Publishing type：Research paper (scientific journal)  

DOI： 10.3390/genes15050571

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

症例は12歳男児で、右前額部痛の精査目的に当科紹介となった。鼻咽喉内視鏡検査では異常所見はみられず、単純CTで右前頭洞から前篩骨洞に軟部陰影を認めたが、骨破壊はみられなかった。前医の単純MRIで右前頭洞から前篩骨洞にかけて、T1強調像で内部が均一な低信号を呈する嚢胞を認めた。以上より右前頭洞・篩骨洞嚢胞と診断し、内視鏡下鼻内副鼻腔手術で嚢胞壁を一部切除した。術直後より右前額部痛は消失し、術後8ヵ月の時点で嚢胞の再発は認めず、良好に経過している。

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

症例は12歳男児で、右前額部痛の精査目的に当科紹介となった。鼻咽喉内視鏡検査では異常所見はみられず、単純CTで右前頭洞から前篩骨洞に軟部陰影を認めたが、骨破壊はみられなかった。前医の単純MRIで右前頭洞から前篩骨洞にかけて、T1強調像で内部が均一な低信号を呈する嚢胞を認めた。以上より右前頭洞・篩骨洞嚢胞と診断し、内視鏡下鼻内副鼻腔手術で嚢胞壁を一部切除した。術直後より右前額部痛は消失し、術後8ヵ月の時点で嚢胞の再発は認めず、良好に経過している。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Neurosurgery Publishing Group (JNSPG)  

OBJECTIVE

The aim of this study was to investigate the impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery.

METHODS

The authors retrospectively reviewed the data of consecutive patients who underwent purely endoscopic endonasal skull base surgery from January 2015 to March 2023. Intraoperative CSF leakage was classified according to the Esposito grade, and skull base repair was tailored to the leakage grade. The patients were divided into two groups: before (group A) and after (group B) collagen matrix implementation. The rates of autologous graft harvesting (fat, fascia, and nasoseptal flap), postoperative CSF leakage, and donor-site complications were compared between the two groups.

RESULTS

In total, 270 patients were included. Group A included 159 patients and group B included 111 patients. There were no differences in patient characteristics, including age, pathology, and Esposito grade, between the two groups. The overall fat usage rate was significantly higher in group A (63.5%) than in group B (39.6%) (p = 0.0001), and the fascia usage rate was also significantly higher in group A (25.8%) than in group B (4.5%) (p < 0.0001). The nasoseptal flap usage rate did not differ between group A (32.7%) and group B (30.6%) (p = 0.79). Postoperative CSF leakage was similar between the two groups (0.63% in group A vs 1.8% in group B, p = 0.57), and the overall rate of CSF leakage was 1.1%. Donor-site complications occurred in 3 patients in group A, including 1 abdominal hematoma, 1 delayed abdominal infection, and 1 fluid collection after fascia lata harvesting.

CONCLUSIONS

Collagen matrix implementation significantly decreased autologous graft harvesting without increasing postoperative CSF leakage, contributing to less invasive surgery.

DOI： 10.3171/2023.12.jns231406

PubMed

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Other Link： https://thejns.org/downloadpdf/journals/j-neurosurg/aop/article-10.3171-2023.12.JNS231406/article-10.3171-2023.12.JNS231406.xml

Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

DOI： 10.3950/jibiinkotokeibu.127.1_54

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

<p>Sinus cysts are epithelial cysts that contain thick mucus and are thought to be primarily caused by obstruction of the natural ostium of the sinus.</p><p>These cysts occur after sinus surgery in most cases, and primary sinus cysts are relatively rare, with only sporadic reports of their occurrence in children.</p><p>We treated a 12-year-old boy with a primary frontal sinus/ethmoid sinus cyst who visited our hospital with a history of headache, but no other symptoms such as proptosis or upper eyelid swelling. He had severe headaches and had been taking analgesics daily, so that we exteriorized the cyst via under an endonasal approach using an endoscope and drained yellowish effusion from the cyst.</p><p>Removal of the cyst wall revealed a single cavity up to the frontal sinus, so that we did not touch the frontal sinus. Pediatric endoscopic sinus surgery is necessary to set the surgical method and surgical scope taking into consideration the stage of growth.</p><p>If age-appropriate settings are made, subjective symptoms can be expected to improve. In this case, the headache disappeared immediately after the surgery, and no recurrence has been observed until date.</p>

DOI： 10.5631/jibirin.117.247

Scopus

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

<p>We report a case of nodular fasciitis in the lacrimal sac. The patient was a 30-year-old man who was referred to our department with the complaints of increased lachrymation and swelling of the medial wall of the right orbit. A biopsy was performed under local anesthesia, and the histopathological findings led to the suspicion of nodular fasciitis. In collaboration with an ophthalmologist, the lesion was resected using an external nasal incision and a transnasal endoscopic approach with a navigation system under general anesthesia. The lesion was completely removed with preservation of the external ocular muscle. Postoperative histopathology revealed that the lesion was indeed nodular fasciitis. Currently, neither obvious postoperative nasolacrimal duct obstruction, nor disturbance of the optical functions is observed. There is also no evidence of either a residual or recurrent lesion.</p><p>Nodular fasciitis has frequently been reported in the buccal area of the head and neck region, but it should be borne in mind that it can also occur in intraorbital lesions.</p>

DOI： 10.5631/jibirin.117.719

Scopus

Language：Japanese   Publisher：Tissue Engineering - Part B: Reviews  

Human vocal folds (VFs), a pair of small, soft tissues in the larynx, have a layered mucosal structure with unique mechanical strength to support high-level tissue deformation by phonation. Severe pathological changes to VF have causes including surgery, trauma, age-related atrophy, and radiation, and lead to partial or complete communication loss and difficulty in breathing and swallowing. VF glottal insufficiency requires injectable VF biomaterials such as hyaluronan, calcium hydroxyapatite, and autologous fat to augment VF functions. Although these biomaterials provide an effective short-term solution, significant variations in patient response and requirements of repeat reinjection remain notable challenges in clinical practice. Tissue engineering strategies have been actively explored in the search of an injectable biomaterial that possesses the capacity to match native tissue’s material properties while promoting permanent tissue regeneration. This review aims to assess the current status of biomaterial development in VF tissue engineering. The focus will be on examining state-of-the-art techniques including modification with bioactive molecules, cell encapsulation, composite materials, and in situ crosslinking with click chemistry. We will discuss potential opportunities that can further leverage these engineering techniques in the advancement of VF injectable biomaterials.

DOI： 10.1089/ten.teb.2024.0134

Scopus

PubMed

Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

<p>　 Using cervical CT and 3D-CT imaging, we measured the lengths of the styloid processes of 242 patients in 484 views. The mean length of the styloid processes was 23.6 mm, and styloid processes with lengths ≥ 30 mm formed 11% and 15.3% of all views and cases, respectively. No difference in length was observed between the left and right views of the styloid processes. With respect to age, patients with ages ≥ 20 years had significantly longer styloid processes than those with ages <20 years. For patients with ages ≥ 20 years, no significant differences were observed among the various age groups. The styloid processes seemed to cease elongation after the growth period. In 37 cases (18[48.6%] bilateral cases and 19 [51.4%] unilateral cases), the lengths of the styloid processes were ≥ 30 mm, and this observation was significantly more frequent among males. The overgrowth of the styloid process was observed in 19.4% of males, 10.6% of females, and 15.3% of all cases. In this cohort, one case of elongated styloid process underwent resection by an external cervical incision. 3D-CT imaging and CT angiography were useful in the preoperative evaluation and surgical manipulation of the patient. Elongated styloid processes are associated with a wide variety of symptoms and have been reported to lead to serious outcomes in certain cases. When an incidental finding of an overgrowth of the styloid process is made on imaging, detailed history of the patient's symptoms and collaboration with other departments are necessary in managing such cases of elongated styloid process.</p>

DOI： 10.3950/jibiinkotokeibu.126.9_1061

Publisher：東京医学社  

DOI： 10.24479/ohns.0000000751

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

当院で撮影された242例484側の頸部CT画像および3D-CT画像から茎状突起の長さを測定し臨床的検討を行った.平均長は23.6mmであった.左右差は認めず,20歳未満と20歳以上では有意差をもって20歳以上で長く,20歳以上の各年代間では有意な差は認めなかった.成長期を過ぎて茎状突起の延長はないものと思われた.30mm以上の過長茎状突起を有するものは37例で,男性に有意に多く,両側例は18例(48.6%),片側例は19例(51.4%)であった.一側でも過長を有する過長茎状突起症例は男性の19.4%,女性の10.6%,全症例の15.3%であった.頸部外切開にて切除した茎状突起過長症の1例を経験し,術前評価および手術操作において,3D-CT画像およびCTAが非常に有用であったため併せて報告する.茎状突起過長症は多種多様な症状を伴い,重篤な転帰につながる例も報告されている.画像検査にて偶発的に過長茎状突起を認めた場合は,詳細な症状聴取が必要であり,他科を含めた茎状突起過長症についての連携も重要と思われる.(著者抄録)

Language：English  

DOI： 10.1259/bjr.20220772

PubMed

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

<p>　 To evaluate the usefulness of 2-methacryloyloxyethyl phosphorylcholine polymer (MPCP) as a gargle, we investigated the bacterial adherence inhibitory effect, moisturizing effect, and anti-inflammatory effect of MPCP37, one of the formulations of MPCP. In an in vitro experiment we counted the numbers of <i>Streptococcus pneumoniae</i> adhering to cultured pharyngeal epithelial cells after exposing the cells to MPCP37. We then counted the numbers of bacteria adhering to the mucosal epithelial cells of 15 healthy subjects three hours after gargling with MPCP37 and various commercially available gargles. The moisturizing effect of MPCP37 was assessed by measuring the humidity of the tongue surface with an oral moisture meter after gargling with MPCP37 and other gargles and absorbing tongue surface water with a paper towel. The anti-inflammatory effect of MPCP37 was assessed by measuring the levels of IL-8 produced by cultured pharyngeal epithelial cells in response to the stimulation with Pam3CSK4 after exposure to MPCP37. The results showed that the numbers of bacteria adhering to the epithelial cells had markedly decreased after exposure to MPCP37 and gargling with MPCP37, even with a 0.05% MPCP37 solution. The change in tongue surface moisture was significantly smaller in the group that had gargled with MPCP37. In addition, IL-8 production by cultured pharyngeal epithelial cells was significantly suppressed by exposure to MPCP37. These findings suggested that MPCP37 possesses moisturizing and anti-inflammatory effects in addition to an inhibitory effect on bacterial adherence and that it might be able to serve as a formulation of a new gargle.</p>

DOI： 10.3950/jibiinkotokeibu.126.5_722

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

2-メタクリロイルオキシエチルホスホリルコリンポリマー(MPCP)の含嗽薬としての有用性を評価するため,その製剤の一つであるMPCP37の上皮細胞への細菌付着抑制作用,保湿作用,抗炎症作用を検討した.まず,培養咽頭上皮細胞をMPCP37で処理したのちに肺炎球菌を添加し,上皮細胞への付着細菌数を測定した.さらに,15名の健常者を対象としてMPCP37および市販されている各種含嗽薬で含嗽を行い,その3時間後の頬粘膜擦過上皮細胞への付着細菌数を測定した.保湿作用は,MPCP37および各種含嗽薬で含嗽したあとにペーパータオルで舌表面の水分を吸収し,その前後での舌表面の乾燥状態を口腔水分計で計測し,両者の差を比較し評価した.抗炎症作用は,培養咽頭癌上皮細胞をMPCP37および各種含嗽薬で処理したのちにPam3CSK4で刺激し,培養液中のIL-8の値を測定し評価した.その結果,MPCP37の前処理および含嗽によって上皮細胞への付着細菌数が有意に減少し,0.05%溶液でも細菌付着の抑制作用が認められた.また,舌表面水分量の変化はMPCP37含嗽群で有意に少なく,上皮細胞のIL-8産生量はMPCP37の前処理によって有意に減少した.これらの結果から,MPCP37は細菌付着抑制作用に加えて保湿作用さらに抗炎症作用を有し,新たな含嗽薬として応用できる製剤であることが示唆された.(著者抄録)

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1411203324

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1411203266

Language：Japanese   Publisher：日本口腔・咽頭科学会  

OK-432(ピシバニール)はA群溶連菌Su株をペニシリンで不活化したもので,癌の免疫療法薬として開発された.ガマ腫に対するOK-432を用いた硬化療法は低侵襲で安全な方法であることから,近年行われるようになっている.今回,当科にてOK-432による硬化療法を行ったガマ腫4例について報告する.3例に希釈置換法,1例に高濃度注入法を行った.全例注入回数は1回であった.1例で注入後に再増大を認めたが,その4ヵ月後には自然消退し,最終的には全例ガマ腫の消失に至った.副作用は,発熱,腫脹,疼痛を認めたが,重大なものはみられなかった.OK-432による硬化療法はガマ腫に対して有効性と安全性が高い治療法であると考えられ,治療の第一選択肢となり得ると思われる.(著者抄録)

Language：Japanese   Publisher：日本口腔・咽頭科学会  

OK-432(ピシバニール)はA群溶連菌Su株をペニシリンで不活化したもので,癌の免疫療法薬として開発された.ガマ腫に対するOK-432を用いた硬化療法は低侵襲で安全な方法であることから,近年行われるようになっている.今回,当科にてOK-432による硬化療法を行ったガマ腫4例について報告する.3例に希釈置換法,1例に高濃度注入法を行った.全例注入回数は1回であった.1例で注入後に再増大を認めたが,その4ヵ月後には自然消退し,最終的には全例ガマ腫の消失に至った.副作用は,発熱,腫脹,疼痛を認めたが,重大なものはみられなかった.OK-432による硬化療法はガマ腫に対して有効性と安全性が高い治療法であると考えられ,治療の第一選択肢となり得ると思われる.(著者抄録)

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Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

DOI： 10.3950/jibiinkotokeibu.126.1_69

Language：Japanese   Publisher：Japan Society of Stomato-pharyngology  

OK-432 （Picibanil^Ⓡ） is a penicillin-inactivated, low-toxicity strain of group A <i>Streptococcus</i>. It is widely used in Japan as an immunotherapeutic agent for malignant tumors. Sclerotherapy with OK-432 is recommended as the optimal treatment for ranula because it is minimally invasive and safe. This study reports four patients with shrunken ranula treated with OK-432 local injection therapy. In three cases, the content of the ranula was aspirated to the maximum extent possible, and then a volume of the OK-432 solution equal to the aspirated volume was injected. In one case, the OK-432 solution was injected at a high concentration without aspirating the contents of the ranula. All cases were followed up using ultrasonography. After 6 weeks, all cases showed shrinkage of the ranula. In one case, a re-enlargement of the ranula was observed 5 months after post-injection, but it resolved spontaneously after 4 months. Eventually, disappearance of the ranula was noted in all cases. Adverse effects, including fever lasting for 2-3 days （3/4 cases） and local swelling for 3-5 days （2/4 cases）, were identified. Sclerotherapy with OK-432 appears to be an effective and safe treatment and may be the first choice for ranula before considering surgery.

DOI： 10.14821/stomatopharyngology.36.59

Language：Japanese   Publisher：Auris Nasus Larynx  

Objective: A phosphorylcholine (PC)-derivative with high binding ability (PCDB) was intranasally administered to mice with ovalbumin (OVA), and immune responses were investigated to determine whether PCDB has antigenicity and adjuvanticity. Methods: BALB/c mice were intranasally immunized with PCDB coupled with OVA, unbound PCDB plus OVA, cholera toxin (CT) plus OVA, OVA alone, and PCDB alone. Then, the production of OVA- and PC-specific antibodies in external secretions and serum, and the secretion of cytokines such as IL-4 and IFN-γ from splenic mononuclear cells by stimulation with PCDB and OVA were examined. Furthermore, the secretion of IL-12p40 from CD11c+ cells following stimulation with PCDB was observed to clarify the adjuvant effect of PCDB through TLR4. Results: Intranasal immunization with PCDB plus OVA increased OVA- and PC-specific IgA in external secretions and OVA- and PC-specific antibodies in the serum. The analysis of IgG subclasses specific to OVA and PC showed a higher production of IgG1 than IgG2, and the secretion of both IL-4 and IFN-γ was enhanced. However, IL-12p40 secretion from CD11c+ cells was increased and OVA-specific IgE production was not promoted by PCDB stimulation. Conclusion: Intranasal administration of the protein antigen with PCDB enhanced immune responses specific to the mixed antigen and PC. Although PCDB acted to bias the immune response toward the Th2-type, antigen-specific IgE production did not increase. These findings suggest that PCDB has the potential to be a mucosal vaccine with both adjuvanticity and antigenicity without causing side effects due to type I allergy.

DOI： 10.1016/j.anl.2023.07.008

Scopus

PubMed

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

<p>We report a case of subdural abscess secondary to abscess of the infratemporal fossa as a complication of odontogenic infection. The patient was an 84-year-old woman who was referred to our hospital because of swelling in her right temporal region and poor oral intake following extraction of the right lower jaw canine and first premolar teeth. Contrast-enhanced computed tomography revealed an infratemporal fossa abscess. Surgical drainage of the abscess was performed under general anesthesia via a temporal skin incision, and intravenous antibiotic therapy was initiated. Although there were no signs of active inflammation, three weeks after the surgery, contrast-enhanced magnetic resonance imaging revealed multiple subdural abscesses extending from the left temporal lobe to the frontal lobe. Thus, craniotomy was performed to drain the abscess. The patient discharged 32 days after the operation, without sequelae.</p><p>While treating an infratemporal abscess, it is necessary to consider the possibility of complication by intracranial abscess formation.</p>

DOI： 10.5631/jibirin.116.677

Scopus

Language：Japanese   Publisher：Indian Journal of Otolaryngology and Head and Neck Surgery  

Adult T-cell leukemia/lymphoma (ATL) is a form of leukemia caused by the human T-cell leukemia virus type I (HTLV-1). Otolaryngologists often diagnose ATL based on cervical lymphadenopathy or Waldeyer ring lesions. However, there are few reports of ATL occurring in the nasal and paranasal cavity. Here, we report four such cases of ATL. Case 1: An 82-year-old man diagnosed with acute-type ATL with a tumor in the nasal cavity underwent 5 courses of THP-COP, but died after 36 months due to ATL. Case 2: A 62-year-old woman diagnosed with lymphoma-type ATL with a tumor in the frontal sinus was treated with 5 courses of VCAP-AMP-VECP, and has survived for more than 10 years. Case 3: A 64-year-old man diagnosed with lymphoma-type ATL with a tumor in the maxillary sinus underwent 8 courses of VCAP-AMP-VECP and 2 courses of mogamulizumab, but died after 34 months due to ATL. Case 4: A 52-year-old woman diagnosed with lymphoma-type ATL with tumors in both ethmoid sinuses received 2 courses of CHOP, 2 courses of DeVIC, radiotherapy (32 Gy) and 2 courses of mogamulizumab, but died after 9 months due to ATL.

