研究者データベース

加納 里志(カノウ サトシ)
北海道大学病院 脳・神経・感覚器科
講師

基本情報

所属

  • 北海道大学病院 脳・神経・感覚器科

職名

  • 講師

学位

  • 医学博士(北海道大学)

ホームページURL

J-Global ID

研究キーワード

  • 唾液腺癌   頭頸部癌   

研究分野

  • ライフサイエンス / 耳鼻咽喉科学

職歴

  • 2018年04月 - 現在 北海道大学大学院医学研究院 耳鼻咽喉科・頭頸部外科学教室 講師
  • 2014年04月 - 2018年03月 北海道大学 医学(系)研究科(研究院) 助教

研究活動情報

論文

  • Junichi Nakagawa, Noriyuki Fujima, Kenji Hirata, Minghui Tang, Satonori Tsuneta, Jun Suzuki, Taisuke Harada, Yohei Ikebe, Akihiro Homma, Satoshi Kano, Kazuyuki Minowa, Kohsuke Kudo
    Cancer imaging : the official publication of the International Cancer Imaging Society 22 1 52 - 52 2022年09月22日 
    BACKGROUND: In nasal or sinonasal tumors, orbital invasion beyond periorbita by the tumor is one of the important criteria in the selection of the surgical procedure. We investigated the usefulness of the convolutional neural network (CNN)-based deep learning technique for the diagnosis of orbital invasion, using computed tomography (CT) images. METHODS: A total of 168 lesions with malignant nasal or sinonasal tumors were divided into a training dataset (n = 119) and a test dataset (n = 49). The final diagnosis (invasion-positive or -negative) was determined by experienced radiologists who carefully reviewed all of the CT images. In a CNN-based deep learning analysis, a slice of the square target region that included the orbital bone wall was extracted and fed into a deep-learning training session to create a diagnostic model using transfer learning with the Visual Geometry Group 16 (VGG16) model. The test dataset was subsequently tested in CNN-based diagnostic models and by two other radiologists who were not specialized in head and neck radiology. At approx. 2 months after the first reading session, two radiologists again reviewed all of the images in the test dataset, referring to the diagnoses provided by the trained CNN-based diagnostic model. RESULTS: The diagnostic accuracy was 0.92 by the CNN-based diagnostic models, whereas the diagnostic accuracies by the two radiologists at the first reading session were 0.49 and 0.45, respectively. In the second reading session by two radiologists (diagnosing with the assistance by the CNN-based diagnostic model), marked elevations of the diagnostic accuracy were observed (0.94 and 1.00, respectively). CONCLUSION: The CNN-based deep learning technique can be a useful support tool in assessing the presence of orbital invasion on CT images, especially for non-specialized radiologists.
  • Noriyuki Fujima, Yukie Shimizu, Masami Yoneyama, Junichi Nakagawa, Hiroyuki Kameda, Taisuke Harada, Seijiro Hamada, Takayoshi Suzuki, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Kohsuke Kudo
    Quantitative imaging in medicine and surgery 12 8 4024 - 4032 2022年08月 
    Background: In head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor histological grade in patients with head and neck squamous cell carcinoma (SCC). Methods: The cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI). Results: ADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of DW-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82. Conclusions: DW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.
  • Noriyuki Fujima, Yukie Shimizu, Masami Yoneyama, Junichi Nakagawa, Hiroyuki Kameda, Taisuke Harada, Seijiro Hamada, Takayoshi Suzuki, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Kohsuke Kudo
    Medicine 101 28 e29457  2022年07月15日 
    The aim of this study was to investigate the utility of amide proton transfer (APT) imaging for the determination of human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (SCC). Thirty-one patients with oropharyngeal SCC were retrospectively evaluated. All patients underwent amide proton transfer imaging using a 3T magnetic resonance (MR) unit. Patients were divided into HPV-positive and -negative groups depending on the pathological findings in their primary tumor. In APT imaging, the primary tumor was delineated with a polygonal region of interest (ROI). Signal information in the ROI was used to calculate the mean, standard deviation (SD) and coefficient of variant (CV) of the APT signals (APT mean, APT SD, and APT CV, respectively). The value of APT CV in the HPV-positive group (0.43 ± 0.04) was significantly lower than that in the HPV-negative group (0.48 ± 0.04) (P = .01). There was no significant difference in APT mean (P = .82) or APT SD (P = .13) between the HPV-positive and -negative groups. Receiver operating characteristic (ROC) curve analysis of APT CV had a sensitivity of 0.75, specificity of 0.8, positive predictive value of 0.75, negative predictive value of 0.8, accuracy of 0.77 and area under the curve (AUC) of 0.8. The APT signal in the HPV-negative group was considered heterogeneous compared to the HPV-positive group. This information might be useful for the determination of HPV status in patients with oropharyngeal SCC.
  • 咽喉頭癌に対するシスプラチン超選択的動注併用放射線治療(RADPLAT)による頸部制御の検討
    加納 里志, 対馬 那由多, 鈴木 崇祥, 浜田 誠二郎, 吉田 大介, 打浪 雄介, 安田 耕一, 本間 明宏
    頭頸部癌 48 2 151 - 151 (一社)日本頭頸部癌学会 2022年05月
  • 高齢の頭頸部悪性腫瘍に対する放射線治療の後ろ向き検討
    安田 耕一, 打浪 雄介, 浜田 誠二郎, 鈴木 崇祥, 対馬 那由多, 田口 純, 清水 康, 加納 里志, 本間 明宏
    頭頸部癌 48 2 200 - 200 (一社)日本頭頸部癌学会 2022年05月
  • 再発・転移唾液腺導管癌に対する抗HER2・抗AR療法の生存への寄与
    川北 大介, 長尾 俊孝, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 富樫 孝文, 近藤 貴仁, 多田 雄一郎
    日本耳鼻咽喉科頭頸部外科学会会報 125 4 706 - 706 (一社)日本耳鼻咽喉科頭頸部外科学会 2022年04月
  • Satsuki Nakano, Yoshihide Okumura, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Satoshi Kano, Kiyoaki Tsukahara, Kenji Okami, Daisuke Kawakita, Toru Nagao, Nobuhiro Hanai, Hiroshi Iwai, Ryo Kawata, Yuichiro Tada, Ken-Ichi Nibu, Hiroshi Inagaki
    Histopathology 80 4 729 - 735 2022年03月 
    AIMS: To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions. METHODS AND RESULTS: Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (>10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment. CONCLUSION: Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.
  • Natsuki Saigusa, Hideaki Hirai, Yuichiro Tada, Daisuke Kawakita, Masato Nakaguro, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Takahito Kondo, Kenji Okami, Takafumi Togashi, Yukiko Sato, Makoto Urano, Manami Kajiwara, Tomotaka Shimura, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Takuro Okada, Takayoshi Suzuki, Yorihisa Imanishi, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Yuichiro Sato, Yoshitaka Honma, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Hideaki Takahashi, Mizuo Ando, Shinji Kohsaka, Takashi Matsuki, Toshitaka Nagao
    Frontiers in Oncology 11 2022年02月03日 
    ObjectiveSalivary 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 MethodsThe 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). ResultsEZH2 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. ConclusionsA 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.
  • Daisuke Kawakita, Toshitaka Nagao, Hideaki Takahashi, Satoshi Kano, Yoshitaka Honma, Hideaki Hirai, Natsuki Saigusa, Kohei Akazawa, Kaori Tani, Hiroya Ojiri, Kiyoaki Tsukahara, Hiroyuki Ozawa, Kenji Okami, Takahito Kondo, Takafumi Togashi, Chihiro Fushimi, Tomotaka Shimura, Akira Shimizu, Isaku Okamoto, Takuro Okada, Yorihisa Imanishi, Yoshihiro Watanabe, Kuninori Otsuka, Akihiro Sakai, Koji Ebisumoto, Yuichiro Sato, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Mizuo Ando, Takashi Matsuki, Masato Nakaguro, Yukiko Sato, Makoto Urano, Yoshitaka Utsumi, Shinji Kohsaka, Takashi Saotome, Yuichiro Tada
    Therapeutic advances in medical oncology 14 17588359221119538 - 17588359221119538 2022年 
    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.
  • 唾液腺導管癌におけるPTEN欠損とその臨床病理学的意義 多施設共同研究
    山本 善也, 平井 秀明, 三枝 奈津季, 浦野 誠, 中黒 匡人, 佐藤 由紀子, 塚原 清彰, 加納 里志, 近藤 貴仁, 大上 研二, 小澤 宏之, 富樫 孝文, 川北 大介, 多田 雄一郎, 長尾 俊孝
    日本唾液腺学会誌 61 43 - 44 日本唾液腺学会 2021年11月
  • 唾液腺導管癌においてEZH2高発現は複合アンドロゲン遮断療法の効果不良予測因子になりうる
    平井 秀明, 三枝 奈津季, 浦野 誠, 中黒 匡人, 佐藤 由紀子, 塚原 清彰, 加納 里志, 近藤 貴仁, 大上 研二, 小澤 宏之, 富樫 孝文, 川北 大介, 多田 雄一郎, 長尾 俊孝, SDC多施設共同研究会
    日本唾液腺学会誌 61 48 - 49 日本唾液腺学会 2021年11月
  • 再発・転移唾液腺導管癌に対する抗HER2・抗AR療法の生存への寄与 大規模個別データを用いた後ろ向きコホート研究
    川北 大介, 長尾 俊孝, 加納 里志, 本間 義崇, 塚原 清彰, 小澤 宏之, 大上 研二, 近藤 貴仁, 富樫 孝文, 高橋 秀聡, 伏見 千宙, 多田 雄一郎
    日本唾液腺学会誌 61 41 - 41 日本唾液腺学会 2021年11月
  • 再発・転移唾液腺導管癌に対する抗HER2・抗AR療法の生存への寄与 大規模個別データを用いた後ろ向きコホート研究
    川北 大介, 長尾 俊孝, 加納 里志, 本間 義崇, 塚原 清彰, 小澤 宏之, 大上 研二, 近藤 貴仁, 富樫 孝文, 高橋 秀聡, 伏見 千宙, 多田 雄一郎
    日本唾液腺学会誌 61 41 - 41 日本唾液腺学会 2021年11月
  • 唾液腺導管癌におけるPTEN欠損とその臨床病理学的意義 多施設共同研究
    山本 善也, 平井 秀明, 三枝 奈津季, 浦野 誠, 中黒 匡人, 佐藤 由紀子, 塚原 清彰, 加納 里志, 近藤 貴仁, 大上 研二, 小澤 宏之, 富樫 孝文, 川北 大介, 多田 雄一郎, 長尾 俊孝
    日本唾液腺学会誌 61 43 - 44 日本唾液腺学会 2021年11月
  • 唾液腺導管癌においてEZH2高発現は複合アンドロゲン遮断療法の効果不良予測因子になりうる
    平井 秀明, 三枝 奈津季, 浦野 誠, 中黒 匡人, 佐藤 由紀子, 塚原 清彰, 加納 里志, 近藤 貴仁, 大上 研二, 小澤 宏之, 富樫 孝文, 川北 大介, 多田 雄一郎, 長尾 俊孝, SDC多施設共同研究会
    日本唾液腺学会誌 61 48 - 49 日本唾液腺学会 2021年11月
  • Keiko Tokuchi, Shinya Kitamura, Takuya Maeda, Masashi Watanabe, Shigetsugu Hatakeyama, Satoshi Kano, Shinya Tanaka, Hideyuki Ujiie, Teruki Yanagi
    Journal of dermatological science 104 2 112 - 121 2021年11月 
    BACKGROUNDS: FAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes. OBJECTIVE: To investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function. METHODS: Immunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution. RESULTS: FAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution. CONCLUSION: Our findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC.
  • Atsushi Fukuda, Satoshi Kano, Yuji Nakamaru, Shinya Morita, Kimiko Hoshino, Keishi Fujiwara, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 42 9 e1389-e1395  2021年10月01日 
    HYPOTHESIS: We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma. BACKGROUND: The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated. METHODS: We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler™ PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively. RESULTS: The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 ± 32.4% and 44.9 ± 17.8%, respectively) were significantly lower than in the EAC skin (83.4 ± 17.5% and 55.7 ± 7.1%, respectively) (p < 0.001 and p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 ± 11.4%) was significantly higher than in the EAC skin (0.5 ± 0.7%) (p < 0.001). CONCLUSION: The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.
  • Noriyuki Fujima, V Carlota Andreu-Arasa, Sara K Meibom, Gustavo A Mercier, Minh Tam Truong, Kenji Hirata, Koichi Yasuda, Satoshi Kano, Akihiro Homma, Kohsuke Kudo, Osamu Sakai
    BMC cancer 21 1 900 - 900 2021年08月06日 
    BACKGROUND: This study aimed to assess the utility of deep learning analysis using pretreatment FDG-PET images to predict local treatment outcome in oropharyngeal squamous cell carcinoma (OPSCC) patients. METHODS: One hundred fifty-four OPSCC patients who received pretreatment FDG-PET were included and divided into training (n = 102) and test (n = 52) sets. The diagnosis of local failure and local progression-free survival (PFS) rates were obtained from patient medical records. In deep learning analyses, axial and coronal images were assessed by three different architectures (AlexNet, GoogLeNET, and ResNet). In the training set, FDG-PET images were analyzed after the data augmentation process for the diagnostic model creation. A multivariate clinical model was also created using a binomial logistic regression model from a patient's clinical characteristics. The test data set was subsequently analyzed for confirmation of diagnostic accuracy. Assessment of local PFS rates was also performed. RESULTS: Training sessions were successfully performed with an accuracy of 74-89%. ROC curve analyses revealed an AUC of 0.61-0.85 by the deep learning model in the test set, whereas it was 0.62 by T-stage, 0.59 by clinical stage, and 0.74 by a multivariate clinical model. The highest AUC (0.85) was obtained with deep learning analysis of ResNet architecture. Cox proportional hazards regression analysis revealed deep learning-based classification by a multivariate clinical model (P < .05), and ResNet (P < .001) was a significant predictor of the treatment outcome. In the Kaplan-Meier analysis, the deep learning-based classification divided the patient's local PFS rate better than the T-stage, clinical stage, and a multivariate clinical model. CONCLUSIONS: Deep learning-based diagnostic model with FDG-PET images indicated its possibility to predict local treatment outcomes in OPSCCs.
  • Satoshi Kano, Nayuta Tsushima, Takayoshi Suzuki, Seijiro Hamada, Taizo Yokokawa, Hiroshi Idogawa, Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Hidefumi Aoyama, Akihiro Homma
    International journal of clinical oncology 26 7 1179 - 1187 2021年07月 
    BACKGROUND: We investigated whether prophylactic percutaneous endoscopic gastrostomy (PEG) is used effectively for patients treated with definitive concurrent chemoradiotherapy (CCRT) and the predictors of the need for PEG. METHODS: 326 patients with laryngeal, oropharyngeal or hypopharyngeal cancers were retrospectively reviewed. RESULTS: The PEG tube use group had more favorable results than the total parenteral nutrition and nasogastric tube groups in terms of rate of serum albumin loss, incidence of severe fever and aspiration pneumonia, CCRT completion rate and hospitalization period. However, it was inferior to oral intake. Analysis of the relative risk of requiring enteral or parenteral nutrition revealed that performance status (PS) 2, primary site (supraglottis, oropharynx, or hypopharynx), N3 disease, and cisplatin were predictors of the need for nutritional support. CONCLUSIONS: Prophylactic PEG is effective for patients treated with definitive CCRT and is especially required for patients with PS2 or oropharyngeal cancer.
  • 咽喉頭扁平上皮癌IMRTの照射中における線量分布変化に関する解析
    安田 耕一, 打浪 雄介, 湊川 英樹, 小泉 富基, 大塚 愛美, 藤田 祥博, 井戸川 寛志, 鈴木 崇祥, 対馬 那由多, 加納 里志, 本間 明宏
    頭頸部癌 47 2 210 - 210 (一社)日本頭頸部癌学会 2021年05月
  • CCRTを施行した頭頸部癌患者に対する予防的胃瘻増設の有用性の検討
    加納 里志, 対馬 那由多, 鈴木 崇祥, 井戸川 寛志, 浜田 誠二郎, 横川 泰三, 安田 耕一, 湊川 英樹, 打浪 雄介, 本間 明宏
    頭頸部癌 47 2 211 - 211 (一社)日本頭頸部癌学会 2021年05月
  • Nayuta Tsushima, Satoshi Kano, Takayoshi Suzuki, Hiroshi Idogawa, Daisuke Yoshida, Koichi Yasuda, Manami Otsuka, Hidefumi Aoyama, Akihiro Homma
    European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 2021年04月18日 
    PURPOSE: We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. METHODS: We assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60 Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1 years. RESULTS: Twenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period. Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. CONCLUSION: Treatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT.
  • Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Seishin Takao, Masaya Tamura, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Takatsugu Mizumachi, Takashi Mori, Kentaro Nishioka, Motoyasu Shido, Norio Katoh, Hiroshi Taguchi, Noriyuki Fujima, Rikiya Onimaru, Isao Yokota, Keiji Kobashi, Shinichi Shimizu, Akihiro Homma, Hiroki Shirato, Hidefumi Aoyama
    Journal of radiation research 62 2 329 - 337 2021年03月10日 
    Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.
  • Naruhiko Morita, Takayuki Murase, Kaori Ueda, Toshitaka Nagao, Kimihide Kusafuka, Masato Nakaguro, Makoto Urano, Ken-Ichi Taguchi, Hidetaka Yamamoto, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Daisuke Kawakita, Kazuo Sakurai, Toru Nagao, Nobuhiro Hanai, Ryo Kawata, Naohito Hato, Naoki Otsuki, Ken-Ichi Nibu, Hiroshi Inagaki
    Cancer science 112 3 1184 - 1195 2021年03月 
    Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.
  • Yuji Nakamaru, Masanobu Suzuki, Satoshi Kano, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Akihiro Homma
    Auris, nasus, larynx 48 1 131 - 137 2021年02月 
    OBJECTIVE: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. METHODS: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. RESULTS: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). CONCLUSION: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC.
  • Noriyuki Fujima, Yukie Shimizu, Daisuke Yoshida, Satoshi Kano, Takatsugu Mizumachi, Akihiro Homma, Koichi Yasuda, Rikiya Onimaru, Osamu Sakai, Kohsuke Kudo, Hiroki Shirato
    The journal of medical investigation : JMI 68 3.4 354 - 361 2021年 
    Purpose : To predict local control / failure by a multiparametric approach using magnetic resonance (MR)-derived tumor morphological and functional parameters in pharynx squamous cell carcinoma (SCC) patients. Materials and Methods : Twenty-eight patients with oropharyngeal and hypopharyngeal SCCs were included in this study. Quantitative morphological parameters and intratumoral characteristics on T2-weighted images, tumor blood flow from pseudo-continuous arterial spin labeling, and tumor diffusion parameters of three diffusion models from multi-b-value diffusion-weighted imaging as well as patients' characteristics were analyzed. The patients were divided into local control / failure groups. Univariate and multiparametric analysis were performed for the patient group division. Results : The value of morphological parameter of 'sphericity' and intratumoral characteristic of 'homogeneity' was revealed respectively significant for the prediction of the local control status in univariate analysis. Higher diagnostic performance was obtained with the sensitivity of 0.8, specificity of 0.75, positive predictive value of 0.89, negative predictive value of 0.6 and accuracy of 0.79 by multiparametric diagnostic model compared to results in the univariate analysis. Conclusion : A multiparametric analysis with MR-derived quantitative parameters may be useful to predict local control in pharynx SCC patients. J. Med. Invest. 68 : 354-361, August, 2021.
  • Yoshihide Okumura, Satsuki Nakano, Takayuki Murase, Kaori Ueda, Daisuke Kawakita, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Satoshi Kano, Kiyoaki Tsukahara, Kenji Okami, Toru Nagao, Nobuhiro Hanai, Hiroshi Iwai, Ryo Kawata, Yuichiro Tada, Ken‐Ichi Nibu, Hiroshi Inagaki
    Cancer Science 2020年09月14日
  • Jun Taguchi, Yasushi Shimizu, Shin Ariga, Tomohiro Goda, Yoshihito Ohhara, Rio Honma, Takuro Noguchi, Satoshi Takeuchi, Ichiro Kinoshita, Toraji Amano, Takatsugu Mizumachi, Satoshi Kano, Miki Takahara, Takahisa Abe, Akihiro Homma, Hirotoshi Dosaka-Akita
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 2020年09月 
    Background The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. Methods Platinum-ineligibility was defined as: elderly (aged >= 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m(2)/day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m(2), followed by 250 mg/m(2)weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Results Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). Conclusions Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN.
  • 上・中・下咽頭癌に対する陽子線治療の初期経験
    安田 耕一, 湊川 英樹, 出倉 康裕, 対馬 那由多, 鈴木 崇祥, 加納 里志, 鬼丸 力也, 清水 伸一, 本間 明宏, 青山 英史
    頭頸部癌 46 2 161 - 161 (一社)日本頭頸部癌学会 2020年07月
  • 休日による総治療期間延長に対して1回線量増加の方法を組み合わせて放射線治療を行った早期声門癌の検討
    出倉 康裕, 安田 耕一, 湊川 英樹, 対馬 那由多, 鈴木 崇祥, 加納 里志, 鬼丸 力也, 本間 明宏, 青山 英史
    頭頸部癌 46 2 179 - 179 (一社)日本頭頸部癌学会 2020年07月
  • 頭頸部粘膜悪性黒色腫に対する術後陽子線治療30GyE/5回の初期経験
    湊川 英樹, 安田 耕一, 出倉 康裕, 鈴木 正宣, 中丸 裕爾, 中薗 彬, 鈴木 崇祥, 対馬 那由多, 加納 里志, 鬼丸 力也, 清水 伸一, 本間 明宏, 青山 英史
    頭頸部癌 46 2 188 - 188 (一社)日本頭頸部癌学会 2020年07月
  • Daisuke Kawakita, Takayuki Murase, Kaori Ueda, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Takuma Matoba, Kazuo Sakurai, Toru Nagao, Nobuhiro Hanai, Ryo Kawata, Naohito Hato, Ken-ichi Nibu, Makoto Urano, Ken-ichi Taguchi, Masato Nakaguro, Kimihide Kusafuka, Hidetaka Yamamoto, Toshitaka Nagao, Hiroshi Inagaki
    International Journal of Clinical Oncology 2020年07月01日 [査読有り][通常論文]
  • Masato Nakaguro, Yukiko Sato, Yuichiro Tada, Daisuke Kawakita, Hideaki Hirai, Makoto Urano, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Natsuki Saigusa, Hideaki Takahashi, Mizuo Ando, Toyoyuki Hanazawa, Toshitaka Nagao
    The American journal of surgical pathology 44 4 526 - 535 2020年04月 [査読有り][通常論文]
     
