[The originality and creativity of leprosy sequelae patients in regard to dental care].

Leprosy sequelae patients surmount the inconvenience by the handicap. When people with the handicap are able to do the same act as healthy people, we may not pay attention to the originality and creativity for it. Therefore, we are not able to notice some risks which are hidden. We turned our attention to the denture in the oral region. The methods of putting in and taking out the denture of leprosy sequelae patients are characteristic. Even a partial denture, there are many patients who take out their denture using only their tongue, without touching a clasp with a finger. And they put in the denture by biting. But we had never not announced the details of their methods. So, we investigated how to handle their denture in National Sanatorium Nagashima Aiseien. We explain their methods and show the results. On the other hand, there are a lot of cases of the denture breakage in National Sanatorium Nagashima Aiseien. We think most of these matters occur due to their handicaps. We researched on the cases with dentures broken. In addition, we also describe our countermeasure.

[The characteristic of oral status and dental treatment of leprosy sequelae patients].

The leprosy sequelae especially the handicap of eyes and hands makes difficult to maintain the oral health status. So, leprosy sequelae patients are controlling themselves by creative and original methods. However even such efforts have hardly reached the level to stop of caries and periodontal disease. More support is required in order for them to maintain the oral health status. Therefore, in National Sanatorium Nagashima Aiseien, we started the periodic preventive system containing oral check-up, mouth cleaning, and early detection early treatment 15 years before. It is the report about this activity. First, the leprosy sequelae handicap which makes oral control difficult is described. Secondly, our periodic preventive system in National Sanatorium Nagashima Aiseien is explained. In order to evaluate this activity, the number of patients and the contents of dental treatment were compared. Furthermore, the number of remaining teeth was compared with the adult Japanese. Our periodic preventive system was received and they have many remaining teeth now. It is sure that this activity for 15 years was successful.

Clinical and immunological assessment of periodontal disease in Japanese leprosy patients.

Periodontitis is a chronic inflammatory disease caused by the infection of periodontopathic bacteria in dental plaque. However, an individual's susceptibility to this disease appears to be associated with multiple genetic factors, as seen in the case of leprosy. In order to gain a better understanding of the pathophysiology of periodontal disease in subjects with leprosy, we investigated the clinical features of periodontitis and the immunological responses against periodontopathic bacteria in 382 subjects with a history of leprosy and 451 age-matched control subjects. The prevalence of periodontitis and the degree of periodontal pocket depth were found to be significantly higher in leprosy patients than in age-matched controls. Furthermore, a comparison of the clinical parameters of lepromatous leprosy (L-lep) and tuberculoid leprosy (T-lep) patients showed that the probing pocket depth of L-lep patients with periodontal disease was significantly higher than that for T-lep patients. In contrast, serum IgG titers against Porphyromonas gingivalis in L-lep patients were significantly lower than in T-lep patients. These results imply that L-lep patients show more severe periodontal disease than T-lep patients or age-matched control subjects, and that low humoral immunity against P. gingivalis might be one of the genetic factors determining periodontal disease susceptibility in leprosy patients.

Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer - a retrospective analysis: JMTO LC03-02.

BACKGROUND: In Japan, high incidences of interstitial lung disease (ILD) and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC). We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. FINDINGS: We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0-1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7-22.0). ILD developed in 17 patients (3.2%; 95% CI 1.9-5.1%), of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. CONCLUSION: The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

Influence of epidermal growth factor receptor (EGFR) gene mutations on the expression of EGFR, phosphoryl-Akt, and phosphoryl-MAPK, and on the prognosis of patients with non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: In this paper we examined the influence of epidermal growth factor receptor (EGFR) gene mutations on EGFR expression, downstream mediators, and survival in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the tumors of 53 patients with completely resected pathological stage I-IIIA NSCLC for the presence of EGFR gene mutations, the expression of EGFR mRNA and protein, phosphoryl-Akt, and phosphoryl-mitogen-activated protein kinase (MAPK) using immunostaining, and patients' prognosis. RESULTS: EGFR mutations were associated with elevations in EGFR mRNA (P = 0.004) and protein (P = 0.029) expression, but not with the expression of phosphoryl-Akt or phosphoryl-MAPK. The 5-year survival rate for all patients who exhibited an EGFR mutation was similar to those who were free of such mutations (71% vs. 56%, P = 0.252). However, the 5-year survival rate of patients with either a stage I adenocarcinoma or large cell carcinoma who had an EGFR mutation was significantly greater than for those who did not have such a mutation (92% vs. 57%, P = 0.037). CONCLUSIONS: EGFR gene mutations were significantly associated with higher EGFR expression, but not with p-Akt or p-MAPK status. In early stage NSCLC, the presence of an EGFR gene mutation bode well for the patient's prognosis.

Maspin expression and its clinical significance in non-small cell lung cancer.

