加藤 久幸

Purpose: Rapidly metabolizing tumor cells have elevated levels of nicotinamide phosphoribosyltransferase, an enzyme involved in NAD(+) biosynthesis, which serves as an important substrate for proteins involved in DNA repair. GMX1777, which inhibits nicotinamide phosphoribosyltransferase, was evaluated in two human head and neck cancer models in combination with radiotherapy. Experimental Design: Effects of GMX1777-mediated radiosensitization were examined via metabolic and cytotoxicity assays in vitro; mechanism of action, in vivo antitumor efficacy, and radiosensitization were also investigated. Results: IC(50) values of GMX1777 for FaDu and C666-1 cells were 10 and 5 nmol/L, respectively, which interacted synergistically with radiotherapy. GMX1777 induced a rapid decline in intracellular NAD(+) followed by ATP reduction associated with significant cytotoxicity. These metabolic changes were slightly increased with the addition of radiotherapy, although poly(ADP-ribose) polymerase activity was significantly reduced when GMX1777 was combined with radiotherapy, thereby accounting for the synergistic cytotoxicity of these two modalities. Systemic GMX1777 administration with local tumor radiotherapy caused complete disappearance of FaDu and C666-1 tumors for 50 and 20 days, respectively. There was also significant reduction in tumor vascularity, particularly for the more sensitive FaDu model. [(18)F]FDG-positron emission tomography/computed tomography images showed reduction in [(18)F]-FDG uptake after GMX1777 administration, showing decreased glucose metabolism in vivo. Conclusions: Our data represent the first report showing that GMX1777 plus radiotherapy is an effective therapeutic strategy for head and neck cancer, mediated via pleiotropic effects of inhibition of DNA repair and tumor angiogenesis, while sparing normal tissues. Therefore, GMX1777 combined with radiotherapy definitely warrants clinical evaluation in human head and neck cancer patients. Clin Cancer Res; 16(3); 898-911. (C) 2010 AACR.

We investigated the prevalence of high-risk human papillomavirus (HR-HPV) in squamous cell carcinoma of the tonsil and tongue-base region, and evaluated its clinical features and prognostic implications according to HPV status and p16 and p53 expression. HR-HPV was positive in 16 (53%) of 30 samples. Of these positive cases, 15 (94%) carried HPV 16 sequences and only 1 (6%) carried a HPV58 sequence. Among the HPV-positive patients, the frequency of heavy smokers and drinkers was significantly lower than among the HPV-negative patients. Among the 30 patients, p16 was overexpressed in 16 (53%), and this overexpression was strongly associated with the presence of HR-HPV (P < 0.0001). In contrast, HPV-negative patients were more likely to have p53 overexpression (75%). On univariate analysis, both HPV-positive status (86% vs. 48%; P = 0.029) and p16 overexpression (100% vs. 31%; P < 0.001) significantly improved the overall survival (OS), respectively. On the other hand, p53 overexpression was significantly associated with inferior OS (42% vs. 83%; P = 0.004). These results indicate that it will be necessary to use these HPV-related biomarkers for decisions on staging and therapeutic strategy. © 2010, Japan Society for Head and Neck Cancer. All rights reserved.

前壁・側壁型中咽頭扁平上皮癌30症例を対象に，ハイリスクタイプHPVの検出，p16とp53発現の検討を行い，HPV検出法およびHPV感染の有無と臨床像，予後，分子生物学的特徴について解析を行った。HPV陽性例は16例（16型15例，58型1例）であった。HPV陽性例では喫煙・飲酒量が陰性例に比べ有意に少なく，p16高発現例が88%と多く，HPV陰性例にはp53高発現例が75%と多くみられた。3年粗生存率の比較では，HPV陰性群48%，HPV陽性群86%（P = 0.029），p16陰性群31%，p16陽性群100%（P < 0.001）であり，HPVおよびp16陽性群は有意に予後良好であった。一方，p53陽性群の3年粗生存率は42%で，p53陰性群の83%に比べ有意に予後不良であった（P = 0.004）。今後，HPV関連バイオマーカーを用いた病期分類や治療方針決定への応用が必要と思われた。

