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This chapter examines how science can co-produce with local communities and what kind of roles it can play for local revitalization in one of the border islands of Japan, Tsushima (Nagasaki Prefecture). Currently, depopulation, declining birthrate, and aging population are accelerating in local regions all over Japan, and the management and survival of local communities is becoming “unsustainable.” Therefore, it has become a major issue on how to build a sustainable local community around Japan, and various efforts have already been made everywhere. Under these circumstances, the case of Tsushima is a practical case study of transdisciplinary research to develop a sustainable local community. This is also one of the Future Earth research which is based on the “co-design, co-production, and co-delivery between science and society.” This chapter will introduce two cases in Tsushima islands, and then, from the perspective of TD research, emphasize the importance of the role of coordinator, social sensitivity to local needs and realities, priority, problem framing, and scale setting.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

It has hitherto been unknown whether the paradise fish Macropodus opercularis that inhabits the Ryukyu Archipelago, Japan, is native to the region or was introduced. This study examined the genetic identity of fish from five islands in the Ryukyu Archipelago (Okinoerabu, Okinawa, Yagaji, Kume, and Minamidaito islands) and compared it with those from Taiwan Island, mainland China, and Hainan Island. Analyses of the mtDNA control (760 bp) and cytb (660 bp) regions showed that haplotypes of specimens from the Ryukyu Archipelago were the same as or were very similar (with a 1- or 2-bp difference) to those from Taiwan. In addition, haplotypes from the Ryukyu Archipelago also showed lower genetic diversity than those from Taiwan Island, mainland China, and Hainan Island. These results suggest a high likelihood that the fish in the Ryukyu Archipelago were artificially introduced from Taiwan. However, the possibility that the fish is indigenous to the Ryukyu Archipelago cannot be completely ruled out, because some haplotypes and a clade from the Ryukyu Archipelago have not been found in the other areas. Regardless of its origin, we emphasize the importance of the conservation of the paradise fish in the Ryukyu Archipelago as an indicator of the threatened wetland environment as well as for its cultural value.

Lifestyle, particularly smoking and alcohol consumption, may induce and/or inhibit drug metabolism. In order to reveal the effects of smoking and alcohol consumption on the 5-fluorouracil (5-FU)-related metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase (DPD; a sole catabolic enzyme of 5-FU), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase, in oral squamous cell carcinomas, the mRNA expression of these enzymes was investigated in 29 surgical specimens and compared by the Brinkman index and drinking years. The surgical specimens were divided into normal and tumor regions and were independently analyzed using quantitative reverse transcription-polymerase chain reaction. There was a significantly positive correlation between DPD mRNA expression in these tissues and Brinkman index/drinking years, with OPRT mRNA expression being significantly correlated to the Brinkman index in tumor tissues. These results revealed that lifestyle habits, including smoking and alcohol consumption, may vary the activity of the 5-FU-related metabolic enzymes. DPD is the initial and rate-limiting enzyme in the catabolic pathway of 5-FU. Therefore, smoking and alcohol consumption may reduce the anticancer activity of 5-FU, possibly through the induction of DPD activity.

Fibrosis is one of the most common pathological alterations in heart failure, and fibroblast migration is an essential process in the development of cardiac fibrosis. Experimental autoimmune myocarditis (EAM) is a model of inflammatory heart disease characterized by inflammatory cell infiltration followed by healing without residual fibrosis. However, the precise mechanisms mediating termination of inflammation and nonfibrotic healing remain to be elucidated. Microarray analysis of hearts from model mice at multiple time points after EAM induction identified several secreted proteins upregulated during nonfibrotic healing, including the anti-inflammatory cathelicidin antimicrobial peptide (CAMP). Treatment with LL-37, a human homolog of CAMP, activated MAP kinases in fibroblasts but not in cardiomyocytes, indicating that fibroblasts were the target of CAMP activity. In addition, LL-37 decreased fibroblast migration in the in vitro scratch assay. P2X7 receptor (P2X7R), a well-known receptor for LL-37, was involved in LL-37 mediated biological effect on cardiac fibroblasts. Stimulation of BzATP, a P2X7R agonist, activated MAPK in fibroblasts, whereas the P2X7R antagonist, BBG, as well as P2X7R deletion abolished both LL-37-mediated MAPK activation and LL-37-induced reduction in fibroblast migration. These results strongly suggest that CAMP upregulation during myocarditis prevents myocardial fibrosis by restricting fibroblast migration via activation of the P2X7R-MAPK signaling pathway.

