記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

DOI： 10.1016/j.oraloncology.2024.106976

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC. METHODS: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics. RESULTS: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026). CONCLUSIONS: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation.

DOI： 10.1016/j.oraloncology.2024.106942

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.

DOI： 10.1007/s10388-024-01078-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear. PATIENTS AND METHODS: We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. RESULTS: In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response. CONCLUSION: Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab.

DOI： 10.21873/anticanres.17235

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記述言語：日本語   出版者・発行元：(株)東京医学社  

＜文献概要＞はじめに 化学放射線治療の普及により,喉頭摘出術,咽頭喉頭摘出術を喉頭温存を目的とした化学放射線治療後の救済手術として,あるいは過去に頭頸部領域に根治治療目的に(化学)放射線治療が行われた後に新規に発生した喉頭癌,下咽頭癌に対する根治切除として行われる機会が増えている。喉頭摘出後の咽頭皮膚瘻はひとたび生じると経口摂取の開始時期が大幅に遅れ,患者の生活の質を著しく低下させる,同術における留意すべき手術関連有害事象である。患者の全身状態や咽頭皮膚瘻の部位,感染状況など経過によっては総頸動脈破裂も生じ得るため適切な対応が求められる。特に化学放射線治療後では治療による組織障害や,全身状態の悪化に起因する創傷治癒障害などにより,咽頭皮膚瘻の発生リスクは高くなると言われている。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01814&link_issn=&doc_id=20240826030067&doc_link_id=%2Faq9johne%2F2024%2F004009%2F058%2F1159-1162%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9johne%2F2024%2F004009%2F058%2F1159-1162%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞はじめに 近年,抗programmed cell death 1(PD-1)抗体であるペムブロリズマブが,再発・遠隔転移頭頸部扁平上皮癌など,根治治療が困難な症例に対して使用されるようになった。それにより,これまで予後不良とされてきた症例において,一部ではあるが長期生存が可能となる例もみられるようになってきている。治療の副作用として,従来の殺細胞性の抗がん薬と異なり免疫関連副作用(immune related adverse events:irAE)があり,治療継続の際に問題となる。今回,われわれはペムブロリズマブ初回投与後にスティーブンス・ジョンソン症候群(Stevens-Johnson syndrome:以下,SJS)をきたし,同治療の継続が困難となったが,その後抗がん治療の追加施行なく,腫瘍の著明縮小が維持された蝶形骨洞癌の1例を経験したので報告する。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

DOI： 10.1111/cas.16230

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

Nuclear protein testis(NUT) carcinomaは頭頸部領域では日本で11例ほどしか報告のない希少癌である.今回われわれは頸部に発生したNUT carcinomaの症例を経験した.症例は51歳男性.左顎下部の腫脹が出現し,組織生検で低分化扁平上皮癌を疑われた.気道狭窄のため気管切開を先行し,頸部郭清術を行った.術後17日目にNUT carcinomaと病理診断された.その後腫瘍は急速に再増大し切除不能となり,術後36日目にペムブロリズマブ1コースを施行したが効果を得られず,術後45日目に死亡した.NUT carcinomaは非常にまれであり,本症例では診断や治療に難渋したため,報告する.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J07551&link_issn=&doc_id=20240628240003&doc_link_id=10.3950%2Fjibiinkotokeibu.127.6_721&url=https%3A%2F%2Fdoi.org%2F10.3950%2Fjibiinkotokeibu.127.6_721&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Factors related to surgical outcomes of type I tympanoplasty for tympanic membrane (TM) perforation in children are controversial. OBJECTIVES: To investigate factors related to anatomical results of type I tympanoplasty for TM perforation 1 year after surgery. MATERIAL AND METHODS: We examined 68 ears. Anatomical results were determined based on the presence or absence of re-perforation, atelectasis, and otitis media with effusion. We retrospectively analyzed factors based on age (≤8 and >8 years), cause and size of TM perforation (<50% and ≥50%), history of asthma and cleft palate, and size of mastoid air cell system in bilateral ears before tympanoplasty. Audiological prognosis was evaluated in ears with anatomical success 1 year after surgery. RESULTS: Anatomical success was achieved in 80.9% (55/68) of the ears. No significant differences were observed between these factors and anatomical results. All children with cleft palate had anatomical success. Mean pure-tone average (0.5-4 kHz) was 16.25 dB HL for ears with both TM perforations <50% and ≥50%. CONCLUSION AND SIGNIFICANCE: We observed no significant relationship between factors considered and surgical outcomes. However, audiological prognosis was favorable for anatomical success regardless of TM perforation size. Accordingly, type I tympanoplasty is considered useful for TM perforation in children.

DOI： 10.1080/00016489.2024.2360970

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：東京医学社  

DOI： 10.24479/ohns.0000000968

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J01814&link_issn=&doc_id=20240122120018&doc_link_id=10.24479%2Fohns.0000000968&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fohns.0000000968&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. METHODS: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. RESULTS: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. CONCLUSION: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

DOI： 10.3389/fimmu.2024.1390873

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Transoral robotic surgery (TORS), introduced by Weinstein et al. in 2005, has been widely adopted as a minimally invasive procedure, particularly for the treatment of patients with early stage oropharyngeal cancer. TORS is typically performed using the da Vinci Surgical System, similar to robot-assisted surgeries for other malignancies. The main difference between TORS and these other robot-assisted surgeries is that it is performed through the natural orifice of the mouth, which limits the surgical working space, and that it progresses from the lumen of the pharynx to the deeper tissues. The advantages of TORS are mainly due to the benefits of using the da Vinci Surgical System, such as three-dimensional high-definition images, magnification, multiple forceps articulation, tremor-stabilization function and motion scale function. To date, many big data and meta-analyses have shown that TORS is superior to conventional surgeries, such as open surgery, in terms of oncological outcomes, post-operative functionality and quality of life. In Japan, TORS is expected to spread across the country, as it has been covered by health insurance since April 2022. This review highlights the procedures of TORS, its unique aspects, its unparalleled advantages as a minimally invasive surgery for treating laryngeal and pharyngeal cancers, and its current status in Japan.

DOI： 10.1093/jjco/hyad168

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Our previous research showed that a high rate of secondary carcinogenesis is observed during follow-up after transoral surgery in patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We speculate that the contributing factors are alcohol drinking, smoking, and aging; however, we could not provide clear evidence. In this study, we aimed to identify the risk factors for secondary carcinogenesis in patients with these cancers, particularly factors associated with drinking and/or smoking. METHODS: The medical records of all-stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients who had undergone definitive treatment were retrospectively analyzed. Assessments included visual and endoscopic observations of the primary site, enhanced cervical CT or US of the primary site and regional lymph nodes, PET-CT, and enhanced whole-body CT. Clinical characteristics were compared in patients with and without secondary carcinogenesis and in patients with hypopharyngeal cancer and patients with other cancers. RESULTS: Hypopharyngeal cancer was an independent risk factor for secondary cancer. The 5-year incidence rate of secondary cancer was 25.5%, 28.6%, and 41.2% in laryngeal, oropharyngeal, and hypopharyngeal cancers, respectively. Radiotherapy was defined as an independent risk factor in hypopharyngeal cancer patients with secondary cancers. No direct correlation was found between secondary carcinogenesis and alcohol consumption, smoking, or aging. CONCLUSIONS: Patients with hypopharyngeal cancer require close follow-up as they are at high risk of developing secondary cancer, possibly because out-of-field radiation exposure may induce systemic secondary carcinogenesis in hypopharyngeal cancer patients with genetic abnormality induced by alcohol consumption.

DOI： 10.1007/s10147-023-02433-8

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

咽喉頭癌に対する低侵襲手術である経口的切除術の一つにtransoral robotic surgery(TORS;経口的ロボット支援手術)がある.米国を中心に広く行われており,その有用性と安全性が多く報告されている.本邦でも2022年4月に咽喉頭癌に対するTORSが保険診療の適用となり,今後急速に普及していくことが予想される.TORSに対して現在薬事承認されているda Vinciサージカルシステムは三次元ハイビジョン画像,拡大視,鉗子の多関節機能,手振れ防止機能,モーションスケール機能といった特徴を有し,従来の経口的切除の技術的欠点を補うことが可能である.一方で,鉗子を介した触覚はなく,豊富な視覚情報で補う必要がある.そのため,TORSでは良好な術野展開と術野に出血がない,クリーンな状態保持が重要である.本稿ではこれらの点を含めたTORSの手術手技の実際と,そのコツについて述べる.(著者抄録)

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記述言語：日本語   出版者・発行元：東京医学社  

DOI： 10.24479/ohns.0000000836

CiNii Research

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

DOI： 10.1002/hed.27471

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記述言語：日本語   出版者・発行元：(一社)日本鼻科学会  

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00296&link_issn=&doc_id=20230725250006&doc_link_id=%2Fab8gtkrc%2F2023%2F005007%2F007%2F0775-0780%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2023%2F005007%2F007%2F0775-0780%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities. PATIENTS AND METHODS: Data of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022 were analyzed. The endpoint was overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). OS and PFS were analyzed comparatively with and without irAEs, and complete response (CR) or partial response (PR), and stable disease (SD) or progressive disease (PD) were compared. RESULTS: One hundred thirty-five patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. For the pembrolizumab only group, the median OS and PFS were 22.7 and 5.1 months, respectively. There were significant differences in OS and PFS between CR or PR and SD or PD (p<0.01, p<0.01, respectively). For pembrolizumab with chemotherapy, the OS was not reached and median PFS was 7.0 months. There was a significant difference in PFS between CR or PR and SD or PD (p<0.01). There was a significant difference in PFS between patients with and without irAEs (p=0.02). CONCLUSION: The real-world therapeutic effect of pembrolizumab for R/M SCCHN was comparable to that observed in the KEYNOTE048 trial. In addition, irAEs and best overall response were considered as prognostic factors.

DOI： 10.21873/anticanres.16438

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This study aimed to identify key molecules associated with the survival of patients with hypopharyngeal squamous cell carcinoma (HpSCC) by combining in silico and in vitro analyses. MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened using the Gene Expression Omnibus database. For DEGs, we performed functional enrichment and protein-protein interaction network analyses to identify potential biological functions and hub genes. Functional analysis of HpSCC cell lines verified the critical roles of the hub genes. RESULTS: DEGs were associated with the extracellular matrix. Among the hub genes, high expression of prolyl 4-hydroxylase subunit alpha 1 (P4HA1) was significantly associated with shorter survival. In addition, P4HA1 knockdown inhibited cell migration and colonization. Suppression of cell proliferation was demonstrated using P4HA1-selective inhibitors. CONCLUSION: P4HA1 may be a useful therapeutic target for the treatment of HpSCC.

DOI： 10.21873/anticanres.16424

PubMed

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記述言語：英語  

DOI： 10.21037/tcr-23-48

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We previously established a patient-derived xenograft (PDX) model, patient-derived organoids (PDOs), and PDX-derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2-positive SDC. METHODS: The therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice. RESULTS: The siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice. CONCLUSION: For the first time, we demonstrated the efficacy of anti-HER2 therapy in HER2-positive SDC using preclinical models of SDC PDX and PDXO.

DOI： 10.1002/hed.27395

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：耳鼻と臨床会  

症例は73歳、男性。嗄声を主訴に受診した。左声帯白板症の経過観察中、初診から13ヵ月後に右声帯前方にポリープ様腫瘤が出現し、全身麻酔下での切除生検時の病理所見と術後の画像診断で紡錘細胞癌(T1aN0M0)と診断した。切除断端が陰性であったため、追加治療は施行しない方針とした。治療後1年6ヵ月経過し、再発なく経過している。紡錘細胞癌は扁平上皮癌と紡錘形細胞の2相性細胞で構成されるものであり、扁平上皮癌の亜型とされている。頭頸部領域では発生部位は喉頭が最多であるが、その発生頻度は喉頭悪性腫瘍の1%程度とまれである。喉頭紡錘細胞癌はポリープ様,外向性発育を示すことが特徴であり、良性病変との鑑別が重要である。治療は手術を施行されることが多いが、症例数が少ないことから放射線治療や薬物治療のエビデンスが乏しく、治療標的を含む分子生物学的な特徴の解明が必要である。(著者抄録)

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記述言語：日本語   出版者・発行元：日本臨床ウイルス学会  

HPV感染は耳鼻咽喉科領域でも大きな注目を集めており,代表的な疾患として中咽頭がんと喉頭乳頭腫がある.中咽頭は口蓋扁桃,舌根,軟口蓋などより構成され,近年日本においても性行動の多様化によりHPV陽性中咽頭がんの割合が増加している.特徴はHPV16が関与,若年発症,口蓋扁桃・舌根原発が多い,嚢胞性頸部リンパ節転移などがある.HPV陰性がんと比較して予後良好であり,合併症を軽減する目的で治療強度を減らす臨床試験が行われているが,一定の見解を得られていない.喉頭乳頭腫は若年発症型と成人発症型があり,HPV6とHPV11が関与している.治療の主体は手術療法であるが,周囲正常粘膜にもHPVが存在することから再発しやすく,播種や瘢痕化などの後遺症を引き起こさないことが重要である.HPVワクチンは男性接種を推進することで,女性のHPV感染率の減少に寄与すること,長期的な視点で中咽頭がん罹患率が減少することが期待されている.また喉頭乳頭腫への効果は一次予防のみならず,無再発期間の延長に寄与する可能性が示唆されている.(著者抄録)

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01814&link_issn=&doc_id=20230217060016&doc_link_id=%2Faq9johne%2F2023%2F003903%2F016%2F0289-0292%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9johne%2F2023%2F003903%2F016%2F0289-0292%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

局所進行頭頸部扁平上皮癌の術後再発高リスク患者を対象としたJCOG1008試験において,weeklyシスプラチンのtri-weeklyシスプラチンに対する全生存期間の非劣性が示された.Weeklyシスプラチンの導入にあたり,治療の標準化と効率化,有害事象対策の強化,患者の理解の促進を図るためクリニカルパスを作成し,運用した.1泊2日を基本とする短期入院でも十分な輸液ができるよう配慮した.当科でtri-weeklyシスプラチン併用放射線治療を受けた患者とweeklyシスプラチン併用放射線治療を受けた患者を後ろ向きに比較したところ,シスプラチン総投与量に有意差は認められなかったが,weeklyシスプラチン群では入院泊数が有意に短く,1泊あたりの診療群分類包括評価(DPC)点数が有意に高かった.Weeklyシスプラチン併用放射線治療の導入は,安全性と治療強度を損なうことなく入院期間の短縮と入院単価の増加が得られる可能性があり,患者,医療者,病院それぞれにとってメリットがある方法であると考えられた.また,クリニカルパスについてはバリアンスに関するデータを蓄積および解析し,改良を続ける必要がある.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07551&link_issn=&doc_id=20230301320007&doc_link_id=%2Fdz0tokei%2F2023%2F012602%2F007%2F0121-0127%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0tokei%2F2023%2F012602%2F007%2F0121-0127%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Previous studies have identified several inflammatory biomarkers that are useful as prognostic biomarkers for various cancer types. However, the fibrinogen-to-lymphocyte ratio (FLR) has not been addressed in head and neck squamous cell carcinoma. Here, we aimed to examine the value of pretreatment FLR as a prognostic marker in patients who received definitive radiotherapy for hypopharyngeal squamous cell carcinoma (HpSCC). PATIENTS AND METHODS: This retrospective study included 95 patients treated with definitive radiotherapy for HpSCC between 2013 and 2020. The prognostic factors for progression-free (PFS) and overall (OS) survival were identified. RESULTS: The optimal cut-off value of pretreatment FLR for discriminating PFS was 2.46. Based on this value, 57 and 38 patients were classified into groups with high and low FLR, respectively. A high FLR was significantly associated with advanced local disease and overall stage, and with the development of synchronous second primary cancer compared with a low FLR. The high FLR group had significantly lower PFS and OS rates than the low FLR group. Multivariate analysis showed that having a high pretreatment FLR was an independent prognostic factor for poorer PFS and OS [PFS: hazard ratio (HR)=2.14, 95% confidence interval (CI)=1.09-4.19, p=0.026; OS: HR=2.86, 95% CI=1.14-7.20, p=0.024]. CONCLUSION: The FLR has a clinical effect on PFS and OS in patients with HpSCC, suggesting that it has potential application as a prognostic factor for patients with HpSCC.

DOI： 10.21873/invivo.13206

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The prognosis of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is poor, although immune checkpoint inhibitors (ICIs), such as nivolumab, have been shown to prolong survival. We investigated the factors that predict the efficacy of nivolumab when selecting an appropriate treatment strategy for patients with R/M SCCHN. PATIENTS AND METHODS: Forty-four Japanese patients with R/M SCCHN treated with nivolumab between May 2017 and October 2021 were analyzed. The primary endpoint of the study was overall survival (OS). We defined pre-treatment tumor size (PTS) as the sum of the size of all measurable lesions, and tumor growth rate (TGR) as the total growth rate of the largest tumor diameter on CT scans taken to determine treatment response, divided by the interval between CT scans. Receiver operating characteristic (ROC) curves were used to identify the cutoff points of PTS and TGR for OS. Cox proportional hazards regression analysis was performed to examine the relationships between various factors, including patient characteristics, PTS, and TGR, as well as treatment outcomes. RESULTS: In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥1, progressive disease (PD) as best overall response (BOR), and TGR >0.60%/day were independent risk factors for poor OS in patients with R/M-SCCHN. CONCLUSION: Higher TGR, poor PS, and PD as BOR may be prognostic factors in patients with R/M SCCHN.

DOI： 10.21873/invivo.13378

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Research Square Platform LLC  

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Purpose: Salivary gland carcinoma (SGC) has poor prognosis depending on the histological subtype. However, due to the scarcity of preclinical experimental models, its molecular biology remains largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study is to generate human SGC experimental models for multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. Methods: Tumor specimens from surgically resected SGC were proceeded for the preparation of PDX and patient-derived organoid (PDO). Specimens from SGC PDX were also proceeded for PDX-derived organoid (PDXO). in vivo tumorigenicity was assessed by orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumor by Immunohistochemistry analysis. The genetic traits of PDO samples were analyzed by RNA-seq. Results: A series of SGC PDOs, PDX and PDXO models using human SGC tumor section for salivary duct carcinoma, mucoepidermoid carcinoma, and myoepithelial carcinoma were successfully generated. Through passaging, each model was confirmed to almost maintain the pathological characteristics of the original tumor and the genetic traits including transcription profiles, genomic variation and the presence of fusion genes of corresponding histological subtypes. Conclusion: We here described success in the generation of in vitro and in vivo SGC models of multiple histological subtypes using organoid culture and PDX, recapitulating the histological and genetical characteristics of original tumor. Thus, our experimental models of SGC could be a powerful resource for the development of novel therapeutic agents and investigating the molecular biology of these malignancies.

DOI： 10.1007/s13402-022-00758-6

PubMed

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その他リンク： https://www.researchsquare.com/article/rs-1621957/v1.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab-chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). METHODS: Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67). RESULTS: At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09-0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25-1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31-1.41]). Pembrolizumab-chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23-2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55-2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55-2.22]). Median PFS was similar for pembrolizumab and pembrolizumab-chemotherapy versus EXTREME in all subgroups. Grades 3-5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab-chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab-chemotherapy died because of treatment-related pneumonitis. CONCLUSION: These results support the use of first-line pembrolizumab and pembrolizumab-chemotherapy for Japanese patients with R/M HNSCC. Clinical trial registry ClinicalTrials.gov, NCT02358031.

DOI： 10.1007/s10147-022-02233-6

PubMed

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記述言語：日本語   出版者・発行元：日本喉頭科学会  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02852&link_issn=&doc_id=20230111160004&doc_link_id=10.5426%2Flarynx.34.65&url=https%3A%2F%2Fdoi.org%2F10.5426%2Flarynx.34.65&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：日本喉頭科学会  

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記述言語：日本語   出版者・発行元：日本唾液腺学会  

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記述言語：日本語   出版者・発行元：日本唾液腺学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To evaluate the feasibility of narrow-field supracricoid partial laryngectomy with cricohyoidoepiglottopexy (NF-SCPL-CHEP). METHODS: Between 2019 and 2020, five patients with glottic cancers underwent NF-SCPL-CHEP. The mean durations of surgical drains, tracheostomy canula, and nasogastric tube use were evaluated. Length of stay following NF-SCPL-CHEP was compared with that of our open SCPL historical controls. A case summary is provided for the first patients, with detailed information about postoperative management and function. RESULTS: All five patients achieved uneventful postoperative recoveries without major complications. The average time for surgical drains, tracheostomy canula, and nasogastric tube use were 2, 15, and 46 days, respectively. The mean overall hospitalization period was 36 days for NF-SCPL-CHEP patients. The mean period of hospitalization based on our early experiences between 1997 and 2005 with classical open SCPL was 72 days. All patients were fully functional and local recurrences or distant metastases were not encountered during a mean observation period of 39 months. CONCLUSIONS: NF-SCPL-CHEP with 6 cm cervical access appeared technically feasible and oncologically sound in this initial clinical experience. An extra 2 cm incision, which enabled lateral neck dissection, was not felt to detract from the overall minimally invasive basis of NF-SCPL-CHEP. The clinical results were encouraging with limited complications and predictable postoperative recovery. The length of stay for patients undergoing NF-SCPL was half that of open SCPL historical controls. Less damages to local circulation may associate with the positive influences. Further study with a large patient sample across multiple institutions are needed to carefully evaluate long-term functional and oncological outcomes.