    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.
  • Hideaki Hirai, Yuichiro Tada, Masato Nakaguro, Daisuke Kawakita, Yukiko Sato, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Natsuki Saigusa, Hideaki Takahashi, Mizuo Ando, Makoto Urano, Toyoyuki Hanazawa, Toshitaka Nagao
    Virchows Archiv : an international journal of pathology 477 2 291 - 299 2020年02月26日 [査読有り][通常論文]
     
    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.
  • HER2陽性再発・転移唾液腺癌患者に対するトラスツズマブ・ドセタキセル併用療法の第II相試験
    木下 一郎, 加納 里志, 清田 尚臣, 多田 雄一郎, 伊地知 圭, 山崎 知子, 西本 尚樹, 畑中 豊, 松野 吉弘, 秋田 弘俊
    日本内科学会雑誌 109 Suppl. 230 - 230 (一社)日本内科学会 2020年02月
  • Kaori Ueda, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Masato Nakaguro, Ken-Ichi Taguchi, Ayako Masaki, Hideaki Hirai, Daisuke Kawakita, Kiyoaki Tsukahara, Naohito Hato, Toru Nagao, Yasushi Fujimoto, Kazuo Sakurai, Nobuhiro Hanai, Satoshi Kano, Tetsuro Onitsuka, Kenji Okami, Ken-Ichi Nibu, Yuichiro Tada, Ryo Kawata, Hiroshi Inagaki
    Head & neck 42 8 1721 - 1727 2020年01月23日 [査読有り][通常論文]
     
    BACKGROUND: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC). METHODS: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation. RESULTS: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants. CONCLUSIONS: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.
  • Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroki Akamatsu, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Satoshi Kano, Akihiro Homma
    Journal of vestibular research : equilibrium & orientation 30 2 101 - 108 2020年 
    OBJECTIVE: The aim of the present study was to investigate the factors influencing semicircular canal function as evaluated by video Head Impulse Test (vHIT) in patients with vestibular schwannoma. METHODS: Twenty-four patients with untreated vestibular schwannoma underwent vHIT examination. The correlations between semicircular canal function and factors including age, tumor size, disease duration and hearing loss were evaluated. RESULTS: The functions of all three semicircular canals on the affected side evaluated by vHIT were significantly lower than those on the unaffected side. Although there were no significant correlations between semicircular canal function and age, tumor size or disease duration, a negative significant correlation between vestibulo-ocular reflex (VOR) gain as evaluated by vHIT and hearing loss was observed. CONCLUSIONS: From the results of the relationship between hearing loss and VOR gain, the damage to the audio and vestibular systems in patients with VS may be correlated. As it has been suggested that tumor size was not a significant factor in the VOR gain evaluated by vHIT, multifactorial causes rather than the simple compression of the vestibular nerves alone may be related to the dysfunction of the semicircular canals in patients with vestibular schwannoma.
  • Takayoshi Suzuki, Satoshi Kano, Masanobu Suzuki, Shinichiro Yasukawa, Takatsugu Mizumachi, Nayuta Tsushima, Kanako C Hatanaka, Yutaka Hatanaka, Yoshihiro Matsuno, Akihiro Homma
    Frontiers in oncology 10 603717 - 603717 2020年 
    Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: "HER2-positive" (HER2+/any AR), "Luminal-AR" (HER2-/AR+), and "Basal-like" (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher's test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.
  • 唾液腺導管癌における脂質関連蛋白発現の臨床病理学的意義
    平井 秀明, 多田 雄一郎, 中黒 匡人, 川北 大介, 佐藤 由紀子, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 伏見 千宙, 清水 顕, 高瀬 総一郎, 岡田 拓朗, 佐藤 宏樹, 今西 順久, 大塚 邦憲, 渡部 佳弘, 酒井 昭博, 戎本 浩史, 富樫 孝文, 植木 雄志, 太田 久幸, 三枝 奈津季, 高橋 秀聡, 安藤 瑞生, 浦野 誠, 花澤 豊行, 長尾 俊孝
    日本唾液腺学会誌 60 24 - 25 日本唾液腺学会 2019年11月 [査読有り][通常論文]
  • 加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 対馬 那由多, 鈴木 崇祥, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
    頭頸部癌 45 3 300 - 304 (一社)日本頭頸部癌学会 2019年10月 
    我々は、局所進行外耳道扁平上皮癌に対する治療成績、特にドセタキセル、シスプラチン、5-FUの併用(TPF)の化学療法同時併用放射線療法(CCRT)の治療成績と安全性、および腫瘍の進展範囲と予後との関係を検討した。対象は当科で根治治療を行った外耳道癌扁平上皮癌で、ピッツバーグ分類のT3-4の21症例とした。その結果、硬膜と顎関節への進展が頸部転移と相関を示し、顎関節への進展が局所再発と相関を示した。全症例の2年粗生存率(OS)は61.1%、2年局所制御率(LC)は52.1%であった。CCRT症例では、TPF併用の2年OSは85.7%、それ以外では25.0%、TPF併用の2年LCは57.1%、それ以外では25.0%であった。また、TPF併用CCRTにおけるG3以上の白血球減少は55%、好中球減少は45%であった。TPF併用のCCRTは局所進行外耳道扁平上皮癌に対して高い有効性と安全性を示した。(著者抄録)
  • Noriyuki Fujima, Yukie Shimizu, Daisuke Yoshida, Satoshi Kano, Takatsugu Mizumachi, Akihiro Homma, Koichi Yasuda, Rikiya Onimaru, Osamu Sakai, Kohsuke Kudo, Hiroki Shirato
    Cancers 11 6 2019年06月10日 [査読有り][通常論文]
     
    The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters and intratumoral characteristics from T2-weighted images, tumor perfusion parameters from arterial spin labeling (ASL) and tumor diffusion parameters of five diffusion models from multi-b-value diffusion-weighted imaging (DWI) were obtained. Machine learning by a non-linear support vector machine (SVM) was used to construct the best diagnostic algorithm for the prediction of local control and failure. The diagnostic accuracy was evaluated using a 9-fold cross-validation scheme, dividing patients into training and validation sets. Classification criteria for the division of local control and failure in nine training sets could be constructed with a mean sensitivity of 0.98, specificity of 0.91, positive predictive value (PPV) of 0.94, negative predictive value (NPV) of 0.97, and accuracy of 0.96. The nine validation data sets showed a mean sensitivity of 1.0, specificity of 0.82, PPV of 0.86, NPV of 1.0, and accuracy of 0.92. In conclusion, a machine-learning algorithm using various MR imaging-derived data can be helpful for the prediction of treatment outcomes in patients with sinonasal SCCs.
  • 舌扁平上皮癌における改訂UICC TNM分類第8版の有用性の検討
    加納 里志, 対馬 那由多, 水町 貴諭, 鈴木 崇祥, 浜田 誠二郎, 本間 明宏
    頭頸部癌 45 2 157 - 157 (一社)日本頭頸部癌学会 2019年05月
  • 多形腺腫由来型唾液腺導管癌に特徴的な遺伝子発現の探索
    鈴木 崇洋, 加納 里志, 浜田 誠二郎, 対馬 那由多, 水町 貴諭, 本間 明宏
    頭頸部癌 45 2 221 - 221 (一社)日本頭頸部癌学会 2019年05月
  • 強度変調X線治療および強度変調陽子線治療における皮膚炎と皮膚線量に関する検討
    安田 耕一, 湊川 英樹, 出倉 康裕, 対馬 那由多, 鈴木 崇祥, 加納 里志, 水町 貴諭, 鬼丸 力也, 清水 伸一, 本間 明宏, 白土 博樹
    頭頸部癌 45 2 134 - 134 (一社)日本頭頸部癌学会 2019年05月
  • 外耳道癌における強度変調陽子線治療と強度変調X線治療との線量分布の比較
    出倉 康裕, 安田 耕一, 湊川 英樹, 対馬 那由多, 鈴木 崇祥, 加納 里志, 水町 貴諭, 鬼丸 力也, 清水 伸一, 本間 明宏, 白土 博樹
    頭頸部癌 45 2 138 - 138 (一社)日本頭頸部癌学会 2019年05月
  • 水町 貴諭, 加納 里志, 本間 明宏, 赤澤 美樹子, 長谷川 千春, 城石 陽子, 岡本 千秋, 熊谷 聡美, 西村 雅勝, 高崎 裕代, 武田 宏司, 安田 耕一, 湊川 英樹, 出倉 康裕, 鬼丸 力也, 白土 博樹, 福田 諭
    癌と化学療法 46 4 685 - 689 (株)癌と化学療法社 2019年04月 
    頭頸部癌に対する化学放射線療法により生じる代表的な副作用には口腔粘膜炎と体重減少があげられる。今回われわれは、中咽頭癌、下咽頭癌症例にてシスプラチンと放射線療法を同時併用する化学放射線療法施行症例において、ω3系脂肪酸高配合栄養機能食品であるプロシュアの口腔粘膜炎と体重減少に対する有用性の検討を行った。放射線治療開始から終了までの期間プロシュアを投与し、最大体重減少率、口腔粘膜炎、化学放射線療法完遂率についてプロシュアの介入を行っていない過去の当科症例を対照群として比較検討を行った。プロシュア投与群は対照群と比べ体重減少率の改善(7.3% vs 10.3%、p<0.01)、口腔粘膜炎の改善を認めた(CTCAE v3.0 Grade 3以上;24% vs 58%、p<0.05)が、化学放射線療法完遂率は両群の差を認めなかった(77% vs 60%、NS)。プロシュアの投与が化学放射線療法施行中において、体重減少や口腔粘膜炎の改善に寄与する可能性が示唆された。(著者抄録)
  • Mizumachi T, Kano S, Homma A, Akazawa M, Hasegawa C, Shiroishi Y, Okamoto C, Kumagai S, Nishimura M, Takasaki H, Takeda H, Yasuda K, Minatogawa H, Dekura Y, Onimaru R, Shirato H, Fukuda S
    Gan to kagaku ryoho. Cancer & chemotherapy 46 4 685 - 689 2019年04月 [査読有り][通常論文]
     
    © 2019 Japanese Journal of Cancer and Chemotherapy Publishers Inc.. All rights reserved. Background: Oral mucositis and body weight loss are the most critical conditions known to lead to the discontinuation of chemoradiotherapy for head and neck cancer. We investigated the effect of a nutritional supplement with a high blend ratio of co-3 fatty acids (Prosure®) on body weight loss, oral mucositis, and the completion rate of chemoradiotherapy in patients with oropharyngeal and hypopharyngeal cancer. Patients and methods: The study group comprised patients with oropharyngeal and hypopharyngeal cancer who were treated with concomitant cisplatin and 70 Gy of radiotherapy. These patients received 2 packs of Prosure® per day during chemoradiotherapy. Results: A total of 17 patients were included in this study. The reduction in body weight was significantly improved compared with that in the historical control group that did not receive Prosure® (7.3% vs 10.3%, p<0.0l), and the rate of Grade 3-4 oral mucositis was significantly reduced for the patient groups that received Prosure® (CTCAE v3.0 Grade≥ 3; 24% vs 58%, p<0.05). The completion rate of chemoradiotherapy was not significantly different between both groups (77% vs 60%, NS). Conclusions: A nutritional supplement with a high blend ratio of ω-3 fatty acids (Prosure®) had effects on oral mucositis and body weight loss in head and neck cancer patients treated with chemoradiotherapy.
  • Fujima Noriyuki, Homma Akihiro, Harada Taisuke, Shimizu Yukie, Tha Khin Khin, Kano Satoshi, Mizumachi Takatsugu, Li Ruijiang, Kudo Kohsuke, Shirato Hiroki
    CANCER IMAGING 19 2019年02月04日 [査読有り][通常論文]
  • Noriyuki Fujima, Akihiro Homma, Taisuke Harada, Yukie Shimizu, Khin Khin Tha, Satoshi Kano, Takatsugu Mizumachi, Ruijiang Li, Kohsuke Kudo, Hiroki Shirato
    Cancer imaging : the official publication of the International Cancer Imaging Society 19 1 5 - 5 2019年02月04日 [査読有り][通常論文]
     
    BACKGROUND: To assess the utility of histogram and texture analysis of magnetic resonance (MR) fat-suppressed T2-weighted imaging (Fs-T2WI) for the prediction of histological diagnosis of head and neck squamous cell carcinoma (SCC) and malignant lymphoma (ML). METHODS: The cases of 57 patients with SCC (45 well/moderately and 12 poorly differentiated SCC) and 10 patients with ML were retrospectively analyzed. Quantitative parameters with histogram features (relative mean signal, coefficient of variation, kurtosis and skewness) and gray-level co-occurrence matrix (GLCM) features (contrast, correlation, energy and homogeneity) were calculated using Fs-T2WI data with a manual tumor region of interest (ROI). RESULTS: The following significantly different values were obtained for the total SCC versus ML groups: relative mean signal (3.65 ± 0.86 vs. 2.61 ± 0.49), contrast (72.9 ± 16.2 vs. 49.3 ± 8.7) and homogeneity (2.22 ± 0.25 × 10- 1 vs. 2.53 ± 0.12 × 10- 1). In the comparison of the SCC histological grades, the relative mean signal and contrast were significantly lower in the poorly differentiated SCC (2.89 ± 0.63, 56.2 ± 12.9) compared to the well/moderately SCC (3.85 ± 0.81, 77.5 ± 13.9). The homogeneity in poorly differentiated SCC (2.56 ± 0.15 × 10- 1) was higher than that of the well/moderately SCC (2.1 ± 0.18 × 10- 1). CONCLUSIONS: Parameters obtained by histogram and texture analysis of Fs-T2WI may be useful for noninvasive prediction of histological type and grade in head and neck malignancy.
  • Satoshi Kano, Shinya Morita, Yuji Nakamaru, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Akira Nakazono, Atsushi Fukuda, Koichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Akihiro Homma
    Japanese Journal of Head and Neck Cancer 45 3 300 - 304 2019年 [査読有り][通常論文]
     
    © 2019, Japan Society for Head and Neck Cancer. All rights reserved. We analyzed the treatment outcomes and safety of concomitant chemoradiotherapy (CCRT), especially with a combination of docetaxel, cisplatin and 5FU (TPF), for local advanced external auditory canal squamous cell carcinomas. In addition, we analyzed the correlation between tumor invasion site and prognosis. The study comprised 21 patients with the following criteria: (1) external auditory canal squamous cell carcinomas which were subject to radical treatment at Hokkaido University Hospital between 2007 and 2017, and (2) T3–4 classified according to the University of Pittsburg system. As a result, tumor invasion into the dura or temporomandibular joint was associated with neck lymph node metastasis, and tumor invasion into the temporomandibular joint was associated with local recurrence. The 2-year overall survival rate (OS) and 2-year local control rate (LC) were 61.1% and 52.1% in all patients, respectively. In patients treated with CCRT, the 2-year OS was 85.7% in CCRT with TPF and 25.0% in CCRT with others, and the 2-year LC was 57.1% in CCRT with TPF and 25.0% in CCRT with others. Grade 3︲4 leucopenia and neutropenia occurred in 55% and 45% of patients treated with CCRT with TPF, respectively. CCRT with TPF shows high efficacy and safety for local advanced external auditory canal squamous cell carcinomas.
  • Makoto Urano, Hideaki Hirai, Yuichiro Tada, Daisuke Kawakita, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Yukiko Sato, Natsuki Saigusa, Masato Nakaguro, Toyoyuki Hanazawa, Toshitaka Nagao
    Histopathology 73 6 943 - 952 2018年12月 [査読有り][通常論文]
     
    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.
  • N Fujima, K Hirata, T Shiga, R Li, K Yasuda, R Onimaru, K Tsuchiya, S Kano, T Mizumachi, A Homma, K Kudo, H Shirato
    Clinical radiology 73 12 1059.e1-1059.e8  2018年12月 [査読有り][通常論文]
     
    AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.
  • 本間 明宏, 加納 里志, 水町 貴諭, 中薗 彬, 鈴木 崇祥, 坂下 智博, 福田 諭, 鬼丸 力也, 安田 耕一, 湊川 英樹, 出倉 康裕, 土屋 和彦, 白土 博樹
    日本気管食道科学会会報 69 5 319 - 320 (NPO)日本気管食道科学会 2018年10月
  • Noriyuki Fujima, Kenji Hirata, Tohru Shiga, Koichi Yasuda, Rikiya Onimaru, Kazuhiko Tsuchiya, Satoshi Kano, Takatsugu Mizumachi, Akihiro Homma, Kohsuke Kudo, Hiroki Shirato
    Quantitative imaging in medicine and surgery 8 8 788 - 795 2018年09月 [査読有り][通常論文]
     
    Background: To investigate the utility of quantitative morphological and intratumoral characteristics obtained by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) for the prediction of treatment outcome in patients with nasal or paranasal cavity squamous cell carcinoma (SCC). Methods: Twenty-four patients with nasal or paranasal cavity SCC who received curative non-surgical therapy (a combination of super-selective arterial cisplatin infusion and radiotherapy) were retrospectively analyzed. From pre-treatment FDG-PET data, a total of 13 parameters of quantitative morphological characteristics (tumor volume, surface area and sphericity), intratumoral characteristics (the maximum and mean standard uptake value, three intratumoral histogram and four textural parameters) and total lesion glycolysis (TLG) were respectively calculated. Information regarding the treatment outcome was determined from the histological diagnosis or clinical follow-up. Each of the 13 quantitative parameters as well as T- and N-stage was assessed for its relation to treatment outcome of local control or failure. Results: In univariate analysis, significant differences in surface area and sphericity between the local control and failure groups were observed. The receiver operating characteristic (ROC) curve analysis showed that sphericity had the highest accuracy of 0.88. In the multivariate analysis, sphericity was revealed as an independent predictor of the local control or failure. Conclusions: The quantitative parameters of sphericity are useful to predict the treatment outcome in patients with nasal or paranasal SCC.
  • Morita S, Mizumachi T, Nakamaru Y, Sakashita T, Kano S, Hoshino K, Fukuda A, Fujiwara K, Homma A
    International journal of clinical oncology 23 6 1029 - 1037 2018年07月 [査読有り][通常論文]
     
    BACKGROUND: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. METHODS: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. RESULTS: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. CONCLUSION: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.
  • Shinichiro Yasukawa, Satoshi Kano, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Masanobu Suzuki, Takayoshi Suzuki, Akira Nakazono, Shinya Tanaka, Hiroshi Nishihara, Akihiro Homma
    International Journal of Clinical Oncology 23 5 1 - 9 2018年05月19日 [査読有り][通常論文]
     
    Background: The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated. Methods: To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing. Results: The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene. Conclusion: Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.
  • 唾液腺導管癌における免疫染色およびRT-PCR法を用いた分子生物学的プロファイルの検討
    鈴木 崇祥, 加納 里志, 畑中 佳奈子, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 畑中 豊, 松野 吉宏, 本間 明宏
    頭頸部癌 44 2 179 - 179 (一社)日本頭頸部癌学会 2018年05月
  • 当科における局所進行外耳道扁平上皮癌の治療成績の検討
    加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
    頭頸部癌 44 2 181 - 181 (一社)日本頭頸部癌学会 2018年05月
  • 当科における局所進行外耳道扁平上皮癌の治療成績の検討
    加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
    頭頸部癌 44 2 181 - 181 (一社)日本頭頸部癌学会 2018年05月 [査読無し][通常論文]
  • 唾液腺導管癌における免疫染色およびRT-PCR法を用いた分子生物学的プロファイルの検討
    鈴木 崇祥, 加納 里志, 畑中 佳奈子, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 畑中 豊, 松野 吉宏, 本間 明宏
    頭頸部癌 44 2 179 - 179 (一社)日本頭頸部癌学会 2018年05月 [査読無し][通常論文]
  • Satoshi Kano, Tomohiro Sakashita, Nayuta Tsushima, Takatsugu Mizumachi, Akira Nakazono, Takayoshi Suzuki, Shinichiro Yasukawa, Akihiro Homma
    International Journal of Clinical Oncology 23 5 1 - 7 2018年04月19日 [査読有り][通常論文]
     
