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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。

Background/Aims: Long-term macrolide therapy is an effective treatment for chronic sinusitis and diffuse panbronchiolitis. However, long-term use of macrolides may promote the growth of drug-resistant bacteria; therefore, development of macrolides with no antibacterial action is desirable. A new erythromycin (EM) derivative, (8R,9S)- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), does not possess antibacterial action. Methods: To determine whether EM900 induced a clinically relevant anti-inflammatory response and repressed mucin gene expression in cells derived from human airway epithelia, we assessed the effects of EM900 on IL-1β-induced inflammatory cytokines in A549 cells and MUC5AC gene expression in HM3-MUC5AC cells. We also investigated the effects of EM900 on IL-1β-induced NF-ĸB activation. We performed reporter gene assays and quantitative PCR in A549 and HM3-MUC5AC cells. Results: Both EM and EM900 suppressed IL-1β-induced IL-8 expression in A549 cells. EM900 also suppressed IL-1β-induced IL-1β and TNF-α expression in A549 cells. EM900 inhibited IL-1β-induced MUC5AC expression in HM3-MUC5AC cells. Both EM and EM900 suppressed IL-1β-induced NF-ĸB activation in A549 cells. Conclusion: This study demonstrated that EM900 suppressed the induction of inflammatory cytokines and MUC5AC gene expression in cells derived from human airway epithelia, and our findings indicate that these effects may be mediated by the suppression of NF-ĸB activation.

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.

Gram-positive bacterium Streptococcus pneumoniae is an important human pathogen that colonizes the upper respiratory tract and is also the major cause of morbidity and mortality worldwide. S. pneumoniae causes invasive diseases such as pneumonia, meningitis, and otitis media. Despite the importance of pneumococcal diseases, little is known about the molecular mechanisms by which S. pneumoniae-induced inflammation is regulated, especially the negative regulatory mechanisms. Here we show that S. pneumoniae activates nuclear factor of activated T cells (NFAT) signaling pathway and the subsequent up-regulation of inflammatory mediators via a key pneumococcal virulence factor, pneumolysin. We also demonstrate that S. pneumoniae activates NFAT transcription factor independently of Toll-like receptors 2 and 4. Moreover, S. pneumoniae induces NFAT activation via both Ca2+-calcineurin and transforming growth factor-β-activated kinase 1 (TAK1)-mitogen-activated protein kinase kinase (MKK) 3/6-p38α/β-dependent signaling pathways. Interestingly, we found for the first time that tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for S. pneumoniae-induced NFAT signaling pathway via a deubiquitination-dependent mechanism. Finally, we showed that CYLD interacts with and deubiquitinates TAK1 to negatively regulate the activation of the downstream MKK3/6-p38α/β pathway. Our studies thus bring new insights into the molecular pathogenesis of S. pneumoniae infections through the NFAT-dependent mechanism and further identify CYLD as a negative regulator for NFAT signaling, thereby opening up new therapeutic targets for these diseases.

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.

In review of the past studies on NF-kappaB regulation, most of them have focused on investigating how NF-kappaB is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-kappaB and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-kappaB-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKKbeta-IkappaBalpha and p38 MAPK pathways are involved in synergistic activation of NF-kappaB via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-kappaB via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-kappaB-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.

The transforming growth factor beta (TGF-beta) pathway represents an important signaling pathway involved in the regulation of diverse biological processes, including cell proliferation, differentiation, and apoptosis. Despite the known role of TGF-betaR-mediated signaling in suppressing immune response, its role in regulating human Toll-like receptors (TLRs), key host defense receptors that recognize invading bacterial pathogens, however, remains unknown. Here, we show for the first time that TGF-betaR-Smad3/4 signaling pathway acts as a positive regulator for TLR2 induction by bacterium nontypeable Hemophilus influenzae (NTHi) in vitro and in vivo. The positive regulation of TLR2 induction by TGF-betaR is mediated via a dual mechanism involving distinct signaling pathways. One mechanism involves functional cooperation between the TGF-betaR-Smad3/4 pathway and NF-kappaB pathway. Another involves MAP kinase phosphatase 1 (MKP-1)-dependent inhibition of p38 MAPK, a known negative regulator for TLR2 induction. Moreover, we showed that TbetaR-mediated signaling is probably activated by NTHi-derived TGF-beta mimicry molecule via an autocrine-independent mechanism. Thus, our study provides new insights into the role of TGF-beta signaling in positively regulating host defense response by tightly controlling the expression level of TLR2 during bacterial infections and may lead to new therapeutic strategies for modulating host defense and inflammatory response.

