Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The AJCC cutoff value of 2 mm for the extranodal extension (ENE) distance was determined from an analysis of patients with or without adjuvant therapy. The purpose of this study was to find out the ENE distance that reflects prognosis only in patients with head and neck squamous cell carcinoma (SCC) who received adjuvant therapy. METHODS: The ENE distance was defined for 109 patients who underwent surgery for SCC of larynx or hypopharynx as a primary tumor. RESULTS: To standardize patient conditions, only 26 patients who received additional postoperative treatment were analyzed. Receiver operating characteristic analysis of the ENE distance for overall survival (OS) and recurrence-free survival (RFS) yielded a cutoff value of 4250 μm. Multivariate analysis showed that the ENE distance was an independent poor prognostic factor for OS and RFS. CONCLUSION: The optimal ENE distance cutoff for OS and RFS in postoperatively treated patients was 4250 μm.

DOI： 10.1002/hed.28090

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The prognosis for T2N0 glottic squamous cell carcinoma (SCC) is generally favorable, with a 5-year overall survival rate of 79%-96% achieved with radiotherapy (RT), the standard nonsurgical treatment for this condition. However, the local control rate for T2N0 glottic SCC treated with RT remains suboptimal, with a 5-year local control rate of only 65%-80%. Local residual disease or recurrence following RT for T2N0 glottic SCC often leads to difficulties in laryngeal preservation. When total laryngectomy is performed as a salvage surgery in such cases, patients lose their physiological ability to speak. Therefore, improving local control and laryngeal preservation rates through RT could substantially improve the quality of life of these patients. Attempts have been made to combine cytotoxic anticancer agents with RT to achieve better local control in patients with T2N0 glottic SCC. In Japan, several studies have evaluated the effects of combining S-1, an oral fluorinated pyrimidine, with RT in these patients. This review highlights the importance of adding chemotherapy to RT in the treatment of patients with T2N0 glottic SCC.

DOI： 10.1093/jjco/hyaf014

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BACKGROUND: The safety and efficacy of endoscopic sinus surgery have improved with the development of new equipment and improved surgical techniques. However, it is accompanied by the risk of complications. Intraoperative blood loss is an important factor in the safe conduct of surgery. Therefore, we examined the factors associated with intraoperative blood loss. METHOD: The amount of intraoperative bleeding experienced by 518 patients with sinonasal disease who underwent endoscopic sinus surgery under general anaesthesia at our hospital over nine years was tabulated. Thirty-four variables were extracted after analysis of patients' background, sinonasal pathology, and haematology results. Multivariate linear regression analysis was performed. RESULTS: Multivariate analysis revealed significant differences in the prothrombin time-international normalized ratio (PT-INR), Lund-Mackay score, operative time, and initial versus repeat surgery. The degree of change between the 25% and 75% points was significant for the following variables: an increase from 5 to 14 points for the Lund-Mackay score at 73 mL. CONCLUSIONS: Preoperative precautionary measures should be implemented in the event of re-operation, expected prolonged operative time, high Lund-Mackay score, and prolonged PT-INR. Intraoperative blood loss in patients with a high Lund-Mackay score requires meticulous attention.

DOI： 10.7759/cureus.76286

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BACKGROUND: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. METHODS: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. RESULTS: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. CONCLUSION: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. CLINICAL TRIAL REGISTRATION: NCT02358031.

DOI： 10.1007/s10147-024-02632-x

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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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Language：Japanese   Publisher：(一社)日本耳科学会  

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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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Language：Japanese   Publisher：(一社)日本耳科学会  

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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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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： 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

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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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Language：Japanese   Publisher：(株)医学書院  

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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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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： 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

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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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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：東京医学社  

DOI： 10.24479/ohns.0000000968

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Other Link： 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

Language：Japanese   Publisher：(公社)神奈川県医師会  

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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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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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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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Language：Japanese   Publisher：(株)全日本病院出版会  

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Language：Japanese   Publisher：東京医学社  

DOI： 10.24479/ohns.0000000836

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Language：Japanese   Publisher：(一社)日本耳科学会  

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Language：Japanese   Publisher：(一社)日本耳科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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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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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Other Link： 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

Language：Japanese   Publisher：(公社)神奈川県医師会  

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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

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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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DOI： 10.21037/tcr-23-48

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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

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：日本外科系連合学会  

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Language：Japanese   Publisher：日本外科系連合学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：日本臨床ウイルス学会  

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Language：Japanese   Publisher：耳鼻と臨床会  

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： 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

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： 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

Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：English   Publishing type：Research paper (scientific journal)  

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

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Language：English   Publishing type：Research paper (scientific journal)  

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Research Square Platform LLC  

Abstract

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

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Other Link： https://www.researchsquare.com/article/rs-1621957/v1.html

Language：Japanese   Publisher：日本喉頭科学会  

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Other Link： 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

Language：English   Publishing type：Research paper (scientific journal)  

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

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Language：Japanese   Publisher：日本喉頭科学会  

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Language：Japanese   Publisher：日本唾液腺学会  

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Language：Japanese   Publisher：日本唾液腺学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：English   Publishing type：Research paper (scientific journal)  

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

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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

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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

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Other Link： 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

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Other Link： 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

Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(NPO)日本気管食道科学会  

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Other Link： 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

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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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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

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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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Language：Japanese   Publisher：(公社)神奈川県医師会  

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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

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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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Language：English   Publisher：(一社)日本癌治療学会  

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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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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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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

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： 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

Language：Japanese   Publisher：(株)癌と化学療法社  

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Other Link： 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

Language：Japanese   Publishing type：Research paper (scientific journal)  

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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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Language：Japanese   Publisher：(株)医学書院  

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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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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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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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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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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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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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：日本癌学会  

DOI： 10.1002/ijc.33315

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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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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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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.114.515

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.114.127

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

DOI： 10.3950/JIBIINKOKA.124.225

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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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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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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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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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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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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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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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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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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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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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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.123.371

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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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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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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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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.113.265

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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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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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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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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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DOI： 10.1016/S0140-6736(19)32591-7

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DOI： 10.1016/j.anl.2019.05.004

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Language：English   Publisher：(一社)日本癌学会  

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Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan, Inc.  