    Background: The revised 8th edition of the AJCC/UICC staging system was released in January 2017, and depth of invasion (DOI) was added to the new criteria for T classification in oral cavity cancer. In this study, we evaluated whether the 8th edition presents the prognosis and risk of nodal metastasis in patients with squamous cell carcinoma of tongue more accurately than did the 7th edition. Methods: The data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition. Results: Seven patients previously staged as T1 based on the criteria in the 7th edition were reclassified as T2 based on the 8th edition, while 19 T2 patients were reclassified as T3, and 9 T4a patients were reclassified as T3. T3 in the 8th edition represents a homogenous population showing the same prognosis, while T2 in the 8th edition represents a heterogenous population. Nodal metastasis was significantly correlated with T classification in both editions and DOI. However, neither the T classification in the 7th or 8th edition, nor DOI could predict the probability of potential nodal metastasis in patients with cN0 disease. Conclusions: The classification on T3 in the 8th edition can be seen as reasonable with regard to prognosis. Nodal metastasis was significantly correlated with T classification and DOI however, the probability of subsequent nodal metastasis in patients with T2N0 was almost same for the criteria in the 7th and 8th editions, therefore, the same careful management as before is required for patients with N0 disease.
  • 安川 真一郎, 加納 里志, 畠山 博充, 中丸 裕爾, 高木 大, 水町 貴諭, 鈴木 正宣, 鈴木 崇祥, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 539 - 539 (一社)日本耳鼻咽喉科学会 2018年04月
  • 鈴木 崇祥, 加納 里志, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 541 - 541 (一社)日本耳鼻咽喉科学会 2018年04月
  • 中丸 裕爾, 高木 大, 鈴木 正宣, 加納 里志, 水町 貴諭, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 567 - 567 (一社)日本耳鼻咽喉科学会 2018年04月
  • 加納 里志, 水町 貴諭, 対馬 那由多, 鈴木 崇祥, 中薗 彬, 安川 真一郎, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 578 - 578 (一社)日本耳鼻咽喉科学会 2018年04月 [査読無し][通常論文]
  • 中丸 裕爾, 高木 大, 鈴木 正宣, 加納 里志, 水町 貴諭, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 567 - 567 (一社)日本耳鼻咽喉科学会 2018年04月 [査読無し][通常論文]
  • 唾液腺導管癌における重要な治療標的分子の遺伝子変異と蛋白発現 その予後・組織発生との関連
    志村 智隆, 多田 雄一郎, 川北 大介, 塚原 清彰, 加納 里志, 清水 顕, 今西 順久, 大上 研二, 佐藤 雄一郎, 平井 秀明, 長尾 俊孝, 小林 一女
    日本耳鼻咽喉科学会会報 121 4 542 - 542 (一社)日本耳鼻咽喉科学会 2018年04月 [査読無し][通常論文]
  • 鈴木 崇祥, 加納 里志, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 541 - 541 (一社)日本耳鼻咽喉科学会 2018年04月 [査読無し][通常論文]
  • 鼻副鼻腔内反性乳頭腫の悪性転化に関与する遺伝子変異の解析
    安川 真一郎, 加納 里志, 畠山 博充, 中丸 裕爾, 高木 大, 水町 貴諭, 鈴木 正宣, 鈴木 崇祥, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 121 4 539 - 539 (一社)日本耳鼻咽喉科学会 2018年04月 [査読無し][通常論文]
  • 咽喉頭直達鏡固定システムの試作
    本間 明宏, 清水 勇一, 畠山 博充, 溝口 兼司, 水町 貴諭, 加納 里志, 坂下 智博, 福田 諭
    耳鼻咽喉科展望 61 1 66 - 67 耳鼻咽喉科展望会 2018年02月 [査読無し][通常論文]
  • Tomotaka Shimura, Yuichiro Tada, Hideaki Hirai, Daisuke Kawakita, Satoshi Kano, Kiyoaki Tsukahara, Akira Shimizu, Soichiro Takase, Yorihisa Imanishi, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Yukiko Sato, Chihiro Fushimi, Hideaki Takahashi, Takuro Okada, Hiroki Sato, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Mizuo Ando, Shinji Kohsaka, Toyoyuki Hanazawa, Hideaki Chazono, Yoshiyuki Kadokura, Hitome Kobayashi, Toshitaka Nagao
    Oncotarget 9 2 1852 - 1867 2018年01月05日 [査読有り][通常論文]
     
    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.
  • 舌扁平上皮癌における新しいTNM分類の有用性の検討
    加納 里志, 中薗 彬, 水町 貴諭, 本間 明宏
    日本癌治療学会学術集会抄録集 55回 P157 - 4 (一社)日本癌治療学会 2017年10月 [査読無し][通常論文]
  • 舌扁平上皮癌における新しいTNM分類の有用性の検討
    加納 里志, 中薗 彬, 水町 貴諭, 本間 明宏
    日本癌治療学会学術集会抄録集 55回 P157 - 4 (一社)日本癌治療学会 2017年10月 [査読無し][通常論文]
  • Hiromitsu Hatakeyama, Kimiko Hoshino, Kenji Mizoguchi, Takayoshi Suzuki, Kanako C. Hatanaka, Yukie Yamaya, Satoshi Kano, Takatsugu Mizumachi, Akihiro Homma
    DIAGNOSTIC CYTOPATHOLOGY 45 10 928 - 933 2017年10月 [査読有り][通常論文]
     
    Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75-year-old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki-67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki-67 expression. Epithelial-mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki-67 and EMT marker expression may support the diagnosis.
  • 舌扁平上皮癌における新しいTNM分類の有用性の検討
    加納 里志, 坂下 智博, 水町 貴諭, 本間 明宏
    口腔・咽頭科 30 3 429 - 429 日本口腔・咽頭科学会 2017年08月 [査読無し][通常論文]
  • Takatsugu Mizumachi, Akihiro Homma, Tomohiro Sakashita, Satoshi Kano, Hiromitsu Hatakeyama, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 22 4 682 - 689 2017年08月 [査読有り][通常論文]
     
    Background Several studies have demonstrated that the seventh edition of the American Joint Committee on Cancer/American Joint Committee on Cancer (AJCC/UICC) TNM staging system does not consistently distinguish between prognostic subgroups for human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPSCC). The eighth edition of the AJCC/UICC TNM staging system came into effect for use with HPV-mediated OPSCC on or after 1 January 2017. This study confirms that the eighth edition of the AJCC/UICC TNM staging system for HPV-mediated OPSCC accurately reflects disease outcomes. Patients and methods We retrospectively analyzed 195 patients with OPSCC treated at Hokkaido University Hospital, Sapporo, Japan between 1998 and 2015. HPV status was evaluated by immunohistochemical analysis of p16. Results Of the 195 OPSCC patients evaluated, 111 (56.9%) were p16 positive and 84 (43.1%) were p16 negative. The 3-year overall survival rate (OS) was significantly lower in the p16-negative patients with stage III-IV in comparison with those with stage I-II (55.0 vs. 93.1%, respectively; p < 0.01). The 3-year OS did not differ significantly between stage I-II and stage III-IV in the p16-positive patients (86.7 vs 87.7%). According to the eighth edition of the AJCC/UICC TNM staging system, stage I-II and stage III can be differentiated on the basis of the 3-year OS in the p16-positive patients (90.9 vs 70.2%, respectively; p < 0.01). Conclusions The seventh edition of the AJCC/UICC TNM staging system is suitable for use with p16-negative patients; however, it does not effectively discriminate between p16-positive patients. Therefore, the eighth edition of the AJCC/UICC TNM staging system is more suitable for HPV-mediated OPSCC in Japan.
  • Soichiro Takase, Satoshi Kano, Yuichiro Tada, Daisuke Kawakita, Tomotaka Shimura, Hideaki Hirai, Kiyoaki Tsukahara, Akira Shimizu, Yorihisa Imanishi, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Yukiko Sato, Chihiro Fushimi, Takuro Okada, Hiroki Sato, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Toyoyuki Hanazawa, Hideaki Chazono, Robert Yoshiyuki Osamura, Toshitaka Nagao
    ONCOTARGET 8 35 59023 - 59035 2017年08月 [査読有り][通常論文]
     
    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, < 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.
  • Hiromitsu Hatakeyama, Noriyuki Fujima, Kazuhiko Tsuchiya, Kenji Mizoguchi, Takatsugu Mizumachi, Tomohiro Sakashita, Satoshi Kano, Akihiro Homma, Satoshi Fukuda
    CANCER IMAGING 17 2017年07月 [査読有り][通常論文]
     
    Background: Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone. Methods: The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis. Results: A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone. Conclusion: Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.
  • Tomohiko Kakizaki, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Tomohiro Sakashita, Satoshi Kano, Akihiro Homma, Satoshi Fukuda
    ONCOLOGY LETTERS 14 1 987 - 992 2017年07月 [査読有り][通常論文]
     
    Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a > 2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.
  • Hatakeyama H, Fujima N, Tsuchiya K, Mizoguchi K, Mizumachi T, Sakashita T, Kano S, Homma A, Fukuda S
    Cancer imaging : the official publication of the International Cancer Imaging Society 17 1 22 - 22 2017年07月 [査読有り][通常論文]
     
    BACKGROUND: Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone. METHODS: The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis. RESULTS: A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone. CONCLUSION: Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.
  • 北海道大学病院における舌癌治療の現況・選択的動注化学療法の意義
    坂下 智博, 本間 明宏, 畠山 博充, 加納 里志, 水町 貴諭, 蠣崎 文彦, 対馬 那由多, 福田 諭
    耳鼻咽喉科展望 60 補冊1 50 - 51 耳鼻咽喉科展望会 2017年06月 [査読無し][通常論文]
  • 北海道大学病院における喉頭癌治療の現況
    中薗 彬, 水町 貴諭, 本間 明宏, 畠山 博充, 加納 里志, 古沢 純, 坂下 智博, 鈴木 章之, 福田 諭
    耳鼻咽喉科展望 60 補冊1 8 - 9 耳鼻咽喉科展望会 2017年06月 [査読無し][通常論文]
  • 舌扁平上皮癌における腫瘍免疫チェックポイントの解析
    加納 里志, 鈴木 崇祥, 倉本 倫之介, 坂下 智博, 水町 貴諭, 畠山 博充, 本間 明宏, 福田 諭
    頭頸部癌 43 2 207 - 207 日本頭頸部癌学会 2017年05月 [査読無し][通常論文]
  • 水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 福田 諭
    日本耳鼻咽喉科学会会報 120 4 611 - 611 (一社)日本耳鼻咽喉科学会 2017年04月 [査読無し][通常論文]
  • 唾液腺導管癌ではFOXA1の発現が予後予測因子となる
    平井 秀明, 多田 雄一郎, 川北 大介, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 長尾 俊孝
    日本病理学会会誌 106 1 329 - 329 (一社)日本病理学会 2017年03月 [査読無し][通常論文]
  • 【頭頸部癌学-診断と治療の最新研究動向-】 頭頸部癌臨床研究の動向 多施設での中咽頭癌の治療成績(手術、放射線)
    加納 里志, 本間 明宏
    日本臨床 75 増刊2 頭頸部癌学 184 - 189 (株)日本臨床社 2017年02月 [査読無し][通常論文]
     
    頭頸部癌グループに属する12施設486症例(男414例、女72例)を対象に、後ろ向きに検討した。根治治療の内訳は手術が41%、放射線単独治療が24%、化学療法同時併用放射線治療(CCRT)が35%であった。手術治療は経口切除が36%、外切開が64%で、喉頭温存できたのは86%であった。再建手術は56%に、頸部郭清は76%に施行された。放射線単独治療のうち2例で小線源治療が行われていた。CCRTにおける化学療法で最も多かったのはシスプラチンと5FUの併用、次いでシスプラチン単剤であった。5年粗生存率は手術群で74.8%、放射線単独群で66.0%、CCRT群で67.1%であった。手術群とCCRT群のmatched-pair解析で抽出された186例の5年無増悪生存率は手術群51.0%、CCRT群54.4%、5年局所制御率はそれぞれ75.2%、80.3%であった。さらにT3-T4の局所進行例に限定すると、5年無増悪生存率は手術群37.6%、CCRT群50.2%、5年局所制御率はそれぞれ64.1%、73.2%であった。
  • Shinya Morita, Yuji Nakamaru, Akihiro Homma, Shinichiro Yasukawa, Hiromitsu Hatakeyama, Tomohiro Sakashita, Satoshi Kano, Atsushi Fukuda, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 22 1 181 - 189 2017年02月 [査読有り][通常論文]
     
    Background The aim of this study was to investigate the expression of p53, p16, cyclin D1, epidermal growth factor receptor (EGFR) and Notch1 in temporal bone squamous cell carcinoma (TBSCC) tissue samples by immunohistochemistry (IHC), and to evaluate the association between these biomarkers and clinicopathological features. Methods We performed a retrospective, single-institution review of 30 TBSCC patients treated with curative intent between April 2006 and March 2015. All tissue samples were obtained from pretreatment biopsy specimens or surgical specimens and using IHC staining. Results Ten patients were categorized as T1, seven as T2, five as T3 and eight as T4. Nine patients had clinically positive lymph node metastasis. The positive expression of p53 and EGFR was significantly associated with T classification (P = 0.042 and P = 0.0039). EGFR expression was significantly more frequent in patients with positive lymph node metastasis compared with patients without node involvement (P = 0.017). In the analysis of the association between protein expression by IHC staining and prognosis, the positive expression of EGFR and Notch1 was significantly correlated with poor survival outcomes in TBSCC (P = 0.015 and P = 0.025) Conclusion Overexpression of p53 and EGFR may be valuable biomarkers for identifying individuals at high risk of developing tumors in TBSCC. Furthermore, the positive expression of EGFR was significantly associated with poor survival outcome. Anti-EGFR therapy has potential for use as the treatment modality of choice for advancedstage TBSCC as well as other head and neck squamous cell carcinomas.
  • Satoshi Kano, Akihiro Homma, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Tomohiro Sakashita, Tomohiko Kakizaki, Satoshi Fukuda
    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 39 2 247 - 253 2017年02月 [査読有り][通常論文]
     
    Background. The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers. Methods. The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Results. Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor. Conclusion. Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. (C) 2016 Wiley Periodicals, Inc.
  • Daisuke Kawakita, Yuichiro Tada, Yorihisa Imanishi, Shintaro Beppu, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Akira Shimizu, Yukiko Sato, Chihiro Fushimi, Soichiro Takase, Takuro Okada, Hiroki Sato, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Tomotaka Shimura, Toyoyuki Hanazawa, Shingo Murakami, Toshitaka Nagao
    ONCOTARGET 8 1 1083 - 1091 2017年01月 [査読有り][通常論文]
     
    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 (>= 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<0.001). Additionally, high C-reactive protein (CRP) (>= 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<0.001). These associations were consistent with multivariate analysis adjusted for established prognostic factors. Although we also found significant association of high NLR (>= 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.
  • Tatsuya Kato, Daiyoon Lee, Licun Wu, Priya Patel, Ahn Jin Young, Hironobu Wada, Hsin Pei Hu, Hideki Ujiie, Mitsuhito Kaji, Satoshi Kano, Shinichi Matsuge, Hiromitsu Domen, Hiromi Kanno, Yutaka Hatanaka, Kanako C. Hatanaka, Kichizo Kaga, Yoshiro Matsui, Yoshihiro Matsuno, Marc De Perrot, Kazuhiro Yasufuku
    International Journal of Oncology 49 6 2411 - 2420 2016年12月 
    Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.
  • 唾液腺導管癌ではFOXA1の発現が予後予測因子となる
    平井 秀明, 多田 雄一郎, 川北 大介, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 清水 顕, 今西 順久, 長尾 俊孝
    日本唾液腺学会誌 57 31 - 31 日本唾液腺学会 2016年11月 [査読無し][通常論文]
  • 加納 里志
    耳鼻と臨床 62 Suppl.1 S9,S28 - S16,S28 耳鼻と臨床会 2016年11月 [査読無し][通常論文]
     
    近年、進行中咽頭癌に対する標準治療が手術から化学療法同時併用放射線治療(CCRT)に変わりつつある。しかしながら、これまでに中咽頭癌に対する手術とCCRTを直接比較した報告はなく、今後も新たなランダマイズ試験が行われることは難しいと思われる。そこで本研究では、多施設より収集した中咽頭癌症例523例から、matched-pair解析という手法を用いて背景をそろえた2群(手術群とCCRT群)を抽出し比較検討したところ、無増悪生存率および局所制御率では有意差なく、治療後の嚥下障害に関してはCCRT群の方が少なかった。また、CCRT施行例での局所再発率は20.6%であり、その内の31.4%に救済手術が施行された。進行中咽頭癌に対するCCRTは手術と同等の治療成績であり、治療後の嚥下機能も優れているが、局所再発した場合の救済率は低いため、慎重な治療方法の選択が必要である。(著者抄録)
  • Nayuta Tsushima, Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Tomohiko Kakizaki, Takayoshi Suzuki, Satoshi Fukuda
    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 273 11 3987 - 3992 2016年11月 [査読有り][通常論文]
     
    Prophylactic neck dissection (PND) for patients with clinically N0 (cN0) tongue carcinoma remains controversial. We assessed the efficacy of PND for patients with cN0 tongue squamous cell carcinoma (SCC) and investigated the prognostic role of tumor thickness as assessed by diagnostic imaging in predicting the risk of nodal micrometastasis or late nodal recurrence. Eighty-eight patients with cN0 tongue carcinomas underwent surgical treatment. Tumor thickness was measured from magnetic resonance (MR) images or computed tomography (CT) scans. The overall survival rates of patients with or without PND were 94 and 81 %, respectively (p = 0.2857). MR images or CT scans were available for 68 patients. A tumor thickness aeyen10 mm or aeyen5 mm did not increase the probability of nodal metastasis, with late nodal metastasis observed in 15 % of patients with graphically undetected small tumors. PND appears to have the potential to improve overall survival for patients with cN0 tongue SCC. Careful follow-up management or PND is considered to be needed regardless of tumor thickness in the pre-treatment evaluation.
  • Takayoshi Suzuki, Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Daisuke Yoshida, Noriyuki Fujima, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Fumiyuki Suzuki, Satoshi Fukuda
    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 273 10 3331 - 3336 2016年10月 [査読有り][通常論文]
     
    We sought to evaluate the efficacy and feasibility of superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed. The ascending pharyngeal artery was targeted for the treatment of RPLN metastasis in 9 patients. The median total dose of cisplatin was 26.6 mg/m(2) (mean 31.5 mg/m(2), range 11.7-87.9 mg/m(2)). In the remaining patient, the RPLN was supplied by the ascending palatine artery. As grade 3 and 4 adverse effects, leukopenia was observed in three, mucositis in four and nausea in one patient. No neurological complications were observed in any patients. Metastatic RPLNs were evaluated as a complete response in all patients. There was no recurrence of RPLN metastasis in any patients. Four patients remain alive without any evidence of disease and six patients died of disease. The 5-year overall survival rate was 50 %. We have shown that superselective intra-arterial cisplatin infusion for RPLNs was a feasible and effective approach for HNSCC patients with RPLN metastasis.
  • 唾液腺導管癌における免疫組織化学的発現解析 多施設共同による152症例の検討
    加納 里志, 高瀬 聡一郎, 多田 雄一郎, 川北 大介, 塚原 清彰, 清水 顕, 今西 順久, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 佐藤 由紀子, 志村 智隆, 花澤 豊行, 長村 義之, 長尾 俊孝
    日本癌治療学会学術集会抄録集 54回 PS - 3 (一社)日本癌治療学会 2016年10月 [査読無し][通常論文]
  • Shinya Morita, Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Atsushi Fukuda, Satoshi Fukuda
    OTOLOGY & NEUROTOLOGY 37 8 1174 - 1182 2016年09月 [査読有り][通常論文]
     
    Objective: We aimed to evaluate the prognostic factors and efficacy of treatment modalities for patients with temporal bone cancer, and to determine if definitive chemoradiotherapy (CRT) for advanced-stage disease can provide a substitute for highly invasive surgeries. Study Design: Retrospective case series. Setting: Tertiary referral center. Patients: Sixty-six patients with previously untreated squamous cell carcinoma of the temporal bone treated with curative intent between April 1997 and March 2015. Intervention: Surgery alone, radiotherapy (RT) alone, surgery followed by RT or definitive CRT. Main Outcome Measure: The overall survival (OS) rate. Results: The 5-year OS rate for each T classification was 100% for T1, 76.2% for T2, 55.6% for T3, and 36.7% for T4. Univariable and multivariable analysis showed that T classification was an independent predictor of the OS rate (hazard ratio 5.66; 95% confidence interval 1.51-27.0; p = 0.015). Analysis by treatment modality revealed that the 5-year OS rate for patients with T1-2 was 100% for surgery and 81.3% for RT alone. The rate for patients with T3-4 was 52.1% for definitive CRT and 55.6% for surgery followed by RT with or without chemotherapy. Conclusions: Patients with T1-2 benefited from surgical intervention without significant morbidity or mortality. Our findings also suggested that definitive CRT might be appropriate as the first-line treatment for T3-4, especially in cases with unresectable tumors.
  • Tatsuya Kato, Daiyoon Lee, Licun Wu, Priya Patel, Ahn Jin Young, Hironobu Wada, Hsin Pei Hu, Hideki Ujiie, Mitsuhito Kaji, Satoshi Kano, Shinichi Matsuge, Hiromitsu Domen, Kichizo Kaga, Yoshiro Matsui, Hiromi Kanno, Yutaka Hatanaka, Kanako C. Hatanaka, Yoshihiro Matsuno, Marc De Perrot, Kazuhiro Yasufuku
    International Journal of Oncology 49 2 448 - 456 2016年08月 
    Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription- polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.
  • 唾液腺導管癌のバイオマーカー発現の包括的解明
    増淵 達夫, 多田 雄一郎, 高瀬 総一郎, 三浦 弘規, 伏見 千宙, 松木 崇, 川北 大介, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二
    国際医療福祉大学学会誌 21 抄録号 82 - 82 国際医療福祉大学学会 2016年08月 [査読無し][通常論文]
  • Akihiro Homma, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rinnosuke Kuramoto, Yuji Nakamaru, Rikiya Onimaru, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    PLOS ONE 11 8 e0161734  2016年08月 [査読有り][通常論文]
     
    Objective Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7-42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports. Methods We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan. Results At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303). Conclusions The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT.
  • Kuninori Otsuka, Yorihisa Imanishi, Yuichiro Tada, Daisuke Kawakita, Satoshi Kano, Kiyoaki Tsukahara, Akira Shimizu, Hiroyuki Ozawa, Kenji Okami, Akihiro Sakai, Yuichiro Sato, Yushi Ueki, Yukiko Sato, Toyoyuki Hanazawa, Hideaki Chazono, Kaoru Ogawa, Toshitaka Nagao
    ANNALS OF SURGICAL ONCOLOGY 23 6 2038 - 2045 2016年06月 [査読有り][通常論文]
     