DOI： 10.1007/s12070-023-04258-3

Scopus

Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

甲状舌管嚢胞に由来する悪性腫瘍は約1%と稀で,多くは乳頭癌であり扁平上皮癌は約5%と更に稀である。われわれは喉頭全摘術を要した甲状舌管嚢胞に由来すると考えられた扁平上皮癌症例を経験した。症例は69歳女性,嗄声とオトガイ下部の腫脹,圧痛が出現した。造影CT,MRI検査上甲状舌管嚢胞の破綻や腫瘍性病変が疑われた。穿刺吸引細胞診検査と組織試験採取から扁平上皮癌の診断となり甲状舌管嚢胞由来の扁平上皮癌と考えられた。腫瘍は喉頭に浸潤しており喉頭全摘術を含めた前頸部悪性腫瘍摘出術を行った。甲状舌管嚢胞に由来する扁平上皮癌ではSistrunk法のみでは不十分であり喉頭全摘術を要する症例があることを示した。(著者抄録)

Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

甲状舌管嚢胞に由来する悪性腫瘍は約1%と稀で,多くは乳頭癌であり扁平上皮癌は約5%と更に稀である。われわれは喉頭全摘術を要した甲状舌管嚢胞に由来すると考えられた扁平上皮癌症例を経験した。症例は69歳女性,嗄声とオトガイ下部の腫脹,圧痛が出現した。造影CT,MRI検査上甲状舌管嚢胞の破綻や腫瘍性病変が疑われた。穿刺吸引細胞診検査と組織試験採取から扁平上皮癌の診断となり甲状舌管嚢胞由来の扁平上皮癌と考えられた。腫瘍は喉頭に浸潤しており喉頭全摘術を含めた前頸部悪性腫瘍摘出術を行った。甲状舌管嚢胞に由来する扁平上皮癌ではSistrunk法のみでは不十分であり喉頭全摘術を要する症例があることを示した。(著者抄録)

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Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

<p>　Tap water disinfected with chlorine is known to have bactericidal activity. However, it has not yet been clarified if gargling with tap water has antiseptic properties. Therefore, the bactericidal activity of tap water and of tap water after various processings was investigated using <i>Streptococcus pneumoniae</i> and the concentrations of residual chlorine were compared. Further, the numbers of bacteria adhering to the scraped buccal mucosal epithelial cells three hours after gargling with tap water, purified water, and gargle medicines were counted and compared. The results revealed that the bactericidal activity disappeared when residual chlorine was removed by boiling. Residual chlorine was not detected in the tap water after gargling or addition of saliva, and there was no difference in the number of bacteria adherent to the buccal epithelial cells between tap water gargling and purified water gargling. The findings suggest that gargling with tap water does not have a bactericidal effect due to deactivation of the residual chlorine by saliva, even though tap water containing residual chlorine has bactericidal activity.</p>

DOI： 10.3950/jibiinkotokeibu.125.8_1298

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1411203114

Language：English   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

咽頭表在癌では腫瘍の厚さがリンパ節転移再発の危険因子の一つであることが報告されている。その厚さを術前に測定する目的で超音波内視鏡検査(EUS)が示す有用性を評価した。2010年12月～2018年3月に当院で咽頭表在癌に対し内視鏡的粘膜下層剥離術を施行し、その直前に全身麻酔下でEUSも実施していた連続患者44名(男性43名、平均67.8±8.7歳)の47病変を組み入れた。EUSで測定した腫瘍厚と、術後、病理組織学的に評価された腫瘍厚とは有意に相関していた(Spearmanの相関係数r=0.88、p<0.001)。病理評価の厚が1000μm以上であることの予測に最適となるEUS測定厚のカットオフ値を受信者動作特性(ROC)解析で求めたところ2.6mmと決定された。そのカットオフ値が示した感度は100%、特異度は82%、陽性的中率は70%、陰性的中率は100%、精度は89%となった。さらに日本食道学会の拡大内視鏡分類システムをEUSと組み合わせて使用した場合、その診断精度は96%となった。EUS評価による腫瘍厚は、病理組織学的計測での腫瘍厚が1000μm以上であることを診断するのに有効であった。咽頭表在癌に対しEUSと拡大内視鏡分類システムを併用すれば、リンパ節転移再発の術前危険因子の評価に有用であると考えられた。

Language：Japanese   Publisher：PLoS ONE  

Background and aims Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach. Methods In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed. Results Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group. Conclusions Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

DOI： 10.1371/journal.pone.0267572

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PubMed

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

2018〜2020年の唾液腺手術245例のうち、黄色肉芽腫性唾液腺炎(XGS)5例(2.0%)の診療録から年齢、性別、理学所見、画像検査所見について検討した。5例の内訳は男性3例、女性2例、平均年齢54歳で、随伴症状は疼痛5例、顔面神経麻痺1例であり、ワルチン腫瘍合併例は1例、粘表皮癌合併は1例、ワルチン腫瘍併存は1例であった。造影MRI検査では内部が低信号で、辺縁の造影パターンが早期濃染型であることが共通しており、穿刺吸引細胞診を施行した3例では全例に炎症性細胞像を認めたが、術前にXGSの診断に至った症例はなかった。XGSでは悪性所見を呈すること、FDG-PET/CT検査などの核医学検査で異常集積を認めること、悪性腫瘍合併例があることから、術前の確定診断は困難と考えられた。治療は手術が第一選択であり、自験例で再発を認めた症例はなかった。

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

2018〜2020年の唾液腺手術245例のうち、黄色肉芽腫性唾液腺炎(XGS)5例(2.0%)の診療録から年齢、性別、理学所見、画像検査所見について検討した。5例の内訳は男性3例、女性2例、平均年齢54歳で、随伴症状は疼痛5例、顔面神経麻痺1例であり、ワルチン腫瘍合併例は1例、粘表皮癌合併は1例、ワルチン腫瘍併存は1例であった。造影MRI検査では内部が低信号で、辺縁の造影パターンが早期濃染型であることが共通しており、穿刺吸引細胞診を施行した3例では全例に炎症性細胞像を認めたが、術前にXGSの診断に至った症例はなかった。XGSでは悪性所見を呈すること、FDG-PET/CT検査などの核医学検査で異常集積を認めること、悪性腫瘍合併例があることから、術前の確定診断は困難と考えられた。治療は手術が第一選択であり、自験例で再発を認めた症例はなかった。

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1411202945

Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

<p>　To clarify the effect of gargling on the removal of oral mucosal epithelial cells with adherent bacteria, in addition to its cleaning action, the numbers of epithelial cells and bacteria adhering to the epithelial cells in the gargled water were counted after tap water gargling three times. Furthermore, the numbers of bacteria adhering to the scraped buccal mucosal epithelial cells three hours after purified water, sodium azulene sulfonate, and or povidone iodine garglings were also counted and compared. Examination revealed numerous epithelial cells with adherent bacteria in the gargled water, and the numbers of epithelial cells and bacteria adhering to the epithelial cells in the gargled water decreased significantly with the number of times a person gargled. Three hours after purified water or sodium azulene sulfonate gargling, numerous bacteria were found adhering to scraped buccal mucosal epithelial cells. In contrast, the number of bacteria adherent to the epithelial cells in the scraped buccal mucosal epithelial cells was remarkably decreased after povidone iodine gargling. The findings suggest that gargling removes epithelial cells with adherent bacteria, which might be an important objective of gargling. Bacteria which proliferate several hours after gargling adhere again to the epithelial cells, and gargling with povidone iodine significantly reduced the number of bacteria adhering to the epithelial cells as compared to purified water or sodium azulene sulfonate gargling. However, as povidone iodine also damages the normal bacterial flora and mucosal epithelial tissue, development of a new compound(s) for gargling that would inhibit bacterial adherence to the buccal mucosal epithelial cells without these harmful effects is desired.</p>

DOI： 10.3950/jibiinkotokeibu.125.3_279

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

含嗽の洗浄作用に加えて口腔内の細菌付着上皮細胞の除去作用を明らかにすることを目的として,水道水で含嗽したのち,含嗽液中の粘膜上皮細胞数ならびに粘膜上皮細胞に付着した細菌数を計測した.さらに,精製水,アズレンスルホン酸ナトリウム含嗽液(アズレン含嗽液),ポビドンヨード含嗽液で含嗽し,その3時間後に採取した頬粘膜擦過上皮細胞に付着する細菌数を計測し比較した.その結果,水道水による含嗽液中には数多くの細菌が付着した粘膜上皮細胞を認め,含嗽を3回繰り返し行うごとに,含嗽液中の上皮細胞数およびそれに付着する細菌数は有意に減少した.また,精製水とアズレン含嗽液による含嗽3時間後に頬粘膜を擦過し得られた上皮細胞には多くの細菌の付着が認められたが,ポビドンヨード含嗽液ではその数が有意に少なかった.以上の所見から,含嗽は細菌が付着した上皮細胞を除去する作用を有していることが証明され,そのことに留意して含嗽を行えば含嗽の効果が増すと推測される.さらに,含嗽の数時間後には口腔内で増殖した細菌が粘膜上皮細胞へ再度付着し,ポビドンヨード含嗽液はその殺菌作用によってそれを強力に阻止することが示された.しかし,ポビドンヨード含嗽液は正常細菌叢の破壊や粘膜組織の傷害が問題となるため,これらの弊害がなく細菌の付着を抑制できる新たな含嗽薬の開発が望まれる.(著者抄録)

Language：Japanese   Publisher：(株)医学書院  

症例は75歳女性。右頬部痛を主訴とした。造影CT検査およびPET/CT検査から上顎洞腫瘍と診断し、生検を施行した。HE染色でびまん性に浸潤する小型の細胞を認め、免疫染色では腫瘍細胞はびまん性にcytokeratinとsynaptophysin陽性、chromograninとSMA陰性であった。以上より、上顎洞神経内分泌癌と診断し、肺小細胞癌に準じてシスプラチン/塩酸イリノテカン療法と放射線療法を施行した。CCRT終了3ヵ月後のMRI検査では、上顎洞に貯留液を認めるも充実性病変は認められなかった。治療終了から約5年経過しているが、再発や遠隔転移は認めなかった。

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

含嗽の洗浄作用に加えて口腔内の細菌付着上皮細胞の除去作用を明らかにすることを目的として,水道水で含嗽したのち,含嗽液中の粘膜上皮細胞数ならびに粘膜上皮細胞に付着した細菌数を計測した.さらに,精製水,アズレンスルホン酸ナトリウム含嗽液(アズレン含嗽液),ポビドンヨード含嗽液で含嗽し,その3時間後に採取した頬粘膜擦過上皮細胞に付着する細菌数を計測し比較した.その結果,水道水による含嗽液中には数多くの細菌が付着した粘膜上皮細胞を認め,含嗽を3回繰り返し行うごとに,含嗽液中の上皮細胞数およびそれに付着する細菌数は有意に減少した.また,精製水とアズレン含嗽液による含嗽3時間後に頬粘膜を擦過し得られた上皮細胞には多くの細菌の付着が認められたが,ポビドンヨード含嗽液ではその数が有意に少なかった.以上の所見から,含嗽は細菌が付着した上皮細胞を除去する作用を有していることが証明され,そのことに留意して含嗽を行えば含嗽の効果が増すと推測される.さらに,含嗽の数時間後には口腔内で増殖した細菌が粘膜上皮細胞へ再度付着し,ポビドンヨード含嗽液はその殺菌作用によってそれを強力に阻止することが示された.しかし,ポビドンヨード含嗽液は正常細菌叢の破壊や粘膜組織の傷害が問題となるため,これらの弊害がなく細菌の付着を抑制できる新たな含嗽薬の開発が望まれる.(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

症例は75歳女性。右頬部痛を主訴とした。造影CT検査およびPET/CT検査から上顎洞腫瘍と診断し、生検を施行した。HE染色でびまん性に浸潤する小型の細胞を認め、免疫染色では腫瘍細胞はびまん性にcytokeratinとsynaptophysin陽性、chromograninとSMA陰性であった。以上より、上顎洞神経内分泌癌と診断し、肺小細胞癌に準じてシスプラチン/塩酸イリノテカン療法と放射線療法を施行した。CCRT終了3ヵ月後のMRI検査では、上顎洞に貯留液を認めるも充実性病変は認められなかった。治療終了から約5年経過しているが、再発や遠隔転移は認めなかった。

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/microorganisms10030527

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland carcinomas, but no effective treatment strategy has been established other than surgical resection. Purkinje cell protein (PCP) 4/peptide (PEP) 19 is a calmodulin-binding antiapoptotic peptide that is expressed and inhibits apoptosis in human breast cancer cells. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor that has been implicated in the pathogenesis of many carcinomas, particularly breast and gastric carcinomas. In the present study, we performed immunohistochemical analyses of samples from 73 patients who underwent surgical resection for MEC of the salivary gland using antibodies against PCP4/PEP19 and HER2. PCP4/PEP19 expression was related to better prognosis, while HER2 expression was associated with worse prognosis. Patients that were PCP4/PEP19-positive and HER2-negative showed similar outcomes to PCP4/PEP19 and HER2 alone. Therefore, PCP4/PEP19 and HER2 are predicted to play important roles in the pathogenesis and progression of MEC.

DOI： 10.3390/cancers14010054

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Language：Japanese   Publisher：The Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.115.650

Language：Japanese   Publisher：Molecular Imaging and Biology  

Purpose: To examine whether the machine learning (ML) analyses using clinical and pretreatment 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography ([18F]-FDG-PET)–based radiomic features were useful for predicting prognosis in patients with hypopharyngeal cancer. Procedures: This retrospective study included 100 patients with hypopharyngeal cancer who underwent [18F]-FDG-PET/X-ray computed tomography (CT) before treatment, and these patients were allocated to the training (n=80) and validation (n=20) cohorts. Eight clinical (age, sex, histology, T stage, N stage, M stage, UICC stage, and treatment) and 40 [18F]-FDG-PET–based radiomic features were used to predict disease progression. A feature reduction procedure based on the decrease of the Gini impurity was applied. Six ML algorithms (random forest, neural network, k-nearest neighbors, naïve Bayes, logistic regression, and support vector machine) were compared using the area under the receiver operating characteristic curve (AUC). Progression-free survival (PFS) was assessed using Cox regression analysis. Results: The five most important features for predicting disease progression were UICC stage, N stage, gray level co-occurrence matrix entropy (GLCM_Entropy), gray level run length matrix run length non-uniformity (GLRLM_RLNU), and T stage. Patients who experienced disease progression displayed significantly higher UICC stage, N stage, GLCM_Entropy, GLRLM_RLNU, and T stage than those without progression (each, p<0.001). In both cohorts, the logistic regression model constructed by these 5 features was the best performing classifier (training: AUC=0.860, accuracy=0.800; validation: AUC=0.803, accuracy=0.700). In the logistic regression model, 5-year PFS was significantly higher in patients with predicted non-progression than those with predicted progression (75.8% vs. 8.3%, p<0.001), and this model was only the independent factor for PFS in multivariate analysis (hazard ratio = 3.22; 95% confidence interval = 1.03–10.11; p=0.045). Conclusions: The logistic regression model constructed by UICC, T and N stages and pretreatment [18F]-FDG-PET–based radiomic features, GLCM_Entropy, and GLRLM_RLNU may be the most important predictor of prognosis in patients with hypopharyngeal cancer.

DOI： 10.1007/s11307-022-01757-7

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PubMed

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

<p>Xanthogranulomatous tissue reaction, which is frequently mistaken for malignant tumor, is known to occur at many sites in the body, but is rarely seen in the salivary glands. Only 11 cases of xanthogranulomatous sialadenitis (XGS) have been reported in the literature. Herein, we report five cases of XGS and summarize the clinical features of these cases and also previously reported cases. Pain, which is the most common complication, was recorded in 11 cases. In general, benign parotid tumors are rarely painful, so we believe that the high frequency of pain in cases of XGS is one of the factors that make it difficult to distinguish it from malignant tumors. The onset site was the parotid gland in 14 cases, the submandibular gland in 1 case, and the sublingual gland in 1 case. No identifiable tumor was observed in 10 cases. Warthin’s tumor was identified in 5 cases, and mucoepidermoid carcinoma in 1 case. The most case of XGS, which was without malignant tumor, presented with facial nerve paralysis. Since it is difficult to confirm the diagnosis of XGS before surgery, rapid intraoperative diagnosis may allow appropriate and timely treatment to be undertaken. Pain, absence of malignant findings on FNA, and focal lesions with rim enhancement on dynamic magnetic resonance imaging may aid in the diagnosis.</p>

DOI： 10.5631/jibirin.115.315

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Language：Japanese   Publisher：Surgical Neurology International  

Background: Anterior inferior cerebellar artery (AICA) aneurysms in the internal auditory canal (IAC) are rare. We have reported a case of dissecting AICA aneurysm in the IAC presenting initially with the eighth nerve palsy followed by the seventh nerve palsy without hemorrhage. Case Description: A 68-year-old woman presented with a sudden onset of vertigo accompanied by deafness and tinnitus on the right side that was preceded by intermittent right retroauricular pain 2 weeks before. Audiogram showed severe sensorineural hearing loss. Computed tomography and magnetic resonance imaging (MRI) indicated absence of prior subarachnoid hemorrhage. Magnetic resonance angiogram (MRA) suggested a tiny aneurysm at the fundus of the IAC accompanied with thinning of the lateral pontine segment of the AICA. Conservative treatment led to moderate improvement of the symptoms. However, the patient developed the right retroauricular pain again, followed by the right facial paralysis 5 months later but still without signs of hemorrhage on MRI. Digital subtraction angiogram showed dissecting aneurysm in the IAC. The patient was managed with oral steroids and direct intervention was avoided due to a risk of ischemia supposed by large area irrigated by the AICA. Follow-up MRA 18 months after the first presentation showed improvement in the narrowing of the AICA proximal to the aneurysm. The patient was functionally independent despite right-sided hearing loss and slight facial paresis. Conclusion: This report warns physicians that a dissecting AICA aneurysm without subarachnoid hemorrhage may cause eighth and seventh nerve palsy.

DOI： 10.25259/SNI_1220_2021

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PubMed

Language：Japanese   Publisher：JAPAN SOCIETY FOR HEAD AND NECK SURGERY  

Malignant tumors originating from thyroglossal duct cysts are rare, accounting for about 1％ of such cases, and most of them are diagnosed as papillary carcinomas; squamous cell carcinomas are extremely rare, accounting for about 5％ of malignant cases. In this paper, we report a case of squamous cell carcinoma thought to be derived from a thyroglossal duct cyst which required tumor resection with total laryngectomy. A 69-year-old woman presented to us with hoarseness, swelling and tenderness in the lower part of the submental region. Contrast-enhanced computed tomography （CT） and contrast-enhanced magnetic resonance imaging （MRI） suggested a disruption of the thyroglossal duct cyst with a neoplastic lesion. The diagnosis of squamous cell carcinoma was confirmed based on puncture aspiration cytology and tissue biopsies. The tumor had invaded into the larynx. The patient subsequently underwent anterior cervical malignant tumor resection including total laryngectomy. Comprehensive preoperative and postoperative histological analyses suggested that the squamous cell carcinoma had originated from a thyroglossal duct cyst. In cases of squamous cell carcinoma derived from thyroglossal duct cysts, the Sistrunk method alone is not always sufficient for tumor control. Total laryngectomy could be required in cases with laryngeal invasion of squamous cell carcinoma.

DOI： 10.5106/jjshns.32.145

Language：Japanese   Publisher：OTO Open  

Objective: To determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC). Study Design: Retrospective cohort study. Setting: Affiliated university hospital. Methods: We reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS). Results: The 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P <.0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P <.001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P <.05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P <.001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P <.001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P <.05). Conclusion: Our study suggests that the HS-mGPS is useful as prognostic factor in HSCC.

DOI： 10.1177/2473974X211067423

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Language：Japanese   Publisher：Diagnostic Pathology  

DOI： 10.1186/s13000-021-01146-8

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Language：Japanese   Publisher：BMC Microbiology  

DOI： 10.1186/s12866-021-02217-y

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Language：English   Publishing type：Research paper (scientific journal)  

The nasal mucosa functions as a frontline biological defense against various foreign substances and pathogens. Maintaining homeostasis of the nasal epithelium is necessary to promote good health. Nasal epithelia are constantly replaced under normal conditions. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Since there is no treatment for this underlying condition, extrinsic manipulation is necessary to recover and maintain nasal epithelia in cases of hereditary diseases. In this study, we explored the use of airway epithelial cells (AECs), including multi-ciliated airway cells (MCACs), derived from human induced pluripotent stem cells (hiPSCs) on porcine atelocollagen vitrigel membranes, as a candidate of a therapeutic method for irreversible nasal epithelial disorders. To confirm the regenerative capacity of iPSC-derived AECs, we transplanted them into nasal cavities of nude rats. Although the transplanted cells were found within cysts isolated from the recipient nasal respiratory epithelia, they survived in some rats. Furthermore, the surviving cells were composed of multiple cell types similar to the human airway epithelia. The results could contribute to the development of novel transplantation-related technologies for the treatment of severe irreversible nasal epithelial disorders.

DOI： 10.1089/ten.TEA.2021.0071

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Diabetes insipidus (DI) is a well-known complication of transsphenoidal surgery. However, the risk factors for DI remain controversial. METHODS: We conducted a retrospective study of patients who underwent endoscopic transsphenoidal surgery for pituitary adenoma at our institution during a 5-year period. The patients were divided into a DI group and a non-DI group. Logistic regression analyses were used to identify risk factors for postoperative DI. In subgroup analysis, the DI group was divided into transient DI and permanent DI groups, and perioperative factors were compared between groups. RESULTS: Of 101 patients, 58 were in the non-DI group (57.4%) and 43 were in the DI group (42.6%). Permanent DI occurred in 7 patients (6.9%). In univariate analyses, statistically significant risk factors were suprasellar extension, tumor functionality, and intraoperative cerebrospinal fluid leaks by Esposito grade. In multivariate logistic regression analysis, Esposito grade was the only statistically significant risk factor (P = 0.015). The frequency of DI increased as the Esposito grade increased (P = 0.0002 for the trend). In subgroup analysis, postoperative nadir sodium concentration was lower in the permanent DI group (128.1 ± 2.78 mmol/L) than in the transient DI group (135 ± 1.22 mmol/L; P = 0.035), and the optimal cutoff value was 124.5 mmol/L, with a sensitivity of 57.1% and a specificity of 91.7% (area under the curve = 0.76, P = 0.034). CONCLUSIONS: Intraoperative cerebrospinal fluid leak by Esposito grade is associated with postoperative DI. These data can be applied to help identify high-risk patients who need more aggressive follow-up and fluid management.