Although food hypersensitivity is a public health concern, its documentation among the elderly is limited. The current study aims to compare the prevalence and characteristics of food hypersensitivity among adolescent women between aged 18-24 with among older women50 years of age.660 female university students between the ages of 18 and 24 who volunteered were enrolled as adolescent subjects. 470 women50 years old who visited the Health Care Centre of Kyoto Katsura Hospital for health check-ups were enrolled as the older subjects. A questionnaire created by ourselves asking the presence of food hypersensitivity, symptoms, causative food, personal or family history of other allergic disorders was distributed.The prevalence of food hypersensitivity was statistically similar between adolescent (8.2%) and older women (8.9%). Among them, only 24.1% of the adolescent women and 26.2% of the older women had been diagnosed by physicians as having food allergy. The main causative foods (fruits, shellfish and fish) and the manifestations relating to food hypersensitivity were almost identical between adolescent and older women. In both adolescent and older women, food hypersensitivity positive group showed significantly higher prevalence of personal or family history of allergic disorders than that in food hypersensitivity negative group.These data indicate that food hypersensitivity in older women should be given more attention because the prevalence of this condition was as common as that in adolescent women.背景与目的：虽然食物过敏是一个公共健康问题，但在老年人中进行的研究有 限。本研究的目的是比较18-24 岁的青年女性和50 岁以上的老年女性食物过 敏的患病率和特点。方法与研究设计：纳入研究的青年研究对象是660 名年龄 在18-24 岁自愿参加的女大学生，老年研究对象是470 名到京都桂医院保健中 心进行健康体检的50 岁以上的女性。采用自编问卷询问研究对象食物过敏的 发生、症状、致敏食物、个人或家族其它过敏性疾病史。结果：青年女性和老 年女性食物过敏的患病率之间的差异无统计学意义，分别为8.2%和8.9%。她 们当中，只有24.1%的青年女性和26.2%的老年女性被医生诊断为食物过敏。 青年女性和老年女性的致敏食物（水果、贝类和鱼类）和食物过敏的表现几乎 相同。与食物过敏阴性组相比，青年女性和老年女性的食物过敏阳性组均显示 出较高的个人或家族过敏性疾病史。结论：这些数据表明，老年女性食物过敏 和年轻女性一样常见，应给予更多的关注。.

Aims Interleukin (IL)-17-producing helper T (Th17) cells have been proposed to participate in the pathogenesis of chronic inflammation, such as autoimmune myocarditis. IL-6 gene ablation confers the resistance to experimental autoimmune myocarditis (EAM). In this study, we have addressed the pathological roles of IL-6 in the regulation of Th17 cells in EAM. Methods and results To induce EAM, mice were immunized twice with α-myosin heavy chain peptide. Three weeks after the first injection, the cardiac expression of the Th17-specific transcription factor, retinoic acid receptor-related orphan nuclear receptor (ROR γt), was up-regulated. Consistently, Th17 cells were recruited into EAM hearts, as analysed by flow cytometry. Using the mice with enhanced green fluorescence protein ( eGFP ) gene knocked-in at RORγt locus ( RORγt-eGFP mice), we observed Th17 cell infiltration into inflamed lesions. Pre-treatment with IL-6 receptor (IL-6R)-blocking antibody (anti-IL-6R Ab) inhibited EAM induction in terms of disease severity score (3.5 ± 0.8; IgG vs. 0.5 ± 0.8; anti-IL-6R Ab, n = 6, P < 0.01) and suppressed the myocardial expression of IL-17 and RORγt. In contrast, the administration of anti-IL-6R Ab 7 days after the first immunization failed to show the inhibitory effects, suggesting that IL-6 plays important roles in EAM initiation. Finally, by generating RORγt-eGFP homozygous mice, we revealed that RORγt gene ablation conferred the resistance to EAM induction. Conclusion IL-6-mediated induction of Th17 cells is critical for the onset of EAM, but not for its progression. IL-6/Th17 signalling could be a promising therapeutic target for the prevention of myocardial inflammation.

