楯谷 一郎

出血性声帯ポリープ12例、非出血性声帯ポリープ4例に対し局所麻酔下で光凝固レーザー(グリーンレーザー)手術を施行し、その治療効果と安全性について検討した。その結果、出血性声帯ポリープに対してはプローブ非接触下での凝固(1〜2回)により、術後音声機能の有意な改善を認めた。また、術後の瘢痕形成は認めず、本法が声帯ポリープの治療として安全かつ有効であることが示された。一方、非出血性声帯ポリープにおいては、非接触下の照射ではレーザー光のオキシヘモグロビンへの吸収が不十分なため、プローブ接触下で上皮のみを蒸散した後、ポリープ内部にレーザーのエネルギーを導入するようにしたところ、術後音声機能の改善傾向が示された。

Objectives/Hypothesis Our previous study demonstrated that a large amount of reactive oxygen species (ROS) is produced during the early phase of vocal fold wound healing. In the current study, we investigated the effect of astaxanthin, which is a strong antioxidant, on the regulation of oxidative stress and scarring during vocal fold wound healing. Study Design Prospective animal experiment with control. Methods Sprague-Dawley rats were dosed with astaxanthin (Ast-treated group, 100 mg/kg/day) or olive oil (sham-treated group) by oral gavage daily from preinjury day 1 to postinjury day 4. After vocal folds were injured under the endoscope, larynges were harvested for histological and immunohistochemical examinations on postinjury days 1, 3, 5, and 56, and quantitative real time polymerase chain reaction (PCR) on postinjury days 1 and 3. Results The expression of 4-hydroxy-2-nonenal, which is an oxidative stress marker, was reduced significantly in the lamina propria of the Ast-treated group as compared to the sham-treated group. Histological examination showed significantly less tissue contraction with favorable deposition of hyaluronic acid in the lamina propria of the Ast-treated group compared to the sham-treated group. Real time PCR revealed significantly upregulated mRNA expression of basic fibroblast growth factor on postinjury day 1 and procollagen type I in the Ast-treated group compared to the sham-treated group. Conclusions These findings suggest that astaxanthin has the potential to prevent vocal fold scarring by regulating oxidative stress during the early phase of vocal fold wound healing. Level of Evidence: NA Laryngoscope, 124:E1-E7, 2014 © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Objectives/Hypothesis Vocal fold scar and sulcus are still challenges. Basic fibroblast growth factor (bFGF) has proven to be effective to resolve scar tissue in animal models. This study reports the efficacy of regenerative treatments using bFGF on vocal fold scar and sulcus in human cases. Study Design Retrospective chart review. Methods Fifteen cases (7 scar; 8 sulcus) were treated by either local injection of bFGF (n = 6) or regenerative surgery using bFGF (n = 9). Injection regimen was to locally apply 10 micrograms of bFGF in 0.5 mL saline into each vocal fold under topical anesthesia repeatedly (4 times with intervals of 1 week between each injection). The regenerative surgical procedure consisted of the dissection of scar tissue and the implant of gelatin sponge with bFGF. Follow-up periods ranged from 6 months to 24 months. Results Maximum Phonation Time (MPT); Voice Handicap Index (VHI)-10; and Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale were assessed in both groups. The injection group showed significant improvement on VHI-10 and GRBAS. The regenerative surgery group showed significant improvement in all parameters. Jitter and shimmer were evaluated in the surgery group, and the results indicated improvement in six and five cases of nine cases, respectively. No major adverse effects were observed in both treatment groups. Conclusions Regenerative treatments using bFGF has shown to be effective for improvement of vocal function in scar and sulcus. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Mechanosensory hair cells and supporting cells develop from common precursors located in the prosensory domain of the developing cochlear epithelium. Prosensory cell differentiation into hair cells or supporting cells proceeds from the basal to the apical region of the cochleae, but the mechanism and significance of this basal-to-apical wave of differentiation remain to be elucidated. Here, we investigated the role of Hedgehog (Hh) signaling in cochlear development by examining the effects of up and downregulation of Hh signaling in vivo. The Hh effector smoothened (Smo) was genetically activated or inactivated specifically in the developing cochlear epithelium after prosensory domain formation. Cochleae expressing a constitutively active allele of Smo showed only one row of inner hair cells with no outer hair cells (OHCs); abnormal undifferentiated prosensory-like cells were present in the lateral compartment instead of OHCs and their adjacent supporting cells. This suggests that Hh signaling inhibits prosensory cell differentiation into hair cells or supporting cells and maintains their properties as prosensory cells. Conversely, in cochlea with the Smo conditional knockout (Smo CKO), hair cell differentiation was preferentially accelerated in the apical region. Smo CKO mice survived after birth, and exhibited hair cell disarrangement in the apical region, a decrease in hair cell number, and hearing impairment. These results indicate that Hh signaling delays hair cell and supporting cell differentiation in the apical region, which forms the basal-to-apical wave of development, and is required for the proper differentiation, arrangement and survival of hair cells and for hearing ability. © 2013. Published by The Company of Biologists Ltd.

Objectives: Previous studies have indicated that although normal wound healing requires low levels of reactive oxygen species (ROS), excessive amounts of ROS impair wound healing. In injured vocal folds, this excess may result in dysphonia due to scarring that is difficult to treat. However, the expression of ROS during vocal fold wound healing has yet to be investigated. In this study, we assessed the expression and localization of ROS in injured vocal folds by immunohistochemical analysis. Methods: Vocal folds of Sprague-Dawley rats were unilaterally injured by stripping the mucosa under transoral endoscopy. The larynges were harvested at specific time points after injury and were immunohistochemically examined for 4-hydroxy-2-nonenal (4-HNE), an ROS marker, and for the presence of inflammatory cells. Results: We found that 4-HNE-immunopositive cells were significantly increased in the lamina propria of the injured vocal folds as compared to the normal vocal folds on postinjury days 1 and 3. More than half of the 4-HNE-immunopositive cells were also immunopositive for a macrophage- and granulocyte-specific antibody. Conclusions: This study suggests that a large amount of ROS is produced during early-phase wound healing, until postinjury day 3, and that this period may be crucial for regulating ROS levels. The results also suggest that inflammatory cells may contribute to ROS generation. © 2012 Annals Publishing Company. All rights reserved.

