西野 宏

BACKGROUND: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. METHODS: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. RESULTS: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. CONCLUSIONS: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

Anteromedial maxillectomy is typically performed in conjunction with low-dose radiotherapy and intraarterial chemotherapy. In doing so, the extent of surgical defects is reduced. However, nasal deviation and oral incompetence may ensue, due to cicatricial contracture of wounds, and may be distressing to these patients. Herein, we report a series of eight free perforator flap procedures (anterolateral thigh [ALT] flap, 6; thoracodorsal artery perforator [TAP] flap, 2) used to correct such deformities. The TAP flap was combined with scapular tip [ST] osseous flap in patients with added zygomatic prominence defects. Three adipocutaneous parts developed from each perforator flap were applied as follows: two to reconstruct nasal lining and oral vestibule, and one to augment cheek volume. All aesthetic results proved satisfactory, although orbital dystopia and contracture of mimic muscles were not resolved completely. These secondary interventions are suitable for sequelae of simple anteromedial maxillectomy. Immediate reconstruction should be considered if orbital floor and mimic muscles are involved. (C) 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

1-day-old male infant was referred to our department for evaluation of multiple malformations in his oral cavity. He was diagnosed duplication of the pituitary gland-plus syndrome with epignathus, cleft palate, duplication of the mandible, and a lobulated tongue. A thumb-sized mass lesion was visible on the hard palate. The duplicated mandible and lower lip was fused at the midline. The alveolar ridge was protruding through a wide-cleft soft palate involving the uvula. Further examination showed a lobulated tongue, which was seen behind the duplicated part of the mandible. Five days after birth, tracheotomy and epignathus resection were performed. At 7 months of age, the excess tissue of the duplicated mandible was resected at the area of adhesion on the lingual side, and the duplicated tongue and lip were reconstructed. A palatoplasty was performed at 20 months of age. Thereafter, the patient's progress was uneventful, with no abnormality in swallowing. No recurrence of epignathus has been observed during 2 years of follow-up.

Immediate reconstruction of orbitomaxillary defects is challenging for head and neck reconstructive surgeons. The primary goals of orbitomaxillary reconstruction are to cover the skin and mucosal defects, fill the defect space, and reconstruct the natural facial contour. This report describes 2 patients who underwent extended orbitomaxillectomy and immediate reconstruction using a combined latissimus dorsi musculocutaneous and scapular angle osseous free flap (LD-SA flap). The LD-SA flap has substantial advantages, such as providing structural support to the malar prominence, filling the large soft tissue defect, and preventing postoperative drooping of the cheek. The surgical technique is relatively straightforward, requires a shorter operative time, and produces less blood loss compared with other reconstruction approaches. The LD-SA flap is a useful option for extended orbitomaxillary defect reconstruction. (C) 2016 American Association of Oral and Maxillofacial Surgeons

BACKGROUND: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers. METHODS: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients. RESULTS: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372). CONCLUSION: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.

Objective: Unilateral vocal cord paralysis (UVCP) not only induces severe dysphonia, but aspiration as well. Although laryngeal framework surgery is usually performed to treat this condition, the procedure is not tolerated by some patients. In the previous study, basic fibroblast growth factor (bFGF) injections for vocal cord scarring and sulcus have been reported to provide favorable outcomes while being minimally invasive. In this study, the authors retrospectively investigated phonological outcomes after bFGF injection in patients with UVCP. Methods: This study was registered in University hospital Medical Information Network - Clinical Trials Registry (UMIN000019347). Nineteen patients with unilateral cord paralysis were treated with bFGF injection. The treatment regimen involved a single injection of 50g of bFGF into the muscle layer. More than six months after the injection, aerodynamic and acoustic outcomes were examined. Results: The voice handicap index, maximum phonation time, mean airflow rate, and pitch range improved significantly after injection of bFGF. No sex-related differences were observed in any phonological parameter. Conclusion: bFGF injection, an easy method and suitable as an office procedure, significantly improved the hoarseness caused by UVCP. It is expected to be widely adopted and effective adjunctive drugs, and procedures are anticipated to be developed.