Pranlukast is a selective cysteinyl leukotriene1 (cysLT1) receptor antagonist, and is now widely used in the treatment of asthma. The anti-asthmatic effect of pranlukast may be rendered not only by antileukotriene activity, but also by other pharmacological activity. This study was designed to investigate whether pranlukast had inhibitory effects on nuclear factor-ĸB (NF-ĸB) activation and mucin gene expression in cultured human epithelial cells. Luciferase assay was mainly used for analysis. Cultured epithelial cells were transfected with NF-ĸB luciferase vector, MUC2 or MUC5AC luciferase vectors. Lipopolysaccharide (LPS) significantly increased NF-ĸB activation in NCI-H292 cells, which was inhibited by the pretreatment by pranlukast in a dose-dependent manner. Either LTD4 or pranlukast alone did not increase NF-ĸB activation in NCI-H292 cells. Pranlukast also inhibited NF-ĸB activation induced by phorbol 12-myristate 13-acetate (PMA). Pranlukast also significantly inhibited LPS-induced MUC2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis in NCI-H292 cells. Pranlukast also inhibited LPS-induced MUC2 gene expression in HM3-MUC2 cells. However, pranlukast did not inhibit MUC5AC gene transcription activity induced by lipoteichoic acid (LTA) in NCI-H292 cells. These results suggest that pranlukast may inhibit NF-ĸB activation and MUC2 gene transcription through pathways distinct from cysLT1 receptor antagonism in cultured human epithelial cells.

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。

Objectives: The purpose of the study is to know if mucin gene expression can be detected in the middle ear effusion and if so, which mucin genes are expressed in the effusions. Methods: Mucin gene expression in the middle ear effusions obtained from five patients with otitis media with effusion were analyzed by reverse transcription-polymerase chain reaction. Ribonucleic acids (RNAs) were extracted from the effusion and the expression of 12 mucin genes was analyzed by reverse transcription-polymerase chain reaction. Results: Mucin gene expression examined by reverse transcription-polymerase chain reaction indicated the expression of MUC1 , MUC4 , MUC5AC , MUC6 , MUC7 , MUC8 , MUC9 , MUC11 and MUC12 mRNA in the effusion. This mucin gene expression was similar to that in BEAS-2B cell, a bronchial epithelial cell line. Conclusion: Middle ear effusion can give us valuable information on mucin gene expression in the middle ear. There is similarity between mucin gene expression in the middle ear effusion and that in the bronchial epithelia.

Objective To clarify 1) which mucin gene expression is influenced by glucocorticoid and 2) whether glucocorticoid influences steady-state mucin expression or mucin gene expression induced by lipopolysaccharide. Methods Dissociated cells obtained from nasal polys were cultured on a collagen gel substrate in an air-liquid interface. Dexamethasone was added to the culture medium in the steady-state and prior to the stimulation by LPS. RNAs were extracted from culture cells, and semiquantitative reverse transcriptase-polymerase chain reaction was performed for MUC2, MUC5AC, MUC5B, MUC8, and β-actin. Results Dexamethasone did not influence steady-state messenger RNA levels of either mucin gene. Dexamethasone suppressed lipopolysaccharide-induced messenger RNA levels of MUC8. Conclusion Glucocorticoid does not influence steady-state mucin gene expression but suppresses mucin gene expression induced by secretagogues such as lipopolysaccharide.

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.

From 1990 through 1998, 143 patients with laryngeal cancer were treated in our department. Of the 143 patients, 94 had glottal, 43 had supraglottal, and 6 had subglottal cancer. The 5-year survival rate in patients with laryngeal cancer was 90.0% for stage I, 81.3% for stage II, 77.9% for stage III, and 42.6% for stage IV. The 5-year survival rate was 86.5% for glottal, 55.9% for supraglottal and 66.7% for subglottal cancer patients. The laryngeal preservation rate was 90.4% for stage I, 60.5% for stage II, 21.4% for stage III and 28.1% for stage IV.A loco-regional recurrence occurred in 24 of 143 patients (16.8%). The salvage rate for these patients was 45.8% (11/24). Six of 11 patients who died of primary disease and nodal failure (including 2 stomal recurrences) had supraglottic stage N carcinoma.In conclusion, laryngeal preservation surgery should be recommended in the early stages of cancer after radiation failure and local recurrence. It is recommended to dissect the anterior compartment including the delphian lymph node, pretracheal, and parathyroidal nodes bilaterally for patients with laryngeal tumors that have significant anterior subglottic extension, tumors arising in the subglottic region, or advanced tumors arising in any region, especially the supraglottis.

