楯谷 一郎

【はじめに】局所進行頭頸部扁平上皮癌に対するCetuximab併用放射線療法(Bioradiotherapy:BRT)では急性期に高度な粘膜炎が出現し、嚥下性肺炎などでしばしば治療中断を余儀なくされる。BRTの治療完遂率向上のため、嚥下性肺炎発現のリスク・時期を把握する必要があると考え、本研究ではBRT中の嚥下性肺炎に関して後方視的に検討を行った。【対象】2009年4月から2016年3月までに中下咽頭・喉頭癌の初回治療として導入化学療法(ICT)後に化学放射線療法(CRT)を行った19例、BRTを行った21例の計40例を対象とした。【結果】ICT後のBRTはCRTよりも有意に誤嚥の頻度が高く、治療開始早期から出現していた。急性期の嚥下障害パターンは喉頭下降期型誤嚥で、嚥下性肺炎の発現は局所進行例で有意に多かった。【結論】局所進行例でBRTを行う場合は早期より嚥下性肺炎に留意する必要がある。(著者抄録)

Objective: Severe mucositis during bioradiotherapy (BRT) with Cetuximab for locally advanced squamous cell carcinoma of the head and neck(LA-SCCHN) sometimes causes interruption of the treatment. The aim of this study was to evaluate the pattern of dysphagia following BRT. Materials and Methods: This retrospective study included 21 patients with BRT and 19 patients with CDDPRT following induction chemotherapy (ICT) as an initial treatment from April 2009 to March 2016. We examined the frequency and risk factors of aspiration pneumonia. Results: During BRT, aspiration was observed in the descending stage of the larynx and it occurred more frequently in LA-SCCHN compared to that in early stages. Aspiration as an acute adverse event was more common in the BRT treated group than in the CDDP-RT treated group following ICT. However, dysphagia as late toxicity tended to be higher in the CDDP-RT treated group than in the BRT treated group following ICT. Further, many BRT treated patients experienced aspiration at an earlier time of the treatment, compared to CDDP-RT treated patients. Conclusion: When selecting BRT for LA-SCCHN, it is important to pay attention to aspiration pneumonia as an acute adverse event.

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.

2012年に本邦でセツキシマブが頭頸部癌に適応拡大されて以来、進行頭頸部癌に分子標的薬併用放射線療法(BRT)を施行されることが増えてきた。それに伴い、一次治療としてのBRT後に腫瘍が残存、もしくは再発し、救済手術が必要となる症例もしばしば認められる。BRTでは化学放射線療法(CRT)に比較し、手術に対する影響が軽度であることが期待されているが、本邦におけるBRT後の救済手術に関する報告は未だ限られており、十分な検討はなされていない。われわれはこれまでBRT後の救済手術を3例経験した。(1)下咽頭癌cT3N0の局所再発に対して咽頭喉頭頸部食道摘出術、右頸部郭清術と遊離空腸による再建を行い、特に問題なく経過している。(2)中咽頭癌cT3N2bM0の頸部再発に対して左頸部郭清術を行い、一時的に創部のわずかな離開を認めたが問題なく経過している。(3)声門上癌cT4aN2bの局所再発に対して喉頭摘出術と右頸部郭清術を行うも、術後創傷治癒が遷延し創部感染をきたし、局所皮弁での再建術を要した。この症例では組織の血流は乏しく、重篤な線維化をきたしていた。症例数が少なく今後更なる検討が必要であるが、BRT後の救済手術でもCRT後と同様慎重な対応が必要と考えられた。(著者抄録)