We validated the effects of a passive integrated transponder (PIT) tagging process on the oriental weather loach Misgurnus anguillicaudatus. Laboratory experiments were conducted to assess the effects of PIT tagging on fish survival, growth, wound healing, and tag omission. Two tagging protocols, standard syringe injection versus insertion through a small hole pierced by a fine needle-shaped awl, were compared using a 12.5 × 2.07 mm2 tag. A control group was also included. In comparison with the awl technique, syringe injection heightened the mortality of the loach and delayed healing of the wound caused by tag insertion. No effects of either PIT tagging method were detected on the growth of surviving loach. We also field-tested similarly tagged populations within a river-based irrigation system of Sado Island, Japan. Two different sized tags (long, 12.5 × 2.07 mm2; short, 8.5 × 2.12 mm2) were compared by using antenna loggers which detected fish movement through gates and automatically logged tagged fish’s tag IDs and timestamps. By comparing logged data and actual fish collection surveys both below and above the gates, 77% and 30% of actual loach movements were confirmed to have been successfully logged for the long and short tags, respectively. The awl insertion technique with the longer tag is therefore recommended for use in similar studies of smaller fish species.

The distribution of the oriental weatherloach, Misgurnus anguillicaudatus, together with related environmental factors were surveyed at 185 paddy field locations on Sado Island in Japan. This was associated with the reintroduction of the Japanese crested ibis, Nipponia nippon, which prefers to feed on the loach. Loach were found to be present at 90 locations (49%). Analysis with GIS, GLM and AIC revealed that positive factors for the loach distribution included the presence of an earth ditch, the connections at outlets and the proportion of paddy field area within an 800 m radius. Conversely, pumping-up water irrigation and flow irrigation affected loach distribution negatively. In an interview survey that was conducted concurrently, older farmers in the area recalled that the loach had once been distributed over almost the entire island (89/96, 93%) about half a century ago. The farmers also suggested that the impact of agricultural chemicals was one of the main reasons for loach reduction or local extinction. A map of the current potential loach distribution was made using the best fit model from GIS variables. The loach was expected to be distributed in the Kuninaka region with high probability (60–100%) and in patches in the Osado and Kosado regions with low–medium probability (10–50%). As a feasible scenario for the conservation of the loach, another predictive map of the loach distributions was made using a model fit based on the GIS variables and outlet connection, in which the all of the outlets were presumed to be connected to the ditches without gaps. In this case, the loach were expected to be distributed almost throughout the paddy fields with medium–high probability (40–100%). In another scenario that presumed the complete land consolidation of all the paddy fields, the probability of loach occurrence was low (0–30%) throughout the island with the exception of the island’s center in the Kuninaka region.

Background: Lafutidine is a unique histamine H2-receptor antagonist (H2RA) that has a sensitizing effect on capsaicin-sensitive afferent neurons (CSAN). This effect may make lafutidine useful for the treatment of burning mouth syndrome (BMS). Methods: To evaluate the efficacy and safety of lafutidine in patients with oral burning sensation, a randomized controlled trial was performed. Patients who had been receiving other H2RAs with no sensitizing effect on CSAN were randomly assigned to receive lafutidine 10 mg twice daily for 12 weeks, instead of the previous H2RAs, plus gargling with azulene sulfonate sodium (ASS) (lafutidine group, n = 36) or to continue to receive the previous H2RAs plus ASS gargling (control group, n = 35). The intensity of burning sensation was scored by means of a visual analog scale (VAS). Results: Thirty-four patients in the lafutidine group and 30 in the control group completed the study. In the lafutidine group, the rate of improvement in the VAS score as compared with the baseline value was significant after 4, 8, and 12 weeks of treatment (P