:Immediate reconstruction of orbitomaxillary defects is challenging for head and neck reconstructive surgeons. The primary goals of orbitomaxillary reconstruction are to cover the skin and mucosal defects, fill the defect space, and reconstruct the natural facial contour. This report describes 2 patients who underwent extended orbitomaxillectomy and immediate reconstruction using a combined latiss

Interleukin-6（IL-6）は代表的な炎症性サイトカインである。IL-6は炎症のみならず癌細胞の生物学的活性に影響を与える。細胞増殖，細胞死抵抗性，浸潤，血管新生，転移，免疫，幹細胞，悪液質に関与していることがわかってきた。IL-6は多くの癌細胞において癌細胞活性を高め，腫瘍形成と転移に関与する重要なサイトカインである。この総説では簡潔にその働きを述べる。

日本は高齢化社会を迎えつつある。本論文は1970年1月から2014年9月までの間に自治医科大学附属病院で治療を受けた75歳以上のstage III/IV 頭頸部癌患者（甲状腺癌を除く）125人を後方視的に検討した。放射線治療は46人に行われ，3人が嚥下性肺炎とせん妄で治療が中断となった。放射線治療終了1か月以内に6人が合併症を生じた。嚥下性肺炎，せん妄，脳梗塞，急性腎不全であった。34人に手術が行われた。喉頭全摘出術が11人，咽頭喉頭食道切除・再建術が10人，舌切除・再建術が3人，切除術が10人であった。舌切除・再建術3人のうち2人は嚥下性肺炎を認めた。緩和治療は28人に選択された。Performance status 2以上の場合には治療関連合併症出現の割合が多かった。

Objectives/Hypothesis: Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. Study Design: Retrospective chart review. Methods: Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 mu g of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. Results: The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. Conclusions: Regenerative treatments by bFGF injection even a single injection effectively improve vocal function in vocal fold lesions.

The natural mandible has 2 arcs, the marginal arc and the occlusal arc. The marginal arc is situated along the lower margin of the mandible and affects the contour of the lower third of the face. The occlusal arc is situated along the dental arc and affects the stability of prosthodontics. The gap between these 2 arcs widens in the molar area. Our developed concept of "double arc reconstruction" involves making these 2 arcs for the reconstructed mandible. For the double-barrel fibula reconstruction, 2 bone segments are used to make both arcs. For reconstructions using the iliac crest, the double arc is made by inclination of the top of the bone graft toward the lingual side. Ten patients underwent double arc reconstruction: 2 underwent reconstruction with the double-barrel fibula, and 8 underwent reconstruction with the iliac crest. Four patients had a removable denture prosthesis, 1 had an osseointegrated dental implant, and 5 did not require further prosthodontic treatment. The shape of the reconstructed mandible after double arc reconstruction resembles the native mandible, and masticatory function is good with the use of a dental implant or removable denture prosthesis, or even without prosthodontics.

Objective: The aim of this study was to reduce misdiagnosis and inappropriate treatment of laryngeal tuberculosis. Methods: Between April 2009 and March 2013, 1660 inpatients with tuberculosis were treated at the Osaka Prefectural Medical Center for Respiratory and Allergic Diseases. Seventeen of these patients were diagnosed with laryngeal tuberculosis. Criteria used for diagnosis were findings of histologic examination of biopsy specimens (2 patients) or clinical response of granuloma to antituberculosis therapy (15 patients). Medical records were used for this retrospective study. Results: Patients' age ranged from 30 to 84 years with an average of 51.4 +/- 14.0 years (mean SE); nine were men and eight were women. The most frequent chief complaint was hoarseness (n = 15). Thirteen patients had persistent cough before they showed otolaryngologic symptoms. Endoscopic findings were categorized into five types of lesions: perichondritic (n = 6), ulcerative (n = 6), granulomatous (n = 6), polypoid (n = 1) and nonspecific inflammatory (n = 1). Laryngeal tuberculosis showed as a single lesion in one patient and as multiple lesions in the other patients. The most commonly involved site was the true vocal cord (n = 16, 94.1%), while 16 patients showed radiographic evidence of active pulmonary tuberculosis. These results indicate that deterioration of the lesions tended to result in the occurrence of multiple lesions. Conclusion: While morbidity in tuberculosis has been decreasing in Japan, a significant number of patients still has laryngeal tuberculosis in association with advanced pulmonary tuberculosis. If a patient has a protracted cough, laryngeal tuberculosis should be taken into consideration for differential diagnosis. Pulmonary imaging study should be performed for early diagnosis and to prevent the infection from spreading. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Background: Blue nevus is a benign dermal melanocyte tumor that mainly arises from the skin. We report an extremely rare case of blue nevus in a pediatric patient with extensive progression from the middle ear and inner ear to the nasopharynx through the Eustachian tube. Case Report: A 2-year-old girl with blue tympanum was referred to our department. Computed tomography scans and magnetic resonance imaging were performed, followed by a tissue biopsy and histopathologic evaluations. Radiologic examinations revealed that the lesion had progressed beyond the middle ear into the inner ear and the nasopharynx through the Eustachian tube. Subsequent histopathologic examinations indicated dermal dendritic melanocytic proliferations, but no evidence of malignancy. Based on the clinical and histopathologic findings, we concluded that the lesion was consistent with blue nevus. Discussion: Blue nevus is a relatively common skin lesion. However, no prior reports have described the extension of blue nevus from the auditory organ to the nasopharynx in a pediatric patient. Despite the benign nature of the lesion, the patient experienced profound hearing loss in the affected ear, which necessitates continued monitoring as the lesion may expand with patient growth.