DOI： 10.1016/j.wneu.2021.11.090

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: A histopathological tumor thickness of ≥1000 μm has been reported as one of many risk factors for recurrent lymph node metastasis in superficial pharyngeal cancer (SPC). However, methods for assessing this risk factor preoperatively have not yet been established. Hence, the current study aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in measuring tumor thickness preoperatively in patients with SPC. METHODS: This single-center retrospective study included 44 consecutive patients with 47 lesions who underwent endoscopic submucosal dissection (ESD). Prior to surgery, EUS examination was performed while under general anesthesia. Further, microvascular irregularity in the target lesion was evaluated using the Japan Esophageal Society (JES) magnification endoscopic classification system. RESULTS: A significant correlation was noted between histopathological and EUS tumor thickness (Spearman's correlation r == 0.879, p < 0.001). In tumors ≥1000 µm thick on histopathology, the cutoff value for EUS tumor thickness was 2.6 mm, and the following values were obtained: sensitivity, 100%; specificity, 81.8%; positive predictive value (PPV), 70%; negative predictive value (NPV), 100%; and accuracy, 87.2%. In B2 lesions ≥1000-μm thick, the following values were obtained: sensitivity, 85.7%; specificity, 90.9%; PPV, 80%; NPV, 93.8%; and accuracy, 89.4%. The diagnostic accuracy rate of combined EUS and the JES magnifying endoscopic classification system was 95.7%. CONCLUSIONS: Tumor thickness assessed using EUS was effective in diagnosing histopathological tumor thickness of ≥1000 μm. The combined use of EUS and the JES magnifying endoscopic classification system may be useful for assessing preoperative risk factors for lymph node metastasis in SPC.

DOI： 10.1016/j.anl.2021.11.003

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1411202792

Language：English   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

インスリン様成長因子1(IGF1)が気道上皮化に及ぼす影響を検討した。13週齢のICRマウスを用いて気道を切除し小型プレート切片を作製して、免疫組織化学染色によってIGF1受容体の発現を測定した。さらに、気道切片を7日間培養し、形態学的変化の有無を調査した。このほか、気道プレートをIGF1 0、0.1、1、10μg/mLの濃度で48時間培養し気道上皮の伸長を測定した。検討の結果、マウスの気道上皮にある全タイプの細胞においてIGF1受容体の免疫活性が認められた。7日間培養後の形態をみると上皮、基底膜、気道軟骨を含めた層構造は温存されており、気道上皮細胞にみられる細胞内結合も7日間を通して保持されていた。気道線毛も維持されており、気道培養による形態的変化は観察されなかった。また、IGF1 0.1、1、10μg/mLを添加したところ、非添加時と比較して気道上皮の伸長が有意に増加していた。IGF1の局所投与により気道上皮の伸長が促進されることが明らかになり、気道再建を要する患者に対してもIGF1投与が有用である可能性が示された。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

多形腺腫内部から生じる癌腫carcinoma ex-pleomorphic adenoma(ex-PA)の構成成分として、上皮-筋上皮癌(EMCa)を発症したEMCa ex-PAの稀少例について、免疫組織化学的/遺伝学的解析を行ったため報告した。症例は83歳女性で、1年前に多形腺腫(PA)疑いと診断され、右耳下腺部腫瘤が急速に増大したため当院に入院となった。腫瘤の穿刺吸引生検により悪性腫瘍が疑われたため、右耳下腺全摘出術を行った。病理組織検査により、結節は硝子化間質で、腫瘍は内側導管細胞と外側筋上皮細胞で構成された二層構造で観察された。また、免疫組織化学的解析結果では内側細胞はEMA陽性で、外側細胞はp40陽性を呈し、遺伝学的解析結果ではHRAS遺伝子変異は検出されなかったが、FISH法によりPleomorphic Adenoma Gene1遺伝子にスプリットシグナルが検出されたことから、EMCa ex-PAと確定診断された。しかし、9ヵ月後に撮像されたFDG-PETで局所再発が認められ、腫瘍切除と放射線療法により再発や転移もなく6年間生存が得られたが、その後原発性肺癌と多発肝転移を伴い死亡した。本例から、EMCa ex-PA診断では筋上皮癌および明細胞癌との鑑別が重要であり、鑑別にはFISH法が有用と考えられた。

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1411202596

Language：Japanese   Publisher：OTO Open  

DOI： 10.1177/2473974X211042302

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Language：Japanese   Publisher：International Journal of Surgical Pathology  

DOI： 10.1177/10668969211036942

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Language：Japanese   Publisher：Otolaryngology - Head and Neck Surgery (Japan)  

Objective: To evaluate the effectiveness of hyperbaric oxygen therapy (HBOT) in the treatment of patients with idiopathic sudden sensorineural hearing loss (ISSHL). Material and methods: Patients with ISSHL were divided into two groups. Steroid therapy group consisted of 35 patients who were treated with steroids and without HBOT. Combination therapy group consisted of 67 patients who were treated with steroids and HBOT. Results: In Grade 3 of 8000 Hz ISSHL patients, significant benefit was observed in the combination therapy group. However, in Grade 4 of ISSHL patients, no significant difference was demonstrated between the two groups. Conclusions: The effect of HBOT is restrictive.

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Language：Japanese   Publisher：Otolaryngology - Head and Neck Surgery (Japan)  

Although multiple sclerosis is a disease that manifests with multiple neurologic symptoms, it rarely presents with isolated acute hearing loss. Here, we report a case of multiple sclerosis in a 27-year-old man presenting with sudden sensorineural hearing loss. Despite experiencing severe sensorineural hearing loss, distortion product optoacoustic emissions amplitude was detected. Abnormal auditory evoked brainstem response and magnetic resonance imaging revealed that it is the first attack of multiple sclerosis. Treatment with steroid pulse therapy, immunoadsorption, and plasmapheresis completely restored his hearing. This case highlights the importance of considering multiple sclerosis in patients with acute sensorineural hearing loss.

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Language：Japanese   Publisher：Otolaryngology - Head and Neck Surgery (Japan)  

Objective: To evaluate the effectiveness of hyperbaric oxygen therapy (HBOT) in the treatment of patients with idiopathic sudden sensorineural hearing loss (ISSHL). Material and methods: Patients with ISSHL were divided into two groups. Steroid therapy group consisted of 35 patients who were treated with steroids and without HBOT. Combination therapy group consisted of 67 patients who were treated with steroids and HBOT. Results: In Grade 3 of 8000 Hz ISSHL patients, significant benefit was observed in the combination therapy group. However, in Grade 4 of ISSHL patients, no significant difference was demonstrated between the two groups. Conclusions: The effect of HBOT is restrictive.

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Language：Japanese   Publisher：Otolaryngology - Head and Neck Surgery (Japan)  

Although multiple sclerosis is a disease that manifests with multiple neurologic symptoms, it rarely presents with isolated acute hearing loss. Here, we report a case of multiple sclerosis in a 27-year-old man presenting with sudden sensorineural hearing loss. Despite experiencing severe sensorineural hearing loss, distortion product optoacoustic emissions amplitude was detected. Abnormal auditory evoked brainstem response and magnetic resonance imaging revealed that it is the first attack of multiple sclerosis. Treatment with steroid pulse therapy, immunoadsorption, and plasmapheresis completely restored his hearing. This case highlights the importance of considering multiple sclerosis in patients with acute sensorineural hearing loss.

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Rapid epithelialization is crucial to maintain tracheal patency and prevent potential graft failure in tracheal reconstruction after tracheal resection for cancer with tracheal infiltration or tracheal stenosis. Insulin-like growth factor 1 is a liver-secreted endocrine molecule that controls cell proliferation, differentiation, and apoptosis and has been reported to promote epithelialization in several organs. Here, we utilized mouse tracheal organ cultures to examine the effect of insulin-like growth factor 1 on tracheal epithelialization. METHODS: The trachea was resected from thirteen-week-old female ICR mice, and cut into small plate-shaped tracheal sections. First, the expression of insulin-like growth factor 1 receptor was assessed by immunohistochemistry. Secondly, the tracheal sections were cultured for seven days in the culture medium, and the morphological change during the seven-day culture was assessed by immunohistochemistry, hematoxylin and eosin staining, and scanning electron microscopy. Moreover, the tracheal sections were cultured for 48 h with different concentration of insulin-like growth factor 1 (0, 0.1, 1 and 10 µg/mL) in the culture medium, and the extension length of the tracheal epithelium during culture was measured in order to assess the effect of topical IGF1 on tracheal epithelialization. RESULTS: Immunohistochemistry showed that insulin-like growth factor 1 receptor was expressed in tracheal epithelium. Immunohistochemistry, hematoxylin and eosin staining, and scanning electron microscopy showed that the tracheal organ cultures were stable for at least seven days without apparent morphological damage. The effect of insulin-like growth factor 1 on tracheal epithelialization was examined in plate-shaped tracheal sections cultured in medium supplemented with or without insulin-like growth factor 1 for 48 h. We also found that the epithelial edge of plate-shaped tracheal sections extended further along the surface of the tracheal section in culture medium containing insulin-like growth factor 1 compared with that in culture medium without insulin-like growth factor 1. CONCLUSION: The current study using an in vitro mouse tracheal organ culture model demonstrated that topical insulin-like growth factor 1 treatment promoted the extension of tracheal epithelium, suggesting the potential utility of insulin-like growth factor 1 in aiding rapid tracheal epithelialization in patients requiring tracheal reconstruction using tissue-engineered tracheas.

DOI： 10.1016/j.anl.2020.09.017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

<sec><title>Objective</title> To investigate the predictive accuracies of the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) as prognostic factors for patients with hypopharyngeal squamous cell carcinoma (HSCC).

</sec><sec><title>Study Design</title> Retrospective study.

</sec><sec><title>Setting</title> University hospital.

</sec><sec><title>Methods</title> The records of 106 patients who were histologically diagnosed with HSCC between January 2007 and December 2017 were reviewed. mGPS, NLR, and PLR were analyzed; univariate and multivariate analyses were performed to evaluate the prognosis of overall survival (OS).

</sec><sec><title>Results</title> The overall 5-year survival rates of patients with mGPS0, mGPS1, and mGPS2 were 82.0%, 41.9%, and 13.5%, respectively. The overall 5-year survival rates of patients with low and high NLRs and with low and high PLRs were 83.8%, 46.2%, 57.0%, and 59.1%, respectively. mGPS ( P &lt; .001) and NLR ( P &lt; .05) were independently associated with OS, whereas PLR was not. For stage IV HSCC, only mGPS was independently associated with OS ( P = .004).

</sec><sec><title>Conclusion</title> mGPS is an excellent prognostic factor for patients with HSCC.

</sec>

DOI： 10.1177/2473974x20978137

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/2473974X20978137

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES/HYPOTHESIS: To regenerate defected recurrent laryngeal nerves (RLNs), various methods have been developed. However, no consistently effective treatments are currently available because of their insufficient functional recovery. RADA16-I, a self-assembling peptide used clinically as a hemostat, reportedly supports neurite outgrowth and functional synapse formation in vitro. The purpose of this study was to investigate the effect of RADA16-I hydrogels on transected RLNs in rats. STUDY DESIGN: Animal experiments with controls. METHODS: Fifteen adult rats were divided into the following three groups: RADA16-I (+), RADA16-I (-), and neurectomy. A 6-mm gap of the left RLN was bridged using an 8-mm silicone tube in the RADA16-I (-) and RADA16-I (+) groups. Subsequently, RADA16-I hydrogel was injected into the tube in the RADA16-I (+) group. The surgical incisions were closed without any further treatment in the neurectomy group. After 8 weeks, laryngoscopy and electrophysiological and histological examinations were performed to evaluate the effect of RADA16-I on nerve regeneration and thyroarytenoid muscle atrophy. RESULTS: Although most rats in the three groups exhibited no improvements of their vocal fold movement, partial recovery was observed in one rat in the RADA16-I (+) group. The neurofilament-positive areas and the number of myelinated nerves in the RADA16-I (+) group were significantly higher than in the RADA16-I (-) group. The area of the left thyroarytenoid muscle in the RADA16-I (+) group was significantly larger than that of the neurectomy group. CONCLUSIONS: Our results suggested that RADA16-I hydrogel was effective for RLN regeneration. LEVEL OF EVIDENCE: NA Laryngoscope, 130:2420-2427, 2020.

DOI： 10.1002/lary.28434

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Language：Japanese   Publisher：The Oto-Rhino-Laryngological Society of Japan, Inc.  

<p>　In this report, we present the positive surgical outcomes, in the form of satisfactory air-bone hearing restoration, for six ears of patients who presented with sensorineural hearing loss, diagnosed by audiometry, as a result of fixed lesions of the ossicles (excluding the stapes footplate). The average preoperative air-bone conduction difference in the six ears was 7.8dB, which was considered to be a small gap. However, as both otoscopy and high-resolution temporal bone CT revealed ossicular fixation, “defixation” surgery was performed. There were 4 cases of fixation of the malleus head to the epitympanic wall and 2 cases of fixation of the incus body to the lateral attic wall. After the release of the ossicular bones via a transcanal atticotomy approach, a hearing improvement in air conduction of 18.6dB, on average, and in bone conduction of 15.3dB, on average, was recorded. We concluded that among cases of suspected sensorineural hearing loss diagnosed based on audiogram data, there are cases in which significant improvement in the hearing ability can be achieved through ossicular bone release. Six cases are presented and discussed in this report.</p>

DOI： 10.3950/jibiinkoka.123.1183

Language：English   Publishing type：Research paper (scientific journal)  

Multiciliated epithelial cells in the airway are essential for mucociliary clearance. Their function relies on coordinated, metachronal and directional ciliary beating, appropriate mucus secretion and airway surface hydration. However, current conventional methods for observing human airway ciliary movement require ciliated cells to be detached from airway tissues. Determining the directionality of cilia is difficult. We developed a novel method to stain airway epithelial cilia to observe their movement without releasing ciliated cells. Human tracheae were obtained from patients (n = 13) who underwent laryngectomies to treat malignancies or swallowing disorders. The tracheae were treated with fluorescently labeled wheat germ agglutinin, which interacts with the acidic mucopolysaccharides present on the cilia. Epithelial surfaces were observed using an epi-fluorescence microscope equipped with a water-immersion objective lens and a high-speed camera. Ciliary movement was observable at 125 fps (13/13 samples). Ciliated cells in close proximity mostly exhibited well-coordinated ciliary beats with similar directionalities. These findings indicated that wheat germ agglutinin renders ciliary beats visible, which is valuable for observing human airway ciliary movements in situ.

DOI： 10.1038/s41598-020-71049-z

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Epithelial-myoepithelial carcinoma (EMCa) is a rare low-grade salivary malignancy. It is rare for EMCa to occur as the carcinomatous component of carcinoma ex-pleomorphic adenoma (PA). We examined one additional case of EMCa ex-PA, immunohistochemically and genetically. The patient was an 83-year-old female, who suffered from swelling of the right parotid region. Histologically, the tumor contained a hyalinized nodule, which displayed elastosis. The main tumor exhibited a bi-layered structure, involving inner ductal cells and clear outer myoepithelial cells. Immunostaining indicated that the inner cells were positive for epithelial membrane antigen, whereas the outer cells were positive for p40. On the genetic level, the carcinoma harbored no HRAS gene mutations, whereas fluorescence in situ hybridization (FISH) of the Pleomorphic Adenoma Gene1 showed splitting signals in the carcinomatous component. We diagnosed this case as EMCa ex-PA. It is necessary to differentiate EMCa ex-PA from myoepithelial carcinoma and clear cell carcinoma, and FISH is useful for such purposes.

DOI： 10.1007/s00795-020-00262-6

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Language：Japanese   Publisher：静岡県立総合病院  

人工内耳埋め込み術は両側高度感音難聴患者の聴力再獲得のために有力な手段である。先天聾の患者では、より早期からの聴覚刺激が聴覚脳、音声コミュニケーションの発達に重要であるとして、人工内耳埋め込み術の低年齢化が進み人工内耳を装用して過ごすlife timeは延長している。また、合併症を有する高齢者への人工内耳埋め込み術を施行する機会も増えており、人工内耳埋め込み術後にMRI検査が必要となる機会が増えている。人工内耳装用患者に対するMRIは、磁石が組み込まれている機器であるという点で事前の厳重な配慮が必要である。現在本邦で発売されている埋め込み人工内耳デバイスは、予防策を講じれば1.5テスラまでのMRI撮影が磁石を摘出せずに施行可能とされ、各社ガイドラインを提供している。今回、その手順に従ってMRI撮影をしたが、埋め込みインプラントの磁石が逸脱した症例を経験したので報告する。症例は44歳女性、Alport症候群による両側重度難聴のため、43歳時に左人工内耳埋め込み術(Cochlear社製CI512)を施行された。その約6ヵ月後に視力低下をきたし、その精査目的でMRI検査を受けることになった。人工内耳埋め込み術後患者のMRI検査に対するガイドラインに準じて、放射線科技師が頭部の包帯圧迫固定を行ったうえで検査を施行したが、初回のMRI検査で人工内耳磁石がシリコンポケットのフランジから半分逸脱し、観血的整復術を要した。ステロイド長期投与例では皮膚および骨膜の脆弱により磁石が逸脱しやすい可能性も考えられ、より慎重な対応と注意喚起が必要と考えられた。(著者抄録)

Language：Japanese   Publisher：静岡県立総合病院  

頸部刺創は頻度としては稀であるが、頸部には気道、消化管、大血管など生命維持に必要な器官が集まっており、それらが損傷することで致命的となり得る。今回、我々は咽頭切創と舌動脈の切断を伴った頸部刺創の一例を経験したので報告する。症例は40代男性、頭部、頸部など複数箇所を包丁にて刺され当院救急外来へ搬送された。到着直後から次第に呼吸困難を生じ、徐々に増悪したため気管内挿管が行われた。創部精査のため施行した造影CT検査においては、左舌動脈の途絶と左頸部から鎖骨上窩に至る広範な皮下気腫を認めた。口腔内から持続的出血を認めていたため当科紹介となり、緊急手術を施行することとなった。出血源は離断していた左舌動脈であり、これを結紮止血した。頸部の最も深い刺創は正面皮膚から中咽頭左側を前後に貫通し頸椎横突起付近に達していた。創部を十分な生理食塩水にて洗浄し、前後の咽頭粘膜縫合および皮膚縫合を行い手術を終了した。術後、濃厚赤血球輸血を行ったものの、その後の経過は順調であり、抜管、経口摂取も問題なく可能であった。神経障害も認めず術後12日目に退院となった。従来、頸部刺創はその損傷部位によって解剖学的に3つの領域(I:胸骨切痕から輪状軟骨の高さ、II:輪状軟骨から下顎角の高さ、III:下顎角から頭蓋底の高さ)に分類(Zone分類)されてきた。本症例では最も高頻度のZone IIの部位に該当し、損傷した血管の処理と創部閉鎖で良好な経過を認めた。幸い喉頭気管損傷は認めなかったため気管切開は不要であった。頸部刺創例において、緊急度が高く生じやすい病態には気道閉塞と出血による循環異常がある。喉頭気管損傷や血液による窒息、大血管損傷による出血性ショックなどは致死的となる。早期に損傷の部位および程度を評価し、適切かつ迅速な対応を行うことが必要である。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To evaluate long-term olfactory outcomes in patients who underwent pituitary surgery through the endoscopic endonasal transsphenoidal approach (EETSA) by T&T olfactometer. METHODS: We retrospectively reviewed 26 patients who underwent pituitary surgery via EETSA. Olfactory function was assessed by T&T olfactometer before and 6 months after surgery. The mean of recognition thresholds for five different odorants was used. The change in the mean recognition threshold values was evaluated in the entire cohort and the subgroup analysis was performed according to the age, sex, past history of pituitary surgery (primary surgery or revision surgery), histopathology (non-functioning adenoma (NFA) or functioning adenoma (FA)), reconstruction procedure (rescue flap or nasoseptal flap), and superior turbinate management (preserved or resected). RESULTS: Of the 26 patients (12 men and 14 women, median age 53 years), 21 patients were newly diagnosed with pituitary gland tumor (16 NFAs, 5 FAs) and the remaining 5 were diagnosed with recurrent pituitary gland tumor (4 NFAs and 1 FA). In the whole cohort, the mean recognition threshold values of T&T olfactometer significantly improved after surgery (P=0.01). Thirteen out of 26 patients (50%) showed olfactory improvement, whereas only 3 (12%) showed deterioration. In the subgroup analysis, olfactory function outcomes were not significantly different between the subgroups with respect to the age, sex, past history of pituitary surgery, histopathology, reconstruction procedure, or superior turbinate management. The olfactory function tended to worsen in the revision surgery group compared to that in the primary surgery group, but not significantly (P=0.06). CONCLUSIONS: The olfactory function was improved or maintained after pituitary surgery via EETSA in 88% of patients, indicating the benefits of low invasiveness of our surgical treatment. On the other hand, three patients (12%) demonstrated deterioration of olfactory function, suggesting that the risk of postoperative olfactory dysfunction should be informed to patients.