DOI： 10.1016/j.anl.2022.09.011

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Nivolumab has antitumor efficacy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who relapse within 6 months after platinum-based therapy; however, the efficacy of nivolumab for platinum-sensitive R/M HNSCC has not been shown. Therefore, this study compared the efficacy and safety of nivolumab for platinum-refractory and platinum-sensitive R/M HNSCC. PATIENTS AND METHODS: This was a retrospective study of patients who received nivolumab for R/M HNSCC who had been previously treated with platinum-based anticancer drugs. Patients were divided into a platinum-sensitive and a platinum-refractory group, and progression-free survival (PFS), overall survival (OS), the overall response rate (ORR) [complete response (CR) + partial response (PR)], the disease control rate (DCR) (CR + PR + stable disease), and the incidence of immune-related adverse events (irAEs) were compared between the two groups. RESULTS: We included 88 patients with squamous cell carcinoma: 60 with platinum-refractory disease and 28 with platinum-sensitive disease. The median PFS in the platinum-refractory and platinum-sensitive groups were 2.7 months and 5.3 months, respectively (p=0.03), and the median OS were 8.8 months and 17.1 months, respectively (p=0.06). There were no significant differences in the ORR, DCR, or incidence of irAEs between the two groups (p>0.99, p=0.11, and p>0.99, respectively). CONCLUSION: Nivolumab is a safe and effective treatment for platinum-sensitive R/M HNSCC.

DOI： 10.21873/anticanres.15996

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The success of type 2 thyroplasty (TP2) for adductor spasmodic dysphonia (AdSD) depends on the selection of optimally sized titanium bridges, which requires accurate assessment of intraoperative vocal changes. While this procedure has traditionally been performed according to the laryngologist's experience, the most appropriate method for voice monitoring and selection of titanium bridge size remains to be determined. This study aimed to investigate evaluation parameters useful for voice monitoring, as these may allow less experienced surgeons to perform TP2 properly. METHODS: In this prospective study, voice monitoring was performed in 18 patients with AdSD patients undergoing TP2. Evaluations were performed preoperatively, intraoperatively, 13 weeks postoperatively, and 52 weeks postoperatively using GRBAS (grade, roughness, breathiness, asthenia, and strain), as well as perceptual judgment and acoustic analyses. RESULTS: Preoperative and intraoperative assessments of the G, R, B, and S parameters, perceptual judgment, and harmonic-to-noise ratio (HNR) were in moderate or better agreement. Intraoperative and 13- or 52-week postoperative measurements of the R, B, and G parameters and strangulation, tremor, and HNR were also in high agreement. When two different sizes of titanium bridges were compared (unselected vs. selected), ratings for G, R, S, strangulation, tremor, jitter, shimmer, HNR, standard deviation of F0, and degree of voice breaks were better for the selected width than the unselected width. CONCLUSION: The candidate items for intraoperative voice monitoring during TP2 for AdSD are G, R, strangulation, tremor, and HNR. The use of these items may help to ensure successful TP2 and contribute to the advancement of laryngeal framework surgery. LEVEL OF EVIDENCE: Level 4.

DOI： 10.1002/lio2.898

PubMed

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本鼻科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This Japanese single-center retrospective cohort study aimed to evaluate the real-world therapeutic outcomes of pembrolizumab or pembrolizumab plus chemotherapy (pembrolizumab regimen) as first-line therapy for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: Thirty-two Japanese patients with R/M SCCHN treated with the pembrolizumab regimen between January 2020 and January 2022 were analyzed. The primary endpoint of the study was overall survival. RESULTS: The median follow-up duration was 9.8 months (range=1.6-25.1 months). Fourteen patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. The 1-year overall and progression-free survival rates were 64.5% (95% CI=38.9-81.6) and 54.9% (95% CI=33.9-71.8), respectively. The objective response rate was 56.2%. The Kaplan-Meier analysis showed that patients with favorable objective responses and an Eastern Cooperative Oncology Group performance status of 0 had longer survival. Immune-related adverse events (irAEs) occurred in 16 out of 32 patients (50.0%) during treatment; however, there were no irAEs greater than grade 4. CONCLUSION: The observed therapeutic efficacy and safety of pembrolizumab in real-world clinical practice was consistent with the data of the KEYNOTE-048 trial.

DOI： 10.21873/anticanres.15948

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本鼻科学会  

放線菌症は嫌気性のグラム陽性桿菌であるActinomyces属によって引き起こされる疾患である。放線菌症は頭頸部に好発するが,副鼻腔における放線菌症は比較的稀である。我々が渉猟しえた範囲で国内の報告例18例全例が外科的処置を併用し治療していた。今回我々は抗菌薬治療のみで治癒しえた副鼻腔放線菌症例を経験したため報告する。症例は77歳男性。前立腺癌の経過観察目的に撮影されたCTで副鼻腔炎を指摘され,副鼻腔CTで歯性上顎洞炎の臨床診断となった。少量マクロライド療法を行ったが改善せず,抜歯後も副鼻腔炎が増悪したため,中鼻道粘膜の生検を行い放線菌症と確定診断した。その後当該疾患に対して外科的治療を行うことなく,アモキシシリン内服を8ヵ月,ピペラシリンタゾバクタム静脈注射を1ヵ月間の抗菌薬加療のみで治癒した。現在まで再発は認めていない。放線菌症の治療は抗菌薬投与と外科的治療が中心となる。内視鏡下に副鼻腔を大きく開放し好気的な鼻副鼻腔環境に変えることは比較的容易であり,我々が渉猟しえた副鼻腔放線菌症の18例では全例で外科的治療が行われていた。副鼻腔放線菌症に対して外科的治療は有効な治療と考えられる一方で,合併症の問題や高齢者であることなど手術が選択しにくい患者や手術拒否例も経験するところである。本症例は本邦初の抗菌薬治療のみで治癒した副鼻腔放線菌症例であり,手術が選択されない場合でも抗菌薬加療のみで治癒が得られる可能性を示唆するものと考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01675&link_issn=&doc_id=20220802360003&doc_link_id=10.7248%2Fjjrhi.61.262&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.61.262&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

症例は64歳女性で、当科初診当日、めまいおよび頭痛、発熱のため当院救急外来へ救急搬送され、両側の難聴を認めたため同日当科へ併診となった。感染症や結核、ベーチェット病、サルコイドーシスは否定的であり、抗菌薬が奏効しない中耳炎、進行性の骨導閾値の上昇、MPO-ANCA陽性および肥厚性硬膜炎を認め他の鑑別疾患が除外されたことから、診断基準よりANCA関連血管炎性中耳炎と診断した。プレドニゾロンを投与するも標準純音聴力検査で両側聾と改善を認めず、第74病日に聴力およびめまいの自覚症状の改善を認めないまま退院となった。その後、人工内耳の適応と考え、第175病日に右人工内耳手術が施行されることとなった。手術1年半後の人工内耳の装用閾値は25～35dB、人工内耳装用下音場語音明瞭度は55.0%で、CI-2004単語検査では72%、CI-2004日常会話文検査では78%であった。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00580&link_issn=&doc_id=20220705240006&doc_link_id=10.5631%2Fjibirin.115.579&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.115.579&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：耳鼻咽喉科臨床学会  

症例は64歳女性で、当科初診当日、めまいおよび頭痛、発熱のため当院救急外来へ救急搬送され、両側の難聴を認めたため同日当科へ併診となった。感染症や結核、ベーチェット病、サルコイドーシスは否定的であり、抗菌薬が奏効しない中耳炎、進行性の骨導閾値の上昇、MPO-ANCA陽性および肥厚性硬膜炎を認め他の鑑別疾患が除外されたことから、診断基準よりANCA関連血管炎性中耳炎と診断した。プレドニゾロンを投与するも標準純音聴力検査で両側聾と改善を認めず、第74病日に聴力およびめまいの自覚症状の改善を認めないまま退院となった。その後、人工内耳の適応と考え、第175病日に右人工内耳手術が施行されることとなった。手術1年半後の人工内耳の装用閾値は25〜35dB、人工内耳装用下音場語音明瞭度は55.0%で、CI-2004単語検査では72%、CI-2004日常会話文検査では78%であった。

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01054&link_issn=&doc_id=20220608270022&doc_link_id=%2Fea4broes%2F2022%2F007302%2F027%2F0098-0101%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2022%2F007302%2F027%2F0098-0101%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.

DOI： 10.1200/JCO.21.01293

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We previously identified hypopharyngeal cancer as an independent risk factor for the incidence of newly diagnosed secondary cancers after the treatment of early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We subsequently used a different patient cohort to validate the usefulness of this factor during the follow-up period in these patients. METHODS: Patients who underwent transoral surgery (TOS) as a definitive treatment between April 1, 2016, and September 30, 2020, were included. The incidence of secondary cancer was evaluated in hypopharyngeal and other cancers. Overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS) outcomes were evaluated. Statistical analyses based on the risk factors were also performed. RESULTS: Incidence of new secondary cancer was 30% in hypopharyngeal cancer patients as compared to 11% in other cancer patients, and the risk was 3.60-fold (95% confidence interval 1.07-12.10) higher after definitive treatment for initial head and neck cancers. The 3-year OS, RFS, and DFS rates were 98%, 86%, and 67%, respectively. CONCLUSIONS: Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, who were initially treated with TOS, hypopharyngeal cancer patients had a higher risk of newly diagnosed secondary cancers as observed during the follow-up period.

DOI： 10.1007/s10147-021-02080-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data. PATIENTS AND METHODS: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety. RESULTS: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups. CONCLUSION: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body.

DOI： 10.21873/anticanres.15635

PubMed

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. MATERIALS AND METHODS: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. RESULTS: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). CONCLUSION: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

DOI： 10.3389/fsurg.2022.1049116

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We had previously identified the following risk factors for insufficient control of early T-stage head and neck cancer by transoral surgery (TOS): (1) tumor thickness > 7 mm on enhanced computed tomography (CT), and (2) poor differentiation in pathological examination. We subsequently used a different patient cohort to validate the usefulness of these factors in determining the need for adaptation of TOS. STUDY SETTING: A prospective observational study METHODS: Patients who received TOS as a definitive treatment between April 1, 2016 and September 30, 2020 were included. Primary control rates (by single TOS and TOS alone) in relation to the above-mentioned risk factors were calculated. Overall (O), recurrence-free (RF), and disease-free (DF) survival (S) outcomes were evaluated. A combination analysis based on the number of risk factors was also performed. RESULTS: Patients with tumor thickness > 7 mm had a 2.88-fold [95% confidence interval (CI) 1.01-8.51] higher risk of incomplete primary resection by single TOS, while patients who showed poor differentiation on pathological assessments had a 13.14-fold (95% CI 3.66-47.14) higher risk of insufficient primary control by TOS alone. The 3 year OS, RFS, and DFS rates were 99%, 83%, and 63%, respectively. Patients with both risk factors had a 93.00-fold (95% CI 4.99-1732.00) higher risk of incomplete primary control by TOS alone. CONCLUSIONS: Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, primary control by TOS alone may not be achieved in patients with both risk factors, that is, tumor thickness > 7 mm as measured by enhanced CT and poor differentiation on pathological examination.

DOI： 10.1007/s10147-021-01992-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.

DOI： 10.1002/cam4.4252

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense. CASE PRESENTATION: A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat. Mycobacterial tissue culture and polymerase chain reaction testing revealed the presence of Mycobacterium abscessus subspecies massiliense in the nasopharyngeal tissue. This patient underwent surgery, followed by multiple rounds of chemotherapy with oral and intravenous antibiotic agents for 16 weeks. She has had no recurrence during the 56 weeks since treatment. CONCLUSION: It is difficult to detect the presence of Mycobacterium abscessus subspecies massiliense in a culture from the swabbing sample. The tissue culture from a biopsy specimen is mandatory for the identification of the species. Currently, no definite treatment policy is available and only empirical treatment is applied. This case is an important for the diagnosis and treatment of this bacterial infection on nasopharynx.

DOI： 10.1186/s40001-021-00578-8

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞POINT ▼手術前の副腎皮質ステロイド投与により,術後悪心嘔吐,術後疼痛の緩和が期待される。周術期の副腎皮質ステロイド単回投与による手術部位感染などの合併症は増加しないと報告されている。▼高催吐リスク抗癌剤に対する制吐療法として副腎皮質ステロイドが有効である。また,免疫チェックポイント阻害薬の投与による有害事象の治療にも副腎皮質ステロイドが重要な役割を果たしている。▼頭頸部癌の緩和医療においても副腎皮質ステロイドが有用である場合がある。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02122&link_issn=&doc_id=20210804030016&doc_link_id=10.11477%2Fmf.1411202788&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1411202788&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Predicting the prognosis of early-onset otitis media with effusion (OME) in children is difficult. OBJECTIVES: To investigate the prognostic factors of OME in children undergoing tympanostomy at 1 year of age. MATERIAL AND METHODS: We examined 66 children (123 ears) followed up to 6 years of age. OME prognosis was determined by a history of re-tympanostomy at the last examination. We retrospectively analysed the prognostic factors based on the duration of first ventilation tube (VT) placed, history of otorrhea, asthma, adenoidectomy, and mastoid air cell system (MACS) size at 1 year before tympanostomy and at 3 years. RESULTS: While 25 ears underwent re-tympanostomy (group 1), 98 did not (group 2). The mean duration of VT placed was 21 months and 25, and the mean MACS size at 3 years was 314 mm2 and 441, respectively, in the corresponding groups. MACS size at 3 years was significantly smaller in group 1 than in group 2. The combination of MACS size at 3 years and duration of VT placed showed the best value of area under the curve. CONCLUSION AND SIGNIFICANCE: The most probable prognostic factor was the combination of the MACS size at 3 years and duration of VT placed.

DOI： 10.1080/00016489.2021.1956690

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00296&link_issn=&doc_id=20210720430008&doc_link_id=%2Fab8gtkrc%2F2021%2F004807%2F009%2F0900-0902%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2021%2F004807%2F009%2F0900-0902%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: We evaluated the impact of FosL1, a member of the activated protein-1 family, on the pathways leading to regional metastasis of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We examined the influence of small interfering RNA (siRNA) and short heparin RNA (shRNA) mediated knockdown of FosL1 on cell migration, invasion, and proliferation in vitro as well as on regional metastasis in vivo. The prognostic significance of FosL1 was also analyzed using the Kaplan- Meier plotter using data from an HNSCC patient database. RESULTS: Down-regulation of FosL1 inhibited cell migration, invasion, and proliferation in vitro, decreased the incidence of regional metastases, and prolonged the survival of mice in vivo. We also determined that HNSCC patients with higher expression levels of FosL1 had a significantly shorter survival time than those with low expression of FosL1. CONCLUSION: FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in HNSCC.

DOI： 10.21873/anticanres.15119

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞POINT ▼ヒト乳頭腫ウイルス(HPV)対する感染予防ワクチン(2価,4価,9価)がすでに本邦で製造販売承認されている。▼HPVワクチン接種が広く実施されている諸外国では,HPV感染や子宮頸癌の前癌病変の発症減少が報告されている。▼頭頸部領域では中咽頭癌,特に扁桃・舌根原発の癌とHPV感染との関連が確実視されている。▼口腔内HPV感染がHPV関連中咽頭癌の発症に先行すると考えられる。▼HPV関連中咽頭癌が好発する中高年男性の口腔内HPV16陽性率は低く,効果的なワクチン接種の時期・年齢について今後検討されなければならない。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES/HYPOTHESIS: Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate- or high-grade budding scores was investigated as a prognostic marker for occult neck metastases. STUDY DESIGN: Retrospective study. METHODS: Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin. RESULTS: Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease-free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate- or a high-grade budding score had a poor prognosis for RC according to the log-rank test. CONCLUSIONS: In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate- or high-grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC. LEVEL OF EVIDENCE: Step 4 (Level 4) Laryngoscope, 2021.

DOI： 10.1002/lary.29589

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記述言語：日本語   出版者・発行元：日本耳鼻咽喉科免疫アレルギー感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The incidence of oropharyngeal cancer (OPC) is increasing remarkably among all head and neck cancers, mainly due to its association with the human papillomavirus (HPV). Most HPVs are eliminated by the host's immune system; however, because HPV has developed an effective immune evasion mechanism to complete its replication cycle, a small number of HPVs are not eliminated, leading to persistent infection. Moreover, during the oncogenic process, the extrachromosomal HPV genome often becomes integrated into the host genome. Integration involves the induction and high expression of E6 and E7, leading to cell cycle activation and increased genomic instability in the host. Therefore, integration is an important event in oncogenesis, although the associated mechanism remains unclear, especially in HPV-OPC. In this review, we summarize the current knowledge on HPV-mediated carcinogenesis, with special emphasis on immune evasion and integration mechanisms, which are crucial for oncogenesis.

DOI： 10.3390/microorganisms9050891

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC). MATERIALS AND METHODS: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy. RESULTS: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177). CONCLUSIONS: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.

DOI： 10.1016/j.anl.2021.01.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Botulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high-quality clinical studies have appeared, and BT is used off-label in most countries. METHODS: We performed a multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty-four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4 weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period. RESULTS: In the adductor SD group, the number of aberrant morae at 4 weeks after injection was reduced by 7.0 ± 2.30 (mean ± SE) in the BT group and 0.2 ± 0.46 in the placebo group (p = 0.0148). The improvement persisted for 12 weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2 weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4 weeks. CONCLUSIONS: Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.

DOI： 10.1111/ene.14714

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本癌学会  

To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC.

DOI： 10.1002/ijc.33315

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Our prospective study of patients with early T-stage head and neck cancer indicated a high incidence of newly diagnosed secondary malignancies during the follow-up period. We aimed to determine the incidence rate and risk factors of secondary malignancies in early-stage head and neck cancer patients. METHODS: We sub-analyzed the patient data of a previous study focusing on secondary cancer incidence. The endpoints were statistical analyses of risk factors and survival and incidence rates. RESULTS: The incidence rate of secondary cancer was 37%, the crude incidence of second primary cancers was 10.6 per 100 person-years, and the 5 year secondary cancer-free survival rate was 63%. The hypopharynx as the primary site was an independent significant predictive factor (odds ratio 3.96, 95% confidence interval 1.07-14.6, p = 0.039). CONCLUSIONS: Early stages of laryngeal, oropharyngeal, and hypopharyngeal cancer had a risk of secondary cancer, especially hypopharyngeal cancer. Attention to the secondary cancer has to be paid during the follow-up period after controlling the early-stage disease. These findings highlight the need for awareness of the incidence of secondary cancer in cases of early-stage primary head and neck cancer.

DOI： 10.1007/s10147-020-01779-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

As the laryngopharynx is closely related to swallowing, speech, and phonation, it is necessary to consider not only disease control but also a minimally invasive approach for the treatment of laryngopharyngeal cancer. Transoral surgery has been reported to be a minimally invasive method for treating these diseases. Transoral videolaryngoscopic surgery (TOVS) and endoscopic laryngo-pharyngeal surgery (ELPS) have been developed in Japan and recently emerged as treatments for patients with early stage pharyngeal and laryngeal cancers. However, securing an appropriate field of view and a narrow operating space during TOVS or ELPS are critical issues to be resolved for these surgeries. The clinical significance and safety of transoral robotic surgery (TORS) using the da Vinci Surgical System have been widely reported to provide surgeons with increased visualization and magnification, resulting in precise surgical margins and rapid functional recovery. In this context, a multi-institutional clinical study was conducted to evaluate the treatment outcomes of TORS for the treatment of laryngopharyngeal cancer in Japan, and the da Vinci Surgical System for oral robot-assisted surgery for these diseases was approved by the Pharmaceutical Affairs Agency in August 2018. This review provides an overview of the therapeutic effects of TOVS, ELPS, and TORS, with a particular focus on these therapeutic results in Japan.