We retrospectively assessed the utility of the LigaSure^TM Vessel Sealing System compared with conventional surgery in 40 cases of free osseous flap harvest comprising 17 fibula flaps ( LigaSure : conventional, 11 : 6 ), 13 scapula flaps ( 4 : 9 ), and 10 iliac crest flaps ( 8 : 2 ). Postoperative duration of suction drain, total fluid collection volume by drain, and avascularized time during fibula flap harvest with a tourniquet did not differ significantly between the LigaSure^TM and conventional techniques. In one case, additional surgery due to hematoma was required 23 days postoperatively in a donor site following scapular tip flap harvest without LigaSure^TM. Reconstructive surgery with free flap transfer is performed with recipient surgery, such as tumor ablation or contracture release; therefore, intraoperative blood loss and total surgical time, which are reportedly significantly decreased by LigaSure^TM, could not be evaluated in this study. LigaSure^TM enables complete hemostasis to be easily accomplished, and the results of hemostasis are at least as favorable as those with the conventional technique.

病気の治療を標準化するためには，何よりもその治療の目的，エンド・ポイントを明確にしなければ議論が不可能である。下顎切除・再建においては，新しい高度な技術が導入されている一方で，多くの症例で大きな機能障害が残存しないため，さまざまな治療法が選択可能となる。これらの多くは治療法として問題ないものなので，優先順位をつけた具体的な治療目標を達成できるかどうかを基準にして選択できるようにするのがこの論文の目的である。具体的には目標を絶対的，標準的，努力目標の3段階に設定し，それぞれに達成率を併記した。

Thyroid cancer is a well-differentiated cancer with favorable prognosis among the malignant tumors of the head and neck. However, extension into the mediastinum is observed in rare cases. Although there is a risk of fatal complications associated with the respiratory tract in such cases, increased surgical stress after sternotomy is predicted to cause frequent postoperative complications. Moreover, clear standards for operability have not yet been established. Therefore, in order to obtain findings related to operability and operative procedure, we focused on cases that differed greatly in operability and procedure based on the time when the operations were performed. We conducted a comparative examination of six cases in the 1980s (early cases) and four recent cases (late cases) in which sternotomy was performed at our department. The cases were compared in terms of the following: (1) background factors and extent of spread, (2) operative procedure, (3) postoperative complications, and (4) treatment outcomes. In the early cases, radical mediastinal dissection was performed aggressively for extensive spreading, including undifferentiated cancers (poorly differentiated cancer and squamous cell carcinoma) and papillary cancer further, the operative procedure was radical. On the other hand, in the late cases, radical mediastinal dissection was performed only for papillary cancer further, resection of the trachea and esophagus was conservative. Thus, patients in the late cases were discharged without any postoperative complications, and all patients survived. Therefore, it is considered that radical mediastinal dissection by sternotomy should be considered only in cases of mediastinal extension of differentiated thyroid cancer, where only few adjacent organs need to be resected.