    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 < 0.001) and N1 and N2 (p = 0.047 and < 0.001, respectively) were independent prognostic factors for OS, whereas the primary site of the minor salivary and sublingual gland (p < 0.001) and N2 (p < 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.
  • 中咽頭扁平上皮癌に対する化学放射線療法施行症例の臨床的検討
    水町 貴諭, 坂下 智博, 加納 里志, 畠山 博充, 本間 明宏, 土屋 和彦, 安田 耕一, 鬼丸 力也, 白土 博樹, 福田 諭
    頭頸部癌 42 2 181 - 181 (一社)日本頭頸部癌学会 2016年05月 [査読無し][通常論文]
  • 化学放射線治療を行った頭頸部扁平上皮癌患者における治療前血中炎症細胞と予後に関する検討
    加納 里志, 本間 明宏, 畠山 博充, 水町 貴諭, 坂下 智博, 福田 諭
    頭頸部癌 42 2 183 - 183 (一社)日本頭頸部癌学会 2016年05月 [査読無し][通常論文]
  • 下咽頭癌に対する化学放射線療法後の嚥下障害 欧米の報告との比較
    本間 明宏, 畠山 博充, 水町 貴諭, 加納 里志, 坂下 智博, 鬼丸 力也, 土屋 和彦, 安田 耕一, 白土 博樹, 福田 諭
    頭頸部癌 42 2 214 - 214 (一社)日本頭頸部癌学会 2016年05月 [査読無し][通常論文]
  • 頭頸部癌における免疫チェックポイント分子と増殖・刺激因子シグナル伝達経路
    畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 本間 明宏, 福田 諭
    頭頸部癌 42 2 220 - 220 (一社)日本頭頸部癌学会 2016年05月 [査読無し][通常論文]
  • 唾液腺導管癌における標的遺伝子変異と免疫組織化学的発現の検討 その臨床病理学的因子との関連
    志村 智隆, 多田 雄一郎, 川北 大介, 塚原 清彰, 加納 里志, 清水 顕, 高瀬 聡一郎, 今西 順久, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 長尾 俊孝
    頭頸部癌 42 2 174 - 174 (一社)日本頭頸部癌学会 2016年05月 [査読無し][通常論文]
  • 根治手術を施行した唾液腺導管癌における術前採血マーカーの予後への影響
    別府 慎太郎, 多田 雄一郎, 川北 大介, 塚原 清彰, 加納 里志, 清水 顕, 今西 順久, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 花澤 豊行, 長尾 俊孝
    頭頸部癌 42 2 174 - 174 (一社)日本頭頸部癌学会 2016年05月 [査読無し][通常論文]
  • 喉頭腫瘍におけるHPV感染の検討
    水町 貴諭, 中薗 彬, 坂下 智博, 加納 里志, 畠山 博充, 本間 明宏, 福田 諭
    日本気管食道科学会会報 67 2 s61 - s61 (NPO)日本気管食道科学会 2016年04月 [査読無し][通常論文]
  • 中咽頭癌に合併し多発骨転移との鑑別が困難であった急性リンパ性白血病の一例
    渡邊 史郎, 真鍋 治, 平田 健司, 菊地 恒矢, 牧野 俊一, 豊永 拓哉, 小林 健太郎, 内山 裕子, 志賀 哲, 加納 里志, 玉木 長良
    核医学 53 1 507 - 507 (一社)日本核医学会 2016年02月 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Jun Furusawa, Satoshi Kano, Takatsugu Mizumachi, Satoshi Iizuka, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 20 6 1081 - 1085 2015年12月 [査読有り][通常論文]
     
    Background Pyriform sinus squamous cell carcinoma (SCC) has one of the worst prognoses of all upper aerodigestive tract cancers. Improving clinical outcomes for patients with hypopharyngeal SCC has been particularly challenging for head and neck surgeons and oncologists. Methods We investigated 30 patients with pyriform sinus SCC to verify the effectiveness of weekly cisplatin chemotherapy with concurrent radiotherapy. Cisplatin was administered at a dose of 40 mg/m(2) on weeks 1, 2, 3, 5, 6, and 7 during definitive radiotherapy with the aim of preserving the larynx. Results All 30 patients achieved definitive radiotherapy at a median dose of 70 Gy (range 64-70 Gy). Cisplatin was administrated concomitantly a median of five times (range 2-6 times). Persistent or recurrent primary disease was observed in four patients (13 %). Persistent or recurrent nodal metastasis was observed in five patients (17 %). Nine salvage surgeries were performed for eight patients, of whom seven survived without any evidence of disease. Post-operative complications were observed in two patients (22 %). The 5-year overall survival and locoregional control rates were 87 and 96 %, respectively. The 5-year laryngeal preservation rate was 74 %. Conclusions The regimen of weekly cisplatin CRT may be effective for pyriform sinus SCC; however, there were problems with strong selection bias in the current study due to the large number of T2 patients. Salvage surgery was safe and was able to improve the survival rate. This chemoradiation regimen was considered successful in preserving laryngeal function.
  • Jun Furusawa, Akihiro Homma, Rikiya Onimaru, Tomohiro Sakashita, Daisuke Yoshida, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    AURIS NASUS LARYNX 42 6 443 - 448 2015年12月 [査読有り][通常論文]
     
    Objective: We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC). Methods: Between April 2000 and March 2013,41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100-120 mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65-70 Gy). Results: During the median follow-up period of 5.5 years, a statistically significant difference in the 5-year overall survival was noted between patients with N0-1 (n = 14) and N2b-3 disease (n = 27). One-half of deaths were observed to be the result of distant metastasis. The 5-year local control and overall survival were significantly better in patients with unilateral than in those with bilateral primary tumors. All the patients with T4b disease (n = 3) died of disease within 2 years. Conclusion: Indications for RADPLAT in patients with HPC were defined as patients with unilateral tumors staged as T3-4a and N0-1. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Akihiro Homma, Yuji Nakamaru, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Jun Furusawa, Tomohiro Sakashita, Toshiaki Shichinohe, Yuma Ebihara, Satoshi Hirano, Hiroshi Furukawa, Toshihiko Hayashi, Yuhei Yamamoto, Satoshi Fukuda
    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 272 11 3551 - 3556 2015年11月 [査読有り][通常論文]
     
    Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.
  • 唾液腺導管癌における標的遺伝子変異と免疫組織化学的発現の検討 その臨床病理学的因子との関連
    志村 智隆, 多田 雄一郎, 川北 大介, 塚原 清彰, 加納 里志, 清水 顕, 今西 順久, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 長尾 俊孝
    日本唾液腺学会誌 56 25 - 25 日本唾液腺学会 2015年11月 [査読無し][通常論文]
  • 唾液腺導管癌におけるHER2下流シグナルの解析
    加納 里志, 本間 明宏, 畠山 博充, 水町 貴諭, 坂下 智博, 鈴木 崇祥, 福田 諭
    日本唾液腺学会誌 56 34 - 34 日本唾液腺学会 2015年11月 [査読無し][通常論文]
  • 唾液腺導管癌の臨床成績と予後因子 多施設共同による141例の検討
    大塚 邦憲, 今西 順久, 多田 雄一郎, 川北 大介, 花澤 豊行, 茶薗 英明, 加納 里志, 清水 顕, 塚原 清彰, 大上 研二, 酒井 昭博, 佐藤 雄一郎, 植木 雄志, 佐藤 由紀子, 小澤 宏之, 小川 郁, 長尾 俊孝
    日本唾液腺学会誌 56 35 - 35 日本唾液腺学会 2015年11月 [査読無し][通常論文]
  • Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Rikiya Onimaru, Shunsuke Terasaka, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiromitsu Hatakeyama, Jun Furusawa, Takatsugu Mizumachi, Satoshi Kano, Hiroki Shirato, Satoshi Fukuda
    AURIS NASUS LARYNX 42 5 377 - 381 2015年10月 [査読有り][通常論文]
     
    Objective: Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes. Methods: A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No patient had lymph node metastasis. Results: Twelve patients were treated with surgery with/without radiotherapy and with/without chemotherapy. Of these, 4 underwent endoscopic surgery without an open approach and 3 required an anterior skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy alone, and 4 and 8 with intravenous and intra-arterial chemotherapy, respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%, 71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a, and T4b disease was 74.1%, 71.4%, and 29.0%, respectively. Conclusion: Our treatment policy for patients with SCC of NC&ES, which basically follows the NCCN guideline, was considered to be appropriate. However, several points in terms of surgery and nonsurgical approach remain to be solved through further research. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • 蠣崎 文彦, 加納 里志, 折舘 伸彦, 本間 明宏, 鈴木 清護, 畠山 博充, 水町 貴諭, 坂下 智博, 福田 諭
    耳鼻咽喉科展望 58 補冊1 12 - 13 耳鼻咽喉科展望会 2015年09月 [査読無し][通常論文]
  • 加納 里志, 本間 明宏, 畠山 博充, 水町 貴諭, 古沢 純, 坂下 智博, 福田 諭
    耳鼻咽喉科展望 58 補冊1 52 - 53 耳鼻咽喉科展望会 2015年09月 [査読無し][通常論文]
  • 頭頸部・口腔がん治療の未来を展望する 頭頸部癌ゲノム・プロテオーム解析からの個別化分子標的治療へ
    畠山 博充, 本間 明宏, 坂下 智博, 水町 貴諭, 加納 里志, 蠣崎 文彦, 福田 諭
    日本癌治療学会誌 50 3 323 - 323 (一社)日本癌治療学会 2015年09月 [査読無し][通常論文]
  • 頭頸部扁平上皮癌患者における治療前血中炎症細胞と予後に関する検討
    加納 里志, 本間 明宏, 畠山 博充, 水町 貴諭, 坂下 智博, 福田 諭
    日本癌治療学会誌 50 3 2350 - 2350 (一社)日本癌治療学会 2015年09月 [査読無し][通常論文]
  • 鈴木 正宣, 渡部 昌, 中丸 裕爾, 高木 大, 加納 里志, 本間 あや, 畠山 鎮次, 福田 諭
    耳鼻咽喉科免疫アレルギー 33 3 185 - 192 日本耳鼻咽喉科免疫アレルギー学会 2015年09月 [査読無し][通常論文]
     
    ユビキチン化修飾は真核生物に広く存在するタンパク質翻訳後修飾の一つであり,多岐にわたる細胞機能を制御する。ユビキチン化修飾系の異常を原因とする疾患も数多く知られており,耳鼻咽喉科領域においても内耳や鼻粘膜の環境恒常性や,自己免疫・炎症性疾患や悪性疾患の病態に関連していることが報告されている。標的タンパク質へのユビキチンの共有結合は,ユビキチン活性化酵素(E1),ユビキチン連結酵素(E2),ユビキチンリガーゼ(E3)の3つの酵素群が担っている。この中でもE3は基質の特異性を決定する酵素であり,その機能と標的である基質を明らかにすることは,さまざまな疾患の病態解明において重要な課題となっている。耳鼻科領域の疾患において,ユビキチン修飾系についての研究は始まったばかりであり,今後,病態の解明,検査法の確立や新規治療法の開発につながる可能性を秘めている。(著者抄録)
  • 多施設共同による唾液腺導管癌の臨床的、病理組織学的、免疫組織化学的研究
    多田 雄一郎, 加納 里志, 清水 顕, 塚原 清彰, 今西 順久, 大上 研二, 佐藤 雄一郎, 花澤 豊行, 佐藤 由紀子, 三浦 弘規, 増淵 達夫, 伏見 千宙, 長尾 俊孝
    国際医療福祉大学学会誌 20 抄録号 57 - 57 国際医療福祉大学学会 2015年08月 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Jun Furusawa, Satoshi Kano, Takatsugu Mizumachi, Satoshi Iizuka, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    ACTA OTO-LARYNGOLOGICA 135 8 853 - 858 2015年08月 [査読有り][通常論文]
     
    Conclusion: Grade >= 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well. Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation. Method: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m(2) was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m(2) of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m(2) weekly during the definitive radiotherapy. Results: The BRT group had a higher incidence of Grade >= 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade >= 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).
  • Takatsugu Mizumachi, Akihiro Homma, Tomohiko Kakizaki, Tomohiro Sakashita, Satoshi Kano, Hiromitsu Hatakeyama, Kazuhiko Tsuchiya, Koichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Jun Taguchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Akita, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 20 3 431 - 437 2015年06月 [査読有り][通常論文]
     
    The aim of this study was to evaluate the feasibility of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Between 2010 and 2013, 30 patients with Stage IV HNSCC were treated in Hokkaido University Hospital with three cycles of induction chemotherapy (docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2), day 1; and 5-fluorouracil 750 mg/m(2)/day 120 h continuous infusion, every 3 weeks) followed by concurrent weekly cisplatin (40 mg/m(2), on weeks 1, 2, 3, 5, 6 and 7) chemoradiotherapy. Three courses of induction chemotherapy were performed in 25 patients (83 %) with grade 3-4 toxicities during induction chemotherapy observed in 22 patients (73 %). The major toxicities were hematologic, with 22 cases (73 %) showing grade 3-4 neutropenia. Radiotherapy was completed (70 Gy) in 29 patients (97 %), while a total of 19 patients (63 %) completed five (13 patients) or six (6 patients) courses of chemotherapy. During concurrent chemoradiotherapy, no grade 4 hematological toxicities were observed. Grade 4 dermatitis was observed in one patient, and grade 3 mucositis was observed in 12 patients. There were no treatment-related deaths during the induction chemotherapy or concurrent chemoradiotherapy. The 1- and 2-year progression-free survival rates and the 1- and 2-year overall survival rates were 86 %, 72 %, and 89 %, 81 %, respectively. Sequential therapy composed of induction chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy is feasible, showing encouraging results in patients with locally advanced HNSCC. Concurrent weekly cisplatin chemoradiotherapy following induction chemotherapy appears to be a suitable alternative to three-weekly high-dose cisplatin therapy.
  • 唾液腺導管癌における免疫組織化学的バイオマーカーの予後因子としての意義 多施設共同研究による検討
    高瀬 聡一郎, 多田 雄一郎, 川北 大介, 加納 里志, 清水 顕, 小澤 宏之, 塚原 清彰, 大上 研二, 佐藤 雄一郎, 長尾 俊孝
    頭頸部癌 41 2 193 - 193 (一社)日本頭頸部癌学会 2015年05月 [査読無し][通常論文]
  • 唾液腺癌を対象としたHER2タンパク過剰発現および遺伝子増幅検査法の臨床的バリデーションに関する検討
    加納 里志, 畑中 豊, 松野 吉宏, 本間 明宏, 秋田 弘俊, 福田 諭
    頭頸部癌 41 2 257 - 257 (一社)日本頭頸部癌学会 2015年05月 [査読無し][通常論文]
  • 水町 貴諭, 中薗 彬, 溝口 兼司, 坂下 智博, 加納 里志, 畠山 博充, 本間 明宏, 福田 諭
    日本耳鼻咽喉科学会会報 118 4 504 - 504 (一社)日本耳鼻咽喉科学会 2015年04月 [査読無し][通常論文]
  • 大塚 邦憲, 多田 雄一郎, 川北 大介, 花澤 豊行, 加納 里志, 清水 顕, 今西 順久, 小澤 宏之, 塚原 清彰, 大上 研二, 佐藤 雄一郎, 長尾 俊孝, 小川 郁
    日本耳鼻咽喉科学会会報 118 4 526 - 526 (一社)日本耳鼻咽喉科学会 2015年04月 [査読無し][通常論文]
  • 頭頸部癌化学放射線療法におけるEPA高配合栄養機能食品(プロシュア)の有用性の検討
    水町 貴諭, 中薗 彬, 坂下 智博, 加納 里志, 畠山 博充, 本間 明宏, 福田 諭
    日本気管食道科学会会報 66 2 s20 - s20 (NPO)日本気管食道科学会 2015年04月 [査読無し][通常論文]
  • 喉頭に生じたInflammatory Myofibroblastic Tumorの一例
    横川 泰三, 加納 里志, 溝口 兼司, 畠山 博充, 本間 明宏, 福田 諭
    日本気管食道科学会会報 66 2 s64 - s64 (NPO)日本気管食道科学会 2015年04月 [査読無し][通常論文]
  • Homma Akihiro, Hatakeyama Hiromitsu, Mizumachi Takatsugu, Furusawa Jun, Kano Satoshi, Sakashita Tomohiro, Fukuda Satoshi
    International Cancer Conference Journal 4 1 57 - 60 Springer 2015年01月 
    The suprasternal space is a narrow space between the superficial and deep layers of the investing layers of the deep cervical fascia above the manubrium of the sternum. The suprasternal space has been paid littleattention as a space with the potential for lymph nodemetastasis from both thyroid cancer and head and neckcancer. We experienced 2 patients who were found to have a lymph node in the suprasternal space preoperatively. Both of them had well-differentiated thyroid papillary carcinomas and level III and IV lymph node metastases as well as metastasis in the suprasternal space. We have not previously dissected the suprasternal space prophylactically in other patients with thyroid papillary cancer, but no patient has developed metastasis in this space to date. Thesuprasternal space is not usually dissected in atients with thyroid cancer. However, suprasternal space metastasis has been reported to occur occasionally in patients with lymph node metastases in levels III and IV. We consider that dissection of the suprasternal space, which is not routinely performed, should be done when preoperative examination suggests lymph node metastasis in the suprasternal space as dissection of this space is less invasive, easy to achieve, and is not time consuming. Greater attention should be paidto the suprasternal space as an area with the otential for lymph node metastasis from thyroid cancer.
  • Akihiro Homma, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Yuji Nakamaru, Daisuke Yoshida, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    ACTA OTO-LARYNGOLOGICA 135 9 950 - 954 2015年 [査読有り][通常論文]
     
    Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery. Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck. Patients and methods: Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/ week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy). Results: Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9; 7) (range = 4; 6-12; 5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4-9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.
  • Hiromitsu Hatakeyama, Takatsugu Mizumachi, Tomohiro Sakashita, Satoshi Kano, Akihiro Homma, Satoshi Fukuda
    ONCOLOGY REPORTS 32 6 2673 - 2679 2014年12月 [査読有り][通常論文]
     
    High-risk human papillomavirus (HPV) infection is associated with carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC) and patients with HPV-positive tumors have a significantly favorable prognosis. However, the underlying mechanism of this favorable clinical outcome remains unclear. Epithelial-mesenchymal transition (EMT) causes aggressiveness of cancer cells and we investigated the expression of the EMT markers and analyzed their correlation with HPV status and prognosis in order to examine the treatment response of HPV-positive OPSCCs. A total of 79 patients with OPSCC were examined in the present study. All high-risk HPV infections were determined with the multiplex PCR kit from each formalin-fixed paraffin-embedded (FFPE) sample. We performed immunohistochemical staining for E-cadherin and vimentin. Expression of the markers was graded and we statistically analyzed the correlation between tumor, node, metastasis (TNM) stages and prognosis. High-risk HPV-positive tumors were detected in 23 cases. The five-year survival rate in HPV-positive and -negative tumors was 82.7 and 48.3%, respectively. High E-cadherin expression rate in HPV-negative samples was 76.7% and 43.4% in HPV-positive samples (p=0.007). Vimentin expression did not show a difference between HPV-positive and -negative tumors. HPV-negative patients presented significantly greater heterogeneity of E-cadherin expression compared to HPV-positive patients (p=0.0349). HPV-positive OPSCCs originally lost their epithelial cell phenotype compared with HPV-negative tumors. Therefore, the paradoxical favorable prognosis of HPV-positive OPSCC may be due to the intratumor homogeneity in EMT.
  • Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Hiromitsu Hatakeyama, Akihiro Homma, Satoshi Fukuda
    Journal of Otolaryngology of Japan 117 12 1463 - 1470 2014年12月01日 [査読有り][通常論文]
     
    In the case of oropharyngeal carcinoma, patients may present with symptoms similar to cervical lymphadenopathy, and the primary lesion may only be diagnosed after cervical mass extirpation/biopsy. We retrospectively analyzed the clinical course in 11 oropharyngeal carcinoma patients that were diagnosed after cervical mass extirpation/biopsy between 1998 and 2013. Before the diagnosis was made of oropharyngeal carcinoma, a cervical lymph node biopsy was performed in six patients the lymph node was extirpated due to an initial diagnosis of lateral cervical cyst in four patients and neck dissection was performed due to an initial diagnosis of primary unknown carcinoma in one patient. The primary tumor site in the oropharynx was the palatine tonsil in six patients and the lingual tonsil in five patients. Five of six patients with palatine tonsil carcinoma and three of five patients with lingual tonsil carcinoma were found to be positive for human papillomavirus (HPV). The duration from cervical lymph node extirpation/biopsy to final diagnosis was 1 to 13 months. All patients finally underwent radiation therapy or chemoradiotherapy, and they had no recurrence or metastasis. As the incidence of HPV-related oropharyngeal carcinoma increases, the number of oropharyngeal carcinomas assumed to be cervical lymphadenopathy due to the presenting symptoms may increase. It is important to investigate the oropharynx thoroughly so as to adequately differentiate the possibility of oropharyngeal carcinoma from that of cervical lymphadenopathy. Metastatic lymph nodes might present as cysts in cases of oropharyngeal carcinoma, it is therefore necessary to take the potential for metastatic lymph nodes in the oropharyngeal cancer into consideration when differentiating this disease from cervical cyst-shaped lesions.
  • Satoshi Kano, Ryuichi Hayashi, Akihiro Homma, Kazuto Matsuura, Kengo Kato, Kazuyoshi Kawabata, Nobuya Monden, Yasuhisa Hasegawa, Tetsuro Onitsuka, Yasushi Fujimoto, Shigemichi Iwae, Kenji Okami, Takashi Matsuzuka, Kunitoshi Yoshino, Masato Fujii
    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 36 11 1567 - 1572 2014年11月 [査読有り][通常論文]
     
    BackgroundWe analyzed the effects of local extension sites on survival in patients with locally advanced maxillary sinus cancer. MethodsThe criteria for inclusion in this study were as follows: (1) previously untreated maxillary sinus cancer; (2) squamous cell carcinoma; (3) T4 disease; and (4) curative-intent treatment. The data for 118 patients were obtained from 28 institutions across Japan and analyzed for overall survival and local control rates by local extension site. ResultsSites with a poor prognosis included the cribriform plate, dura, nasopharynx, middle cranial fossa, and cranial nerves other than V2. There was a significant correlation among these sites, except for the cranial nerves. Additionally, the hard palate was the only site that correlated with nodal involvement and showed a poor treatment outcome. ConclusionEven in cases presenting with similar T4 maxillary sinus cancer, treatment should be performed in consideration of the local extension site. (c) 2013 Wiley Periodicals, Inc. Head Neck 36: 1567-1572, 2014
  • 唾液腺導管癌における免疫組織化学的バイオマーカーの予後因子としての意義 多施設共同研究による147例の検討
    高瀬 聡一郎, 多田 雄一郎, 川北 大介, 加納 里志, 清水 顕, 小澤 宏之, 塚原 清彰, 大上 研二, 佐藤 雄一郎, 長尾 俊孝
    日本唾液腺学会誌 55 26 - 26 日本唾液腺学会 2014年11月 [査読無し][通常論文]
  • 加納 里志, 本間 明宏, 鈴木 清護, 畠山 博充, 古沢 純, 水町 貴諭, 坂下 智博, 折舘 伸彦, 福田 諭
    頭頸部癌 40 3 344 - 348 (一社)日本頭頸部癌学会 2014年10月31日 [査読無し][通常論文]
     