DOI： 10.3389/fonc.2021.804933

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

Nasal septal abscess has rarely been encountered in clinical practice in recent years. We report the case of a 75-year-old man who had a nasal septal abscess, probably caused by nasal tinkering. The patient presented with an approximately 1-year history of episodes of nasal bleeding. He had been prescribed an ointment for topical nasal application by a neighborhood doctor and had applied the ointment with his fingers. He then visited the local doctor with complaints of nose pain, low-grade fever, and nasal congestion. As the symptoms did not improve with the prescribed treatment, he was referred to our hospital. Medical examination at our department led to the suspicion of nasal septal abscess
therefore, an incision was made under local anesthesia, followed by administration of antibiotic and steroid therapy for 4 days. However, this treatment also failed, and local incision and drainage was repeated under local anesthesia in the operating room. The abscess resolved, and no recurrence has been observed for 6 months after the operation, and there are no sequelae, such as saddle nose. With the advances in the development of effective antibacterial drugs, nasal septal abscess has become a rarely encountered disease in recent years. However, the clinical course of cases with severe nasal septal abscess can be complicated by meningitis and sepsis. There is also the possibility of sequelae, such as saddle nose, after treatment. In patients presenting with symptoms such as nasal obstruction, nasal pain, and low-grade fever, it is important to have a high index of suspicion and make an early diagnosis of nasal septal abscess by proactive endoscopy. In this patient reported herein, the traumatic effect of frequent application of an ointment with unwashed fingers for about one year was considered to have caused a nasal septal abscess.

DOI： 10.5631/jibirin.114.515

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: We previously presented the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This study aimed to evaluate the prognostic significance of pretreatment inflammatory biomarkers in patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy as a supplementary study of our previous retrospective cohort study. PATIENTS AND METHODS: The treatment outcomes of 100 patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy were compared according to patient characteristics and pretreatment inflammatory biomarkers using a Cox proportional hazards regression model. Survival was evaluated using the Kaplan-Meier method. RESULTS: In multivariate analysis, a lymphocyte-to-monocyte ratio (LMR) of <1.944 and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 were independent risk factors for poor overall and progression-free survival. Furthermore, we found that the PS-LMR score based on the ECOG PS and LMR could stratify patients to extract the poor prognostic characteristics of R/M-SCCHN patients treated with the EXTREME regimen as first-line therapy. CONCLUSION: Further evaluation is warranted to study the reliability and applicability of this novel scoring system in predicting the prognosis of R/M-SCCHN patients in the future.

DOI： 10.21873/cdp.10047

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Oto-Rhino-Laryngology Tokyo  

The main symptoms of SAPHO syndrome are cutaneous and bony symptoms. The most common skin manifestations include palmoplantar pustulosis, psoriasis, cellulitis, and pyogenic sweat glands. Bone symptoms include arthralgia due to bony hyperplasia, and are most common at the sternoclavicular joints. The cause of the disease is unknown, and while the frequency of occurrence has not yet been determined in Japan, it is estimated to occur at an incidence rate of about 0.04% worldwide. There are no established diagnostic and therapeutic criteria, but the long―term prognosis is good. In general, nonsteroidal anti―inflammatory drugs（NSAIDs）are the mainstay of symptomatic treatment. Recently, however, it has been reported that palatine tonsillectomy could improve the joint and skin symptoms. In the present study, we report a case of SAPHO syndrome in which palatine tonsillectomy clearly improved the arthralgia.

DOI： 10.3950/JIBIINKOKA.124.225

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

Eruption of a tooth into the nasal cavity is rarely encountered. We report a case of an inverted supernumerary tooth in the nasal cavity. A 16-year-old man was referred to our hospital after examination at a local otorhinolaryngology clinic for right nasal obstruction. CT revealed a tooth-like structure in the right nasal cavity. Endoscopic surgery was performed under general anesthesia. The tooth-like structure, protruding from the floor of the nasal cavity and extending to the maxilla, was endoscopically removed in spite of its being strongly adherent to the floor of the nasal cavity. The diagnosis was an inverted tooth caused by abnormal eruption of a supernumerary tooth into the nasal cavity. Inverted intranasal eruption of a supernumerary tooth is rare: the majority of supernumerary teeth have been reported in the maxilla and impacted. We, otorhinolaryngologists, should bear in mind the possibility of inverted intranasal eruption of a tooth when a calcified structure is noted on the floor of the nasal cavity.

DOI： 10.5631/jibirin.114.127

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Long-term outcomes of children with and without cleft palate receiving early treatment for otitis media with effusion (OME) are unclear. OBJECTIVES: To compare long-term otological and audiological outcomes between children with and without cleft palate treated with tympanostomy for OME before the age of 2 years. MATERIAL AND METHODS: Ninety-five children (180 ears) with cleft palate (study group) and 97 children (185 ears) without (control group) were followed-up to a maximum age of 7 years. We retrospectively analyzed the audiological outcomes at the age of 7 years, and the otological outcomes at the last examination. RESULTS: The percentages of children with OME resolution before the age of 7 years were 47.4% and 60% in the study and control groups, respectively, and those of ears with healed tympanic membrane were 71.7% and 79.5% in the corresponding groups. Significantly more ears were subjected to retympanostomy in the study (31.1%) than in the control group (21.6%). Mean pure-tone average (0.5‒4 kHz) was 15.6 dB HL and 14.3 dB HL for the corresponding groups. CONCLUSIONS/SIGNIFICANCE: Otological and audiological outcomes in both groups were similar. The audiological prognosis was favorable regardless of the cleft palate condition.

DOI： 10.1080/00016489.2020.1802508

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab's efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.

DOI： 10.1038/s41598-020-73965-6

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: To evaluate the long-term treatment outcome of type 1 thyroplasty with novel rearrangeable titanium medialization laryngoplasty implant (TMLI) combined with arytenoid adduction (AA) for unilateral vocal cord paralysis (UVFP) in the authors' institution. Methods: A total of 16 Japanese patients with UVFP who received type 1 thyroplasty using TMLI with arytenoid adduction was enrolled in this single-arm, non-randomized interventional study. The results of the auditory perceptual assessment, aerodynamic examination, acoustic measurement, and patient-based survey on these patients were evaluated preoperatively and at 3, 6, and 12 months postoperatively. Results: Type 1 thyroplasty using TMLI with arytenoid adduction for our patient series presented significant improvements in maximum phonation time, mean flow rates, GRBAS scale, the Voice Handicap Index and the Voice-Related Quality of Life score over the 12-month postoperative period. Conclusion: Type 1 thyroplasty using TMLI with arytenoid adduction was quite effective for obtaining satisfactory postoperative voice improvement without any surgical complication over the long-term period.

DOI： 10.1002/lio2.462

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

DOI： 10.1002/cncr.33062

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To present the clinical findings of 10 cases of bilateral vocal fold immobility (adducted type) and suggest potential treatment options. METHODS: This retrospective study included 10 patients who underwent tracheostomy for restricted airway due to bilateral vocal fold immobility of the adducted type during the period from 2007 to 2017. All 10 patients underwent unilateral laterofixation surgery with or without additional arytenoidectomy using a CO2 laser. The effect of laterofixation surgery for decannulation was evaluated. Statistical analysis was performed to assess the effects of laterofixation based on the results of preoperative and intraoperative examinations including endoscopic examinations, electromyography, and the intraoperative traction-mobility test. RESULTS: Initial laterofixation surgery for decannulation was effective in 6 cases. In the 4 cases that exhibited laterofixation failure, additional endoscopic subtotal arytenoidectomy was performed. Statistical analysis of the effects of laterofixation revealed that, in cases with bilateral preserved muscle tone, unilateral simple laterofixation surgery was unable to achieve a significantly effective glottal airway. Additional subtotal arytenoidectomy was also ineffective in a case with bilateral ankylosis. CONCLUSION: Based on the clinical findings in these 10 cases of bilateral vocal fold immobility of the adducted type, treatment options are suggested and a severity classification system of bilateral vocal fold immobility is proposed that focuses mainly on electromyography results for assessment of dynamic restenosis and traction-mobility test results for assessment of static restenosis. Validation of the classification system is needed in a larger cohort of cases of bilateral vocal fold immobility.

DOI： 10.1016/j.anl.2020.02.005

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: In this study, we examine the relationship between developmental insufficiency of mastoid air cells and abnormal morphology of the paranasal sinuses in patients with chronic otitis media (COM) and acquired middle ear cholesteatoma (AMEC) using precise image assessment, in order to evaluate whether the anatomical features of paranasal sinuses has any impact on the pathogenesis in COM and AMEC. METHODS: A total of 127 patients, including 45 COM patients and 82 AMEC patients, were enrolled for this study. The existence of nasal septal deviation, the existence of paranasal sinus opacification, the modified Lund-Mackay score, the diameters of the paranasal sinuses, the Vidic classification, mastoid development, and cranial size were assessed by CT examination. A further 76 adult patients who underwent high-resolution CT imaging of their skull bone for other diseases were enrolled as the control. RESULTS: The AMEC group showed a significantly shorter sphenoid length (P < 0.01) and lower Vidic classification score (P < 0.01) compared to the control group in this study. In addition, we observed that patients with AMEC had less pneumatization of the mastoid air cells compared to the control individuals, and that the sphenoid length of the poor MC score group was significantly shorter than that of the good MC score group. CONCLUSION: Our results suggested that the developmental deficiency in sphenoid length caused by long-standing pediatric rhinosinusitis might indicate the potential of chronic middle ear inflammation in childhood and impact the pneumatization of mastoid air cells. Therefore, chronic rhinosinusitis during the childhood and adolescence might play a role in the pathophysiology of AMEC.

DOI： 10.1016/j.anl.2019.09.008

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

Velopharyngeal insufficiency is one of the common complications of adenoidectomy, but conservative treatments are sufficient for obtaining improvement in most cases. We encountered a patient who presented with severe hypernasality developing after adenoidectomy and required surgical treatment for improvement. A five―year―old girl with bilateral otitis media with effusion and adenoid vegetation underwent adenoidectomy. After the surgery, she developed hypernasality with decreased speech clarity. Speech training was started 4 months after the operation and applied for 10 months, but the symptoms showed no improvement. Radiologic investigations revealed a very deep nasopharynx. Congenital velopharyngeal incompetence was considered as the cause of the velopharyngeal insufficiency, which had been asymptomatic prior to the adenoidectomy, probably as a result of the valve effect of the adenoids. The patient underwent surgery wherein the costal cartilage was transplanted into the posterior pharyngeal wall, which led to resolution of the hypernasality. Here, we discuss the possibility of preoperative detection and treatment methods for velopharyngeal insufficiency after adenoidectomy.

DOI： 10.3950/jibiinkoka.123.371

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP, that is, open partial horizontal laryngectomies OPHL Type IIa) has been described using a flexible next generation robotic surgical platform for manipulation. We sought to evaluate the feasibility of performing this procedure using endoscopic transoral (EndoT) surgical techniques without robotics. METHODS: Preclinical cadaveric study using two human cadavers. Hybrid SCPL-CHEP was performed with a flexible endoscope for visualization and hand-held instruments for manipulation (SILS Hook monopolar and Dissect, HAVAS LaryngoFIT malleable straight jaw instruments, and Stratafix 4-0 spiral knotless barbed suture). RESULTS: EndoT hybrid SCPL-CHEP was successfully performed. The hand-manipulated rigid instruments allowed for transoral incisions and mucosal suturing. We provide the procedural steps of EndoT hybrid techniques. CONCLUSIONS: EndoT hybrid SCPL-CHEP was technically feasible in the preclinical cadaveric laboratory setting and appeared comparable to the hybrid SCPL-CHEP via transoral robotic surgery (TORS). Selected handheld instruments and flexible endoscopy appear to facilitate minimally invasive surgery of the larynx. This novel procedure and technique warrant further clinical study for consideration of feasibility, applicability, and patient benefit.

DOI： 10.1177/0003489419885139

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

FLCN is a tumor suppressor gene which controls energy homeostasis through regulation of a variety of metabolic pathways including mitochondrial oxidative metabolism and autophagy. Birt-Hogg-Dubé (BHD) syndrome which is driven by germline alteration of the FLCN gene, predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas, pulmonary cysts and less frequently, salivary gland tumors. Here, we report metabolic roles for FLCN in the salivary gland as well as their clinical relevance. Screening of salivary glands of BHD patients using ultrasonography demonstrated increased cyst formation in the salivary gland. Salivary gland tumors that developed in BHD patients exhibited an upregulated mTOR-S6R pathway as well as increased GPNMB expression, which are characteristics of FLCN-deficient cells. Salivary gland-targeted Flcn knockout mice developed cytoplasmic clear cell formation in ductal cells with increased mitochondrial biogenesis, upregulated mTOR-S6K pathway, upregulated TFE3-GPNMB axis and upregulated lipid metabolism. Proteomic and metabolite analysis using LC/MS and GC/MS revealed that Flcn inactivation in salivary gland triggers metabolic reprogramming towards the pentose phosphate pathway which consequently upregulates nucleotide synthesis and redox regulation, further supporting that Flcn controls metabolic homeostasis in salivary gland. These data uncover important roles for FLCN in salivary gland; metabolic reprogramming under FLCN deficiency might increase nucleotide production which may feed FLCN-deficient salivary gland cells to trigger tumor initiation and progression, providing mechanistic insight into salivary gland tumorigenesis as well as a foundation for development of novel therapeutics for salivary gland tumors.

DOI： 10.1016/j.bbrc.2019.11.184

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study evaluated the combination of tumor budding and depth (BD model) and worst pattern of invasion (WPOI) as histopathological prognostic factors in clinical N0 early oral tongue carcinoma. METHODS: Data from 62 patients were retrospectively analyzed. Associations between histopathological factors (differentiation, stage, lymphatic invasion, blood vessel invasion, WPOI, and BD model) and regional control (RC) or disease-free survival (DFS) were evaluated. RESULTS: The five-year RC and DFS rates were 74% and 65%, respectively. Univariate analysis identified blood vessel invasion, lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, and BD model, as predictive factors for RC. Univariate analysis identified lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, as predictive factors for DFS. CONCLUSION: The pathological invasion patterns should be considered when determining the follow-up plan for patients with clinical N0 early oral tongue carcinoma.

DOI： 10.1002/hed.25994

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Intraductal carcinomas are rare, malignant tumors that arise from the salivary glands. They commonly grow from the parotid gland and no cases growing from the parapharyngeal space have been reported to date. We report a 76-year-old man who was inadvertently found to have a parapharyngeal lesion by CT scans and MR imaging. The tumor was resected through an upper neck approach and diagnosed histopathologically as intraductal carcinoma. As far as we are aware, this is the first case of intraductal carcinoma arising from the parapharyngeal space. Here, we describe the management of this disease together with a review of the relevant literature.

DOI： 10.1159/000511677

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

We report the case of a 59-year-old male patient who developed a deep neck abscess. Ten days after he sustained blunt trauma to his anterior chest and left shoulder, he developed redness and pain in his anterior neck and chest. Seventeen days after the injury, he was referred to our hospital and diagnosed as having a left deep neck abscess. The patient was initiated on antibiotic therapy with cefazolin and vancomycin, however, as his symptoms did not improve, incision and drainage was performed. This procedure was followed by improvement in both the signs and symptoms. A deep neck abscess often results from tonsillar or periodontal infection. It has been reported that the initial infection site remains unknown in about 3% of cases of deep neck abscess. Blunt trauma is known as the cause in some of the cases. Abscess formation after blunt trauma is caused by infection of the hematoma through blood-borne organisms and requires about 10 to 14 days to form. The presence of hematoidin crystals in the abscess supports the diagnosis. An injury should be considered as a cause of deep neck abscess when there is no evidence of a primary infection site.

DOI： 10.5631/jibirin.113.265

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. RESULTS: Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. CONCLUSION: The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.

DOI： 10.21873/anticanres.13898

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Transoral surgery (TOS) has been widely applied for early T-stage head and neck cancer (HNC). The resection is performed with a minimum safety margin for function preservation under a limited surgical field; therefore, it is difficult to have a strong conviction about the complete resection. This study aims to evaluate the completeness of the initial TOS procedure; possibility of primary control by TOS alone; and predictive factors in patients with early T-stage laryngeal, oropharyngeal, and hypopharyngeal cancer. METHODS: Patients were treated by TOS at the primary site with or without neck dissection. The patients were divided into two groups based on the pathological evaluation of their surgical specimens: the control (observation) group, in that the resection was considered complete and the intervention (second-look procedure) group, in that incomplete tumor resection was suspected. The predictive factors for the possibility and/or limitations of complete resection by TOS were then analyzed. RESULTS: The study enrolled 26 and 25 patients in the control and intervention group, respectively. The success rate for single resection was 66% and the predictive factor was tumor depth obtained by enhanced computed tomography (CT) examination (odds ratio, 7.870, P = .0243). The success rate for definitive therapy by TOS alone was 83% and the predictive factor was poor differentiation observed on pathological examination (odds ratio, 6.800, P = .0248). CONCLUSIONS: TOS has the potential for both definitive resection and function preservation with minimal invasiveness. Identification of the risk factors for TOS is advantageous for accurate treatment selection in patients with early T-stage HNC.

DOI： 10.1002/cam4.2588

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan. MATERIALS AND METHODS: This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared. RESULTS: Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013). CONCLUSIONS: The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study.

DOI： 10.1016/j.oraloncology.2019.104454

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掲載種別：研究論文（学術雑誌）  

Background: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response. Methods: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031. Findings: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45–0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64–0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71–1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63–0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45–0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53–0·80], p<0·0001) at final analysis. Neither pembrolizumab alone nor pembrolizumab with chemotherapy improved progression-free survival at the second interim analysis. At final analysis, grade 3 or worse all-cause adverse events occurred in 164 (55%) of 300 treated participants in the pembrolizumab alone group, 235 (85%) of 276 in the pembrolizumab with chemotherapy group, and 239 (83%) of 287 in the cetuximab with chemotherapy group. Adverse events led to death in 25 (8%) participants in the pembrolizumab alone group, 32 (12%) in the pembrolizumab with chemotherapy group, and 28 (10%) in the cetuximab with chemotherapy group. Interpretation: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC. Funding: Merck Sharp & Dohme.

DOI： 10.1016/S0140-6736(19)32591-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.anl.2019.05.004

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

人工内耳の術側を決定する際、判断に迷う症例を多々経験する。本研究では、非良聴耳への人工内耳の選択の是非を判断するために非良聴耳へ人工内耳を施行した症例の術後聴取成績について比較検討した。2008年10月より2017年12月までの間に当科で手術を行った人工内耳初回患者例の内、言語習得後失聴成人患者で一側人工内耳手術施行症例を対象とした。良聴耳の定義として、片側のみの補聴器装用であれば装用側を良聴耳とし、両側補聴器装用もしくは両側非装用の場合は平均聴力閾値で群分けした。症例数は、良聴耳群13例、非良聴耳群11例、同等耳群11例計35例となった。各群間で病因、性別、難聴期間、術前平均聴力、使用人工内耳、メーカーで有意差を認めなかった。非良聴耳群の人口内耳の術後成績は、人工内耳装用下音場語音明瞭度(70.0%)、CI-2004単語検査(80%)、CI-2004日常会話文検査(74%)3項目すべてにおいて、良聴耳群・同等耳群と比較し統計学的有意差のない成績であった。本報告は症例数も限られるが、術後成績に影響する他の因子(年齢・病因・良聴耳の純音聴力・人工内耳メーカー・遺伝学的背景)をよく考慮し、患者と相談の上、非良聴耳への人工内耳は術側として選択しうるオプションであると考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan, Inc.  

DOI： 10.3950/jibiinkoka.123.251

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ANNONC/MDZ428

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21037/TCR.2019.04.02

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

The glomus tympanicum tumor is a vascular-rich tumor arising from the paraganglion. We report herein on the case of a 70-year-old female case of with a glomus tympanicum tumor. A red pulsating mass in the tympanic cavity was observed on otoscopic examination. CT findings showed an 8 mm tumor in the meso-tympanic area. Without preoperative embolization, the tumor was completely resected. The blood loss was minor. No recurrence was seen during a 3-year postoperative follow-up. Based on our experience, preoperative embolization may not be necessary for Glasscock type I tumors.

DOI： 10.5631/jibirin.112.425

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ANNONC/MDZ252.028

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society for Head and Neck Cancer  

Preclinical animal xenograft tumor models are widely used for modeling the growth and spread of disease in translational cancer research. In particular, orthotopic xenograft models of head and neck cancer, by implanting head and neck cancer cell lines into the tongue of the mouse, have advantages for their ability to mimic local tumor growth and recapitulate the pathways of cervical lymph node metastasis seen in human head and neck cancers. However, these animal models have limitations due to the issues related with using established cell lines, suggesting that it is difficult for these animal models to recapitulate tumor heterogeneity and microenvironment. This review summarizes the advantages and limitations of animal models for head and neck cancers and discusses the future directions of the role of animal models in translational cancer research.