The purpose of this study was to evaluate the incidence of lymph node metastasis among patients with T4 maxillary sinus squamous cell carcinoma (MS-SCC) as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. Consecutive series of all patients (n = 128) with previously untreated T4 maxillary sinus SCC between 2006 and 2007 were obtained from 28 institutions belonging to or cooperating in the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group. Of the 128 patients, 28 (21.9 %) had lymph node metastasis, and six patients (4.7 %) had distant metastasis at diagnosis. Among the 111 patients who were treated with curative intent, 98 had clinically N0 neck disease and did not receive prophylactic neck irradiation. A total of 11 patients (11.2 %) subsequently developed evidence of lymph node metastasis, of whom eight were among the 83 patients with an N0 neck and had not received elective neck treatment. There were 15 patients who received an elective neck dissection as part of the initial treatment, of whom three had pathologically positive for lymph node metastases. Of 11 patients, six patients with nonlateral retropharyngeal lymph node metastasis without primary or distant disease were successfully salvaged. This study identified the incidence of lymph node metastasis among patients with T4 MS-SCC as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. These results will be of assistance in selecting treatment strategy for T4 MS-SCC in the future.

放射線性頭蓋底骨壊死は，局所病変であるが，不快な症状を呈し，内頸動脈破裂など重篤な合併症をきたすことがある。疾患の認知と，積極的な対応が望まれる。症例は，61歳男性。上咽頭癌化学放射線治療後再発癌に再照射を行い，局所的な頭蓋底骨壊死を生じた症例の治療を経験した。鼻内内視鏡下手術による腐骨除去が，治療効果においても内頸動脈破裂予防においても有効な治療法と考えられる。しかし，手術操作で内頸動脈露出が懸念される場合は，むしろ内頸動脈破裂を誘発してしまう可能性があり，適応は慎重にすべきである。また，手術に際しては，頭蓋底の構造を理解し，内視鏡手術の技量や技術を駆使した慎重な操作を要すると考えられた。

Background: Epithelioid hemangioendotheliomas (EHEs) of the head and neck region are uncommon malignant neoplasms that exhibit various biologic behaviors characteristic of both low- and high-grade malignancy. A subgroup of EHEs identified as "high-risk" EHEs because of their size and mitotic activity is associated with an unfavorable clinical course and poor prognosis. Materials and Results: We describe the treatment of the first and, in terms of size, largest case of high-risk EHE arising from the neck. Despite wide excision, recurrence occurred 9 months after surgery, as had been expected. However, the tumor was found to express both vascular endothelial growth factor (VEGF) and VEGF receptor 2, indicating the potential of anti-VEGF therapy in the treatment of such cases. Conclusion: The finding that a high-risk EHE arising from the head and neck region is characterized by expression of VEGF and its receptor provides further support for the development of targeted molecular therapies. © 2012 Wiley Periodicals, Inc.

Background Current goals for the treatment of maxillary sinus carcinoma include the preservation of vision, eating, communication, and appearance, as well as the achievement of a cure. Methods Japanese patients (n = 121) with maxillary sinus carcinoma were analyzed retrospectively. All patients underwent multidisciplinary therapy including minimally invasive resection, 20 Gy irradiation, and intra-arterial infusion of 5-fluorouracil. Results The 5- and 10-year overall survival rates were 73% and 68%, respectively. In 97 patients with squamous cell carcinoma (SCC), the 5- and 10-year overall survival rates were 76% and 70%, respectively. All 29 patients with orbital invasion retained the orbital contents, and 21 of these patients demonstrated adequate visual acuity. There were 16 complications, including trismus (5 patients), double vision (5 patients), fistula formation (3 patients), and cataract (3 patients). Conclusion A multidisciplinary therapy, consisting of minimally invasive resection, irradiation, and regional chemotherapy, can yield good patient prognosis and quality of life after treatment. © 2012 Wiley Periodicals, Inc.

Recurrent respiratory papillomatosis (RRP), a chronic upper respiratory condition characterized by diffuse multiple recurring papillomas, is thought to result from human papillomavirus (HPV) type 6 or 11 infection. Although RRP is an intractable disease, malignant transformation of RRP is rare. The underlying mechanism, however, has not been elucidated. We describe the clinical course of a patient who underwent more than 130 operations for RRP associated with HPV type 6 infection and subsequently suffered spontaneous malignant transformation to squamous cell carcinoma. Immunohistochemical analysis revealed that malignant transformation might result from a genomic defect, such as p53 inactivation, leading to stimulation of uncontrolled cell proliferation by HPV type 6 for an extended period, but not directly because of HPV itself. Our results could help in the development of novel therapeutic strategies for severe RRP, although further studies are required before clinical application of molecular targeted therapies. © 2013 Kanazawa et al.