A good prognosis can be expected for most, but not all, cases of thyroid papillary cancer. Numerous molecular studies have demonstrated beneficial treatment and prognostic factors in various molecular markers. Whereas most previous reports have focused on genomics and proteomics, few have focused on lipidomics. With the advent of mass spectrometry (MS), it has become possible to identify many types of molecules, and this analytical tool has become critical in the field of omics. Recently, imaging mass spectrometry (IMS) was developed. After a simple pretreatment process, IMS can be used to examine tissue sections on glass slides with location information. Here, we conducted an IMS analysis of seven cases of thyroid papillary cancer by comparison of cancerous with normal tissues, focusing on the distribution of phospholipids. We identified that phosphatidylcholine (16:0/18:1) and (16:0/18:2) and sphingomyelin (d18:0/16:1) are significantly higher in thyroid papillary cancer than in normal thyroid tissue as determined by tandem mass (MS/MS) analysis. These distributional differences may be associated with the biological behavior of thyroid papillary cancer. © 2012 Ishikawa et al.

Objectives/Hypothesis: Vocal fold injury can cause intractable scarring resulting in dysphonia. Mesenchymal stem cells (MSCs) have great therapeutic potential in wound healing. They continuously circulate in the peripheral blood and migrate into wound sites where they induce regenerative effects. However, their roles in vocal fold wound healing are poorly understood because few MSCs exist in the peripheral blood and there is no specific marker to identify them. The present study evaluates how intravenously injected MSCs affect vocal fold wound healing using Green Fluorescent Protein (GFP) -labeled MSCs. Study Design: Prospective study using animal model. Methods: GFP-labeled MSCs were obtained from femurs of GFP transgenic Sprague-Dawley rats and incubated in culture. Sprague-Dawley rats underwent intravenous injection of GFP-labeled MSCs (1.0 × 106 cells) immediately after vocal fold injury. Histological examination was performed. Results: Injected MSCs were distributed throughout the vocal fold wound site from day 1 up to day 56. These vocal folds showed increased hepatocyte growth factor (HGF)-positive cells within the wound and improved wound healing compared with sham-treated folds. Conclusion: Circulating MSCs can migrate to vocal fold wound sites and upregulate the expression of HGF during wound healing; thus, they are considered to play a significant role in wound healing within the vocal folds. Laryngoscope, 2012 Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

瘢痕声帯・声帯溝症に対して音声治療を行い、音声症状の改善が認められた3症例を報告した。症例1は他院での声帯粘膜切除術後の嗄声を主訴とする64歳男性で、瘢痕声帯と診断し、瘢痕切除、bFGF注入など音声外科治療を行ったが、粘膜波動は不十分であった。症例2は49歳男性で、20歳代より嗄声を自覚し、2010年に両側声帯溝症と診断された。bFGFの注入により粘膜波動・振動振幅の改善が認められたが不十分であった。症例3は2007年より嗄声を自覚している30歳女性で、Fordらの重傷度ステージ分類でtype IIに該当する両側声帯溝症であった。これらの症例に対し、1)声の衛生指導、2)過緊張性発生の緩和、3)声域拡大訓練、から成る音声治療プログラムを、症例1では約1週間に1回、計24週間、症例2では約2週間に1回、計24週間、症例3では約1週間に1回、計8週間実施した。その結果、全例で粘膜波動と自覚的評価の改善が認められ、音声治療の有効性が示された。

7歳11ヵ月男児。頸部痛と発熱が生じ、加えて開口時痛と開口制限が出現し、頸部リンパ節炎を疑い、近医の耳鼻咽喉科へ入院となった。対処としてセフトリアキソン、アジスロマイシンによる治療が開始されたが、肝酵素の上昇およびエコーにて肝腫大がみられた。一方、造影CTでは第2〜6頸椎レベルに咽後嚢腫様の低吸収域が認められたが、膿瘍に特徴的なring enhancementは伴っておらず、精査目的で著者らの施設へ転院となった。入院時、頸部痛を伴った頸部リンパ節腫脹に加え、転院日の夜から両側眼球結膜の充血、不定形発疹、手足の浮腫ほか、紅斑といちご舌の出現を認められた。川崎病と診断後、セフトリアキソン、アジスロマイシンの投与を継続し、更にガンマグロブリン、イブプロフェンによる治療を開始した。その結果、翌日より川崎病症状は改善傾向を示し、第6病日目には解熱、第7病日目のCTでは咽後嚢腫様の低吸収域はほとんど消失し、第11病日目に退院となった。

Objectives/Hypothesis: Aged vocal folds are characterized by atrophy of the mucosa, which causes mucosal wave deficiency and glottal insufficiency. This clinical trial examined the regenerative effects and safety considerations of basic fibroblast growth factor (bFGF) on restoration of aged vocal folds. Study Design: Institutional review board-approved human clinical trial. Methods: Ten patients (6 men and 4 women; mean age, 70.1 years) were recruited in the trial. Ten micrograms of bFGF was injected into each treated vocal fold. Injection was performed unilaterally or bilaterally according to each patient's need and repeated up to seven times if necessary. Patient follow-up continued for at least 6 months. The effectiveness of the treatment was assessed by stroboscopic, acoustic, and aerodynamic measurements. Results: All patients showed improvement of voice. Significant improvements in maximum phonation time, mean flow rate, jitter, shimmer, and noise-to-harmonic ratio lasted for at least 1 year. No allergic or long-term adverse effects were noted. Conclusions: This clinical trial suggests that bFGF may be effective and safe as a regenerative agent for aged vocal folds. © 2011 The American Laryngological.

