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

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INTRODUCTION: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors may lead to discontinuation and treatment-related death. Acute aortitis is a rare but severe irAE. CASE PRESENTATION: A 67-year-old man with recurrent lower gingival carcinoma received nivolumab therapy. Twenty-three months later, he experienced chest compression, which resulted in syncope. Following a whole-body computed tomography (CT) scanning, which revealed diffuse thickening of the aorta, and systemic assessments of the causes of aortitis, he was diagnosed with acute aortitis due to irAE. Nivolumab discontinuation and oral steroids improved CT findings. However, 11 months after nivolumab discontinuation, he developed an aortic aneurysmal rupture. Endovascular aortic repair rescued him. A durable anti-cancer response was still observed 4 months after the aortic rupture. CONCLUSION: Although severe irAE, such as acute aortitis, occurred, the patient may still achieve a durable response. A broad examination and prompt treatment of irAE can help improve the patient's survival.

DOI： 10.1007/s00405-024-08495-2

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BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.

DOI： 10.1007/s10147-023-02423-w

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The sarcopenia index (SI), calculated as [(serum creatinine/serum cystatin C) × 100], maybe a simpler alternative for measuring muscle mass than computed tomography (CT) and bioelectrical impedance analysis (BIA). We enrolled 112 patients with head and neck cancers (HNC). The correlation of the SI with muscle surface area measured by CT (CTMSA, n = 82) and muscle mass by BIA (BIA-MM, n = 41) was tested. Cutoff values were set for SI, CTMSA, and BIA-MM. Overall survival (OS) was compared between the high- and low-SI/CTMSA/BIA-MM groups. The SI was correlated with CTMSA (r = 0.43) and BIA-MM (r = 0.52). The optimal cutoff values of SI, CTMSA, and BIA-MM were 76.1 (area under the curve [AUC] = 0.67), 129.2 (AUC = 0.59), and 46.1 (AUC = 0.62), respectively. OS was significantly lower in the low-SI group (78% at 1 year and 69% at 2 years) than in the high-SI group (94% at 1 year and 86% at 2 years; p = 0.006). There was no significant difference in OS between the low-and high-CTMSA and -BIA-MM groups. The SI, which only requires a blood sample, is a useful marker of muscle mass that correlates with short-term prognosis in patients with HNC.

DOI： 10.1080/01635581.2023.2290299

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Background: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen. Methods: We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75 years and those with an estimated glomerular filtration rate (eGFR) < 60 mL/min were classified as ineligible for cisplatin. Results: The median age was 70 (27–81) years. The median eGFR at treatment initiation was 63.2 (41.1–89.7) mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed. Conclusion: NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy.

DOI： 10.1007/s10147-024-02545-9

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.oor.2023.100107

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INTRODUCTION: Immune-related adverse events (irAEs) are prognostic factors for patients on nivolumab. However, predictors of irAEs have not yet been identified. We aimed to investigate the predictors of irAEs occurrence and nivolumab discontinuation due to irAEs. METHODS: Sixty-two patients with recurrent/metastatic head and neck squamous cell carcinoma received nivolumab therapy between June 2017 and December 2020. Treatment outcome was compared between the groups with or without irAEs. The irAE (+) group was further divided by nivolumab discontinuation. Progression-free survival (PFS) and overall survival (OS) were compared between the groups. Predictors of irAE occurrence were analyzed. RESULTS: Twenty-one patients (33.9%) developed irAEs, and six (28.6%) discontinued nivolumab due to severe irAEs. The irAE (+) group had significantly longer PFS and OS than the irAE (-) group (median PFS, 12.7 vs. 1.9 months; median OS, 33.1 vs. 12.8 months). The treatment outcomes in the discontinuation group were comparable to those in the non-discontinuation group. The maximum absolute eosinophil count (AEC) during nivolumab therapy was significantly higher in the irAE (+) group than in the irAE (-) group (548.8 vs. 182) and higher in the discontinuation group than in the non-discontinuation group (729.3 vs. 368.6). The receiver operating characteristic curve showed that the maximum AEC had a moderate-to-high accuracy for predicting irAE occurrence (area under the curve [AUC], 0.757) and nivolumab discontinuation (AUC, 0.893). DISCUSSION: Monitoring AEC during nivolumab therapy may be useful in predicting irAE occurrence, nivolumab discontinuation, and disease prognosis.

DOI： 10.1002/cam4.6648

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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：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：English   Publisher：(一社)日本癌治療学会  

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

OBJECTIVE: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treatment has changed dramatically with the introduction of immune checkpoint inhibitors (ICIs). However, there are few reports of treatment outcomes on HNSCC with distant metastasis (M1) at initial diagnosis, and its treatment strategy has not been standardized. We aimed to analyze the treatment outcome and prognostic factors of patients with HNSCC with initial M1 disease. METHODS: In this multi-institutional retrospective study, 98 patients with HNSCC were initially diagnosed with M1 disease between 2007 and 2021. The patients were divided into the non-palliative (received any systemic chemotherapy, n = 60) and palliative (did not receive systemic chemotherapy, n = 38) groups. Overall survival (OS) was compared between the groups. In the non-palliative group, predictors of OS were explored based on patient characteristics and treatment details. RESULTS: The median OS in the non-palliative group was 15 months (95% confidence interval [CI], 10-20), which was significantly longer than that in the palliative group (3 months, 95% CI, 2-5) (p < 0.001). Multivariate analysis revealed that administration of locoregional radiation therapy (RT) (hazard ratio [HR] 0.407 [95% CI 0.197-0.844]; p = 0.016), ICIs (HR 0.216 [95% CI 0.088-0.532]; p < 0.001) and RT/surgery for distant metastasis (HR 0.373 [95% CI 0.150-0.932]; p = 0.034) were the independent prognostic factors of OS. CONCLUSION: An intensive treatment strategy combining systemic therapy using ICIs with RT/surgery for locoregional or distant metastasis may yield a survival benefit for patients with HNSCC with M1 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.

DOI： 10.1002/lary.31047

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BACKGROUND: During oral and head and neck surgery, oral vestibular incisions may require a transverse incision on the upper lip mucosa, resulting in possible sensory disturbances in the area innervated by infraorbital nerve (ION) branches. Although sensory disturbances are attributed to nerve injuries, anatomy textbooks have not showed the precise distribution patterns of the ION branches in the upper lip. Furthermore, no detailed study has been available on this issue. This study aimed to reveal the precise distribution patterns of ION branches in the upper lip by dissecting the detached upper lip and cheek area using a stereomicroscope. METHODS: During a gross anatomy course at Niigata University (2021-2022), nine human cadavers were examined with special focus on the relationship between ION branches in the upper lip and the layered structure of facial muscles. RESULTS: The ION branched to the inferior palpebral (IP), external and internal nasal, and superior labial (lateral and medial) nerves. The ION branches in the upper lip did not run in a horizontal pattern from outside to inside but showed a predominantly vertical pattern. Considering their course, incising the upper lip mucosa transversely may cause paresthesia of the ION branches. The internal nasal (IN) and medial superior labial (SLm) branches tended to penetrate the orbicularis oris and descend between this muscle and labial glands, whereas the lateral superior labial (SLl) branches tended to innervate the skin. CONCLUSIONS: These findings suggest that a lateral mucosal incision is recommended for oral vestibular incisions of the upper lip and that deeper incisions to the labial glands should be avoided when incising the medial side to preserve the ION during surgery from an anatomical point of view.