Introduction. Primary involvement of the salivary glands in small cell carcinoma is rare, and has one of the worst prognoses of salivary gland neoplasms. However, it has been reported that some cases have a favorable outcome, although the prognostic factors are still under consideration. Multidisciplinary therapy was usually required to achieve long-term survival. Recently, a resemblance of some small cell carcinomas of the salivary gland to cutaneous Merkel cell carcinoma was suggested the latter have the potential for spontaneous regression, which is related to a favorable clinical outcome. Case presentation. We present a locoregional advanced parotid small cell carcinoma with multiple lymph node metastases in an 87-year-old Asian woman. The tumor was controlled by surgery alone, and nine-year disease-free survival was achieved without any adjunctive therapy. To the best of our knowledge, this is the longest reported follow-up of head and neck small cell carcinoma. Conclusion: We believe this to be the first case of small cell carcinoma with involvement of the salivary glands reported in the literature with a good outcome after surgery alone without any adjunctive therapy. © 2012 Kanazawa et al. licensee BioMed Central Ltd.

今回われわれは2000年から10年間に当科で入院，手術を行った鼻副鼻腔乳頭腫62 例について検討を行った。年齢は平均56歳，男性47人，女性15人，主訴は一側性の鼻閉，発症部位は上顎洞内側壁，病理組織診断はinverted papillomaが最も多かった。Krouseの分類ではT1 4例，T2 27例，T3 28例，T4 3例であった。治療は全例手術（Denker 29例，ESS 34例（うちEMM 6例））を施行した。再発は11例にみられた。鼻副鼻腔乳頭腫は完全摘出が必要な腫瘍だが，その手術方法は，近年内視鏡手術を中心とした低侵襲な手術法が選択されるようになってきている。しかし再発する例もみられ，適切な手術法の選択と術後の厳重な経過観察が必要と考えられた。

Several options exist for reconstruction after total esophagectomy in patients with esophageal carcinoma. However, the options for a major resection after previous head and neck surgery in these patients are extremely limited. The procedure performed in 2 patients requiring esophagectomy after resection for previous head and neck malignancies is described. Both patients underwent previous chemoradiation therapy and free jejunal transfer for hypopharyngeal squamous cell carcinoma. Esophagectomy and reconstruction with a cervical gastrojejunal anastomosis combined with deltopectoral flaps were performed after the diagnosis of esophageal disease. Soft tissue defects were closed with a modified deltopectoral flap using de-epithelization. The deltopectoral flap is effective not only for cutaneous resurfacing, but also to promote delayed wound healing after radiation therapy. This report demonstrates a useful multidisciplinary approach for resection and reconstruction in patients after a previous free jejunal transfer.

Conclusion: Glucocorticoid (GC) administration enhanced apoptotic changes in mature olfactory receptor neurons (ORNs). GC administration may enhance regeneration of olfactory epithelium (OE). Objectives: The mechanism underlying olfactory epithelial cells turnover involves apoptosis replaced by new ORNs. On regeneration of OE, we evaluated the apoptotic changes in OE. Our aim was to corroborate the enhancement of apoptosis of ORNs induced by GCs that are generally administered locally or systemically to patients with olfactory dysfunction. Materials and methods: For the in vitro study, we established cultured murine ORNs. Triamcinolone acetonide was added to culture supernatants. ORNs were then cultured for another 2 weeks. In the in vivo study, triamcinolone acetonide was administered to mice 5 or 10 times. The mice were dissected 3 days after the final injection, and the olfactory regions were removed and embedded in paraffin. All samples were examined by immunohistochemical staining and the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Results: Glucocorticoid receptor (GR) expression of cultured murine ORNs was observed among ORNs at the mature stage. Expression of GRs by murine OE was localized on mature ORNs and supporting cells. Administration of GC to both cultured ORNs and mice resulted in proportions of apoptotic cells that were significantly higher than those in the control groups.