[緒言]局所進行喉頭癌(特にT4)に対する喉頭温存治療は確立しているとはいえない。京都大学がん診療部では頭頸部外科医と放射線治療医が一緒に患者診察を行い、局所進行喉頭癌に対しても喉頭温存治療の可能性を検討している。今回、主に導入化学療法を用いた喉頭温存治療の試みについて報告する。[対象]京大がん診療部が発足した2008年から2011年6月までに当診療部を受診した喉頭癌患者52例のうち、T3、T4症例7例について検討を行った。[結果]1例では基礎疾患の関係から喉頭全摘が行われたが、T3の1例では放射線療法(多分割照射)を、残りの5例にはTPFを用いた導入化学療法を施行した。5例中1例でCR、3例でPRがえられ、2例では化学放射線療法、2例では喉頭温存手術を行った。喉頭温存治療を完遂できた5例において、1〜3年(平均2年)の観察期間において再発を認めず、喉頭機能も温存できている。[考察]T3、4喉頭癌においても導入化学療法と化学放射線療法(IMRT)、喉頭温存手術を用いることで喉頭温存が可能となる可能性を示した。(著者抄録)

Background: Early detection of pharyngeal cancer has been difficult. We reported that narrow-band imaging (NBI) endoscopy can detect superficial pharyngeal cancer, and these lesions can be treated endoscopically. Objective: To assess the safety and long-term efficacy of transoral organ-preserving pharyngeal endoscopic resection (TOPER) for superficial pharyngeal cancer. Design and Setting: Retrospective 2-center cohort study. Patients: The study included 104 consecutive patients with superficial pharyngeal cancer. Intervention: TOPER with the patients under general anesthesia. Main Outcome Measurements: Safety of the procedure, long-term survival, clinical outcome. Results: A total of 148 consecutive lesions were resected in 104 patients. There was no severe adverse event. Temporary tracheostomy was required in 17 patients (16%) to prevent airway obstruction. The median fasting period and hospital stay after TOPER were 2 days (range 1-20 days) and 8 days (range 3-58 days), respectively. Ninety-six patients (92%) had no local recurrence or distant metastases. Local recurrence at the primary site developed in 6 patients, but all were resolved by repeat TOPER. With a median follow-up period of 43 months (range 3-96 months), the overall survival rate at 5 years was 71% (95% CI, 59-82). Cause-specific survival rate at 5 years was 97% (95% CI, 93-100). The cumulative development rate of multiple cancers in pharyngeal mucosal sites at 5 years was 22% (95% CI, 12-33). The pharynx was preserved in all patients, and they experienced no loss of function. Limitation: Retrospective design. Conclusions: Peroral endoscopic resection of superficial pharyngeal cancer is a feasible and effective treatment with curative intent. © 2011 American Society for Gastrointestinal Endoscopy.

Objectives/Hypothesis: Radiotherapy is one of the most effective treatments for head and neck cancer. However, in addition to the target tumor, normal salivary glands are also included in the irradiation field. This unavoidably results in dry mouth syndrome as a side effect. In this study, the protective efficacy of basic fibroblast growth factor (bFGF) was investigated in radiation-damaged salivary glands. Study Design: Prospective animal experiment with control. Methods: Nine-week-old female C57BL/6 mice were divided into three groups. All mice in two of the three groups were irradiated (10 Gy) at the same time. In the bFGF-treated group, bFGF was administered to the submandibular glands for 3 consecutive days after neck irradiation. Mice in the untreated control group were administered distilled water. Mice in the third group were not irradiated and did not receive any additional treatments. Saliva flow rate and submandibular gland morphology were assessed, and the apoptotic response of irradiated submandibular glands was also evaluated. Results: Administration of bFGF improved hyposalivation 8 weeks after irradiation, and histologic analysis revealed that bFGF-treated glands contained more acinar cells compared to untreated glands. The apoptotic response to irradiation, examined 1 and 2 days after irradiation, was reduced, and quantitative real-time polymerase chain reaction revealed a paracrine effect for bFGF in the glands that received bFGF treatment. Conclusions: Our study indicates that bFGF prevents salivary gland dysfunction after irradiation. The protective benefits of bFGF may be attributed to the inhibition of radiation-induced apoptosis as well as the paracrine effect it has in these tissues. © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Objectives: Radiotherapy is one of the most effective treatments for head and neck cancer. However, the development of dry mouth syndrome is an unavoidable side effect because, in addition to the tumor, the normal salivary glands are included in the irradiation field. Previously, we investigated the protective efficacy of basic fibroblast growth factor (bFGF) in radiation-damaged salivary glands. In this study, we investigated the efficacy of adipose-derived stromal cell (ADSC) transplantation for the regeneration of radiation damaged salivary glands. Study Design: Prospective animal experiment with control. Methods: ADSCs (500,000 cells isolated from green fluorescent protein mice) were transplanted into submandibular glands of C57BL/6 mice 10 weeks after 10 Gy irradiation (ADSC group). Phosphate-buffered saline was administered to mice as a control (sham group). Submandibular gland morphology and saliva flow rate were assessed just prior to transplantation and at 5 and 10 weeks posttransplantation. Quantitative RT-PCR was performed to examine the response of irradiated submandibular glands to ADSC transplantation. Results: Saliva flow rate in the ADSC group was improved compared to the sham group. Although acinar cell damage was detected in both groups, the proliferation of blood vessels and other paracrine effects were observed only in the ADSC group. Additionally, the differentiation of ADSCs into blood endothelial cells and ductal cells was also observed. Conclusions: Our study indicates that ADSCs have the potential to restore salivary gland function after irradiation. The restoration of blood flow within submandibular gland tissue may explain the beneficial effects of ADSCs. © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Objectives: Endolaryngeal microsurgery using a direct laryngoscope is a well-established procedure in phonosurgery. Adequate laryngeal exposure is essential, but in some cases sufficient view of the glottis cannot be obtained, leading to treatment failure. This study reports how to manage vocal fold lesions in difficult laryngeal exposure (DLE) cases. Methods: From 2003 to 2009, 212 patients underwent endolaryngeal microsurgery at Kyoto Medical Center and Kyoto University Hospital. Phonomicrosurgery was performed under sniffing (Boyce-Jackson) position with triangular shaped laryngoscope for laryngeal exposure. However, in DLE cases, the posture and laryngoscope were modified as needed to adequately expose the lesion. Fiberoptic laryngeal surgery (FLS) with local anesthesia was also used for the most difficult cases. Results: The number of the patients with DLE was 14 (6.6%). Endolaryngeal microsurgery was possible in DLE cases by selecting the appropriate posture and laryngoscope. However, the procedure could not be completed in two patients with an anterior web and a vocal fold cyst, both of which required a subsequent revision procedure. Fiberoptic laryngeal surgery with topical anesthesia was a feasible alternative for these cases. Conclusions: Phonosurgery was possible even in DLE cases. It is important to modify the setup of direct laryngoscopy as needed to obtain adequate exposure. Fiberoptic surgery may also be used in certain difficult cases. © 2010 Elsevier Ireland Ltd.