The development of preoperative diagnosis for thyroid cancer has restricted the surgical indication for benign thyroid disease, but surgical management should still be performed for hyperthyroidism, enlarged thyroid tumors and so on. Also, it is possible to diagnose for thyroid papillary carcinoma preoperatively, but it is difficult to do so for follicular carcinoma. Therefore, we must operate for some solitary tumor cases in order to rule out the latter type of cancer. In this study, we evaluated the thyroid patients treated in our department and proposed indications for benign solitary thyroid tumor.Between 1989 and 1998, 555 patients with thyroid disease were treated in our department. 204 cases were benign, and 351 showed thyroid malignancy. 185 cases were benign thyroid nodules, and 17 were follicular carcinoma. In this study, the tumors that were large in size were found to be follicular carcinoma more frequently. We concluded that a case with a solitary tumor≥40-50mm should undergo a thyroid operation for the purpose of ruling out follicular carcinoma.

Two cases of esophageal perforations caused by endoscopy were treated at our hospital.The cause was flexible fiberscopy in one patient and rigid esophagoscopy in the other patient. Both patients were treated surgically and cured.We concluded that: (1) rigid esophagoscopy should be performed under general anesthesia; (2) a barium esophagogram indicative of an esophageal perforation should not be a contra-indication; and (3) the operation should be performed as soon as possible, and primary suture of the perforation should also be performed if possible.

Recently, we have performed microvascular anastomoses in the reconstructive surgery of the esophagus: 3 cases at the Department of Surgey of Yamada Red Cross Hospital, and 3 cases at the Department of Surgery of Saiseikai Matsusaka Hospital. In these 6 cases, a gastric pull-up technique in 3 cases, a colonic pull-up technique in 2 cases, and a pedicled jejunum technique in 1 case were performed to reconstruct the esophagus.Microvascular anastomoses were performed in the cervical region in all 6 cases; for the artery alone in 1 case, the vein alone in 1 case, and for both vessels in 4 cases.Major complications (except for the minor leakage in 1 case) were not observed, and the reconstructions by organ transfer were successful.Microvascular anastomoses in the cervical region for adjuvant circulation is safe and easy, bacause the cervical region has many adequate vessels for anastomoses and is a stable in terms of respiratory movement.For head and neck surgeons, participation in a team operation of the thoracic esophagus is important and necessary in order to be able to examine the laryngeal findings and detect double cancers in the head and neck regions.

Thirty-six patients with epistaxis requiring hospitalization evaluated over the previous five years were statistically. Twelve patients could not be controlled by the conventional packing method. Ligation of the ethmoidal arteries was perfomed in 4 cases, selective catheter embolization in 5 cases, and turbinectomy and electro-cauterization in 3 cases. In one patient treated by ligation of the ethmoidal artery, and in four patients treated by selective catheter embolization, control of epistaxis failed. All 4 patients were subsequently treated by turbinectomy and electro-cauterization. Because of its relative simplicity and effectiveness, turbinectomy from the infra turbinal posterior end is proposed as the standard method for treatment of epistaxis. Ligation of the ethmoidal arteries should be used for the treatment of epistaxis originating from the olfactory cleft, and selective catheter embolization for treatment of those cases in which the bleeding points were undetectable.

Since we use fine-needle aspiration cytology under ultrasonographic imaging for the diagnosis of thyroid tumors, we can easily detect small thyroid cancers.However, there is a question whether to operate on the small well-differentiated thyroid cancers or not, because the majority of the thyroid cancer have a good prognosis.Therefore, we studied 95 patients with pre-operative T1NO thyroid cancer who had been treated in our department from 1986 to 1996. 35 patients of the 95 had positive nodes (38.9%), 21 had intrathyroidal metastases (22.1%) ; and 7 had extra-thyroidal invasions (7.4%) . Two patients out of these 7 showed an invasion of the trachea that might have had an influence on survival.We feel that surgical treatment is indicated for small thyroid cancer based on.