DOI： 10.1016/j.anl.2019.07.002

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Language：Japanese   Publisher：(NPO)日本気管食道科学会  

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Language：English   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

内視鏡下経鼻経蝶形骨アプローチ(EETSA)を介して下垂体手術を受けた患者にみられる長期嗅覚アウトカムについて検討した。下垂体手術を施行した下垂体腺腫患者26例(男性12例、女性14例、中央値53歳)を対象に、術前と術後6ヵ月にT&T嗅覚計を用いて嗅覚機能を評価した。術前における嗅覚計検査では認知閾値は-0.4～5.6であり、正常が6例、軽度嗅覚障害が8例、中等度嗅覚障害が8例、重度嗅覚障害が3例、無嗅覚が1例であった。術後6ヵ月における嗅覚計検査の結果、認知閾値は0.2～5.4と有意に改善しており、正常が13例、軽度嗅覚障害が8例、中等度嗅覚障害が4例、重度嗅覚障害が1例で、無嗅覚例はなかった。嗅覚改善は13例(50%)、安定は10例(38%)、悪化は3例(12%)となっていた。また、年齢、性別、下垂体手術の既往、組織病理学的所見、再建術式および上鼻甲介処理が術後嗅覚機能に及ぼす有意な影響は認められなかったが、再手術施行群では嗅覚機能が悪化する傾向にあった。EETSAによる下垂体手術後、症例の88%で嗅覚の改善または安定が得られていた。

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 2019 The Author(s) Vocal fold (VF)mucosal fibrosis results in substantial voice impairment and is recalcitrant to current treatments. To reverse this chronic disorder, anti-fibrotic therapies should target the molecular pathology of aberrant collagen accumulation in the extracellular matrix. We investigated the therapeutic potential of siRNA against Serpinh1, a collagen-specific chaperone that enables cotranslational folding and assembly of procollagens in the endoplasmic reticulum. We implemented a previously validated siRNA construct, conducted transfection experiments using in vitro and in vivo rat models, and measured knockdown efficiency, dose responses, delivery strategies, and therapeutic outcomes. Liposome-mediated delivery of Serpinh1-siRNA downregulated collagen production in naive and scar VF fibroblasts as well as naive VF mucosa; moreover, sustained Serpinh1 knockdown in fibrotic VF mucosa reversed scar-associated collagen accumulation within 4 weeks. Analysis of therapeutic effects at the transcriptome level showed evidence of cell cycle upregulation, catabolism, matrix disassembly, and morphogenesis. These findings indicate that Serpinh1-siRNA holds potential as a molecular therapy for chronic VF mucosal fibrosis.

DOI： 10.1016/j.omtn.2019.04.014

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© 2019 John Wiley & Sons, Ltd. Tracheal resection is often performed for malignant tumours, congenital anomalies, inflammatory lesions, and traumatic injuries. There is no consensus on the best approach for the restoration of tracheal functionality in patients with tracheal defects. Artificial grafts made of polypropylene and collagen sponge have been clinically used by our group. However, 2 months are required to achieve adequate epithelialization of the grafts in humans. This study aimed to investigate the feasibility of transplantation therapy using an artificial trachea with human-induced pluripotent stem cell (hiPSC)-derived multiciliated airway cells (hiPSC-MCACs). Collagen vitrigel membrane, a biocompatible and absorbable material, was used as a scaffold to cover the artificial trachea with hiPSC-MCACs. Analyses of hiPSC-MCACs on collagen vitrigel membrane were performed by immunocytochemistry and electron microscopy and by assessing ciliary beat frequency. Along with the artificial trachea, hiPSC-MCACs were transplanted into surgically created tracheal defects of immunodeficient rats. The survival of transplanted cells was histologically evaluated at 1 and 2 weeks after the transplantation. The hiPSC-MCACs exhibited motile cilia on collagen vitrigel membrane. The surviving hiPSC-MCACs were observed in the endotracheal epithelium of the tracheal defect at 1 and 2 weeks after transplantation. These results suggest that hiPSC-MCAC is a useful candidate for tracheal reconstruction.

DOI： 10.1002/term.2849

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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© 2019 John Wiley & Sons, Ltd. Tracheal epithelia have barrier and mucociliary clearance functions that prevent invasion of extraneous particles and infectious materials. Hence, following tracheal reconstructions, functional and morphological regeneration of epithelia is required to prevent respiratory declines and infectious diseases. Although growth factors (GFs) promote the regeneration of tracheal epithelial morphologies, it remains unclear whether tracheal grafts containing GFs are beneficial for regeneration of tracheal epithelial functions. Thus, we fabricated collagen sponge scaffolds containing insulin-like GF-1 (IGF-1) and the basic fibroblast, hepatocyte, and epidermal GFs (bFGFs, HGFs, and EGFs, respectively), and we evaluated the effects of the grafts on the functional regeneration of tracheal epithelia. Partial tracheal defects were imposed surgically, and collagen sponges containing IGF-1, bFGF, HGF, or EGF were then transplanted to defect sites. Subsequent immunofluorescence studies suggested that EGF and bFGF contribute to regular distributions of tight junction molecules, and tracer permeability assays suggested that EGF and bFGF promote regeneration of barrier function. Increased ciliogenesis was also observed using scanning electron microscopy in reconstructed regions treated with EGF- and bFGF-supplemented collagen sponges. However, bFGF-supplemented collagen sponges led to greater microsphere transport than did EGF-supplemented sponges. The present data suggested that collagen sponge scaffold containing bFGF promotes functional regeneration of tracheal epithelial tissues.

DOI： 10.1002/term.2835

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© 2018 The American Laryngological, Rhinological and Otological Society, Inc. Objectives: Macrophages are prominent inflammatory cells in wounds, and their phenotypes are altered during wound healing. They are reported to contribute to not only inflammatory responses but also tissue remodeling. However, few studies in vocal fold biology have focused on the function of macrophages. The purpose of this study was to investigate macrophage polarization and distribution in injured murine vocal folds. Study Design: Animal experiments with controls. Method: Unilateral vocal fold stripping was performed on C57BL/6 mice, and larynges were harvested 1, 3, 5, 7, and 14 days postinjury. Immunohistochemical analysis of the vocal fold lamina propria was performed to detect the expression of classically activated (M1) and alternatively activated (M2) macrophage markers (inducible nitric oxide synthase [iNOS] and CD206, respectively) in F4/80 + macrophages. Results: The proportion of F4/80 + iNOS + cells out of all F4/80 + cells tended to increase from day 1. F4/80 + iNOS + cell percentage tended to be high at days 1 through 7 and declined to close to a normal level by day 14. F4/80 + CD206 + cell percentage tended to decrease at day 1 and then to increase the rest of the time. In the normal vocal fold, the majority of F4/80 + macrophages were only positive for CD206. F4/80 + iNOS + CD206 + cells were observed at days 1 through 7. Conclusion: The main population of injured sites gradually shifted from M1 to M2 marker-positive macrophages in murine vocal folds. However, coexistence of M1 and M2 markers in the same macrophages was observed. Our results suggest that macrophage phenotypes are regulated by complex tissue-derived signals and exhibit dynamic changes during wound healing. Level of Evidence: NA Laryngoscope, 129:E135–E142, 2019.

DOI： 10.1002/lary.27523

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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DOI： 10.3950/jibiinkoka.122.79

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Publisher：(一社)日本頭頸部癌学会  

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Publisher：(一社)日本頭頸部癌学会  

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Publisher：(NPO)日本呼吸器内視鏡学会  

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Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publisher：(一社)日本耳鼻咽喉科学会  

鼻腔神経芽細胞腫患者22例(男性10例、女性12例、平均49.0歳)を対象に、内視鏡下鼻内アプローチ(EEA)の安全性と有用性を後ろ向きに検討した。受診時のDulguerovステージはT1が6例、T2が9例、T3が5例、T4が2例、修正KadishステージはAが4例、Bが5例、Cが13例であった。頸部浸潤または遠隔転移をきたした症例はなく、Hyamsグレード分類ではグレードIが2例、グレードIIが19例、グレードIIIが1例であった。22例のうち12例に両側切除、10例に片側切除を施行し、20例に術後放射線療法を行った。21例に切除断端陰性が認められ、重篤な手術合併症の発現はみられなかった。平均フォローアップ期間44ヵ月において、5年無病生存率は95.5%という成績であり、再発を認めた1例も最終経過観察時に生存を認めた。この1例は初回手術の12ヵ月後に局所再発をきたし、頭蓋内アプローチを併用したEEAを施行し、術後化学療法を受けていた。鼻腔神経芽細胞腫に対する内視鏡下鼻内治療は安全で有用性が高い手技であることが示された。

Language：English   Publishing type：Research paper (scientific journal)  

© 2017 Elsevier B.V. Objective: The aim of the present study was to illustrate the safety and utility of the endoscopic endonasal approach (EEA) for the treatment of esthesioneuroblastomas (ENB). Methods: We retrospectively reviewed patients with a diagnosis of ENB between March 2008 and February 2016 at 10 tertiary referral hospitals in Japan, and assessed demographic data, stage of disease, surgical approach, outcomes and postoperative complications. Results: A total of 22 patients (10 males and 12 females; mean age at presentation, 49.0 years) underwent endoscopic endonasal resection of newly diagnosed ENBs. Dulguerov staging at presentation was T1, 6 patients; T2, 9 patients; T3, 5 patients; and T4, 2 patients. As surgical procedures, unilateral resection via EEA was performed in 12 patients aiming preservation of the contralateral olfactory system, and bilateral resection via EEA was done in 10 patients. Post-operative radiotherapy was done in 20 patients. Pathological margin studies revealed margin-free resections in 21 patients (95.5%). The mean period of follow-up was 44 months. Local recurrence was observed in one T2 patient 12 months after bilateral resection. All patients were alive at the last follow-up, and 21 patients showed no evidence of disease. No post-operative complications including bleeding, CSF leak and meningitis were identified. Preservation of olfactory function was achieved in 11 patients (91.7%). Conclusion: The results of the present study indicate the safety and utility of multilayer resection using EEA for treatment of ENBs.

DOI： 10.1016/j.anl.2017.05.001

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© 2017 The American Laryngological, Rhinological and Otological Society, Inc. Objectives/Hypothesis: The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Study Design: Animal experiments with controls. Methods: Normal and vocal fold–injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. Results: TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. Conclusions: It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. Level of Evidence: NA. Laryngoscope, 128:E150–E156, 2018.

DOI： 10.1002/lary.26959

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Language：English   Publishing type：Research paper (scientific journal)  

© 2018 The Author(s). Background: Planar cell polarity (PCP) coordinates the patterning and orientation of cells and their structures along tissue planes, and although its acquisition during the formation of airway epithelium has been described, the mechanisms for its maintenance and reconstruction are poorly understood. We aimed to clarify whether ambient environment change by orthotropic autologous transplantation affected PCP at the cellular level. Methods: We performed orthotropic autologous transplantation by inverting tracheal segments in rats, and then performed morphological evaluation by microscopy. The PCP of the tracheal epithelium was assessed over time by analyzing the directions of mucociliary transport and ciliary beat, the positional relationship between the basal body and basal foot, and the bias of Vang-like protein 1 (Vangl1) at 2, 4, and 6 months postoperatively. Results: After 2 months, the directions of mucociliary transport and ciliary beat were preserved toward the lung in the inverted tracheal segments. The positional relationship between the basal body and the basal foot, and the bias of Vangl1, also indicated preservation of PCP in the inverted tracheal segments. Similar results were obtained at 6 months. Conclusion: The PCP of ciliated epithelium was preserved in reversed trachea, even after long-term observation.

DOI： 10.1186/s12931-018-0726-y

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Language：Japanese   Publisher：耳鼻咽喉科展望会  

DOI： 10.11453/orltokyo.61.6_355

Publisher：耳鼻咽喉科展望会  

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Publisher：耳鼻と臨床会  

本邦での嗅神経芽細胞腫に対する内視鏡下経鼻手術応用の現況を調べるために、原則的に内視鏡下経鼻アプローチによるMulti-layer resectionにて手術操作を行う国内10施設による後ろ向き研究を行った。32例で内視鏡下経鼻単独手術あるいは経頭蓋併用手術が行われており、30例が新鮮例、2例が再発例であった。Dulguerovの病期分類でT1:6例、T2:10例、T3:8例、T4:8例であった。内視鏡下経鼻単独手術例は24例、経頭蓋併用が8例であった。32例中31例で病理組織学的な断端陰性であった。重篤な術後合併症は認められなかった。嗅覚温存手術を行った14例中13例で嗅覚温存が可能であった。平均観察期間40.3ヵ月で、1例で局所再発、1例で遠隔転移が認められたが、観察期間中の死亡例はなかった。以上から、嗅神経芽細胞腫の手術治療において、内視鏡下経鼻手術は有用なアプローチと考えられ、本アプローチの鼻腔および篩骨洞悪性腫瘍への適切な応用が次の課題と考えられる。(著者抄録)

Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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Publisher：耳鼻と臨床会  

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Publisher：耳鼻咽喉科臨床学会  

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Publisher：(一社)日本頭頸部癌学会  

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Publisher：(一社)日本頭頸部癌学会  

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Publisher：(一社)日本耳鼻咽喉科学会  

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Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：耳鼻と臨床会  

本邦での嗅神経芽細胞腫に対する内視鏡下経鼻手術応用の現況を調べるために、原則的に内視鏡下経鼻アプローチによるMulti-layer resectionにて手術操作を行う国内10施設による後ろ向き研究を行った。32例で内視鏡下経鼻単独手術あるいは経頭蓋併用手術が行われており、30例が新鮮例、2例が再発例であった。Dulguerovの病期分類でT1:6例、T2:10例、T3:8例、T4:8例であった。内視鏡下経鼻単独手術例は24例、経頭蓋併用が8例であった。32例中31例で病理組織学的な断端陰性であった。重篤な術後合併症は認められなかった。嗅覚温存手術を行った14例中13例で嗅覚温存が可能であった。平均観察期間40.3ヵ月で、1例で局所再発、1例で遠隔転移が認められたが、観察期間中の死亡例はなかった。以上から、嗅神経芽細胞腫の手術治療において、内視鏡下経鼻手術は有用なアプローチと考えられ、本アプローチの鼻腔および篩骨洞悪性腫瘍への適切な応用が次の課題と考えられる。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00581&link_issn=&doc_id=20171228090007&doc_link_id=10.11334%2Fjibi.63.Suppl.1_S60&url=https%3A%2F%2Fdoi.org%2F10.11334%2Fjibi.63.Suppl.1_S60&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：耳鼻咽喉科展望会  

DOI： 10.11453/orltokyo.60.6_319

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Head and Neck Cancer  

© 2017, Japan Society for Head and Neck Cancer. All rights reserved. A tracheal resection is sometimes required because of malignancies or stenosis due to traumas or inflammatory diseases, and the consequent tracheal defect causes cosmetic and functional problems. Although early closure of the stoma is expected, the closure of a huge stoma is still challenging. We have developed an artificial trachea according to the concept of in situ tissue engineering in the past few decades, aiming to establish a safe and easy procedure for tracheal reconstruction. The long-term safety and efficacy of our in situ regeneration-inducing artificial trachea composed of a porcine collagen sponge and polypropylene framework have been confirmed by previous non-clinical and clinical studies. In order to obtain approval for our in situ regeneration-inducing artificial trachea as a new medical device under Japan’s Pharmaceutical and Medical Device Law, we are now running a multi-institutional, investigator-initiated clinical trial of tracheal reconstruction using our artificial trachea. Patients with a stoma unable to be reconstructed with existing treatment options, or with malignancies affecting no less than half of the tracheal cartilage as well as three tracheal rings, will be included in this trial. When the safety and efficacy of the artificial trachea are proven with this trial, we plan to apply for approval of the artificial trachea as a new medical device.

DOI： 10.5981/jjhnc.43.367

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Language：Japanese   Publisher：耳鼻と臨床会  

気管は生命維持に不可欠な臓器であるが、時として悪性腫瘍、もしくは、外傷、炎症などによる狭窄性疾患のため切除を余儀なくされる。切除により生じる気管欠損は整容的にも、機能的にもハンディキャップとなるため、早期の閉鎖が望ましいが、大きな欠損の再建には難渋することも多い。気管の安全かつ簡便な再建方法の確立を目指して、われわれはかねてよりin situ tissue engineeringのコンセプトに基づき人工気管の開発に取り組んできた。コラーゲンの足場をポリプロピレンで補強した生体内組織再生誘導型人工気管は、非臨床試験で長期的な安全性、有効性が確認されており、さらに、施設内倫理委員会の承認のもと行った臨床研究でも良好な治療成績が確認されている。現在われわれは、この人工気管の医療機器としての薬事承認および保険収載を最終的な目標とし、有効性、安全性を確認するための多施設共同医師主導治験を行っている。対象は既存治療で気管切開孔を閉鎖できない患者と悪性腫瘍切除に伴い気管軟骨の1/2周以上かつ3輪以上の欠損が生じることが予想される患者である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00581&link_issn=&doc_id=20171101010006&doc_link_id=10.11334%2Fjibi.63.5_183&url=https%3A%2F%2Fdoi.org%2F10.11334%2Fjibi.63.5_183&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.67.99

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Other Link： http://search.jamas.or.jp/link/ui/2016228753

Publisher：耳鼻咽喉科臨床学会  

症例は60歳男性で、HBV関連慢性肝炎と肝硬変の既往があった。肝細胞癌に肝動脈化学塞栓療法、ラジオ波焼灼術で肝内病変は制御されていた。FDG-PET CTで肝門部リンパ節と左蝶形骨洞に集積を認め、左蝶形骨洞病変精査で当科を受診した。造影CTで左蝶形骨洞内に腫瘤陰影を認め、蝶形骨洞上壁と翼口蓋窩に骨破壊を伴い、腫瘍前縁は中鼻甲介基板まで達していた。造影MRIで左蝶形骨洞から翼口蓋窩、中頭蓋窩底、海綿静脈洞に達する腫瘍を認め、血管造影で栄養血管が外頸動脈の分岐と判明し、左頸動脈をコイル塞栓した。鼻内内視鏡下採取組織の病理所見は低分化悪性腫瘍だが肝細胞癌転移と断定できず、肛門部リンパ節郭清の組織像が一致し、肝細胞癌の転移と診断した。動脈塞栓術後に蝶形骨洞病変の縮小を認め、全身化学療法と姑息的照射を行い、FDG-PET CTで左蝶形骨洞の集積消失を認めたが、肛門部リンパ節再発、大腿骨転移、全身状態悪化で塞栓術後4年6ヵ月に死亡した。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved. OBJECTIVE: Spasmodic dysphonia (SD) is a complex neurological communication disorder characterized by a choked, strain-strangled vocal quality with voice stoppages in phonation. Its symptoms are exacerbated by situations where communication failures are anticipated, and reduced when talking with animals or small children. Symptoms are also reduced following selected forms of treatment. It is reasonable to assume that surgical alteration reducing symptoms would also alter brain activity, though demonstration of such a phenomenon has not been documented. The objective of this study is to reveal brain activity of SD patients before and after surgical treatment.METHODS: We performed lateralization thyroplasties on three adductor SD patients and compared pre- and post-operative positron emission tomography recordings made during vocalization.RESULTS: Pre-operatively, cordal supplementary motor area (SMA), bilateral auditory association areas, and thalamus were activated while reading aloud. Such activity was not observed in normal subjects. Type II thyroplasty was performed according to Isshiki's method and the strained voice was significantly reduced or eliminated in all three patients. Post-operative PET showed normal brain activation pattern with a significant decrease in cordal SMA, bilateral auditory association areas and thalamus, and a significant increase in rostral SMA compared with pre-operative recordings.CONCLUSION: This is the first report showing that treatment to a peripheral organ, which reverses voice symptoms, also reverses dysfunctional patterns of the central nervous system in patients with SD.