Objectives: Vocal fold scarring remains a therapeutic challenge. A new regenerative approach is needed to restore disorganized extracellular matrix. Tissue regeneration requires appropriate cells and a scaffold. Bone marrow - derived mesenchymal stromal cells (BMSCs) are multipotent and secrete many kinds of growth factors to regenerate tissues. Atelocollagen sponges have many large pores that permit cell entry. The present study was performed to evaluate whether implantation of an atelocollagen sponge plus BMSCs is effective for the treatment of vocal fold scarring. Methods: Twelve beagles underwent implantation of an atelocollagen sponge or of an atelocollagen sponge with autologous BMSCs (1.0 × 106 cells) in the subepithelial pockets of scarred vocal folds. Six months after the operation, vibratory examinations and histologic examinations were performed. Results: Mucosal vibrations improved significantly for the atelocollagen sponge - implanted vocal folds. Histologic analyses revealed favorable restoration of the extracellular matrix in the lamina propria. Increased distribution of hyaluronic acid and decreased dense collagen deposition were also noted. These improvements were enhanced by implantation of BMSCs. Conclusions: Implantation of atelocollagen sponges with autologous BMSCs into scarred vocal folds significantly increased hyaluronic acid distribution and decreased dense collagen deposition in the lamina propria, leading to better mucosal vibration. © 2011 Annals Publishing Company. All rights reserved.

Notch-mediated lateral inhibition has been reported to regulate auditory hair cell and supporting cell development from common precursors. While the Notch effector genes Hes1, Hes5 and Hey1 are expressed in the developing cochlea, inactivation of either of them causes only mild abnormality, suggesting their functional redundancy. To explore the roles of Hes/. Hey genes in cochlear development, we examined compound heterozygous or homozygous mutant mice that lacked Hes1, Hes5 and Hey1 alleles. We found that a reduction in Hes/. Hey gene dosage led to graded increase of hair cell formation. However, if at least one allele of Hes1, Hes5 or Hey1 was intact, excessive hair cells were accompanied by overproduction of supporting cells, suggesting that the hair cell increase does not occur at the expense of supporting cells, and that each Hes/. Hey gene functions to induce supporting cells. By contrast, when all alleles of Hes1, Hes5 and Hey1 were inactivated, the number of hair cells increased more drastically, whereas that of supporting cells was unchanged compared with control, suggesting that supporting cell formation was balanced by their overproduction and fate conversion into hair cells. The increase of the cell numbers seemed to occur after the prosensory domain formation in the mutants because the proliferation state and the size of the prosensory domain were not affected. Thus, Hes1, Hes5 and Hey1 cooperatively inhibit hair cell formation, and one allele of Hes1, Hes5 or Hey1 is sufficient for supporting cell production probably by lateral inhibition in the sensory epithelium. Strikingly, Hes/. Hey mutations lead to disorganized cell alignment and polarity and to hearing loss despite hair cell overproduction. These results suggest that Hes/. Hey gene dosage is essential not only for generation of appropriate numbers of hair cells and supporting cells by controlling cell proliferation and lateral inhibition but also for the hearing ability by regulating the cell alignment and polarity. © 2011 Elsevier Inc.

As concurrent chemoradiotherapy becomes increasingly common in organ preservation even in advanced head and neck cancer, postchemoradiotherapy has raised many difficult problems in salvage surgery. We report the case of a 61-year-old man developing severe facial edema and sternum osteonecrosis following treatment for hypopharyngeal cancer with bilateral cervical lymphnode metastasis (T2N2cM0). Following induction chemotherapy with cisplatin and 5-fluorouracil, then concurrent chemoradiotherapy with a total dose of 70 Gy with cisplatin (80 mg/m2 every three weeks), computed tomography (CT) showed bilateral residual lymph node metastasis. Salvage surgery involved level II and III right radical and selective left neck dissection. Some 40 days post operatively, the man developed severe facial, pharyngeal, and laryngeal edema difficult to control despite intensive antibiotics, hydrocortisone, and glycerin administration. CT subsequently detected cellulitis around the tracheal stoma wound and sternum osteonecrosis necessitating emergency surgery totally removing necrotic tissue. Final wound healing and resolution of the facial edema took few months. Salvage surgery following concurrent chemoradiotherapy may cause severe complications, meaning that dissection damage to tissue should be minimized, making it also important to consider about minimallyinvasive surgery to preserve remnant tissue function.