DOI： 10.1016/j.aanat.2023.152118

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Language：English   Publishing type：Research paper (international conference proceedings)  

DOI： 10.1007/s00520-023-07786-4

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Ectopic parathyroid lesions can be difficult to detect. In the present study, we used near-infrared autofluorescence imaging (NIFI) in three cases of ectopic parathyroid lesions. Our results suggest that NIFI may be a confirmation tool for parathyroid pathology and an intraoperative navigation tool in vivo and ex vivo. Laryngoscope, 2023.

DOI： 10.1002/lary.30728

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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：日本脳腫瘍病理学会  

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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：日本脳腫瘍病理学会  

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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：(一社)日本耳鼻咽喉科頭頸部外科学会  

新潟県では,1986年より新潟県頭頸部悪性腫瘍登録委員会が新規症例の腫瘍登録を開始した.このたび本研究では,頭頸部悪性腫瘍発生の経時変化を見ることを目的とし,1986～2018年までの登録症例において年毎の頭頸部悪性腫瘍総数,原発部位別数,粗罹患率を分析し,さらにT分類別でT2以上症例に対するT1以下症例の比率(T1以下/T2以上)を指標として検討した.総数は12,443例で,男性8,619例(69.3%),女性3,824例(30.7%)だった.登録初年度と比べ2018年の年次毎症例数は3.7倍(599例/160例)に増加し,年平均増加率は4.2%で,粗罹患率は4.3倍(26.7/6.2)に増加していた.年齢中央値は4歳(64歳→68歳)上昇しており,高齢化が粗罹患率上昇の要因と考えられた.「T1以下/T2以上」は頭頸部悪性腫瘍全部位では,1986～1996年,1997～2007年,2008～2018年の3年代の間で差はなかったが,下咽頭癌では2008～2018年で,ほかの2年代と比較し有意に上昇していた.すなわち,頭頸部悪性腫瘍全体では30年経過しても早期診断に至っていなかったが,内視鏡などが診断に寄与できる下咽頭では早期発見が可能になってきたことが示唆された.この結果から,頭頸部癌の早期発見のためには,癌検診,特に下咽頭を対象とした検診が有用である可能性が示唆された.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07551&link_issn=&doc_id=20230201440008&doc_link_id=%2Fdz0tokei%2F2023%2F012601%2F009%2F0038-0045%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0tokei%2F2023%2F012601%2F009%2F0038-0045%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73-13.1, p = 7.8 × 10-6). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies.

DOI： 10.1038/s41698-022-00324-1

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PURPOSE: Persistent hypoparathyroidism (hypoPT) is a major complication of total thyroidectomy. Nonetheless, previous reports may have underestimated the prevalence of hypoPT due to patient selection bias. We aimed to estimate the actual prevalence of persistent hypoPT after total thyroidectomy and to find predictive factors for postoperative hypoPT. METHODS: This study retrospectively reviewed data from a health insurance claims-based database provided by the Japan Medical Data Center Co., Ltd. From 2009 to 2019, 2388 patients who underwent total thyroidectomy were identified using the medical procedure codes. Persistent hypoPT was defined as the prescription of active vitamin D supplements for >1 year postoperatively and the assignment of hypoPT codes. The prevalence of persistent hypoPT was estimated at two different levels: minimum and maximum estimations with or without postoperative osteoporosis and/or renal failure codes. Correlates for persistent hypoPT were investigated among several demographic and clinical variables. RESULTS: Of the 2388 patients, 1752 (73.4%) were women with a mean age of 45 years. The types of diseases were: benign thyroid disease (n = 235), malignant thyroid tumors (n = 1570), Graves ' disease (n = 558), and malignancy combined with Graves' disease (n = 25). The minimum and the maximum estimation of the prevalence of persistent hypoPT were 15.0 and 20.3%, respectively. Multivariate logistic regression analysis showed that the malignant tumor (odds ratio, 1.8) independently correlated with persistent hypoPT. CONCLUSIONS: The prevalence of persistent hypoPT after total thyroidectomy estimated by the claims-based database was higher than previously recognized. Comprehensive attempts to preserve parathyroid function, especially in malignant diseases, are essential.

DOI： 10.1007/s12020-022-03153-1

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OBJECTIVE: The management for malodour of malignant fungating wounds (MFWs) in head and neck cancer (HNC) is unestablished. We evaluated the effects of a novel odour transferrer on malodour generated by MFWs in patients with HNC. METHODS: A spray-type odour transferrer approved by the Japanese government for safe use in humans produces a good scent by binding to bad odour. The odour of MFWs in 13 patients with HNC was scored by 37 medical staff and the patients' families using an odour scale ranging from 0 to 4 before and 1 week after application of the odour transferrer. RESULTS: The odour score marked by all investigators (n=37), nurses (n=21) and doctors (n=11) decreased significantly (p<0.01). The odour score decreased by more than 2 points for 73% of all investigators after odour transferrer application. CONCLUSION: This novel odour transferrer functions as an effective deodorant for MFWs in patients with HNC. It can be used by non-medical staff and may benefit patients with bad odours arising from MFWs as well as their families and medical staff.

DOI： 10.1136/spcare-2022-003824

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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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Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

DOI： 10.1177/17588359221119538

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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: Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM. METHODS: Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated. RESULTS: The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period. CONCLUSIONS: ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

DOI： 10.3389/fsurg.2022.1032626

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OBJECTIVE: The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2. METHODS: A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated. RESULTS: The median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia. CONCLUSION: The survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia.

DOI： 10.3389/fsurg.2022.1035349

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DOI： 10.1136/bcr-2021-246906

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OBJECTIVES: To examine the role of autofluorescence (AF) monitoring with near-infrared fluorescence imaging (NIFI) in identifying parathyroid lesions in primary or secondary hyperparathyroidism (P-HPT or S-HPT) surgeries. STUDY DESIGN: Prospective study. METHODS: Twelve lesions each were resected from 12 and 3 patients with P-HPT and S-HPT, respectively. The mean and maximum AF intensities of the lesions normalized to that of the thyroid tissue for in situ and ex vivo preparations were compared between P-HPT and S-HPT. Subjective visual classifications of AF intensity were compared with postoperative quantitative assessments. The unevenness of AF distribution inside the lesions was assessed by determining the ratio of maximum to mean AF intensity and comparing them with the corresponding ratio for normal parathyroid glands (PGs). RESULTS: In all quantitative comparisons (in situ/ex vivo, mean, and maximum AF), AF intensities of P-HPT were stronger than those of S-PHT. The AF-positive rate in in situ subjective visual classification was higher for P-HPT (100% vs. 33%). Subjective visual classifications showed a positive correlation with AF intensities. The ratio of maximum to mean AF was higher in P-HPT and S-HPT than in normal PGs. CONCLUSIONS: For P-HPT, AF intensity in both in situ and ex vivo preparations was sufficiently high and correlated with the subjective visual classification, suggesting that NIFI may be useful for confirming P-HPT lesions. In contrast, NIFI may have only a minor role in S-HPT surgeries owing to the weak-AF of S-HPT lesions. HPT lesions show an uneven AF intensity distribution compared with normal PGs. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2097-E2104, 2021.