DOI： 10.1016/j.anl.2014.08.012

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Language：English   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

喉頭鏡検査による喉頭所見と発声障害に基づいて、内転型痙攣性発声障害(SD)と診断された被験者3例(29歳男性、32歳女性、14歳女性)に甲状軟骨形成術II型を施行し、PET画像法により術前と術後における脳賦活に変化があるかどうかについて検討した。術前では、音読時に両側の上側頭回、中側頭回、横側頭回、ブローカ野、両側の感覚運動皮質(SMC)と視覚野、補足運動野(SMA)の尾側部、小脳、右視床、左被殻が有意に賦活化した。健常者で活性化されるSMAの吻側部は賦活化されなかった。術後では右上側頭回、両側の一次聴覚野、両側のSMCと視覚野、SMAの吻側部、小脳が賦活化された。両側の聴覚連合野、SMAの尾側部、視床、小脳の活動は顕著に低下して、正常な脳活動パターンを呈した。

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：COMPANY OF BIOLOGISTS LTD  

© 2015, Company of Biologists Ltd. All rights reserved. The vocal fold (VF) mucosa confers elegant biomechanical function for voice production but is susceptible to scar formation following injury. Current understanding of VF wound healing is hindered by a paucity of data and is therefore often generalized from research conducted in skin and other mucosal systems. Here, using a previously validated rat injury model, expression microarray technology and an empirical Bayes analysis approach, we generated a VF-specific transcriptome dataset to better capture the system-level complexity of wound healing in this specialized tissue. We measured differential gene expression at 3, 14 and 60 days post-injury compared to experimentally naïve controls, pursued functional enrichment analyses to refine and add greater biological definition to the previously proposed temporal phases of VF wound healing, and validated the expression and localization of a subset of previously unidentified repair- and regeneration-related genes at the protein level. Our microarray dataset is a resource for the wider research community and has the potential to stimulate new hypotheses and avenues of investigation, improve biological and mechanistic insight, and accelerate the identification of novel therapeutic targets.

DOI： 10.1242/dmm.018366

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© Springer Japan 2015. The laryngeal framework consists of complex tissues including the thyroid cartilage, cricoid cartilage, and arytenoid cartilage. This framework contributes to protecting the inner aerodynamic tract from external impact and aids in maximizing vocal fold motion through intra-laryngeal muscular contraction. This structure is affected by malignant tumors, laryngeal trauma, congenital anomalies, stenosis, or intractable inflammatory diseases. Once this rigid structure is damaged, restoration of mechanical power sufficient to compensate for normal laryngeal function is quite difficult. Conventionally, laryngeal defects have been reconstructed with autologous tissues or flaps. These reconstructive surgeries, however, required donor tissue, skilled technique and multiple surgeries. Locoregional blood supply also had to be carefully considered to maintain living donor tissue. Tissue regeneration strategies for the laryngeal framework, therefore, have been sought to alleviate these problems. Recently, tissue engineering has attracted great attention as a means of recreating organs. There are three fundamental components in tissue engineering: Cells, scaffolds, and growth factors. Among these, scaffolds play a central role in laryngeal framework regeneration because great mechanical power is required immediately after surgery to maintain airway structure. In situ tissue engineering techniques, which allow in vivo regeneration of organs through the application of scaffolds, have shown recent advancement due to biomaterial innovations. In this chapter, current progress and limitations of laryngeal framework regeneration will be discussed. To date, intraluminal epithelialization and subepithelial tissue regeneration have achieved some success after laryngeal resection. Research into the next steps, including functional tissue regeneration and development of suitable scaffolds for children, is now warranted.

DOI： 10.1007/978-4-431-54856-0_10

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© Springer Japan 2015. We previously conducted a study in which a tracheal prosthesis was placed in dogs. The tracheal prosthesis was made from tissue regenerated from autologous cells. We successfully regenerated the mucosal epithelium and cilia along the tracheal lumen. The maximum length of the defect was six tracheal rings. Based on the results of this study, we conducted studies on clinical application of such prosthesis in human subjects with tracheal stenosis or defect after cancer surgery or injury. These studies have yielded good results. However, in clinical application for pediatric patients, a regenerated trachea must grow as the patients grow. Thus, it is necessary to develop a scaffold that has the strength to maintain a patent tracheal lumen, enables cartilage regeneration to progress, and completely degrades when regeneration is complete. There is much anticipation in future studies using cultured cartilage tissue and iPS cells.

DOI： 10.1007/978-4-431-54856-0_15

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Objectives/Hypothesis: Most cases of chronic otitis media (OMC) are associated with poor development of the mastoid air cells (MACs) and poor Eustachian tube (ET) function. We have previously reported that MAC regeneration can effectively eliminate intractable OMC. In this study, we assessed the ability of regenerated MACs to restore normal gas exchange function and contribute to improved ET function. Study Design: Clinical trial with control. Setting: General hospitals. Materials and Methods: Seventy-six patients with OMC, including cholesteatoma and adhesive otitis media, received tympanoplasty and MAC regeneration therapy. At the first-stage of tympanoplasty, artificial pneumatic bones and/or autologous bone fragments were implanted into the opened mastoid cavity. At the 2nd-stage operation, a nitrous oxide (N2O) gas study was performed in 10 patients to measure middle ear pressure (MEP). For the control group, MEP was measured in five patients with good MAC development during cochlear implantation or facial nerve decompression. ET function was measured twice in each patient, once before the 1st operation and 6 months after the second operation. Results: At the 2nd-stage operation, in all cases with regenerated MACs and in the normal control group, MEP changed after administration of N2O. In contrast, no change in MEP was observed in cases with unregenerated MACs. In 70% (n = 37/53) of the regenerated MAC group, ET function was improved, whereas improvement of ET function was observed in only 13% (n = 3/23) of the unregenerated MAC group. Conclusions: Tissue-engineered regeneration of MACs improves ET function and gas exchange in the middle ear. Laryngoscope, 2012 Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

DOI： 10.1002/lary.23626

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Language：Japanese   Publisher：(一社)日本耳科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

The vocal fold mucosa is a biomechanically unique tissue comprised of a densely cellular epithelium, superficial to an extracellular matrix (ECM)-rich lamina propria. Such ECM-rich tissues are challenging to analyze using proteomic assays, primarily due to extensive crosslinking and glycosylation of the majority of high Mr ECM proteins. In this study, we implemented an LC-MS/MS-based strategy to characterize the rat vocal fold mucosa proteome. Our sample preparation protocol successfully solubilized both proteins and certain high Mr glycoconjugates and resulted in the identification of hundreds of mucosal proteins. A straightforward approach to the treatment of protein identifications attributed to single peptide hits allowed the retention of potentially important low abundance identifications (validated by a cross-sample match and de novo interpretation of relevant spectra) while still eliminating potentially spurious identifications (global single peptide hits with no cross-sample match). The resulting vocal fold mucosa proteome was characterized by a wide range of cellular and extracellular proteins spanning 12 functional categories. © 2011 Welham et al.

DOI： 10.1371/journal.pone.0017754

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Publisher：TAYLOR & FRANCIS AS  

Conclusion: This new regenerative therapy shows great potential for the treatment of stenosis of the trachea and/or cricoids (STC). Objectives: To estimate the potential of tissue-engineered artificial trachea (AT) for treatment of STC in clinical applications. We previously reported that AT was a useful material for implantation into a tracheal defect after resection of cancer. There are many causes of stenosis of the respiratory tract and STC is particularly difficult to treat. Methods: The AT was a spiral stent composed of Marlex mesh made of polypropylene and covered with collagen sponge made from porcine skin. Three patients with STC were treated by this tissue-engineering method. All of them suffered from STC caused by long endotracheal intubations. They underwent a two-stage operation. In the first operation, after resection of the stenotic regions, the edge of the tracheal cartilage was sutured to the edge of the skin. The tracheal lumen was exposed and a T-shaped cannula was inserted into the large tracheostoma. At 3 weeks to 2 months after the first operation, the trachea and skin were separated. The trimmed AT with venous blood and basic fibroblast growth factor (b-FGF) was then implanted into the cartilage defect. Results: Postoperatively, all patients were able to breathe easily and had no discomfort in their daily activities. Six months after the second operation, we observed enough air space in the trachea and cricoid by computed tomography (CT) imaging and fiber endoscopy. © 2010 Informa Healthcare.

DOI： 10.3109/00016489.2010.496462

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Relative quantification by normalization against a stably expressed reference gene is a widely used data analysis method in microarray and quantitative real-time polymerase chain reaction (qRT-PCR) platforms; however, recent evidence suggests that many commonly utilized reference genes are unstable in certain experimental systems and situations. The primary aim of this study, therefore, was to screen and identify stably expressed reference genes in a well-established rat model of vocal fold mucosal injury. We selected and evaluated the expression stability of nine candidate reference genes. Ablim1, Sptbn1, and Wrnip1 were identified as stably expressed in a model-specific microarray dataset and were further validated as suitable reference genes in an independent qRT-PCR experiment using 2-ΔCT and pairwise comparison-based (geNorm) analyses. Parallel analysis of six commonly used reference genes identified Sdha as the only stably expressed candidate in this group. Sdha, Sptbn1, and the geometric mean of Sdha and Sptbn1 each provided accurate normalization of target gene Tgfb1; Gapdh, the least stable candidate gene in our dataset, provided inaccurate normalization and an invalid experimental result. The stable reference genes identified here are suitable for accurate normalization of target gene expression in vocal fold mucosal injury experiments. © 2010 Elsevier Inc.

DOI： 10.1016/j.ab.2010.07.021

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DOI： 10.3109/00016489.2010.496462

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Mouse experimental models are commonly utilized tools in biomedical research but remain underrepresented in vocal fold biology, presumably due to the small size of the larynx and limited description of the anatomical, cellular and extracellular composition of the vocal folds. In this study, we provide a whole-mount serial section-based histological description of vocal fold morphology of wild-type FVB strain mice, alongside a histological and immunohistochemical (IHC)-based quantitative analysis of extracellular matrix (ECM) alteration 1, 7, 14, 28, 42 and 56 days following unilateral vocal fold injury. IHC was specific for procollagen type I, collagen type I, collagen type III, collagen type IV, elastin, decorin, fibronectin and hyaluronic acid binding protein 2. The histological description confirmed the presence of a laryngeal alar structural complex in the mouse, which appears to be a morphological feature unique to rodents. The lamina propria appeared uniform without evidence of a distinct layer structure as has been reported in larger animals and humans. Time-dependent alterations in vocal fold morphology, ECM organization and ECM protein/glycoconjugate abundance were observed in injured vocal folds compared to control. The presence of a mature scar was observed between 28 and 42 days postinjury. Morphological and ECM changes following vocal fold injury in the mouse were generally consistent with those reported in other animal models, particularly the rat, although wound repair in the mouse appears to occur at a faster rate. Copyright © 2010 S. Karger AG, Basel.

DOI： 10.1159/000315476

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

Fibrocytes hold a prominent role in inflammatory and tissue repair processes in various organ systems. In this study, we identified and quantified a reactive fibrocyte population in the vocal fold mucosa postinjury using immunohistochemistry and stereological analysis. These cells, which expressed CD11b on their surface and prolyl-4-hydroxylase β (P4H-β) intracellularly, were largely restricted to the lamina propria, and were morphologically and immunochemically distinguishable from newly recruited epithelial cells. We validated our immunohistochemistry findings using flow cytometry, and additionally characterized a reactive fibrocyte population in circulating peripheral blood using a novel detection panel (CD16 -CD11b+P4H-β+). Fibrocyte recruitment peaked at 3 days postinjury in peripheral blood, and 5 days postinjury in the vocal fold mucosa. These findings suggest that circulating fibrocytes are recruited to sites of tissue injury in the vocal fold mucosa, and may play an important role in vocal fold tissue repair. The results of this study are consistent with published data from other organ systems and strongly suggest the importance of fibrocytes as therapeutic targets. Our newly reported antigen panel facilitating the direct characterization of fibrocytes via flow cytometry is a useful tool with the potential to facilitate improved study of this cell population. © 2010 by the Wound Healing Society.

DOI： 10.1111/j.1524-475X.2010.00618.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: The larynx must be resected in some cases of cancer or stenosis, and various techniques are generally employed to fill the resulting defect. No ideal way, however, has been established to restore vocal function after this form of insult. The aim of this preliminary feasibility study in a canine model was to investigate the effectiveness of a polypropylene-based tissue engineering approach to repair a partial glottal defect. Methods: Eight dogs were used in this study. A laryngeal defect involving resection of the left vocal fold was created through a thyroid cartilage window. A scaffold made of polypropylene and collagen was preclotted and wrapped with autologous fascia lata, inserted through the window, and sutured to the laryngeal defect in 5 dogs. The defect was reconstructed with an adjacent sternohyoid muscle flap in 3 control dogs. The surgical site was evaluated 3 months after operation by fiberscopic examination, computed tomographic imaging, histologic evaluation, and study of excised larynges. Results: On fiberscopic examination, the experimental group implants were completely covered with regenerated mucosa in all cases, and a favorable vocal fold contour was found in 4 of the 5 cases. One case was characterized by a concave vocal fold shape and red granulation. In the control group, the muscle flap was replaced by scarred mucosa with a concave vocal fold contour in 2 cases, and there was soft white granulation at the anterior resected edge in the third case. The histologic data revealed the regeneration of lined epithelium, subepithelial tissue, and muscle structure in both groups. The excised larynx phonatory data revealed reduced vibratory amplitude in the experimental group compared with the control group; however, excised phonation was not achieved in 2 of the 3 cases in the control group. Conclusions: This polypropylene-based tissue engineering technique appears to be a viable tool for glottal reconstruction; however, additional refinement is required to maximize long-term phonatory function. © 2010 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348941011900208

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

The vocal fold mucosa plays an important role in voice production. Its cellular composition and density frequently change under various pathological conditions, often contributing to altered extracellular matrix production, tissue viscoelasticity, and voice quality. In this study, cellular changes in the rat mucosa following a unilateral stripping injury were investigated and analyzed semi-quantitatively. Distinctive and sequential changes in cellular morphology, composition, and density were observed in the mucosa post-injury. Cellular recruitment was a major event during the early stage of injury and reached its peak level by day 5 post-injury. Several types of cells, including neutrophil-like cells, epithelial cells, and fibroblast-like cells, were sequentially recruited. The sequential emergence of reactive cell populations following injury and subsequent reconstruction of the mucosa suggests their involvement in vocal fold tissue repair and scar formation processes. © 2009 by the Wound Healing Society.

DOI： 10.1111/j.1524-475X.2009.00550.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Background: After successful trials of tracheal reconstruction using mesh-type prostheses in canine models, the technique has been applied clinically to human patients since 2002. To enhance tissue regeneration, we have applied a new tissue engineering approach to this mesh-type prosthesis. Methods: The prosthesis consists of a polypropylene mesh tube reinforced with a polypropylene spiral and atelocollagen layer. The cervical tracheas of 18 beagle dogs were replaced with the prosthesis. The collagen layer was soaked with peripheral blood in 6 of the dogs, with bone marrow aspirate in another 6, and with autologous multipotential bone marrow-derived cells (mesenchymal stem cells) in another 6. The dogs were humanely killed at 1 to 12 months after the operation. Results: All 18 dogs survived the postoperative period. Bronchoscopically, 3 of 4 dogs in the peripheral blood group showed stenosis, whereas no stenosis was evident in all 8 of the dogs in the bone marrow and mesenchymal stem cell groups 6 months after the operation. Faster epithelialization and fewer complications, such as mesh exposure and luminal stenosis, were observed in these two groups than in the peripheral blood group. Histologically, the cells from autologous bone marrow were found to proliferate into the tracheal tissue during the first month. Cilial movement in these two groups was faster than that in the peripheral blood group and recovered to 80% to 90% of the normal level. Conclusions: Bone marrow aspirate and mesenchymal stem cells enhance the regeneration of the tracheal mucosa on this prosthesis. This in situ tissue engineering approach may facilitate tracheal reconstruction in the clinical setting. © 2009 The American Association for Thoracic Surgery.

DOI： 10.1016/j.jtcvs.2008.07.072

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

Background and Objectives: Disruption of the vocal fold extracellular matrix (ECM) can induce a profound and refractory dysphonia. Pulsed dye laser (PDL) irradiation has shown early promise as a treatment modality for disordered ECM in patients with chronic vocal fold scar; however, there are limited data addressing the mechanism by which this laser energy might induce cellular and extracellular changes in vocal fold tissues. In this study, we examined the inflammatory and ECM modulating effects of PDL irradiation on normal vocal fold tissues and cultured vocal fold fibroblasts (VFFs). Study Design/Materials and Methods: We evaluated the effects of 585nm PDL irradiation on inflammatory cytokine and collagen/collagenase gene transcription in normal rat vocal folds in vivo (3-168 hours following delivery of ∼39.46 J/cm2 fluence) and VFFs in vitro (3-72 hours following delivery of 4.82 or 9.64 J/cm 2 fluence). We also examined morphological vocal fold tissue changes 3 hours, 1 week, and 1 month post-irradiation. Results: PDL irradiation altered inflammatory cytokine and procollagen/collagenase expression at the transcript level, both in vitro and in vivo. Additionally, PDL irradiation induced an inflammatory repair process in vivo that was completed by 1 month with preservation of normal tissue morphology. Conclusions: PDL irradiation can modulate ECM turn-over in phenotypically normal vocal folds. Additional work is required to determine if these findings extend to disordered ECM, such as is seen in vocal fold scar. © 2009 Wiley-Liss, Inc.

DOI： 10.1002/lsm.20839

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Vocal fold scarring remains a significant problem. Although several animal models have been developed to improve our understanding of the histopathology, the histologic features of scarred human vocal folds have rarely been reported. The present case studies aimed to define the histologic changes of scarred human vocal folds caused by cordectomy or cordotomy. Ten patients with the scarred vocal folds were involved in this study. Nine patients with early glottic cancer underwent endoscopic cordectomy, and one patient underwent superficial cordotomy for idiopathic scar. The postcordectomy or cordotomy scar was biopsied or resected 3-13 months after the original procedure. After confirming absence of any tumor in cancer patients, the remaining specimens were used in the present study. Histologic examination investigated deposition of extracellular matrix (ECM) including collagen, elastin, hyaluronic acid (HA), fibronectin, and decorin in the lamina propria of the scarred vocal folds. There was a wide range of variation in the deposition of ECM in scarred vocal folds. Excessive and disorganized collagen deposition was observed in most cases that had undergone deep resection of the lamina propria, whereas deposition of collagen was mild and well organized after superficial resection. Decorin was retained in all cases after superficial cordectomy or cordotomy, but varied after deep resection. Deposition of elastin, HA, and fibronectin varied regardless of depth of injury. Histology of scarred vocal folds may vary with degree of injury and individual healing mechanism. © 2009 The Voice Foundation.

DOI： 10.1016/j.jvoice.2007.12.002

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Language：English  

DOI： 10.1364/oe.17.006688

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DOI： 10.3950/jibiinkoka.112.104

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

The aim of this study was to measure the shear modulus of the vocal fold in a human hemilarynx, such that the data can be related to direction of applied stress and anatomical context. Dynamic spring rate data were collected using a modified linear skin rheometer using human hemilarynges, and converted to estimated shear modulus via application of a simple shear model. The measurement probe was attached to the epithelial layer of the vocal fold cover using suction. A sinusoidal force of 3 g was applied to the epithelium, and the resultant displacement logged at a rate of 1 kHz. Force measurement accuracy was 20 μg and position measurement accuracy was 4 μm. The force was applied in a transverse direction at the midmembranous point between the vocal process and the anterior commissure. The shear modulus of the three female vocal folds ranged from 814 to 1232 Pa. The shear modulus of the three male vocal folds ranged from 1021 to 1796 Pa. These data demonstrate that it is possible to obtain estimates for the shear modulus of the vocal fold while preserving anatomical context. The modulus values reported here are higher than those reported using parallel plate rheometry. This is to be expected as the tissue is attached to surrounding structures, and is under natural tension. © 2009 The Voice Foundation.

DOI： 10.1016/j.jvoice.2007.09.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: The goal of this study was to develop a surgical method for the creation of vocal fold injuries in mice, as a precursor to the use of genetically engineered mouse models in the study of vocal fold wound healing and scar formation. Methods: Seven FVB strain mice were used in this study. A laryngoscope and 3 micro-instruments were designed and fabricated to facilitate endoscopic vocal fold visualization and the creation of vocal fold surgical injuries. The larynges were harvested 1 and 7 days after surgery, and the vocal fold injury sites were evaluated by routine hematoxylin and eosin staining. Additional immunohistochemical analysis of collagen type I and elastin distribution in the lamina propria was performed for an uninjured control larynx. Results: Endoscopic visualization and vocal fold stripping resulting in thyroarytenoid muscle exposure were successful in all animals. Histologic and immunohistochemical analyses revealed a simple lamina propria structure with relatively even collagen type I and elastin distribution in the control vocal fold, obliteration of vocal fold mucosa 1 day after surgery, and complete reepithelialization by 7 days. Conclusions: These results demonstrate the feasibility of creating reproducible vocal fold injuries via an endoscopic approach in mice. The observation that the mouse lamina propria may have a relatively simple histologic structure indicates that additional characterization should be performed and caution used in translating findings between this and other model systems. © 2009 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940911800209

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Conclusion: Calcium alginate (CA) membrane prevents excessive fibrous tissue intrusion and/or dislocation of a bone scaffold. However, CA membrane did not always accelerate cranial bone regeneration. Objective: We previously reported skull regeneration using a bone substitute material (BSM), which consisted of collagen-coated beta-tricalcium phosphate and autologous bone fragments, and bone marrow-derived stromal cells (BSCs). However, excessive fibrous tissue intrusion or dislocation of the BSM occasionally interrupted bone regeneration. To avoid such problems, we examined CA membrane, which is useful for guided bone regeneration (GBR), to investigate whether this material maintains the bone regenerative space. Materials and methods: Bone defects (2×2 cm) were created in the skulls of 12 adult beagle dogs using the same clinical procedure. Four experimental models were tested with or without BSM plus BSCs or CA membrane. In group I, the original free bone flap was replaced at the defect. In group II, after replacing the bone flap, the defect was covered with CA membrane. In group III, BSM plus BSCs were used as a gap filler. In group IV, BSM plus BSCs and CA membrane were applied. Histological examinations were performed 3 and 6 months after the operation. Results: In groups I and II, bone regeneration was not observed but fibrous tissue intrusion was prevented in group II. Bone neogenesis was more observed in group III than in group IV at 3 months (p<0.05). At 6 months, the regenerated areas were larger than those observed at 3 months, but the differences between groups III and IV were not statistically significant. © 2009 Informa UK Ltd.