In the past 4 years, middle ear surgery has been performed on 166 ears. A total of 42 ears operated on by modified type III tympanoplasties, and 19 ears operated on by type IV tympanoplasties were reviewed. The type III tympanoplasty group included 12 ears with cholesteatoma and 20 with chronic otitis media. The type IV tympanoplasty group included 9 cases of cholesteatoma and 5 cases of chronic otitis media. Postoperative hearing results were evaluated, and success rates in hearing results were 81.6% of type III patients, and 66.7% of type IV tympanoplasty patients. Second surgeries were performed on 7 ears previously operated on at other hospitals, and success was observed in 6 ears. In 18 ears, artificial columella (hydroxyapatite) was used for reconstruction of the ossicular chain, and discharge of the columella was observed in only 1 ear. In 21 ears with cholesteatoma and reconstruction of the ossicular chain, residual recurrence of cholesteatoma was observed in 3, but true recurrence of cholesteatoma was not experienced.

Seventy-nine patients with head and neck abscesses were treated at our clinic between 1995 and 1997. Sixty-three cases had a peritonsillar abscess, seven were cases of deep neck infection and nine cases were other sorts of abscesses.Of the seven patients with deep neck infection, two were treated only with chemotherapy and steroids. Surgical drainage was performed in the remaining five patients.For the effective treatment of head and neck abscess, enhanced CT scanning is useful, in addi-tion, prompt surgical drainage of the abscess and therapy with antibiotics for anaerobic pathogens and with steroids for a short period are required.

Malignant lymphoma is a systematic disease which frequently manifests itself first in the head and neck region.Although the diagnosis of a malignant lymphoma is not difficult, the addition of infection in the affected lymphoid tissues makes the histological diagnosis complicated. A prudent evaluation and repeated biopsies are required in cases complicated by infected lymphoid tissues. On the other hand, the administration of antibiotics, drainage and debridement of the affected region are essential for the severe inflammation of the deep neck. We recently experienced a 60-year-old male patient with a malignant lymphoma and severe infection of the neck.Debridement of the infected neck region and subsequent reconstruction of the defect in the neck were performed in this case.A pectoralis major musculocutaneous flap was elevated, passing through the retro-clavicular space, and the defect in the neck was then covered by this flap without any complication.Combined chemotherapy was performed by the medical department, and achieved a complete response.This reconstructive procedure enabled the satisfactory covering of defects in the upper neck region.

Giant cell reparative granuloma (GCRG) is an uncommon and nonneoplastic reactive tumor that involves the maxilla and mandible in the region of the head and neck. It is rare in the nasal cavity, and it might be misdiagnosed. We reported a very aggressive GCRG with intracranial invasion, which was treated surgically via a combined approach of a lateral rhinotomy with a craniotomy by bilateral coronal incision. The pathology was consistent with GCRG. A short literature review about diagnosis, clinical behavior, and treatment of this tumor entity is given.

Osteosarcoma arising from the maxilla is a rare tumor of the head and neck region, accounting for only 6% to 7% of all osteosarcomas. Although therapy for maxillary cancer is well established, that for sarcoma of the maxilla, especially osteosarcoma is less clearly defined. In our department, a case of osteosarcoma arising from the maxilla was treated with surgery and chemo-radiotherapy. Surgery preceded postoperative irradiation with adjuvant intra-arterial chemotherapy. In the literature, surgery is the most readily available form of therapy, whereas radiotherapy and chemotherapy are not commonly used in the treatment of osteosarcoma. The Japanese literature suggests that a combination of chemotherapy and surgery might improve the outcome in cases of osteosarcoma of the maxilla.In cases of osteosarcoma, recurrence at the primary site is common, and the prognosis in these cases is generally poor. Therefore, precise evaluation of the extent of the osteosarcoma is more essential. In our patient, 3-dimension CT was used preoperatively, and proved useful for the evaluation of the extent of disease and the determination of suitable operative procedures.

To clarify long-term outcome of benign paroxysmal positional vertigo (BPPV), 50 patients were followed up for a mean of 52 months. Overall recurrence rate by Kaplan-Meier estimation was 37% at 60 months. The patients with horizontal canal BPPV (n = 19) had a significantly higher recurrence rate (50%) at 60 months than those with posterior canal BPPV (n = 28; 26%). There was no significant association between recurrence rates and sex or age.

