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Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence.This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008.Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR.At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure. more...

OBJECTIVES To assess the impact of a history of liver metastases on survival in patients undergoing surgery for lung metastases from colorectal carcinoma. METHODS We reviewed recent studies identified by searching MEDLINE and EMBASE using the Ovid interface, with the following search terms: lung metastasectomy, pulmonary metastasectomy, lung metastases and lung metastasis, supplemented by manual searching. Inclusion criteria were that the research concerned patients with lung metastases from colorectal cancer undergoing surgery with curative intent, and had been published between 2007 and 2014. Exclusion criteria were that the paper was a review, concerned surgical techniques themselves (without follow-up), and included patients treated non-surgically. Using Stata 14, we performed aggregate data and individual data meta-analysis using random-effect and Cox multilevel models respectively. RESULTS We collected data on 3501 patients from 17 studies. The overall median survival was 43 months. In aggregate data meta-analysis, the hazard ratio for patients with previous liver metastases was 1.19 (95% CI 0.90-1.47), with low heterogeneity (I2 4.3%). In individual data meta-analysis, the hazard ratio for these patients was 1.37 (95% CI 1.14-1.64; p more...

Highlights • A resection of a thoracic duct cyst in the right upper mediastinum resulted in post-operative chylopericardium. • Chylous complications in thoracic duct cysts are frequent when intraoperative diagnosis is not reached, such as in cases with anomalous cyst location. • A review on post-surgical chylopericardium is performed, which will provide information for future management of this rare complication., Introduction Thoracic duct cysts are very rare, and diagnosis is often difficult. We report a rare case of chylopericardium following thoracic duct cyst resection. There are no established guidelines on the management of such cases. We reviewed the literature on postoperative complications after thoracic duct cyst resection, and conducted the first thorough review of the etiology and management of chylopericardium in surgical cases. Presentation of case A 54-year-old male presented with cardiac tamponade due to chylopericardium. He had undergone resection of a thoracic duct cyst 2 years previously, which was complicated by postoperative chylothorax. Chyle accumulation resolved with conservative treatment. Discussion Chylothorax is a frequent complication following thoracic duct cyst resection, especially in cases where no intraoperative diagnosis is reached. Diagnosis may be difficult due to anomalous location of the cyst, as in our case. Chylopericardium is rarely reported, and may have occurred in our case because of prior pleurodesis. Chyle accumulation can reportedly be managed with diet restrictions in over half of reported cases, especially in cases of lung or mediastinal tumor resection. Conclusion The most important points highlighted by this rare case of chylopericardium secondary to thoracic duct cyst resection are: 1) pedicles should be ligated in cyst resections, regardless of location; 2) careful assessment in the initial surgery may help identify the point of leakage; 3) low-fat diet is the first choice in the initial management of postoperative chylopericardium, but surgical repair may be considered in cases with no response after > 2 weeks of conservative treatment. more...

Objectives Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy. Methods This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta_num) was also evaluated. Results The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P = 0.004). Before adjusting for the propensity score, the delta_num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P = 0.001); however, after adjustment, there was no difference in the delta_num (thoracoscopy: 0.04, open: 0.19, P = 0.114). Conclusions Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era. more...

OBJECTIVES New chemotherapeutic regimens (i.e. FOLFOX or FOLFIRI with molecular targeted drugs) have improved the prognosis of patients with unresectable or recurrent colorectal cancer. To estimate the prognostic impact of these chemotherapies, we examined the chronological change in survival rates of patients who underwent pulmonary metastasectomy for colorectal cancer metastasis. METHODS Using a large database, we conducted a retrospective, multi-institutional study to collect data of 1223 eligible patients from 26 institutions who had undergone pulmonary metastasectomy with curative intent. We divided those patients who underwent metastasectomy in different time periods according to the major trend of chemotherapy regimens for recurrent colorectal cancer: those who underwent metastasectomy between 1990 and 1999 ( N = 451, Group A), between 2000 and 2004 ( N = 433, Group B) or between 2005 and 2007 ( N = 339, Group C). RESULTS Five-year overall survival rates after metastasectomy were 45% in Group A, 56% in Group B and 66% in Group C ( P more...

