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ObjectiveThis study aimed to clarify whether circulating miR-21 represents a predictive biomarker in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, and to investigate the effect of miR-21 inhibitor for chemoradiation in human SCC cells.MethodsPlasma samples were obtained from 22 patients with HNSCC and 25 non-cancer volunteers. Plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. The effects of miR-21 inhibitor in human SCC cells were investigated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blot analysis.ResultsPlasma miR-21 expression was higher in HNSCC patients than in control patients (p< 0.001). Seven patients with recurrence showed significantly higher plasma miR-21 than the 15 patients without recurrence. Moreover, miR-21 inhibition significantly enhanced cisplatin- or radiation-induced apoptosis. Western blot analysis suggested the programmed cell death 4 (PDCD4) protein as a potential target of miR-21 in relation to apoptosis. Adding miR-21 inhibition to radiation or cisplatin treatment provided clear and potent suppression of tumor cell proliferation.ConclusionThis study provides new insights into the role of miR-21 as a predictive biomarker for HNSCC treated with chemoradiotherapy, and suggests a potential target to improve the effects of chemoradiotherapy against HNSCC.

To determine the efficacy of endoscopic electrocauterization for pyriform sinus fistula (PSF) using a flexible Bugbee cautery electrode. From 2009 to 2016, a total of eight patients with acute suppurative thyroiditis or cervical abscess secondary to PSF were retrospectively registered in our study (three males, five females; median age 6.5 years). All patients underwent endoscopic electrocauterization as treatment for PSF. Six of eight patients had no recurrence after the initial endoscopic electrocauterization of PSF. One patient with recurrence developed symptoms 9 days after cauterization and another experienced recurrence after 2 years. Mean follow-up for the eight patients was 50 months (range 5-96 months). No post-operative complication was reported. Endoscopic electrocauterization appears to be a less-invasive, safe, and effective method for the treatment of PSF.

The present study aimed to clarify the incidence and clinical outcomes of nasopharyngeal carcinoma (NPC) in the Chubu region of Japan from 2006 to 2015, compared with previous reports. A retrospective analysis was conducted based on medical records from 40 hospitals located in the Chubu region in the central Japanese main island, with a population of around 22.66 million individuals. This study was designed in line with to two previous clinical studies into NPC conducted in the same area of Japan. We recruited NPC patients diagnosed in hospitals across this area over a 10-year period (2006&ndash, 2015) using a questionnaire about sex, age, primary site, clinical symptoms, pathology, Union for International Cancer Control (UICC) staging, serological exam, treatment, and survival. A total of 620 NPC patients were identified. The age-standardized incidence of NPC from 2006 to 2015 was 0.27 per 100,000 individuals per year. There were no significant differences between this study and the previous two studies conducted in the same area of Japan. The five-year overall survival rate for all patients was 75.9%, while those for patients with stages I, II, III, and IVA were 97%, 91%, 79%, and 68%, respectively. The age-standardized annual incidence of NPC in the present study was 0.27 per 100,000 individuals per year, which was relatively low and stable. The five-year overall survival rate for all NPC patients was significantly improved in this decade compared with previous studies. The smoking rates in male and female NPC patients were 64.5% and 18.8%, respectively, thereby suggesting the involvement of smoking in the incidence of NPC.

The aim of the study is to investigate plasma miR-21 for a possible therapeutic effect determination marker in head and neck squamous cell carcinoma (HNSCC). Plasma samples are obtained from 86 HNSCC patients and 29 non-cancer volunteers who had been treated at Mie University Hospital between May 2015 and December 2016, and plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. In addition, plasma miR-21 level of advanced HNSCC patients including 22 non-recurrent cases and 11 recurrent cases before and after treatment was analyzed using a longitudinal design. Plasma miR-21 expression in 86 HNSCC patients was obviously higher than in 29 control patients (P < 0.0001). The area under the curve (AUC) for plasma miR-21 was 0.756 (95% confidence interval: 0.661-0.851). Furthermore, our longitudinal study of plasma miR-21 showed that the expression level of plasma miR-21 was significantly reduced at the time point of 2 months after treatment in case of no recurrence. On the other hand, plasma miR-21 was not decreased after treatment in case of 10 patients who had developed recurrences during the follow-up period. This study may provide new insights into the role of plasma miR-21 as a biomarker for HNSCC, and plasma miR-21 would be useful for early detection of tumor recurrence after operation or chemoradiotherapy.

Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.