DOI： 10.5981/jjhnc.45.366

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

Because muscular dystrophy progressively causes respiratory failure, tracheotomy is necessary in most cases. Scoliosis and chest deformity are associated with deformation of the trachea resulting in complications occurring during tracheal cannulation. Herein, we present a case of Duchenne-type muscular dystrophy who developed an enlarged tra-cheostoma and deformation of the vertebrae during long-term ventilatory management. Careful supervision of tracheal cannulation, such as fixation per se of the tracheal cannula, selection of the proper tracheal cannula and dispersion of the cuff pressure was required for his care at home.

DOI： 10..3950/jibiinkoka.122.1229

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

The aim of this study was to identify prognostic factors for the hearing outcome in patients with profound ISSHL （pure tone average: PTA !90dB）receiving triple combined therapy, namely, intravenous steroid（IVS）, hyperbaric oxygen（HBO）, and intratympanic steroid（ITS）. Between August―, 2010 and September―, 2017, 136 patients（72 men and 64 women）with profound ISSHL were started on the triple combined therapy within 30 days from the onset. The hearing outcome was assessed based on the Ministry of Health, Labour and Welfare of Japan Study. The prognostic factors for the hearing outcome were retrospectively examined by multivariate analyses. Complete recovery, significant recovery, slight recovery, and no change were observed in 21 patients（15.4%）, 71 patients（52.2%）, 31 patients（22.8%）, and 13 patients（9.6%）, respectively. Hearing recovery from ISSNHL was significantly associated with the initial pure tone threshold（p＜0.05）, but not with the age（p＞0.05）or interval to the start of treatment（p＞0.05）. Receiver operating characteristic（ROC）curve analysis revealed a cut―off level of the initial pure tone threshold of 104dB. Better overall hearing improvement was observed in the group with an initial pure tone threshold of under 104dB as compared to the group with a threshold of over 105dB（p＜0.05）. Furthermore, hearing improvement in all the frequencies examined was significantly better in the group with an initial threshold of under 104dB（p＜0.05）.

DOI： 10.3950/JIBIINKOKA.122.757

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

Syphilis is a systemic infectious disease caused by Treponema pallidum, resulting in specific symptoms. We experienced a case of syphilis in a 57-year-old woman whose complaint was cervical lymphadenopathy. Both the syphilis qualitative blood tests (TPLA and RPR) were positive and the serum soluble IL-2R level was 1,300 U/L. A cervical lymph node biopsy was performed, the results of which demonstrated a granulomatous lesion consistent with syphilis lymphadenitis. The number of syphilis patients in Japan has been rapidly increasing since 2010, mainly in the metropolitan area and a warning announcement was issued from the Japanese Society for Sexually Transmitted Infections in 2016. Both mucosal plaque and angular cheilitis are typical, but not specific findings. In any case, with lymphadenopathy as the sole symptom, detailed medical history inquiry sometimes leads to the diagnosis.

DOI： 10.5631/jibirin.112.833

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

The aim of this retrospective study was to assess whether the possibility of oral intake could be estimated with an endoscopic swallowing examination(VE)in patients with dysphagia after surgery for digestive diseases. The study subjects were 28 patients who had dysphagia after surgery for digestive diseases in Yokohama City University Hospital between January, 2013 and September, 2017. Oral intake status(possibility of oral intake and dependence on alternative nutrition)was evaluated up to 80 days after the first VE. The relationship between oral intake status and patient characteristics (age, sex, history of aspiration pneumonia, presence of tracheostomy, presence of vocal cord paralysis, American Society of Anesthesiologists physical status, operative time), the Hyodo score and the presence of aspiration during VE were examined. The time course for oral intake status(the start of oral intake and the transition from alternative nutrition) was also evaluated by the Kaplan-Meier method according to the Hyodo score(with a cut-off value of 6)and aspiration during VE. In the followup period for up to 80 days after the first VE, 26 patients started oral intake and the remaining 2 did not. Nine patients were dependent on alternative nutrition and 19 were not. There were no statistical differences on the final oral intake status according to the patient characteristics. At the first VE, 19 and 9 patients had a Hyodo score of≤6 and &gt
6, respectively. The numbers of patients with and without aspiration were 10 and 18, respectively. There were no statistical differences on the final oral intake status according to the indexes at the first VE. The Kaplan-Meier estimation revealed that patients with a Hyodo score &gt
6 experienced a later start of oral intake and a slower transition from alternative nutrition than patients with a Hyodo score ≤6. Patients with aspiration at the first VE had a longer dependence on alternative nutrition than those without. Although the first VE after the surgery for digestive diseases was not a definitive predictor of the final oral intake status, it could predict the time course for the transition from alternative nutrition as well as the start of oral intake.

DOI： 10.3950/jibiinkoka.122.1304

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The Hyodo scoring system during the endoscopic procedure has been proposed as a new tool for evaluating oral intake feasibility. However, the effectiveness of the information obtained from this procedure in predicting aspiration is not fully elucidated. The aim of this study was to assess the significance of clinical factors, including Hyodo scores, for predicting the risk of aspiration. METHODS: Five hundred and twenty-eight endoscopic swallowing examinations were performed. Clinical factors, including age, sex, disease type, history of aspiration pneumonia, cognitive function, presence of tracheostomy, presence of vocal cord paralysis, consciousness level on the Japan Coma Scale, ECOG Performance Status, serum albumin level and Hyodo score, were obtained for each examination. The relationship between each of these factors and the presence of aspiration during endoscopic procedure was evaluated. RESULTS: Three hundred and thirty-two patients (62.9%) were scored less than 5, 153 (29.0%) were scored between 5 and 8, and 43 (8.1%) were scored above 8. The number of patients with aspiration was 133 (25.2%). ROC analysis revealed that a cut-off point of 6 for Hyodo score was effective for predicting aspiration, with a sensitivity of 0.65 and a specificity of 0.86. History of aspiration pneumonia (OR 1.87, P<0.001), vocal cord paralysis (OR 2.23, P<0.001), PS≥3 (OR 2.47, P<0.001) and Hyodo score>6 (OR 9.08, P<0.001) were found to be independent predictive factors for aspiration. CONCLUSION: The Hyodo scoring method was easy for otolaryngologists to perform and the scores were useful for predicting aspiration with moderate sensitivity and high specificity. Hyodo score>6, history of aspiration pneumonia, vocal cord paralysis, and PS≥3 were independent predictive factors for aspiration and that a Hyodo score above 6 was the statistically strongest predictor for aspiration.

DOI： 10.1016/j.anl.2018.03.005

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掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The purpose of this study is to investigate the prognostic significance of the pretreatment F-NLR score, which is based on fibrinogen (F) and neutrophil-to-lymphocyte ratio (NLR) in patients with advanced hypopharyngeal carcinoma (HPC). MATERIALS AND METHODS: A total of 111 advanced HPC patients treated with radiotherapy, chemoradiotherapy, or bioradiotherapy were classified into three groups: F-NLR score of 2 (fibrinogen ≥341 mg/dl and NLR≥3.59), score of 1 (fibrinogen ≥341 mg/dl or NLR≥3.59), and score of 0 (fibrinogen <341 mg/dl and NLR<3.59). RESULTS: F-NLR score of 2 was an independent prognostic factor for overall (OS) and progression-free survival (PFS) in patients with advanced HPC in the multivariate analysis. Both OS and PFS were significantly lower in patients with an F-NLR score of 2 than in those with an F-NLR score of 0. CONCLUSION: F-NLR score was useful to stratify patients to extract poor prognostic characteristics in patients with advanced HPC.

DOI： 10.21873/anticanres.12859

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We confirmed the safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel in a small number of patients with cis-platinum-intolerant core high-risk head and neck cancer. OBJECTIVE: To assess treatment efficacy, we planned a phase 2 study of postoperative bio-chemoradiotherapy for patients with cis-platinum-intolerant core high-risk head and neck cancer and will compare the results to those of previously collected radiotherapy data. METHODS: Patients who underwent definitive surgery for oral cavity, laryngeal, oropharyngeal, or hypopharyngeal advanced cancer, whose postoperative pathological results indicated core high risk for recurrence (eg, positive margin in the primary site or extranodal extension) and who were cis-platinum-intolerant, will undergo postoperative bio-chemoradiotherapy. The primary end point is 2-year disease-free survival. RESULTS: The expected 2-year disease-free survival is set at 55%, and the calculated sample size is 35 patients, according to a statistical analysis based on previous reports. CONCLUSIONS: This treatment method is expected to improve the survival rate of patients with severe head and neck cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000031835; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000036355 (Archived by WebCite at http://www.webcitation.org/71fejVjMr).

DOI： 10.2196/11003

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掲載種別：研究論文（学術雑誌）  

Background: The purpose of this study was to elucidate the efficacy of concurrent chemotherapy and analyze prognostic factors in the radiation-based therapy for early stage laryngeal squamous cell carcinoma (ELSCC). Methods: The records of 97 patients with ELSCC treated by radiation-based therapy from 2004 to 2016 were retrospectively reviewed. Eighty-one patients were treated with the combined-agent regimens during the treatment. Of the 81 patients, 58 were treated with S-1 regimen and 23 with other regimens. Clinical factors, such as concurrent chemotherapy, non-glottic subsite and the incidence of second primary cancer (SPC) were analyzed for their association with survival. Results: From the analysis of all patients, the 5-year overall survival (OS) rates were found to be significantly poorer for patients with non-glottic cancer compared to those with glottic cancer (P < 0.001), and non-glottic subsite was shown to be the only poor prognostic factor for OS by the multivariate analysis (P=0.006). SPC was responsible for two-thirds of all deaths. In the analysis of patients with stage II ELSCC, the 5-year disease-free survival (DFS) rates were significantly better for patients treated by concurrent chemoradiotherapy (CCRT) with S-1 compared to those treated by the other treatment methods, and a combination with the S-1 regimen was shown to be the only good prognostic factor for DFS by the multivariate analysis (P=0.015). Conclusions: Non-glottic subsite and SPC were associated with worsened survival. CCRT with S-1 can be a useful treatment option for stage II ELSCC.

DOI： 10.21037/tcr.2018.06.15

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The purpose of this study is to validate the concept of lymph node ratio (LNR) in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 63 patients with HNSCC who underwent resection of the primary tumor combined with neck dissection in our institution were analyzed in this study. LNR was defined as the number of positive lymph nodes divided by the total number of lymph nodes excised. LNR was categorized into two groups (<0.068 and ≥0.068) according to the results of receiver-operating characteristic plots for determination of the cut-off value. RESULTS: LNR≥0.068 was associated with poor overall survival (OS), progression-free survival (PFS) and locoregional recurrence-free survival (LRFS) after resection of the primary tumor combined with neck dissection in patients with HNSCC. Univariate and multivariate data analysis showed that LNR≥0.068 was an independent prognostic factor for OS, PFS and LRFS. Both pathological T stage status (pT3 or 4) and ≥3 positive LNs were also an independent prognostic factors for PFS in patients with HNSCC in our univariate and multivariate analysis. CONCLUSION: These results suggested that LNR could be useful tools in identifying HNSCC patients with poor outcomes.

DOI： 10.1016/j.anl.2017.11.015

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掲載種別：研究論文（学術雑誌）  

DOI： 10.18869/ACADPUB.IJRR.16.2.257

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The purpose of this study is to validate the applicability of new TNM classification for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) in the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system in Japan. METHODS: A total of 91 OPC patients treated with radiation-based therapy between November 2001 and July 2015 were analyzed retrospectively in this study. HPV infection status was evaluated using tumor p16 expression. RESULTS: 40 OPC patients (44.0%) had HPV-positive disease in this study. The distribution of disease stage of HPV-positive OPC patients dramatically changed from the 7th edition to the 8th edition of AJCC/UICC TNM classification. However, neither the 8th edition nor the 7th edition of the AJCC/UICC TNM staging system could adequately predict outcomes of HPV-positive OPC patients in our patient series. On the other hand, our multivariate analysis indicated that matted nodes and age ≥63 were independent prognostic factors for progression-free survival. In addition, HPV-positive OPC patients with stage I without matted nodes showed significantly better overall and progression-free survival compared with those with stage I with matted nodes and stages II and III in the 8th edition of the AJCC/UICC TNM staging system (P=0.008, and P=0.043, respectively). CONCLUSION: Our results suggested that matted nodes of HPV-positive OPC patients might be additionally examined to apply the 8th edition of AJCC/UICC TNM classification for more adequate predicting outcomes of HPV-positive OPC patients.

DOI： 10.1016/j.anl.2017.07.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AME Publishing Company  

Background: Although dihydropyrimidine dehydrogenase (DPD) expression has been reported to correlate with 5-fluorouracil (5-FU) resistance in several cancers, the relationship between DPD expression and chemotherapeutic resistance to 5-FU remains unclear in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine the impact of DPD expression on 5-FU sensitivity and survival in HNSCC patients receiving 5-FU-based treatment. Methods: To study the correlation between DPD expression and clinical outcome of HNSCC patients who had undergone concurrent chemoradiotherapy with 5-FU-based regimens, we first examined DPD mRNA expression of these patient samples. We next developed a 5-FU-resistant HNSCC cell line (HSC-3R) to clarify the association between DPD expression and 5-FU resistance. Clonogenic survival assay was performed to determine the sensitivity of HSC-3 cells and HSC-3R cells to 5-FU. DPD expression levels in parental HSC-3 and HSC-3R cell lines were then examined by Western blotting and real-time quantitative polymerase chain reaction analysis. Lastly, we performed WST-8 assay to examine the effects of 5-Chloro-2,4-dihydroxypyridine (CDHP), a 5-FU modulator to competitively inhibit DPD, on 5-FU cytotoxicity in the HSC-3 and HSC-3R cells, to evaluate if inhibition of DPD can restore the sensitivity of HNSCC cells to 5-FU. Results: Nineteen HNSCC patients who had undergone concurrent chemoradiotherapy with 5-FU-based regimens were enrolled in this study. The cut-off value for DPD mRNA expression calculated from the ROC curve was 8.53 against cancer-specific survival of these patients. The high-level DPD expression group showed significantly shorter overall and cancer-specific survival compared to the low-level DPD expression group (P=0.0018 and 0.0004, respectively). Both of protein and mRNA expression levels were greater in the HSC-3R cells than that in the HSC-3 cells. While HSC-3R cells showed 12.64-fold greater resistance to 5-FU compared with HSC-3 cells, the combination of 5-FU with CDHP had a significant inhibitory effect on 5-FU cytotoxicity in HSC-3R cells in CDHP exposure. Conclusions: In this study, we clarified that the high-level DPD expression group of HNSCC patients undergoing concurrent chemoradiotherapy with 5-FU-based regimens showed significantly shorter overall survival. The 5-FU-resistant cells established from HNSCC cells showed increased DPD expression and attenuated 5-FU resistance induced by CDHP. Our results suggested that a high level of DPD expression was correlated with 5-FU resistance and that DPD expression level might be a predictive biomarker in 5-FU-based chemoradiotherapy for HNSCC patients.

DOI： 10.21037/tcr.2018.03.38

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The preservation of residual hearing after conventional cochlear implantation (CI) is frequently observed when atraumatic soft surgery is adopted. The purpose of this study was to elucidate the predictive factors for residual hearing preservation after atraumatic CI. PATIENTS: This study included 46 patients who underwent CI based on an atraumatic technique using a standard-length flexible electrode implant through a round window approach. MAIN OUTCOME MEASURE: Cochlear volume was measured using magnetic resonance imaging (MRI). Cochlear duct length (CDL) was taken as the length of the scala media measured using computed tomography (CT). The association between residual hearing preservation and cochlear volume/CDL was then examined. RESULT: Cochlear volume and CDL were significantly larger in patients with complete hearing preservation than in those with hearing loss. Multivariate logistic regression analysis revealed that cochlear volume was a significant predictive factor for residual hearing preservation. CONCLUSION: Residual hearing preservation after conventional CI was observed in patients with a larger cochlear volume and longer CDL. Cochlear volume could be a predictive factor for residual hearing preservation after conventional CI.

DOI： 10.1080/00016489.2017.1393840

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科頭頸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

Purpose: To identify the risk factors for the development of tracheo-innominate artery fistula, which is a serious postoperative complication after laryngotracheal separation and laryngectomy. Methods: The subjects were 21 patients with severe motor and intellectual disabilities who had undergone laryngotracheal separation or laryngectomy at Yokohama City University Medical Center. We classified the patients into three groups, as follows: group A?n?2?, consisting of patients who needed tracheal cannulation after surgery and had postoperative tracheal hemorrhage
group B?n?6?, consisting of patients who needed tracheal cannulation after surgery and did not have postoperative tracheal hemorrhage
group C?n?13?, consisting of patients who neither needed tracheal cannulation nor developed postoperative tracheal hemorrhage. We conducted a retrospective review of the preoperatively obtained images and measured the anteroposterior diameters of the trachea and thorax and the Cobb angle. Results: The anteroposterior diameter of the trachea in groups A, B and C was 6.6 mm, 14 mm and 13 mm, respectively, with no significant differences among the groups. The anteroposterior diameter of the thorax in groups A, B and C was 21 mm, 35 mm and 40 mm, respectively, with a significant difference between groups A and C?p?0.03?. The Cobb angle in groups A, B and C was 81, 24 and 29 degrees, respectively, with significant differences between groups A and B?p?0.04?and groups A and C?p?0.05?. Group A patients had shorter anteroposterior diameters of the trachea and thorax, and a larger Cobb angle than group B and C patients. Conclusions: The present study showed that preoperative imaging is useful to estimate the risk of tracheo-innomi-nate artery fistula in patients undergoing laryngotracheal separation or laryngectomy. Patients with an anteroposterior diameter of the thorax of less than 20 mm or a Cobb angle of greater than 80-90 degrees appear to be at a higher risk for developing this serious postoperative complication.

DOI： 10.3950/jibiinkoka.121.215

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

We report a case of posterior glottic adhesion developing after tracheal intubation. A 75-year-old male patient presented with dyspnea 1 month after extubation, and tracheostomy was performed 2 months later because of fixation of the left vocal cord and limited abduction of the right vocal cord. Endoscopy performed via the tracheostoma revealed the presence of posterior glottic adhesion. Mobility of the right arytenoid was obtained by dissecting the adhesion under transoral CO2 laser microsurgery (TLM), and the tracheostoma was closed 3 months after the TLM, despite sustained fixation of the left vocal cord. No re-adhesion has observed for one year after the TLM. A standard endoscopic examination of the larynx often fails to detect posterior glottic adhesion, and patients with this condition tend to be misdiagnosed as having bilateral vocal cord paralysis.

DOI： 10.3950/jibiinkoka.121.1389

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) has been widely applied for early T stage head and neck cancer. The resection is performed with a minimum safety margin for function preservation under a limited surgical field of view, making it difficult to be certain of complete resection. OBJECTIVE: Our aim is the evaluation of the completeness of resection by initial TOVS resection, and the possibility of primary control by TOVS alone, allowing for repeat procedures for function preserving treatment in early T stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients. METHODS: Patients are treated by TOVS for the primary site with or without neck dissection. Patients are divided in two groups based on the results of the pathological evaluation of the surgical specimen; the control group in which the resection is considered to be complete, and the intervention (second-look procedure) group in which incomplete tumor resection is suspected. The predictive factors for the possibility of complete resection by TOVS will then be analyzed. RESULTS: Patient enrollment started on January 1, 2014, and closed on March 31, 2016, with 54 patients. The control group consists of 27 patients, the intervention group is 21 patients, and 6 patients were excluded. There were no clinical differences between the control and intervention groups. The observation period will end on December 31, 2018. CONCLUSIONS: TOVS has potential for both definitive resection and function preservation with minimal invasiveness. Identifying the limitations of TOVS is beneficial to ensure accurate treatment selection in early T stage head and neck cancer patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000012485; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000014472 (Archived by WebCite at http://www.webcitation.org/6v1b741Iw).

DOI： 10.2196/resprot.8907

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (p < 0.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (p < 0.01). The combination of a tumor depth ≥ 3 mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.

DOI： 10.1007/s12105-017-0814-1

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/23772484.2017.1376587

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記述言語：日本語   出版者・発行元：耳鼻と臨床会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC. METHOD: We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group). RESULTS: The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05). CONCLUSION: The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer.