Purpose A significant proportion of oropharyngeal squamous cell carcinomas (OSCC) are associated with the human papilloma virus (HPV), particularly HPV16. The optimal method for HPV determination on archival materials however, remains unclear. We compared a quantitative real-time polymerase chain reaction (qRT-PCR) assay for HPV16 mRNA to a DNA in situ hybridization (ISH) method, and evaluated their significance for overall (OS) and disease-free (DFS) survival. Patients and Methods Matched, archival biopsies from 111 patients with OSCC were evaluated for HPV16 using a qRT- PCR for E6 mRNA and ISH for DNA. Immunohistochemistry for p16, p53, and epidermal growth factor receptor were also performed. Results HPV16 E6 mRNA was positive in 73 (66%) of 111 samples; ISH was positive in 62 of 106 samples (58%), with 86% concordance. P16 was overexpressed in 72 samples (65%), which was strongly associated with HPV16 status by either method. E6 mRNA presence or p16 overexpression were significantly associated with superior OS; E6 mRNA, HPV16 ISH, or p16 were all significantly associated with DFS. On multivariate analysis adjusted for age, stage, and treatment, positive E6 mRNA was the only independent predictor for superior OS; for DFS, p16 expression or HPV16 status determined by either method was significant. Conclusion The prevalence of HPV16 in OSCC ranges from 58% to 66%, in a recently treated Canadian cohort. Classification of HPV-positivity by HPV16 E6 mRNA, HPV16 ISH or p16 immunohistochemistry (IHC) is associated with improved DFS. However, the latter two assays are technically easier to perform; hence, HPV16 ISH or p16 IHC should become standard evaluations for all patients with OSCC.

It has become clear that superselective intraarterial infusion therapy has demonstrated extremely high effectiveness for advanced head and neck cancer in combination with radiation therapy. It is expected to contribute in particular to improvement of patients' quality of life following treatment and improvement of the prognosis through organ preservation. However, some problems currently rto be solved, such as indications or complications. We report herein on our cases and those in the literature, and discuss superselective intraarterial infusion therapy in Japan.

It has become clear that superselective intraarterial infusion therapy has demonstrated extremely high effectiveness for advanced head and neck cancer in combination with radiation therapy. It is expected to contribute in particular to improvement of patients’ quality of life following treatment and improvement of the prognosis through organ preservation. However, some problems currently remain to be solved, such as indications or complications. We report herein on our cases and those in the literature, and discuss superselective intraarterial infusion therapy in Japan.<br>

60代、男性に認められたCASTLEの1例を報告する。腫瘍は甲状腺右下極から上縦隔に存在していた。組織学的には不整形島状上皮胞巣にリンパ球浸潤を伴う胸腺癌に類似する像を呈し、頸部リンパ節転移を認めた。本症例の臨床像と腫瘍進展形式はCASTLEの特徴を良く表していると思われ、甲状腺未分化癌、扁平上皮癌との鑑別にCD5,bcl-2の陽性所見が有用であった。併せてGraves病患者の甲状腺内に偶然発見された甲状腺内異所性胸腺組織を提示し、CASTLEの組織発生について考察した。(著者抄録)

56歳男.嗄声と咽喉頭異常感があるも放置していたところ,約3ヵ月後に呼吸困難で倒れているところを地下鉄駅前で発見され,救急搬送され気管内挿管が試みられたが不可能であったため紹介された.喉頭ファイバーにて喉頭内に充満する腫瘤を認め,頸部CTにて輪状軟骨への浸潤が疑われた.緊急気管切開術を行い,数回の生検を行うも確定診断はできなかった.全身麻酔にて直達喉頭鏡での生検を行い,低分化型扁平上皮癌と診断された.その後の画像診断にて声門癌T4N0M0と診断して喉頭全摘術と両頸部郭清術を行った.2年を経過した時点では再発はなく,経過良好である.摘出標本の病理組織学的検討の結果,周囲への浸潤のない紡錘細胞癌と診断され,最終診断はpT1aN0M0であった.本疾患は本邦での報告例は38例と稀な疾患である