Pyriform sinus fistula (PSF) is an anomaly that can arise due to failure of involution of the third or fourth branchial cleft during embryogenesis. It can manifest clinically as sinuses, cysts, or abscesses in the neck and is common in childhood. Herein, we describe a neonate who presented with neck swelling and respiratory distress, which was secondary to a fourth branchial pouch sinus. Physical examination revealed swollen areas in the posterolateral pharyngeal wall and on the external left side of the neck. Computed tomography imaging showed a left-sided mass that was filled with air and fluid. Eventually, the pyriform sinus cyst and the entire fistulous tract were excised. The postoperative course was uneventful. Follow-up after 18 months showed no recurrence.

Circulating microRNAs (miRNAs) are emerging as promising non-invasive biomarkers for human cancer. Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy worldwide, but its overall survival has remained unchanged in the past 3 decades. Biomarkers for evaluating efficacy of cancer therapy are urgently needed. To explore circulating miRNAs as cancer therapy biomarkers, we initially identified that 8 miRNAs were distinctly dysregulated in cancerous tissues compared with adjacent non-cancerous counterparts from 16 patients, using microarray and real-time PCR. Based on this discovery, the comparison study was performed between pre- and 6 months post-operative paired plasma samples on 9 patients. MiR-99a, which was down-regulated in cancerous tissues, was significantly increased in plasma after operation. Meanwhile, oncomiR miR-21 and miR-223 that were up-regulated in cancerous tissues, were significantly reduced in post-operative plasma samples. We firstly report the significant changes of miR-99a in plasma of HNSCC patients after surgery. Furthermore, plasma miR-223 was inversely increased in a patient whose cancer relapsed within 6 months after operation. We conclude that these circulating miRNAs may serve as biomarkers to evaluate the efficacy of therapy and the prognosis of HNSCC.

Foreign body ingestion is a commonly encountered clinical problem. In particular, sharp foreign bodies lodged in the esophagus or hypopharynx can cause complications and require urgent removal. Removal by flexible esophagogastroduodenoscopy or rigid esophagoscopy is the treatment of choice and has high success rates, but cases in which these methods are unsuccessful must be treated with an external incision. A 62-year-old man was referred for a fish bone lodged in the hypopharynx that could not be removed by flexible esophagogastroduodenoscopy. We removed the bone transorally using a specially designed rigid curved laryngoscope. Based on our experience, this method may have clear practical value due to advantages of a wide field of view and use of multiple rigid forceps. Indications may be limited, but this novel method may reduce the limitations of noninvasive removal of foreign bodies.

We report a case of papillary carcinoma of the thyroid gland and cervical lymph node metastases with concurrent tuberculous lymphadenitis that was diagnosed preoperatively. A 35-year-old woman presented with multiple lymph node swellings and an anterior neck mass. No findings suggesting the coexistence of pulmonary tuberculosis were present. The patient underwent a total thyroidectomy with bilateral neck dissection together with medication. Measures to prevent tuberculosis were undertaken during the perioperative period. The histopathological diagnosis was papillary carcinoma with both metastatic and tuberculous lymphadenitis of the lymph nodes in the neck. The possible coexistence of tuberculous lymphadenitis must be ruled out when lymph node swellings are observed in patients with head and neck cancer, including thyroid carcinoma.

Cetuximab is remarkable for the relatively high rate and severity of hypersensitivity reactions (HR) being reported in the literature. Screening for cetuximab‐specific IgE in serum via immunoassay has been found to be useful in preventing HR; however, these tests are known to have a low positive predictive rate. In an attempt to remedy this, we evaluated the interaction between cetuximab and IgE on basophils for predicting severe cetuximab‐induced HR. Twelve head and neck cancer patients were enrolled in this single‐institution study: four with a history of cetuximab‐induced HR and eight with no such history. Cetuximab‐specific and galactose‐α‐1,3‐galactose (α‐gal) specific IgEs in serum were measured in vitro using an enzyme‐linked immunosorbent assay (ELISA). IgE‐cetuximab binding on basophils was also analyzed to evaluate the decrease in cetuximab molecules on basophils after dissociation of IgE from FcεRI. The positive predictive value associated with the presence of cetuximab‐ or α‐gal‐specific IgE in serum was found to be only 0.67, whereas the negative predictive value was 1.00. On the other hand, in all four patients who developed HR, the cetuximab molecules on basophils were decreased significantly due to the dissociation of IgE from basophils (P

