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We clinically reviewed 33 surgery patients and 15 non-surgery patients aged 80 years or older with primary lung cancer treated at our hospital. The surgery group consisted of 21 males and 12 females (82.0 +/- 1.9 years old). The surgical procedures were 1 pneumonectomy, 19 lobectomies (1 bronchoplasty), 4 segmentectomies and 9 partial resections. The cancer types were 17 adenocarcinomas, 14 squamous cell carcinomas and 2 others. The stagings were 24 in stage I, 4 in stage II and 5 in stage III. There were no direct surgical deaths within 30 days post operatively. There have been 9 other disease-related deaths to date (27%). The non-surgery group consisted of 9 males and 6 females (81.7 +/- 1.5 years old). Treatment procedures consisted of radiationtherapy in 11, chemotherapy in 2 and best supportive care in 3. The cancer types were 2 adenocarcinomas, 11 squamous cell carcinomas and 2 others. The stagings were 7 in stage I, 4 in stage II and 4 in stage III. There have been 3 other disease-related deaths to date (20%). We must carefully select the therapeutic approach for elderly lung cancer patients, because the other disease-related death rates of both groups were high. The 5-year survival rate of stage I patients in the surgical group was relatively good (60.2%). There were long-term survival (7 5-year survivors) in the surgical group. Since there were some cases of radiation pneumonia in the group receiving radiation therapy, it would be better to perform surgery for elderly patients with lung cancer, especially those with stage I disease. For elderly patients, it is important to consider quality of life as well as the survival rate.

Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI:15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability.

The thymus has been implicated as a possible site of origin that triggers autoimmunity in myasthenia gravis (MG). Although several groups have suggested that the decrease in the number of regulatory T (Treg) cells contributes to the onset of MG, the exact role of Treg cells in MG remains unclear. To address this point, we examined the number and distribution of Treg cells in a large number of patients with MG.Immunohistofluorescence analysis of Foxp3 along with CD4 and CD8 was performed in thymic sections of MG (+) (n = 24) and MG (-) patients (n = 27). Circulating CD4(+)CD25(+) cells in the peripheral blood of patients with MG (n = 15) and age-matched healthy subjects (n = 15) were also analyzed.Foxp3(+)CD4(+)CD8(-) cells were predominantly found in the thymic medulla and their number declined with age. There was no significant difference in the number or the distribution of Foxp3(+)CD4(+)CD8(-) cells in the thymus between MG (+) and MG (-) patients. The number of circulating CD4(+)CD25(+) cells in the peripheral blood of patients with MG was not significantly altered compared to that in healthy subjects.The cellularity of Treg cells in the thymus and circulation is not diminished in patients with myasthenia gravis.

We report a case of anaplastic carcinoma of the thyroid administered peroral fluorinated pyrimidine, providing longterm survival during three years. Three years ago, a 70-year-old woman diagnosed with anaplastic carcinoma of the thyroid was admitted for chemoradiation therapy after tumor resection and tracheostomy. The tumor was confirmed to remain on the margin of resected specimens by postoperative histopathology. Combination chemotherapy, including docetaxel, 5-fluorouracil, cisplatin, and radiotherapy, was performed for four weeks. After completion of radiotherapy, CT scan showed residual tumor and lytic clavicular bone findings. But the patient did not desire the same heavy chemotherapy, wishing rather to undergo chemotherapy as an outpatient, if possible. She received chemotherapy with S-1 which was peroral fluorinated pyrimidine for 9 months. In this period, PET-CT showed that accumulation of FDG and lytic clavicular bone findings were continuously confirmed. She was changed to tegafur-uracil(UFT)from S-1, because of myelosuppression. She is alive at this writing in good physical condition. CT shows no tumor growth and no remote metastasis.

Fluorescence diagnosis of lymph node metastasis of non-small cell lung cancer has not been reported previously. This study was conducted to evaluate the feasibility of fluorescence detection using 5-aminolevulinic acid and mono-L-aspartyl chlorine e6 for lymph node metastasis in a lung cancer mouse model. Human lung cancer cell line Ma44-3, which forms metastatic lymph nodes in the mediastinum, was injected into the left lungs of 6 severe combined immunodeficiency disease mice. Two weeks after implantation, 2 groups of 3 mice received oral administration of 5-aminolevulinic acid (100 mg/kg) or intraperitoneal administration of mono-L-aspartyl chlorine e6 (5 mg/kg). Both lungs and mediastinal organs were removed en-bloc and illuminated with blue light (405 nm) to evaluate the detectability of lung tumors and metastatic lymph nodes in the mediastinum. These organs were evaluated histopathologically. Clear red fluorescence was observed in the lung tumors of all mice. Metastatic lymph nodes had formed in 5 of 6 mice and were detected by fluorescent detection in all 5 mice even though one of the lymph nodes was invisible macroscopically under white light. In conclusion, fluorescence diagnosis of lymph node metastasis is possible in a mouse model. The successful result with small lymph node metastasis suggests the possibility of clinical application.