    われわれは、原発不明頸部リンパ節転移におけるヒト乳頭腫ウイルス(HPV)の解析により原発巣の推定が可能であるか検討した。対象は1991年から2011年に北海道大学病院で根治治療を行った原発不明癌新鮮例で、組織型が扁平上皮癌か未分化癌、遠隔転移を認めず、転移リンパ節の組織学的解析が可能な32症例とした。HPVの検出はPCR法を用い、また免疫組織染色法によりp16の発現も解析した。その結果、PCRにてHPV-DNAが検出されたのが8症例(25%)であり、その8症例は全てp16陽性であった。HPV陽性群と陰性群の比較では、陽性群で有意に若年者が多かった。またHPV陽性の8症例中4症例で原発が判明したが全例中咽頭であった。HPV陽性群の5年粗生存率は80.0%で陰性群では52.1%であった。本研究結果から、転移頸部リンパ節のHPVを検出することで中咽頭癌原発を推定することは十分可能であると考えられた。(著者抄録)
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Jun Furusawa, Daisuke Yoshida, Noriyuki Fujima, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 271 10 2767 - 2770 2014年10月 [査読有り][通常論文]
     
    The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3 % (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2 % (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.
  • 術前細胞診にて悪性が確定しなかった甲状腺結節におけるエコー陽性所見の数と悪性リスクの関係について
    坂下 智博, 本間 明宏, 畠山 博充, 水町 貴諭, 加納 里志, 古沢 純, 飯塚 さとし, 干野 季美子, 畑中 佳奈子, 福田 諭
    日本内分泌・甲状腺外科学会雑誌 31 Suppl.2 S234 - S234 日本内分泌外科学会・日本甲状腺外科学会 2014年09月 [査読無し][通常論文]
  • 再発転移唾液腺導管癌に対する新しい個別化治療戦略の構築
    多田 雄一郎, 三浦 弘規, 増淵 達夫, 伏見 千宙, 長村 義之, 長尾 俊孝, 大上 研二, 花澤 豊行, 佐藤 雄一郎, 今西 順久, 清水 顕, 加納 里志
    国際医療福祉大学学会誌 19 抄録号 71 - 71 国際医療福祉大学学会 2014年08月 [査読無し][通常論文]
  • 多施設共同による多形腺腫由来癌の病態組織型と臨床像の比較検討研究
    伏見 千宙, 多田 雄一郎, 三浦 弘規, 増淵 達夫, 長村 義之, 長尾 俊孝, 大上 研二, 花澤 豊行, 佐藤 雄一郎, 今西 順久, 清水 顕, 加納 里志
    国際医療福祉大学学会誌 19 抄録号 74 - 74 国際医療福祉大学学会 2014年08月 [査読無し][通常論文]
  • 坂下 智博, 本間 明宏, 畠山 博充, 水町 貴諭, 加納 里志, 古沢 純, 飯塚 さとし, 畑中 佳奈子, 福田 諭
    日本内分泌・甲状腺外科学会雑誌 31 2 130 - 133 日本内分泌外科学会・日本甲状腺外科学会 2014年06月 [査読無し][通常論文]
     
    穿刺細胞診で悪性が確定しなかった場合にも画像的に甲状腺癌が疑わしいなどの理由により手術を行うことが少なくない。術後病理診断と画像所見との関係について比較し、どのような画像所見が癌予測因子として有用であるかについて検討した。対象は甲状腺腫瘍摘出を行ったもののうち、術前細胞診で悪性以外であった58症例。術前エコー検査所見(微細石灰化、辺縁不整、内部low echo、縦横比1以上、Haloの消失)が陽性であった場合に、術後病理で悪性であった陽性適中率(PPV)、陰性であった場合に術後病理が良性であった陰性適中率(NPV)をそれぞれ算出した。前述した各エコー所見のそれぞれのPPVは74、89、71、89、65%。NPVはいずれの所見も51〜58%にとどまった。辺縁不整および縦横比1以上がみられた場合のPPVは89%であり、これらの所見は有用な癌予測因子となりうると考えられた。(著者抄録)
  • 局所進行頭頸部癌に対する導入化学療法後のweekly CDDP併用化学放射線療法の安全性と有用性の検討
    水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 清水 康, 秋田 弘俊, 土屋 和彦, 安田 耕一, 鬼丸 力也, 白土 博樹, 福田 諭
    頭頸部癌 40 2 177 - 177 (一社)日本頭頸部癌学会 2014年05月 [査読無し][通常論文]
  • セツキシマブ投与におけるEGFRリガンド発現変化と効果
    畠山 博充, 坂下 智博, 水町 貴諭, 加納 里志, 本間 明宏, 福田 諭, 古沢 純
    頭頸部癌 40 2 187 - 187 (一社)日本頭頸部癌学会 2014年05月 [査読無し][通常論文]
  • 唾液腺導管癌におけるHER2下流シグナルの解析
    加納 里志, 本間 明宏, 畠山 博充, 古沢 純, 水町 貴諭, 坂下 智博, 福田 諭
    頭頸部癌 40 2 191 - 191 (一社)日本頭頸部癌学会 2014年05月 [査読無し][通常論文]
  • 下咽頭癌に対するRADPLATとweekly CDDP併用化学放射線治療の比較検討
    古沢 純, 本間 明宏, 坂下 智博, 畠山 博充, 加納 里志, 水町 貴諭, 土屋 和彦, 吉田 大介, 安田 耕一, 白土 博樹, 福田 諭
    頭頸部癌 40 2 198 - 198 (一社)日本頭頸部癌学会 2014年05月 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Jun Furusawa, Daisuke Yoshida, Noriyuki Fujima, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Fumiyuki Suzuki, Satoshi Fukuda
    BRITISH JOURNAL OF ORAL & MAXILLOFACIAL SURGERY 52 4 323 - 328 2014年04月 [査読有り][通常論文]
     
    Our aim was to evaluate the feasibility of salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively analysed the records of 61 patients with cancer of the maxillary sinus who were treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra-arterial infusions of cisplatin given a median of 4 times weekly (range 2-5). Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy). Persistent or recurrent cancer of the maxillary sinus was found in 17 patients, of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7 of the 11 survived with no evidence of disease. Their 5-year overall survival was 61%. Two of the 11 developed serious operative complications. Salvage surgery for patients with persistent or recurrent cancer of the maxillary sinus treated by superselective chemoradiotherapy is both safe and successful. Salvage surgery is a good option when this sort of persistent or recurrent cancer is followed up after the regimen of chemoradiotherapy described. (C) 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
  • 加納 里志, 多田 雄一郎, 花澤 豊行, 今西 順久, 清水 顕, 大上 研二, 佐藤 雄一郎, 長尾 俊孝
    日本耳鼻咽喉科学会会報 117 4 571 - 571 (一社)日本耳鼻咽喉科学会 2014年04月 [査読無し][通常論文]
  • Burns spaceに転移を来した甲状腺乳頭癌の2例
    本間 明宏, 畠山 博充, 水町 貴諭, 古沢 純, 加納 里志, 坂下 智博, 福田 諭
    日本耳鼻咽喉科学会会報 117 4 605 - 605 (一社)日本耳鼻咽喉科学会 2014年04月 [査読無し][通常論文]
  • Sakashita T, Homma A, Hatakeyama H, Kano S, Mizumachi T, Furusawa J, Yoshida D, Fujima N, Onimaru R, Tsuchiya K, Yasuda K, Shirato H, Suzuki F, Fukuda S
    Br J Oral Maxillofac Surg 52 4 323 - 8 2014年 [査読有り][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Jun Furusawa, Satoshi Iizuka, Kimiko Hoshino, Kanako C Hatanaka, Koji Oba, Satoshi Fukuda
    Frontiers in oncology 4 261 - 261 2014年 [査読有り][通常論文]
     
    OBJECTIVE: Fine-needle aspiration cytology (FNAC) is considered to be the most reliable method of examination for thyroid nodules. However, when thyroid nodules are evaluated as Bethesda I-V, the role of ultrasonography is considered to be enhanced. We investigated the association between a number of ultrasonographic (US) characteristics and the risk of thyroid malignancy, and assessed the optimal compromise on the number of US characteristics for predicting thyroid malignancy. METHODS: Seventy-three patients, whose thyroid nodules were evaluated as Bethesda I-V by FNAC prior to surgery, were treated surgically. A number of US characteristics, such as microcalcification, irregular margins, hypoechogenicity, a taller-than-wide shape, and the absence of halo sign, were assessed before surgery. The optimal compromise on the number of US characteristics was analyzed using a receiver operating characteristics (ROC) curve. The area under the ROC curve (AUC) represents the overall discriminatory ability of a test. RESULTS: The risk of malignancy was 11.8% in patients without any US characteristics, 44.4% in those with one characteristic, 61.5% in those with two characteristics, 75% in those with three characteristics, 90% in those with four characteristics, and 100% in those with five characteristics. The AUC was favorable (0.81599). At least two US characteristics were revealed to be the optimal compromise on the number of US characteristics based on the ROC curve. CONCLUSION: We proved the role of the number of US characteristics in predicting thyroid malignancy. It was thought that a surgical approach should be considered for patients with at least two US characteristics.
  • 水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 土屋 和彦, 安田 耕一, 鬼丸 力也, 白土 博樹, 福田 諭
    頭頸部癌 40 1 66 - 70 (一社)日本頭頸部癌学会 2014年 [査読無し][通常論文]
     
    当院にてCDDP 40mg/m2/週併用の化学放射線療法を行った中咽頭扁平上皮癌新鮮例22例に対して臨床的検討を行った。22例中13例がHPV陽性であった。放射線治療は本人希望にて50Gyで終了した1例以外は全例70Gy完遂できた。CDDPの平均投与量は179mg/m2であった。有害事象はGrade4以上は認めなかったが、Grade3の粘膜炎が16例(73%)、好中球減少、皮膚炎が各4例(18%)認めた。原発病変に対する一次治療効果は、HPV陰性の1例がPRであったが、21例はCRとなった。頸部に対しては22例全例CRとなった。HPV陽性例の3年粗生存率は92.3%であったのに対し陰性例は66.7%であった。統計学的有意差は得られなかったが、HPV陽性例の方が予後が良好な傾向にあった。HPV陽性例は導入化学療法を先行させた症例が多かったものの、本治療における治療成績は良好で十分な効果が期待できると思われた。HPV陰性例に対しては一次治療効果は良好であるものの再発や転移を来す症例が陽性例に比べ多く生じた。(著者抄録)
  • 西村 剛志, 加納 里志, 佐久間 直子, 佐野 大佑, 小松 正規, 折舘 伸彦
    耳鼻咽喉科免疫アレルギー 31 4 237 - 246 日本耳鼻咽喉科免疫アレルギー学会 2013年12月 [査読無し][通常論文]
     
    患者自身の希望があれば受けることが可能と考えられる癌免疫療法として、養子免疫療法、ワクチン療法、BRM(生物学的反応修飾物質)製剤について概説した。養子免疫療法にはLAK療法、TIL療法、αβT細胞療法、γδT細胞療法、NK細胞療法、癌ワクチン療法にはペプチドワクチン療法、DCワクチン療法がある。BRMにはOK-432、漢方薬の十全大補湯、補中益気湯、人参養栄湯が用いられる。試験管レベルで期待された効果が得られない一因として腫瘍免疫回避機構があり、腫瘍細胞側の要因とリンパ球側の要因が考えられている。
  • 水町 貴諭, 畠山 博充, 加納 里志, 坂下 智博, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 39 3 334 - 338 (一社)日本頭頸部癌学会 2013年10月28日 [査読無し][通常論文]
     
    HPV関連中咽頭癌の多くはp16が過剰発現していることから、p16がHPV感染のsurrogate markerであると考えられている。しかし、p16発現の判定基準は統一されておらず、HPV感染以外の機序でもp16が過剰発現することもある。今回われわれは中咽頭扁平上皮癌91例に対してHPV感染とp16の発現について検討した。91例中HPV陽性であったのは29例(32%)で、p16陽性であったのは31例(34%)であった。HPV陽性であった29例中24例(83%)がp16陽性で、HPV陰性であった62例中7例(11%)がp16陽性であった。3年粗生存率はp16陽性例が82.2%、p16陰性例が65.1%でp16陽性例の方が有意に生存率は良好であったが、HPV陰性p16陽性例の予後はHPV陰性p16陰性例と同様に不良であった。以上のことからp16の発現がHPV感染の完全なsurrogate markerとはなり難いと考えられた。(著者抄録)
  • Satoshi Kano, Akihiro Homma, Ryuichi Hayashi, Kazuyoshi Kawabata, Kunitoshi Yoshino, Shigemichi Iwae, Yasuhisa Hasegawa, Kenichi Nibu, Takakuni Kato, Kiyoto Shiga, Kazuto Matsuura, Nobuya Monden, Masato Fujii
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 18 5 817 - 823 2013年10月 [査読有り][通常論文]
     
    The current study aimed to assess the role of salvage surgery for failure cases of oropharyngeal cancer (OPC) undergoing initial chemoradiotherapy (CRT). The data for 523 patients with previously untreated OPC were gathered from 12 institutions belonging to the Head and Neck Cancer Study Group in Japan Clinical Oncology Group (JCOG). Of the 170 patients who received CRT, 35 patients (21 %) had local recurrence or residual disease. Only 11 patients underwent further salvage surgery, and 24 patients received nonsurgical treatment. There were statistically significant differences between the two groups in terms of patient age and the presence of a simultaneous regional recurrence. The 5-year overall survival rates for the patients who underwent salvage surgery were 49.1 %, whereas those for the patients who received nonsurgical treatment were 16.3 %. The initial treatment method for OPC should be decided carefully and the limitations of salvage surgery should be fully considered.
  • Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Hiromitsu Hatakeyama, Seigo Suzuki, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 18 5 824 - 828 2013年10月 [査読有り][通常論文]
     
    The prevalence of oropharyngeal carcinoma is rising in western Europe and the United States, where there appears to be a strong association between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC). However, such a correlation has not yet been fully evaluated in Japan. We performed a retrospective analysis of the association between tumour HPV status and the demographic and clinicopathological parameters of 71 patients with OPSCC at Hokkaido University Hospital, Japan, between 1998 and 2009. The parameters included age, gender, survival, tumour subsite, tumour-node-metastasis (TNM) stage, smoking history, second primary tumour status, recurrence/residual disease at the primary site, and overall survival. HPV status was established by multiplex polymerase chain reaction (PCR) analysis. Of the 71 oropharyngeal cancers, 20 were positive for HPV-16, two for HPV-18, and one for HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumours (p = 0.0038) compared with HPV-negative tumours. Of the 45 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients (p = 0.0032). In a multivariate analysis, the survival benefit of HPV-positive patients was independent of age and T and N classification. HPV status is a significantly favourable prognostic factor in oropharyngeal cancer and could be used as a marker to optimize the treatment of patients with this type of cancer in Japan.
  • 水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 鈴木 清護, 折舘 伸彦, 福田 諭
    耳鼻咽喉科展望 56 5 334 - 337 耳鼻咽喉科展望会 2013年10月 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Seigo Suzuki, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Nobuhiko Oridate, Satoshi Fukuda
    ACTA OTO-LARYNGOLOGICA 133 9 984 - 991 2013年09月 [査読有り][通常論文]
     
    Conclusion: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent. Objective: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC. Methods: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens. Results: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14-21.69, p = 0.0304).
  • 中咽頭癌に対する放射線化学療法の検討 多施設による後方視的観察研究
    加納 里志, 本間 明宏, 林 隆一, 川端 一喜, 吉野 邦俊, 岩江 信法, 長谷川 泰久, 丹生 健一, 加藤 孝邦, 志賀 清人, 松浦 一登, 門田 伸也, 藤井 正人
    日本癌治療学会誌 48 3 1248 - 1248 (一社)日本癌治療学会 2013年09月 [査読無し][通常論文]
  • 多施設共同による唾液腺導管癌の後方視的観察研究
    多田 雄一郎, 鎌田 信悦, 長村 義之, 三浦 弘規, 増淵 達夫, 伏見 千宙, 丸屋 信一郎, 長尾 俊孝, 大上 研二, 花澤 豊行, 佐藤 雄一郎, 今西 順久, 清水 顕, 加納 里志
    国際医療福祉大学学会誌 18 抄録号 77 - 77 国際医療福祉大学学会 2013年08月 [査読無し][通常論文]
  • 水町 貴諭, 加納 里志, 本間 明宏, 折舘 伸彦, 福田 諭
    口腔・咽頭科 26 2 161 - 166 日本口腔・咽頭科学会 2013年06月 [査読無し][通常論文]
     
    HPV陽性中咽頭癌は陰性例に比べ予後が良好であるが、陽性例であっても予後不良例も存在する。Spectorらは"matted nodes"というリンパ節の転移様式のみられる症例は遠隔転移しやすく予後不良であると報告した。中咽頭扁平上皮癌症例61例に対してretrospectiveに"matted nodes"および臨床的検討を行った。このうち"matted nodes"を認めたのは9例であった。全症例における"matted nodes"の有無別の生存率には有意差を認めなかったが、"matted nodes"あり群の方が有意に遠隔転移しやすい傾向にあった。HPV陽性例のみでの検討では"matted nodes"あり群の方がなし群に比べ有意に予後が不良であった。HPV陽性であっても"matted nodes"のある症例は遠隔転移のリスクが高く予後不良であるので導入化学療法を行った方が望ましいと考えられた。(著者抄録)
  • 本間 明宏, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 古沢 純, 水町 貴諭, 坂下 智博, 鈴木 章之, 瀧 重成, 稲村 直哉, 福田 諭
    耳鼻咽喉科展望 56 補冊2 130 - 131 耳鼻咽喉科展望会 2013年05月 [査読無し][通常論文]
  • 土屋 和彦, 安田 耕一, 西川 由記子, 木下 留美子, 鬼丸 力也, 原田 慶一, 井上 哲也, 加藤 徳雄, 清水 伸一, 白土 博樹, 西岡 健, 鈴木 恵士郎, 田口 大志, 長谷川 雅一, 折舘 伸彦, 本間 明宏, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 福田 諭, 竹内 啓, 田口 純
    耳鼻咽喉科展望 56 補冊2 174 - 175 耳鼻咽喉科展望会 2013年05月 [査読無し][通常論文]
  • 化学放射線療法の現状と役割 動注化学療法による化学放射線療法 上顎洞癌を中心に
    本間 明宏, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 吉田 大介, 鬼丸 力也, 土屋 和彦, 安田 耕一, 白土 博樹, 藤井 正人, 福田 諭
    頭頸部癌 39 2 134 - 134 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • 多施設共同による唾液腺導管癌の後方視的観察研究 導管癌および多形腺腫由来導管癌の臨床像
    清水 顕, 伊藤 博之, 高瀬 聡一郎, 鈴木 衞, 長尾 俊孝, 今西 順久, 大塚 邦憲, 多田 雄一郎, 加納 里志, 花澤 豊行, 茶園 英明
    頭頸部癌 39 2 137 - 137 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • HPV陽性中咽頭癌に対するweekly CDDP併用化学放射線治療の臨床的検討
    水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 福田 諭
    頭頸部癌 39 2 139 - 139 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • HPV陽・陰性中咽頭扁平上皮癌の上皮間葉移行における特性
    畠山 博充, 水町 貴諭, 坂下 智博, 加納 里志, 本間 明宏, 福田 諭
    頭頸部癌 39 2 188 - 188 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • 上顎洞原発扁平上皮癌T4症例の進展部位別予後解析 多施設後ろ向き観察研究
    加納 里志, 林 隆一, 本間 明宏, 松浦 一登, 加藤 健吾, 川端 一喜, 松塚 崇, 大上 研二, 岩江 信法, 藤井 正人
    頭頸部癌 39 2 201 - 201 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • 上顎洞扁平上皮癌に対する超選択的動注併用放射線治療後の救済手術に関する検討
    坂下 智博, 本間 明宏, 鈴木 章之, 畠山 博充, 加納 里志, 水町 貴諭, 古沢 純, 福田 諭
    頭頸部癌 39 2 202 - 202 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • 両側に生じたHPV陽性舌根癌症例
    水町 貴諭, 坂下 智博, 加納 里志, 畠山 博充, 本間 明宏, 福田 諭
    頭頸部癌 39 2 228 - 228 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • 甲状腺未分化癌・低分化癌症例における分化機構についての免疫組織学的検討
    干野 季美子, 畠山 博充, 坂下 智博, 加納 里志, 水町 貴諭, 本間 明宏, 畑中 佳奈子, 福田 諭
    頭頸部癌 39 2 244 - 244 (一社)日本頭頸部癌学会 2013年05月 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Nobuhiko Oridate, Seigo Suzuki, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    AURIS NASUS LARYNX 40 2 211 - 215 2013年04月 [査読有り][通常論文]
     
    Objectives: Although three-weekly high-dose (100 mg/m(2)) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40 mg/m(2) has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis. Methods: We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a "wait and see" approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone. Results: Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23 of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan-Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively. Conclusion: Concomitant weekly cisplatin at a dose of 40 mg/m(2) chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • 頭頸部癌化学放射線療法における小野寺栄養指数の意義
    折舘 伸彦, 倉本 倫之介, 本間 明宏, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 蠣崎 文彦, 福田 諭
    日本気管食道科学会会報 64 2 s55 - s55 (NPO)日本気管食道科学会 2013年04月 [査読無し][通常論文]
  • 当科における導入化学療法後の放射線化学療法例の検討
    蠣崎 文彦, 本間 明宏, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 福田 諭
    日本耳鼻咽喉科学会会報 116 4 524 - 524 (一社)日本耳鼻咽喉科学会 2013年04月 [査読無し][通常論文]
  • 水町 貴諭, 折舘 伸彦, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 鈴木 清護, 福田 諭
    頭頸部外科 22 3 317 - 321 (NPO)日本頭頸部外科学会 2013年02月 [査読無し][通常論文]
     
    2004年から2008年に当科にて治療を行った声門下癌を除く喉頭癌T3症例27例の治療成績を検討した。治療内容は喉頭全摘手術が7例、化学放射線治療が14例、放射線単独治療が6例であった。治療法別の疾患特異的3年生存率は手術群が85.7%、化学放射線治療群が77.9%、放射線単独治療群が66.7%であったが各群間に統計学的有意差は認めなかった。喉頭温存を希望する症例に対して、化学放射線治療は有用な治療法であると考えられた。T3規定因子別の検討では、声門周囲腔進展例は声帯固定例および喉頭蓋前方進展例と比べ統計学的有意差をもって予後が良好であり、声門周囲腔進展しているが声帯固定していない症例は喉頭温存治療を積極的に行って良いのではと考えられた。(著者抄録)
  • Homma A, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, Suzuki F, Yasuda K, Hatakeyama H, Furusawa J, Mizumachi T, Kano S, Inamura N, Taki S, Shirato H, Fukuda S
    Br J Cancer 109 12 2980 - 6 Nature publishing group 2013年 [査読有り][通常論文]
     