Objectives: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. Methods: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. Results: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. Conclusions: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

重度誤嚥で苦しむ2症例に対し，鹿野らにより修正された声門閉鎖術を行った。甲状軟骨ならびに輪状軟骨を鉗除した後に正中にて喉頭内腔に侵入し視野を展開した。その後，上下声帯粘膜弁ならびに胸骨舌骨筋弁を用いて声門閉鎖を行った。この術式はこの2症例に対し成功し，かつ術後経過も良好であった。結論として，成人の嚥下性肺炎の治療としては，本術式は効果的でリスクも少ないと思われた。

Objectives: Eosinophilic chronic rhinosinusitis (ECRS) is considered a refractory and intractable disease with thick mucus production, long-term nasal congestion, loss of sense of smell and intermittent acute exacerbations secondary to bacterial infections. In this study, we investigated which growth factor is deeply involved in the mucin overproduction in ECRS. Method: We employed fluorescence immunohistochemical analysis to evaluate whether or not TGF-α expression was upregulated in the nasal tissue of ECRS patients. We also examined MUC5AC transcription using a luciferase reporter plasmid in HM3-MUC5AC cells and A549 cells in order to assess the role of TGF-α in human epithelial cells. Results: TGF-α immunoreactivity was found markedly increased in the submucosal tissue in the ECRS patient compared with that of a normal patient and with noneosinophilic CRS. TGF-α synergized with TNF-α to upregulate MUC5AC expression in human epithelial cells through the ERK signaling pathway. Conclusion: Our results demonstrated that TGF-α was highly expressed in the upper airway tract in ECRS patients and is deeply involved in mucus hypersecretion.

2005年から2009年の間に当科で初回治療を行った下咽頭扁平上皮癌53例に対し検討を行った。そのうち40例は800mg/m2の5-FUを1日目から5日目にかけて投与し，6日目に80mg/m2のシスプラチンを投与するレジメンを用いた同時化学放射線療法にて治療を行った。局所CRに至ったのは40例中34例，85%であり，切除可能例では97%であった。全体では疾患特異的5年生存率は51%であり，切除可能例では68%であった。主な有害事象は白血球減少と粘膜炎であるが，それらは許容範囲内であり，死に至るような重篤な例はみられなかった。今回の検討でシスプラチン（80mg/m2）と5-FU（800mg/m2）を用いた同時併用化学放射線療法は下咽頭扁平上皮癌に対し効果的な治療法であり，有害事象も共用できる範囲であると思われた。しかしながら進行下咽頭癌に対する新しい治療戦略における更なる見当が必要と思われた。

Head and neck cancer is frequently accompanied with other primary cancers, especially esophageal cancer. Among 337 cases with head and neck cancers treated at Mie University Hospital from January 2001 to December 2005, 31 cases (9.2%) had multiple cancers. Oropharyngeal cancer and hypopharyngeal cancer cases showed esophageal cancer significantly more frequently than other head and neck cancer cases (25.0-26.7%). Brinkman's index was significantly higher in the group with cancer of the oropharynx associated with esophageal cancer than in the group without any other primary cancer. Sake index was significantly higher in the group with cancer of the oropharynx or hypopharinx associated with esophageal cancer than in the group without any other primary cancer. Endoscopic examinations should be routinely performed after the treatment of head and neck cancer.

A retrospective clinical study was conducted involving 143 patients with laryngeal cancer treated in our department between 1998 and 2006. The subjects consisted of 138 males and 5 females, with a ratio of 28:1. The mean age was 68.1 years old. The subsite of origin comprised 78 (54.5%) in the glottis, 61 (42.7%) in the supraglottis, and 4 (2.8%) in the subglottis. The clinical stage according to the 1997 UICC TMN classification system was I in 53 cases (37.1%), II in 34 (23.8%), III in 20 (14.0%), and IV in 36 (25.2%). The 5-year overall survival rate was 71.2% in the total cases, 84.4% in stage I, 89.6% in stage II, 51.2% in stage III, and 38.9% in stage IV. The disease-specific 5-year survival rate was 88.3% in the total cases, 75.5% in the supraglottic type, 98.1% in the glottic type, and 100% in the subglottic type. The preservation rate of the larynx at 5 years was 83.3% in T1, 56.5% in T2, and 0% in T3 and T4.