DOI： 10.1016/j.oraloncology.2017.05.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To confirm the efficacy and safety of cetuximab and docetaxel in postoperative radiotherapy for high-risk head and neck cancer patients who cannot to be administered high-dose cisplatin. PATIENTS AND METHODS: The eligibility criteria required stage III-IVB head and neck cancer patients who had undergone total resection, and for whom pathological evaluation revealed positive or close margins in the primary site and/or extracapsular nodal extension and/or two or more nodal metastases. In each case, the patients general condition prevented the use of high-dose cisplatin. Instead, they received cetuximab and docetaxel every week during a 66.6 Gy course of postoperative radiotherapy. RESULTS: Eleven patients were enrolled; the median follow-up period was 22 months, and the 1- and 2-year disease free survival rates were 91 and 55%, respectively. Grade 3 adverse events included oral mucositis, radiation dermatitis, reduced white blood cell and neutrophil counts, lung infection, aspiration, and hyponatremia; however, no grade 4 adverse events were observed. CONCLUSION: Administration of cetuximab and docetaxel during postoperative radiotherapy for high-risk poor condition head and neck cancer patients in poor general condition was both feasible and tolerable. With the safety of this treatment confirmed, we propose a phase trail to further clarify the efficacy of cetuximab and docetaxel use for high-risk cisplatin-intolerant patients.

DOI： 10.1007/s00280-017-3352-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Type II thyroplasty (TPII) is one of the surgical options offered in the management of adductor spasmodic dysphonia (AdSD); however, there have been no detailed reports of its safety and associated complications during the perioperative period. Our aim was to assess the complications and safety of TPII. TPII was performed for consecutive 15 patients with AdSD from April 2012 through May 2014. We examined retrospectively the perioperative complications, the degree of surgical invasion, and recovery process from surgery. All patients underwent successful surgery under only local anesthesia. Vocal fold erythema was observed in 14 patients and vocal fold edema in 10 patients; however, all of them showed complete resolution within 1 month. No patient experienced severe complications such as acute airway distress or hemorrhage. Fourteen patients were able to have oral from the 1st postoperative morning, with the remaining patient able to have oral intake from the 2nd postoperative day. In addition, no patient experienced aspiration postoperatively. In conclusion, only minor complications were observed in association with TPII in this study. No dysphagia was observed postoperatively, which is an advantage over other treatments. The results of our study suggest that TPII is a safe surgical treatment for AdSD.

DOI： 10.1007/s00405-017-4463-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies showed that human papillomavirus (HPV) integration contributes to the genomic instability seen in HPV-associated head and neck squamous cell carcinoma (HPV-HNSCC). However, the epigenetic alterations induced after HPV integration remains unclear. To identify the molecular details of HPV16 DNA integration and the ensuing patterns of methylation in HNSCC, we performed next-generation sequencing using a target-enrichment method for the effective identification of HPV16 integration breakpoints as well as the characterization of genomic sequences adjacent to HPV16 integration breakpoints with three HPV16-related HNSCC cell lines. The DNA methylation levels of the integrated HPV16 genome and that of the adjacent human genome were also analyzed by bisulfite pyrosequencing. We found various integration loci, including novel integration sites. Integration loci were located predominantly in the intergenic region, with a significant enrichment of the microhomologous sequences between the human and HPV16 genomes at the integration breakpoints. Furthermore, various levels of methylation within both the human genome and the integrated HPV genome at the integration breakpoints in each integrant were observed. Allele-specific methylation analysis suggested that the HPV16 integrants remained hypomethylated when the flanking host genome was hypomethylated. After integration into highly methylated human genome regions, however, the HPV16 DNA became methylated. In conclusion, we found novel integration sites and methylation patterns in HPV-HNSCC using our unique method. These findings may provide insights into understanding of viral integration mechanism and virus-associated carcinogenesis of HPV-HNSCC.

DOI： 10.1002/ijc.30589

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

OBJECTIVE/HYPOTHESIS: We previously reported that the metabolic tumor volume (MTV) of a primary tumor was an independent prognostic factor for survival in laryngeal carcinoma treated by radiotherapy (RT)-based protocol. The purpose of this study was to evaluate the difference in survival outcomes between surgery-based and RT-based treatment in patients with a MTV laryngeal cancer. STUDY DESIGN: An individual retrospective cohort study. METHODS: We reviewed the records of 63 patients with laryngeal cancer showing a primary tumor with a high MTV value (≥ 4.9 mL). The patients were separated into two groups by primary treatment strategy: 22 patients were included in the surgery group, and 41 patients were included in the RT group. Clinical factors and treatment modalities were analyzed for their association with survival. RESULTS: Multivariate analysis, including age, sex, subsite, T classification, nodal metastasis, and treatment modality, showed that the subsite (hazard ratio [HR] 2.55, P = 0.043) and treatment modality (HR 3.98, P = 0.019) were independent predictors for survival. The Kaplan-Meier curves for 2-year relapse-free survival rates and overall survival rates for patients in the surgery and RT groups were 74.2% versus 38.8% (P = 0.025) and 80.1% versus 66.7% (P = 0.078). CONCLUSIONS: Patients with a high metabolic volume laryngeal cancer treated by a surgery-based protocol showed better relapse-free survival and overall survival than did those undergoing RT-based treatment. Pretreatment MTV assessment could be useful in planning the treatment strategy for patients with a laryngeal cancer. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:862-867, 2017.

DOI： 10.1002/lary.26233

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

Orbital complications caused by acute sinusitis represent emergency conditions that need precise evaluation and prompt management. Herein, we report 5 surgically treated patients with orbital complications caused by acute sinusitis. Three presented with orbital subperiosteal abscess, one with incomplete cavernous sinus syndrome, and one with optic neuritis. In all cases, emergent endoscopic sinus surgery was performed for orbital decompression. After the surgery, 4 of the patients showed full recovery from the visual disturbances, while the remaining one patient, in whom the preoperative visual acuity deterioration was severe, did not. We would like to emphasize that prompt diagnosis of orbital complications and immediate surgical drainage for orbital decompression are essential to avoid severe loss of visual acuity.

DOI： 10.3950/jibiinkoka.120.1079

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The purpose of this study was to elucidate the prognostic significance of the pretreatment metabolic tumor volume (MTV) in patients with piriform sinus carcinoma treated by radiation-based therapy. METHODS: This retrospective study included 100 patients with piriform sinus carcinomas who had received treatment by radiation-based therapy. The MTV values were obtained from pretreatment positron emission tomography (PET). The association between clinical factors, including the MTV, and survival was analyzed. RESULTS: Kaplan-Meier estimates revealed the 5-year disease-free survival (DFS) rates were significantly poorer for patients with a high MTV compared to those with a low MTV. In the multivariate analysis, MTV (p < .001), nodal metastasis (p = .011), and applied chemotherapy regimen (p = .004) were found to be independent prognostic factors for DFS. CONCLUSION: The locoregional MTV is a prognostic factor for DFS in patients with piriform sinus carcinoma treated by radiation-based therapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

DOI： 10.1002/hed.24488

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

BACKGROUND: For primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival. METHODS: The records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed. RESULTS: A total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5 %, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5 %). CONCLUSIONS: Salvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

DOI： 10.1007/s10147-016-0964-2

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The masticator space is located between the masseteric fascia and the pterygoid muscle fascia.
Here we report two cases of masticator space abscesses spreading from infections of mandibular teeth.
Case 1 is an 85-year-old lady who were referred to Yokohama City University Hospital with a left-cheek swelling and trismus. An enhanced CT scan revealed an abscess extending from the left infratemporal fossa to the temporal fossa. A purulent discharge was observed from her left lower gingiva. We performed surgical drainage under general anesthesia. After infection control, the affected teeth were extracted.
Case 2 is an 82-year-old lady who was administered oral bisphosphonate for osteoporosis. She presented to another hospital with fever, trismus and swelling anterior to the right ear after right lower tooth extraction. Because MRI revealed persistent osteomyelitis of her mandible even after antibiotic treatment, she was referred to us. Enhanced CT showed an abscess in the right infratemporal fossa. After surgical drainage similar to Case 1, antibiotics were administered for approximately 4 months to control the osteomyelitis.
It is important to recognize that infections of the mandibular teeth can cause an abscess in the masticator space through the pterygomandibular and infratemporal spaces.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recently, the incidence of oropharyngeal cancer (OPC) has increased markedly in comparison to that of HNSCC, which is associated with the use of tobacco or alcohol or both. This increase has resulted mainly from the global rise in the number of human papillomavirus (HPV)-related oropharyngeal cancers (HPV-OPCs). HPV-OPC has several unique characteristics, including presentation in younger patients, better response rates to treatment, and better prognosis compared to alcohol- and smoking-related HNSCC. HPV infection status is now an independent prognostic factor for survival in patients with OPC. In general, HPV oncoproteins E6 and E7 are the primary viral factors responsible for the initiation and progression of HPV-related cancers via the inactivation of p53 and pRb. However, alterations in additional factors, including genomic instability, HPV DNA integration, and epigenetic alterations, could be equally important for neoplastic transformation and tumor progression. The impact of genomic instability and external environmental factors on the initiation of cervical cancer development through high-risk HPV infection has been well characterized, although less is known about the mechanism underlying HPV-induced carcinogenesis in HNSCC. This review provides an overview of the biology and molecular mechanisms of HPV-related cancers, including a particular focus on several recent studies on the comprehensive characterization of genomic alterations in HPV-associated HNSCC.

DOI： 10.1007/s10147-016-1005-x

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Definitive chemoradiotherapy (CRT) is used to treat lymph node metastatic head and neck cancer patients. Regional control of the neck disease is important to improve the prognosis, and the accuracy of the method used to evaluate the metastatic lymph node(s) after CRT is crucial to the decision-making process for any following salvage surgery. METHODS: Patients undergoing CRT were divided in two groups of patients of those showing complete clinical response (CR) and those showing clinical non-response (non-CR), as assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI), ultrasonography, fluorodeoxyglucose-positron emission tomography (FDG-PET), and fine needle aspiration cytology. The responses (CR vs. non-CR) were compared with the actual clinical outcomes. For the interim analysis, the study period was broken down into two periods, namely, the exploratory phase (patients treated between January 2002 and April 2012) and the validating phase (patients treated between May 2012 and January 2014). RESULTS: The sensitivity, specificity, and accuracy were as follows: CT and/or MRI, 66.7, 73.8, and 72.8 %, respectively, in the exploratory phase; ultrasonography, 91.7, 70.6, and 73.4 %, respectively, in the exploratory phase and 80.0, 82.8, and 82.4 %, respectively, in the validating phase; FDG-PET, 50.0, 97.5, and 91.3 %, respectively, in the exploratory phase and 60.0, 100, and 94.1 %, respectively, in the validating phase; cytology, 68.4, 95.9, and 90.3 %, respectively, in the exploratory phase and 66.7, 100, and 85.7 %, respectively, in the validating phase. CONCLUSIONS: Based on our results, CT and/or MRI appear to be inadequate methods for the evaluation of the response of lymph node(s) to CRT. In contrast, ultrasonography appears to be a highly sensitive and useful tool for positive screening at 6-8 weeks after CRT, and FDG-PET appears to be a highly specific and useful tool for negative screening at 8-12 weeks after CRT.

DOI： 10.1007/s10147-015-0936-y

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A certain percentage of patients with gastroesophageal reflux disease (GERD) have laryn- gopharyngeal symptoms such as hoarseness, cough, and lump sensation in the throat. An updated meta-analysis showed that proton pump inhibitors (PPIs) reduced laryngopharyngeal symptoms significantly compared with placebo in patients suspected to have these symptoms caused by gastroesophageal reflux(GER). Although PPIs are often used to confirm the diagnosis of GERD (so-called "PPI test"), it is still not clear whether the -test can be applied to patients with laryngopharyngeal symptoms. We therefore have to conclude that no solid diagnostic tool is available to determine whether GER is an actual cause of chronic pharyngitis and laryngitis.

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2016-4054

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Endoscopic transnasal approach is an excellent technique for resecting orbital tumors located inferiorly and/or medially to the optic nerve. The aim of this study was to present four cases of orbital tumor which were, at least in part, resected by an endoscopic transnasal approach and to discuss both indications and limitations of this approach through a comparison of the location and tumor status, including the pathology, of these cases. In two cases with orbital tumor located in a medial-inferior quadrant, we were able to resect it only by an endoscopic transnasal approach. Because we experienced transient diplopia and dyschromatopsia after resecting intraconal tumors, a careful choice for the best approach is suggested in view of the location, size and properties of the tumor. In the third case, with tumor located in an inferior-lateral quadrant, it was eventually resected using a frontal-zygomatic approach because the medial and inferior borders of the tumor could not be identified and the lateral border was beyond the limits of manipulation by an endoscopic transnasal approach. In the last case with possible malignant tumor adhered to the lateral vital, the tumor was resected using a transantral approach. Based on these experiences, we introduce the indications for an endoscopic transnasal resection of orbital tumors.

DOI： 10.1016/j.anl.2015.10.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Although locally advanced head and neck squamous cell carcinoma (HNSCC) can be effectively treated using chemoradiotherapy (CRT) with docetaxel (DTX), and cisplatin (CDDP) plus 5-fluorouracil (TPF-CRT), severe adverse events (especially neutropenia) can limit treatment adherence. Therefore, we evaluated the safety and efficacy of a new chemotherapy regimen that consisted of DTX and CDDP plus cetuximab (Cmab) with concurrent radiotherapy. METHODS: Bio-chemoradiotherapy (B-CRT) using DTX, CDDP, and Cmab was administrated to patients with locally advanced HNSCC, and its safety and efficacy were evaluated. RESULTS: Interim analysis of nine patients revealed severe neutropenia in five patients (56 %) and leukopenia in seven patients (78 %); hence, the study was terminated. One patient experienced disease-free survival using only B-CRT. CONCLUSIONS: Neutropenia was equally severe for B-CRT, compared to TPF-CRT. Based on the limited sample size, it is impossible to conclude that B-CRT has non-inferior efficacy, compared to TPF-CRT.

DOI： 10.1007/s00280-016-3052-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Both central giant cell granuloma (CGCG) and ossifying fibroma (OF) are relatively common diseases. The synchronous presentation of CGCG and OF is, however, an extremely rare occurrence. We present an unusual case with the synchronous presentation of these two diseases in the maxilla and introduce a surgical strategy based on a combination of the stereolithographic model and navigation system for the treatment of gigantic OF with secondary CGCG.

DOI： 10.1016/j.anl.2015.08.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Chemoradiotherapy (CRT) is used to treat cervical lymph node(s) metastatic head and neck cancer patients. Evaluation and treatment of lymph node(s) after CRT is important to improve the prognosis. METHODS: Prior to CRT, we determined the TNM stage by visual and imaging examinations. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated from the results of fluorodeoxyglucose-positron emission tomography (FDG-PET). After CRT, the patients were divided in two groups-complete response (CR) and non-CR-and their responses were compared with the clinical characteristics. RESULTS: T4, N2b, N2c and TLG2.5 ≥ 18.8 were statistically significant predictive indices before CRT. The odds ratio, 95 % confidence interval and p value were, respectively-T4: 2.73, 1.15-6.51, 0.0230; N2b: 6.96, 1.50-32.3, 0.0132; N2c: 11.80, 2.37-58.50, 0.00258; and TLG2.5 ≥ 18.8: 6.25, 2.17-18.00, 0.000672. CONCLUSIONS: TLG was found to be a good predictive factor for metastatic lymph node(s) prior to CRT treatment. After CRT treatment, FDG-PET was found to be highly specific and useful for negative screening.

DOI： 10.1007/s10147-015-0890-8

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

A retrospective study was conducted to examine the implementation status of newborn hearing screening (NHS) of 6,063 infants born in a single community hospital in Japan between 2005 and 2013. An automated auditory brainstem response device was used for NHS and an auditory brainstem response was mainly used for further diagnostic evaluation. Although the participation rate in the NHS was 88.8% in 2013, increasing year by year, it failed to reach 100% probably because NHS is a charged option under the current Japanese healthcare system. Among 40 (0.66%) infants who finally failed their NHS, 34 were referred for subsequent diagnostic evaluation and the remaining 6 were lost to follow-up. Thirty-one of these 34 were diagnosed as having hearing impairment and 3 (0.05%) were identified as having normal hearing, which is considered as a false positive. Both the final referral rate and the hearing impairment rate were significantly higher in the high-risk than in the low-risk group. Compared to the previous national report, the rate of bilateral hearing impairment (0.33%) was significantly higher in this study. Ten (38.5%) out of 26 in the high-risk group were most often diagnosed with otitis media with effusion (OME), while 4 (50%) out of 8 in the low-risk group were diagnosed as having sensorineural hearing loss. Seven (35%) out of 20 with bilateral hearing impairment attained a normal hearing level at a median age of 18 months. Although the primary aim of NHS is early detection of congenital permanent hearing loss, OME is observed commonly in NHS-failed infants. It is therefore important to examine the middle ear status carefully as part of the diagnostic evaluation. Thirty-four infants underwent further diagnostic evaluation at a median age of 46 days, and hearing aids were given in 10 of them at a median age of 5.6 months without delay. Because high-risk patients often tend to be lost to follow-up, otolaryngologists have to give a detailed explanation to caregivers and to build a solid support system for children with hearing impairment.

DOI： 10.3950/jibiinkoka.119.187

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

The diagnosis of the genetic etiology of deafness contributes to the clinical management of patients. We performed the following four genetic tests in three stages for 52 consecutive deafness subjects in one facility. We used the Invader assay for 46 mutations in 13 genes and Sanger sequencing for the GJB2 gene or SLC26A4 gene in the first-stage test, the TaqMan genotyping assay in the second-stage test and targeted exon sequencing using massively parallel DNA sequencing in the third-stage test. Overall, we identified the genetic cause in 40% (21/52) of patients. The diagnostic rates of autosomal dominant, autosomal recessive and sporadic cases were 50%, 60% and 34%, respectively. When the sporadic cases with congenital and severe hearing loss were selected, the diagnostic rate rose to 48%. The combination approach using these genetic tests appears to be useful as a diagnostic tool for deafness patients. We recommended that genetic testing for the screening of common mutations in deafness genes using the Invader assay or TaqMan genotyping assay be performed as the initial evaluation. For the remaining undiagnosed cases, targeted exon sequencing using massively parallel DNA sequencing is clinically and economically beneficial.

DOI： 10.1038/jhg.2015.143

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ Publishing Group  

Actinomycosis is a common treatable disease caused by Actinomyces, and generally has a good prognosis. However, we report a fatal case of actinomycosis of the nasal cavity. A 54-year-old man, reporting of left nasal obstruction, swelling and sharp pain around the root of the nose, was referred to our hospital. Histopathological examinations led to a definitive diagnosis of actinomycosis, and oral antibiotics were administered in an outpatient setting. However, the patient discontinued follow-up at the outpatient clinic because of the adverse effects of intravenous delivery, and poor compliance with oral antibiotic therapy led to him receiving a less than adequate dose. Thus, in the absence of sufficient antibiotic treatment, necrosis gradually progressed in the lesion, and the patient died of multiple organ failure and disseminated intravascular coagulation caused by local infection.

DOI： 10.1136/bcr-2015-213747

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: While treatment failure in cases of head and neck squamous cell carcinoma (HNSCC) frequently takes the form of locoregional recurrences and distant metastasis, our understanding of the mechanisms of metastasis in HNSCC is limited. We initially performed the upstream and key nodes analysis together with whole gene microarray analysis characterized by distant metastatic potential in vivo with HNSCC cell lines and identified JunB, a member of the activator protein-1 (AP-1) family, as a key molecule in the regulation of the pathways related to distant metastasis in HNSCC. We have therefore tested the hypothesis that JunB plays a crucial role in distant metastasis in HNSCC. METHODS: To study the role of JunB on metastatic potential of HNSCC, small interfering RNA (siRNA)-mediated knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (cas9) system (CRISPR/Cas9)-mediated knockout of JunB in HNSCC cells were established and the abilities of cell invasion and migration in vitro were examined. The efficacy of knockout of JunB was also examined using an experimental lung metastatic mouse model of HNSCC. In addition, to study if the role of JunB in HNSCC cell migration and invasiveness is related to epithelial-to-mesenchymal transition (EMT), cell morphology and expression of mesenchymal or epithelial marker on siRNA mediated JunB knockdown in HNSCC cells were examined with or without TGF-β stimulation. RESULTS: siRNA knockdown and sgRNA knockout of JunB in metastatic HNSCC cells significantly suppressed both cell invasion and migration in vitro. In addition, the knockout of JunB in metastatic HNSCC cells significantly repressed the incidence of lung metastases and prolonged the survival in vivo. However, we did not observe any change in cell morphology with the down-regulation of mesenchymal markers and up-regulation of epithelial markers in response to siRNA-mediated JunB knockdown in HNSCC cells. CONCLUSION: These results suggested that JunB could play an important role in promoting cell invasion, migration and distant metastasis in HNSCC via pathways other than EMT and that the down-regulation of JunB may become an effective strategy for patients with invasive HNSCC.