A 76-year-old man undergoing haemodialysis for chronic renal failure presented with swelling in the right lower gingiva. Biopsy of the oral mass revealed clear cell carcinoma, and whole body computed tomography and magnetic resonance imaging revealed a mass in the left kidney. The patient was treated with local radiotherapy and immunotherapy and remains alive with cancer at the time of writing. © 2009 Asian Association of Oral and Maxillofacial Surgeons.

Interleukin-6 (IL-6) is a multifunctional regulator of immune response and hematopoiesis. Recently, it has been reported that expression of IL-6 is correlated with prognosis in various cancer patients. In this study, we investigated whether the proliferation and invasion potential of head and neck squamous cell carcinomas (HNSCCs) were influenced by IL-6. All HNSCC cell lines, HEp-2, HSC-2, HSC-4, and SAS, were tested by reverse transcription-polymerase chain reaction (RT-PCR) and expressed the IL-6 receptor (IL-6R), and glycoprotein 130, which is responsible for signal transduction. HEp-2, HSC-2, and HSC-4 also produced IL-6. IL-6 inhibited the proliferation of HSC-2 and SAS, but the invasion potential of all the cell lines increased. Moreover, IL-6 down-regulated soluble IL-6R expression. Anti-IL-6R antibody abrogated the inhibited proliferation and increased invasion induced by IL-6. IL-6 stimulation also induced the extracellular regulated protein kinase 1/2 activation and increased vascular endothelial growth factor release. These results suggest that IL-6 can directly influence cell proliferation and the invasion potential as the first step of tumor metastasis.

Background: Previous studies suggest that human RAD9 ( hRad9), encoding a DNA damage checkpoint molecule, which is frequently amplified in epithelial tumor cells of breast, lung, head and neck cancer, participates in regulation of the tumor suppressor p53- dependent transactivation of pro- survival P21(WAF1). This study examined the exact mechanism of the hRad9 function, especially through the phosphorylation of the C- terminus, in the transcription regulation of P2(1WAF1). Results: The transfection of phosphorylation- defective hRAD9 mutants of C- terminus resulted in reduction of the p53- dependent P21(WAF1) transactivation; the knockdown of total hRad9 elicited an increased P21(WAF1) mRNA expression. Immunoprecipitation and a ChIP assay showed that hRad9 and p53 formed a complex and both were associated with two p53- consensus DNA- binding sequences in the 5&apos; region of P21(WAF1) gene. The association was reduced in the experiment of phosphorylation- defective hRAD9 mutants. Conclusion: The present study indicates the direct involvement of hRad9 in the p53- dependent P21(WAF1) transcriptional mechanism, presumably via the phosphorylation sites, and alterations of the hRad9 pathway might therefore contribute to the perturbation of checkpoint activation in cancer cells.

Arytenoid cartilage dislocation is a known complication of tracheal intubation and is also a type of laryngeal injury. Although spontaneous recovery has been reported, most patients require reduction via pharyngoscopy under general or neuroleptic anesthesia, and some must be treated by open reduction such as laryngoplasty. We report 8 cases of arytenoid cartilage dislocation between August 2003 and August 2004. Excluding 3 patients who recovered spontaneously, we conducted reduction under local anesthesia as an ambulatory procedure in the other 5 with anterior dislocation, i.e., 2 men and 3 women aged 53 to 75 years old. Of these 5, dislocation occurred after tracheal intubation in 4, and in 1 after wearing a laryngeal mask. The outcome was favorable in all 5. Surgery was conducteded after a fiberscope was inserted nasally and a urethral balloon catheter was inserted via the other nasal cavity under topical anesthesia with 4% lidocaine for both nasal cavities and the larynx. While monitoring the larynx, we expanded the balloon and pulled it away from the glottis. The expanded balloon was then placed at the arytenoid region for a few seconds. This procedure was repeated several times to achieve reduction. Three patients recovered well within 1 to 2 weeks of the first reduction, while 2 requierd a second reduction because of insufficient improvement after the first. These two both showed improved vocal cord movement and recovery from hoarseness within 1 to 2 weeks after the second reduction. We conducted 7 reductions without complications in any patient. Our approach is usable in the ambulatory setting, and is simple, minimally invasive, and effective. We consider it to be useful treatment for anterior arytenoid cartilage dislocation.