Summary The RECK gene is a novel tumor suppressor gene that regulates matrix metalloproteinases (MMPs) to inhibit tumor angiogenesis, invasion and metastasis. We investigated the methylation status of the RECK gene in 40 primary oral squamous cell carcinomas (OSCC) and 20 paired adjacent normal mucosa by methylation-specific PCR. Furthermore, we determined the prognostic importance of RECK hypermethylation in OSCC patients. Our findings showed that the RECK gene was methylated in 52.5% (21 of 40) of the primary OSCC. Among the 20 cases with corresponding normal tissues, RECK hypermethylation was detected in both primary tumor (55%, 11 of 20) and adjacent normal mucosa (30%, 6 of 20). Methylation of the RECK gene was not detected in all normal oral mucosa samples of the 12 healthy controls. In univariate analysis, RECK hypermethylation was inversely correlated with recurrence-free survival ( p = 0.027) and overall survival ( p = 0.023) of the OSCC patients. Multivariate analysis showed that the methylation status of the RECK gene was the only independent prognostic factor affecting overall survival ( p = 0.037). The result indicates that hypermethylation of RECK promoter is a common event in human OSCC, occurs concurrently in tumor–adjacent normal mucosa and is correlated with poor prognosis in OSCC patients. Although additional work is needed, hypermethylation of the RECK gene is a promising biomarker in early detection and prognosis for oral cancer patients.

A re-recurrent case of ameloblastoma in an autogenous iliac bone graft is reported. A 49-year-old woman was referred to our department because of swelling and pain in the left side of the mandible. Her past medical history revealed that she had undergone mandibulectomy and reconstruction with antogenous iliac bone grafts two times, 25 and 15 years ago, for a diagnosis of ameloblastoma. Radiographic examination showed an osteolytic lesion in the central area of the grafted bone, and MRI images of the lesion showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. An intraoral biopsy was done, and the pathological diagnosis was ameloblastoma. Under general anesthesia, continuous resection of the grafted bone and reconstruction of the mandible with microvascularized fibula bone were carried out. The postoperative course was uneventful.

We report a case of osteonecrosis of the mandible associated with an oral bisphosphonate (BP) in apatient with osteoporosis and describe its cure.A 84-year-old woman received oral alendronate sodium hydrate from September 2004 through April 2006. Shewas referred to our department because of a fistula that developed after extraction of the lower right first and secondpremolars in April 2006 by her dentist. Physical examination revealed diffuse swelling of the right mandible, and hypoesthesia was present in the right mental region. Imaging of the lesion revealed an extensive radiolucentarea and a tumor-like mass in the right side of the mandible. Antibiotic therapy was started, and initial biopsy andexcisional biopsy were carried out to rule out malignant lesions. Histopathological examination showed granulationtissue and bone necrosis. BP-associated osteonecrosis of the jaw was diagnosed. BP medication was withdrawn, and conservative therapy was performed. Cure of the lesion, including bone regeneration, was observed 1year later.

A 54-year-old man presented with an 8-year history of a hard asymptomatic mass of the left submandibular area. Total excision of the left submandibular gland with radical neck dissection was performed under a diagnosis of a submandibular tumor, probably a malignant mixed tumor. The pathologic diagnosis was carcinosarcoma consisting of carcinomatous and sarcomatous elements. The epithelial component was composed of squamous cell carcinoma, undifferentiated carcinoma, and adenocarcinoma. The nonepithelial component was composed of chondrosarcoma, osteosarcoma, spindle cell sarcoma, rhabdomyosarcoma, and liposarcoma. In the central area of the tumor, a few remnants of benign pleomorphic adenoma were identifiable. The finding suggested that in our patient, the carcinosarcoma arose from a preexisting pleomorphic adenoma. In view of the expected aggressive nature of the tumor, the patient was treated with postoperative radiotherapy of 60 Gy total, in 30 daily fractions of 2 Gy, and chemotherapy. He currently remains well and free of disease 24 months after treatment.