DOI： 10.1002/lary.29310

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

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DOI： 10.1002/lary.29425

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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)日本耳鼻咽喉科学会  

末梢挿入型中心静脈カテーテル(peripherally inserted central catheter、PICC)は安全性が高く頭頸部癌の薬物療法でも用いられるが、留置側の左右差に着目した報告は少ない。PICC留置後の先端位置移動と合併症発生率の左右差について検討した。PICC留置を行った頭頸部癌145例172件を対象とし後方視的な調査を行った。留置側は右36件、左136件で、留置期間中央値は65日であった。121例137件でX線による留置時・留置後の先端位置評価が可能であった。先端位置をZone A:上大静脈下半分と右心房上部、Zone B:上大静脈上半分と左腕頭静脈合流部、Zone C:左腕頭静脈に分類し、Zone A・Bを適正位置とした。右側では留置時33件(100%)、留置後30件(91%)が適正位置であったのに対し、左側では留置時97件(93%)、留置後82件(79%)が適正位置で、留置時と留置後では有意な変化を認めた(p=0.001)。そのほかの合併症発生率に左右差は認めなかった。左側からのPICC留置では上大静脈右側壁にカテーテル先端が当たり、Zone Aへの留置率が低い。さらに留置後の体位・肢位の変化により先端が移動し、適正位置であるZone A・Bに留まりにくい。不適正な先端位置は遅発性の上大静脈壁損傷や血栓症を招くため、右側からのPICC留置が望ましいと考えられた。(著者抄録)

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Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

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We examined the role of lateral temporal bone resection (LTBR) in the treatment of external ear canal (EAC) carcinoma between 2007 and 2018. The estimated 3-year disease-free survival (DFS) and disease-specific survival (DSS) according to the tumor stage and treatments were investigated in 36 patients with EAC squamous cell carcinoma. T stage classification according to the University of Pittsburgh staging system was as follows: 14 patients in T1, four patients in T2, nine patients in T3, and nine patients in T4. The 3-year DFS rate was 77.4% for T1 tumors, 100% for T2, 44.4% for T3 tumors, and 11.1% for T4 tumors (p < 001). The 3-year DSS rate was 100% for T1/T2 tumors, 87.5% for T3 tumors, and 11.1% for T4 tumors (p < 0.01). T1/T2 patients received mostly LTBR. Among nine T3 tumors, five patients (56%) received LTBR combined with preoperative chemotherapy and/or postoperative radiation (RT). Four of them had negative surgical margin and survived with no evidence of disease. The DFS of T3 patients who underwent concurrent chemoradiotherapy and LTBR was 0 and 80%, respectively (p = 0.048). For T1/T2 tumors, surgery achieved an excellent outcome. For T3 tumors, LTBR achieved negative surgical margin and showed good survival when combined with preoperative chemotherapy and/or postoperative RT. In contrast, the prognosis of T3 patients who could not undergo surgery was as poor as that of T4 patients. Therefore, in addition to subtotal temporal bone resection, LTBR-based treatment strategy may be a treatment option for limited cases of T3 patients.

DOI： 10.3389/fsurg.2021.708245

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BACKGROUND: Early detection of head and neck carcinoma (HNC) as superficial HNC (SHNC) identified using recently developed optical techniques, such as magnifying endoscopy and narrow-band imaging (NBI), in combination with endoscopic surgeries enables minimally invasive treatment with favorable outcomes for HNC. This study aimed to identify the predictive factors for the rare but important clinical issue of SHNC, namely cervical lymph node metastasis (CLNM), following endoscopic resection. METHODS: Sixty-nine patients with SHNC who underwent endoscopic resection were enrolled in the study. Clinical data, preoperative endoscopic findings, pathological findings, and treatment outcomes were retrospectively reviewed. Because the pharyngeal mucosa lacks the muscularis mucosa, we measured tumor thickness in permanent pathology as an alternative to the depth of invasion. Correlations with the occurrence of CLNM were statistically examined. RESULTS: The 5-year disease-specific survival rate was 100%. Of 69 patients, 3 (4.3%) developed CLNM. All had subepithelial but not epithelial tumors. The 0-IIa type in the macroscopic findings, type B2/B3 vessels in narrow-band imaging, tumors ≥ pathological stage T2, lymphatic invasion, positive surgical margins, and tumor thickness >1,000 μm showed significant correlations with CLNM following endoscopic resection. Furthermore, the classification of type B vessels was significantly associated with tumor thickness. CONCLUSION: The treatment outcomes following endoscopic resection for SHNC were favorable. The risk of CLNM following endoscopic resection in SHNC can be predicted by several preoperative endoscopic and postoperative pathological findings. Among them, the classification of type B vessels, which correlated with both tumor thickness and CLNM, might be a useful predictive factor.

DOI： 10.3389/fsurg.2021.813260

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OBJECTIVE: Salivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy. MATERIALS AND METHODS: The EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases). RESULTS: EZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups. CONCLUSIONS: A high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

DOI： 10.3389/fonc.2021.779882

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Objective: We aimed to compare the outcomes and safety of chemoradiotherapy (CRT) between elderly and non-elderly patients with head and neck squamous cell carcinoma (HNSCC). It is difficult to assess the causal effect of age because of possible differences in general conditions among individuals. Therefore, we adjusted the background factors of elderly and non-elderly patients using propensity score matching (PSM). Methods: A total of 146 patients with HNSCC who received CRT were divided into an elderly (≥70 years, n = 35) and non-elderly group (<70 years, n = 111). Pre-treatment characteristics, including the performance status, Charlson comorbidity index, body mass index, primary site, and TNM stage were adjusted by PSM. We compared the outcomes and safety of CRT with high-dose single-agent cisplatin (CDDP) as well as outcomes following recurrence between the groups, before and after PSM. Results: The total dose of CDDP administered during CRT was significantly lower in the elderly group before PSM. However, it became comparable to the non-elderly group and adverse events did not differ between the groups following PSM, resulting in a comparable CRT completion rate. Overall-, disease specific-, and progression-free survivals of elderly patients were comparable to those of non-elderly patients following PSM. In contrast, elderly patients with recurrence could receive fewer salvage treatments than their non-elderly counterparts, resulting in worse survival. Conclusions: CRT with high-dose CDDP is safe and effective for the treatment of elderly patients with HNSCC. However, salvage treatments can be rarely conducted for elderly patients with a recurrence, considering a deterioration of their general condition.

DOI： 10.3389/fsurg.2021.753049

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OBJECTIVES/HYPOTHESIS: To assess the ability of near-infrared fluorescence imaging (NIFI) to identify parathyroid glands (PGs) among histologically proven PG/non-PG specimens compared with a surgeon's visual acumen, and to determine NIFI sensitivity in detecting incidentally resected PGs from thyroidectomy specimens, compared to the surgeon's visual inspection. STUDY DESIGN: Prospective study. METHODS: With mean age of 61 years, 36 patients with various thyroid diseases were enrolled. Possible PGs (n = 28) and lymph nodes (n = 32) were identified by the experienced surgeon's visual inspection. Using NIFI, 15 PGs were further identified from thyroidectomy specimens. For these 75 specimens, the surgeon's judgments (PG vs. non-PG) were recorded. Histological evaluation was performed after examining the NIFI auto-fluorescence of each specimen. RESULTS: There were no significant differences in sensitivity, specificity, positive predictive value, and negative predictive value between the surgeon's visual inspection and NIFI in identifying PGs, with values of 100%/97.1%, 85.0%/87.5%, 85.4%/87.2%, and 100%/97.2%, respectively. The sensitivity of NIFI (82.9%) for detection of PGs from thyroidectomy specimens was significantly higher than that of the surgeon's visual inspection (61.0%). False negative specimens contained bleeding/congestion and/or encapsulation by thick tissues, whereas false positive specimens contained electrocoagulated tissues. CONCLUSIONS: NIFI showed results comparable to the experienced surgeon's visual inspection in identifying PGs. This could benefit novice surgeons. NIFI may be useful for experienced surgeons to locate incidentally resected PGs within thyroidectomy specimens for auto-transplantation. Prevention of intra-gland bleeding and congestion, careful removal of thick capsules, and bloodless surgeries without electrocoagulation are important for reducing false positive and false negative results. Laryngoscope, 2020.