DOI： 10.3109/00016480902801212

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DOI： 10.11334/jibi1954.54.5_271

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: The objective of the present study was to demonstrate the efficacy of the clinical application of in situ tissue engineering using a scaffolding technique for laryngeal and tracheal tissue. Methods: We have developed a tissue scaffold made from a Marlex mesh tube covered by collagen sponge. Based on successful animal experimental studies, in situ tissue engineering with a scaffold implant was applied to repair the larynx and trachea in 4 patients. Results: In 1 patient with subglottic stenosis, the thyroid cartilage, cricoid cartilage, and cervical trachea with scarring and granulation were resected and reconstructed by use of the scaffold. In 3 patients with thyroid cancer, the trachea and cricoid cartilage with tumor invasion were resected and the scaffold was implanted into the defect. Postoperative endoscopy during the observation period of 8 to 34 months showed a well-epithelialized airway lumen without any obstruction. Conclusions: Our current technique of in situ tissue engineering using a scaffold shows great potential for use in the regeneration of airway defects. © 2008 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940811700908

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: The purpose of the current study was to demonstrate the efficacy of in situ tissue engineering of the cricoid and trachea in a canine model. Methods: Marlex mesh tube reinforced with polypropylene threads and covered by collagen sponge was used as a tissue scaffold for airway regeneration in 9 beagle dogs. The anterior half of the cricoid cartilage was resected in 5 dogs, whereas the cricoid cartilage and cervical trachea were simultaneously resected in 4 dogs. The tissue scaffold was implanted into the resultant defect. Results: Endoscopic examination showed no airway obstruction for a postoperative period of 3 to 40 months in all dogs. Granulation tissue was observed in 2 dogs, and slight mesh exposure in 1 dog, although all were asymptomatic. Light microscopy and electron microscopy showed the endolaryngeal and endotracheal lumen to be covered by ciliated epithelium. According to strain-force measurement, the framework was firmly supported by regenerated tissue, as well as the normal cricoid and trachea. Conclusions: Our current tissue scaffold provides a rigid framework for the airway, and the collagen coating invites tissue regrowth around the tube. This study presents the possibility of successful reconstruction of the cricoid and trachea with epithelial regeneration by means of in situ tissue engineering. © 2008 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940811700811

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Vocal fold scarring remains a therapeutic challenge. Our research group has indicated that bone marrow-derived stromal cells (BSCs) may have therapeutic potential in restoration of injured vocal folds. However, it is still unclear how BSCs restore the viscoelasticity of vocal fold mucosa. Since a feature of vocal fold scarring is the disorganization of the extracellular matrix (ECM), it is important to understand how BSCs produce ECM. The present study aimed to clarify ECM gene expression in BSCs, and also examined the effects of hepatocyte growth factor (HGF) on this expression. BSCs obtained from the femurs of four Sprague-Dawley rats were cultured with or without HGF. The mRNA expression of ECM components (type I procollagen, decorin, Has2, CD44, MMP-1, and GAPDH) were examined in cultured BSCs and the vocal fold mucosa by the reverse transcription-polymerase chain reaction (RT-PCR). The mRNA expression of Has2 and MMP-1 was significantly stronger in BSCs than in the vocal folds (P < 0.05). Expression of Has2 in BSCs was significantly increased by the administration of HGF (P < 0.05). There was no significant difference in the gene expression of other ECM molecules between BSCs and vocal fold mucosa. Increased expression of Has2 and MMP-1 genes from BSCs may have a positive potential in the treatment of vocal fold scarring. © 2007 Springer-Verlag.

DOI： 10.1007/s00405-007-0522-7

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Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

It is important to fully expose the posterior glottis to achieve adequate phonomicrosurgical resection of lesions in the posterior glottis. However, it is often difficult to obtain a sufficient view of the posterior glottis by ordinary direct laryngoscopy. We attempted to expose posterior glottic lesions using a triangular laryngoscope for adequate achievement of the surgery. We have performed phonomicrosurgery for 14 lesions in the posterior glottis including 5 early cancers, 1 dysplasia, 1 hemangioma, and 7 granulomatous lesions. Under general anesthesia, a triangular laryngoscope was set lateral to an intubation tube, shifting the tube anterolaterally toward the opposite side to expose the posterior glottis, which allowed simultaneous visualization of the vocal fold, the lateral wall, and a part of the posterior wall of the posterior glottis. The procedures were completed successfully in all cases. Modified placement of the triangular laryngoscope provided an excellent surgical view including the membranous portion of the vocal fold through the posterior glottis. All lesions have been well controlled during the follow up periods of 6-23 months. The triangular laryngoscope enables an alternative method for posterior glottic exposure. Modified placement of the laryngoscope can be easily performed and provides sufficient exposure of posterior glottic lesions for an adequate resection of those lesions. © 2007 Springer-Verlag.

DOI： 10.1007/s00405-007-0484-9

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Publisher：(一社)日本耳鼻咽喉科学会  

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DOI： 10.2492/inflammregen.27.570

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Publisher：(一社)日本炎症・再生医学会  

癌または外傷を有する患者の頭部と頸部の外科的手術では気管切除がしばしば必要となる。気管壁の再構築のためには幾つかのアプローチがあるが、それらのほぼ全てで、自己移植片または人工移植片で欠損部位を塞ぎ、新しい気道空間を作製するための、手術の豊富な経験が必要である。再生医療は著しい進歩を遂げ、幾つかの臓器では臨床適用されている。気道再構築のための組織工学的アプローチの有用性を評価した。部分的欠損をイヌの頸部気管内に作製した。ポリプロピレンとコラーゲンスポンジで作製したscaffoldを欠損部位に縫合した。術後状態を内視鏡検査、X線検査、組織学により評価した。5症例全てで変形または合併症もなく、scaffold管腔表面での上皮形成が見られた。組織学的データも、気道の機能的再生を支持するものであった。この簡便な組織工学的アプローチは、部分的欠損のある気道を再生する優れた方法であると思われた。

Language：English   Publishing type：Research paper (scientific journal)  

Objectives: The regenerative processes of the vocal fold, or the existence of stem cells in the folds, are unknown. Side population (SP) cells are defined as cells that have the ability to exclude the DNA binding dye, Hoechst 33342. They are regarded as a cell population enriched with stem cells and can be isolated from non-SP cells by a fluorescence-activated cell sorter. This study was designed to determine whether SP cells exist in the human vocal fold, as a first step in elucidating the regenerative mechanisms of the vocal fold. Methods: Seven human excised larynges were used in this study. Two were used for fluorescence-activated cell sorter analysis, and 5 were subjected to immunohistochemical analysis with antibodies against an adenosine triphosphate binding cassette transporter family member, ABCG2, which is expressed in SP cells. Results: The number of SP cells in the human vocal fold was about 0.2% of the total number of cells. ABCG2-positive cells were identified in both the epithelium and subepithelial tissue throughout the entire vocal fold. Conclusions: This preliminary study demonstrated the existence of SP cells in the human vocal fold. Further studies are warranted to clarify how these cells work in the vocal fold, particularly in the regenerative process. © 2007 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940711601110

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: Vocal fold scarring remains a therapeutic challenge. Previous studies have indicated that hepatocyte growth factor (HGF), a strong antifibrotic element, has therapeutic potential for restoring scarred vocal folds. To enhance the effect of HGF in vivo, we developed a novel drug delivery system (DDS) in which HGF is embedded in gelatin hydrogel and continuously released over a period of 2 weeks. In the present study we investigated the therapeutic efficacy of the HGF DDS on vocal fold scarring by using a canine model. Methods: The vocal folds of 8 beagles were unilaterally scarred by stripping the entire layer of the lamina propria. The contralateral vocal folds were kept intact as normal controls. One month after the procedure, hydrogels (0.5 mL) containing 1 μg of HGF were injected into the scarred vocal folds of 4 dogs (HGF-treated group), whereas hydrogels containing saline solution were injected in the other 4 dogs (sham group). Histologic and vibratory examinations were completed for each group 6 months after the initial surgery. Results: The excised larynx experiments showed significantly better vibration in terms of mucosal wave amplitude and glottal closure in the HGF-treated group compared to the sham group. Histologic evaluation of the vocal folds indicated remarkable reduction in collagen deposition and tissue contraction, with favorable restoration of hyaluronic acid and elastin in the HGF-treated group. Conclusions: The present findings suggest that the novel HGF DDS may provide favorable effects in restoring the vibratory properties of scarred vocal folds. © 2007 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940711601008

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Language：English   Publisher：(一社)日本耳鼻咽喉科学会  

floppy epiglottisに対する新規手術法を紹介した。症例は37歳男性で、主訴は吸気性呼吸困難であった。内視鏡検査により、強制吸気中に喉頭蓋が後咽頭壁の中に脱出し、全気道閉塞を引き起こしていることが明らかになった。内視鏡による喉頭蓋の視覚化後に、KTPレーザーを用いてV型喉頭蓋部分切除を行った。術直後に症状の改善がみられ、6ヵ月後、正常吸気中には喉頭蓋の後咽頭壁中への脱出は認められなかった。最大の強制吸気中には上記脱出が観察されたが、その間も気道空間は十分であった。術後合併症をもたらさない喉頭蓋の適切な切除容積の決定は非常に困難であるが、本法は、簡易、単純で有用であることが示された。

Language：English   Publisher：(一社)日本耳鼻咽喉科学会  

症例は76歳男性で、散発性の窒息発作により受診した。内視鏡検査により、声帯の傍正中固定が認められ、結果として喉頭気道の狭窄を伴っていた。内視鏡下観察において、塩化エドロホニウムの静脈内注射後、喉頭機能の改善が認められたが声の変化はみられなかった。アセチルコリン受容体に対する血清抗体検査を行い、確定診断した。声帯の外転に関与しているのは後輪状披裂筋のみなので、呼吸困難は本筋肉の選択的麻痺によるものと考えられる。コルチコステロイドと抗コリンエステラーゼ治療により、呼吸困難は改善した。退院1年後現在、抗コリンエステラーゼ継続服用により悪化はみられない。以上より、病因不明の声帯麻痺例においては、重症筋無力症が考慮されるべきと思われた。

It is important to properly control intraoperative bleeding during phonomicrosurgery in order to achieve optimal results and outcomes. The present study investigated the usefulness of the subepithelial infusion of epinephrine and the photocoagulation of microvascular lesions using the KTP laser to control of bleeding. Forty-seven cases were treated by phonomicrosurgery using this strategy to control intraoperative bleeding. Forty-three procedures showed an excellent controls of intraoperative bleeding by means of infusion and/or KTP laser photocoagulation, thus indicting the usefulness of these strategies for the prevention of bleeding.

DOI： 10.11334/jibi1954.53.5_268

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

This report describes a very rare case of myasthenia gravis (MG) localized to the larynx, with the onset of dyspnea requiring tracheotomy. The vocal cords of this patient were fixed in the paramedian position. Under fiberscopic observation, improvement of laryngeal function was demonstrated after intravenous injection of edrophonium. However, no voice change occurred. The posterior crico-arytenoid muscle has the sole responsibility of abducting the vocal cord; thus, it is concluded that the dyspnea was caused by the selective paralysis of this muscle. We suggest that MG should be considered in cases of vocal cord paralysis of unknown etiology. © 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2006.11.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

A new operative technique for the treatment of floppy epiglottis is introduced in this report. Though its diagnosis is not so difficult by close observations using a flexible fiberscope, it is likely to be treated as an asthma attack or a paradoxical vocal cord movement. In previous reports of upper airway obstruction caused by adult floppy epiglottis: epiglottis prolapse during inspiration, the cause of this condition has been divided broadly into two categories: idiopathic cases and secondary cases. Partial or total epiglottectomy has been usually reported for the treatment of the relief of airway obstruction caused by a floppy epiglottis. It is very difficult to decide adequately how much volume of epiglottis to cut without postoperative sequelae. A V-shaped partial epiglottidectomy is described for its treatment. This technique is very easy, simple, and effective. © 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2007.01.009

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Publisher：(一社)日本炎症・再生医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVE: The aim of this study was to regenerate high-quality cranial bone using tissue engineering techniques, with subsequent extension to clinical application. Our previous study with a 3-month observation period indicated that a composite scaffold composed primarily of β-tricalcium phosphate (TCP) had the potential for cranial bone regeneration. In this study, we investigated whether bone marrow derived stromal cells (BSCs) could promote the regeneration of cranial bone as determined after 3 and 6 months. STUDY DESIGN: The pilot study was conducted with 14 adult beagle dogs. MATERIALS AND METHODS: Craniotomy was performed in the same manner used clinically. The bone defect (2 × 2 cm) was created at each canine temporoparietal region. The test animals were divided into three groups. In group I, the bone defect was closed by replacing the original free bone flap without filling the residual gaps. In group II, the gap was filled with a composite scaffold consisting of collagen coated β-TCP and autologous bone fragments with fibrin glue. In group III, autologous cultured BSCs and the composite scaffold were used to fill the gap. The sites of craniotomy were analyzed with three-dimensional computed tomography and histologic examination 3 and 6 months after the operation. RESULTS: Bone regeneration was observed in groups II and III, with more extensive formation in group III than in group II. In group I, bone regeneration was not observed. CONCLUSION: This study showed that BSCs have the potential to promote cranial bone regeneration and confirmed the efficacy of a composite scaffold made of β-TCP and autologous bone fragments with fibrin glue. © The American Laryngological, Rhinological & Otological Society, Inc.

DOI： 10.1097/MLG.0b013e3180471459

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Language：Japanese  

Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.58.201

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Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.58.197

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Publisher：(一社)日本耳鼻咽喉科学会  

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Publisher：(一社)日本耳鼻咽喉科学会  

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Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publishing type：Doctoral thesis  

Language：English   Publishing type：Doctoral thesis  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVES: The aims of this study are to investigate the efficiency of a tissue engineering approach to partial tracheal reconstruction and to improve epithelialization of the reconstructed trachea. The trachea must be resected in some cases of cancer or trauma. Various restructuring techniques are used, with no consensus on the best approach. Two problems that arise when treating tracheal defects by conventional techniques are an inability to regenerate ciliated epithelium at the reconstructed site and having to perform multiple procedures to achieve the desired repair. This study is designed to address these problems. STUDY DESIGN: Preliminary, an animal experiment. METHODS: Surgery was performed on five adult beagles under anesthesia. After the making of a longitudinal cervical skin incision, the trachea was exposed and a circular defect created. A polypropylene and collagen scaffold preclotted with peripheral blood was inserted to the defect site. Postoperatively, the site was evaluated fiberscopically, histologically, and radiographically. RESULTS: All dogs did well postoperatively. Fiberscopic examination showed that the implanted scaffolds were completely covered with regenerated mucosa with capillaries in all cases. Histologic data showed ciliated epithelium regenerated at the operated site from 1 month postoperatively. Newly formed cartilage was detected in the specimens from 8 to 12 postoperative months. Computed tomography images revealed the fine luminal contour of the regenerated site. CONCLUSIONS: Good epithelial regeneration was observed after repair of a round tracheal resection using a simple tissue engineering technique, making the technique a good substitute for conventional approaches to tracheal reconstruction in patients with cancer or trauma. © The American Laryngological, Rhinological & Otological Society, Inc.

DOI： 10.1097/MLG.0b013e31802e223d

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Conclusion: Since this tissue engineering technique is cost-effective and is less invasive to patients, it may replace conventional approaches in laryngeal reconstructive surgeries. Objective: Laryngeal cancer is one of the most prevalent cancers in the head and neck region, and frequently requires surgical resection. Although there are many ways to reconstruct the larynx after resection, donor tissue is usually required. Recently, tissue engineering techniques have become widely accepted in clinical medicine and have already been applied to some organs. This animal experiment was designed to elucidate the efficacy of laryngeal regeneration using tissue engineering technique. Materials and methods: A bioartificial scaffold was designed from a replica of a canine larynx. A dental cast was used to replicate the intricate inside shape of the larynx. After copying its shape on a polypropylene mesh sheet, this sheet was coated with spongy collagen from porcine skin. A hemilaryngectomy was performed on beagle dogs under general anesthesia. Then the scaffold, preclotted with a mixture of peripheral blood and bone marrow-derived stromal cells, was implanted and fixed. The postoperative status was examined fiberscopically. Results: On the eighth day after the operation, the surface of the implant was covered with soft tissue. Finally, the implant was completely covered with regenerated mucosa. © 2007 Taylor & Francis.

DOI： 10.1080/00016480601068014

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Publisher：TAYLOR & FRANCIS AS  

Conclusion: It is important to prevent regional lymph node recurrence and distant metastasis to achieve better survival of laryngeal cancer. Objective: Therapeutic outcomes of 130 cases with laryngeal cancer treated at Kyoto University Hospital between 1995 and 2004 were reviewed. Patients and methods: In all, 121 males and 9 females were involved. Their ages ranged from 40 years to 92 years (average 66 years). All tumors were squamous cell carcinoma - arising at the glottis in 111 cases, the supraglottis in 18, and the subglottis in 1 case. Most glottic cancers (77.5%) were classified as stage I or II, while most supraglottic cancers (77.8%) were at stage III or IV. Stage I/II cancers were basically treated by conventional radiotherapy (60-66 Gy) and twice-daily hyperfractionated radiotherapy (70-74 Gy), respectively, attempting to preserve the larynx. Total laryngectomy with neck dissection was performed in the treatment of stage III/IV cases. Results: Five-year disease-specific survival rates were 100%, 96%, 100%, and 68% for stage I, II, III, and IV, respectively. Five-year laryngeal preservation rates were 98%, 100%, 86%, 0%, and 0% for T1a, T1b, T2, T3, and T4 of glottic cancer, respectively. Local recurrence occurred in five cases of stage I/II glottic cancer, which was successfully salvaged. Regional lymph node recurrence occurred in five cases including four patients with glottic cancer and one with supraglottic cancer. Two of them died of disease despite undergoing salvage therapy. Distant metastasis occurred in the lung in four cases including one glottic and three supraglottic cancer patients after initial treatment. © 2007 Taylor & Francis.

DOI： 10.1080/00016480601067990

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVES/HYPOTHESIS: Our aim was to evaluate the combined effect of 5-fluorouracil (5-FU) and myringotomy for the treatment of otitis media with effusion (OME). OME is usually treated with medication, myringotomy, or insertion of a ventilation tube (VT). Except for VT insertion, however, treatment effects are short-lived. VT insertion has numerous sequelae: increased susceptibility to infection, large perforation of the tympanic membrane, cholesteatoma, and eventual hearing deterioration. We estimated the depressant action of 5-FU on normal cell proliferation in vitro. In addition, clinically, we assessed whether 5-FU has the potential to prolong the effect of myringotomy. STUDY DESIGN: An in vitro study and a clinical study were conducted. MATERIALS AND METHODS: In study I, fibroblasts harvested from the peritoneum of three green fluorescent protein transgenic mice were cultured with different doses of 5-FU. After 2 weeks, their proliferation rates were compared. In study II, patients (54 males, 47 females) were selected randomly from a group of patients with intractable OME. Myringotomy with or without a single dose of 5-FU ointment (approximately 0.10-0.30 mg) was performed in group I (n = 64) and group II (n = 37), respectively. The natural closure rates of the tympanic membrane were assessed in both groups. RESULTS: In vitro, 5-FU inhibited the growth of fibroblasts in a dose-dependent manner. The average time to tympanic membrane closure was 20.5 days in group I and 8.1 days in group II. No adverse events were observed in either group. CONCLUSIONS: Topical application of 5-FU ointment is useful in prolonging the effect of myringotomy. 5-FU ointment therapy is easy, safe, and cost-effective and may be of wide application. © The American Laryngological, Rhinological & Otological Society, Inc.