Conclusions Medialization thyroplasty was effective in improving swallowing function as well as vocal function in most cases with unilateral vocal fold paralysis The impact of medialization thryoplasty was insufficient for the case with severe atrophy and that in which the vocal fold was fixed in the lateral position Objectives To evaluate the impacts and limitations of medialization thyroplasty on swallowing function of the patients with unilateral vocal fold paralysis Methods Eight cases (mean age 68 5 years) with unilateral vocal fold paralysis chiefly complaining of swallowing disturbance were studied All patients underwent thyroplasty type I The causes of the paralysis were lung cancer in four cases, esophageal cancer in one case, aortic aneurysm in one case, subarachnoid hemorrhage in one case, and unknown in one case Subjective swallowing function score, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), and pitch perturbation quotient (PPQ) were examined pre- and postoperatively Results The swallowing score improved in all except two cases However, bilateral thryoplasty was necessary for the case with severe vocal fold atrophy and arytenoid adduction was needed for the case in which the vocal fold was fixed in the lateral position The swallowing score, MPT, and MFR showed significant improvement after surgery

Conclusion: Organ preservation surgery with partial pharyngectomy preserving the larynx is feasible for the treatment of advanced hypopharyngeal cancer with comparable local control and preservation of function. Objectives: To examine the feasibility and therapeutic effects of organ preservation surgery for advanced hypopharyngeal cancer. Methods: Fourteen patients with stage III/IV hypopharyngeal cancer were treated by partial pharyngectomy with or without partial laryngectomy to preserve the larynx. Ten cases were T1/2 primary while four cases had T3/4 tumors. Reconstruction of the pharyngolarynx was completed by primary mucosal suture in six, while free forearm flap was used in eight cases. Induction chemotherapy was administered for six cases including three with T3/4 tumors. Results: Five-year overall survival and disease-specific survival rates were 57.1% and 66.7%, respectively. The 5-year locoregional control rate was 66.7% and the larynx preservation rate was 100%. No patients presented with local recurrence at the pharyngolaryngeal segment, while two cases showed nodal recurrence, from which they died. Tracheal stoma was closed in 9 of 14 cases. Vocal function was excellent in five cases, moderate in five, and poor in three. Swallowing function was excellent to moderate in eight cases and poor in six. © 2010 Informa Healthcare.

Conclusion Treatment of advanced hypopharyngeal cancer has become more conservative and more multidisciplinary, and the prognosis has been improved Induction chemotherapy has the potential to extend organ preservation therapy even in cases with locally advanced primary lesion It is also important to develop a strategy to reduce distant metastasis and to keep track of second primary cancers Objectives To update the therapeutic outcome of advanced hypopharyngeal cancer Methods A total of 72 cases with stage III/IV hypopharyngeal cancer were treated at Kyoto University Hospital during 2000-2008 Surgery was performed in 56 cases, total pharyngolaryngoesophagectomy (TPLE) in 39 cases and partial pharyngectomy (PPX) preserving the larynx in 17 cases Radiotherapy (RT) with or without concurrent chemotherapy was applied m 16 cases Induction chemotherapy (ICT) has been applied for 14 cases since 2006 to achieve organ preservation and reduction of distant metastasis The follow-up period varied from 12 months to 96 months (mean 32 months) Therapeutic outcomes were chart reviewed Results Five years cumulative overall and disease-specific survival (DSS) rates were 52 1% and 63 8%, respectively DSS rates in cases treated with surgery and those with RT were 65 1% and 56 1%, respectively N2c status showed the worst prognosis according to nodal disease classification Local control rates for cases treated with TPLE, PPX, and RT were 97 3%, 100%, and 80 4%, respectively The effective rate of ICT was 79%, and laryngeal preservation was achieved m 79% of the cases with ICT Recurrence occurred in 20 cases Approximately half of the recurrence was distant disease In the end, 17 cases died of the primary disease, while 10 cases died of other causes, mainly second primary cancers

Conclusions: The prognosis of patients was related to the initial stage at diagnosis. These results suggest that early diagnosis and treatment are the most important factors to improve the prognosis in oral cancer patients. Adjuvant treatment is also warranted to improve locoregional control of advanced cases. Objectives: To update the therapeutic outcome of oral cancer. Methods: In all, 129 cases with oral cancer were treated at Kyoto University Hospital during 20002008. Surgery with/without irradiation was performed for 34 cases in stage I, 27 in stage II, 15 in stage III, 42 in stage IVa, and 1 case in stage IVb. Brachytherapy was performed for three cases in stage II. Definitive radiotherapy was performed for three cases in stage III and five cases in stage IV. The follow-up period varied from 12 to 96 months (mean 30 months). Results: The 5-year cumulative overall and disease-specific survival (DSS) rates were 74.5% and 75.3%. DSS was 86.2% in stage I, 91.6% in stage II, 70.7% in stage III, 60.2% in stage IVa, and 0% in stage IVb. DSS shows worse prognosis with advanced nodal status. Locoregional recurrence occurred in 32 of 129 cases, including local recurrence in 8 cases, nodal recurrence in 18, retropharyngeal node metastasis in 1, and local and nodal recurrence in 5 cases. Salvage operation with/without postoperative radiotherapy was performed for 22 cases with locoregional recurrence and 7 of them have survived. © 2010 Informa Healthcare.

Conclusion It is important to suppress lymph node recurrence and distant metastasis to achieve better survival of advanced laryngeal cancer, especially supraglottic cancer Objective The therapeutic outcomes of 33 cases with advanced laryngeal cancer treated at Kyoto University Hospital between 2000 and 2008 were reviewed Methods Thirty-one males and two females were involved Their ages ranged from 49 to 81 years (average 65 6 years) All tumors were squamous cell carcinoma, arising at the glottis in 21 cases and the supraglottis in 12 cases Most glottic cancers (90 5%) and supraglottic cancers (83 3%) were classified as T3 or T4 Total laryngectomy with neck dissection was performed in the treatment of T3 or T4 cases Two cases of T2 cancers were treated by radiotherapy (66-72 Gy) with neck dissection, and one case of T2 cancer was treated by radiotherapy (66 Gy) Partial laryngectomy with neck dissection was performed in one T3 case Results Five-year overall survival rates for stage III of glottic cancer, stage IV of glottic cancer, stage III of supraglottic cancer, and stage IV of supraglottic cancer were 100%, 40 9%, 100%, and 24 2%, respectively Five-year disease-specific survival rates for stage III of glottic cancer, stage IV of glotuc cancer, stage III of supraglottic cancer, and stage IV of supraglottic cancer were 100%, 56 3%, 100%, and 28 1%, respectively No local recurrence occurred Regional lymph node recurrence occurred in two cases One patient with glotuc cancer and one with supraglottic cancer Both of them died of disease despite undergoing chemotherapy One case initially had lung metastasis, and post-treatment distant metastasis occurred in the lung in four cases, in the skin in one, and in multiple organs in one case