DOI： 10.1002/lary.29163

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Endoscopic submucosal dissection (ESD) has gained wide acceptance as a minimally invasive and curative surgery for superficial head and neck carcinoma. However, the safety of ESD for superficial pharyngeal carcinoma after radiotherapy has not been elucidated. Superficial hypopharyngeal carcinoma of the left pyriform sinus developed in a 76-year-old man who had undergone concurrent chemoradiotherapy for T2N2bM0 pyriform sinus carcinoma on the opposite side 12 months before. He underwent ESD without complications. Because tumor invasion into the muscular layer was a concern, the muscular layer was partially resected with the tumor. Twelve days after discharge, he presented with a sore throat and difficulty in swallowing. Endoscopy and computed tomography revealed necrosis due to wound infection with abscess formation around the left carotid artery. The common carotid artery subsequently ruptured. Although the surgical intervention was performed, he passed away 46 days after ESD due to carotid blowout. ESD is a minimally invasive treatment for superficial head and neck carcinoma, but carotid blowout can occur in cases after radiation. Prior radiotherapy and deeper dissection into the muscular layer may hamper wound epithelization, resulting in infection-induced necrosis and carotid blowout. Diligent monitoring of wound healing is essential in patients who have previously undergone irradiation.

DOI： 10.1016/j.anl.2020.08.020

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PURPOSE: Sarcopenia, defined as a decrease in the skeletal muscle mass and its function, is associated with a poor clinical outcome in several malignancies. We aimed to examine whether sarcopenia can be a predictor of incompletion of concurrent chemoradiotherapy (CCRT) and survival for head and neck cancer (HNC) patients. METHODS: Forty-one male HNC patients who received CCRT were enrolled in the study. Cross-sectional muscle areas at the third lumbar vertebral level were normalized by the squared height of the patients and were termed the lumbar skeletal muscle index (LSMI, cm2/m2), a marker of sarcopenia. Patients were divided into high (30/41, 73%) and low (11/41, 27%) LSMI groups. The LSMI cut-off value was set at 39.7 cm2/m2 based on a receiver operating characteristic curve for incompletion of CCRT. The groups were compared for survival rate by the Kaplan-Meier method. Factors predicting incompletion of CCRT were investigated among several variables. RESULTS: Multivariate analysis showed that a pre-treatment low LSMI (P = 0.033) and age over 70 years (P = 0.023) were the only significant predictors for incompletion of CCRT. The 2-year disease-specific survival (DSS) rate was significantly lower in the low LSMI group (61%) than in the high LSMI group (97%, P = 0.012), whereas there were no differences in the DSS rate between the low and high body mass index groups. CONCLUSION: The prevalence of sarcopenia in HNC patients receiving CCRT was 27%. Its presence before treatment was a significant predictor of incomplete CCRT and poor DSS rate in HNC patients.

DOI： 10.1007/s00405-020-06273-4

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PURPOSE: The importance of nivolumab for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rapidly increasing. However, prognostic factors have not been determined for predicting treatment outcome. We aimed to investigate the prognostic factors in R/M HNSCC patients treated with nivolumab. METHODS: This retrospective study included 42 patients with R/M HNSCC who received nivolumab therapy. Correlations of overall survival (OS) with various patient characteristics including age, recurrent/metastatic site, performance status (PS), programmed death-ligand 1 positivity, body mass index, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score (mGPS), previous cetuximab administration, and immune-related adverse events were investigated. RESULTS: The overall response rate and disease control rate were 16.7% and 45.2%, respectively. Estimated 1-year OS and progression-free survival (PFS) were 56.4% and 24.5%, respectively. Multivariate analysis revealed that PS = 2 (hazard ratio 0.147; 95% CI 0.041-0.527; p = 0.003) and mGPS = 2 (hazard ratio 0.188; 95% CI, 0.057-0.620; p = 0.006) were independent predictors of poor OS. Given that the PS and mGPS were independent prognostic factors, we classified patients into three groups according to PS and mGPS: Group 1, both PS and mGPS were 0 or 1 (n = 30); Group 2, either PS or mGPS was 2 (n = 9); Group 3, both PS and mGPS were 2 (n = 3). The OS curves were significantly stratified among the three groups. CONCLUSION: The combination of PS and mGPS accurately predicted OS after nivolumab therapy. Preventive intervention to maintain general condition without simultaneously exceeding level 2 of PS and mGPS might be important for improving treatment outcomes of nivolumab.

DOI： 10.1007/s00405-020-05945-5

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BACKGROUND: It was reported that treatment outcomes of the salvage chemotherapy (SCT) following nivolumab are fairly good compared with those of nivolumab itself. However, predictive factors of SCT for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) were not determined. METHODS: Twenty-one R/M HNSCC patients received SCT following nivolumab. The treatment outcome and predictive factors for the favorable response to SCT were investigated. RESULTS: The objective response rate (ORR) and the disease control rate of SCT were 52.4% and 81.0%, respectively. The median progression-free survival and the median overall survival time were 5.4 and 12.9 months, respectively. Patients with positive programmed death-ligand 1 (PD-L1) expression showed greater tumor shrinkage evaluated by the response evaluation criteria in solid tumors and higher ORR than those with negative PD-L1 expression. CONCLUSIONS: Treatment outcome of SCT following nivolumab in R/M HNSCC was favorable. PD-L1 expression may be a predictive factor of SCT.

DOI： 10.1002/hed.26374

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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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Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.

DOI： 10.1097/PAS.0000000000001413

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Language：Japanese   Publisher：(一社)日本内分泌外科学会  

症例は71歳女性で、血液検査にてPTH-intactが1246pg/mlと著明高値であったため当院代謝内分泌内科を紹介初診となった。頸胸腹部CT上、甲状腺左葉背側の腫瘍性病変と硬化性、溶骨性の混在した多発性骨病変が指摘され、副甲状腺癌および多発骨転移が疑われた。高カルシウム血症の補正目的にシナカルセトが開始されたが改善が得られず、手術目的に当科紹介となった。術前画像所見からは副甲状腺腫瘍と甲状腺左葉の境界が不明瞭であったことから、副甲状腺腫瘍摘出の際に甲状腺左葉も合併切除した。病理所見では線維性の被膜を有し、好酸性細胞がシート状に増殖する像を認めた。核異型は軽度であるものの、脈管侵襲を認めること、Ki-67 indexは10%でhot spotを認めることから副甲状腺癌の診断となった。骨病変に対する治療については、腰椎病変に対してのみ病的骨折予防目的に放射線治療を行い、臨床経過から副甲状腺癌にBrown tumorを合併したものと判断した。

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Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)-positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism-related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.

DOI： 10.1007/s00428-020-02777-w

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Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers.