Background: Interleukin-31 (IL-31) is a newly discovered T helper lymphocyte-derived cytokine that plays an important role in allergic inflammation. However, the effects of IL-31 on mucus production in nasal allergic inflammation are completely unknown. Objective: To investigate the effects of IL-31 on mucin gene expression (MUC5AC) in patients with allergic rhinitis and in human airway epithelial cells. Methods: Expression levels of IL-31 and IL-31 receptor A (IL-31RA) were evaluated in the inferior turbinate of patients with allergic rhinitis and non-allergic rhinitis with immunohistochemistry. IL-31-induced MUC5AC gene expression was measured with a MUC5AC luciferase reporter assay in human epithelial HM3-MUC5AC cells and quantified by quantitative real-time polymerase chain reaction in human airway epithelial A549 cells. Results: IL-31RA was primarily localized in submucosal glands and upregulated in allergic rhinitis. IL-31 was detected in submucosal tissue and increased in allergic inflammation. MUC5AC gene expression was induced by IL-31 stimulation both in HM3-MUC5AC and A549 cells. Additionally, IL-31 cooperated with Th2 cytokines on MUC5AC gene expression in HM3-MUC5AC cells. Conclusion: IL-31 and IL-31RA are upregulated in patients with allergic rhinitis, and induce MUC5AC gene expression in human airway epithelial cells. These findings suggest that IL-31 plays an important role in mucus overproduction in nasal allergic inflammation.

This study aims to identify predisposing characteristics of descending necrotizing mediastinitis (DNM) arising from deep neck infection (DNI) and to determine appropriate therapeutic intervention strategies. We retrospectively reviewed 54 patients (male, n = 34; female, n = 20; mean age, 64.5 years) who had been treated at Mie University Hospital for DNI between April 2001 and October 2011. Eight of nine patients who developed DNM confirmed by computed tomography of the neck and chest, underwent mediastinal drainage (video-assisted thoracic surgical drainage, n = 6; mediastinoscopy-assisted drainage, n = 2). A patient developed uncontrolled acute respiratory distress syndrome after aggressive surgery, resulting in a mortality rate of 12 %. High blood CRP values, and the pharynx and tonsils as origins of infection were factors involved in the development of DNM arising from DNI. In conclusion, DNM remains a destructive and fatal disease that requires aggressive treatment including mediastinal exploration.

It is unclear whether remodeling exists in allergic rhinitis in man. The aim of this study was to establish a guinea pig model of allergic rhinitis with remodeling and to examine the effects of dexamethasone and pranlukast on nasal mucosa remodeling.In the first experiment, three groups of ovalbumin-sensitized Hartley guinea pigs received intranasal challenges with ovalbumin for 1, 8, 12 weeks, respectively. In the second experiment, to examine the effect of dexamethasone and pranlukast, the animals were divided into 4 groups: negative control group; ovalbumin-sensitized group; ovalbumin + dexamethasone group; and ovalbumin + pranlukast group. During 12 weeks of intranasal exposure to ovalbumin, the latter two groups received daily intraperitoneal injections of dexamethasone and pranlukast, respectively.In the first experiment, in contrast to the negative control group, the ovalbumin-sensitized group exhibited significant goblet cell hyperplasia, epithelial damage and deposition of extracellular matrix in the nasal septal mucosa and conchae. In the second experiment, these changes were significantly inhibited by dexamethasone and pranlukast, respectively.We have established a model of upper airway remodeling in guinea pigs. The tissue remodeling was inhibited by early intervention with the antiallergic-inflammatory agents dexamethasone and pranlukast.

The TGF-beta (transforming growth factor-beta) pathway represents an important signalling pathway involved in regulating diverse biological processes, including cell proliferation, differentiation and inflammation. Despite the critical role for TGF-beta in inflammatory responses, its role in regulating NF-kappaB (nuclear factor-kappaB)-dependent inflammatory responses still remains unknown. In the present study we show that TGF-beta1 synergizes with proinflammatory cytokine TNF-alpha (tumour necrosis factor-alpha) to induce NF-kappaB activation and the resultant inflammatory response in vitro and in vivo. TGF-beta1 synergistically enhances TNF-alpha-induced NF-kappaB DNA binding activity via induction of RelA acetylation. Moreover, synergistic enhancement of TNF-alpha-induced RelA acetylation and DNA-binding activity by TGF-beta1 is mediated by PKA (protein kinase A). Thus the present study reveals a novel role for TGF-beta in inflammatory responses and provides new insight into the regulation of NF-kappaB by TGF-beta signalling.