Conclusions: Once-daily radiotherapy for stage I glottic cancer and hyperfractionated radiotherapy for stage II glottic cancer achieved satisfactory results in terms of prognosis and laryngeal preservation. The treatment strategy for stage II glottal cancer with subglottal invasion needs to be reconsidered to further improve the outcome. Objectives: Although early glottic carcinomas are highly curable by radiation therapy, the laryngeal preservation rate is not always sufficient. We reviewed the stage I/II glottal cancer treated in our institute during a recent 15-year period to improve the outcome and prognosis. Methods: In all, 113 cases of stage I/II glottic cancer (81 stage I cases and 32 stage II cases) were treated in Kyoto University hospital from 1994 to 2008. In 81 cases with stage I glottic cancer, radiation was performed for 66 cases, transoral laser excision (TLE) was performed for 14 cases, and hyperfractionated radiotherapy was done for one case. Among 32 cases with stage II glottic cancer, 24 cases were treated with hyperfractionated radiotherapy, 6 cases were treated with radiation, and one case with partial laryngectomy. Total laryngectomy was performed for one patient who suffered mixed connective tissue disease. KaplanMeier estimates were used for the analysis of survival rate and laryngeal preservation rate. Results: The 5-year overall survival rates were 88.4% in stage I cases and 89.1% in stage II cases. The 5-year disease-specific survival rates were 100% in stage I cases and 93% in stage II cases. The 5-year laryngeal preservation rates were 99% in stage I cases and 90% in stage II cases. Two cases of stage II glottal cancer with subglottal invasion failed to be controlled and the patients died from local recurrence and mediastinum lymph node metastasis, respectively. © 2010 Informa Healthcare.

Conclusions It is suggested that radiotherapy might be the first choice for stage I/II hypopharyngeal cancer, and that adjuvant treatment might be necessary for stage II patients to prevent distant metastasis Objectives To update the therapeutic outcome of early hypopharyngeal cancer Methods Twenty-eight patients with stage hypopharyngeal cancer (8 in stage I, 20 in stage II) were treated at Kyoto University Hospital between 1995 and 2007 Of 8 cases in stage I, radiotherapy was applied for 4 cases, and surgical treatment for another 4, while 13 of 20 cases in stage II underwent radiotherapy and the remaining 7 cases underwent surgery Results The 5-year cumulative disease-specific survival and larynx preservation rates were 74 6% and 73 2%, respectively Recurrent tumors were found in two cases in stage I treated by surgery and in five cases in stage II treated with radiotherapy Two of five recurrent cases in stage II were rescued by salvage surgery Distant metastasis to the lung appeared in two cases in stage II after initial treatment

Conclusions: It is suggested that radiotherapy might be the first choice for stage I/II hypopharyngeal cancer, and that adjuvant treatment might be necessary for stage II patients to prevent distant metastasis. Objectives: To update the therapeutic outcome of early hypopharyngeal cancer. Methods: Twenty-eight patients with stage I/II hypopharyngeal cancer (8 in stage I, 20 in stage II) were treated at Kyoto University Hospital between 1995 and 2007. Of 8 cases in stage I, radiotherapy was applied for 4 cases, and surgical treatment for another 4, while 13 of 20 cases in stage II underwent radiotherapy and the remaining 7 cases underwent surgery. Results: The 5-year cumulative disease-specific survival and larynx preservation rates were 74.6% and 73.2%, respectively. Recurrent tumors were found in two cases in stage I treated by surgery and in five cases in stage II treated with radiotherapy. Two of five recurrent cases in stage II were rescued by salvage surgery. Distant metastasis to the lung appeared in two cases in stage II after initial treatment. © 2010 Informa Healthcare.

Conclusions Once-daily radiotherapy for stage I glottic cancer and hyperfractionated radiotherapy for stage II glottic cancer achieved satisfactory results m terms of prognosis and laryngeal preservation The treatment strategy for stage II glottal cancer with subglottal invasion needs to be reconsidered to further improve the outcome Objectives Although early glottic carcinomas are highly curable by radiation therapy, the laryngeal preservation rate is not always sufficient We reviewed the stage I/II glottal cancer treated in our institute during a recent 15-year period to improve the outcome and prognosis Methods In all, 113 cases of stage I/II glottic cancer (81 stage I cases and 32 stage II cases) were treated in Kyoto University hospital from 1994 to 2008 In 81 cases with stage I glottic cancer, radiation was performed for 66 cases, transoral laser excision (TLE) was performed for 14 cases, and hyperfractionated radiotherapy was done for one case Among 32 cases with stage II glottic cancer, 24 cases were treated with hyperfractionated radiotherapy, 6 cases were treated with radiation, and one case with partial laryngectomy Total laryngectomy was performed for one patient who suffered mixed connective tissue disease Kaplan-Meier estimates were used for the analysis of survival rate and laryngeal preservation rate Results The 5-year overall survival rates were 88 4% in stage I cases and 89 1% in stage II cases The 5-year disease-specific survival rates were 100% in stage I cases and 93% in stage II cases The 5-year laryngeal preservation rates were 99% in stage I cases and 90% in stage II cases Two cases of stage II glottal cancer with subglottal invasion failed to be controlled and the patients died from local recurrence and mediastinum lymph node metastasis, respectively