DOI： 10.1016/j.isci.2020.100850

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

Background and purpose: Concurrent chemoradiotherapy (CCRT) for head and neck cancer (HNC) is a risk factor for oral candidiasis (OC). As Candida spp. are highly virulent, we conducted a retrospective study to determine whether OC increases the severity of dysphagia related to mucositis in HNC patients. Patients and methods: We retrospectively analyzed the cases of consecutive patients with carcinomas of the oral cavity, pharynx, and larynx who underwent CCRT containing cisplatin (CDDP) at our hospital. The diagnosis of OC was based on gross mucosal appearance. We performed a multivariate analysis to determine whether OC was associated with the development of grade 3 dysphagia in the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Criteria. The maximum of the daily opioid doses was compared between the patients with and without OC. Results: We identified 138 HNC patients. OC was observed in 51 patients (37%). By the time of their OC diagnosis, 19 (37%) had already developed grade 3 dysphagia. Among the 30 patients receiving antifungal therapy, 12 (40%) showed clinical deterioration. In the multivariate analysis, OC was independently associated with grade 3 dysphagia (OR 2.75; 95%CI 1.22-6.23; p = 0.015). The patients with OC required significantly higher morphine-equivalent doses of opioids (45 vs. 30 mg/day; p = 0.029). Conclusion: Candida infection causes refractory dysphagia. It is worth investigating whether antifungal prophylaxis reduces severe dysphagia related to candidiasis.

DOI： 10.1016/j.ctro.2019.10.006

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Language：Japanese   Publisher：日本唾液腺学会  

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再発転移頭頸部癌に対する外来化学療法の増加に伴い、安全な血管アクセスデバイス(VAD)が求められている。VADとしての末梢挿入型中心静脈カテーテル(PICC)27例と埋込型PICCである上腕ポート13例の安全性について比較した。両者に患者背景や治療内容に有意差を認めなかった。合併症発生数は上腕ポート群0例(0%、0/1,000カテーテル留置日)、PICC群8例(30%、1.8/1,000カテーテル留置日)で、上腕ポート群で有意に少なかった(p=0.037)。PICC群の合併症内訳はカテーテル閉塞4例、血栓症2例、カテーテル関連血流感染症1例、自己抜去1例であった。上腕ポートは安全なVADであり、頭頸部癌の外来化学療法において有用な選択肢と考えられた。(著者抄録)

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Language：Japanese   Publisher：(一社)日本内分泌外科学会  

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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)日本頭頸部癌学会  

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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)日本内分泌学会  

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Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

Nivolumab(Nivo)が再発・転移頭頸部癌の全生存期間を有意に延長することが報告され、本邦では2017年3月から保険収載となった。本研究では2017年6〜10月に当院でNivoを投与した再発・転移頭頸部癌10例の臨床像に関して検討した。年齢は44〜75歳で中央値62.5歳、PSは0が7例、2が3例、Cetuximab(Cetu)暴露例は8例であった。観察期間の中央値6ヵ月における効果判定はPR3例、SD2例、PD5例であり、PS不良例や急速進行例では治療効果不良、Cetu暴露の有無やPD-L1染色の陽性・陰性と治療効果の間には相関がなかった。有害事象は許容範囲内であった。CheckMate-141試験と比較すると本研究の方がPS0の患者の割合が多く、Nivo投与期間が長い傾向にあった。今後、Nivoの適応決定や投与のタイミングに関して検討する必要があると思われた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04210&link_issn=&doc_id=20190312410012&doc_link_id=10.5106%2Fjjshns.28.313&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.28.313&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

AIMS: Salivary duct carcinoma (SDC) is an uncommon, aggressive tumour that, histologically, resembles high-grade mammary ductal carcinoma, and is characterised by the expression of androgen receptor (AR). The androgen signalling pathway, a potential therapeutic target, can be regulated by FOXA1. This study aimed to evaluate the clinicopathological implications of FOXA1 in SDC. METHODS AND RESULTS: We examined the relationship between the immunoexpression of FOXA1 and FOXA1 mutations and clinicopathological factors, including the biomarker status and clinical outcome, in 142 SDCs. FOXA1 was expressed in 128 SDCs (90.1%); the immunoexpression was heterogeneous. SDCs with a higher FOXA1 labelling index (LI) (≥20%) more frequently showed less advanced tumors on T classification (P = 0.002). FOXA1 LI was correlated positively with the AR expression value (r = 0.430, P < 0.001). PI3K and p-mTOR positivity, and intact-PTEN, were associated with a higher FOXA1 LI. Twenty-two of 121 SDCs (18.2%) harboured FOXA1 gene mutations at the flanking regions in and around the forkhead DNA binding domain; however, the given gene mutation and the expression of FOXA1 were not significantly correlated. A multivariate analysis revealed that SDCs with a higher FOXA1 LI were associated with longer overall survival and progression-free survival (P = 0.029 and 0.016, respectively). CONCLUSIONS: In SDC, FOXA1, which may biologically interact with the AR and PI3K signalling pathways, is a putative biomarker that may be associated with a favourable prognosis. Further studies are needed to apply the findings to the development of targeted personalised therapy for patients with SDC.

DOI： 10.1111/his.13706

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

Objective: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100 mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. Methods: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II–IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70 mg/m2 for level 0, 80 mg/m2 for level 1, and 100 mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200 mg/m2, response rate, and incidences of adverse events. Results: A CDDP dose of 100 mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200 mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. Conclusion: The present phase I study indicated that a CDDP dose of 80 mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80 mg/m2 as compared with a dose of 100 mg/m2, and a dose of 80 mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR
identification No. UMIN000010369).

DOI： 10.1016/j.anl.2018.02.008

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Language：Japanese   Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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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：(一社)日本病理学会  

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

The molecular characteristics of therapeutically-relevant targets and their clinicopathological implications in salivary duct carcinomas (SDCs) are poorly understood. We investigated the gene alterations and the immunoexpression of crucial oncogenic molecules in 151 SDCs. The mutation rates that were identified, in order of frequency, were as follows: TP53, 68%; PIK3CA, 18%; H-RAS, 16%; BRAF, 4%; and AKT1, 1.5%. PIK3CA/H-RAS/BRAF mutations were more common in de novo SDC than in SDC ex-pleomorphic adenoma. Furthermore, these mutations were mutually exclusive for HER2 overexpression/amplification. TP53 mutations were frequently detected in cases with the aberrant p53 expression, and TP53 missense and truncating mutations were associated with p53-extreme positivity and negativity, respectively. DISH analysis revealed no cases of EGFR amplification. The rates of PI3K, p-Akt, and p-mTOR positivity were 34%, 22%, and 66%, respectively; PTEN loss was observed in 47% of the cases. These expressions were correlated according to the signaling axis. Cases with PI3K negativity and PTEN loss appeared to show a lower expression of androgen receptor. In the multivariate analysis, patients with SDC harboring TP53 truncating mutations showed shorter progression-free survival. Conversely, p-Akt positivity was associated with a favorable outcome. This study might provide information that leads to advances in personized therapy for SDC.

DOI： 10.18632/oncotarget.22927

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Diffuse idiopathic skeletal hyperostosis (DISH) is a common disease in which ossification lesions occur in the bones including the vertebrae. Dysphagia may occur in advanced cases, but there are few cases that require treatment. A 68-year-old man was diagnosed with hypopharyngeal cancer of the left pyriform sinus and asymptomatic DISH on the anterior cervical vertebrae. Due to prior history of radiation, partial laryngopharyngectomy was performed. After surgery, severe dysphagia and aspiration pneumonia occurred, and the patient needed to undergo total laryngectomy. It was determined that dysphagia was due to multiple factors, including insufficient laryngeal elevation and esophageal compression by osteophytes of DISH. Asymptomatic DISH can cause severe dysphagia after partial laryngopharyngectomy. We suggest that evaluation of the swallowing function and surgical options, including laryngeal suspension and cricopharyngeal myotomy should be considered when performing partial laryngopharyngectomy in patients with DISH, even if they demonstrated no difficulties in swallowing before treatment.