下咽頭癌5例(男4例・女1例,平均60.4歳)に対し,喉頭を温存した下咽頭部分切除術を施行した.原発部位はすべて梨状陥凹で,T分類はT1が3例,T2が2例,N分類はN1が1例,N2bが1例であった.手術はまず患側の側頸部郭清術を行い,舌骨上から軟骨レベルの下咽頭側壁を舌骨および甲状軟骨の患側と共に合併切除した.披裂軟骨は癌の浸潤がなければ温存し,欠損部は前腕皮弁で再建した.初期の1例では術後嚥下障害が増悪し,喉頭挙上術と健側咽頭筋切断術を追加した.以後の4例は初回より両手術を併用し,経口摂取は14〜26日後に開始して全例常食摂取が可能となった.転帰は,1例に健側の頸部リンパ節再発と肺転移を認め,頸部郭清術および胸腔鏡下腫瘍摘出術を行った.また,1例で術後6ヵ月に喉頭癌の合併を認め,放射線療法を行った.術後15〜39ヵ月経過し,全例局所制御は良好である

To detect probable mechanisms of local heated aerosol inhalation in nasal allergy, we measured nasal resistance before and after house dust antigen challenge to the nasal mucosa in 13 patients with perennial allergic rhinitis treated with local hyperthermia for 2 weeks and in 15 untreated patients. Mean nasal resistance either on expiration or inspiration 15min. and 8 hours after antigen challenge in treated patients was significantly lower than in untreated patients. We measured nasal resistance before and after histamine challenge to the nasal mucosa in 9 perennial allergic rhinitis patients before and after hyperthermial treatment and 6 voluntary healthy subjects. Mean nasal resistance right after histamine challenge either on expiration or inspiration in patients before treatment was significantly higher than in patients after treatment or healthy subjects. The frequency of sneezing due to histamine challenge to the nasal mucosa in patients after treatment was significantly lower than in patients before treatment, and no significant difference in frequency of sneezing was seen between patients after local hyperthermia and healthy subjects. Local heated aerosol therapy for more than 1 week, twice a day, may suppress both early- and late- phase allergic reaction and nonspecific hypersensitivity by histamine in the allergic nasal mucosa.

A case of mucoepidermoid carcinoma in the maxillary sinus is reported. The patient was an 88-year-old female who complained of swelling of the left cheek. CT scan showed a low density tumor mass in the left maxillary sinus, and the tumor infiltrated into the hard palate. Histopathological examination revealed a high grade mucoepidermoid carcinoma. Although partial maxillectomy performed, she relapsed with a lesion in the maxillary sinus 6 months after the operation. We performed radiotherapy for a total of 50Gy, and the relapsed tumor disappeared completely after irradiation. However, she died of bone metastasis 12 months after radiotherapy.

1. Five cases of parotid cancer are reported, in which the patients underwent parotidectomy under diagnosis of benign tumor in another hospital or department, were postoperatively diagnosed with malignant tumor, and then received reoperation in our department.<br>2. The age and sex distribution of the cases was 3 males and 2 females with a mean age of 40 years, ranging from 10 to 77 years, including 2 child cases under 15 years.<br>3. Histopathologically, the cancer was classified as adenoid cystic carcinoma in 2 cases, mucoepider-moidcarcinoma in 2 cases, and acinic cell carcinoma in 1 case, and one each of adenoid cystic carcinoma and mucoepidermoid carcinoma occurred in the children.<br>4. The patients underwent reoperation within 8 weeks after the first surgery. The surgical technique was total parotidectomy in 1 case and superficial lobectomy in the remaining 4 cases, with the facial nerve being preserved in all 5 patients.<br>5. Palpation in the examinations conducted at follow-up in our department detected no localized tumor remnant, but the tumor was still found to be histologically residual in 4 of the 5 cases.<br>6. The postoperative clinical course was found to be excellent, without recurrence or metastasis of the cancer.

類上皮肉腫は軟部組織に発生する悪性腫瘍である.本疾患は若年男性の四肢に好発し, 頭頸部領域には稀である.<BR>今回我々は12歳男児の頬粘膜に発生した類上皮肉腫例を経験したので報告する.約1ヵ月前からの左側口腔内疼痛を主訴に受診した.初診時, 左頬粘膜に15×10mm大の腫瘍を認めた.生検にて類上皮肉腫と診断され口内法で腫瘍摘出術を行った.病理診断ではmarginfreeでありサイトケラチン, CEA陽性, EMA弱陽性であった.退院2ヵ月後, 術前とほぼ同様な腫瘍を形成したため再度生検行い再発と診断された.そのため, 再手術を行ったが, 摘出標本の病理診断では炎症性肉芽, 線維化組織からなる瘢痕組織であった