1991年から2007年までに当科で治療を行った原発不明頸部転移癌症例27例を対象として，retrospectiveに検討した。病期はN1症例は0例，N2aは8例，N2bは9例，N2cは1例，N3は9例であった。治療としては，15例に頸部郭清が施行されており，8例に頸部郭清ならびに術後放射線治療が行われていた。5年生存率は全体で31.0%，根治治療例で45.0%であった。4例が治療開始後に原発巣が判明した。生存結果は臨床的N分類によく相関していた。結論として，潜在的原発部位に放射線治療を行うこと，N進行例には術後化学放射線同時併用療法を行っていくべきと思われた。

Fish bones as a foreign body are often present in the palatine tonsil and the base of the tongue. Such foreign bodies can often be diagnosed with inspection only. However, it is difficult to diagnose and extirpate a foreign body when it is buried in the oral/pharyngeal mucosa. We experienced a case of a fish bone foreign body buried in the tongue muscle layer. We report herein on the case of a 49-year-old man with a fish bone foreign body buried in his tongue. The patient had noticed a sore throat since eating a sea bream and was referred to our department. Visual inspection revealed no foreign body, but CT imaging revealed a fish bone in the tongue. We performed an emergency surgical exploration of tongue to locate the fish bone. Because the fish bone as a foreign body was unable to be confirmed by palpation, we identified the location of the fish bone by intraoperative CT. This is a rare case of a fish bone buried in the tongue muscle layer, and intraoperative CT was useful in identifying the positon of the foreign body.

甲状腺癌手術において反回神経麻痺は可及的に避けねばならない合併症であるが, 時に, 癌の浸潤のために反回神経を犠牲にせざるをえない場合がある。一側の反回神経麻痺は致命的ではないが, 患者の苦痛は深刻である。正常な声帯の可動性が再獲得できないことから, 従来から神経の再建は必要ないとされてきたが, 声帯の萎縮防止と発声時に声帯が緊張するため, 音声は良好である。今回, 反回神経の即時再建を13例に施行した。神経間移植が5例, 頸神経ワナ-反回神経吻合が8例に行われた。声帯の可動性は全例で認められなかった。MPTが9例において正常に, 呼気流量 (VC/MPT) が11例において正常範囲に復帰した。一方で, 非再建群では, MPT, VC/MPTとも正常化したものはなかった。MPT, VC/MPTによる音声機能評価では, 神経の即時再建は有用であると言える。

Background Pendred's syndrome (PS) is an autosomal recessive disorder characterized by goiter and congenital sensorineural hearing loss. Recent advances in molecular biology revealed the gene responsible for PS (PDS) and provided an important aid for the diagnosis of this condition. Methods A case of PS with huge goiter and congenital hearing impairment was diagnosed by mutational analysis of the PDS gene. Results Physical examination and computer tomography CT revealed a diffuse swelling of the thyroid gland. Thyroid function tests were normal, and the perchlorate discharge test was negative. Audiologic examination confirmed sensorineural hearing loss, and temporal bone CT revealed bilateral enlarged vestibular aqueducts. The mutational analysis revealed that the patient was homozygous for His 723 Arg (2168AG) in exon 19, a missense mutation. Conclusions The results of thyroid function tests in PS patients are usually normal, and the positive perchlorate discharge test has been used for the diagnosis. However, this is a nonspecific test and is not sensitive enough for PS. In our case, despite a negative perchlorate test, the patient was diagnosed by mutational analysis and received total thyroidectomy to relieve respiratory distress caused by thyroid enlargement. This is the first report of a mutation detected in the thyroid tissue and clearly shows that the mutation caused histopathologic change in that gland. © 2002 Wiley Periodicals, Inc.

We report the case of a 42-year-old male with Harada's disease who showed impairment of bilateral, vestibular and cochlear function. He showed bilateral sensorineural hearing loss on an audiogram and canal paresis in Caloric response. The systemic administration of betamethasone was effective: his visual acuity and hearing level normalized and vertigo subsided.