DOI： 10.1080/23772484.2018.1477508

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

Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs (P = 0.015, &lt; 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR-and CK5/6+ were associated with shorter progression-free survival (P = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival (P = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: 'apocrine A' (AR+/HER2-/Ki-67-low) (24%), 'apocrine B' (AR+/HER2-/Ki-67-high) (18%), 'apocrine HER2' (AR+/HER2+) (35%), 'HER2-enriched' (AR-/HER2+) (12%), and 'double negative' (AR-/HER2-) (11%). 'Double negative' was further subclassified into 'basal-like' (EGFR and/or CK5/6+) (7%) and 'unclassified' (3%). Consequently,patients with 'apocrine A' showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.

DOI： 10.18632/oncotarget.19812

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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：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

The prognostic role of modified Glasgow Prognostic Score (mGPS), neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with salivary duct carcinoma (SDC) remains unclear. We conducted a multi-institutional retrospective cohort study of 140 SDC patients. The survival impact of these hematological markers was evaluated using multivariate proportional hazard models. High mGPS (&gt;= 1) was significantly associated with worse survival (3-year overall survival (OS): 16.7% vs 66.1%, p-value=0.003; 3-year progression-free survival (PFS): 0.0% vs 27.9%, p-value&lt;0.001). Additionally, high C-reactive protein (CRP) (&gt;= 0.39 mg/dl) was significantly associated with worse survival (3-year OS: 32.1% vs 68.2%, p-value= 0.001; 3-year PFS: 7.1% vs 31.1%, p-value&lt;0.001). These associations were consistent with multivariate analysis adjusted for established prognostic factors. Although we also found significant association of high NLR (&gt;= 2.5) with OS (HR 1.80; 95% confidence interval, 1.05-3.08) in multivariate analysis, this association were inconsistent with the results of PFS. In addition, we found no significant associations of PLR with survival. In conclusion, we found that mGPS, CRP and NLR were identified as prognostic factors associated with survival in SDC patients.

DOI： 10.18632/oncotarget.13565

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Language：English  

Salivary duct carcinoma (SDC) has a poor prognosis owing to the high incidence of distant metastasis. Approximately 40 % of SDCs are positive for human epidermal growth factor receptor 2 (HER2), suggesting that anti-HER2 therapy for cases with distant metastasis may be effective. However, the pathological response of SDC metastases to anti-HER2 therapy has not been reported. A 44-year-old man was diagnosed with HER2-positive SDC of the submandibular gland with multiple distant metastases. After six cycles of trastuzumab/docetaxel therapy, the patient achieved clinical partial response for the primary tumor and complete response for the neck and distant metastases. Subsequently, the patient underwent submandibular gland resection and neck dissection. On histopathological examination, very few viable cancer cells were identified in the resected primary tumor. Unfortunately, the patient died of multiple distant metastases 12 months after initial treatment. Trastuzumab/docetaxel therapy can elicit a clinical and pathological response in HER2-positive SDC.

DOI： 10.1007/s13691-016-0247-9

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

Among salivary gland malignancies, the prognosis of salivary duct carcinoma (SDC) is assumed to be the poorest. However, because of its low incidence, reliable survival estimates and prognostic factors based on a large number of patients remain to be elucidated, thereby making it impossible to standardize the optimal treatment for SDC.
We performed this multi-institutional, retrospective analysis by collecting the clinical information of 141 patients with SDC without distant metastasis who underwent curative surgery as the initial treatment to elucidate overall survival (OS) and disease-free survival (DFS) along with their prognostic factors.
The 3-year OS and DFS rates were 70.5 and 38.2 %, respectively. Multivariate analysis revealed that age a parts per thousand yen65 years (p &lt; 0.001) and N1 and N2 (p = 0.047 and &lt; 0.001, respectively) were independent prognostic factors for OS, whereas the primary site of the minor salivary and sublingual gland (p &lt; 0.001) and N2 (p &lt; 0.001) were those for DFS. The most common treatment failure was distant metastasis (55 patients, 39.0 %). For early parotid SDC, neither total parotidectomy in the patients with early T stage nor nerve resection in the patients without facial nerve palsy showed survival benefits.
Advanced N stage independently affects both OS and DFS. Partial parotidectomy with facial nerve preservation could be a less invasive standard surgical procedure for parotid gland SDC in the early T stage without facial nerve palsy. Effective systemic therapy is imperative to improve DFS of SDC.

DOI： 10.1245/s10434-015-5082-2

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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)日本耳鼻咽喉科学会  

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

The Niigata Prefecture Head and Neck Malignant Tumor Registration Committee gathers data from cancer treatment centers in the region and has maintained a database of nearly all cases of malignancy during the last 25 years. Although the data are useful for cancer registration, it became clear that treatment centers had differing protocols and outcomes for radiation therapy and chemotherapy, and that the reliability of data on prognosis had decreased. Therefore, we designed the "Multicenter phase I/II study in Niigata Prefecture on high-dose CDDP + RT for head and neck squamous cell carcinoma", to examine treatment safety and effectiveness. Twelve cases were registered in phase I, and maximum tolerated dose, dose limiting toxicity, rules for reduction and termination of chemotherapy, and recommended CDDP dose for phase II were investigated. The phase II study will be started in the future. The recommended CDDP dose for that study is 80 mg/m2, and the primary endpoint is CCRT completion rate. The present study may become a model for the treatment of head and neck malignancies in the country. This report describes the current findings.

DOI： 10.5981/jjhnc.42.70

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

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.

DOI： 10.3950/jibiinkoka.118.1150

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

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.

DOI： 10.3950/jibiinkoka.118.1150

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Language：Japanese   Publisher：新潟県立がんセンター新潟病院  

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Language：Japanese   Publisher：新潟県立がんセンター新潟病院  

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Language：Japanese   Publisher：日本内分泌外科学会・日本甲状腺外科学会  

【症例】43歳男性。家族歴、既往歴に特記事項なし。20xx年2月から咳嗽あり、近医CTにて甲状腺腫瘍+多発肺転移の診断となり5月に当科紹介初診された。PET-CTでは甲状腺、頭部皮膚、両肺野に集積を認めた。頭部皮膚腫瘍を生検したが良性の血管平滑筋腫の診断であり、6月に甲状腺全摘およびD1郭清を施行した。術後病理診断では筋線維腫症であり、血小板由来成長因子受容体β(platelet-derived growth factor receptor β、PDGFRB)蛋白の過剰発現を認めることから、PDGFRB遺伝子変異を伴った内臓病変を有する成人全身型筋線維腫症例と考えられた。化学療法を施行するも、肺・膵臓などの内臓病変が増悪し、初診後8ヵ月で原病死した。【まとめ】非常に稀な成人筋線維腫症例を経験した。PDGFRB遺伝子変異が診断の決め手となったが、内臓病変を伴う全身型は予後不良で、治療法の確立が望まれる。(著者抄録)

DOI： 10.11226/jaesjsts.32.3_211

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Language：Japanese   Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s13691-014-0191-5