This report is of a 64-year-old woman with insulin-dependent diabetes and hypertension with a parapharyngeal and retropharyngeal space infection of odontogenic origin. The patient presented with submandibular swelling. After treatment with antimicrobial agents and diabetes control measures, she had initial improvement. Progressive dysphagia, increasing neck pain, and mild dyspnoea occurred on day 8, and imaging revealed abscess formation in the parapharyngeal and retropharyngeal spaces requiring transcervical drainage. On day 15, the associated teeth were extracted. She recovered uneventfully and was discharged from hospital after 30 days.

Several genetic alterations have been reported to contribute to the development of oral squamous cell carcinoma (OSCC). Recent studies have shown roles of promoter hypermethylation of tumor suppressor genes, including p16 and MGMT, in several types of cancers. The purpose of this study is to examine the hypermethylation status of p16 and MGMT genes in both oral cancers and normal mucosa, surrounding the cancers.Promoter hypermethylation status of p16 and MGMT genes were examined by the methylation-specific PCR (MSP) in OSCC (n = 51), verrucous carcinoma (n = 2), and carcinoma in situ (n = 2) tissues. Moreover, normal mucosa surrounding the cancers were also examined in 22 cases out of the 51 OSCCs. As a normal control, oral mucosa from healthy volunteers (n = 18) was used.Aberrant promoter hypermethylation of p16 and MGMT genes was detected in 50.9% (28 of 55) and 56.4% (31 of 55) of the total malignant cases, respectively. As for the 22 OSCC cases, in which paired cancerous tissues and the surrounding normal mucosa were examined simultaneously, promoter hypermethylation of p16 and MGMT genes was confirmed in 72.73% (16 of 22) and 68.18% (15 of 22), respectively. In contrast, as for the surrounding normal mucosa, promoter hypermethylation of p16 and MGMT genes was recognized in 27.27% (6 of 22) cases and 40.91% (9 of 22), respectively.Hypermethylation of both p16 and MGMT genes was frequently detected in not only OSCC tissues, but also the surrounding normal mucosa around the cancerous tissues. Thus promoter hypermethylation of p16 and MGMT genes are an important, probably early event in oral carcinogenesis.

Intraoral occurrence of Schwannoma is relatively rare. This report is of 4 patients with Schwannoma of the oral cavity. The presenting complaint for all patients was Intraoral submucosal swelling. The tumour arose in the tongue in 2 patients, the retromolar region in 1, and the buccal mucosa in 1. One of the tumours originating in the tongue was located in an unusual site, beneath the hyoglossal muscle layer All 4 patients underwent surgery for tumour excision and the tumours were then diagnosed as schwannomas. Histologically, Antoni A tissue was observed in all tumours and was the predominant feature in 3 tumours; Antoni B tissue associated with cystic degeneration and necrosis was also identified in 1 tumour

In order to characterize the chromosomal alterations in ameloblastomas, a combination of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) techniques was performed on 9 tumors. Chromosomal alterations including a gain at 1q and losses at 1pter, 10q, and 22q could be detected by CGH only in 1 tumor. Interphase FISH analysis, using centromeric probes for chromosomes 1, 10, and 22 as well as region-specific probes for 1p36 and 10q26, revealed the most frequent alterations to exist in the tumor with the abnormal CGH profile. These alterations included marked to slight increases of monosomic cells for chromosome 10 (91.5%), 10q26 (35.8%), 1p36 (24.4%), and chromosome 22 (18.8%), as well as significant elevations of trisomic cells for chromosome 1 (41.2%). Moreover, FISH analysis revealed a frequent loss of chromosome 22 in all tumors examined, except for one lesion, indicating that loss of the entire or a part of this chromosome is a common event in ameloblastomas, possibly being a predisposing factor to ameloblastoma tumorigenesis.