DOI： 10.1097/01.mlg.0000248231.62834.e3

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DOI： 10.1080/00016480601067990

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In the field of head and neck surgery, tracheal resection is frequently required for patients with cancer or trauma. There are several approaches for reconstructing the tracheal wall, but almost all require repeated skilled surgeries, which intend to fill the defect and create new airway space using autologous or artificial grafts.&lt;BR&gt;Regenerative medicine has made remarkable progress and has been applied clinically in some organs. Thus in this study, the usefulness of a tissue engineering approach for tracheal reconstruction was evaluated. A partial defect was created in canine cervical tracheas. A scaffold made of polypropylene and collagen sponge was sutured at the defect site. Postoperative status was evaluated by endoscopy, radiography, and histology. In all five cases, epithelialization of the scaffold luminal surface was observed without deformity or complications. Histological data also supported the functional regeneration of the trachea using this approach. This simple tissue engineering approach is a good method for reconstruction of the trachea with partial defects.

DOI： 10.2492/inflammregen.27.570

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Language：Japanese  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2007077768

Language：Japanese  

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Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.57.153

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Other Link： http://search.jamas.or.jp/link/ui/2006160608

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: Ectasias and varices of the vocal fold are microvascular lesions that are often due to chronic abuse of the voice, and are occasionally encountered in association with other disorders such as polyps, Reinke's edema, and hematoma. The KTP laser can be used for photocoagulation of small vascular lesions, because the laser beam is well absorbed by hemoglobin, and damage to the epithelium is minimal. The present pilot study examined how the KTP laser could be used for microvascular lesions and their associated lesions. Methods: Twelve patients who had undergone phonomicrosurgery were enrolled in the present study. The microvascular lesions were treated by photocoagulation with the laser set at a low power of 1.5 W in the continuous mode, while preserving the epithelium, and associated lesions were then treated by microdissection with cold instruments. The postoperative phonatory function was assessed by maximum phonation time, a perceptual test rating (GRBAS scale), and stroboscopy. Results: The procedures were completed successfully in all cases. An exceptional case of a small hemorrhagic polyp allowed treatment with the laser only. The postoperative stroboscopic findings, maximum phonation time, and perceptual test rating all showed significant improvement compared with the preoperative state. No adverse effects, such as scarring or reduction of the mucosal wave, were observed in the current series. Conclusions: KTP laser photocoagulation is a relatively simple and safe procedure for treating microvascular lesions of the vocal fold. It is not recommended for photocoagulation of hemorrhagic polyps or hematomas, because such lesions have little blood flow inside and thus photocoagulation is usually impossible or requires too much laser energy. However, photocoagulation of perimeter or feeding vessels of such disorders may facilitate the following procedure by avoiding unnecessary bleeding, as well as preventing recurrence of hemorrhagic lesions. © 2006 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940611500402

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVE: The aim of our study was to examine the tissue response and new bone formation induced by β-tricalcium phosphate (β-TCP), collagen, and autologous bone fragments with fibrin glue implanted into a cranial bone defect. MATERIALS AND METHODS: Granulated β-TCP and collagen from porcine skin were mixed and freeze-dried. The weight ratio of both materials was 98:2. The composite scaffold for bone regeneration was composed of this artificial material and autologous bone fragments. Five adult beagle dogs were used. A cranial bone defect (2 cm × 2 cm) was created in each dog. The animals were divided into two groups. In group 1 (n = 3), the cranial bone defect was closed by replacing the original free bone flap, and the residual fissure and burr holes were filled with the composite scaffold with fibrin glue. In group 2 (n = 2), the bone defect was closed only by replacing the original free bone flap. Three months after the treatment, computed tomography and histologic examinations were done in all animals. RESULTS: In all dogs in group 1, the defects were almost closed by new bone; whereas in group 2, the defects were filled with fibrous tissues instead of bone. CONCLUSION: This study showed that the composite scaffold made of β-TCP, collagen, and autologous bone fragments with fibrin glue enabled reconstruction of cranial bone defects without the usual fixation materials. © 2006 The American Laryngological, Rhinological and Otological Society, Inc.

DOI： 10.1097/01.mlg.0000191468.45536.3f

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Language：English   Publisher：The Japanese Association for Chest Surgery  

DOI： 10.2995/jacsurg.20.751_2

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ANNALS PUBL CO  

Objectives: The aim of this study was to investigate the destiny of implanted autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem cells. We previously reported the successful regeneration of an injured vocal fold through implantation of BSCs in a canine model. However, the fate of the implanted BSCs was not examined. In this study, implanted BSCs were traced in order to determine the type of tissues resulting at the injected site of the vocal fold. Methods: After harvest of bone marrow from the femurs of green fluorescent transgenic mice, adherent cells were cultured and selectively amplified. By means of a fluorescence-activated cell sorter, it was confirmed that some cells were strongly positive for mesenchymal stem cell markers, including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the injured vocal fold of a nude rat. Immunohistologic examination of the resected vocal folds was performed 8 weeks after treatment. Results: The implanted cells were alive in the host tissues and showed positive expression for keratin and desmin, markers for epithelial tissue and muscle, respectively. The implanted BSCs differentiated into more than one tissue type in vivo. Conclusions: Cell-based tissue engineering using BSCs may improve the quality of the healing process in vocal fold injuries. © 2005 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940511401203

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Language：Japanese   Publisher：耳鼻と臨床会  

KTPレーザーによる光凝固療法を施行した6症例(男性3例・女性3例,年齢33〜57歳)を対象に,いずれも随伴病変に対するラリンゴマイクロサージャリーを行い,その際に血管拡張性病変のレーザー治療を合わせて行った.随伴病変は声帯ポリープ3例,ポリープ様声帯・白斑症・Tla声門癌各1例であった.その結果,光凝固は容易に可能であり,粘膜上皮を温存のまま病変を凝固することができ,術後も声帯振動に対する障害は認めず,全例音声機能の改善が得られた.以上より,KTPレーザーによる光凝固療法は声帯血管拡張性病変の治療に容易かつ安全な治療法であると考えられた

Publisher：耳鼻と臨床会  

65歳女.僧帽弁置換術(経口挿管24時間)後47日目に嗄声・翌日には呼吸困難を生じ,精査により声門下に腫瘤を認め緊急入院となった.入院時,血液凝固能の低下を認め,気管切開拒否のため全麻下喉頭直達鏡手術による肉芽腫切除を断念して局麻下の経鼻的喉頭手術を施行した.手術時,喉頭モニターには電子内視鏡システムを使用し,肉芽腫の切除には可撓チューブと上部消化管内視鏡用穴開き鉗子を用いた.術後,呼吸困難は消失し,肉芽腫は術後2ヵ月まで残存を認めたが,その後徐々に縮小し術後4ヵ月後には消失し,それに伴い嗄声は改善した.術後13ヵ月の現在,再発の徴候は認めていない

A relatively large granuloma in the subglottis was successfully removed with transnasal laryngeal surgery, in which the lesion was repeatedly snatched off with a flexible forceps inserted through a transnasal flexible tube while the larynx was monitored with an endolaryngoscopy through another nasal way. Immediately after surgery, a respiratory distress disappeared and her voice was normalized. Four months after surgery, the granuloma perfectly disappeared. Tracheotomy was not necessary and the patient was satisfied with these results. Our method of transnasal laryngeal surgery is useful as a minimally-invasive surgery for resection of a laryngeal lesion.

DOI： 10.11334/jibi1954.51.5_370

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

Objectives: The objective of the present study was to demonstrate regenerative medicine of the tracheal tissue by using an in situ tissue engineering technique for airway reconstruction. Methods: Based on the previous successful experimental animal studies, the current regenerative technique was applied to repair of the trachea of a 78-year-old woman with thyroid cancer. A Marlex mesh tube covered by collagen sponge was used as a tissue scaffold. The operative intervention included right hemithyroidectomy. resection of the trachea, and tracheoplasty using the scaffold. The right half of three rings of the trachea was resected, and the scaffold material was sutured to the defect of the trachea. Results: After 2 weeks, the mesh collagen structure of the artificial material could be seen with endoscopy in most of the implanted area. The artificial material was covered with epithelial growth after 2 months. Epithelialization continued to cover the artificial material completely for 2 years without any complications. Conclusions: The current regenerative technique avoided tracheotomy, a second operation, and deformity. Good epithelialization has been observed on the tracheal luminal surface without any complications for 2 years. Although long-term observation is required, regenerative medicine of the tracheal tissue appears feasible for airway reconstruction. © 2005 Annals Publishing Company. All rights reserved.

DOI： 10.1177/000348940511400603

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY, INC  

A 50-year-old woman presented with a 30-year history of nasal obstruction. She had been treated for paranasal sinusitis at other hospitals and she was referred to our hospital for further examination. Flexible endoscopy revealed a mass in the posterior aspect of the right nasal cavity to the posterior aspect of the left nasal cavity around the posterior edge of the nasal septum. Copyright © 2005 by the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc.

DOI： 10.1016/j.otohns.2004.09.065

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Language：Japanese  

? The present study demonstrates regeneration of the laryngeal and tracheal tissue using in situ tissue engineering technique for airway reconstruction. As the tissue scaffold, Marlex mesh reinforced with polypropylene rings covered by a collagen sponge was developed as the tissue scaffold. This scaffold material was implanted into the defect of the larynx and tracheas in beagle dogs. Post-operative endoscopy showed a well-epithelized surface of the subglottis and trachea. Based on the histological evaluations, regeneration of the cilial epithelium over the scaffold and good incorporation of the scaffold material into the host tissue were observed. Based on a mechanical test, the airway framework was firmly supported by the regenerated tissue. From the successful results of the experimental animal studies, the current regenerative technique was used to repair the trachea of a 78-year-old female patient with thyroid cancer. The right half of the three rings of the trachea was resected and the scaffold material was sutured to the defect. Epithelization continued to cover the artificial material completely for ten months without any complications. The current regenerative technique avoided tracheotomy, a second operation and cervical deformity. Although long-term observation is required, regenerative medicine of the tracheal tissue appears feasible to use for airway reconstruction.

DOI： 10.2199/jjsca.25.310

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objectives: To regenerate of the mastoid air cells and their functions for the treatment of incurable otitis media. Materials and Method: In situ tissue-engineered mastoid air cells using three-dimensional hydroxy apatite (3D-HA) of honeycomb-like structure were used as artificial pneumatic bones. This 3D-HA is made of calcium phosphate and has a high ratio of micropores, 90%. Its surface is coated with collagen. Ten patients (4 males, 6 females) for this clinical study were randomly selected among the patients with severe cholesteatoma, adhesive otitis media, and purulent chronic otitis media, and they were to be received a staged operation. At the first stage of tympanoplasty, collagen-coated 3B-HA was put into the newly opened mastoid cavity, and it was fixed by fibrin glue. Recovery of mastoid aeration and regeneration of the pneumatic air cells of the mastoid cavity were estimated by images of high-resolution computed tomography (HRCT) after the first operation. At the second stage of operation, histopathologic examinations of specimens of HA taken from the reopened mastoid cavity were performed. Results: Aerations in the mastoid cavity were observed in 9 of the 10 patients within 12 months after the second operation. Moreover, the pneumatic structure in the mastoid cavity was partially regenerated in five patients. In these successful cases, mucosa with newly formed capillaries was observed on the surface of the implanted HA at the second stage of operation. In the failure cases, however, connective tissues and granulations invaded the space of the 3D-HA. They were observed as soft-tissue density areas in the HRCT scan images. Conclusions: This study indicates that mucosa can grow on the surface of implanted artificial 3D-HA and can have a gas exchange function in the newly opened mastoid cavity. These tissue-engineered mastoid air cells may be a possible treatment for intractable otitis media.

DOI： 10.1097/01.mlg.0000154728.23657.3a

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY, INC  

DOI： 10.1016/j.otohns.2004.09.043

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Publisher：The Society of Practical Otolaryngology  

Basaloid squamous cell carcinoma (BSC) is an uncommon aggressive variant of squamous cell carcinoma (SCC). Association with SCC components is often identified as BSC's important cytologic feature. We treated two patients with BSC without association of SCC in the pharynx. Case 1 was a 42-year-old woman with left otalgia. A left tonsil tumor was suspected and incisional biopsy was performed. The diagnosis of the tumor was BSC (T3NOMO). Irradiation (40.8 Gy) with chemotherapy (Nedaplatin 100 mg) were not effective. Then tumor resection with mandibular swing and bilateral neck dissection was performed. The histopathological diagnoses were BSC and no metastatic lymph node was found. All surgical margins were negative (pT4N0). About 3 years after the tumor resection, there is no evidence of disease. Case 2 was a 56-year-old man with left lateral neck mass of 7 months' duration. Because the neck mass rapidly enlarged in the latest month, he visited the Nishi-kobe Medical Center. Clinical examination revealed a small exophytic mass in the left piriform sinus and two lateral neck masses (30 mm × 2), anterior and posterior to the internal jugular vein that were suspected to be metastatic lymph nodes. A twenty-seven mm mass in the liver was also found in the abdominal echo image. Fiberoptic biopsy from the left piriform sinus tumor, incisional biopsy from the lateral neck mass and needle biopsy from the liver mass were performed. Histopathological diagnosis was BSC in the left piriform sinus with lymph nodes and liver metastasis (T1N2bM1). The patient hoped to receive ambulatory peroral chemotherapy with TS-1® (100 mg/day). During the chemotherapy, bone metastasis was revealed. Palliative irradiation was effective to reduce bone and neck pain. The patient died due to the BSC about 1 year after diagnosis.

DOI： 10.5631/jibirin.98.637

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Language：Japanese  

頭頸部腫瘍患者の特徴とリエゾン・コンサルテーション精神医学の実際を報告した.医療センター神経科,耳鼻咽喉科にて共診した患者に関して,後方視的に年齢,性別など患者の特徴と介入方法を調べた.その結果,男性52例,女性12例と圧倒的に男性が多かった.喫煙歴は男性34例,女性2例で,飲酒歴は男性34例,女性1例であった.咽頭癌,喉頭癌,舌癌37例のうち,83.8%が大酒家,ヘビースモーカーであった.DSM-IV診断では適応障害が20%,睡眠障害が20%,不安障害が19%,うつ病性障害が17%,アルコール離脱が15%,その他が9%に認められ,向精神薬が90.7%に必要であった.41例は術前から精神科医が関与し,うち32例は咽頭癌・喉頭癌・舌癌患者であった.術前からの関わりをもち,人柄,喫煙歴・飲酒歴などの心理社会的背景を把握しておくことが術後の心理的援助に重要であった

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Language：Japanese  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society of Logopedics and Phoniatrics  

Phonosurgery is one of the most suitable indication of day surgery. Under local anesthesia, 260 cases have undergone functional videoendoscopic laryngeal surgery at the Nishi Kobe Medical Center. The transoral approach was adopted for endoscopic monitoring of the vocal folds and voice during surgery. In 225 of these cases, the operative procedure was fully accomplished. In 40 laryngeal polyp cases, good vocal function was obtained postoperatively. Clinical Pathway process has been used for patients and medical staff members at the Day Surgery Unit of Kyoto University Hospital since 2000. Interviews of the patients were conducted by a nurse pre- and post- operatively. The most common complaint was limitation of phonation for 3 to 7 days after operation. In cases with unfavorable postoperative vocal function, medication and/or voice therapy were applied. Informed consent with explanation of the operative procedure and postoperative clinical course is most important for avoiding medical problems with patients. For the best phonosurgery treatment program, a voice care team should be organized to include a speech therapist, anesthesiologist, nurse, and others under the leadership of the otolaryngologist.

DOI： 10.5112/jjlp.45.168

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Publisher：TAYLOR & FRANCIS AS  

The objective of this study was to establish a method for regenerating mastoid air cells and their functions for clinical use in incurable otitis media. For this clinical study three patients (one male, two female) were randomly selected from patients with severe cholesteatoma about to undergo staged operations. Hydroxy-apatite in three-dimensional, honeycomb-like structures (3D-HA) were used as artificial pneumatic bones. This 3D-HA is made of calcium phosphate and has a high percentage of micropores (90%). Its surface is coated with collagen. At the first stage of tympanoplasty, collagen-coated 3D-HA was put into the opened mastoid cavity and fixed by fibrin glue. Recovery of mastoid aeration and regeneration of the pneumatic air cells of the mastoid cavity were estimated on CT scan images after the first operation. Aeration was recovered in all cases. The mastoid air cells were regenerated in two cases. In the failed case, subcutaneous connective tissues and granulations invaded into the spaces of the 3D-HA. This study demonstrated that mucosa would grow on the surface of a 3D-HA implant and could provide gas exchange functions in the newly opened mastoid cavity. This tissue engineering method may be a possible treatment for intractable otitis media.

DOI： 10.1080/03655230310016690

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

高度の慢性中耳炎で乳突蜂巣の発育が不十分で,含気腔がないか,あってもごく僅かな5症例を対象とし,in situ tissue engineeringという組織工学的手法を用いて乳突蜂巣構造の再生を試みた.第1段階手術終了後に第2段階手術を行い,乳突腔内の含気腔の形成と蜂巣構造の再生は,術後に施行した高分解能CTによる画像で判断した.CTは第1段階手術前,第2段階手術直前と術後6ヵ月の計3回撮影した.観察期間は9〜24ヵ月であった.その結果,5症例のうち,評価の時点で上鼓室から乳突腔にかけて部分的にでも含気を認めたものは4症例で,このうちハイドロキシアパタイトによる蜂巣構造が認められたものは3症例,残る1症例は含気が認められるものの,ハイドロキシアパタイト周囲は軟部組織(液体も含む)陰影が観察され,蜂巣構造形成にまでは至っていなかった.また,含気を全く認めなかった1症例は,軟部組織(液体も含む)陰影が乳突腔全体に充満していた

PubMed

DOI： 10.1080/03655230310016690

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The aim of this study is to evaluate bone marrow cells on the novel artificial tracheal as a cell source of autologous tissue regeneration. We have succeeded to reconstruct the trachea with peripheral blood and its long term efficacy was demonstrated in animal experiments. In this study we used bone marrow aspirate and mesenchymal stem cell from the bone marrow and it epithelization was examined. Tracheal prosthesis was fabricated with Marlex mesh and spiral stent (L=50mm). It was dipped in 1% collagen solution and dried. Collagen sponge layers were made on both. Dehydro-thermal cross-linkage of collagen molecules was performed at 140 C in vacuo 24 h. 9 beagle dogs divided into 3 group, this prosthesis was implanted into a cervical tracheal 5-cm defect. Before implantation collagen was soaked with autologous bone marrow aspirate (n=3), autologous mesenchymal stem cell(n=3), and as a control peripheral blood (n=3). After the operation the epithelization on the reconstructed site was evaluated with a bronchoscope. Construction of airway was measured by MR-imaging. Observation time continued up to 2 years. All the 9 dogs survived uneventfully until they were sacrificed (1M, 12M, 24 M). Complete epithelization was accomplished at 1- 3 months in all the dogs. Early recovery of epithelium was evident in bone marrow aspirate group and MSC group. However even in long term result there was no significant difference between bone marrow group and MSC groups in performance. This experiment indicates that application of bone marrow or MSC may facilitate the tissue regeneration on the tracheal wall.

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Publisher：WORLD SCIENTIFIC PUBL CO PTE LTD  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Society of Practical Otolaryngology  

The aim of this study was to regenerate the pneumatic air cells and their gas exchange function in the poorly developed mastoid cavities of patients with chronic otitis media. Five patients with severe chronic otitis media whose mastoid air cells were poorly developed took part in this clinical trial. Four of 5 patients underwent staged operation of tympanoplasty. Honeycomb-like structures made of hydroxyapatite (HA) coated with collagen was used as a framework for artificial pneumatic bones. At the first stage of tympanoplasty, collagen-coated HA was implanted into the newly opened mastoid cavity and was fixed by fibrin glue. After the first operation, recovery of mastoid aeration and regeneration of the pneumatic air cells of the newly opened mastoid cavity were assessed on CT scan images. In 4 of 5 cases, aeration was recovered. The pneumatic air cells were regenerated in 3 cases. This study demonstrated that the mastoid air cells could be regenerated with implanted HA in the newly opened mastoid cavity. This tissue engineering method may be a possible treatment for intractable otitis media because it can recover the gas exchange function.