Conclusion Organ preservation surgery with partial pharyngectomy preserving the larynx is feasible for the treatment of advanced hypopharyngeal cancer with comparable local control and preservation of function Objectives To examine the feasibility and therapeutic effects of organ preservation surgery for advanced hypopharyngeal cancer Methods Fourteen patients with stage III/IV hypopharyngeal cancer were treated by partial pharyngectomy with or without partial laryngectomy to preserve the larynx Ten cases were T1/2 primary while four cases had T3/4 tumors Reconstruction of the pharyngolarynx was completed by primary mucosal suture in six, while free forearm flap was used in eight cases Induction chemotherapy was administered for six cases including three with T3/4 tumors Results Five-year overall survival and disease-specific survival rates were 57 1% and 66 7%, respectively The 5-year locoregional control rate was 66 7% and the larynx preservation rate was 100% No patients presented with local recurrence at the pharyngolaryngeal segment, while two cases showed nodal recurrence, from which they died Tracheal stoma was closed in 9 of 14 cases Vocal function was excellent in five cases, moderate in five, and poor in three Swallowing function was excellent to moderate in eight cases and poor in six

Conclusion: Treatment of advanced hypopharyngeal cancer has become more conservative and more multidisciplinary, and the prognosis has been improved. Induction chemotherapy has the potential to extend organ preservation therapy even in cases with locally advanced primary lesion. It is also important to develop a strategy to reduce distant metastasis and to keep track of second primary cancers. Objectives: To update the therapeutic outcome of advanced hypopharyngeal cancer. Methods: A total of 72 cases with stage III/IV hypopharyngeal cancer were treated at Kyoto University Hospital during 20002008. Surgery was performed in 56 cases; total pharyngolaryngoesophagectomy (TPLE) in 39 cases and partial pharyngectomy (PPX) preserving the larynx in 17 cases. Radiotherapy (RT) with or without concurrent chemotherapy was applied in 16 cases. Induction chemotherapy (ICT) has been applied for 14 cases since 2006 to achieve organ preservation and reduction of distant metastasis. The follow-up period varied from 12 months to 96 months (mean 32 months). Therapeutic outcomes were chart reviewed. Results: Five years cumulative overall and disease-specific survival (DSS) rates were 52.1% and 63.8%, respectively. DSS rates in cases treated with surgery and those with RT were 65.1% and 56.1%, respectively. N2c status showed the worst prognosis according to nodal disease classification. Local control rates for cases treated with TPLE, PPX, and RT were 97.3%, 100%, and 80.4%, respectively. The effective rate of ICT was 79%, and laryngeal preservation was achieved in 79% of the cases with ICT. Recurrence occurred in 20 cases. Approximately half of the recurrence was distant disease. In the end, 17 cases died of the primary disease, while 10 cases died of other causes, mainly second primary cancers. © 2010 Informa Healthcare.

Conclusions: Medialization thyroplasty was effective in improving swallowing function as well as vocal function in most cases with unilateral vocal fold paralysis. The impact of medialization thryoplasty was insufficient for the case with severe atrophy and that in which the vocal fold was fixed in the lateral position. Objectives: To evaluate the impacts and limitations of medialization thyroplasty on swallowing function of the patients with unilateral vocal fold paralysis. Methods: Eight cases (mean age 68.5 years) with unilateral vocal fold paralysis chiefly complaining of swallowing disturbance were studied. All patients underwent thyroplasty type I. The causes of the paralysis were lung cancer in four cases, esophageal cancer in one case, aortic aneurysm in one case, subarachnoid hemorrhage in one case, and unknown in one case. Subjective swallowing function score, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), and pitch perturbation quotient (PPQ) were examined pre- and postoperatively. Results: The swallowing score improved in all except two cases. However, bilateral thryoplasty was necessary for the case with severe vocal fold atrophy and arytenoid adduction was needed for the case in which the vocal fold was fixed in the lateral position. The swallowing score, MPT, and MFR showed significant improvement after surgery. © 2010 Informa Healthcare.

Conclusions The prognosis of patients was related to the initial stage at diagnosis These results suggest that early diagnosis and treatment are the most important factors to improve the prognosis in oral cancer patients Adjuvant treatment is also warranted to improve locoregional control of advanced cases Objectives To update the therapeutic outcome of oral cancer Methods In all, 129 cases with oral cancer were treated at Kyoto University Hospital during 2000-2008 Surgery with/without irradiation was performed for 34 cases in stage I, 27 in stage II, 15 in stage III, 42 in stage IVa, and 1 case in stage IVb Brachytherapy was performed for three cases in stage II Definitive radiotherapy was performed for three cases in stage III and five cases in stage IV The follow-up period varied from 12 to 96 months (mean 30 months) Results The 5-year cumulative overall and disease-specific survival (DSS) rates were 74 5% and 75 3% DSS was 86 2% in stage I, 91 6% in stage II, 70 7% in stage III, 60 2% in stage IVa, and 0% in stage IVb DSS shows worse prognosis with advanced nodal status Locoregional recurrence occurred in 32 of 129 cases, including local recurrence in 8 cases, nodal recurrence in 18, retropharyngeal node metastasis in 1, and local and nodal recurrence in 5 cases Salvage operation with/without postoperative radiotherapy was performed for 22 cases with locoregional recurrence and 7 of them have survived

Conclusion: It is important to suppress lymph node recurrence and distant metastasis to achieve better survival of advanced laryngeal cancer, especially supraglottic cancer. Objective: The therapeutic outcomes of 33 cases with advanced laryngeal cancer treated at Kyoto University Hospital between 2000 and 2008 were reviewed. Methods: Thirty-one males and two females were involved. Their ages ranged from 49 to 81 years (average 65.6 years). All tumors were squamous cell carcinoma, arising at the glottis in 21 cases and the supraglottis in 12 cases. Most glottic cancers (90.5%) and supraglottic cancers (83.3%) were classified as T3 or T4. Total laryngectomy with neck dissection was performed in the treatment of T3 or T4 cases. Two cases of T2 cancers were treated by radiotherapy (6672 Gy) with neck dissection, and one case of T2 cancer was treated by radiotherapy (66 Gy). Partial laryngectomy with neck dissection was performed in one T3 case. Results: Five-year overall survival rates for stage III of glottic cancer, stage IV of glottic cancer, stage III of supraglottic cancer, and stage IV of supraglottic cancer were 100%, 40.9%, 100%, and 24.2%, respectively. Five-year disease-specific survival rates for stage III of glottic cancer, stage IV of glottic cancer, stage III of supraglottic cancer, and stage IV of supraglottic cancer were 100%, 56.3%, 100%, and 28.1%, respectively. No local recurrence occurred. Regional lymph node recurrence occurred in two cases one patient with glottic cancer and one with supraglottic cancer. Both of them died of disease despite undergoing chemotherapy. One case initially had lung metastasis, and post-treatment distant metastasis occurred in the lung in four cases, in the skin in one, and in multiple organs in one case. © 2010 Informa Healthcare.