We describe a case of intractable cheek phlegmon arising from an odontogenic infection that extended to the interpositional alloplastic material of the temporomandibular joint.A 75-year-old man was referred to our department because of a painful swelling in the right temporal region occurring after an acute odontogenic infection of right upper molar teeth. The past history revealed reconstruction surgery with iliac bone transplantation following a right hemimandibulectomy to treat an ameloblastoma about 26 years ago. Physical examination and imaging findings of CT and MM revealed a diffuse swelling in the temporobuccal region and a foreign body in the temporomandibular joint region. The clinical diagnosis was temporal cellulitis from an infection involving the interpositional alloplastic material of the temporomandibular joint. Initial chemotherapy was effective, and the swelling gradually disappeared. However, a fistula formed at the buccal region and pus discharge continued in spite of conservative therapy with irrigation. Under local anesthesia, we carried out curettage of the fistula two times, and the silicone-like foreign body, which might have been implanted at mandibular reconstruction surgery, was removed. Then, the symptoms of the infection rapidly and completely disappeared.

We report a case of florid cemento-osseous dysplasia (FCOD) occurring in the mandibular ramus. The patient was a 21-year-old woman who had had discomfort in the right mandibular gingiva. Since a panoramic radiograph by her dental practitioner showed a radiopacity in the right side of the mandible, she was referred to our department. A radiographic examination revealed a massive radiopaque lesion, measuring approximately 3×3cm, involving the entire mandibular ramus. The lesion was removed under general anesthesia. The lesion was diagnosed as a FCOD or other cemento-osseous dysplasia. There was no evidence of recurrence 18 months after the operation.

The objective of this study was to investigate the causes of failure of oral reconstruction by free tissue transfer and thereby improve outcome. Oral microvascular reconstruction was performed in 171 patients between April 1995 and March 2002, and these patients were examined. In this series, rupture and thrombi in anastomotic vessels were found in 12 patients (7.0%). The number of cases of rupture, arterial thrombi, and venous thrombi in the anastomotic vessels were 5, 2, and 5, respectively. Although 6 cases responded to secondary microvascular anastomosis, 6 (3.5%) had total flap necrosis. In conclusion, ruptures and thrombi in anastomotic vessels may be prevented by prophylaxis of cervical infection, relief of pressure on anastomotic vessels, and meticulous surgical technique. Postoperatively cervical rest, close observation, and accurate evaluation of flap status are essential to avoid flap necrosis.

Two cases of nasoalveolar cysts presenting with characteristic clinical features are reported.A 42-year-old woman was referred to our hospital because of upper lip swelling by her dentist. A computed tomographic (CT) scan revealed bilateral nasoalveolar cysts.A 50-year-old woman was referred to our hospital because of a swelling at the right nasal ala with epiphora by her dentist. A CT scan revealed a right-side nasoalveolar cyst, possibly developing from the nasolacrimal duct. Both cysts were removed surgically under general anesthesia, and they adhered to the nasal mucous membrane.Histopathological examination revealed that the cyst walls consisted of columnar epithelium with goblet cells and fibrous connective tissue with minor glands.

口底扁平上皮癌N0症例のうち, 原発巣が制御された53例を対象に頸部に対する処置法を検討した。性別は男性48例, 女性5例で, 平均年齢は60.3歳であった。T分類はT1: 14例, T2: 35例, T3: 4例であった。初回治療法は手術単独: 29例, 放射線単独: 7例, 手術放射線併用: 14例, 手術化学療法併用: 3例であり, 16例に予防的頸部郭清術 (以下END) が行われた。ENDを施行した16例中2例, 治療的頸部郭清術 (以下TND) を施行した37例中8例に病理組織学的転移を認めた。潜在的なリンパ節転移の頻度は18.9%であった。初回治療法別およびT分類別での後発転移の発現頻度には差はみられなかった。転移レベルは1例を除きいずれもレベルIIIまでの転移であった。END施行群とTND施行群の5年累積生存率はそれぞれ73.1%, 66.9%であった。以上から, 今回検討した限りでは, 口底扁平上皮癌N0症例に関しては初回治療時にあえて頸部郭清術を行う必要はないものと考えられた。