DOI： 10.5631/jibirin.97.205

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Language：Japanese  

Language：English  

Language：Japanese  

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手術前後の音声を評価する場合,まず簡便なのが聴覚印象評価を記載することである.音響分析については,周期ゆらぎ,振幅ゆらぎ,調波成分と雑音成分の音響エネルギー比の3つのパラメータでよい.発生機能的検査としては,最長発声持続時間が簡便であり,呼気流率,更に声の強さも重要である.局所麻酔での喉頭手術は,患者の声を聞きながら操作できる点で有利である.電子内視鏡下の喉頭手術は低侵襲で主に声帯ポリープ,喉頭肉芽腫がよい適応となり,頸部外切開による喉頭形成手術は声帯麻痺や痙攣性発声障害などが適応となる.患者の音声障害が十分改善された時点或いは少し過矯正した時点で手術を終了する.一方,全身麻酔での喉頭手術は,喉頭直達鏡により安定した視野が得られることからより複雑な手技が可能である

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Language：Japanese   Publisher：JIBI TO RINSHO KAI  

We report a case of interarytenoid adhesion at the vocal processes. A nineteen-year-old male with dyspnea due to traffic accident had an endotracheal intubation for three weeks. Two months later, he complained dyspnea and stridor at the first visit to our outpatient clinic. Laryngoscopy showed bilateral vocal cord immobility, however it did not show the intrarytenoid adhesion at that time. Tracheotomy was performed for acquiring the sufficient air way. Six months later, fiberoptic endoscopy under local anesthesia revealed the adhesion between the vocal processes. Under general anesthesia, the adhesion was excised by a cold instrument and steroid was injected into both vocal processes. Good vocal cord mobility on both sides was obtained just after the operation. Tracheostoma was closed. Two months later, contact granuloma was observed at both vocal processes, but the lesions disappeared after four months of voice therapy and proton pump inhibitor medication. There has not been re-adhesion at the vocal processes for two years and three months. Observing and touching the vocal processes by endoscopy or direct laryngoscopy can provide important information for the precise diagnosis of bilateral vocal cord immobility.

DOI： 10.11334/jibi1954.49.1_41

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Publisher：耳鼻咽喉科臨床学会  

突発性難聴と診断し,副腎皮質ステロイド製剤による点滴治療を行った265例270耳についての成績を調べた.治癒と著明回復とを合わせた改善率は48%であり,高齢,めまいを伴う症例,発症から治療までの期間が長い例での治療成績が不良であった.また,コハク酸メチルプレドニゾロンナトリウム群の改善率は50%,コハク酸プレドニゾロンナトリウム群では47%であり,投与したステロイドの抗炎症作用の力価を1/3としたものの,両者の間に有意差は認めなかった

Language：Japanese  

Language：Japanese   Publisher：(地独)神戸市民病院機構  

1994年8月〜2001年2月の6年半における言語外来受診者は1006例で,そのうち構音障害が認められたのは小児63例,成人62例の計125例であった.言語外来での小児症例に対する構音指導の適応は,精神発達年齢が4歳以上で,精神発達年齢に応じた構音が獲得できていない場合とした.その結果,機能性構音障害19例では,全例が本の朗読など意識すると正しい構音が可能となった.しかし会話になると19例中4例では時に構音の誤りを認め,うち3例は精神発達遅滞を伴っていた.又,会話で認められた構音の誤りは,発達途上に見られる省略,置換等の構音の誤りでは17例中1例のみであったのに対し,声門破裂音,口蓋化構音,側音化構音など舌の誤った操作による構音の誤りでは,6例中3例と高率を示した.従って,精神発達遅滞や構音の誤りの種類が,会話への汎化に影響を及ぼす要因になると考えられた

Publisher：耳鼻咽喉科臨床学会  

75歳男,53歳男,59歳男及び67歳の女の喉頭結核の症例を報告した.4例とも嗄声を主訴とし,うち2例は明らかな肺結核の既往があった.4例とも抗結核薬の投与にて治癒した.文献的検討から,喉頭結核は声帯に肉芽腫型の病巣を作り,嗄声を主訴とすることが多いという特徴があることが明らかとなった.本症は局所所見上では喉頭癌との鑑別が難しく喉頭隆起性病変の鑑別に際しては常に念頭におく必要がある

Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

We report a 32-year-old woman with a foreign body perforating the cervical esophageal mucosa completely.&lt;br&gt;Five months prior to coming to our hospital, she felt left neck pain on swallowing after a fish meal. Although she underwent esophagoscopy at another hospital the next day, no abnormal findings were obtained. Since she complained of persistent discomfort on swallowing, radiographic examinations were also undergone at the same hospital. They revealed a foreign body located between the left lobe of the thyroid gland and the esophagus, but she refused to undergo an operation because of her mild symptom.&lt;br&gt;Five months after the foreign body ingestion, she came to our institution and wanting to remove the fish bone. We approached using a collar neck skin incision, and extracted a fish bone embedded in the esophageal muscle layer without damage to mucosa.&lt;br&gt;Extraluminal esophageal foreign bodies are very rare, but sometimes their complications are fatal. Therefore, great care is required with foreign bodies, even if the ingestion occurred a long time prior to examination, or if esophagoscopy reveals no remarkable abnormality.

DOI： 10.2468/jbes.53.45

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS PUBL CO  

The purpose of this report is to present a rare case of anterior spinal artery syndrome (ASAS) in which there proved to be a combined lesion of paralysis and adhesion. A 26-year-old woman with a history of ASAS complained of difficulty of tracheal decannulation. In 1988, she was intubated and underwent tracheotomy because of respiratory muscle weakness, and she was decannulated in 1990. In 1998, she had cesarean delivery under general anesthesia, and postdelivery dyspnea necessitated tracheotomy again. On her first visit to us, endoscopic examination revealed bilateral vocal fold immobility at the midline without an apparent web. Direct laryngoscopy under general anesthesia revealed a posterior glottic adhesion and scarring, which were treated by excision of the scar and local steroid injection. The left vocal fold gradually regained mobility, permitting decannulation 3 months after treatment. This complicated vocal fold immobility was found to be due to adhesion and partial paralysis combined.

DOI： 10.1177/000348940211100804

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Language：Japanese   Publisher：The Society of Practical Otolaryngology  

We treated 265 patients (270 ears) with idiopathic sudden deafness by intravenous corticosteroid hormone administration. Complete recovery occurred in 31% of patients, definite improvement in 17%, slight improvement in 19%, and no improvement in 33%. Prognostic factors for better hearing were as follows: younger age, absence of vestibular symptoms, hearing loss configuration without high tone impairment, mild initial hearing loss, and early initial treatment after onset. In the past 10 years, only three reports analyzing more than 200 patients were found in the Japanese literature. All papers reported complete recovery in approximately 30%.

DOI： 10.5631/jibirin.95.673

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症例は59歳の男性で,鼻閉を主訴とした.10年前より通年性の鼻閉を自覚していた.両側下鼻甲介粘膜は蒼白で,腫脹し,少量の水様性鼻汁を認めた.両鼻腔内に鼻茸はみられなかった.ハウスダストとダニによる通年性アレルギー鼻炎と診断しプランルカストと局所ステロイド薬の併用による薬物療法を開始した.投与開始後2週間で鼻閉の改善を認め,下鼻甲介粘膜腫脹の改善を認めた

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Language：Japanese   Publisher：Nishinihon Journal of Dermatology  

Epidemiological investigations of Japanese patients with psoriasis have been performed and accumulated by the Japan Psoriasis Society since 1986. But the data of the Japan Psoriasis Society may not properly reflect the real status of psoriasis patients, because those data were obtained only from special core hospitals in Japan. We surveyed psoriasis patients from the general population of many dermatological clinics in Kagoshima prefecture. A total of 402 case cards were gathered, and 379 of the 402 patients lived in Kagoshima prefecture. The male to female ratio of psoriasis was about 2.5: 1. Concerning the clinical types, more than 90% of the patients had psoriasis vulgaris. The date obtained in this investigation basically correlated with those from the Japan Psoriasis Society. © 2000, Western Division of Japanese Dermatological Association. All rights reserved.

DOI： 10.2336/nishinihonhifu.62.361

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Publisher：耳鼻咽喉科臨床学会  

58歳女.眼窩内蜂窩織炎を続発したことによって複視をきたした歯性上顎洞炎例である. 1)炎症は歯牙より副鼻腔を介して直接眼窩内に波及したものと考えられた. 2)抗生物質の発達した今日でも,重篤化する歯性上顎洞炎例が存在することを再認識すべきである

Publisher：耳鼻咽喉科臨床学会  

Publisher：耳鼻咽喉科臨床学会  

非典型的なリンパ節転移をきたした甲状腺乳頭癌新鮮例の2例を報告した.症例1(72歳男)は,甲状腺微小癌(乳頭癌)が患側の所属リンパ節に転移せず,いきなり対側のリンパ節に広範に転移をきたした稀な例で,症例2は(57歳女)は,甲状腺乳頭癌新鮮例で咽後リンパ節まで転移をきたした極めて稀な症例と考えられた

Publisher：耳鼻咽喉科臨床学会  

ステロイド漸減投与にて改善したエアバッグ作動による急性感音難聴症例(22歳女)を報告した.交通外傷患者の診察にあたっては,外傷部位にのみ気をとられることなく,エアバッグ作動の有無や,難聴,耳鳴の自覚の有無についても問診することが必要である

Language：English   Publisher：(一社)日本耳鼻咽喉科学会  

人工内耳手術前の補聴器装用時と術後の言葉のききとりについて良聴耳35〜90dBの残存聴力のある患者で比較した.5例の患者について検討を行ったところ,全例,補聴器よりも言葉のききとりが改善し,筆談を必要としなくなった.これは両側高度難聴者の成績よりも良好であった

Objective: The postoperative speech perception abilities of severely hearing-impaired patients with multi-channel cochlear implant were compared with preoperative speech perception performance with conventional hearing aids. Methods: Cochlear implantation was performed in six severely to profoundly hearing-impaired patients. They had unaided pure-tone thresholds of 70-100-dB HL and aided thresholds of 35-90-dB HL in the better ear, but were not able to perceive speech sounds well with hearing aids. Results: Postoperatively, all the patients had significantly improved speech perception performance, exceeded the average skills of profoundly deaf cochlear implant users, and were able to communicate without writing. Conclusion: These results imply that cochlear implant may be indicated for severely to profoundly deaf subjects, if they receive little or no benefit from conventional hearing aids. Copyright (C) 1999 Elsevier Science Ireland Ltd.

DOI： 10.1016/S0385-8146(99)00016-4

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Publisher：(一社)日本耳鼻咽喉科学会  

人工内耳手術前の補聴器装用時と術後の言葉のききとりについて良聴耳35〜90dBの残存聴力のある患者で比較した.5例の患者について検討を行ったところ,全例,補聴器よりも言葉のききとりが改善し,筆談を必要としなくなった.これは両側高度難聴者の成績よりも良好であった

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Language：Japanese   Publisher：(株)北隆館  

喉頭声門下,気管狭窄は様々な原因で生じ得る。外傷,熱傷,長期挿管,慢性炎症性疾患,感染などの他,原因が不明な特発性のものがある。治療としては呼吸困難の解除が最優先であるが,狭窄部の切開・拡大のみではしばしば再狭窄を伴う。気道から皮膚に開窓し,チューブ留置にて内腔拡大を図ったり,短い場合は切除して上下端の縫合なども行われる。治療経過においての狭窄再燃にも局所における慢性炎症の関与が示唆されている。将来的にはドナー組織の不要な人工材料による再生医療の実用化も期待される。(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞処方のポイント　●急性喉頭炎では対症療法薬の処方が中心となる.●急性喉頭蓋炎に対しては抗菌薬,副腎皮質ステロイド製剤の点滴投与を行う.●急性声門下喉頭炎では副腎皮質ステロイド製剤の全身投与,アドレナリンのネブライザー吸入が有効である.

Language：Japanese   Publisher：(株)日本医事新報社  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞処方のポイント ●急性喉頭炎では対症療法薬の処方が中心となる.●急性喉頭蓋炎に対しては抗菌薬,副腎皮質ステロイド製剤の点滴投与を行う.●急性声門下喉頭炎では副腎皮質ステロイド製剤の全身投与,アドレナリンのネブライザー吸入が有効である.

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：(株)日本医事新報社  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞POINT　▼上・中咽頭疾患の診断に内視鏡検査は必須である。▼先入観をもたず,できるだけ多くの鑑別疾患を考える。▼内視鏡検査に加え,病理組織学的検査,採血検査,画像検査を組み合わせ,正確な診断を得る。

Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞POINT ▼上・中咽頭疾患の診断に内視鏡検査は必須である。▼先入観をもたず,できるだけ多くの鑑別疾患を考える。▼内視鏡検査に加え,病理組織学的検査,採血検査,画像検査を組み合わせ,正確な診断を得る。

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Language：Japanese   Publisher：(株)全日本病院出版会  

本邦では超高齢社会を迎え、否応なく訪れるサルコペニアやフレイルに抗い、さらに健康寿命を延長することが望まれている。声の老化は声帯内の筋の体積減少に加え、粘膜内の細胞外マトリックスの性状変化による声帯構造の変化が主因と考えられる。しかし、このような声帯の器質的変化のみではなく、その他、分泌物の減少による粘膜表面の性状変化や呼吸筋の筋力低下、共鳴腔の変化による影響などについても無視することはできない。声のアンチエイジングを目指し、これまでにも様々なアプローチが用いられている。良好な声帯衛生環境の維持を心がける予防に加え、治療として音声治療、声帯内注入療法、さらには再生医学的アプローチについても検討が行われてきている。個々の症例に応じた適切な評価ならびに治療選択が望まれる。本稿では、声の老化メカニズムおよびアンチエイジングについて概説する。(著者抄録)

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞POINT　▼適切なABCD評価,問診,理学的所見評価,検査を速やかに行う。▼障害臓器の特定と治療の緊急度を判断する。▼気道確保と治療法の正しい選択を行う。▼幅広い疾患の可能性を考慮する。

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞POINT ▼適切なABCD評価,問診,理学的所見評価,検査を速やかに行う。▼障害臓器の特定と治療の緊急度を判断する。▼気道確保と治療法の正しい選択を行う。▼幅広い疾患の可能性を考慮する。

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Language：Japanese   Publisher：(株)全日本病院出版会  

本邦では超高齢社会を迎え、否応なく訪れるサルコペニアやフレイルに抗い、さらに健康寿命を延長することが望まれている。声の老化は声帯内の筋の体積減少に加え、粘膜内の細胞外マトリックスの性状変化による声帯構造の変化が主因と考えられる。しかし、このような声帯の器質的変化のみではなく、その他、分泌物の減少による粘膜表面の性状変化や呼吸筋の筋力低下、共鳴腔の変化による影響などについても無視することはできない。声のアンチエイジングを目指し、これまでにも様々なアプローチが用いられている。良好な声帯衛生環境の維持を心がける予防に加え、治療として音声治療、声帯内注入療法、さらには再生医学的アプローチについても検討が行われてきている。個々の症例に応じた適切な評価ならびに治療選択が望まれる。本稿では、声の老化メカニズムおよびアンチエイジングについて概説する。(著者抄録)

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：Japanese   Publisher：Journal of Cutaneous Immunology and Allergy  

DOI： 10.1002/cia2.12210

Scopus

J-GLOBAL

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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J-GLOBAL

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Publisher：(株)先端医学社  

Language：Japanese   Publisher：耳鼻咽喉科展望会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00579&link_issn=&doc_id=20190111560022&doc_link_id=10.11453%2Forltokyo.61.6_355&url=https%3A%2F%2Fdoi.org%2F10.11453%2Forltokyo.61.6_355&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Publisher：耳鼻咽喉科臨床学会  

Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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Publisher：(一社)日本耳鼻咽喉科学会  

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J-GLOBAL

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Publisher：(一社)日本頭頸部癌学会  

気管は生命維持に不可欠な臓器であるが、時として悪性腫瘍の浸潤、外傷、炎症などによる狭窄のため切除を余儀なくされる。切開により生じる気管欠損は整容的にも、機能的にもハンディキャップとなるが、大きな欠損の再建には難渋することも多い。われわれはin situ tissue engineeringのコンセプトに基づき、コラーゲンの足場をポリプロピレンで補強した生体内組織再生誘導型人工気管を開発した。これまでに、この人工気管を用いた非臨床試験および臨床研究を行い良好な成績が確認されている。現在われわれは、この人工気管の医療機器としての薬機承認および保険収載を目標とし、有効性、安全性を確認するための多施設共同医師主導治験を行っている。対象は既存治療で気管切開孔を閉鎖できない患者と悪性腫瘍切除に伴い気管軟骨の1/2周以上かつ3輪以上の欠損が生じることが予想される患者である。この治験を完遂し、有効性・安全性が確認されれば薬機承認申請を行う予定である。(著者抄録)

Publisher：耳鼻と臨床会  

気管は生命維持に不可欠な臓器であるが、時として悪性腫瘍、もしくは、外傷、炎症などによる狭窄性疾患のため切除を余儀なくされる。切除により生じる気管欠損は整容的にも、機能的にもハンディキャップとなるため、早期の閉鎖が望ましいが、大きな欠損の再建には難渋することも多い。気管の安全かつ簡便な再建方法の確立を目指して、われわれはかねてよりin situ tissue engineeringのコンセプトに基づき人工気管の開発に取り組んできた。コラーゲンの足場をポリプロピレンで補強した生体内組織再生誘導型人工気管は、非臨床試験で長期的な安全性、有効性が確認されており、さらに、施設内倫理委員会の承認のもと行った臨床研究でも良好な治療成績が確認されている。現在われわれは、この人工気管の医療機器としての薬事承認および保険収載を最終的な目標とし、有効性、安全性を確認するための多施設共同医師主導治験を行っている。対象は既存治療で気管切開孔を閉鎖できない患者と悪性腫瘍切除に伴い気管軟骨の1/2周以上かつ3輪以上の欠損が生じることが予想される患者である。(著者抄録)

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

気道は呼吸、嚥下、発声、構音という生命維持や社会生活を送る上で必須の機能を持つ。癌や外傷などで気道の組織が侵された場合、これらを切除した後に機能障害なく再建することは難しい。臓器再生には足場、細胞、成長因子が必要とされている。これらを組み合わせて臓器を再生させようとする研究が数多く展開されているが、臨床に到達した分野はまだ少ない。気管については、Tissue Engineeringの概念を提唱したLanger、Vacantiが、動物実験で体外での気管様の管腔組織再生を報告したが、体内に移植すると吸収されるため臨床応用に用いるのは難しい。一方、われわれは、生体内で組織を再生させるin situ Tissue Engineeringの概念に基づいて、生体内で自己の組織再生を誘導する人工材料(ポリプロピレンメッシュ+コラーゲンスポンジ)を開発した。犬を用いて人工材料を足場として移植し、気管、輪状軟骨弓部などの組織再生に成功した。電子顕微鏡での観察で内腔面に線毛上皮の再生を認め、機械的圧縮試験で再生組織は正常組織と同等の支持力を示した。最長5年の観察期間で狭窄などの合併症を認めず良好な組織再生が得られ、安全性が確認された。2002年より、世界に先駆けて喉頭・気管の再生医療のヒトへの応用を開始した。頸部気管、輪状軟骨の欠損例を対象として、甲状腺癌気管浸潤の即時再建3例、喉頭・気管狭窄の気道再建5例に行い、9ヵ月から最長4年の観察期間でほぼ経過良好である。再建時には気管孔を同時に閉鎖し早期に日常生活に復帰できた。喉頭・気管の再生医療は部分欠損に対してではあるが臨床応用段階に到達しており、日本発の治療技術といえる。今後の課題は、より広い範囲の欠損例への対応、上皮化の加速や声帯隆起再生のための新規技術開発であり、線維芽細胞や脂肪組織由来幹細胞を用いたハイブリッド型人工材料の開発状況を紹介する。(著者抄録)

Publisher：耳鼻と臨床会  

Publisher：(一社)日本炎症・再生医学会  

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Publisher：MARY ANN LIEBERT INC  

Web of Science

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Language：Japanese   Publisher：(株)メディカルレビュー社  

Language：Japanese  

CiNii Books

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Publisher：(株)先端医学社  

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Publisher：日本臨床麻酔学会  

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Publisher：日本音声言語医学会  

術後,音声改善が不十分な場合は薬物治療や音声治療を行う.音声外科手術は比較的低侵襲だが,合併症に局所麻酔でリドカイン中毒,全身麻酔で喉頭痙攣などがあり,詳細な手術の説明と記録により医事紛争の予防を図る.音声外科的治療プログラムの構築には,耳鼻咽喉科医のリーダーシップにより,麻酔科医,言語聴覚士,看護師などを含めたチーム医療が重要である

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Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.55.145

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Publisher：(株)東京医学社  

手術前後の音声を評価する場合,まず簡便なのが聴覚印象評価を記載することである.音響分析については,周期ゆらぎ,振幅ゆらぎ,調波成分と雑音成分の音響エネルギー比の3つのパラメータでよい.発生機能的検査としては,最長発声持続時間が簡便であり,呼気流率,更に声の強さも重要である.局所麻酔での喉頭手術は,患者の声を聞きながら操作できる点で有利である.電子内視鏡下の喉頭手術は低侵襲で主に声帯ポリープ,喉頭肉芽腫がよい適応となり,頸部外切開による喉頭形成手術は声帯麻痺や痙攣性発声障害などが適応となる.患者の音声障害が十分改善された時点或いは少し過矯正した時点で手術を終了する.一方,全身麻酔での喉頭手術は,喉頭直達鏡により安定した視野が得られることからより複雑な手技が可能である

Language：Japanese   Publisher：日本肺癌学会  

CiNii Books

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