoscopic sequestrectomy is very effective for relief of symptoms and prevention of the rupture of the internal carotid artery. But, if we accidentally expose the internal carotid artery during surgery, we may induce rupture of said artery. So, we must choose the method of treatment carefully. Furthermore, we should understand the structure of the skull base in detail and work cautiously during surgery.

Conclusion: Similar to combined arytenoid adduction and medialization laryngoplasty (i.e. combined surgery) under local anesthesia, general anesthesia by intubation or by the laryngeal mask airway (LMA) method significantly improves phonological outcome. Thus, laryngeal framework surgery under general anesthesia is a promising surgical approach for selected patients with unilateral vocal cord paralysis (UVCP). Objective: The advantages of laryngeal framework surgery under local anesthesia have been described, but no studies exist concerning the difference in phonological outcome of laryngeal framework surgery performed under general anesthesia. To add new information, we retrospectively investigated the phonological outcome of the combined surgery performed under three different anesthesia protocols. Methods: Thirty-nine consecutive patients with severe UVCP underwent the combined surgery under three anesthesia protocols performed by a single surgeon: (1) under general anesthesia by intubation, (2) under general anesthesia using LMA, and (3) under local anesthesia. Results: Under all anesthesia protocols, the vocal cords of most patients could be positioned such that the best vocal outcome could be expected. Statistical analyses demonstrated improved maximum phonation time and mean airflow rate, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale in all patients, regardless of their anesthesia protocol. Furthermore, of the three protocols, local anesthesia had the shortest operation time.

BackgroundEpithelioid hemangioendotheliomas (EHEs) of the head and neck region are uncommon malignant neoplasms that exhibit various biologic behaviors characteristic of both low‐ and high‐grade malignancy. A subgroup of EHEs identified as “high‐risk” EHEs because of their size and mitotic activity is associated with an unfavorable clinical course and poor prognosis.Materials and ResultsWe describe the treatment of the first and, in terms of size, largest case of high‐risk EHE arising from the neck. Despite wide excision, recurrence occurred 9 months after surgery, as had been expected. However, the tumor was found to express both vascular endothelial growth factor (VEGF) and VEGF receptor 2, indicating the potential of anti‐VEGF therapy in the treatment of such cases.ConclusionThe finding that a high‐risk EHE arising from the head and neck region is characterized by expression of VEGF and its receptor provides further support for the development of targeted molecular therapies. © 2012 Wiley Periodicals, Inc. Head Neck 35: E317–E320, 2013