    Background: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Methods: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120mgm(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). Results: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n-5), brain necrosis (n-1), and ocular/ visual problems (n = 14) were observed as late adverse reactions. Conclusion: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.
  • Satoshi Kano, Akihiro Homma, Ryuichi Hayashi, Kazuyoshi Kawabata, Kunitoshi Yoshino, Shigemichi Iwae, Yasuhisa Hasegawa, Kenichi Nibu, Takakuni Kato, Kiyoto Shiga, Kazuto Matsuura, Nobuya Monden, Masato Fujii
    ONCOLOGY 84 5 290 - 298 2013年 [査読有り][通常論文]
     
    Objective: The current study aimed to compare the therapeutic outcomes of surgery with those of chemoradiation for patients with advanced oropharyngeal cancer (OPC). Methods: The data for 523 patients with previously untreated OPC were obtained from 12 institutions belonging to the Head and Neck Cancer Study Group in the Japan Clinical Oncology Group from April 2005 to March 2007. In this study, we matched a group of patients who underwent surgery with a second group treated with chemoradiation according to age, gender, subsite, and T and N classification, and analyzed the overall survival, progression-free survival, local control and swallowing function. Results: The final matched-pair analysis included 186 patients. The 5-year overall survival, progression-free survival and local control rates were 69.8 and 71.4% (p = 0.762), 51.0 and 54.4% (p = 0.531), and 75.2 and 80.3% (p = 0.399), respectively, in patients treated with surgery and those treated with chemoradiation. Swallowing function in patients treated with chemoradiation was significantly better than that in patients treated with surgery (p = 0.015). Conclusion: Although this study was not randomized, this matched-pair analysis of patients treated with surgery or chemoradiation showed that chemoradiation is as effective as surgery in the treatment of OPC. Copyright (C) 2013 S. Karger AG, Basel
  • 本間 明宏, 林 隆一, 川端 一喜, 吉野 邦俊, 岩江 信法, 長谷川 泰久, 加納 里志, 丹生 健一, 加藤 孝邦, 志賀 清人, 松浦 一登, 門田 伸也, 藤井 正人
    頭頸部癌 39 4 449 - 455 (一社)日本頭頸部癌学会 2013年 [査読無し][通常論文]
     
    全国12施設で中咽頭癌に対する治療を調査した。【対象】2005年4月から2年間に参加施設を受診し治療を受けた中咽頭癌新鮮例。【結果】523例が登録され、486例(92.9%)は根治的、37例(7.1%)は非根治的治療を受けていた。重複癌は中咽頭癌の治療前後を合わせると166例(31.7%)にみられた。扁平上皮癌根治治療の471例のうち手術主体の治療が186例(39.5%)に行われ、経口的腫瘍摘出:71例、外切開:115例であった。T分類では、T1の51.5%、T2〜4の35.9〜37.0%に手術が行われていた。照射主体の治療は285例(60.6%)に行われ、照射に化学療法を併用したのは167例あり、内訳はCDDP+5FU:65例、CDDP単剤:41例などであった。導入化学療法は79例(16.8%)、維持化学療法は28例(5.9%)に行われていた。全体の2年、5年粗生存率は、それぞれ85.0%、69.9%であった。【結論】後ろ向き試験であるが治療法の選択、その治療成績に関して一定の傾向を把握することができた。今後、中咽頭癌に前向き試験を行う際に有用なデータになるものと思われる。(著者抄録)
  • 本間 明宏, 折舘 伸彦, 鈴木 清護, 鈴木 章之, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 吉田 大介, 鬼丸 力也, 土屋 和彦, 安田 耕一, 白土 博樹, 福田 諭
    耳鼻と臨床 58 Suppl.1 S52 - S56 耳鼻と臨床会 2012年11月 [査読無し][通常論文]
     
    大量シスプラチンの超選択的動注療法と放射線治療の同時併用療法を1999年から2009年までに北海道大学病院で行った上顎洞原発扁平上皮癌未治療例41例についての救済手術について検討した。原発巣が残存あるいは再発した例は12例あり、そのうちの9例に救済手術が行われた。9例のうち7例は、その後原発巣の再発なく経過し、原発巣の救済率は全体で7/12=58.3%、T別ではT3:66.7%(2/3)、T4a:66.7%(4/6)、T4b:33.3%(1/3)であった。全症例の5年粗生存率は73.6%であった。術後合併症は、遊離皮弁による再建を行った症例で重篤な合併症が出現した。救済率が比較的良好であったのは、再発が前方に生じた例が多かったためと考えられた。以上の結果を、今後の症例の初回治療の選択、救済手術を行うかどうかの参考にしていきたい。(著者抄録)
  • 唾液腺導管癌の免疫組織化学・分子病理学的検討 多施設共同研究
    増淵 達夫, 多田 雄一郎, 長村 義之, 丸屋 信一郎, 佐藤 由紀子, 加納 里志, 長尾 俊孝
    日本唾液腺学会誌 53 28 - 28 日本唾液腺学会 2012年11月 [査読無し][通常論文]
  • Shigenari Taki, Akihiro Homma, Fumiyuki Suzuki, Nobuhiko Oridate, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Jun Furusawa, Tomohiro Sakashita, Naoya Inamura, Daisuke Yoshida, Rikiya Onimaru, Hiroki Shirato, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 17 5 441 - 446 2012年10月 [査読有り][通常論文]
     
    Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.
  • Tomohiro Sakashita, Akihiro Homma, Nobuhiko Oridate, Seigo Suzuki, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Daisuke Yoshida, Noriyuki Fujima, Satoshi Fukuda
    ACTA OTO-LARYNGOLOGICA 132 10 1121 - 1125 2012年10月 [査読有り][通常論文]
     
    Conclusion: We conclude that intra-arterially injected cisplatin passed via lymph flow into sentinel nodes (SNs) as the platinum concentration in the SNs was higher than that in the non-sentinel nodes (NSNs). It is possible that preoperative intra-arterial chemotherapy targeting primary cancer also has a therapeutic effect on subclinical metastatic SNs. Objectives: Intra-arterial chemoradiotherapy has been reported to be effective against not only primary tumors but also nodal metastases. We considered the hypothesis that intra-arterially injected cisplatin passed via lymph flow into regional nodes. This study aimed to investigate intra-arterially injected cisplatin distribution to regional nodes by comparing platinum concentrations in SNs and NSNs. Methods: Five patients with T1-2 N0 tongue cancer were treated with preoperative intra-arterial chemotherapy (cisplatin, 100 mg/m(2)) targeting primary cancer. Partial glossectomy together with SN biopsy and elective neck dissection were performed 2 weeks after intra-arterial chemotherapy. Platinum concentrations in the lymph nodes were measured using a Zeeman atomic absorption spectrometer. Results: Thirteen SNs were harvested together with eight NSNs from the areas adjacent to the SNs. Platinum concentrations were then measured, revealing a significant difference in platinum concentration between the SNs and the NSNs (mean +/- SD, 0.682 +/- 0.246 mu g/g vs 0.506 +/- 0.274 mu g/g; p = 0.049).
  • 頭頸部癌化学放射線療法における経管栄養の役割に関する検討
    倉本 倫之介, 折舘 伸彦, 本間 明宏, 及川 敬太, 藤田 香, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 福田 諭
    嚥下医学 1 2 359 - 363 日本嚥下医学会 2012年10月 [査読無し][通常論文]
     
    頭頸部癌における化学放射線併用療法(CRT)では粘膜炎により経口摂取困難をきたすため、胃ろうを造設することも少なくない。胃ろうと栄養状態・完遂率との関連について北海道大学病院において平成18年6月から平成23年1月までの間にCRTを施行した声門上癌、中咽頭癌、下咽頭癌52例についてレトロスペクティブに検討した。胃ろう使用群は非使用群と比較して治療前からの体重、アルブミン値が有意に低下を認め、当科での現在の胃ろうの使用方法をより栄養状態を向上のため工夫する必要があると考えられた。また、胃ろう留置群は非留置群よりも有意にCRT完遂率が高く、胃ろう造設がCRT完遂に寄与していると考えられた。原発部位別に見ると、声門上癌・下咽頭癌では胃ろう造設はCRT完遂に寄与しており、中咽頭癌では胃ろうを留置してもCRT完遂率は十分ではなく、今後検討が必要と思われる。(著者抄録)
  • 坂下 智博, 本間 明宏, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 福田 諭
    耳鼻咽喉科展望 55 5 364 - 368 耳鼻咽喉科展望会 2012年10月 [査読無し][通常論文]
     
    5mm以上の深部浸潤を認めるT1-2N0舌癌10例を対象に、センチネルリンパ節(SN)生検を施行し、同定されたSNの領域分布、潜在的リンパ節転移の領域分布を調査した。領域はHasegawaらの定めるLNDSGの分類に従った。採取したSNは、HE染色およびサイトケラチン抗体免疫染色を用いて病理学的に分析を行った。その結果、全例でSNが同定でき、6例(60%)に病理学的リンパ節転移を認めた。SNの同定部位については患側上頸部が最も多く、全例において同部位にSNを認め、4例(40%)に同部位のSN転移を認めた。健側頸部には2例(20%)にSNを認めたが、病理組織学的に転移は認めなかった。
  • 加納 里志, 折舘 伸彦, 福田 諭
    日本気管食道科学会会報 63 4 331 - 336 (NPO)日本気管食道科学会 2012年08月 [査読無し][通常論文]
     
    近年、わが国において中咽頭や下咽頭の早期癌に対するendoscopic submucosal dissection(ESD)による治療が普及してきている。外切開や放射線治療に比べ、低侵襲かつ治療期間が短いことが大きな利点である。さらに近年、臓器温存の観点より放射線治療の占める割合が大きくなってきており、そのため経過観察中に発見された重複癌に対して再照射ができないといった症例も多く経験する。今回われわれは、照射歴のある下咽頭の表在癌症例に対してESDを施行し、その後反復感染をきたしたため、最終的に喉頭全摘術を施行した1症例を経験した。当院では、2008年1月から2011年10月までに本症例も含め6例の照射歴のあるESD症例を経験した。本症例以外は合併症なく経過しており、照射野内の早期頭頸部癌もESDの適応になると考えられる。しかし、本症例のような合併症の可能性もあり、盲目的なESDの乱用は危険である。内視鏡医との術前術中の十分な協議による適切な治療方針の選択と施行が重要であると考える。(著者抄録)
  • HPV陽性中咽頭癌の転移リンパ節の臨床像
    水町 貴諭, 加納 里志, 本間 明宏, 折舘 伸彦, 福田 諭
    口腔・咽頭科 25 3 295 - 295 日本口腔・咽頭科学会 2012年08月 [査読無し][通常論文]
  • 加納 里志, 本間 明宏, 折舘 伸彦, 鈴木 章之, 畠山 博充, 水町 貴諭, 古沢 純, 坂下 智博, 吉田 大介, 鬼丸 力也, 白戸 博樹, 福田 諭
    北海道醫學雜誌 = Acta medica Hokkaidonensia 87 4 2012年08月01日 [査読無し][通常論文]
  • PET-CT検査にてはじめて原因が特定しえた喉頭麻痺の2症例
    折舘 伸彦, 溝口 兼司, 加納 里志, 本間 明宏, 福田 諭
    耳鼻咽喉科臨床 補冊 補冊133 110 - 110 耳鼻咽喉科臨床学会 2012年07月 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Nobuhiko Oridate, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Satoshi Fukuda
    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 269 6 1671 - 1676 2012年06月 [査読有り][通常論文]
     
    This retrospective study aimed to compare the accuracy of two nodal evaluation criteria using computed tomography after intra-arterial chemoradiation in node-positive head and neck squamous cell carcinomas. Computed tomography was used to evaluate radiographic nodal response 4-8 weeks after intra-arterial chemoradiation. We compared the accuracy of two different criteria: criterion 1 (radiographic complete response was recorded in the absence of focal abnormalities and if the maximum diameter of the metastatic node was less than 15 mm), and criterion 2 (radiographic complete response was recorded in the absence of focal abnormalities and if the minimum diameter of metastatic nodes was less than 7 mm in level II and if the minimum diameter of metastatic nodes in the rest of the neck was less than 6 mm). Positive predictive values were criterion 1: 69.2%, criterion 2: 47.8%; negative predictive values were criterion 1: 88.5%, criterion 2: 90.5%. Positive likelihood ratios were criterion 1: 7.50, criterion 2: 3.06. The difference between each criteria was statistically significant using McNemar's test ( = 0.0016). Computed tomography evaluation accuracy of nodal response after intra-arterial chemoradiation was comparable to recent reports, and it was feasible to perform salvage neck dissection by computed tomography evaluation for nodal response. We recommend using criterion 1 because of its simplicity and reliability.
  • 中咽頭扁平上皮癌症例におけるHPV感染とp16の発現に関する検討
    水町 貴諭, 鈴木 清護, 畠山 博充, 加納 里志, 坂下 智博, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 38 2 161 - 161 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 原発不明頸部リンパ節転移におけるp16とヒト乳頭腫ウイルスの解析
    加納 里志, 折舘 伸彦, 本間 明宏, 鈴木 清護, 畠山 博充, 水町 貴諭, 坂下 智博, 福田 諭
    頭頸部癌 38 2 162 - 162 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 頭頸部扁平上皮癌根治切除症例の切除断端における免疫組織学的予後因子の検討
    坂下 智博, 折舘 伸彦, 本間 明宏, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 福田 諭
    頭頸部癌 38 2 182 - 182 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 中咽頭癌に対する治療の現状(第2報) 多施設による後ろ向き観察研究
    林 隆一, 川端 一嘉, 吉野 邦俊, 岩江 信法, 長谷川 泰久, 加納 里志, 丹生 健一, 加藤 孝邦, 志賀 清人, 本間 明宏, 藤井 正人
    頭頸部癌 38 2 205 - 205 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 多施設共同による唾液腺導管癌の後方視的観察研究 免疫組織学的・分子病理学的検討
    多田 雄一郎, 花澤 豊行, 今西 順久, 佐藤 雄一郎, 金澤 丈治, 福島 啓文, 清水 顕, 加納 里志, 矢島 陽子, 大上 研二, 長尾 俊孝
    頭頸部癌 38 2 209 - 209 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 多施設共同による唾液腺導管癌の後方視的観察研究 術前病理組織学的診断における検査法と診断率の現状
    茶薗 英明, 多田 雄一郎, 今西 順久, 佐藤 雄一郎, 金澤 丈治, 福島 啓文, 清水 顕, 加納 里志, 矢島 陽子, 大上 研二, 大塚 邦憲, 花澤 豊行, 長尾 俊孝
    頭頸部癌 38 2 210 - 210 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 多施設共同による唾液腺導管癌の後方視的観察研究 生存率および予後因子に関する検討
    大塚 邦憲, 多田 雄一郎, 今西 順久, 花澤 豊行, 佐藤 雄一郎, 金澤 丈治, 福島 啓文, 清水 顕, 加納 里志, 矢島 陽子, 大上 研二, 長尾 俊孝
    頭頸部癌 38 2 210 - 210 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 頭頸部癌化学放射線療法における経管栄養の役割に関する検討
    折舘 伸彦, 倉本 倫之介, 本間 明宏, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 及川 敬太, 福田 諭
    頭頸部癌 38 2 210 - 210 (一社)日本頭頸部癌学会 2012年05月 [査読無し][通常論文]
  • 加納 里志, 折舘 伸彦, 福田 諭
    日本気管食道科学会会報 63 2 s87 - s87 (NPO)日本気管食道科学会 2012年04月 [査読無し][通常論文]
  • 水町 貴諭, 加納 里志, 畠山 博充, 坂下 智博, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    日本耳鼻咽喉科学会会報 115 4 466 - 466 (一社)日本耳鼻咽喉科学会 2012年04月 [査読無し][通常論文]
  • 坂下 智博, 本間 明宏, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 福田 諭
    日本耳鼻咽喉科学会会報 115 4 519 - 519 (一社)日本耳鼻咽喉科学会 2012年04月 [査読無し][通常論文]
  • 舌根部癌に対する喉頭機能温存治療 中咽頭前壁原発扁平上皮癌に対する超選択的動注化学療法と照射の同時併用療法
    本間 明宏, 坂下 智博, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 福田 諭
    日本気管食道科学会会報 63 1 77 - 78 (NPO)日本気管食道科学会 2012年02月 [査読無し][通常論文]
  • 鈴木 崇祥, 加納 里志, 折舘 伸彦, 本間 明宏, 鈴木 清護, 畠山 博充, 水町 貴諭, 古沢 純, 坂下 智博, 福田 諭
    頭頸部外科 = Journal of Japan Society for Head and Neck Surgery 21 2 195 - 201 特定非営利活動法人 日本頭頸部外科学会 2011年10月30日 [査読無し][通常論文]
     
    Salivary duct carcinoma histologically resembles an invasive mammary ductal carcinoma and is a malignant tumor with a poor prognosis. The rarity of this carcinoma has resulted in a lack of consensus on its chemotherapy regimen. In recent years, HER2 overexpression has been reported in not only breast cancer but also salivary duct carcinoma, so we performed an immunostaining on the surgical specimens of salivary duct carcinoma and analyzed the relationship between HER2 expression and the clinical background. As a result, 3 cases were found to be HER2-positive. In salivary gland carcinomas, t...
  • Tomonobu Sato, Fumihiko Okumura, Satoshi Kano, Takeshi Kondo, Tadashi Ariga, Shigetsugu Hatakeyama
    JOURNAL OF CELL SCIENCE 124 20 3492 - 3502 2011年10月 [査読有り][通常論文]
     
    Retinoic acid (RA), a metabolite of vitamin A, plays versatile roles in development, differentiation, cell cycles and regulation of apoptosis by regulating gene transcription through nuclear receptor activation. Ubiquitinylation, which is one of the post-translational modifications, appears to be involved in the transcriptional activity of intranuclear receptors including retinoic acid receptor alpha (RAR alpha). Mutations in the tripartite motif-containing protein 32 gene (TRIM32; also known as E3 ubiquitin-protein ligase) have been reported to be responsible for limb-girdle muscular dystrophy type 2H in humans, and its encoded protein has been shown to interact with several other important proteins. In this study, we found that TRIM32 interacts with RAR alpha and enhances its transcriptional activity in the presence of RA. We also found that overexpression of TRIM32 in mouse neuroblastoma cells and embryonal carcinoma cells promoted stability of RAR alpha, resulting in enhancement of neural differentiation. These findings suggest that TRIM32 functions as one of the co-activators for RAR alpha-mediated transcription, and thereby TRIM32 is a potential therapeutic target for developmental disorders and RA-dependent leukemias.
  • 機能温存をめざした下咽頭癌の治療 下咽頭癌に対する超選択的動注化学療法と照射の同時併用療法の有用性
    本間 明宏, 加納 里志, 水町 貴諭, 福田 諭
    口腔・咽頭科 24 3 229 - 229 日本口腔・咽頭科学会 2011年08月 [査読無し][通常論文]
  • HPV感染による中咽頭癌治療の層別化戦略
    水町 貴諭, 加納 里志, 本間 明宏, 折舘 伸彦, 福田 諭
    口腔・咽頭科 24 3 353 - 353 日本口腔・咽頭科学会 2011年08月 [査読無し][通常論文]
  • Akihiro Homma, Naoya Inamura, Nobuhiko Oridate, Seigo Suzuki, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 8 980 - 986 2011年08月 [査読有り][通常論文]
     
    Objective: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. Methods: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. Results: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). Conclusions: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.
  • Satoshi Kano, Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Jun Furusawa, Tomohiro Sakashita, Daisuke Yoshida, Rikiya Onimaru, Hiroki Shirato, Satoshi Fukuda
    ORAL ONCOLOGY 47 7 665 - 670 2011年07月 [査読有り][通常論文]
     
    The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success. (C) 2011 Elsevier Ltd. All rights reserved.
  • 個別化を目指す薬物療法 HPV陽性中咽頭癌に対する個別化治療戦略
    水町 貴諭, 畠山 博充, 加納 里志, 坂下 智博, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 37 2 191 - 191 (一社)日本頭頸部癌学会 2011年05月 [査読無し][通常論文]
  • 頭頸部癌におけるNF-kBパスウエイの活性化とセツキシマブ耐性
    畠山 博充, 鈴木 清護, 坂下 智博, 加納 里志, 水町 貴諭, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 37 2 230 - 230 (一社)日本頭頸部癌学会 2011年05月 [査読無し][通常論文]
  • 頭頸部扁平上皮癌N+症例における放射線動注化学療法後の頸部評価 Wait and See Policyは成立するか
    坂下 智博, 本間 明宏, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 古沢 純, 稲村 直哉, 福田 諭, 吉田 大介, 鬼丸 力也, 安田 耕一, 白土 博樹
    頭頸部癌 37 2 231 - 231 (一社)日本頭頸部癌学会 2011年05月 [査読無し][通常論文]
  • 頭頸部進行癌に対する集学的治療 "導入化学療法→化学放射線同時併用療法"
    本間 明宏, 清水 康, 折舘 伸彦, 鬼丸 力也, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 安田 耕一, 秋田 弘俊, 白土 博樹, 福田 諭
    頭頸部癌 37 2 233 - 233 (一社)日本頭頸部癌学会 2011年05月 [査読無し][通常論文]
  • 唾液腺悪性腫瘍におけるEGFR、HER2、c-KITの発現解析
    加納 里志, 鈴木 清護, 折舘 伸彦, 本間 明宏, 畠山 博充, 水町 貴諭, 坂下 智博, 福田 諭
    頭頸部癌 37 2 270 - 270 (一社)日本頭頸部癌学会 2011年05月 [査読無し][通常論文]
  • Satoshi Kano, Shigetsugu Hatakeyama, Satoshi Fukuda, Hiromitsu Hatakeyama
    CANCER RESEARCH 71 2011年04月 [査読有り][通常論文]
  • Homma A, Inamura N, Oridate N, Suzuki S, Hatakeyama H, Mizumachi T, Kano S, Sakashita T, Onimaru R, Yasuda K, Shirato H, Fukuda S
    Jpn J Clin Oncol 41 8 980 - 6 2011年 [査読有り][通常論文]
  • 秦 浩信, 山崎 裕, 今待 賢治, 村井 知佳, 佐藤 淳, 水町 貴諭, 加納 里志, 本間 明宏, 福田 諭, 北川 善政
    頭頸部癌 37 4 486 - 493 (一社)日本頭頸部癌学会 2011年 [査読無し][通常論文]
     