症例は70歳女性で、2週間前に呼吸困難感を自覚し受診した。CTで甲状腺由来と思われる腫瘍が気管内に浸潤し、気道は高度に狭窄していた。気管支内視鏡下に生検を行い、甲状腺乳頭癌と診断された。脈拍81回/分、血圧134/69mmHg、体温37.1℃、SpO2は95%、嗄声および喘鳴は著明であったが、安静時には酸素投与の必要はない状態であった。前頸部には可動性不良で、4cm大の腫瘤を触知した。また、両側鎖骨上窩には3cm大のリンパ節を触知した。喉頭内視鏡所見は左声帯は副正中位に固定し、声帯萎縮を伴っていた。気管内を観察したところ、腫瘍は第4気管輪より尾側の気管軟骨部左側〜内腔へ突出し、同部より頭側の粘膜はクモ状血管腫様の血管拡張を認め、粘膜下へ浸潤が疑われた。気管内腔狭窄は著しく、3mm径の内視鏡の通過が困難で、腫様の下端は評価できなかった。頸部造影CTで甲状腺左葉を主体とする石灰化を伴う5cm大の腫瘍が気管内に高度に浸潤し、また、頸部には複数のリンパ節転移を認めた。また、縦隔リンパ節、多発肺転移を認めた。PET-CTでは頸部・縦隔・肺門のリンパ節に集積を認め、また、肺・肝・腸骨にも集積を認めた。検査結果より甲状腺乳頭癌、cT4aN1bM1と診断し、甲状腺全摘術・D3c郭清術を施行し、術後には放射線ヨード治療を行った。入院後はMSコンチン錠20mg/日投与で呼吸困難感は軽減し、酸素投与を要することなく経過した。腫様が気管内に高度に浸潤しているため気道確保をどのように行うかが問題となり、経口挿管や内視鏡下挿管は不能と考えた。経口挿管、通常気管切開、縦隔気管切開のいずれの方法でも気道確保は困難であった。第1〜2気管輪で気管切開を行い、そこから挿管することで気道確保するのがよいと考えられた。VA-ECMO補助下に第1〜2気管輪を縦切開し同部より挿管を試みた。全身麻酔導入後、VA-ECMOを離脱した。

Papillary thyroid carcinoma progresses slowly and carries a relatively good prognosis. However, invasion of important adjacent structures, such as the recurrent laryngeal nerve, trachea and esophagus, worsens the patient's QOL. While cases of thyroid carcinoma invading the trachea are sometimes encountered, cases of advanced thyroid carcinoma are raraly encounterd in which tracheal intubation is impossible. While performing surgery in these cases, sufficient consideration should be given before the operation to methods for maintaining the airway. Herein, we report a case of thyroid carcinoma invading the trachea, in which tracheotomy needed to be performed under extracorporeal membrane oxygenation (ECMO). A 70-year-old woman presented to a neighborhood doctor with a history of difficulty in breathing. CT showed severe tracheal invasion by a thyroid carcinoma, and the patient was referred to our hospital. A PET-CT revealed its metastases in the lung, liver, and bones. Biopsy of the tumor invading the trachea revealed the diagnosis of papillary carcinoma. Because the airway stenosis was severe, usual tracheal intubation, as well as usual tracheotomy and mediastinal tracheotomy, was difficult. Therefore, we incised the first and second tracheal rings not invaded by tumor and carried out intubation through the tracheotomy stoma. We used ECMO in anticipation of airway obstruction due to bleeding, and were therefore able to maintain the airway. Thereafter, we performed total thyroidectomy, D3c neck dissection, and tracheal fenestration. After the operation, radioactive iodine therapy was administered and the fenestrated trachea was closed by staged operations.