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Other Link： http://link.springer.com/article/10.1007/s13691-014-0191-5/fulltext.html

Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

頭頸部領域に再発を繰り返した類上皮血管内皮腫の1例を報告する。症例は40歳女性で、過去12年間に頭蓋骨左側、下顎骨左側、左耳下腺、鼻中隔左側の類上皮血管内皮腫に対して複数の医療機関で摘出術を施行され、経過観察目的に当科紹介となった。初診時は頭頸部領域に腫瘍性病変を認めなかったが、経過中に鼻中隔左側に腫瘤が出現した。生検にて類上皮血管内皮腫再発の診断となり、腫瘍切除術を施行した。腫瘍径と病理組織像から低危険度群に分類されたため、追加治療をせず経過観察を行っており、術後18ヵ月再発を認めていない。本症例では頭頸部領域の片側性再発を繰り返しており、今後も慎重な経過観察が必要と思われた。(著者抄録)

DOI： 10.5106/jjshns.25.55

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J04210&link_issn=&doc_id=20150721380009&doc_link_id=10.5106%2Fjjshns.25.55&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.25.55&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

Basaloid squamous cell carcinoma (BSCC) is a rare carcinoma with both basaloid and squamous components. We report a case of BSCC arising in the larynx. A 61-year-old man presented with hoarseness and sore throat. Laryngeal endoscopy revealed a tumor from the left laryngeal vestibule to both vocal cords, which caused paralysis of the left vocal cord. Squamous cell carcinoma (SCC) was confirmed in a biopsy specimen. Additional imaging studies confirmed a diagnosis of laryngeal cancer (supraglottic SCC, T3N2bM0, stage IV A). After preoperative chemotherapy, total laryngectomy and bilateral neck dissection were performed. Histopathological analysis of an operative specimen revealed BSCC, with extracapsular spread in metastatic lymph nodes. Despite adjuvant radiotherapy, multiple lung metastases rapidly developed. Chemotherapy with cisplatin, 5-fluorouracil, and cetuximab was temporarily effective, but metastasis later progressed quickly. BSCC is associated with a poor prognosis and high potential for distant metastasis and thus requires multidisciplinary therapy, including potent chemotherapy.

DOI： 10.5981/jjhnc.41.51

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

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

Typical osteomyelitis is reportedly caused by Pseudomonous aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. We have experiensed 5 cases of skull base osteomyelitis at our hospital. All patients were male with a mean age of 75.2 years. Four patients had diabetes. Regarding the clinical and radiographic findings, patients 1, 2, and 3 had typical osteomyelitis after malignant external otitis, whereas patients 4 and 5 had atypical osteomyelitis without temporal bone findings. Sample culturing revealed Pseudomonas aeruginosa in 4 cases and Aspergillus in one. Intravenous antibiotics were administered to all patients. Two patients responded positively and survived, while 3 died. Typical osteomyelitis is reportedly caused by P. aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. The prognosis of skull base osteomyelitis is still poor in Japan. Early diagnosis and long-term antibiotic administration is required to improve outcome.

DOI： 10.3950/jibiinkoka.118.40

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

Typical osteomyelitis is reportedly caused by Pseudomonous aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. We have experiensed 5 cases of skull base osteomyelitis at our hospital. All patients were male with a mean age of 75.2 years. Four patients had diabetes. Regarding the clinical and radiographic findings, patients 1, 2, and 3 had typical osteomyelitis after malignant external otitis, whereas patients 4 and 5 had atypical osteomyelitis without temporal bone findings. Sample culturing revealed Pseudomonas aeruginosa in 4 cases and Aspergillus in one. Intravenous antibiotics were administered to all patients. Two patients responded positively and survived, while 3 died. Typical osteomyelitis is reportedly caused by P. aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. The prognosis of skull base osteomyelitis is still poor in Japan. Early diagnosis and long-term antibiotic administration is required to improve outcome.

DOI： 10.3950/jibiinkoka.118.40

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

We present herein an 85-year-old patient with advanced hypopharyngeal carcinoma who developed thrombocytopenia during treatment with cetuximab plus radiotherapy. He had a medical history of diabetes mellitus and atrial fibrillation and was taking 3.5 mg of oral warfarin per day. At the time when the third dose of cetuximab was administered, the patient experienced a high-grade fever - thought to be an infusion reaction - followed by thrombocytopenia, which improved with platelet transfusion. After radiotherapy was finished, a hematoma was observed in the iliopsoas muscle on a CT scan. The prothrombin time-international normalized ratio (PT-INR) was elevated to an extremely high level of &gt
8.0, which caused by warfarin. Thrombocytopenia owing to cetuximab is a very rare but adverse event that may occur severely in elderly patients. Therefore, it is necessary to choose the treatment carefully for them. In addition, patients with carcinoma receiving anti-coagulant therapy should be assessed for risk factors and frequently monitored for blood coagulation during anti-cancer treatment.

DOI： 10.5631/jibirin.108.63

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Language：Japanese   Publisher：(株)へるす出版  

症例は40代の男性で、入所中の施設にて全身痙攣発作を起こして転倒し、顔面から窓ガラスに突っ込み受傷し、直ちに救急搬送された。受診時検査所見よりzone IIの鋭的頸部気道損傷と診断し、経口的に気管挿管を行い、助手が創部で用手的にチューブを誘導したところ気道確保に成功した。気道確保後は循環動態が安定し、造影CTにて活動性の出血が示唆されたため、上甲状腺動脈、前頸静脈などを結紮止血した。次いで創部の尾側に気管切開を造設し、気管チューブを移動し、気管損傷部の浮腫が著しく一期的な修復は気管狭窄のリスクが高いと考え、開放創断端と皮膚を縫合し確実な気管皮膚瘻を作成し手術を終了した。その後の経過は良好で、第7病日に気管皮膚瘻を閉鎖後、気道を再建し、第33病日に退院となった。

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Other Link： http://search.jamas.or.jp/link/ui/2015007202

Language：Japanese   Publisher：新潟市民病院  

症例は84歳の女性で、右側胸部痛を主訴に当院救急外来を受診し、高カルシウム血症、腎機能低下を認め内分泌内科に緊急入院となった。原因検索のため、血液検査、超音波検査、単純CTを施行、甲状腺左葉下極に接した石灰化を伴う20mm大の腫瘤と、i-PTHの高値を認めた。さらに副甲状腺シンチグラムで異常集積がみられ、原発性副甲状腺機能亢進症と診断した。保存的治療をおこなったが、高カルシウム血症及び腎機能が徐々に増悪したため、手術目的に当科紹介となった。全身麻酔下に副甲状腺腫瘍摘出術を施行し、術中所見で周囲への浸潤は認めず、迅速病理診断は腺腫であったが、最終的な永久病理診断は副甲状腺癌となった。副甲状腺癌は非常に稀な疾患であり、術前診断が困難な事も多い。本例も手術後に診断が確定したが、術前から副甲状腺癌に特徴的な症状を念頭に置き治療にあたる必要があると思われた。(著者抄録)

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Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

唾液腺導管癌(salivary duct carcinoma、以下SDC)の中でも顎下腺原発はまれである。今回顎下腺原発SDC 4例につき検討を行った。治療前の病期分類はstage Iが1例、stage IIが2例、stage IVaが1例であった。術前細胞診断で悪性を疑いえたのは1例のみで、術中迅速診断でSDCの疑いが1例、他の3例は悪性の診断であった。HER-2の過剰発現が3例にみられた。全例で頸部郭清術に加え術後照射が行われたが、3例で遠隔転移をきたし、2例は原病死した。SDCは集学的治療を行ってもなお予後不良の疾患であるが、HER-2の過剰発現が高頻度にみられることから、Trastuzumabなどの分子標的薬剤による新しい治療法の確立が期待される。(著者抄録)