Summary Streptococcus pneumoniae ( S. pneumoniae ) causes high early mortality in pneumococcal pneumonia, which is characterized by acute lung injury (ALI). The molecular mechanisms underlying ALI and the high early mortality remain unknown. Despite recent studies that identify deubiquitinating enzyme cylindromatosis (CYLD) as a key regulator for T cell development, tumor cell proliferation, and NF-κB transcription factor signaling, its role in regulating bacteria-induced lethality, however, is unknown. Here, we showed that CYLD deficiency protected mice from S. pneumoniae pneumolysin (PLY)-induced ALI and lethality. CYLD was highly induced by PLY, and it inhibited MKK3-p38 kinase-dependent expression of plasminogen activator inhibitor-1 (PAI-1) in lung, thereby potentiating ALI and mortality. Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia.

Transforming growth factor-beta (TGF-beta) family members are multifunctional growth factors involved in regulating diverse biological processes. Despite the critical role for TGF-beta in regulating cell proliferation, differentiation, migration and development, its role in regulating NF-kappaB-dependent inflammatory response still remains unclear. Here, we show that TGF-beta1 induces acetylation of NF-kappaB p65 subunit to synergistically enhance bacterium nontypeable Haemophilus influenzae-induced NF-kappaB activation and inflammatory response in vitro and in vivo. The TGF-beta1-induced acetylation of p65 is mediated via a Smad3/4-PKA-p300-dependent signaling pathway. Acetylation of p65 at lysine 221 by TGF-beta1 is critical for synergistic enhancement of bacteria-induced DNA-binding activity, NF-kappaB activation, NF-kappaB-dependent transcription of TNF-alpha and IL-1beta and interstitial polymorphonuclear neutrophil infiltration in vitro and in vivo. These studies provide new insights into the novel regulation of NF-kappaB by TGF-beta signaling.

In review of the past studies on NF-kappaB regulation, most of them have focused on investigating how NF-kappaB is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-kappaB and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-kappaB-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKKbeta-IkappaBalpha and p38 MAPK pathways are involved in synergistic activation of NF-kappaB via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-kappaB via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-kappaB-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.

The transforming growth factor beta (TGF-beta) pathway represents an important signaling pathway involved in the regulation of diverse biological processes, including cell proliferation, differentiation, and apoptosis. Despite the known role of TGF-betaR-mediated signaling in suppressing immune response, its role in regulating human Toll-like receptors (TLRs), key host defense receptors that recognize invading bacterial pathogens, however, remains unknown. Here, we show for the first time that TGF-betaR-Smad3/4 signaling pathway acts as a positive regulator for TLR2 induction by bacterium nontypeable Hemophilus influenzae (NTHi) in vitro and in vivo. The positive regulation of TLR2 induction by TGF-betaR is mediated via a dual mechanism involving distinct signaling pathways. One mechanism involves functional cooperation between the TGF-betaR-Smad3/4 pathway and NF-kappaB pathway. Another involves MAP kinase phosphatase 1 (MKP-1)-dependent inhibition of p38 MAPK, a known negative regulator for TLR2 induction. Moreover, we showed that TbetaR-mediated signaling is probably activated by NTHi-derived TGF-beta mimicry molecule via an autocrine-independent mechanism. Thus, our study provides new insights into the role of TGF-beta signaling in positively regulating host defense response by tightly controlling the expression level of TLR2 during bacterial infections and may lead to new therapeutic strategies for modulating host defense and inflammatory response.

Malignant external otitis is a severe infection of the external auditory canal, generally caused by Pseudomonas aeruginosa in elderly diabetics patients. We describe a case of malignant external otitis in a 63-year-old man with severe otalgia, purulent otorrhea and polypoid granulation of the external auditory canal. Local debridement, insulin treatment and 6-week intravenous antibiotic therapy with carbapemens were very effective and the granulation tissue disappeared completely. However, the patient readmitted for recurrent disease 3 weeks later, despite the oral and ear drop administration with new quinolone. No recurrence has been noted after 4-week additional treatment with intravenous carbapenems followed by 3-week treatment with Burow's solution as ear drops.