DOI： 10.1186/s13046-016-0284-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: While treatment failure in cases of head and neck squamous cell carcinoma (HNSCC) frequently takes the form of locoregional recurrences and distant metastasis, our understanding of the mechanisms of metastasis in HNSCC is limited. We initially performed the upstream and key nodes analysis together with whole gene microarray analysis characterized by distant metastatic potential in vivo with HNSCC cell lines and identified JunB, a member of the activator protein-1 (AP-1) family, as a key molecule in the regulation of the pathways related to distant metastasis in HNSCC. We have therefore tested the hypothesis that JunB plays a crucial role in distant metastasis in HNSCC.
Methods: To study the role of JunB on metastatic potential of HNSCC, small interfering RNA (siRNA)-mediated knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (cas9) system (CRISPR/Cas9)-mediated knockout of JunB in HNSCC cells were established and the abilities of cell invasion and migration in vitro were examined. The efficacy of knockout of JunB was also examined using an experimental lung metastatic mouse model of HNSCC. In addition, to study if the role of JunB in HNSCC cell migration and invasiveness is related to epithelial-to-mesenchymal transition (EMT), cell morphology and expression of mesenchymal or epithelial marker on siRNA mediated JunB knockdown in HNSCC cells were examined with or without TGF-beta stimulation.
Results: siRNA knockdown and sgRNA knockout of JunB in metastatic HNSCC cells significantly suppressed both cell invasion and migration in vitro. In addition, the knockout of JunB in metastatic HNSCC cells significantly repressed the incidence of lung metastases and prolonged the survival in vivo. However, we did not observe any change in cell morphology with the down-regulation of mesenchymal markers and up-regulation of epithelial markers in response to siRNA-mediated JunB knockdown in HNSCC cells.
Conclusion: These results suggested that JunB could play an important role in promoting cell invasion, migration and distant metastasis in HNSCC via pathways other than EMT and that the down-regulation of JunB may become an effective strategy for patients with invasive HNSCC.

DOI： 10.1186/s13046-016-0284-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

Aspiration pneumonia resulting from cerebrovascular or neurodegenerative disorders could be a fatal disease. In patients with repeated episodes of aspiration pneumonia despite conservative management, surgeries to prevent aspiration, such as laryngectomy and laryngotracheal separation, may be indicated. Here, we report two patients with intractable aspiration pneumonia in whom we performed laryngotracheal separation using the B-type tracheal flap method, with no postoperative complications. Both patients were relieved from the frequent sputum-sucking after the surgery, which resulted in an improved QOL for both the patients themselves and their caregivers. The tracheal flap method is less invasive than Lindeman surgery, because the membranous portion of the trachea is left intact in this method, whereas the trachea is cut circumferentially in Lindeman surgery
this could lead to the shorter operation time and lower incidence of postoperative complications of the tracheal flap method. Furthermore, in this method, in which the skin flap is sutured directly to the tracheal membrane, a wider tracheal stoma can be obtained, leading to the possibility of tracheotomy-tube-free management. Thus, this surgery is beneficial to improve the QOL of both patients with repeated episodes of aspiration pneumonia and their caregivers.

DOI： 10.5631/jibirinsuppl.145.110

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本気管食道科学会  

DOI： 10.2468/jbes.67.85

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Practical Otolaryngology  

The incidence of syphilis has decreased remarkably after the appearance of penicillin. On the other hand sometimes we still see syphilis cases that were infected via sexual behavior. Very few of them manifest hearing impairment and vertigo like Meniere's disease. We report herein on the case of an otosyphilis patient. A 29-year-old man was referred to our department in order to evaluate bilateral progressive hearing impairment. Hearing loss in his right ear and left ear occurred suddenly 2 weeks previously and 1 week previously, respectively. On pure tone audiometry the patient showed mild and sensorineural hearing loss in the left and right ear, respectively. No rash was seen anywhere on his body. The serological and spinal fluid examinations were syphilis positive and the patient was diagnosed as having neurosyphilis. He was prescribed a 9-day course of betamethasone disodium phosphate and 14-day course of doxycycline. The hearing impairments in both of his ear improved partially. This case suggests that we must think of otosyphilis in patients with progressive bilateral hearing impairment.

DOI： 10.5631/jibirinsuppl.145.8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Several randomized trials have shown that concurrent chemoradiotherapy (CCRT) either with or without adjuvant chemotherapy is more effective than radiotherapy-alone for treating nasopharyngeal carcinoma (NPC). The present study retrospectively evaluated the efficacy and toxicity of CCRT with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy in patients with NPC.
PATIENTS AND METHODS: The study regimen consisted of two cycles of TPF chemotherapy [docetaxel (90 mg/m(2)), cisplatin (60 mg/m(2)), and continuous 5-fluorouracil (600 mg/m(2)/day: 5 days)] during definitive radiotherapy. Radiotherapy was performed 5 days a week with a single daily fraction of 1.8 or 2.0 Gy totalling to 70-Gy doses. A total of 24 patients with NPC were enrolled and evaluated.
RESULTS: Treatment completion rate was 70.8%, with an overall response rate of 100%. The 5-year overall survival rate was 82.4%, and 5-year progression-free survival rate was 78.3%.
CONCLUSION: CCRT with TPF resulted in excellent survival rates for patients with NPC.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

BACKGROUND/AIM: Several randomized trials have shown that concurrent chemoradiotherapy (CCRT) either with or without adjuvant chemotherapy is more effective than radiotherapy-alone for treating nasopharyngeal carcinoma (NPC). The present study retrospectively evaluated the efficacy and toxicity of CCRT with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy in patients with NPC. PATIENTS AND METHODS: The study regimen consisted of two cycles of TPF chemotherapy [docetaxel (90 mg/m(2)), cisplatin (60 mg/m(2)), and continuous 5-fluorouracil (600 mg/m(2)/day: 5 days)] during definitive radiotherapy. Radiotherapy was performed 5 days a week with a single daily fraction of 1.8 or 2.0 Gy totalling to 70-Gy doses. A total of 24 patients with NPC were enrolled and evaluated. RESULTS: Treatment completion rate was 70.8%, with an overall response rate of 100%. The 5-year overall survival rate was 82.4%, and 5-year progression-free survival rate was 78.3%. CONCLUSION: CCRT with TPF resulted in excellent survival rates for patients with NPC.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

Systemic steroid therapy is the only standard drug therapy for severe idiopathic sudden sensorineural hearing loss (ISSHL). We have treated severe ISSHL patients with double combined therapy, intravenous steroids (IVS) and hyperbaric oxygen (HBO). In this study, we retrospectively examined the effects of intratympanic steroids (ITS) by adding it to the double combined therapy. The study subjects were 172 patients with severe ISSHL. Eighty patients (38 men and 42 women) were treated with the double combined IVS and HBO therapy between April, 2007 and July, 2010 (A group: Historical control arm). Ninety-two patients (51 men and 41 women) were treated with triple therapy, combined therapy with IVS and HBO plus ITS, between August, 2010 and October, 2013 (B group: Current protocol arm). Each group was divided into two subgroups; one with a pure-tone average (PTA) between 60 and 89 dB (A1 and B1) and the other with a PTA ≥ 90 dB. A 1, A2, B1, and B2 sub-groups had 56 (29 men, 27 women), 24 (9 men, 15 women), 64 (36 men, 28 women), and 28 (15 men, 13 women) patients, respectively. All patients were treated within 30 days from the onset. There was a statistically significant difference in hearing improvement between the A2 and B2 groups, whereas no significant difference was observed between the A1 and B1 groups. Furthermore, a significant difference was observed in all frequencies but 2 kHz between at the A2 group and B2 group, but not between the A1 and B1 groups. Multivariate logistic analysis revealed that the treatment method (double vs.. triple combined therapies) had the strongest impact on hearing improvement in the ISSHL patients with a PTA ≥ 90 dB. These results indicated that the B2 group demonstrated better hearing improvement than the A2 group and suggested that the addition of the ITS could be effective for profound ISSHL patients with a PTA ≥ 90 dB.

DOI： 10.3950/jibiinkoka.118.867

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記述言語：英語   出版者・発行元：ELSEVIER SCI LTD  

DOI： 10.1016/j.anl.2015.02.014

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記述言語：英語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS INC  

OBJECTIVES: We present 3 patients with congenital sensorineural hearing loss (SNHL) caused by novel PTPRQ mutations, including clinical manifestations and phenotypic features. METHODS: Two hundred twenty (220) Japanese subjects with SNHL from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel DNA sequencing of all known nonsyndromic hearing loss genes was performed to identify the genetic cause of hearing loss. RESULTS: Four novel causative PTPRQ mutations were identified in 3 cases. Case 1 had progressive profound SNHL with a homozygous nonsense mutation. Case 2 had nonprogressive profound SNHL with a compound heterozygous mutation (nonsense and missense mutation). Case 3 had nonprogressive moderate SNHL with a compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. CONCLUSION: Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlations between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutations appeared to be responsible for vestibular dysfunction.

DOI： 10.1177/0003489415575041

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

BACKGROUND: The precise comparison of the voice characteristics of Parkinson disease (PD) patients with age-matched normal subjects is still one of the important research projects. The present study aimed at comparing the voice characteristics in sustained phonations of PD patients with an age-matched control group. METHODS: The subjects were 30 Japanese PD patients (15 males and 15 females). The control group consisted of 30 age-matched normal Japanese subjects (15 males and 15 females). Each subject was required to phonate into a mouthpiece attached to Vocal Function Analyzer (PS-77E; Nagashima Medical Instrumental Corporation, Tokyo, Japan) with the airway interruption system, and expiratory lung pressure, mean flow rate, fundamental frequency and intensity of voice, and pitch range were measured. Maximum phonation time was also assessed. RESULTS: The highest pitch level was significantly lower in the PD group than that of the control group in both sexes, whereas the lowest pitch level was significantly higher in the PD group only in males. In both sexes, the pitch range was significantly narrower in the PD group than in the control group. There was no significant difference in intensity, mean flow rate, expiratory pressure, or maximum phonation time between the two groups, for both males and females. CONCLUSION: Only remarkable difference in the voice characteristics between PD patients and age-matched normal elderlies was limited to the narrowing of the pitch range in PD patients. The restriction in pitch regulation in PD patients was considered to be because of difficulty in reciprocal control of the laryngeal muscles secondary to latent rigidity.

DOI： 10.1016/j.jvoice.2014.08.012

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記述言語：英語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

OBJECTIVE: Chronic rhinosinusitis (CRS) is thought to be a multifactorial disease, and it is classified into a number of subtypes according to clinicohistological features. Periostin, a 90-kDa secreted protein, was reported to exist in nasal polyps (NPs) associated with CRS. We compared the expression of periostin with the degree of eosinophilic infiltration as well as tissue remodeling. MATERIALS AND METHODS: Tissue samples were collected from 28 patients of CRS with NPs, and clinicohistological features were evaluated. The pattern of periostin expression was assessed immunohistochemically. RESULT: Two patterns of periostin expression was observed in nasal polyps: "diffuse type", in which periostin was expressed throughout the lamina propria starting just below the basement membrane, and "superficial type", in which the protein was detected only in the subepithelial layers between the basement membrane and the nasal gland. The average infiltrated eosinophil count in the diffuse type was significantly higher than that in the superficial type (diffuse type 360.5±393.0 vs. superficial type 8.46±13.81, p=0.001). Tissue remodeling was observed in 17 (85.0%) of the 20 diffuse-type nasal polyps, but only in one (12.5%) of the eight superficial-type nasal polyps (p<0.001). CONCLUSION: At least two distinct patterns of periostin expression were observed in the nasal polyps associated with CRS in accordance with the heterogeneous mechanisms underlying the pathogenesis of CRS with NPs.

DOI： 10.1016/j.anl.2014.09.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

PURPOSE: Severe oral and pharyngeal mucositis is one of the most critical toxicities known to lead to the discontinuation of chemoradiotherapy (CRT) for head and neck cancer (HNC). Hangeshashinto (TJ-14) is a Kampo medicine that relieves chemotherapy-induced oral mucositis. We investigated the effect of TJ-14 on mucositis, nutritional status, and the completion rate of CRT. METHODS: The study group comprised patients with advanced HNC who were treated with concomitant weekly cisplatin and 70 Gy of radiotherapy. The primary endpoint was the completion rate of chemotherapy, and the secondary endpoints were the grade of mucositis and the nutritional status. RESULTS: A total of 57 patients were included in this study. The completion rate of CRT among patients who were treated with TJ-14 was 91.4%. There was a significant difference in the completion rate of CRT between the groups treated with and without TJ-14 (p = 0.0452). The reduction in body weight was significantly improved from 10.89 to 5.89% with TJ-14 administration (p = 0.003), and the reduction in serum albumin was also significantly decreased from 17.37 to 8.73%. (p = 0.024). CONCLUSION: This therapy allowed a high completion rate of CRT as well as significant benefits in terms of nutritional status. We plan to carry out a further large-scale study of TJ-14.

DOI： 10.1159/000381026

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記述言語：日本語   出版者・発行元：日本口腔・咽頭科学会  

濾胞樹状細胞肉腫 (FDCS) はリンパ濾胞内に局在し抗原提示などをおこなう瀘胞樹状細胞由来のまれな腫瘍である. 症例は80歳男性で歯科受診の際に, 左扁桃腫瘍を指摘された. 近医耳鼻科にて腫瘍の生検を施行し低～中等度の悪性腫瘍が疑われたため当院紹介となった. 画像上, 頸部リンパ節および遠隔転移を認めず根治的切除目的に拡大扁桃摘出術を施行した. 術中迅速診断では扁平上皮癌であったが, 免疫組織化学的にはサイトケラチン (-), CD21 (+), CD23 (+), CD35 (+) であり, FDCS の確定診断に至った. 本症例では予後不良因子の一つとされる有糸分裂像15/10HPF という所見を認めたが, 年齢と全身状態を考慮して術後補助療法は施行しなかった. 現在術後1年2ヵ月経過しているが再発を認めていない.

DOI： 10.14821/stomatopharyngology.28.187

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

PURPOSE: To evaluate the predictive and prognostic value of pretreatment metabolic tumor volume (MTV) in patients with treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: We reviewed the records of 118 patients with newly diagnosed laryngeal carcinoma, who had been treated by RT or CCRT. Pretreatment positron emission tomography (PET) was performed, and MTV values were obtained by contouring margins of standardized uptake value. Clinical factors and MTV were analyzed for their association with survival. RESULTS: Patients with residual disease showed a significantly higher MTV than those with a complete response (CR) after primary treatment. Univariate analysis showed that the patients with a high MTV had a significantly lower disease-free survival (DFS) (p < 0.001). Subsite (p = 0.010), T-stage (p < 0.001), nodal metastasis (p < 0.001) and clinical stage (p < 0.001) also correlated significantly with DFS. In the multivariate analysis, MTV and clinical stage were both found to be independent prognostic factors for DFS (p = 0.001, p = 0.034, respectively). The 3-year DFS for patients with a high MTV were significantly poorer than those with a low MTV (p < 0.001). CONCLUSIONS: MTV of the primary tumor is a significant prognostic factor for DFS in patients with laryngeal carcinoma treated by RT or CCRT. The results imply that MTV could be an important factor when planning treatment and follow-up for patients with laryngeal carcinoma.

DOI： 10.1371/journal.pone.0117924

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記述言語：日本語   出版者・発行元：The Oto-Rhino-Laryngological Society of Japan, Inc.  

DOI： 10.3950/jibiinkoka.118.395

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

OBJECTIVE: The goals of treatment for head and neck cancer are cure and organ-function preservation. For organ preservation, primary treatment via radiotherapy alone is thought to be insufficient for Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx. The objective of the present study was to investigate the efficacy and safety of concurrent chemoradiotherapy with S-1 for patients with Stage II squamous cell carcinoma of the pharynx or larynx for primary organ preservation. METHODS: Previously untreated patients with Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx received three courses of S-1 (40 or 50 mg twice a day; 2 weeks of administration followed by 1 week of rest every 3 weeks) during conventional radiotherapy (a single daily fraction of 1.8 Gy) to a total dose of 70.2 Gy. The primary endpoint was the local control rate at 3 years. RESULTS: From August 2009 to October 2012, 37 patients were evaluated for the study. The overall response rate was 100%. The 3-year local control rate was 89.0% (95% confidence interval, 78.9-99.2%), and the 3-year overall survival rate was 97.2% (95% confidence interval, 91.8-100%). Mucositis and dermatitis in the radiation field were the most common acute adverse events observed. The rates of Grade 3 mucositis and dermatitis were 27 and 35%, respectively. No patients experienced Grade 4 acute adverse events. The treatment completion rate was 89.2%. CONCLUSION: Concurrent chemoradiotherapy with S-1 was safe and effective in improving local control for Stage II squamous cell carcinoma of the pharynx or larynx.

DOI： 10.1093/jjco/hyu154

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

OBJECTIVE: To investigate the clinical factors associated with temporary facial nerve dysfunction (TFND) following surgery for benign parotid gland tumors. METHODS: We reviewed the records of 175 patients with benign parotid gland tumors who underwent partial parotidectomy at Yokohama City University Medical Center in Japan. TFND was found in 33 patients (18.9%). We used two hypothetical lines in magnetic resonance imaging (MRI) images to define the tumor location (upper/lower or anterior/posterior) in the parotid gland. We then studied the associations of TFND with the following clinical factors: patient age, tumor size, histopathological diagnosis, and the location of the tumor within the parotid gland (superficial lobe/deep lobe; upper part/lower part; and anterior part/posterior part). RESULTS: Tumors located in the upper parts, anterior parts or the deep lobes of the parotid gland had statistically higher incidences of TFND compared with tumors located in the lower parts, posterior parts or the superficial lobe (P<0.001, <0.001, <0.01, respectively). The odds ratio for the risk of TFND was significantly high if tumors were located in the upper parts, the anterior parts or the deep lobes with stepwise multivariate regression analysis. The other factors, including patient's age, tumor size, histopathology of the tumor, and inadequate surgeon's experience, were not apparent risks for TFND. CONCLUSIONS: Parotid gland tumors located in the upper parts, the anterior parts or the deep lobes had a higher risk of TFND. The two hypothetical lines we used were shown to be useful to define the tumor location, eventually the risk of TFND.

DOI： 10.1016/j.anl.2014.05.001

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記述言語：日本語   出版者・発行元：(一社)日本耳科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

OBJECTIVE: The aim of the present study was to investigate the rate of post-tonsillectomy hemorrhage (PTH) in a single institution and to evaluate the clinical risk factors for PTH. METHODS: We reviewed the records of 692 patients who underwent tonsillectomy (TE) at Yokohama Minami Kyosai Hospital in Japan. PTH grades were grouped into three categories according to the severity of the hemorrhagic episode: (I) minimal hemorrhage that stopped after noninvasive treatment, (II) hemorrhage requiring treatment with local anesthesia, and (III) hemorrhage requiring reoperation under general anesthesia in the operating room. Clinical risk factors such as sex, age (adults vs. children), TE indication, surgeon's skill level, operative time, ligature type, and duration of antibiotic administration for PTH were investigated. RESULTS: Among the 692 patients, 80 (11.6%) showed PTH, with primary and secondary hemorrhage accounting for 1.6% and 10.0%, respectively. A category III PTH was observed in 18 patients; thus, the overall risk of reoperation was 2.6%. The PTH episode most frequently occurred on postoperative days 5 and 6. The frequency of PTH was significantly higher in male patients and in adults (P<0.01, for both factors). Surgeon's skill was also associated with PTH rate. A stepwise multivariate logistic regression revealed that adult age (odds ratio [OR]=18.9) and male gender (OR=3.78) were the clinical risk factors for PTH. It also revealed that male gender (OR=82065335), adult age (OR=10.6), and surgeon's skill level (OR=7.50) were the clinical risk factors for the category III PTH. CONCLUSIONS: The risk of PTH was higher in this report compared with previous reports, which may be associated with the definition of PTH. Clinical risk factors for PTH were adult age and male gender. The surgeon's skill level was an additional risk factor for category III PTH.

DOI： 10.1016/j.anl.2014.02.007

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is used to treat advanced head and neck cancer. The accuracy of evaluating lymph nodes metastases following CCRT is important for subsequent therapy. PATIENTS AND METHODS: Patients were divided into two groups according to the nodal status, the complete response (CR) and the non-CR groups, as determined by imaging and fine-needle aspiration cytology (FNAC) performed 4-8 weeks after the CCRT, and the findings were compared with the status 6 months after the treatment completion. RESULTS: The sensitivity, the specificity, positive predictive value, negative predictive value and accuracy of each evaluation method were as follows: 66.7%, 73.5%, 26.7%, 93.8% and 72.5%, respectively, for computer tomography (CT) and magnetic resonance imaging (MRI); 91.7%, 69.9%, 30.6%, 98.3% and 72.6% for ultrasonography (US) ; 50.0%, 96.4%, 66.7%, 93.0% and 90.5% for fluorodeoxyglucose-positron emission tomography (FDG-PET) or PET-CT; and 68.4%, 96.1%, 81.3%, 92.5% and 90.6% for FNAC. CONCLUSION: To evaluate the response of lymph node(s) treated by CCRT, US is useful as a positive screening tool and FDG-PET and PET-CT as negative screening tools. FNAC is useful in evaluating suspicious lymph nodes in both positive and negative cases.