1989年から1999年の早期頭頸部癌に対する根治照射後に, 遅発性気道狭窄をきたした7例を検討した。対象は54歳から77歳の男性6例, 女性1例であった。内訳は喉頭癌声門型T1a, T1b各1例, T2; 3例, 声門下T2; 1例, 原発不明癌1例であった。照射終了からの期間は3ケ月から3年11ケ月 (中央値7ケ月) であった。線源はすべて60Coで, ライナックは1例もなかった。照射線量は60Gy3例, 70Gy4例であった。1例は1側の声帯運動障害を伴い計4回の再燃を来たした。3例で気管切開を行い, 両側声帯運動障害が主因であった。同期間に根治照射をした喉頭癌90例をコントロールとして, 背景, 治療方法, 粘膜反応性を比較した。その結果, 照射線源 (60Co), 線量, 頸部手術, 使用鎮痛薬と使用時期, 粘膜炎の出現時期, 照射中の喉頭浮腫が危険因子としてあげられ, 特に照射中の粘膜炎の出現時期と程度が重要と考えられた。

最近24年間に当科にて治療を行った頭頸部腺様嚢胞癌40例を対象として, 累積生存率, 病期別, 原発部位別, 組織型別, 放射線治療の有無, 遠隔転移の有無についてそれぞれ検討を加えた。結果は5年及び10年生存率はそれぞれ74.8%と47.4%であった。病期別では stage III-IVは stage I-IIに比して有意に予後不良であった。原発部位別では上顎・鼻副鼻腔が他部位にして予後不良であった。放射線治療併用の有無, 遠隔転移の有無で予後については統計学的に有意差は認められなかった。遠隔転移例で手術可能例はその他の群に比して有意に予後が改善された。結論は1) 上顎や鼻副鼻腔は手術時に十分な切除がされていない場合が多く, より拡大切除が望まれた。2) 放射線による予後改善までは認められなかった。3) 遠隔転移例でも可能であれば手術を考慮すべきである。

The patient was an 82-year-old female with a swelling at the left side of the soft palate. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large cystic tumor in the left parapharyngeal space. The cystic tumor was removed via a cervical approach with mandibulotomy (mandibular swing approach). Postoperative histological examination revealed a pleomorphic adenoma with cystic formation.Pleomorphic adenoma with large cystic formation is rare in the parapharyngeal space and a differential diagnosis includes branchial cleft cyst, abcess, cystic hygroma, metastatic lymph node with central necrosis and aneurysm. CT and MRI are essential for diagnosis and provide information on the size and location of the tumor. There are several possible approaches to tumors in the parapharyngeal space: transoral excision, cervical approach with or without mandibulotomy and transparotid approach. It is preferable to perform a mandibular swing approach for the removal of the large tumor in the parapharyngeal space.

One hundred fifty patients have been tracheostomised in the past five years at Yamada Red Cross Hospital. Of these 150 patients, 90 were proposed for tracheostomy by other departments, and such cases are on the increase. Thirty-two patients showed indications for tracheostomy in the stenosis of the aero-tract caused by the tumors or mucosal swelling. Prophylactic tracheostomy was performed in 23 cases due to a delayed stenosis of the aero-tract. Emergent tracheostomy was performed in 31 cases, and, of these cases, an incision of the cricothyroid membrane was performed in one case. Though tracheostomies have been performed in many departments, the determination of accurate indications and safe operative techniques for different cases are best assisted when performed by head and neck surgeons.

Frequently, double cancer and distant metastases have been detected by means of therapeutic techniques for head and neck cancers. Between January 1997 and February 1999, we experienced 59 cases of head and neck Squamous cell carcinoma in the department of otolaryngology at the Yamada Red Cross Hospital. Eight patients of 59 (13.6%) had pulmonary metastases and/or primary lung cancers, detected by chest CT scans. However, such lesions in 4 patients of 59 (6.8%) were detected by normal Chest X-rays. Positive correlations were observed between T stage and positive CT scans.CT scanning of the chest is more effective than chest X-ray, and is now used routinely in our department prior to undertaking major head and neck surgery.

Recurrent laryngeal nerve (RLN) paralysis is a major complication after thyroidectomy. Immediate reconstruction of the RLN is proposed in such cases.Four cases underwent concurrent recurrent laryngeal nerve reconstruction at our department between 1997 and 1998.Nerve transfer was performed in three cases and the great auricular nerve and the ansa cervicalis were chosen as nerve grafts. Direct anastomosis of the ansa cervicalis to the peripheral end of the RLN was conducted in one case. Both procedures resulted in a good post-operative status, and hoarseness and mis-swallowing in no cases were observed.The operated-side vocal cords in all cases were observed to be fixated at the paramedian portion, without atrophy. The average maximum phonation time (MPT) was 14.5 seconds, and this was longer than that in cases who had not undergone reconstruction of the recurrent laryngeal nerve (their average MPT was 8.9 seconds).We concluded that an immediate reconstruction of the RLN should be disirable for cases who need a nerve resection in a thyroid operation.