上顎洞癌に対する集学治療の主たる治療は切除手術と考える。当科で施行されている分割切除による腫瘍全摘出術を呈示する。手術は顔面皮膚切開をおかずに上顎歯肉部を切開しおこなう。腫瘍組織を覆う被膜様線維組織を確認し,剥離操作を行うことが手術操作のポイントである。可能なかぎり腫瘍組織に切り込まずに腫瘍組織を周囲より剥離摘出する。広範囲に眼窩底骨や骨膜が切除された場合には残存骨膜を絹糸でできるだけよせ,眼球の下方への偏位を少なくする。頭蓋底の骨欠損を認め硬膜に腫瘍組織が接する場合には,手術用顕微鏡下に硬膜と腫瘍組織を剥離する。

Adeno-associated virus (AAV) is a non-pathogenic virus with a single-strand DNA genome. AAV vectors have several unique properties suited for gene therapy applications. However, an obstacle to their application is a low efficiency of transgene expression, mainly due to a limited second-strand synthesis. Previously, we reported that gamma-rays enhanced the transduction efficiency and cytocidal effect of AAV vector harboring the herpes simplex virus-thymidine kinase (AAVtk) and ganciclovir (GCV) system. In the present study, we investigated whether topoisomerase inhibitors (etoposide and camptothecin) enhance the AAV vector-mediated transgene expression and the killing effect by AAVtk/GCV system. The enhancement of transgene expression was observed in a concentration -dependent manner on human laryngeal carcinoma cells (HEp-2 cells) and HeLa cells. Southern analysis confirmed that etoposide enhanced the double-strand synthesis of the AAV vector genome in HEp-2 cells and HeLa cells. The cells were efficiently killed by AAVtk/GCV system, as expected. More importantly, both etoposide and camptothecin augmented the cytocidal effect of the AAVtk/GCV system. These findings suggest that the combination of AAV-mediated suicide gene therapy and treatment with topoisomerase inhibitors may have synergistic therapeutic effects in the treatment of cancers.

We report a case of tracheoesophageal fistula (TEF) secondary to chemotherapy for primary thyroid lymphoma. A 65-year-old man with a short history of a rapidly enlarging neck mass was diagnosed as having thyroid lymphoma of diffuse, large B-cell type. The TEF occurred during the first course of chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisolone. After placing a feeding gastrostomy without oral intake, eight cycles of chemotherapy were completed and complete remission was achieved. Although the cervical mass disappeared, TEF and esophageal stenosis persisted. Total thyroidectomy and resection of the stenotic cervical esophagus were carried out followed by interposition of the revascularized jejunum and its mesenteric patch to cover the TEF. This seems to be the first report of a TEF caused by chemotherapy for primary thyroid B-cell lymphoma. A variety of treatments for TEF including simple closure, tracheal resection, colonic bypass and muscle flap have been reported with low success rates. Our procedure using a jejunal mesenteric patch seems to be unique and may be a new treatment strategy for TEF.

Objective: The purpose of the study was to examine the oncological. and functional outcomes of multimodality therapy for patients with advanced malignant maxillary sinus tumors that invaded the orbit. Study Design: Retrospective study. Methods: The medical records of 26 patients with orbital invasion were retrospectively analyzed. The patient group consisted of 16 men and 10 women, with a median age of 58 years. The mean follow-up period was 73 months. The most common disease was squamous cell carcinoma. Seven patients had nodal disease. All patients underwent simultaneous combined therapy consisting of conservative surgery through a sublabial incision, radiotherapy, and regional chemotherapy. Patients with nodal disease were treated with either irradiation- or selective neck dissection. Results: The 5- and 10-year overall survival rates were 68% and 51%, respectively. The 5- and 10-year local control rates were 66% and 51%, respectively. Overall survival rates and local control rates were significantly worse in patients with disease other than squamous cell carcinoma. Local control rates were significantly worse in patients with orbital apex disease than in patients without orbital apex disease. All 26 patients, despite orbital involvement, retained their orbital contents. Nineteen of these patients demonstrated adequate ocular function. Conclusions: Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy is an effective method for local control and preservation of ocular function. However, performing orbital conservation procedure in patients with disease other than squamous cell carcinoma and with orbital apex disease must be considered carefully.