Summary Background Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma. Methods We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features. Results Fifteen (47%) of 32 thymic epithelial tumours showed aberrant methylation. Aberrant methylation was more frequent in thymic carcinoma (86%) than in thymoma (29%). Moreover, the frequency of tumours with methylation of multiple genes in thymic carcinoma was higher than in thymoma (60% vs 20%). In thymoma, the frequency of tumour methylation, including the type A tumour component (28%), was lower than that of tumours with type B tumour component (42%). MGMT methylation was detected in 23% of thymoma and in 83% of thymic carcinoma. The frequency of methylation of the MGMT gene in both tumours was high compared with the other 3 genes. Conclusions Aberrant DNA methylation was more frequent in thymic carcinoma than in thymoma, and the frequency of DNA methylation in thymic epithelial tumours is roughly parallel to their malignant behaviour.

Lymphoepithelioma-like carcinoma (LELC) of the esophagus is extremely rare and the prognosis has been described to be favorable. Herein, the case is reported of esophageal LELC showing non-progressive course for 1 year. The patient was a 70-year-old Japanese man with a submucosal tumor in the lower esophagus. The tumor was endoscopically regarded as a benign leiomyoma. One year after the first endoscopic examination, the size of the lesion remained unchanged despite no treatment. Histologically, the tumor showed undifferentiated carcinoma associated with dense lymphocytic and plasma cell infiltration. Lymphoid follicles surrounded the tumor cell nests. Immunohistochemically, Ki-67 labeling index of the tumor cells were 76.0%, and there were few single-strand DNA-positive apoptotic cells. In situ hybridization using a digoxigen-labeled Epstein-Barr virus (EBV)-encoded small RNA (EBER)-1 riboprobe failed to detect the presence of EBV infection. Physicians should be aware that esophageal LELC endoscopically mimics benign submucosal tumor. This case may demonstrate that esophageal LELC is a slow-growing tumor and it is related to immune reaction.

Patients with large pulmonary emphysematous bullae often present therapeutic problems because of their poor respiratory function. We performed computed tomography (CT)-guided drainage in two patients with large pulmonary bullae who were considered poor surgical candidates. This method could be safely accomplished in a few minutes under local anesthesia and sufficient collapse of the bullae was obtained in both cases. We could control prolonged air leak from the catheter with bronchofiberoptic bronchial occlusion in one patient. CT-guided bulla drainage is a simple, speedy and minimally invasive treatment method for inoperable patients with large pulmonary bullae.

Summary Background Photodynamic therapy (PDT) using Talaporfin is an attractive treatment for central-type early lung cancer. It was noted that some patients had altered levels of arterial oxygen saturation as indicated by pulse oximeter (SpO 2 ) and arterial oxygen saturation levels in blood gas analysis (SaO 2 ) during PDT. The present experiments were designed to provide an explanation for these findings. Methods The influence of Talaporfin on SpO 2 using in vitro and in vivo experiments, and clinically, was examined. Results Our in vitro and in vivo experiments showed a linear relationship between Talaporfin concentration in the plasma and the SpO 2 level ( R = 0.9957 and 0.9837). The apparent SpO 2 level decreased according to the increase of Talaporfin concentration in the plasma. In two patients with PDT, SpO 2 levels at 4–6 h and 24 h after Talaporfin administration were 93% and 97%, respectively. Conclusions Talaporfin raised blood absorbance at 660 nm with a pulse oximeter. It appeared that the presence of the drug falsely decreased the level of SpO 2 since SpO 2 did not actually change.

In our previous studies, we established a lymphogenous metastatic SCID mouse model using orthotopic implantation of human lung cancer cell lines. However, the lymphogenous metastatic potential of each cell line in our models does not reflect that of a primary tumor. In this study, we made orthotopic implanted models using primary cultured cells from surgically-resected lung cancer tissues. Tissues of 5 patients with non-small cell lung cancer (NSCLC) were applied to a primary culture method using a collagen gel coated flask. Suspensions of 2.0x10(4) cancer cells were injected into the left lung of SCID mice. We could maintain primary culture cells from 2 (FM205 and FT821 cells) of 5 lung cancers, and made orthotopically implanted SCID mouse models. The size of both tumors in implanted sites of the lung increased with time. The FM205 cells microscopically were metastasized to the mediastinum by 4 weeks after implantation and macroscopically metastasized by 16 weeks. The FT821 cells were microscopically metastasized to the mediastinum by 4 weeks after implantation and macroscopically metastasized by 6 weeks. The lymphogenous metastatic potential of these primary culture cells was similar to that of clinical tumors. As the lymphogenous metastatic potential of this model reflects that of the clinical tumor, it is useful for elucidating the mechanism of lymphogenous metastasis and selecting anticancer drugs suitable for an individual patients.