Objectives: The overarching goal of this line of research is to translate basic fibroblast growth factor (bFGF) treatment for vocal fold scarring into practical clinical use. In a previous canine investigation, we demonstrated that bFGF improves phonation threshold pressure, mucosal wave amplitude, and histologic measures in vocal folds treated after injury. In the present study, we studied the effects of bFGF on gene expression of the extracellular matrix and growth factors in rat vocal fold fibroblasts. Methods: Fibroblasts harvested from the vocal folds of 5 rats were treated with 3 concentrations of bFGF (0, 10, and 100 ng/mL). The fibroblasts were collected at 24 hours and 72 hours after bFGF administration. Quantitative polymerase chain reaction was then used to investigate the gene expression of the investigated growth factors and extracellular matrices. Results: The results revealed significantly down-regulated expression of procollagen I and significantly up-regulated expression of hyaluronic acid synthase (HAS) 2 and fibronectin in fibroblasts treated with bFGF. The administration of bFGF also resulted in the up-regulation of bFGF and hepatocyte growth factor (HGF). No changes in the expression of HAS-1, tropoelastin, or procollagen III were observed between the treatment and control conditions. Conclusions: Treatment with bFGF induces the down-regulation of procollagen I and the up-regulation of HAS-2 in vocal fold fibroblast cell cultures. These gene expression alterations to key mediators of the wound healing process may translate into potential benefits in the remediation of vocal fold injury. The up-regulation of HGF, an antifibrotic effector molecule, may demonstrate additional benefits by optimizing the wound healing environment and by accelerating the wound repair cascade. These findings may provide fuel for additional discoveries into the development of growth factor therapy for the treatment of vocal fold scar. © 2010 Annals Publishing Company. All rights reserved.

Educational Objective: At the conclusion of this presentation, the participants should be able to understand that basic fibroblast growth factor prevents radiation induced damage in salivary glands. Objectives: Radiotherapy is one of the most effective treatments for head and neck cancer. However, it is unavoidable to develop dry mouth syndrome as the common side effect because not only the tumor but also the normal salivary glands are included in the irradiation field. In this study, the protective efficacy of basic fibroblast growth factor (bFGF) was investigated in radiation damaged salivary glands. Study Design: Prospective animal experiment with control. Methods: C57BL/6 mice were divided into two groups. All mice in both groups were irradiated (10Gy) at one time. Mice in group I were administered by bFGF for 3 days after neck irradiation. Mice in group II were administered by distilled water as control. Submandibular glands morphology and saliva flow rate were assessed at 1 and 2 months after irradiation, and the apoptotic response of irradiated submandibular glands was also evaluated with and without bFGF treatment. Results: The decrease of saliva flow rates were severe in group II compared with group I. The submandibular glands in group I contained more acinar cells than in group II in histology. The glands with bFGF treatment examined at 1 and 2 days after irradiation did not almost detect apoptosis in comparison with no treatment. Conclusions: Our study indicates that bFGF prevents salivary gland dysfunction after irradiation. This protective effect of bFGF may be caused by the inhibition of radiation induced apoptosis. Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.

Localized laryngotracheal amyloidosis is rare, and therapeutic strategy yet to be determined. We report a case of localized laryngotracheal amyloidosis as an intraluminal tracheal mass compromising respiration. A 53-year-old woman was seen for severe dyspnea. Flexible laryngoscopy indicated subglottic stenosis, with computed tomography and magnetic resonance imaging showing a large mass lesion in the tracheal membrane. After tracheotomy, laryngotracheofissure was done for biopsy and to reduce the mass at the trachea and subglottic region, preserving as much mucosa as possible. Postoperative pathology was amyloidosis. Due to the limited effect of surgical reduction, another laryngotracheal fissure was done to completely remove the tracheal mass. The raw postresection surface was covered by atelocollagen sheet, with posterior cricoid split added to enlarge the subglottic area. The Postoperative airway was sufficient and the tracheostoma closed. No recurrence has been found 6 months after final surgery. Complete resection using laryngotracheal fissure and simultaneous laryngotracheal reconstruction with atelocollagen sheet is thus effective in treating of laryngotrahceal amyloidosis and resolving airway stenosis.

Objectives/Hypothesis: The maturation process of scarred vocal folds has previously been investigated using animal models. However, in human models the features of scarred vocal folds have rarely been described, and the process by which the scar changes with time is not well known. The present study aimed to investigate the maturation process of human vocal folds scarred by cordectomy in terms of vibratory and aerodynamic functions. Study Design: Prospective case series. Methods: Eight patients with early glottic carcinoma and two patients with leukoplakia of the vocal fold underwent endoscopic cordectomy at Kyoto University Hospital between 2006 and 2008. The temporal changes in their vocal functions were evaluated using acoustic and aerodynamic analyses and videostroboscopic examination. Results: Normalized mucosal wave amplitude, mean flow rate, and the amplitude perturbation quotient appear to stabilize about 6 months after the procedure. Although there were individual variations in the changes in normalized glottal gap and maximum phonation time, it appears to take at least 6 months to reach plateau. The other parameters - pitch perturbation quotient and noise to harmonic ratio - varied by individual, and thus it was difficult to identify commonalities in the healing process. Conclusions: Some individual variation was observed in the temporal changes of vocal function of scarred vocal folds after cordectomy. However, in terms of vibratory and aerodynamic functions, this study suggests that it takes at least 6 months for maturation of vocal fold scarring. © 2010 The American Laryngological, Rhinological and Otological Society, Inc.