Adeno-associated virus (AAV) vector has several unique properties suited for gene therapy applications. However, relatively low efficiency of transgene expression, which is mainly due to a limited second-strand synthesis from the single-stranded AAV genome, can be a problem in some applications that require potent gene expression such as antitumor applications. Recently, gamma -ray irradiation has been reported to enhance the second-strand synthesis of the AAV genome, and consequently transgene expression. We demonstrate here that an AAV vector harboring the herpes simplex virus type-1 thymidine kinase (HSVtk) is able to kill cancer cells more efficiently when used in combination with gamma -ray irradiation. A human maxillary sinus cancer cell line, NKO-1, was efficiently killed in combination with HSVtk transduction and ganciclovir (GCV), as expected. More importantly, gamma -ray irradiation of practical dosages augmented the cytocidal effect of the HSVtk/GCV system. Southern analysis indicated that gamma -rays enhanced the double-strand synthesis of the rAAV genome in NKO-1 cells. These findings suggest that the combination of rAAVtk/GCV suicide gene therapy with radiotherapy has synergistic effects in the treatment of cancers and may lead to a reduction of the potential toxicity of both rAAVtk/GCV and gamma -ray irradiation.

BACKGROUND. Current goals for the treatment of carcinoma of the maxillary sinus include the preservation of vision, ability to eat, ability to communicate, and appearance as well as cure. METHODS. Seventy-five Japanese patients who presented with maxillary sinus carcinoma between 1979 and 1997 were analyzed retrospectively. There were 48 males and 27 females with a median age of 62 years. The mean follow-up period was 73 months. All patients underwent multimodality therapy including surgery through a sublabial incision, radiotherapy, and regional chemotherapy. The regional lymph nodes were treated only in those patients with cervical lymph node involvement. RESULTS. The 5-year and 10-year overall survival rates were 76% and 66%, respectively. In 65 patients with squamous cell carcinoma, the 5-year and 10-year overall survival rates were 77% and 66%, respectively. All 23 patients with orbital involvement retained the orbital contents and 17 patients demonstrated adequate ocular function. There was no disease recurrence reported among patients with involvement of the foramen rotundum or the foramen ovale, whereas two of the three patients with invasion of the foramen lacerum developed disease recurrence. There were 12 complications in 12 patients, including double vision (4 patients), cataracts (3 patients), trismus (4 patients), and fistula formation (1 patient). CONCLUSIONS. Control of the primary tumor site is important in the curative treatment of patients with maxillary sinus carcinoma. Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy appears to be an effective method for local control and the preservation of ocular function. (C) 2000 American Cancer Society.

Pleomorphic adenoma (PA) is the most common benign tumor of the major salivary glands. It can also occur in the minor salivary glands, mainly in the oral cavity, and in other sites in the head and neck region. We pre sent a very I are case of PA in the pterygopalatine fossa. Surgical resection of the tumor was performed via the transmaxillary approach. The patient has experienced neither surgical complications nor recurrence in the past 3 years. This case suggests that a localized benign tumor in the pterygopalatine fossa can be removed safely and efficaciously via a transmaxillary approach.

To achieve the visualization of regional lymph nodes by lymphoscintigraphy, 21 patients with head-and-neck cancer were studied with the aid of 99mTc-labeled rhenium sulfur colloid (99mTc Re). Four injection sites were selected the injections were given into the subcutaneous tissue of the parietal area of 11 patients, into the submucosa of the retromolar area of 6 patients, into the subcutaneous tissue of the postauricular area of 2 patients, and into the thyroid glands of 2 patients. Lymphoscintigraphy was done three hours after the injection. The cervical regions were visible in 85.7% of the patients on the affected side and in 90.5% on the healthy side. The visualization comprised the following regions: submental, submandibular, deep cervical, accessory, and supraclavicular regions. In total, 102 nodes were visualized on the affected side (average 4.8 per patient) and 110 nodes in the healthy side (average 5.5). Histologically, 15 of 21 patients had lymph nodes metastases and 6 did not. Of these 21 patients, 66.7% (14/21) had confirmed lymph node metastases in the visualized regions. This technique appears to be a relatively easy and efficient method of imaging the regional lymph nodes in head-and-neck cancer both before treatment and after neck surgery. © 1992, Sage Publications. All rights reserved.