BACKGROUND: Maspin is a member of the serpin (serine protease inhibitor) superfamily, and its exact function in the development and progression of malignant tumors remains controversial, though some experimental studies have revealed potential tumor-suppressor activities. In addition, there have been only a few clinical studies on maspin expression in malignant tumors including non-small cell lung cancer (NSCLC). The purpose of this study was to assess maspin expression and its clinical significance in NSCLC. METHODS: A total of 210 consecutive patients with completely resected pathological (p-) stage I-IIIA NSCLC were retrospectively reviewed. Maspin expression along with intratumoral microvessel density, proliferative activity, and p53 status were evaluated immunohistochemically. The incidence of apoptotic cell death was also evaluated. RESULTS: The incidence of strong maspin expression was significantly higher in lung squamous cell carcinoma (56/76, 73.7%; P < .001) than in other histological types. The incidence of aberrant expression of p53 was significantly higher in maspin-strong than in maspin-weak tumors (56.2% and 35.8%, respectively; P = .005). There was no difference in prognosis according to maspin status for all patients. However, for squamous cell carcinoma patients, univariate analysis showed that enhanced maspin expression was a significant factor in predicting a favorable prognosis (5-year survival rates, 70.1% for maspin-strong tumors and 41.5% for maspin-weak tumors; P = .014), which was confirmed in a multivariate analysis (hazard ratio = .475, 95% confidence interval .241-.936; P = .032). CONCLUSIONS: Enhanced maspin expression was a significant and independent factor in predicting a favorable prognosis in lung squamous cell carcinoma.

Lessons from gefitinib-induced interstitial lung disease in Japan: problems in approval, pharmacovigilance, and regulatory decision-making procedures

Objective: The objective of this study was to identify problems in the approval, pharmacovigilance, and post-approval regulatory decision-making procedures involving gefitinib and to propose countermeasures to prevent further drug-induced suffering in Japan in the future. Methods: We comprehensively reviewed reports regarding gefitinib published during the period from 2000 to 2006 by regulatory agencies, the manufacturer of the gefitinib-containing drug, cancer clinical study groups, and a scientific society. Results: We identified the following major problems in the approval, pharmacovigilance, and regulatory decision-making procedures: 1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly reflected in the label; 2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and 3) despite many serious cases of interstitial lung disease (ILD) being spontaneously reported, well-designed post-marketing surveillance was not immediately performed. Conclusions: We propose a mandatory total registry of all drug users and surveillance (i.e. a prospective outcome study) as one of the rational solutions for preventing further drug-induced suffering in Japan (AU)

Objetivo: Identificar los problemas en el registro, farmacovigilancia y toma de decisiones post-registro relativas al gefitinib y proponer contramedidas para prevenir futuros problemas producidos por medicamentos en Japón. Métodos: Revisamos intensamente los informes sobre gefitinib publicados durante el periodo 2000 a 2006 por las agencias reguladoras, el fabricante de medicamentos que contenían gefitinib, grupos de ensayos clínicos sobre medicamentos anti-cáncer, y una sociedad científica. Resultados: Identificamos los siguientes problemas principales en la aprobación, farmacovigilancia y proceso de toma de decisiones reguladoras: 1) los resultados de los estudios en animales y los ensayos clínicos pre-comercialización y los informes de reacciones adversas de otros países no se reflejaron correctamente en las fichas técnicas; 2) se expandieron las indicaciones del medicamento sin una estricta evaluación de la validez externa de los ensayos clínicos pre-comercialización; y 3) a pesar de que se comunicaron espontáneamente reacciones adversas graves de ILD, no se realizó inmediatamente una vigilancia post-comercialización bien diseñada. Conclusiones: Proponemos un registro obligatorio de todos los usuarios de medicamentos y vigilancia (p.e. un estudio retrospectivo de resultados) como una de las soluciones racionales para evitar futuros sufrimientos producidos por medicamentos en Japón (AU)

Maspin gene expression is a significant prognostic factor in resected non-small cell lung cancer (NSCLC). Maspin in NSCLC.

Maspin is a member of the serpin (serine protease inhibitor) superfamily, and some experimental studies revealed a potential tumor suppressor activity of maspin. To reveal clinical significance of maspin status in non-small cell lung cancer (NSCLC), we quantitatively evaluated maspin gene expression in lung primary tumors cut from a total of 55 resected NSCLC patients. Maspin expression in squamous cell carcinoma (Sq) was significantly higher than that in adenocarcinoma (Ad, p=0.011). Five-year overall survival rates of maspin-high and maspin-low patients were 67.7 and 41.4%, respectively, demonstrating a significant favorable prognosis of maspin-high patients (log-rank, p=0.042). A multivariate analysis confirmed that high maspin expression was an independent and significant factor to predict a favorable overall survival (p=0.031). These results suggested that maspin expression was significantly increased in Sq than in Ad, and that increased maspin expression was a significant factor to predict a favorable prognosis in resected NSCLC.

Lessons from gefitinib-induced interstitial lung disease in Japan: Problems in approval, pharmacovigilance, and regulatory decision-making procedures.

OBJECTIVE: The objective of this study was to identify problems in the approval, pharmacovigilance, and post-approval regulatory decision-making procedures involving gefitinib and to propose countermeasures to prevent further drug-induced suffering in Japan in the future. METHODS: We comprehensively reviewed reports regarding gefitinib published during the period from 2000 to 2006 by regulatory agencies, the manufacturer of the gefitinib-containing drug, cancer clinical study groups, and a scientific society. RESULTS: We identified the following major problems in the approval, pharmacovigilance, and regulatory decision-making procedures: 1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly reflected in the label; 2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and 3) despite many serious cases of interstitial lung disease (ILD) being spontaneously reported, well-designed post-marketing surveillance was not immediately performed. CONCLUSIONS: We propose a mandatory total registry of all drug users and surveillance (i.e. a prospective outcome study) as one of the rational solutions for preventing further drug-induced suffering in Japan.