DOI： 10.3950/jibiinkoka.123.251

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Head and Neck Cancer  

DOI： 10.5981/jjhnc.45.366

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DOI： 10.1093/ANNONC/MDZ252.028

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.112.425

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DOI： 10.21037/TCR.2019.04.02

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DOI： 10.1093/ANNONC/MDZ428

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DOI： 10.3950/jibiinkoka.122.1304

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.112.833

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/JIBIINKOKA.122.757

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10..3950/jibiinkoka.122.1229

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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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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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Language：Japanese   Publisher：(一社)日本耳科学会  

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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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DOI： 10.21037/tcr.2018.06.15

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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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DOI： 10.18869/ACADPUB.IJRR.16.2.257

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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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DOI： 10.21037/tcr.2018.03.38

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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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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.121.1389

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.121.215

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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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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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DOI： 10.1080/23772484.2017.1376587

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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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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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DOI： 10.1007/s00405-017-4463-5

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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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DOI： 10.1002/lary.26233

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DOI： 10.3950/jibiinkoka.120.1079

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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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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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DOI： 10.1007/s10147-016-0964-2

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DOI： 10.1007/s10147-016-1005-x

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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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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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DOI： 10.1158/1538-7445.AM2016-4054

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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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DOI： 10.1016/j.anl.2015.10.009

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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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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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DOI： 10.1038/jhg.2015.143

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.119.187

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DOI： 10.1136/bcr-2015-213747

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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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.67.85

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirinsuppl.145.110

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DOI： 10.5631/jibirinsuppl.145.8

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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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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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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.118.867

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DOI： 10.1016/j.anl.2015.02.014

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DOI： 10.1177/0003489415575041

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Language：English   Publisher：(一社)日本頭頸部癌学会  

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DOI： 10.1016/j.jvoice.2014.08.012

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DOI： 10.1016/j.anl.2014.09.003

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Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm arising from follicular dendritic cells, which are antigen-presenting cells in the lymphoid follicules. An 80-year-old man visited a dental clinic, and an asymptomatic tonsillar tumor was incidentally discovered. A histological examination of the biopsy specimen raised the suspicion of a low or intermediate malignancy. A transoral lateral pharyngotomy was performed for the purpose of total resection of the tumor. The intraoperative frozen pathological diagnosis was squamous cell carcinoma. However the final diagnosis was FDCS based on the immunohistochemical examination of permanent sections. Histologically, a high mitotic count was observed (≧5/10HPF), which is considered as a poor prognostic factor for FDCS. Considering the patient's age and general status, postoperative adjuvant therapy was not applied. He remains disease-free for more than a year and two months after surgery.

DOI： 10.14821/stomatopharyngology.28.187

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DOI： 10.1159/000381026

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DOI： 10.3950/jibiinkoka.118.395

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DOI： 10.1371/journal.pone.0117924

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DOI： 10.1093/jjco/hyu154

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DOI： 10.1016/j.anl.2014.05.001

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DOI： 10.1016/j.anl.2014.02.007

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DOI： 10.3950/jibiinkoka.117.899

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DOI： 10.1007/s00280-014-2448-2

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DOI： 10.3950/jibiinkoka.117.802

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DOI： 10.1093/jjco/hyu026

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DOI： 10.1007/S13691-013-0106-X

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Language：English   Publisher：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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Language：English   Publisher：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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DOI： 10.1371/journal.pone.0114121

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DOI： 10.1007/s10147-012-0469-6

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.116.1126

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DOI： 10.1007/s00280-013-2261-3

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DOI： 10.3109/00016489.2013.795287

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DOI： 10.1016/j.anl.2012.07.002

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Language：English   Publisher：Springer  

DOI： 10.1007/s13691-012-0044-z

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DOI： 10.3109/00016489.2012.680494

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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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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DOI： 10.1152/ajpgi.00462.2011

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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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DOI： 10.1177/0194599811424044

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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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DOI： 10.1097/ICU.0b013e32834bdfe2

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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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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DOI： 10.1016/j.oraloncology.2011.04.015

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DOI： 10.1097/RLU.0b013e3182177284

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DOI： 10.1177/0194599811398786

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Language：Japanese   Publisher：(NPO)日本気管食道科学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.114.126

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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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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.

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DOI： 10.1007/s00405-011-1814-5

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DOI： 10.1248/bpb.34.704

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DOI： 10.4193/Rhino10.015

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DOI： 10.1007/s00405-010-1274-3

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Language：Japanese   Publisher：日本口腔・咽頭科学会  

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DOI： 10.1002/hed.21158

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DOI： 10.1210/en.2009-0633

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.113.9

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Language：English  

DOI： 10.1055/s-0030-1255520

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/cncr.24515

Web of Science

PubMed

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English  

DOI： 10.1055/s-0029-1214647

Web of Science

PubMed

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(NPO)日本気管食道科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/s-0029-1214488

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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

Web of Science

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/s-0028-1096201