Three-phase bone scintigraphy was undertaken to check the anastomotic patency and monitor the viability of vascularized bone grafts. Ten consecutive patients who underwent vascularized bone grafting of the mandible were reviewed. A successful clinical outcome was achieved in 8 patients. The graft failed in 2 patients. In this series, 3-phase bone scintigraphy of radiolabeled (99m)Tc-methylene-diphosphonate was performed at 7 days, and at 1, 3, 6, and 12 months after reconstruction. Assessments made using 3-phase bone images were compared with the clinical findings. The clinical outcome of the cases presented in our series correlated extremely well with 3-phase bone images. Three-phase bone scintigraphy is a useful method for the assessment of patency and viability of vascularized bone grafts. The use of this method can be very helpful in assessing the anastomotic patency and viability of a graft which for clinical reasons is suspected of being non-viable.

Objective: Determination of whether an enlarged cervical lymph node is metastatic or not is clinically important in head and neck oncology. Differential diagnosis of the lymph node, however, is still a diagnostic problem. The purpose of this study is to clarify the ultrasonographic findings of the metastatic lymph nodes of head and neck squamous cell carcinoma and to establish the criteria. Methods: We investigated 36 metastatic lymph nodes in head and neck squamous cell carcinoma and 24 non-metastatic nodes in benign disease with a 10-MHz transducer. We examined the size, shape, and internal echo (echo level, punctate bright echogenic spots, hilus echogenic line, cystic pattern) of these nodes. Based on this investigation, we evaluated 70 lymph nodes from 25 other patients by ultrasonography. Results: The short axis diameter and shape of metastatic nodes were larger and rounder than those of non-metastatic ones. Of the metastatic nodes, 69% showed hypoechoic and 31% isoechoic levels, and 78% exhibited punctate bright echogenic spots. Of the non-metastatic nodes, 92% showed hypoechoic and 8% isoechoic levels, and none of them showed the spots. The hilus echogenic line was not present in any metastatic node, but it was seen in 58% of non-metastatic ones. Of the metastatic nodes, 19% exhibited a cystic pattern; none of the non-metastatic nodes showed the pattern. According to our criteria based on these results, the accuracy rate was 98.6% (69/70). The sensitivity and specificity were 97.2% (35/36) and 100% (34/34), respectively. The false positive rate and the false negative rate were 0% (0/70) and 1.4% (1/70), respectively. Conclusion: Internal echo findings and shape of lymph nodes can be an important diagnostic tool, and our ultrasonographical criteria of the lymph nodes are very useful for the differential diagnosis of the cervical lymph nodes.

We investigated the role of phosphatidylinositol 3-kinase (PI 3 K) in tumor cell invasion. Two cloned tumor cell lines, designated SAS-L 1 (low invasiveness) and SAS-H 1 (high invasiveness), were isolated from a human oral squamous cell carcinoma (OSCC), SAS. SAS-L 1 and SAS-H 1 cells exhibited high and low motility, respectively. To compare the function of PI 3 K between the two tumor lines, the signaling mechanism after serum stimulation was examined.In SAS-H 1 cells, tyrosine phosphorylation of focal adhesion kinase (p125FAK) in response to serum stimulation was markedly inhibited by both wortmannin and LY294002, a dosedependent inhibitor of PI 3 K, but inhibition was not observed in SAS-L 1 cells. Futhermore, wortmannin inhibited adhesiveness to extracellular matrices and cell motility in SAS-H 1 cells.PI 3 K activity induced by serum stimulation was higher in SAS-H 1 cells than in SAS-L 1 cells. Activation of PI 3 K was abolished by wortmannin or LY294002. The correlation between PI 3 K activation and invasive potential suggested that inhibition of activated PI 3 K would decrease the invasiveness of SAS-H 1 cells. Wortmannin or LY294002 inhibited invasion by SAS-H 1 cells, but not SAS-L 1 cells on endothelial monolayer invasion assay.Our results suggest that a PI 3 K-dependent signal transduction pathway plays an essential role in cell adhesion and cell motility of the highly-invasive OSCC cell line (SAS-H 1), which leads to the phosphorylation of p125FAK.