Narrow band imaging(NBI)をはじめとする内視鏡診断技術が頭頸部領域にも応用され、従来では発見し得なかった微小な表在癌を診断できるようになってきた。これらの表在癌は当初は消化器内科医によってEndoscopic submucosal dissection(ESD)などにより治療されていたが、咽喉頭病変の治療に特化した術式として佐藤らによりEndoscopic laryngo-pharyngeal surgery(ELPS)が開発された。その特徴は彎曲型喉頭鏡とNBI機能付き上部消化管拡大内視鏡によって視野を確保し、耳鼻咽喉科医が切除を行うことにあり、初期には表在癌に対してのみ行われていたが、最近ではその適応が浸潤癌にも拡大されつつある。ELPSのメリットは彎曲型喉頭鏡とNBI機能付き上部消化管拡大内視鏡による良好な術野、ウォータージェット機能をはじめとする拡大内視鏡のさまざまな機能的サポートが受けられること、上皮化注射により深部組織を温存することで術後の声帯運動制限・嚥下機能低下を最低限に抑える超低侵襲治療であること、頸部食道に病変が進展している場合にもESDをその場で併用することで対処可能なことにある。咽喉頭癌治療における選択肢の一つとして経口的ロボット支援手術が世界的に普及しつつある現在、わが国で独自に開発された安価で低侵襲な治療法であり、今後の更なる発展・普及が期待される。(著者抄録)

36歳男。13ヵ月前より無痛性の下顎左側の腫脹を自覚し、腫脹の増大とともに左下6〜8番歯の自然脱落を認め、近医にてエナメル上皮腫が疑われ当科紹介となった。パノラマX線では下顎骨左側に多房性の透亮像を認め、造影CTでは下顎骨左側の内部に造影効果を伴う多房性腫瘤を認めた。また、骨皮質には菲薄化を認めた。MRIではT1強調像で低信号、T2強調像で不均一な高信号を呈する嚢胞性変化を伴う病変として描出された。画像所見より歯原性腫瘍が疑われ、病理組織学的検査を再度行ったところエナメル上皮癌の診断に至った。初診3ヵ月後に下顎骨区域切除術、右遊離腓骨皮弁移植術、両側頸部郭清術、気管切開術を施行し、最終的にエナメル上皮腫から二次的に発生したエナメル上皮癌と診断された。術後経過良好で、術後1年経過した現在、再発・転移は認めていない。

The specialized microanatomy of the vocal folds is essential for the voice production. Intimate knowledge of vocal fold histology is fundamental for understanding voice disorders and necessary for approaching treatment. This chapter is focused on how the histologic features of human vocal folds are developed from the fetal period. The process of vocal fold development is mainly characterized by two events: The organization of fibrous proteins that leads to the formation of vocal ligament, and the appearance of macular flavae. Recent contributions to our growing understanding of these events are addressed. The factors that promote vocal fold development are also discussed and lastly a future direction of vocal fold histophysiology is suggested.

IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentrations, tissue infiltration by IgG4-positive plasma cells and formation of pseudotumor with fibrosis. Occuurence of IgG4-RD has been described in multiple sites, from salivary glands, thyroid gland, pancreas and bile duct retroperitoneum. IgG4-RD with pseudotumor of the larynx is extremely rare, with only 5 cases reported in the literarure until date. A 62-year-old female patient was admitted to our hospital with a submucosal tumor in the right supraglottic area. Biopsy was performed under general anesthesia twice. The histological findings showed only fibrosis and chronic inflammatory plasma cells. However, the serum IgG4 level was clearly elevated to 1460 mg/dl. In addition, immunohistological staining of the larynx, parotid gland and lymph node confirmed the diagnosis of IgG4-RD. Treatment was started with a high dose of prednisolone (0.6 mg/kg/day) for 2-4 weeks, with tapering of the dose subsequently tapered to 8 mg/day. About 3 days after the initiation of treatment, the pseudotumor of the larynx disappeared completely. This case is only the sixth report of the association of IgG4-RD with pseudotumor of the larynx. The initial symptom in all patients was hoarseness, and only one gave a history of dyspnea. All the case had been treated with prednisolone and showed improvement of the laryngeal symptoms, except in one case which developed persistent vocal cord immobility. There is an urgent need for prompt treatment when the larynx is involved, considering the potential for irreversible damage. Long term follow-up and careful check up of whole body are required.