DOI： 10.3950/jibiinkoka.117.899

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

This study investigated the efficacy of intratympanic steroid (ITS) therapy as a salvage treatment for idiopathic sudden sensorineural hearing loss after failure of intravenous steroid (IVS) therapy. Systemic steroid therapy is the only standard drug therapy. However, ethically, we could not simply compare ITS with IVS. Conventionally, we have treated idiopahic sudden sensorineural hearing loss patients after failure of systemic steroid therapy with the double combined therapy IVS and hyperbaric oxygen (HBO), as the salvage modality. We examined the effect of ITS by adding it to the double combined therapy with IVS and HBO. Retrospectively, we clinically examined the effect of double combined therapy with IVS and HBO (A group) for 31 patients (12 men and 19 women) (median age: 54 years) with sudden hearing loss after failure of systemic steroid therapy between June, 2003 and July, 2010. Prospectively, we also examined clinically the effect of triple combined therapy with IVS and HBO, ITS (B group) for 29 patients (17 men and 12 women) (median age: 51 years) with sudden hearing loss after failure of systemic steroid therapy between August, 2010 and April, 2012. In the examination of patients treated within 30 days from the onset, one patient (3.2%) demonstrated remarkable recovery, 6 patients (19.4%) demonstrated mild recovery, while no change was noted in 24 patients (77.4%) in the A group. In the B group, 5 patients (17.2%) demonstrated complete recovery, 3 patients (10.3%) demonstrated remarkable recovery, mild recovery was seen in 14 patients (48.3%), and the remaining 7 patients (24.1%) showed no change. There was a significant difference (p < 0.05) between the A group and the B group. Furthermore, the hearing improvement in group B in five pure tone average was significantly better than in the group A (p < 0.05). We concluded that the B group demonstrated better hearing improvement than the A group. Therefore, ITS could be effective for idiopathic sudden sensorineural hearing loss patients after failure of systemic steroid therapy.

DOI： 10.3950/jibiinkoka.117.802

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

PURPOSE: The purpose of the study is to review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma(SCC) of the hypopharynx and to evaluate the factors affecting survival and larynx preservation. STUDY DESIGN: Retrospective study. METHODS AND MATERIALS: T he records of 102 patients with Stage III or IV resectable SCC of the hypopharynx treated with CCRT between January 1998 and August 2010 were reviewed. Of the 102 patients, 62 were treated with high dose regimens including cisplatin, 5-fluorouracil, methotrexate, leucovorin or docetaxel, cisplatin, and 5-fluorouracil. The remaining 40 were treated with low-dose regimens including carboplatin and uracil-tegafur, weekly docetaxel, or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8–2.0 Gray (Gy), to a total dose of 64.8–70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan–Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for OS, DSS, and DSS with larynx preservation. RESULTS: The 5-year OS and DSS for all patients treated with CCRT were 51.3 and 64.3 %, respectively. The 5-year DSS with larynx preservation was 55.5 %. On multivariate analysis, the content of chemotherapy was a significant predictor of OS and DSS for patients undergoing CCRT ; N stage was a significant prognostic factor for DSS and larynx preservation. CONCLUSION: T he treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the N stages of SCC of the hypopharynx.

DOI： 10.1007/s00280-014-2448-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

OBJECTIVE: Compared with radiotherapy alone, concurrent chemoradiotherapy significantly improves survival rates for patients with squamous cell carcinoma of the head and neck. The aim of this study was to retrospectively evaluate the efficacy, toxicity and long-term prognosis of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil chemotherapy. METHODS: A total of 140 patients were enrolled and evaluated. Patients were received two cycles of docetaxel, cisplatin and 5-fluorouracil chemotherapy (docetaxel [50 mg/m(2): Day 1], cisplatin [60 mg/m(2): Day 4] and continuous 5-fluorouracil [600 mg/m(2)/day: Days 1-5]) during definitive radiotherapy. RESULTS: The overall response rate was 97.1%. The 3 and 5-year overall survival rates were 83.3 and 79.2%, respectively. The 3 and 5-year disease-specific survival rates were 84.2 and 80.0%, respectively. Among patients with laryngeal or hypopharyngeal carcinoma, the 5-year laryngectomy-free survival rate was 64.9%. CONCLUSIONS: Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil showed excellent survival and organ preservation rates for the patients with locally advanced squamous cell carcinoma of the head and neck.

DOI： 10.1093/jjco/hyu026

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/S13691-013-0106-X

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA). In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth. These findings demonstrate that TRUE gene silencing of cyclin D1 leads to inhibition of the growth of HNSCC cells and suggest that these sgRNAs alone or combined with cisplatin may be a useful new therapy for HNSCCs.

DOI： 10.1371/journal.pone.0114121

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Secondary placement of a voice prosthesis is often difficult to perform due to inability in flexing the neck after total laryngectomy and radiation therapy. We report a technique of secondary voice prosthesis placement using a curved rigid esophagoscope. An endotracheal tube and a flexible endoscope are inserted into the esophagus. In creating a tracheoesophageal puncture, a sharp forceps is inserted through the tip of esophagoscope. Then, a guide wire is introduced through the esophagoscope and the voice prosthesis is placed by back-loading method. This method is safe and easy because there is no risk of perforation through the posterior esophageal wall.

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記述言語：英語   出版者・発行元：The Society of Practical Otolaryngology  

Orbital infection mainly develops as a complication of sinusitis, and often disturbs the functions of the eye by raising orbital pressure due to abscess formation. We herein report on a case of an intraorbital abscess in the upper-lateral part of the orbit following acute sinusitis occurred in a 59-year-old male. At presentation, the sinusitis itself had already been improved and the abscess did not have contact with frontal or the ethmoid sinuses. A quick and correct diagnosis of sinusitis followed by orbital infection is essential. An urgent surgical drainage along with an adequate use of antibiotics is required to preserve the eyesight.

DOI： 10.5631/jibirinsuppl.140.54

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記述言語：英語   出版者・発行元：The Society of Practical Otolaryngology  

There have been recent reports that autoimmune inner ear disease (AIED) has been found in some cases of refractory hearing loss such as idiopathic bilateral sensorineural hearing loss. McCabe first reported that patients with AIED responded to immunosuppressive therapy. Corticosteroid therapy alone is effective in the early phase of AIED, but becomes ineffective in a repeated series and immunosuppressive therapy is recommended in such cases. We experienced a case of idiopathic bilateral sensorineural hearing loss in which corticosteroid therapy was not effective after the recurrence and immunosuppressive therapy was applied, although the presence of the inner ear autoantibodies was not tested. In this case, the immunosuppressive therapy seemed effective for preventing the progression of the hearing loss and for improving the speech discrimination scores. This therapeutic strategy may be indicated in some cases of idiopathic bilateral sensorineural hearing loss which have proved refractory to corticosteroid therapy.

DOI： 10.5631/jibirinsuppl.140.12

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

Percutaneous endoscopic gastrostomy (PEG) has been generally used as a long-term enteral nutrition route for patients in whom oral intake is impossible. Percutaneous trans-esophageal gastrotubing (PTEG) is useful for the patients in whom PEG insertion has not been indicated. A gastroenterologist usually performs PTEG in Japan, but in our hospital otolaryngologists have performed this procedure. From 2006 to 2012, we experienced 9 patients who underwent PTEG insertion without a life-threatening adverse event. An otolaryngologist who is accustomed to the cervical procedures can safely perform PTEG insertion.

DOI： 10.3950/jibiinkoka.116.1126

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

BACKGROUND: The prevalence of oropharyngeal carcinoma is rising in western Europe and the United States, where there appears to be a strong association between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC). However, such a correlation has not yet been fully evaluated in Japan. METHODS: We performed a retrospective analysis of the association between tumour HPV status and the demographic and clinicopathological parameters of 71 patients with OPSCC at Hokkaido University Hospital, Japan, between 1998 and 2009. The parameters included age, gender, survival, tumour subsite, tumour-node-metastasis (TNM) stage, smoking history, second primary tumour status, recurrence/residual disease at the primary site, and overall survival. HPV status was established by multiplex polymerase chain reaction (PCR) analysis. RESULTS: Of the 71 oropharyngeal cancers, 20 were positive for HPV-16, two for HPV-18, and one for HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumours (p = 0.0038) compared with HPV-negative tumours. Of the 45 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients (p = 0.0032). In a multivariate analysis, the survival benefit of HPV-positive patients was independent of age and T and N classification. CONCLUSIONS: HPV status is a significantly favourable prognostic factor in oropharyngeal cancer and could be used as a marker to optimize the treatment of patients with this type of cancer in Japan.

DOI： 10.1007/s10147-012-0469-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

OBJECTIVE: To review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and to evaluate the factors affecting survival and larynx preservation. STUDY DESIGN: Retrospective study. SUBJECTS AND METHODS: The records of 102 patients with stage III or IV resectable SCC of the larynx treated with CCRT between February 1994 and March 2009 were reviewed. Of 102 patients, 59 were treated with high-dose regimens, including cisplatin, 5-fluorouracil (5-FU), methotrexate, and leucovorin or docetaxel, cisplatin, and 5-FU, and 43 were treated with low-dose regimens, including carboplatin and uracil-tegafur or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8–2.0 Gray (Gy), to a total dose of 66.0–70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan–Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for DSS and DSS with larynx preservation. RESULTS: The 5-year OS and DSS for all patients treated with CCRT were 63.9 and 70.7 %, respectively. The 5-year DSS with larynx preservation was 54.1 %. On multivariate analysis, N stage, synchronous multiple primary cancers, and the contents of chemotherapy were significant predictors of OS for patients undergoing CCRT; T stage, N stage, and the contents of chemotherapy were significant prognostic factors for larynx preservation. CONCLUSION: The treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the T and N stages of laryngeal SCC. It is important to diagnose multiple synchronous primary cancers before CCRT.

DOI： 10.1007/s00280-013-2261-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

CONCLUSION: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent. OBJECTIVE: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC. METHODS: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens. RESULTS: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14-21.69, p = 0.0304).

DOI： 10.3109/00016489.2013.795287

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

OBJECTIVES: Although three-weekly high-dose (100mg/m(2)) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40mg/m(2) has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis. METHODS: We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a "wait and see" approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone. RESULTS: Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan-Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively. CONCLUSION: Concomitant weekly cisplatin at a dose of 40mg/m(2) chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases.

DOI： 10.1016/j.anl.2012.07.002

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記述言語：英語   出版者・発行元：Springer  

Squamous cell carcinoma of the nasal vestibule (SCC-NV) is rare among head and neck malignancies. It behaves differently from cancers arising in the nasal cavity and paranasal sinuses, and skin cancer of the external nose. Prognosis is more favorable than nasal cavity tumors and less favorable than skin cancers. We experienced two cases of SCC-NV who were treated with rapid superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT). A 56-year-old male and a 68-year-old female with SCC-NV, classified as T4aN0M0 according to UICC and T2 according to Wang classification, were given superselective intra-arterial infusions of cisplatin, with simultaneous intravenous infusions of thiosulfate to neutralizecisplatin toxicity, together with conventionalradiotherapy. In both cases, the internal maxillary artery and the facial artery were considered to be feeders of the tumor. No serious adverse events have been observed in either patient to date during follow-up of 7.3 and 5.3 years, respectively. Both patients are alive without disease and show excellent cosmetic results. RADPLAT is considered to be useful for the treatment of patients with SCC of the nasal vestibule.

DOI： 10.1007/s13691-012-0044-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.

DOI： 10.1007/s10147-011-0308-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Background : The concept of sentinel node (SN) has been established in oral cancer. This study aimed to investigate distribution of the area where SN was located. Method : Ten patients with T1-2 N0 tongue cancers underwent SN biopsy following partial glossectomy. SNs were detected using gamma camera and gamma probe and were analyzed pathologically. Result : SN was localized in 9 submandibular, 14 upper jugular, 5 middle jugular, 1 lower jugular area in disease side. SN was also localized in 1 upper jugular, and 1 middle jugular area in the opposite side. Occult SN metastasis was observed in 6 of 10 patients (60%). Conclusions : It was concluded that the most likely site where SN was detected was upper jugular area in disease side.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.

DOI： 10.1007/s10147-011-0308-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

CONCLUSION: We conclude that intra-arterially injected cisplatin passed via lymph flow into sentinel nodes (SNs) as the platinum concentration in the SNs was higher than that in the non-sentinel nodes (NSNs). It is possible that preoperative intra-arterial chemotherapy targeting primary cancer also has a therapeutic effect on subclinical metastatic SNs. OBJECTIVES: Intra-arterial chemoradiotherapy has been reported to be effective against not only primary tumors but also nodal metastases. We considered the hypothesis that intra-arterially injected cisplatin passed via lymph flow into regional nodes. This study aimed to investigate intra-arterially injected cisplatin distribution to regional nodes by comparing platinum concentrations in SNs and NSNs. METHODS: Five patients with T1-2 N0 tongue cancer were treated with preoperative intra-arterial chemotherapy (cisplatin, 100 mg/m(2)) targeting primary cancer. Partial glossectomy together with SN biopsy and elective neck dissection were performed 2 weeks after intra-arterial chemotherapy. Platinum concentrations in the lymph nodes were measured using a Zeeman atomic absorption spectrometer. RESULTS: Thirteen SNs were harvested together with eight NSNs from the areas adjacent to the SNs. Platinum concentrations were then measured, revealing a significant difference in platinum concentration between the SNs and the NSNs (mean ± SD, 0.682 ± 0.246 µg/g vs 0.506 ± 0.274 µg/g; p = 0.049).

DOI： 10.3109/00016489.2012.680494

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

Gastroesophageal reflux disease (GERD) is often associated with decreased upper gastrointestinal motility, and ghrelin is an appetite-stimulating hormone known to increase gastrointestinal motility. We investigated whether ghrelin signaling is impaired in rats with GERD and studied its involvement in upper gastrointestinal motility. GERD was induced surgically in Wistar rats. Rats were injected intravenously with ghrelin (3 nmol/rat), after which gastric emptying, food intake, gastroduodenal motility, and growth hormone (GH) release were investigated. Furthermore, plasma ghrelin levels and the expression of ghrelin-related genes in the stomach and hypothalamus were examined. In addition, we administered ghrelin to GERD rats treated with rikkunshito, a Kampo medicine, and examined its effects on gastroduodenal motility. GERD rats showed a considerable decrease in gastric emptying, food intake, and antral motility. Ghrelin administration significantly increased gastric emptying, food intake, and antral and duodenal motility in sham-operated rats, but not in GERD rats. The effect of ghrelin on GH release was also attenuated in GERD rats, which had significantly increased plasma ghrelin levels and expression of orexigenic neuropeptide Y/agouti-related peptide mRNA in the hypothalamus. The number of ghrelin-positive cells in the gastric body decreased in GERD rats, but the expression of gastric preproghrelin and GH secretagogue receptor mRNA was not affected. However, when ghrelin was exogenously administered to GERD rats treated with rikkunshito, a significant increase in antral motility was observed. These results suggest that gastrointestinal dysmotility is associated with impaired ghrelin signaling in GERD rats and that rikkunshito restores gastrointestinal motility by improving the ghrelin response.

DOI： 10.1152/ajpgi.00462.2011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This retrospective study aimed to compare the accuracy of two nodal evaluation criteria using computed tomography after intra-arterial chemoradiation in node-positive head and neck squamous cell carcinomas. Computed tomography was used to evaluate radiographic nodal response 4-8 weeks after intra-arterial chemoradiation. We compared the accuracy of two different criteria: criterion 1 (radiographic complete response was recorded in the absence of focal abnormalities and if the maximum diameter of the metastatic node was less than 15 mm), and criterion 2 (radiographic complete response was recorded in the absence of focal abnormalities and if the minimum diameter of metastatic nodes was less than 7 mm in level II and if the minimum diameter of metastatic nodes in the rest of the neck was less than 6 mm). Positive predictive values were criterion 1: 69.2%, criterion 2: 47.8%; negative predictive values were criterion 1: 88.5%, criterion 2: 90.5%. Positive likelihood ratios were criterion 1: 7.50, criterion 2: 3.06. The difference between each criteria was statistically significant using McNemar's test (p = 0.0016). Computed tomography evaluation accuracy of nodal response after intra-arterial chemoradiation was comparable to recent reports, and it was feasible to perform salvage neck dissection by computed tomography evaluation for nodal response. We recommend using criterion 1 because of its simplicity and reliability.

DOI： 10.1007/s00405-011-1814-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ANNALS PUBL CO  

OBJECTIVES: To investigate the biological factors related to the onset of Bell's palsy, we sought to identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and plasma of patients with Bell's palsy and Ramsay Hunt syndrome (RHS). METHODS: We carried out DNA microarray analyses using PBMCs taken from patients with Bell's palsy at their initial visit and 2 to 4 weeks later. To validate these analyses, we measured the relative messenger RNA levels of alpha-defensin in paired PBMCs by reverse transcription-polymerase chain reaction. The plasma concentrations of alpha-defensin in patients and healthy volunteers were quantified by enzyme-linked immunosorbent assay. RESULTS: The DNA microarray analysis identified alpha-defensin as a candidate gene related to the onset of Bell's palsy. Reverse transcription-polymerase chain reaction analysis showed that the relative alpha-defensin messenger RNA levels in PBMCs from the later visit were increased at least twofold in 9 of 13 patients (69%) with Bell's palsy and in 4 of 6 patients (67%) with RHS. The plasma alpha-defensin concentrations in the patients with RHS were significantly higher than those in healthy volunteers (p = 0.0013) and in the patients with Bell's palsy (p = 0.0306). Elevations of plasma alpha-defensin were observed in 5 of the 9 patients with Bell's palsy who demonstrated alpha-defensin overexpression in PBMCs. CONCLUSIONS: alpha-Defensin may be one of the biological factors related to the onset of Bell's palsy and RHS.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3-ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3-ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3-ANCA (P = .001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P = .007). Crust formation (P = .001), saddle nose (P = .024), and sinusitis (P = .001) were more common in patients with proteinase 3-ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.

DOI： 10.1177/0194599811424044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective. To know the characteristics of endoscopic laryngeal and pharyngeal abnormalities in Japanese patients with laryngopharyngeal reflux symptoms (LPRS). Methods. A total of 146 endoscopic images of the larynx and pharynx (60 pairs for the rabeprazole group and 13 pairs for the control group) were presented to 15 otolaryngologists blinded to patient information and were scored according to several variables potentially associated with laryngopharyngeal reflux. The median value of the 15 scores for each item from each image was obtained. The mean pretreatment scores of each item and total score were assessed in both rabeprazole and control groups. In the rabeprazole group, the endoscopic findings before and after the 4-week treatment with rabeprazole were compared. Changes between corresponding duration in the control group were also evaluated. Results. The median and mean pretreatment total score was 3 and 3.02, respectively, from the 73 patients with LPRS. No significant differences were observed before and after treatment in either the rabeprazole or control groups for any item or total score. In 24 patients with a high pretreatment score (total score ≥ 4) from the rabeprazole group, significant decreases in scores for "thick endolaryngeal mucous" (0.54 to 0.17, P = 0.017) and total (4.77 to 3.58, P = 0.0003) were observed after the 4-week treatment.

DOI： 10.1155/2012/908154

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose of review
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) may be localized or systemic, and can involve the eyes. This review presents the major disease features and treatments of these forms of systemic vasculitis.
Recent findings
It is increasingly recognized that ocular disease in AAV can occur in the absence of systemic disease, and that in limited eye disease the ANCA is frequently undetected. Ocular disease in AAV can take many forms, from orbital pseudotumor to scleritis, keratitis, and retinitis. Management of eye disease in ANCA-associated vasculitis includes local anti-inflammatory and moisturizing therapies, local and systemic glucocorticosteroid therapies. Systemic therapies are highly effective for the management of organ involvement of AAV including eye disease, and include the chemotherapies cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. The results of recent, randomized, clinical trials have demonstrated the efficacy of a new tool in the therapeutic armamentarium for AAV, the use of B-cell-depleting therapy with rituximab.
Summary
Ocular disease in AAV can occur in isolation or more commonly as a manifestation of systemic disease. With recent advances in treatment, the organ and overall life expectancy of patients suffering from AAV has markedly improved.