1. Five cases of parotid cancer are reported, in which the patients underwent parotidectomy under diagnosis of benign tumor in another hospital or department, were postoperatively diagnosed with malignant tumor, and then received reoperation in our department. 2. The age and sex distribution of the cases was 3 males and 2 females with a mean age of 40 years, ranging from 10 to 77 years, including 2 child cases under 15 years. 3. Histopathologically, the cancer was classified as adenoid cystic carcinoma in 2 cases, mucoepidermoidcarcinoma in 2 cases, and acinic cell carcinoma in 1 case, and one each of adenoid cystic carcinoma and mucoepidermoid carcinoma occurred in the children. 4. The patients underwent reoperation within 8 weeks after the first surgery. The surgical technique was total parotidectomy in 1 case and superficial lobectomy in the remaining 4 cases, with the facial nerve being preserved in all 5 patients. 5. Palpation in the examinations conducted at follow-up in our department detected no localized tumor remnant, but the tumor was still found to be histologically residual in 4 of the 5 cases. 6. The postoperative clinical course was found to be excellent, without recurrence or metastasis of the cancer.

A case of mucoepidermoid carcinoma in the maxillary sinus is reported. The patient was an 88-year-old female who complained of swelling of the left cheek. CT scan showed a low density tumor mass in the left maxillary sinus, and the tumor infiltrated into the hard palate. Histopathological examination revealed a high grade mucoepidermoid carcinoma. Although partial maxillectomy performed, she relapsed with a lesion in the maxillary sinus 6 months after the operation. We performed radiotherapy for a total of 50 Gy, and the relapsed tumor disappeared completely after irradiation. However, she died of bone metastasis 12 months after radiotherapy.

喉頭癌15症例を対象にヘリカルCT又はマルチスライスCTを施行して得られたデータをもとに多断面再構成像(MPR)と三次元CT像を再構成し,検討した.喉頭癌の進展範囲の診断における三次元画像の有用性について摘出喉頭の大切片標本と比較検討した.その結果,MPR像は腫瘍の進展範囲の診断には極めて有用であると考えられた.マルチスライスCTでは声帯運動び動的評価も可能であったが,甲状軟骨浸潤の診断には限界があると思われた.三次元CT像は腫瘍の浸潤範囲の立体的把握が容易ではあるが,実用には更に改良が必要であると考察した

We report here two cases of spontaneous retropharyngeal and cardiomediastinal emphysema. The patients were a 15-year-old boy, who developed a foreign body sensation in the pharynx after he ran and a 16-year-old boy who developed pain in the anterior neck after he spoke loudly. X-ray and CT examination findings revealed air in the retropharyngeal and cardiomediastional regions in both patients. Antibiotics and a week of rest were prescribed and these complaints disappeared. Sixty-four cases of spontaneous mediastinal emphysema, including our two cases, reported in the Japanese literature in the period between 1992 and 2001 are also reviewed and discussed in this paper.

10歳男児.右鼻閉と繰り返す右鼻出血を主訴として来院した.造影CTにて腫瘍は鼻咽腔,鼻腔,篩骨洞,蝶形骨洞,側頭下窩,翼突窩に拡がり,一部眼窩深部と前頭蓋底に浸潤していた.手術の前日にセルジンガー法による超選択的塞栓術を行い,腫瘍は経頭蓋顔面アプローチにて全摘された.術後の合併症や顔面の変形は認めず,再発なく経過良好である

We report here two cases of spontaneous retropharyngeal arid cardiomediastinal emphysema. The patients were a 15-year-old boy, who developed a foreign body sensation in the pharynx after he ran and a 16-year-old boy who developed pain in the anterior neck after he spoke loudly. X-ray and CT examination findings revealed air in the retropharyngeal and cardiomediastional regions in both patients. Antibiotics and a week of rest were prescribed and these complaints disappeared. Sixty-four cases of spontaneous mediastinal emphysema, including our two cases, reported in the Japanese literature in the period between 1992 and 2001 are also reviewed and discussed in this paper.