Robotic surgery is ushering in a new era in surgery by offering patients better outcomes and has already become one of standard modalities in urology and gynecology. In the otolaryngological field, after the FDA clearance in 2009, transoral robotic surgery (TORS) has now been widely adopted by head and neck surgeons for treatment of benign and malignant conditions of the pharynx and larynx. TORS has also been adopted for treatment of parapharyngeal tumors, sleep apnea, recurrent nasopharyngeal cancer, retropharyngeal node metastasis. Another use of surgical robots in otolaryngology is thyroidectomy and neck surgery. Robotic thyroidectomy has been developed mainly by Korean surgeons and the technique evolved into robotic neck dissection. Despite the 2nd biggest market of surgical robots in the world, the access to surgical robot for otolaryngology is very limited in Japan because da Vinci has not been approved for otolaryngological field by pharmaceuticals and medical devices agency (PMDA) yet. Multi-institutional clinical study of TORS is currently conducted in order to clear PMDA. The limitations and future directions of surgical robots in otolaryngology are also discussed.

We report herein on a case of minocycline-induced black thyroid with papillary thyroid carcinoma. A 60-year-old female, who had taken oral minocycline intermittently for osteomyelitis of the mandible for two years, noticed a palpable thyroid nodule. Fine needle aspiration of the nodule revealed atypical cells and the serum thyroglobulin level was high. Under the diagnosis of suspected thyroid carcinoma, a hemithyroidectomy with central compartment neck dissection was performed. The color of the tumor, which was diagnosed as a papillary carcinoma, was white. On the other hand, the color of the normal thyroid gland was dark red to black with minocycline pigmentation. Minocycline therapy may induce headache, nausea, vomiting, liver dysfunction and dental hyperpigmentation in children. But a minocycline-induced black thyroid is uncommon. Recently, there have been some reports that the risk of malignancy in black thyroid glands is higher than in non-black thyroids.

Ameloblastic carcinoma is a rare odontogenic tumor which arises in the mandible or maxilla. It is classified into the primary and secondary types, and the latter one is extremely rare. We report herein on a case of secondary ameloblastic carcinoma in a 36-year-old man who complained of indolent swelling at the left side of the mandible. CT and MRI images revealed a multiocular mass with bone destruction in the mandible, and the existence of the ameloblastic carcinoma was confirmed with multiple biopsies. The lesion was resected en bloc with a 1.5 cm safety margin, and reconstructed with an osteocutaneous fibula flap. The histological features of the tumor were consistent with secondary ameloblastic carcinoma. Neither recurrence nor metastasis has been found for one year after the surgery. The clinical, radiological and histological features of the ameloblastic carcinoma are discussed with reference to the relevant literature.

62歳女。嗄声を主訴とし、喉頭内視鏡で右仮声帯から喉頭室にかけて隆起性腫瘍を認めた。MRIでは右仮声帯から傍声帯間隙にT2強調像で低信号、拡散強調像で高信号を示す15×20mmの腫瘤を認めた。PET-CTで遠隔転移は認めなかった。喉頭癌を疑い、生検目的に2度にわたり喉頭顕微鏡下手術を施行したが、形質細胞や好中球の浸潤、線維化を伴う肉芽組織の像であり、悪性所見は認めなかった。サルコイドーシス等を疑い免疫内科で精査したところ、血清IgG4が1460mg/dlと高値を示し、IgG4関連疾患が疑われた。生検組織の免疫染色を追加し検討した結果、IgG4染色でIgG4陽性形質細胞の平均が303個/HPF、IgG4/IgG比が56.3%で、IgG4関連疾患に矛盾しない所見が得られた。更に、10年以上持続する両側耳下腺の腫脹が判明し、生検を施行しIgG4関連疾患に矛盾しない所見を認めた。喉頭に偽腫瘍を合併したIgA関連ミクリッツ病と診断し、プレドニゾロンの内服を開始したところ、3日後に腫瘍は縮小し、420日後に血清IgG4は240mg/dlに低下した。