DOI： 10.5106/jjshns.23.403

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Other Link： http://search.jamas.or.jp/link/ui/2014224602

Publishing type：Research paper (scientific journal)   Publisher：Hindawi Publishing Corporation  

DOI： 10.1155/2014/141307

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

Hematogenous metastasis is the most common form of metastasis in head and neck cancer, and reports have described successful resection of pulmonary metastases of such cancers. We report treatment outcomes after surgical resection of pulmonary metastases of head and neck cancer and identify prognostic factors. This clinicopathologic study investigated the clinical records of 16 patients with pulmonary metastases of head and neck cancer (excepting cases of thyroid cancer) who had undergone metastasectomy at our center during the period 2001–2012. The mean age of the 16 patients (11 men and 5 women) was 62.1 years. The mean interval between completion of successful treatment of the primary tumor and detection of pulmonary metastasis was 21 months (range, 6–56 months). All patients underwent pulmonary resection. The overall 1-year survival rate was 79.4 %, and the 2- to 5-year survival rate was 63.2 %. These rates compare favorably to those in previous reports on resection of pulmonary metastases. When prognostic factors for survival rates were compared, the factors associated with a negative prognosis were a disease-free interval of &lt
12 months and partial resection of pulmonary metastases. Multivariate analysis did not reveal any prognostic factors associated with negative outcomes. Surgical resection of pulmonary metastases of head and neck cancer might improve outcomes.

DOI： 10.1007/s12070-014-0799-y

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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)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：耳鼻咽喉科臨床学会  

The clinical data of 56 patients with hypopharyngeal squamous cell carcinoma who were seen between 1991 and 2011 were evaluated at our department. The overall 5-year disease-free survival rate was 43.6%. The survival rates in the patients with stage I (n=3), stage II (n=13), stage III (n=3), stage IV (n=37) disease were 66.7%, 83.8%, 0%, and 31.4%, respectively. Among the patients with stage III/stage IV disease, the survival rate in those who underwent surgery (n=8) was 83.8%, while that in those who underwent concurrent chemoradiotherapy (CCRT) (n=30) was only of 22.3%. The survival rate in patients who underwent adjuvant chemotherapy with S-1 (n=16) was 46.3%, and that in patients who underwent adjuvant chemotherapy without S-1 (n=24) was 20.5%. These results suggest that surgery plays a very important role in the treatment of advanced hypopharyngeal carcinoma and that appropriate adjuvant chemotherapy improves the outcome in these patients.

DOI： 10.5631/jibirin.106.997

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00990&link_issn=&doc_id=20130222020016&doc_link_id=%2Fdg3nigta%2F2012%2Fs12609%2F007%2F0505-0505%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2012%2Fs12609%2F007%2F0505-0505%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

A total of 40 patients with previously untreated mucosal malignant melanoma of the head and neck underwent resection at our hospital between 1980 and 2010. We reviewed the clinical data of these 40 patients. There were 20 men and 20 women, aged 24-79 years (median: 62 years). The site of the primary lesion was the nasal/paranasal cavity in 28 patients, oral cavity in 9 patients, and pharynx in 3 patients. The clinical TNM classification according to the 7th AJCC/UICC was as follows: Stage III, 6 cases
Stage IVA, 23 cases
Stage IVB, 9 cases
T3, 8 cases
T4a, 23 cases
and T4b, 9 cases. The 5-year overall survival rate according to the TNM Stage was 100% for Stage III, 46% for Stage IVA, and 11% for Stage IVB. The 5-year overall survival rate (Kaplan-Meier method) was 43%, the 5-year local control rate was 70%, and the disease-free survival rate was 29%. In this study, the TNM classification was well correlated with the clinical outcome
especially, the prognosis of patients with T4b and N1 was poor. A local recurrence was a therapeutic challenge for the maxillary tuberosity and the pterygoid direction. The subsequent cervical lymph node metastasis rate was high, but neck dissection was considered to have a definitive beneficial effect on survival.

DOI： 10.5981/jjhnc.38.74

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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)日本耳鼻咽喉科頭頸部外科学会  

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

Hereditary angioedema (HAE) due to an inherited Cl-inhibitor (CHNH) deficiency causes localized swelling of the oral cavity, pharynx, larynx, and face, that may be life-threatening when the larynx is involved. A 26-year-old woman seen 3 times previously for pharyngeal or laryngeal edema while in her teens, and seen this time for dyspnea was found in computed tomography (CT) to have esophageal edema and pleural effusion. Her C1-INH activity was low, yielding a definitive diagnosis of HAE for her 10-year-plus-disease history. While it is comparatively rare, HAE should be kept in mind in the differential diagnosis of idiopathic edema.

DOI： 10.3950/jibiinkoka.112.747

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

Sweet病は特有の皮疹に発熱,好中球増多を伴う疾患で,なかでも脳炎,髄膜炎などの神経合併症を伴うものはneuro-Sweet病といわれている.今回,感音難聴を合併したneuro-Sweet病と考えられた33歳男性の症例を経験した.本例は髄膜炎症状に随伴,前後して急性感音難聴を左右で計5回繰り返し,明らかに病勢を反映した難聴であった.反復性髄膜炎の所見,頭部MRIでの白質病変,HLA-B54,CW1陽性であることより,neuro-Sweet病と診断された.ステロイド治療により,難聴は改善を認めるも病勢に伴い再発を繰り返した.難聴の原因は自記オージオグラム,SISI検査,ABR,SPECTなどから内耳と中枢の複合病変が考えられた.原因不明の急性感音難聴に髄膜炎などの神経症状を伴う場合には本症も念頭におく必要があると考えられた(著者抄録)

DOI： 10.4295/audiology.49.254

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

IgA nephropathy is the most common type of glomerulonephritis, and is characterized by glomerular mesangial proliferation with predominant IgA deposition in the mesangial areas. Long-term observation showed that approximately 40% of patients with IgA nephropathy progress to end-stage renal failure after showing clinical manifestations for 20 years. In recent years, tonsillectomy in IgA nephropathy patients has become prevalent because the treatment has been found efficacious in improving renal survival. We present a case report of IgA nephropathy for which renal transplantation was performed in a 40-year-old man. The patient developed IgA nephropathy that resulted in renal graft dysfunction. To prevent disease progression, he underwent tonsillectomy under general anesthesia. The tonsillar beds were edematous and fragile, and it was very difficult to coagulate the oozing from the tonsillar beds intraoperatively. An argon beam coagulator (ABC) was found to be very useful and safe for bleeding hemostasis. After tonsillectomy, the renal function was stabilized with steroid pulse therapy. For patients progressing to end-stage renal failure, recurrent disease after transplantation remains a clinically important problem. Tonsillectomy may serve as both prophylactic and curative treatment for recurrent IgA nephropathy following renal transplantation.

DOI： 10.5631/jibirin.99.467

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Language：Japanese   Publisher：日本唾液腺学会  

J-GLOBAL

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

DOI： 10.3950/jibiinkoka.117.522

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

J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：日本内分泌外科学会  

J-GLOBAL

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Language：Japanese   Publisher：新潟医学会  

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