    我々は2007年から北海道大学病院において、頭頸部がん治療患者に対する口腔ケアを開始した。2010年度までの4年間に頭頸部がん患者254名の患者に対して行った、口腔ケアの臨床統計的調査結果と当院の口腔ケアシステムの概要を紹介する。本調査において、口腔ケア介入を行った頭頸部がん患者の約8割が放射線治療の患者であり、放射線治療に伴う口腔有害事象に対する対応が重要であった。頭頸部の放射線治療時には、できるだけ早期に口腔ケア介入を開始することが望ましいが、本調査結果では照射開始4日以上前からの口腔ケア介入開始率は2009年度まで徐々に上昇し、約60%に達したにも関わらず、2010年度は過去最低の37.9%であった。今後、放射線治療予定患者は可能な限り入院前から、口腔ケアが開始できるようにシステムの見直しが必要である。また、退院後に当院耳鼻咽喉科で外来経過観察を行わなかった74例について引き続き地元歯科医院で歯科医療連携が行われたのは19例(27.0%)であった。退院後にも歯科介入が継続できる医療連携システムの構築が、今後の大きな課題といえる。(著者抄録)
  • 水町 貴諭, 畠山 博充, 加納 里志, 坂下 智博, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 37 3 394 - 397 (一社)日本頭頸部癌学会 2011年 [査読無し][通常論文]
     
    中咽頭扁平上皮癌83例を対象にHPV感染と治療成績との関連について検討した。HPV陽性例は26例(HPV16陽性22例、HPV18陽性2例、HPV35陽性1例、HPV58陽性1例)であった。5年粗生存率の比較ではHPV陽性例は78.1%、陰性例は48.9%であり、HPV陽性例の方が有意に(p=0.0024)生存率が高かった。放射線化学療法施行症例においてもHPV陽性例の方が有意に高い生存率であった(85.9% vs 38.9%、p=0.0037)。しかし、HPV陽性例に対して放射線単独治療を行った5例のうち3例が再発した。HPV陽性中咽頭癌症例は予後が良好で放射線化学療法に対する治療成績も良好であるが、欧米で試みられている治療強度を下げた治療を本邦で行うには現時点では時期尚早であると考えられた。(著者抄録)
  • 北尾 恭子, 本間 明宏, 折舘 伸彦, 鈴木 清護, 鈴木 章之, 原 敏浩, 加納 里志, 水町 貴諭, 瀧 重成, 稲村 直哉, 福田 諭
    日本耳鼻咽喉科學會會報 114 3 126 - 132 日本耳鼻咽喉科学会 2011年 [査読有り][通常論文]
     
    過去20年間の顎下腺原発の悪性腫瘍1次症例14例について検討した. 組織型は, 腺様嚢胞癌5例, 扁平上皮癌3例, 粘表皮癌2例, 多形腺腫由来癌2例, 癌肉腫1例, 大細胞癌1例であった. TNM分類ではT1: 1例, T2: 7例, T3: 4例, T4: 2例, N0: 9例, N1: 1例, N2: 4例であった. 初診時に遠隔転移を来していた症例はなかった. 治療内容は, 手術が13例, うち, 手術のみが7例, 放射線治療を加えたものが3例, 手術と放射線治療に化学療法を加えたものが2例あった. 1例は手術を行わず対症療法のみとなった. 手術は, 腫瘍の進展範囲に合わせて行い, 頸部郭清は9例に行った. 根治治療を行った1次症例13例の5年粗生存率は全体で57%であった. 組織型別でみると, 多型腺腫内癌, 大細胞癌は100%, 腺様嚢胞癌80%, 粘表皮癌50%, 扁平上皮癌, 癌肉腫は0%であった. Stage分類別でみると, Stage I: 100%, Stage II: 83%, Stage III: 50%, Stage IV: 0%であった. Stage IVおよび扁平上皮癌, 癌肉腫は予後不良であった. 腫瘍の進展範囲に合わせた切除と, 被膜を越えて軟部組織浸潤があった場合には術後照射を加える方針で治療を行い, Stage I-IIは良好な成績であ...
  • 水町 貴諭, 畠山 博充, 加納 里志, 坂下 智博, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 = Head and neck cancer 37 3 394 - 397 2011年 [査読無し][通常論文]
     
    We performed a retrospective analysis of the association between tumor HPV status and the demographic and clinicopathological parameters of 83 patients with oropharyngeal squamous cell carcinoma at Hokkaido University Hospital, Japan, between 1998 and 2010. The parameters included age, gender, tumor subsite, Tumor-Node-Metastasis (TNM) stage, and overall survival. HPV status was established by multiplex polymerase chain reaction analysis. Of the 83 oropharyngeal cancers, 22 were positive for HPV-16, two for HPV-18, and one for HPV-35 and HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumors (p = 0.0024) compared with HPV-negative tumors. Of the 51 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients (p = 0.0024). HPV status is a significantly favorable prognostic factor in oropharyngeal cancer in Japan.
  • 秦 浩信, 山崎 裕, 今待 賢治, 村井 知佳, 佐藤 淳, 水町 貴諭, 加納 里志, 本間 明宏, 福田 諭, 北川 善政
    頭頸部癌 = Head and neck cancer 37 4 486 - 493 2011年 [査読無し][通常論文]
     
    We have been providing oral care for patients with head and neck cancer in Hokkaido University Hospital since 2007. In this paper, we report clinical statistics of the 254 head and neck cancer patients who received oral care. About 80 percent of these patients were treated with radiation therapy, so it is important to cope with adverse events related to such therapy. Oral care is helpful for cancer patients when it is started as soon as possible (at least 1 week before radiation therapy is started). The percentage of patients who could start oral care 4 days before radiation therapy gradually increased to about 60 percent by fiscal 2009. In fiscal 2010, the percentage decreased to its lowest level of 37.9 percent. To start oral care for all patients 7 days before irradiation, we are going to change our system and start oral care in the outpatient period. In their hometowns, oral care was continued for only 19 (27.0 percent) of the 74 patients who could not visit our hospital. An important task for our project is to establish a medical cooperation system for discharged patients treated for head and neck cancer.
  • 本間 明宏, 折舘 伸彦, 鈴木 章之, 原 敏浩, 真栄田 栄行, 加納 里志, 水町 貴諭, 瀧 重成, 稲村 直哉, 古沢 純, 福田 諭
    耳鼻と臨床 56 Suppl.1 S66 - S70 耳鼻と臨床会 2010年11月 [査読無し][通常論文]
     
    2000年から2009年1月までに超選択的動注化学療法と放射線の同時併用療法を下咽頭原発扁平上皮癌新鮮例34例に行った。観察期間は1年3ヵ月-6年4ヵ月(中央値:3年7ヵ月)で、粗生存率(5年)は42.8%で、RADPLATによる局所制御率(5年)は77.8%であった。N0-1症例(10例)は全例生存しているが、N2b-3(24例)の5年生存率は19%と不良であった。下咽頭癌への動注は難しく、リスクも他の部位よりもやや高いといえる。最近は、T4a以下かつN1以下で、原発巣が片側に限局している動注のメリットを発揮できる症例を適応としている。(著者抄録)
  • 中咽頭側壁・前壁癌に対する放射線化学療法の検討
    加納 里志, 本間 明宏, 折舘 伸彦, 福田 諭
    口腔・咽頭科 23 3 373 - 373 日本口腔・咽頭科学会 2010年08月 [査読無し][通常論文]
  • 加納 里志, 折舘 伸彦, 本間 明宏, 鈴木 清護, 鈴木 章之, 原 敏浩, 水町 貴諭, 稲村 直哉, 福田 諭
    耳鼻咽喉科展望 53 補冊1 6 - 7 耳鼻咽喉科展望会 2010年06月 [査読無し][通常論文]
     
    著者らは1998年1月〜2007年12月に根治治療を施行した中咽頭癌新鮮例157例(平均年齢62歳)を対象に後方視的に検討した。1)5年粗生存率は1989〜1996の成績と比較して52%から65%と改善し、特に前壁癌で30%から59%と著明に改善していた。2)前壁癌の約4割にはRADPLATが施行されており、治療成績向上に寄与したものと考えられた。3)治療別の検討では早期癌に対しては手術が最も良い生存率であり、進行癌に対しては経静脈的なCRTに比べてRADPLATによる生存率、局所制御率が高かった。特に腫瘍の栄養血管が比較的単純な前壁癌や側壁癌にはRADPLATが良い適応と考えられた。4)原発の再発率は17%、その救済率は35%で、主にT3-4症例の原発再発の救済はほとんどできていなかった。また頸部の再発率は16%で、その救済率は26%であった。したがって、原発の再発に対してはRADPLATの側壁癌への適応の拡大や再発の早期発見による救済手術、強力な化学療法の開発等が必要であると考えられた。
  • 化学放射線治療後の頸部郭清の必要性について
    本間 明宏, 折舘 伸彦, 鈴木 章之, 鈴木 清護, 原 敏浩, 加納 里志, 水町 貴諭, 古沢 純, 稲村 直哉, 福田 諭, 吉田 大介, 鬼丸 力也, 安田 耕一, 白土 博樹
    頭頸部癌 36 2 191 - 191 (一社)日本頭頸部癌学会 2010年05月 [査読無し][通常論文]
  • 中咽頭扁平上皮癌におけるHPV感染と治療成績の検討
    水町 貴諭, 加納 里志, 原 敏浩, 鈴木 章之, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 36 2 205 - 205 (一社)日本頭頸部癌学会 2010年05月 [査読無し][通常論文]
  • 頭頸部癌に対するweekly cisplatinと放射線同時併用療法の検討
    稲村 直哉, 本間 明宏, 折舘 伸彦, 鈴木 清護, 鈴木 章之, 原 敏浩, 真栄田 裕行, 加納 里志, 水町 貴諭, 福田 諭, 鬼丸 力也, 長谷川 雅一, 安田 耕一, 白土 博樹
    頭頸部癌 36 2 206 - 206 (一社)日本頭頸部癌学会 2010年05月 [査読無し][通常論文]
  • 【耳鼻咽喉・頭頸部画像アトラス】 鼻副鼻腔 嗅神経芽細胞腫
    加納 里志, 福田 諭
    JOHNS 26 3 402 - 403 (株)東京医学社 2010年03月 [査読無し][通常論文]
  • 水町 貴諭, 加納 里志, 原 敏浩, 鈴木 章之, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 = Head and neck cancer 36 4 498 - 501 2010年 [査読無し][通常論文]
     
    We analyzed the presence of HPV from 53 patients diagnosed with oropharyngeal squamous cell carcinoma. In total 14/53 (26%) were HPV-positive. In 14 HPV-positive patients, 12 patients (86%) were HPV-16-positive, 1 patient was HPV-18-positive, and 1 patient was HPV-58-positive. HPV-positive patients had significantly better disease-specific survival rates than HPV-negative patients. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after chemoradiation treatment. For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with chemoradiation response and survival. © 2010, Japan Society for Head and Neck Cancer. All rights reserved.
  • Hiroyuki Maeda, Naoto Miyajima, Satoshi Kano, Tadasuke Tsukiyama, Fumihiko Okumura, Satoshi Fukuda, Shigetsugu Hatakeyama
    MOLECULAR CANCER RESEARCH 7 9 1553 - 1562 2009年09月 [査読有り][通常論文]
     
    The ubiquitin-proteasome system has a crucial role in maintaining and regulating cellular homeostasis including carcinogenesis. UBE2Q2, also designated Ubci, is one of the ubiquitin-conjugating enzymes (E2), and it has been reported that mRNA of UBE2Q2 is highly expressed in human head and neck squamous cell carcinoma, particularly hypopharyngeal carcinoma. However, the involvement of UBE2Q2 in carcinogenesis has not been fully elucidated. Most cases of head and neck carcinoma are treated with cis-diamminedichloroplatinum (II; CDDP) or docetaxel, which are the most effective chemotherapeutic agents against squamous cell carcinomas. Nevertheless, some head and neck cancers develop resistance to these drugs, although the causes and mechanisms remain unknown. In this study, we found high expression levels of UBE2Q2 in human head and neck carcinoma cell lines and cancer tissues by using an anti-UBE2Q2 antibody at the protein level. We also found that the expression level of UBE2Q2 is decreased in cell lines and cancer tissues that have resistance to CDDP or docetaxel and in cancer tissues treated with CDDP or docetaxel. Furthermore, we found that overexpression of UBE2Q2 affects cell proliferation and anchorage-independent cell growth. These findings suggest that UBE2Q2 is a novel oncosuppressor that inhibits tumor growth and is related to the resistance to anticarcinoma agents and that UBE2Q2 likely functions as a novel diagnostic tool and a potentially therapeutic target for head and neck squamous cell carcinoma. (Mol Cancer Res 2009;7(9):1553-62)
  • ユビキチン結合酵素UBE2Q2の頭頸部悪性腫瘍に対する調節機能の分子生化学的解析(Ubiquitin-conjugating enzyme UBE2Q2 suppresses cell proliferation and is down-regulated in recurrent head and neck cancer)
    真栄田 裕行, 宮島 直人, 加納 里志, 築山 忠維, 奥村 文彦, 福田 諭, 畠山 鎮次
    日本生化学会大会プログラム・講演要旨集 82回 4P - 480 (公社)日本生化学会 2009年09月 [査読無し][通常論文]
  • 化学放射線療法後の救済手術 問題点とその対策 喉頭下咽頭癌に対する化学放射線療法後の救済手術
    鈴木 章之, 本間 明宏, 折舘 伸彦, 鈴木 清護, 水町 貴諭, 加納 里志, 瀧 重成, 稲村 直哉, 鬼丸 力也, 長谷川 雅一, 白土 博樹, 古田 康, 福田 諭
    頭頸部癌 35 2 61 - 61 (一社)日本頭頸部癌学会 2009年05月 [査読無し][通常論文]
  • 臨床パネル「頭頸部癌とヒト乳頭腫ウイルス(HPV)」 頭頸部癌におけるヒト乳頭腫ウイルスによる発癌のメカニズムと検出について
    水町 貴諭, 瀧 重成, 加納 里志, 原 敏浩, 鈴木 章之, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭, 古田 康
    頭頸部癌 35 2 68 - 68 (一社)日本頭頸部癌学会 2009年05月 [査読無し][通常論文]
  • UBE2Q2は細胞増殖を抑制し、再発性頭頸部癌においてはその発現が抑制されている(UBE2Q2 suppresses cell proliferation and is down-regulated in recurrent head and neck cancer)
    真栄田 裕行, 加納 里志, 畠山 鎮次, 福田 諭
    日本耳鼻咽喉科学会会報 112 4 315 - 315 (一社)日本耳鼻咽喉科学会 2009年04月 [査読無し][通常論文]
  • 鈴木 章之, 本間 明宏, 折舘 伸彦, 鈴木 清護, 水町 貴諭, 加納 里志, 瀧 重成, 稲村 直哉, 鬼丸 力也, 長谷川 雅一, 白土 博樹, 古田 康, 福田 諭
    頭頸部癌 35 4 344 - 349 (一社)日本頭頸部癌学会 2009年 [査読無し][通常論文]
     
    頭頸部癌における機能温存療法として化学療法同時併用放射線療法(CCRT)が普及してきた。しかし、CCRT後の救済手術においては合併症の発生率が高いことが報告されており、慎重な対応を要する。当科では1995年から2008年5月の間に、喉頭癌131例、下咽頭癌107例に対して根治的CCRTを施行した。喉頭癌では131例中43例(33%)に原発再発を認め、うち38例(88%)に救済手術を施行し、30例(79%)に局所制御が得られた。一方、下咽頭癌では107例中30例(28%)に原発再発を認め、うち10例(33%)に救済手術を施行し、6例(60%)に局所制御が得られた。また、当科で救済手術として喉頭全摘または咽喉食摘術を施行した34例(喉頭癌28、下咽頭癌6)において術後合併症を検討したところ、軽症を含むすべての局所合併症は53%、重度局所合併症は29%、咽頭皮膚瘻は26%に認められた。CCRT症例では高度の組織障害による創傷治癒機転の障害のため、救済手術後に感染や瘻孔などの合併症を生じやすい。我々は合併症の予防対策として皮膚切開線の工夫、前頸筋や甲状腺の保存、主要静脈の保存などによる組織血流の保存や死腔防止に努める他、喉頭全摘後の咽頭粘膜縫合部と皮膚の間に大胸筋弁を挟む方法(pharyngeal interposition graft)を行なっている。CCRT開始前には救済手術時の高い合併症発生率と創傷治癒が不良であることを考慮した上で適応を判断するべきであり、救済手術においては、合併症を防止するための対策が重要であると考えられた。(著者抄録)
  • 水町 貴諭, 瀧 重成, 加納 里志, 原 敏浩, 鈴木 章之, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭, 古田 康
    頭頸部癌 35 4 356 - 359 (一社)日本頭頸部癌学会 2009年 [査読無し][通常論文]
     
    ヒト乳頭腫ウイルス(human papillomavirus:HPV)は子宮頸癌の発生に関与することが知られているが、近年の分子疫学的検索から頭頸部扁平上皮癌、とくに扁桃原発中咽頭癌へのHPVの関与が明らかになりつつある。HPV感染の有無は扁桃原発の中咽頭癌においては診断としても有用であるばかりでなく、ワクチンの開発、普及が進めば予防、さらには発症数の減少につながる可能性があり、今後の発展が望まれる分野である。本稿ではこれまでに報告されているHPVによる頭頸部癌の発癌メカニズムおよびHPV検出法について概説するとともに当科における中、下咽頭癌症例でのHPV検出についても述べる。(著者抄録)
  • 水町 貴諭, 瀧 重成, 加納 里志, 原 敏浩, 鈴木 章之, 鈴木 清護, 本間 明宏, 折舘 伸彦, 福田 諭, 古田 康
    頭頸部癌 = Head and neck cancer 35 4 356 - 359 2009年 [査読無し][通常論文]
     
    Cervical cancer is initiated by infection with high-risk human papillomaviruses (HPVs). It has been suggested that the link between HPV and head and neck squamous cell carcinoma is specific to carcinoma of the tonsil. We systematically summarize HPV infection, carcinogenic mechanisms and detection of HPV in head and neck cancer. It will be necessary to develop preventive and therapeutic strategies aimed at reducing the incidence and mortality of HPV-associated cancers. © 2009, Japan Society for Head and Neck Cancer. All rights reserved.
  • 鈴木 章之, 本間 明宏, 折舘 伸彦, 鈴木 清護, 水町 貴諭, 加納 里志, 瀧 重成, 稲村 直哉, 鬼丸 力也, 長谷川 雅一, 白土 博樹, 古田 康, 福田 諭
    頭頸部癌 = Head and neck cancer 35 4 344 - 349 2009年 [査読無し][通常論文]
     
    Complication rates for salvage surgery after concurrent chemoradiotherapy (CCRT) have been reported to be high. From 1995 to 2008, 131 patients with laryngeal cancer and 107 with hypopharyngeal cancer underwent CCRT at Hokkaido University Hospital, Japan. Of the 131 patients with laryngeal cancer, a local recurrence developed in 43 (33%), of whom 38 (88%) underwent salvage surgery. The local control rate after salvage surgery was 79% (30/38). On the other hand, a local recurrence developed in 30 (28%) of 107 patients with hypopharyngeal cancer, of whom only 10 (33%) underwent salvage surgery, the local control rate after which was 60% (6/10). In 34 patients who underwent salvage laryngectomy or laryngopharyngectomy in our hospital (laryngeal cancer 28, hypopharyngeal cancer 6), overall wound complications, major wound complications and pharyngocutaneous fistulas were observed in 53%, 29% and 26%, respectively. CCRT can cause difficulties in wound healing and wound complications, such as infection or pharyngocutaneous fistulas. To reduce the incidence of wound complications, we have taken steps including appropriate skin incisions, preservation of the strap muscles, thyroid glands and major veins, and pectoralis major myofascial flap transfer to reinforce the primary pharyngeal closure (pharyngeal interposition graft). High incidences of wound complications and poor wound recovery in patients undergoing salvage surgery following CCRT should be taken into account before the initiation of CCRT, and emphasis should be placed on taking steps to prevent wound complications associated with salvage surgery. © 2009, Japan Society for Head and Neck Cancer. All rights reserved.
  • 頭頸部癌における集学的治療 頭頸部癌に対する超選択的動注療法・照射同時併用療法
    本間 明宏, 折舘 伸彦, 鈴木 清護, 鈴木 章之, 原 敏浩, 水町 貴諭, 加納 里志, 瀧 重成, 浅野 剛, 吉田 大介, 西岡 健, 鬼丸 力也, 長谷川 雅一, 白土 博樹, 福田 諭
    日本癌治療学会誌 43 2 284 - 284 (一社)日本癌治療学会 2008年10月 [査読無し][通常論文]
  • Satoshi Kano, Naoto Miyajima, Satoshi Fukuda, Shigetsugu Hatakeyama
    CANCER RESEARCH 68 14 5572 - 5580 2008年07月 [査読有り][通常論文]
     
    Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs.
  • Naoto Miyajima, Satoru Maruyama, Miyuki Bohgaki, Satoshi Kano, Masahiko Shigemura, Nobuo Shinohara, Katsuya Nonomura, Shigetsugu Hatakeyama
    CANCER RESEARCH 68 9 3486 - 3494 2008年05月 [査読有り][通常論文]
     