放射線治療後に甲状腺転移をきたした60歳男,声門癌T2N0症例を報告した.甲状腺全摘術,頸部郭清術を行い,局所制御は可能であったが,手術後5ヵ月で肺転移のため死亡した.渉猟し得た限りでは,喉頭癌治療後に甲状腺転移を認めた症例は本邦では自験例を含め2例のみであり,極めて稀な症例であった

喉頭全摘施行例83例を対象にその治療成績を検討した.その結果,喉頭摘除例は全喉頭癌の34.2%であった.声門癌喉頭摘除例48例では15例の死亡例がありその死因は原病死8例,他病死7例であった.声門上癌喉頭摘除例33例では原病死7例,他病死4例の死亡があった.全喉頭摘除例83例では15例の原病死が認められ,その内訳は原発死2例,リンパ節死8例,遠隔転移死5例であった.一次治療例よりも二次治療例の方が原病死が少なく,早期に再発を診断し適切な治療を行えばサルベージ可能と思われた.また喉頭摘除例の予後の改善には多発リンパ節転移例に対する術後治療の必要性が示唆された

We conducted aerodynamic inspection, including subglottic pressure measurement, and clinical evaluation of aerodynamic parameters for various disorders. In total, 1,072 examples were examinas, including normal vocal cords, polyp, reeurrent nerve paralysis and glottic cancor. Phonation function inepection was carried out by measuring height (Hz). sound pressure (dBspl) and mean flow rate (ml/sec). By combining these parameters, the diseased state of glottic vibration was discussed. In particular, measuremenis of subglottic preseure were necessary for direct calculation of larynx resistance, subglottic power and glottal efficiency. Results were characteristic for each diseased state. It is important in terms of evaluating phonation, to observe the vibrational state of the vocal cords and to measure acrodynamic conditions in both normal and disessed vocal cords. It also seems important for disordar chsracterbtion to be detected in conjuaetion with optical and macroscopic observations of the vocal cords. © 1999, The Japan Society of Logopedics and Phoniatrics. All rights reserved.

声門下圧測定を含む, 空気力学的検査を行い, 各疾患ごとに空気力学的パラメーターについて, 正常・声帯ポリープ・反回神経麻痺・声門癌の1072例について臨床的評価を試みた.空気力学的検査は発声に関わる能力を, 高さ (基本周波数) , 強さ (音圧) , 呼気流率などを物理量として表すことである.日常臨床において, 他の検査所見とともに発声障害・発声困難の原因の究明や, 治療前後の比較, 手術の評価・経過観察にも有効であると考える.<BR>発声機能検査を行い個々の測定結果を比較した場合, 単一のパラメーターの値は発声機能の複雑な一面を示し, 疾患に特異的な結果を示さなかった.パラメーターを組み合わせることで, 声門閉鎖の状態などの病態を検討できることを示した.特に声門下圧の測定は, 喉頭抵抗, 声門下パワー, 喉頭効率などの直接的な算出に必要であり, 2次パラメーターの結果は, 発声障害の病態を評価する上で有用と思われる.

66歳男,主訴は左難聴.鼻咽腔ファイバー上にて直径約2cmの白苔に覆われた有茎性腫瘍が左耳管隆起に認められた.腫瘍生検にて基底様扁平上皮癌と診断され,放射線治療71.2Gy,5-FU5000mg投与したが腫瘍は縮小するも残存したため,軟口蓋横切開によるアプローチにて腫瘍摘出術を行った.摘出標本より上咽頭小唾液腺由来の基底細胞腺癌と診断された.術後15ヵ月経過しているが局所再発,遠隔転移は認めていない

前癌病変としての声帯hyperplasiaおよびdysplasiaにつき, 抗PCNA (proliferating cell nuclear antigen), 抗MIB-1 (Ki-67) モノクロナール抗体を使用し免疫組織化学的検討を行い, 細胞異型の程度と増殖能との相関および臨床的予後, 癌化との関係につき検討した. hyperplasia, dysplasia, 浸潤癌においてはhematoxylin-eoxin (HE) 染色上の細胞異型度が高くなるにつれPCNA index, MIB-1陽性率が高値を示し, 細胞増殖能の増加が示唆された. 再発例およびhyperplasia・dysplasiaからの癌化例のなかにはPCNA index, MIB-1陽性率が高値を示すものが存在した. PCNA indexとMIB-1陽性率との間に統計学的に一次相関傾向が認められた.