DOI： 10.1097/ICU.0b013e32834bdfe2

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We introduced our experiences of transoral surgery of the larynx and pharynx, such as resection of early stage hypopharyngeal carcinoma or epiglitoc cysts and removal of foreign body, using Weerda-type videolaryngoscope along with telescope and Hi-vison CCD camera system in Hokkaido University Hospital.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Objective: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer.
Methods: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks.
Results: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%).
Conclusions: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.

DOI： 10.1093/jjco/hyr086

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. METHODS: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. RESULTS: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). CONCLUSIONS: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.

DOI： 10.1093/jjco/hyr086

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

We report a case that fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) depicted systemically multiple lesions of methotrexate (MTX)-associated lymphoproliferative disorders. A 70-year-old man receiving MTX for rheumatoid arthritis complained of neck swelling. FDG PET/CT revealed multiple FDG-avid lesions in lymph nodes, lungs, bones, and muscles. Lesions in bones and muscles were not detected on X-CT. Final diagnosis of cervical node was confirmed as MTX-associated lymphoproliferative disorders. FDG PET/CT performed 148 days after discontinuing MTX demonstrated complete remission.

DOI： 10.1097/RLU.0b013e3182177284

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success.

DOI： 10.1016/j.oraloncology.2011.04.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

OBJECTIVE: To identify unique epigenetic signature in cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Molecular and microarray studies. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Head and neck CSCs were isolated in HNSCC cells by CD44 staining and flow cytometry sorting. CSCs with highest CD44 expression (CD44(hi)) and non-stem cells (non-SCs) with lowest CD44 expression (CD44(low)) were then characterized for stemness gene expression and their responses to chemotherapeutic agents, followed by high-throughput epigenetic profiling using the Illumina BeadChip Array, targeting 28,544 CpG sites covering more than 14,956 genes. RESULTS: CD44(hi) CSCs expressed higher levels of stem cell markers and were more resistant to chemotherapeutic agents as compared to CD44(low) non-SCs. By DNA methylation microarray analysis, 17 hypomethylated and 9 hypermethylated genes were identified in CD44(hi) CSCs as compared to non-SCs in most HNSCC cell lines. Cluster analysis using these 26 genes showed that CD44(hi) CSCs were epigenetically distinct from the CD44(low) non-SCs in all 5 HNSCC cell lines. CONCLUSION: A unique epigenetic profile consisting of 17 hypomethylated and 9 hypermethylated genes was seen in HNSCC CSCs. These genes may be critically required in maintaining the stemness or pluripotency of CSCs and may represent novel molecular targets for anticancer therapies aimed at eradicating CSCs in HNSCC.

DOI： 10.1177/0194599811398786

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

The 14 cases of malignant submandibular tumor whose treatment outcome we analyzed between 1989 and 2008 included 5 of adenoid cystic carcinoma, 3 of squamous cell carcinoma, 2 each of mucoepidermoid carcinoma, and carcinoma ex pleomorphic adenoma, and 1 each of carcinosarcoma and large-cell carcinoma. One subject was diagnosed with T1, 7 with T2, 4 with T3, and 2 with T4. Lymph node involvement occurred in 5, -1 with N1 and 4 with N2. None had distant metastasis on the first visit. Seven were treated by surgery alone, 3 by surgery followed by radiotherapy, 2 by surgery followed by radio-and chemotherapy, and 1 by optimized supportive care. The surgical resection area was decided by tumor extension. Neck dissection was done in 9. Overall 5-year survival for all cases based on the Kaplan-Meier method was 57%. All with carcinoma ex pleomorphic adenoma, carcinosarcoma, or large-cell carcinoma remain alive. For those with adenoid cystic carcinoma 5-year survival is 80%, with mucoepidermoid carcinoma 50%, with squamous cell carcinoma 0%, and with carcinosarcoma 0%, respectively. The 5-year survival for stage I subjects was 100%, for stage II 83%, for stage III 50%, and for stage IV 0%. Surgical resection and postoperative radiotherapy were done in cases of minimal extraglandular extension or microscopically positive margins, with satisfactory results. Treatment efficacy for high-grade and advanced stage, however, requires more improvement.

DOI： 10.3950/jibiinkoka.114.126

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

We retrospectively investigated treatment outcomes in patients with glottic T1 carcinoma treated with 65 Gy in 26 fractions four times a week and discuss the importance of the overall treatment time.
Two hundred one patients with glottic T1 carcinoma were evaluated. Sixty-five Gray in 26 fractions were delivered for 200 patients, whereas 1 patient received 62.5 Gy in 25 fractions. We delivered radiotherapy once daily four times a week in this period, for a weekly dose of 10 Gy. Weekdays except Wednesday were treatment days.
The overall survival rate was 96.8 +/- 1.3% (standard error) at 3 years and 90.8 +/- 2.2% at 5 years. The local control rate was 91.9 +/- 2.0% at 3 years and 89.8 +/- 2.3% at 5 years. In patients with an overall treatment time equal to or longer than 47 days, the local control rate was 82.6 +/- 6.0% at both 3 and 5 years. In the patients with overall treatment time equal to or less than 46 days, the local control rate was 94.6 +/- 1.9% at 3 years and 91.8 +/- 2.4% at 5 years. There was a significant difference between these two groups (P = 0.0349). A severe late radiation reaction occurred in one patient. He experienced severe laryngeal edema that required tracheotomy at 6 months after the completion of radiotherapy. The tracheotomy was closed at 14 months after completion of radiotherapy.
Overall treatment time seems to be an important factor for a good local control rate for glottic T1N0 carcinoma even when treated with slight hypofractionation.

DOI： 10.1093/jjco/hyq153

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We retrospectively investigated treatment outcomes in patients with glottic T1 carcinoma treated with 65 Gy in 26 fractions four times a week and discuss the importance of the overall treatment time. METHODS: Two hundred one patients with glottic T1 carcinoma were evaluated. Sixty-five Gray in 26 fractions were delivered for 200 patients, whereas 1 patient received 62.5 Gy in 25 fractions. We delivered radiotherapy once daily four times a week in this period, for a weekly dose of 10 Gy. Weekdays except Wednesday were treatment days. RESULTS: The overall survival rate was 96.8 ± 1.3% (standard error) at 3 years and 90.8 ± 2.2% at 5 years. The local control rate was 91.9 ± 2.0% at 3 years and 89.8 ± 2.3% at 5 years. In patients with an overall treatment time equal to or longer than 47 days, the local control rate was 82.6 ± 6.0% at both 3 and 5 years. In the patients with overall treatment time equal to or less than 46 days, the local control rate was 94.6 ± 1.9% at 3 years and 91.8 ± 2.4% at 5 years. There was a significant difference between these two groups (P = 0.0349). A severe late radiation reaction occurred in one patient. He experienced severe laryngeal edema that required tracheotomy at 6 months after the completion of radiotherapy. The tracheotomy was closed at 14 months after completion of radiotherapy. CONCLUSIONS: Overall treatment time seems to be an important factor for a good local control rate for glottic T1N0 carcinoma even when treated with slight hypofractionation.

DOI： 10.1093/jjco/hyq153

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DOI： 10.1007/s00405-011-1814-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

To elucidate the altered function of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD), we evaluated the motility proximal to LES using force transducers, contraction and relaxation responses to neurotransmitters in LES strips, and gene expression of neurotransmitter receptors in GERD rats. Force transducers were applied to the proximal LES, and contraction of the LES was monitored during free moving. In addition, LES was isolated from sham-operated and GERD rats to investigate the LES function in an organ bath, and to determine gene expression. The in vivo motility proximal to LES (% motility index) in conscious rats was decreased by atropine treatment and increased by cisapride (5-HT(4) receptor agonist) treatment. Acetylcholine- and serotonin (5-HT)-induced LES contraction and sodium nitroprusside-induced relaxation in LES strips of GERD rats markedly decreased compared to sham-operated rats. The mRNA expressions of 5-HT(4) and muscarinic acetylcholine 3 receptors were significantly reduced in esophageal LES strips of GERD rats compared with sham-operated rats. Intraperitoneal administration of cisapride improves the erosive damage in the esophagus in GERD rats. It is suggested that the reduction of 5-HT-induced contraction in LES strips in GERD rats may be partly due to the decrease in 5-HT(4)-receptor activation. The reduction of LES function may be due to the decrease in neurotransmitters signal transduction, leading to the deterioration of histopathological damage in GERD.

DOI： 10.1248/bpb.34.704

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT RHINOLOGIC SOC  

BACKGROUND: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP). METHODOLOGIES: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumors arising from the anterior part of the maxillary sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer`s test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery. RESULTS: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumors. No patients suffered tumor recurrence. There was no difference in lacrimal duct function between the diseased side and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100. CONCLUSIONS: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.

DOI： 10.4193/Rhino10.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This retrospective study aimed to assess the role of salvage surgery for local recurrence in hypopharyngeal cancer (HPC) patients who had received radiotherapy (RT) or concomitant chemoradiotherapy (CRT) as an initial treatment. The local recurrence rate, salvage rate after local recurrence and overall survival rate were investigated in 104 HPC patients who received treatment between 1991 and 2005. Local recurrence in the primary site was observed in 41 patients (rate, 39.4%) of whom only 12 could undergo further salvage surgery. Disease control was achieved in seven of these patients (successful salvage rate, 17.1%). The 5-year overall survival rate was 40.6% in the RT/CRT patient group and successful salvage rates for T1, T2, T3 and T4 primary disease were 33.3% (1/3), 20.0% (4/20), 16.7% (2/12) and 0% (0/6), respectively. Severe postoperative complications such as pharyngo-cutaneous fistula were seen in six patients (50.0%). Prognosis of patients with locally recurring HPC after RT/CRT is poor at any primary T-stage and the incidence of postoperative complication is relatively high. This should be taken into consideration when the initial treatment plan is decided and the choice of salvage surgery for such recurrent cases should be carefully determined.

DOI： 10.1007/s00405-010-1274-3

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記述言語：日本語   出版者・発行元：日本口腔・咽頭科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS INC  

BACKGROUND: Comorbidity has an impact on survival in laryngeal cancer in several reports. However, the importance of comorbidity in hypopharyngeal cancer (HPC) has not been reported. METHODS: A retrospective medical record review of 156 patients with HPC treated between 1995 and 2005 was performed. Comorbid illness was measured by the Adult Comorbidity Evaluation-27. A Cox proportional hazards model was used to determine the factors related to overall survival. RESULTS: Comorbidity was absent in 55 (35.2%) of the patients, mild in 39 (25%), moderate in 28 (17.9%), and severe in 34 (21.8%). There were statistically significant differences between the survival rates in accord with age, stage, subsite, and comorbidity (45.1% for none or mild vs 27.7% for moderate or severe; p = .0073). Age, stage, and comorbidity were identified as independent prognostic factors in the multivariate analysis. CONCLUSION: Comorbidity, along with the clinical stage, should be considered in treatment planning for patients with HPC.

DOI： 10.1002/hed.21158

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

目的:化学放射線療法後の喉頭癌再発例に対する喉頭全摘出術においては、咽頭皮膚瘻孔など創合併症に発生率が高いことが報告されている。その予防策として、咽頭粘膜縫合部を血流に富む新鮮な組織で覆う方法(pharyngeal interposition graft)の有用性が報告されている。今回、喉頭癌に対する化学放射線療法後の再発例において、喉頭全摘出術とともに大胸筋弁をpharyngeal interposition graftとして用いた4症例の術後経過について検討した。対象:化学放射線療法後に再発を来した喉頭癌4症例(声門上癌3例、声門癌1例)を対象とした。喉頭全摘出術後、咽頭粘膜を一次縫合し、さらに咽頭粘膜縫合部と挙上した皮膚の間に大胸筋弁を挟みpharyngeal interposition graftとした。結果:4例中3症例に軽度創合併症が生じた。気管孔周囲の局所感染、皮下小膿瘍、皮膚縫合部の表層壊死が各1例であり、いずれも局所処置で改善した。4症例ともに咽頭皮膚瘻孔などの重度創合併症は来さなかった。また、大胸筋弁の血流不全および採取に伴う合併症は認められなかった。結論:大胸筋弁を用いたpharyngeal interposition graftは安全であり、化学放射線療法後の喉頭全摘出術において咽頭皮膚瘻孔などの重度創合併症の発生を抑えるため有用であると考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J01099&link_issn=&doc_id=20100202420002&doc_link_id=10026611843&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10026611843&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ENDOCRINE SOC  

Aging is associated with decreased food intake, a phenomenon termed the anorexia of aging. In this study, we sought to clarify changes in peripheral and central appetite-related factors in aged mice. Furthermore, we investigated the effects of rikkunshito, a traditional Japanese medicine, on age-related anorexia. C57BL/6J mice that were 6 or 75 wk old were studied. We investigated changes in food intake, ghrelin and leptin levels, and the expression of appetite-related genes with age. In addition, we verified the effects of ghrelin, rikkunshito, phosphodiesterase 3 (PDE3), and phosphoinositide 3-kinase inhibitors on appetite. Food intake was significantly decreased in 75-wk-old mice compared with the 6-wk-old mice. In 75-wk-old mice, plasma acylated ghrelin levels under fasting conditions were lower than in 6-wk-old mice, whereas leptin levels under feeding conditions were substantially higher. The expression levels of hypothalamic preproghrelin under feeding conditions and the expression levels of neuropeptide Y and agouti-related protein under fasting conditions were lower compared with those of the 6-wk-old mice. Ghrelin supplementation (33 microg/kg) failed to increase food intake in 75-wk-old mice. Conversely, oral administration of LY294002, a phosphoinositide 3-kinase inhibitor, and cilostamide, a PDE3 inhibitor, increased food intake in 75-wk-old mice. Moreover, rikkunshito increased food intake in aged mice. The components of rikkunshito (nobiletin, isoliquiritigenin, and heptamethoxyflavone) had inhibitory effects on PDE3. These results suggest that dysregulation of ghrelin secretion and ghrelin resistance in the appetite control system occurred in aged mice and that rikkunshito ameliorated aging-associated anorexia via inhibition of PDE3.

DOI： 10.1210/en.2009-0633

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oto-Rhino-Laryngological Society of Japan Inc.  

There is an increased risk of wound complications in patients undergoing salvage laryngectomy following chemoradiotherapy. To reduce the rate of wound complications after a salvage total laryngectomy, a fresh tissue reinforcement of the pharyngeal suture line (pharyngeal interposition graft) has been reported to be useful. In the present study, wound complications after a salvage total laryngectomy with a pectoralis major muscle flap as a pharyngeal interposition graft were analyzed. Four patients with recurrent laryngeal cancer (three with supraglottic, and one with glottic cancer) after chemoradiotherapy underwent salvage total laryngectomy using a pectoralis major muscle interposition flap. Minor wound complications were observed in three of the four patients, with an infection around the tracheostoma, a minor subcutaneous abscess, and a superficial skin necrosis in one patient each. These complications were managed with local wound care. No patients had major wound complications such as pharyngocutaneous fistulas. There were no necroses or wound complications of the pectoralis major muscle flap. This study has suggested that the pectoralis major muscle flap as a pharyngeal interposition graft is safe and useful for prevention of wound complications in salvage total laryngectomy following chemoradiotherapy.

DOI： 10.3950/jibiinkoka.113.9

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記述言語：英語  

DOI： 10.1055/s-0030-1255520

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/cncr.24515

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

2002年5月から2007年12月までに北大病院放射線科にて強度変調放射線治療(Intensity modulated radiation therapy,IMRT)を行った37例を検討した。上咽頭13例、中咽頭19例、下咽頭3例、上顎1例、口腔1例であった。死亡は4例で認められた。治療終了後4ヵ月で中咽頭癌(後壁T3N0)が咽頭膿瘍後の誤嚥性肺炎で死亡したが、他の3名は他癌死であった。原発・頸部リンパ節残存・再発は、上咽頭癌で原発巣再発1例、中咽頭癌では原発巣再発が3例、頸部リンパ節転移・残存が2名、下咽頭癌では1例で頸部リンパ節残存があった。重篤な晩期反応は、中咽頭後壁の1名で咽頭膿瘍の発生による死亡があり、1例の上咽頭癌症例(CDDP併用)で聴力低下と偶角閉塞がみられた。(著者抄録)

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記述言語：英語   出版者・発行元：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0029-1214647

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：GEORG THIEME VERLAG KG  

Patients with early stage hypopharyngeal carcinoma can be treated with endoscopic resection. However, strict indication for endoscopic resection in cases of hypopharyngeal carcinoma is unclear. in this paper, we evaluated the long-term outcome after endoscopic resection in patients with hypopharyngeal carcinoma invading the subepithelium. Among 16 patients with hypopharyngeal carcinoma who underwent endoscopic resection, eight patients who were histologically confirmed to have tumors with shallow invasion of the subepithelium were studied. Depth of tumor invasion in the subepithelium in those patients ranged from 300 to 720 mu m (mean +/- SD, 490 140 pm). During a median follow-up period of 40 months, none of the eight patients had local recurrence or metastasis. Kaplan-Meier estimates of relapse-free survival rates at 5 years in the eight patients were 100%. The results of this study suggest that hypopharyngeal carcinoma with slight invasion to the subepithelium can be successfully treated by endoscopic resection.

DOI： 10.1055/s-0029-1214488

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本気管食道科学会  

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記述言語：日本語   出版者・発行元：(一社)日本耳鼻咽喉科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER MEDICAL ASSOC  

Objective: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires.
Design: The VRQOL and VHI-10 questionnaires.
Setting: University hospital.
Patients: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey.
Main Outcome Measure: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires.
Results: The mean VRQOL scores for patients who had undergone radiotherapy (n=63), chemoradiotherapy (n=29), laser surgery (n=14), or total laryngectomy (n=27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively.
Conclusion: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

DOI： 10.1001/archoto.2009.8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER MEDICAL ASSOC  

OBJECTIVE: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires. DESIGN: The VRQOL and VHI-10 questionnaires. SETTING: University hospital. PATIENTS: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey. MAIN OUTCOME MEASURE: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires. RESULTS: The mean VRQOL scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. CONCLUSION: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

DOI： 10.1001/archoto.2009.8

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記述言語：日本語   出版者・発行元：(株)医学書院  

42歳男。4ヵ月前に嗄声が出現し、保存的治療でいったん改善したが、再増悪を来たした。間接喉頭鏡で左披裂部内側壁、左声帯に3ヶ所、右声帯に2ヶ所の喉頭腫瘍を認め、喉頭ファイバースコピーで腫瘍は乳頭状増殖を示した。喉頭乳頭腫の診断で喉頭直達鏡による腫瘍切除術を施行し、一部採取した腫瘍の迅速病理では悪性所見なしの結果であった。喉頭用スキマーブレード(2.9mm)を装着したマイクロデブリッダーを用いて腫瘍切除を行い、腫瘍自体は軟らかく、ブレード内に吸引された腫瘍のみを切除可能であった。回転数はブレードの熱による瘢痕化を防ぐため、毎分60回転の超低速とした。ごく少量の出血を認めたが、マイクロデブリッダーによる吸引と20万倍エピネフリン塗布で対処できた。切除組織の病理組織像は核異型、分裂像に乏しく、乳頭腫と診断された。術後は沈黙療法を行い、4日目に退院した。嗄声は改善し、術後5ヵ月で再増悪、腫瘍再発はない。

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：THIEME MEDICAL PUBL INC  

OBJECTIVES: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors. DESIGN: Retrospective analysis. PARTICIPANTS: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases). MAIN OUTCOME MEASURES: Perioperative complications and risk factor associated with their incidence. RESULTS: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported. CONCLUSIONS: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.

DOI： 10.1055/s-0028-1096201

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

BACKGROUND: The current study aimed to evaluate the significance of an immunohistochemical assessment of tumor suppressor p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) patients treated with docetaxel and radiotherapy. METHODS: The expression of tumor suppressor p53 and its phosphorylated form at the Ser392 residue was retrospectively evaluated by immunohistochemistry in 51 Stage T1-3N0-2M0 (except T1N0 glottis) HNSCC patients who were treated with 10mg/m(2)/week docetaxel four to six times and received concurrent chemoradiotherapy. RESULTS: Kaplan-Meier univariate analysis revealed that no difference in rates for overall and disease-free survival (DFS) between patients with p53-positive and -negative tumors (p=0.786 and p=0.924, respectively). The prognostic significance of phosphorylated p53 at the Ser392 residue was neither observed. CONCLUSIONS: An immunohistochemical assessment of the expression of p53 and its phosphorylated form might not be of clinical use in defining subgroups of patients with poor prognosis.

DOI： 10.1016/j.anl.2008.02.002