    The androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors that mediate the action of androgen. AR plays an important role in normal development of the prostate, as well as in the progression of prostate cancer. AR is regulated by several posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. In this study, we found that the putative E3 ubiquitin ligase TRIM68, which is preferentially expressed in prostate cancer cells, interacts with AR and enhances transcriptional activity of the AR in the presence of dihydrotestosterone. We also found that TRIM68 functionally interacts with TIP60 and p300, which act as coactivators of AR, and synergizes in the transactivation of AR. Overexpression of TRIM68 in prostate cancer cells caused an increase in secretion of prostate-specific antigen (PSA), one of the most reliable diagnostic markers for prostate cancer, whereas knockdown of TRIM68 attenuated the secretion of PSA and inhibited cell growth and colony-forming ability. Moreover, we showed that TRIM68 expression is sigmficantly up-regulated in human prostate cancers compared with the expression in adjacent normal tissues. These results indicate that TRIM68 functions as a cofactor for AR-mediated transcription and is likely to be a novel diagnostic tool and a potentially therapeutic target for prostate cancer.
  • 北海道大学病院における口腔底癌の治療成績
    瀧 重成, 本間 明宏, 折舘 伸彦, 鈴木 清護, 鈴木 章之, 加納 里志, 水町 貴諭, 古田 康, 福田 諭
    頭頸部癌 34 2 229 - 229 (一社)日本頭頸部癌学会 2008年05月 [査読無し][通常論文]
  • 頭頸部扁平上皮癌におけるユビキチンリガーゼTRIM32の機能解析
    加納 里志, 真栄田 裕行, 畠山 鎮次, 福田 諭
    日本耳鼻咽喉科学会会報 110 4 326 - 326 (一社)日本耳鼻咽喉科学会 2007年04月 [査読無し][通常論文]
  • 体外式酸素化装置を使用した気管内手術の2例
    柏村 正明, 武市 紀人, 古沢 純, 加納 里志, 小原 修幸, 福田 諭
    日本耳鼻咽喉科学会会報 109 4 368 - 368 (一社)日本耳鼻咽喉科学会 2006年04月 [査読無し][通常論文]
  • 加納 里志, 古田 康, 本間 明宏, 折舘 伸彦, 樋口 榮作, 鈴木 章之, 永橋 立望, 澤村 豊, 福田 諭
    日本耳鼻咽喉科學會會報 109 5 433 - 439 社団法人 日本耳鼻咽喉科学会 2006年 [査読有り][通常論文]
     
    Olfactory neuroblastoma is such a rare malignancy that no consensus has been reached on its management. We analyzed 17 patients with olfactory neuroblastoma treated between April 1980 and March 2004-9 men and 8 women, aged 16 to 76 years old (mean: 50.4 years). Follow-up of current survivors was 1 year 8 months to 16 years 6 months (average: 7 years 9 months). Initially, 2 were treated with surgery alone, 5 with surgery and radiotherapy, and 2 with a combination of these and chemotherapy. Without surgery, radiotherapy alone was conducted in 3 and combined of radiation and chemotherapy in 5....
  • 当科における嗅神経芽細胞腫の治療経験
    加納 里志, 古田 康, 本間 明宏, 折舘 伸彦, 樋口 榮作, 鈴木 章之, 永橋 立望, 福田 諭
    日本耳鼻咽喉科学会会報 108 4 457 - 457 (一社)日本耳鼻咽喉科学会 2005年04月 [査読無し][通常論文]
  • 当科における難治性外耳道炎及び中耳炎に対するブロー液の治療経験
    加納 里志, 山本 潤, 川浪 貢
    岩見沢市立総合病院医誌 30 1 55 - 58 岩見沢市立総合病院 2004年04月 [査読無し][通常論文]
     
    難治性耳瘻を呈する19例19耳に13%酢酸アルミニウム液(ブロー液)を用い,治療効果を疾患や検出菌別に検討し,その他の治療抵抗因子に関し考察した.耳瘻が停止したものを治癒とすると治癒率は73.7%で,ブロー液単独での治癒率は70.6%であり,ブロー液の優れた有効性が証明された.検出菌別では,真菌単独では100%の治癒率で,真菌と細菌の重複例でも80%であった.有効の1例でも視診上は真菌が消失しており,真菌に対してはその属にこだわらず100%の効果があった.細菌単独例では治癒例はなかった.原因疾患別では,術後性乳突腔障害で治癒率は50%,外耳道・湿疹と肉芽性鼓膜炎では100%の治癒率であった.穿孔性中耳炎では,治癒率が71.4%と外耳道炎や鼓膜炎に比べてやや低かった.治癒に至らなかった5症例を検討した結果,治療抵抗因子として,真珠腫の合併,ポリープの合併,補聴器の使用,粘稠性耳瘻が考えられた
  • 舌に発生した異所性脳組織の1症例
    加納 里志, 鈴木 清護, 劉 澤周, 木田 毅, 大湯 淳功, 渡辺 麻衣子, 山田 豊
    道南医学会誌 37 303 - 305 道南医学会 2002年07月 [査読無し][通常論文]
     
    日齢0の男児.主訴は舌腫瘤.MRIの矢状断では,正常舌の上に,口腔内を占拠するほど巨大な腫瘤を認めた.腫瘤はT1強調で筋肉と同程度の信号を示し,T2強調でやや不均一に高信号を示していた.この腫瘤により硬口蓋が挙上され鼻腔が狭くなり,又,軟口蓋付近では気道の狭小化を認めた.呼吸苦が出現し経口エアウェイを挿入した.全身麻酔下に生検施行し,呼吸状態が悪化してきたため気管切開を施行し,舌腫瘤切除となった.摘出物は約4cmの半球型の腫瘤であった.その後,特に問題なく気管孔は自然閉鎖した.現在,経口摂取可能で呼吸状態も良好である
  • 先天性舌腫瘍(異所性脳組織)の1例
    渡辺 麻衣子, 城 和歌子, 大湯 淳功, 木田 毅, 水上 晋, 屋敷 憲章, 山田 豊, 加納 里志, 鈴木 清護, 劉 澤周
    日本小児科学会雑誌 106 6 817 - 817 (公社)日本小児科学会 2002年06月 [査読無し][通常論文]
  • ESSにて治療した上顎含歯性嚢胞の1症例
    加納 里志, 加藤 明夫
    日本耳鼻咽喉科学会会報 105 1増刊 93 - 94 (一社)日本耳鼻咽喉科学会 2002年01月 [査読無し][通常論文]
  • 乳突充填型鼓室形成術にて治療した中耳コレステリン肉芽腫症例
    加藤 明夫, 加納 里志
    日本耳鼻咽喉科学会会報 105 1増刊 96 - 96 (一社)日本耳鼻咽喉科学会 2002年01月 [査読無し][通常論文]
  • 当科におけるシスプラチンの超選択的動注療法
    本間 明宏, 畠山 博充, 加納 里志, 永橋 立望, 八木 克憲, 古田 康, 福田 諭, 犬山 征夫
    日本耳鼻咽喉科学会会報 104 5増刊 640 - 641 (一社)日本耳鼻咽喉科学会 2001年05月 [査読無し][通常論文]
  • 結核性頸部リンパ節炎の2症例
    加納 里志, 加藤 明夫
    砂川市立病院医学雑誌 18 1 63 - 66 砂川市立病院 2001年03月 [査読無し][通常論文]
     
    症例1:61歳男.両頸部腫瘤を主訴とした.症例2:70歳女.右頸部腫瘤を主訴とした.症例1では悪性リンパ腫を,症例2では結核性リンパ節炎を疑い,診断確定のため腫瘤を摘出した.2例とも病理組織学的検査で初めて結核と診断し,ツ反で強陽性を示した.症例1では術後に創部浸出液を用いて,症例2では自壊したリンパ節の浸出液と摘出したリンパ節を用いてPCR検査を試行したが,全て陰性であった.術後13日目,2日目からそれぞれ抗結核療法を開始した.2例とも肺結核の既往はなく,肺病変も認めなかったが,頸部腫瘤を認めた場合,常に鑑別疾患として結核性リンパ節炎も念頭において診察,検査を進めていく必要がある
  • 頸部原発脂肪肉腫の1症例
    加納 里志, 飯尾 光博, 本間 明宏, 八木 克憲, 福田 諭, 犬山 征夫
    日本耳鼻咽喉科学会会報 103 5増刊 699 - 699 (一社)日本耳鼻咽喉科学会 2000年05月 [査読無し][通常論文]

その他活動・業績

  • 唾液腺導管癌における脂質関連蛋白発現の臨床病理学的意義
    平井 秀明, 多田 雄一郎, 中黒 匡人, 川北 大介, 佐藤 由紀子, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 伏見 千宙, 清水 顕, 高瀬 総一郎, 岡田 拓朗, 佐藤 宏樹, 今西 順久, 大塚 邦憲, 渡部 佳弘, 酒井 昭博, 戎本 浩史, 富樫 孝文, 植木 雄志, 太田 久幸, 三枝 奈津季, 高橋 秀聡, 安藤 瑞生, 浦野 誠, 花澤 豊行, 長尾 俊孝 日本唾液腺学会誌 60 24 -25 2019年11月 [査読無し][通常論文]
  • Ichiro Kinoshita, Satoshi Kano, Yasushi Shimizu, Naomi Kiyota, Yuichiro Tada, Kei Ijichi, Tmoko Yamazaki, Akihiro Homma, Yoichi M. Ito, Kota Ono, Keiko Kobayashi, Toshiyuki Isoe, Yutaka Hatanaka, Hitoshi Tsuda, Shojiroh Morinaga, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita CANCER RESEARCH 79 (13) 2019年07月
  • 志村 智隆, 多田 雄一郎, 川北 大介, 塚原 清彰, 加納 里志, 清水 顕, 今西 順久, 大上 研二, 佐藤 雄一郎, 平井 秀明, 長尾 俊孝, 小林 一女 日本耳鼻咽喉科学会会報 121 (4) 542 -542 2018年04月 [査読無し][通常論文]
  • 唾液腺導管癌における重要な治療標的分子の遺伝子変異と蛋白発現 その予後・組織発生との関連(学位甲)
    志村 智隆, 多田 雄一郎, 川北 大介, 塚原 清彰, 加納 里志, 清水 顕, 今西 順久, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 平井 秀明, 長尾 俊孝, 小林 一女 昭和学士会雑誌 78 (2) 198 -199 2018年04月 [査読無し][通常論文]
  • 渡部 涼子, 丸川 活司, 望月 抄苗, 清水 知浩, 宮越 里絵, 安孫子 光春, 岡田 宏美, 加納 里志, 畑中 佳奈子, 三橋 智子, 松野 吉宏 北海道臨床細胞学会会報 26 29 -33 2017年
  • 唾液腺導管癌ではFOXA1の発現が予後予測因子となる
    平井 秀明, 多田 雄一郎, 川北 大介, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 清水 顕, 今西 順久, 長尾 俊孝 日本唾液腺学会誌 57 31 -31 2016年11月 [査読無し][通常論文]
  • 唾液腺導管癌における免疫組織化学的発現解析 多施設共同による152症例の検討
    加納 里志, 高瀬 聡一郎, 多田 雄一郎, 川北 大介, 塚原 清彰, 清水 顕, 今西 順久, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 佐藤 由紀子, 志村 智隆, 花澤 豊行, 長村 義之, 長尾 俊孝 日本癌治療学会学術集会抄録集 54回 PS -3 2016年10月 [査読無し][通常論文]
  • T. Nagao, Y. Tada, S. Kano, D. Kawakita, S. Takase VIRCHOWS ARCHIV 469 S121 -S121 2016年09月 [査読無し][通常論文]
  • 渡邊史郎, 真鍋治, 平田健司, 菊地恒矢, 牧野俊一, 豊永拓哉, 小林健太郎, 内山裕子, 志賀哲, 加納里志, 玉木長良 核医学(Web) 53 (1) 507(J‐STAGE) 2016年 [査読無し][通常論文]
  • Jun Furusawa, Akihiro Homma, Rikiya Onimaru, Tomohiro Sakashita, Daisuke Yoshida, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda Journal of Otolaryngology of Japan 119 (5) 782 -783 2016年01月01日 [査読無し][通常論文]
  • 鈴木正宣, 鈴木正宣, 渡部昌, 中丸裕爾, 高木大, 加納里志, 本間あや, 畠山鎮次, 福田諭 耳鼻咽喉科免疫アレルギー(Web) 33 (3) 185-192 (J-STAGE) 2015年 [査読無し][通常論文]
  • A. Homma, T. Sakashita, D. Yoshida, R. Onimaru, K. Tsuchiya, F. Suzuki, K. Yasuda, H. Hatakeyama, J. Furusawa, T. Mizumachi, S. Kano, N. Inamura, S. Taki, H. Shirato, S. Fukuda British Journal of Cancer 109 (12) 2980 -2986 2013年12月10日 [査読無し][通常論文]
     
    Background:The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS).Methods:Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m-2 per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy).Results:One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions.Conclusion:We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS. © 2013 Cancer Research UK.
  • 佐藤由紀子, 多田雄一郎, 川北大介, 長村義之, 長尾俊幸, 花澤豊行, 花薗英明, 加納里志, 清水顕, 高瀬総一郎, 今西順久, 大塚邦憲, 佐藤雄一朗, 富樫孝文, 大上研二, 酒井昭博 日本唾液腺学会誌 54 23 -23 2013年11月10日 [査読無し][通常論文]
  • 茂木洋晃, 寺坂俊介, 小林浩之, 本間明宏, 加納里志, 畠山博充, 水町貴諭, 福田諭, 寳金清博 日本脳腫瘍の外科学会プログラム・抄録集 18th 2013年
  • 坂下 智博, 本間 明宏, 折舘 伸彦, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 吉田 大介, 藤間 憲幸, 福田 諭 北海道醫學雜誌 = Acta medica Hokkaidonensia 87 (6) 261 -261 2012年11月01日 [査読無し][通常論文]
  • Takatsugu Mizumachi, Satoshi Kano, Naoya Inamura, Toshihiro Hara, Fumiyuki Suzuki, Seigo Suzuki, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda RECENT ADVANCES IN TONSILS AND MUCOSAL BARRIERS OF THE UPPER AIRWAYS 72 208 -208 2011年 [査読無し][通常論文]

共同研究・競争的資金等の研究課題

  • 個別化治療確立に向けた唾液腺癌の分子病理学的解析:大規模多施設共同研究
    日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 稲垣 宏, 加納 里志, 中黒 匡人, 奥村 嘉英, 岩井 大, 丹生 健一, 草深 公秀, 櫻井 一生, 山元 英崇, 河田 了, 村瀬 貴幸, 田口 健一, 正木 彩子, 羽藤 直人, 多田 雄一郎, 川北 大介, 花井 信広, 大上 研二, 長尾 徹, 長尾 俊孝
  • IMPTを用いた「辛くない」頭頸部癌放射線治療法の開発
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2019年04月 -2023年03月 
    代表者 : 安田 耕一, 加納 里志, 水町 貴諭, 高尾 聖心, 田村 昌也
     
    後ろ向き観察研究の自主臨床計画書を作成し、当施設の審査会にて承認された。 スポットスキャニングIMPTにおける皮膚、唾液腺、舌、粘膜の線量を大幅に低減させる手法の開発に取り組んだ。皮膚に関しては当院で過去に実施された放射線治療患者の線量分布および皮膚炎の程度を解析し、皮膚炎発症に最も関連する皮膚線量のパラメーターを解析した。DVH(dose-volume histogram)解析において、皮膚のV65Gy(65Gy以上照射される皮膚の体積)が皮膚炎グレード3発症に関連する独立因子であることを突き止めた。皮膚炎発症と線量に関するモデル作成について検討を開始した。スポットスキャニングIMPTにおいて、局所的な皮膚線量を低減するプランニング法の開発を開始した。耳下腺及び舌に関しても同様に、線量低減のプランニング法の開発を開始した。粘膜線量低減のために、頭頸部癌におけるPTV(planning target volume) margin(照射ターゲットの位置の不確かさのために付与するマージン)の検証を行った。照射中に撮像可能なCBCT(cone-beam CT)を用いて照射前後の頭頸部の各領域の動きの変化を検証した。各領域に最適なPTV marginを個別に付与する(variable PTV marginの設定)方法の基礎的知見を得た。従来の放射線治療法で治療された頭頸部癌患者に対しQOL調査を行った。四大副作用、つまり皮膚炎、口渇、味覚障害、粘膜炎に関して、患者が感じる「辛さ」を客観的に把握するための調査項目を決定し、調査を開始した。
  • 個別化治療を見据えた唾液腺癌の分子病理学的解析:大規模多施設共同研究
    日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 稲垣 宏, 加納 里志, 中黒 匡人, 奥村 嘉英, 岩井 大, 丹生 健一, 草深 公秀, 櫻井 一生, 山元 英崇, 河田 了, 村瀬 貴幸, 田口 健一, 正木 彩子, 羽藤 直人, 多田 雄一郎, 川北 大介, 花井 信広, 大上 研二, 長尾 徹, 長尾 俊孝, 内藤 健晴
     
    唾液腺癌の発生・進展に関する分子異常およびそれらの治療への応用が進みつつある。しかし唾液腺癌は稀な腫瘍であり、影響力のある成果を発信するには、多数の症例解析が必須である。我々は本邦の代表的研究者・臨床医から賛同を得て、この分野では難しかった多施設共同研究を開始した。多数の唾液腺腫瘍症例が研究事務局である名古屋市立大学に収集され、さらに唾液腺腫瘍を専門とする病理医による病理中央診断が行われた。その結果、質が病理学的に担保された腺様嚢胞癌、粘表皮癌症例がそれぞれ200例以上解析できる体制が整った。これらの症例を用いて、分子病理学的、臨床的な研究が進められている。これまでに共同研究施設が参加する会議が2回(2018年、2019年)行なわれたが、研究内容および研究の方向性について検討が行われた。2019年には2つの研究が論文化された:腺様嚢胞癌における病理中央診断の意義(Head Neck 2020)、粘表皮癌におけるEGFR経路遺伝子変異の臨床病理学的意義(Histopathology 2020)。論文化直前の研究として以下がある。①腺様嚢胞癌における臨床病態および予後因子の解析、②粘表皮癌におけるCRTC1/3-MAML2キメラ遺伝子の意義、③FISH法および次世代シーケンサーによる遺伝子解析の術前細胞診診断への応用。その他、様々な研究が進行中であり、その成果が期待される。これらの研究により、唾液腺癌の分子病態が解明され、その成果が唾液腺癌の層別化・個別化治療へ直接的・間接的に応用されることが期待できる。
  • 高悪性度唾液腺癌に対する網羅的遺伝子解析による新規治療標的分子の発見
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 加納 里志
     
    唾液腺導管癌症例における、保存検体を用いての遺伝子変異および遺伝子発現解析を行った。遺伝子変異に関しては有意な結果が得られなかったが、遺伝子発現に関しては、遺伝子発現プロファイルによりサブタイピングマーカー遺伝子計14遺伝子のうち、9つの遺伝子AR、ERBB2、ESR1、GATA3、GLI1、GRB7、KRT18、KRT19、SLC39A8、TFF3、VEGFA、XBP1でDi Palma分類間(過去に報告されている免疫染色に基づいた唾液腺導管癌の分類。HER2-positive群、Luminal-AR群、Basal-like群の3つに分類されている。)における遺伝子発現の有意差を認めた。また、発症様式間(多形腺腫由来型 vs de novo型)における遺伝子発現の比較検定において、ERBB2、IGF1R、PTEN、RB1、SLIT2、VEGFA、XBP1において遺伝子発 現の有意差を認めた。ERBB2、IGF1R、RB1、VEGFA、XBP1は多形腺腫由来型優位の遺伝子発現、PTEN、SLIT2はde novo型優位の遺伝子発現であった。発症様式間において有意差を認めた発現遺伝子は血管新生とAKT-PI3Kシグナルにその機能が集中していたのも、興味深い結果であった。これらの結果より、de novo型ではLuminal-AR群、Basal-like群が多く、多形腺腫由来型ではHER2-positive群が多いということが判明した。現在、英文投稿中である。 また、唾液腺癌細胞株の樹立に関しては、二次元培養では唾液腺癌細胞が十分に増殖しなかったことから、三次元培養の手法を用いて細胞株樹立を目指している。
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2013年04月 -2016年03月 
    代表者 : 加納 里志
     
    唾液腺癌組織における発現タンパク質を解析したところ、EGFRは76%、HER2は20%、c-KITは38%で陽性であり、中でもHER2陽性例が有意に予後不良であった。さらに、HER2陽性例ではその下流シグナルであるPI3K経路の活性化を認めた。また、HER2は唾液腺導管癌に多く発現していたが、de novoに比べ多形腺腫由来癌で多く認めており、多形腺腫からの発癌に強く関与している可能性が示唆された。 これらの結果から、HER2を標的とした薬物治療の開発を検討した。既に乳癌や胃癌で臨床応用されている抗HER2抗体トラスツズマブとドセタキセル併用薬物治療による第2相臨床試験を現在進行中である。
  • 日本学術振興会:科学研究費助成事業 若手研究(B)
    研究期間 : 2010年 -2012年 
    代表者 : 加納 里志
     
    頭頸部癌細胞を用いて,TRIM32に特異的に結合するマイクロRNAを網羅的に同定し,そのマイクロRNAがTRIM32によって活性化されているかを解析することを目的とした。その結果、TRIM32に特異的に結合するマイクロRNAとしてhas-miR-134を同定した。has-miR-134は舌癌での高発現が報告されており、そのターゲット遺伝子としてVEGF-AとABCC1が候補に考えられた。しかし、TRIM32によるhas-miR-134の活性化は確認できなかった。また、TRIM32を過剰発現させた細胞株、またはノックダウンさせた細胞株でもhas-miR-134の活性化、発現量の変化を確認できなかった

教育活動情報

主要な担当授業

  • 基本医学研究
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療,頭頸部外科学,耳科学、平衡科学,鼻科学,口腔咽頭科学,喉頭科学,音声言語学,気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • 基本医学総論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療,頭頸部外科学,耳科学、平衡科学,鼻科学,口腔咽頭科学,喉頭科学,音声言語学,気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • 医学総論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療,頭頸部外科学,耳科学、平衡科学,鼻科学,口腔咽頭科学,喉頭科学,音声言語学,気道食道科学 Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology
  • 基盤医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療,頭頸部外科学,耳科学、平衡科学,鼻科学,口腔咽頭科学,喉頭科学,音声言語学,気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • 臨床医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療,頭頸部外科学,耳科学、平衡科学,鼻科学,口腔咽頭科学,喉頭科学,音声言語学,気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • 耳鼻咽喉科学
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 耳鼻咽喉科、診断、治療,頭頸部外科学,耳科学、平衡科学,鼻科学,口腔咽頭科学,喉頭科学,音声言語学,気道食道科学


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