Transoral robotic surgery (TORS) was developed by Weinstein as a minimally invasive surgery mainly for laryngo-pharyngeal cancer. Da Vinci surgical system is a robot which enables to perform surgery safely and precisely under 3D vision. Since TORS had been cleared by FDA in 2009, it has been spreading explosively all over the world. However, it has not been approved by Pharmaceutical and Medical Devices Agency (PMDA) in Japan. We have attended the advanced course of TORS training held in Yonsei University prior to start the clinical trial of TORS and have performed radical tonsillectomy, tongue base resection, supraglottic laryngectomy, and piriform sinus resection for a cadaver. It was easy to adapt the movement of Da Vinci and transoral anatomy was a key to perform TORS safely. PMDA approval is desired in the otolaryngological field.

Over the years, numerous articles have appeared concerning voice therapy for the treatment of dysphonia in non-singers, including some with evidence-based medicine. However, evidence for voice therapy for singers has largely been lacking. Here we report nine singers with vocal fold nodules, vocal fold scarring, vocal fold atrophy or hyperfunctional dysphonia whose disorders were successfully treated by voice therapy. The nine patients (5 men and 4 women; mean age, 53.3 years) underwent voice therapy consisting of forward focus, such as semi-occluded vocal tract therapies, vocal function exercises (VFE) and resonant voice therapy (RVT). The effectiveness of the treatment was assessed by GRBAS, stroboscopic examinations, aerodynamic assessment, acoustic and formant analysis, and voice handicap index (VHI)-10 performed before and after voice therapy. All patients showed improvement of voice. Significant improvements were shown in maximum phonation time, GRBAS and VHI-10. One of the major changes in the singers was a more prominent formant cluster. These results indicate that voice therapy consisting of forward focus can help improve vocal function in singers with dysphonia.

IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentrations, tissue infiltration by IgG4-positive plasma cells and formation of pseudotumor with fibrosis. Occuurence of IgG4-RD has been described in multiple sites, from salivary glands, thyroid gland, pancreas and bile duct retroperitoneum. IgG4-RD with pseudotumor of the larynx is extremely rare, with only 5 cases reported in the literarure until date. A 62-year-old female patient was admitted to our hospital with a submucosal tumor in the right supra-glottic area. Biopsy was performed under general anesthesia twice. The histological findings showed only fibrosis and chronic inflammatory plasma cells. However, the serum IgG4 level was clearly elevated to 1460 mg/dl. In addition, immunohistological staining of the larynx, parotid gland and lymph node confirmed the diagnosis of IgG4-RD. Treatment was started with a high dose of prednisolone (0.6 mg/kg/day) for 2-A weeks, with tapering of the dose subsequently tapered to 8 mg/day. About 3 days after the initiation of treatment, the pseudotumor of the larynx disappeared completely. This case is only the sixth report of the association of IgG4-RD with pseudotumor of the larynx. The initial symptom in all patients was hoarseness, and only one gave a history of dyspnea. All the case had been treated with prednisolone and showed improvement of the laryngeal symptoms, except in one case which developed persistent vocal cord immobility. There is an urgent need for prompt treatment when the larynx is involved, considering the potential for irreversible damage. Long term follow-up and careful check up of whole body are required.

We report herein on a case of minocycline-induced black thyroid with papillary thyroid carcinoma. A 60-year-old female, who had taken oral minocycline intermittently for osteomyelitis of the mandible for two years, noticed a palpable thyroid nodule. Fine needle aspiration of the nodule revealed atypical cells and the serum thyroglobulin level was high. Under the diagnosis of suspected thyroid carcinoma, a hemithyroidectomy with central compartment neck dissection was performed. The color of the tumor, which was diagnosed as a papillary carcinoma, was white. On the other hand, the color of the normal thyroid gland was dark red to black with minocycline pigmentation. Minocycline therapy may induce headache, nausea, vomiting, liver dysfunction and dental hyperpigmentation in children. But a minocycline-induced black thyroid is uncommon. Recently, there have been some reports that the risk of malignancy in black thyroid glands is higher than in non-black thyroids.