The Japanese Murrelet Synthliboramphus wumizusume is listed as a vulnerable species by IUCN, but little information is available on its movements during the non-breeding season. We tracked three murrelets during the non-breeding season using light-level geolocators in 2012–2014. Birds from Eboshijima in Kyushu and Koujima in Shikoku were each tracked for one year, and one bird from Birojima in Kyusyu was tracked for two years. All three moved northward in the Pacific Ocean off Shikoku and Honshu in the spring then to the Pacific and the Sea of Japan off Hokkaido and off Sakhalin. In the fall and early winter two movement patterns were observed: (1) southwestward along the coast of Primorskii, the People's Democratic Republic of Korea, and the Republic of Korea; (2) southwestward movement along the east and south coasts of Honshu and Shikoku. In winter, two stayed in the southwestern part of the Sea of Japan, while the third moved southward into the Pacific Ocean. more...

Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease. We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.3%) patients with a mortality rate of 43.9% (72/164). Univariate and multivariate analyses were carried out to identify possible risk factors of fatal AEIP. We then analyzed the 164 patients who developed postoperative AEIP and identified the preoperative and postoperative risk factors. A multivariate regression analysis identified that the sex, percent vital capacity, neoadjuvant radiation, preoperative history of AEIP, preoperative use of steroids, usual interstitial pneumonia pattern on CT, and surgical procedures were independent preoperative risk factors for death due to AEIP. ILD patients with emphysema somehow showed a lower risk of fatal AEIP than those without emphysema in this study. This study revealed eight risk factors for fatal AEIP. more...

背景．自然気胸を初発とする肺癌は稀であり，自然気胸を契機に発見された微小肺癌症例を経験したので報告する．症例．53歳，男性．2006年5月，呼吸困難感を自覚し，前医を受診した．左自然気胸と診断され，当院紹介となり，胸腔ドレナージが施行された．自然気胸は改善したが，胸部CTにて左S1＋2胸膜直下に胸膜陥入を認め，周囲にGGOを伴った径10 mmの結節影を認めた．2ヶ月の経過観察にて結節影は消退せず，充実部分の増大および胸膜陥入の増悪傾向がみられたため，同年7月胸腔鏡下肺生検を施行し，肺腺癌と診断した．左肺上大区域切除およびリンパ節郭清術を引き続き行い，病理組織学的には腫瘍径7×7×5 mmの，高分化型腺癌pT1N0M0 stage IAと診断した．結論．近年，CT画像の向上とともに微小肺癌が発見される機会が増えつつあり，自然気胸症例といえどもCTの画像評価は，腫瘍性病変を見落とさないように慎重に行うべきである．周囲にGGOを伴う結節性小型病変は，悪性である可能性があり，経過観察にて消退しない場合，肺癌の可能性を念頭において精検すべきである． more...

背景．胸腺癌は比較的稀な腫瘍であり，特に進行期症例では，その治療法は未だ確立されていない．症例．55歳男性．職場健診にて胸部異常影を指摘され当科紹介となった．胸部X線写真では左肺門部に巨大な腫瘤影を認め，CTでは前縦隔から左胸腔内に大きく突出する長径9.5 cmの腫瘤影を認めた．腫瘤は左腕頭静脈，大動脈，肺動脈起始部と接して存在しており，各々への浸潤を疑った．また腫瘍マーカーはAFP：24.9 ng/ml，NSE：26.0 ng/ml，CYFRA：34.0 ng/mlと高値を示しており前縦隔腫瘍の診断にて入院となった．入院後，経皮的吸引細胞診及び組織診を行い，胸腺癌（正岡III期）と診断した．CDDP＋VNRによる化学療法を2コース施行したところ著明な腫瘍の縮小を認め，腫瘍マーカーも正常範囲となったため，腫瘍を左肺上葉とともにen blocに摘出した．病理診断は胸腺未分化癌であった．術後放射線治療及び化学療法を施行し，現在術後12ヶ月が経過したが再発なく，元気に社会復帰している．結論．進行期胸腺癌症例では，術前化学療法に外科切除術の併用が治療の1選択肢となる可能性が示唆された． more...

Introduction:A subset of non–small-cell lung cancer (NSCLC) patients with malignant pleural effusion and/or malignant pleural nodules is now classified as stage IV and is generally considered a contraindication to surgery. However, several reports have demonstrated that the prognosis of patients with pleural carcinomatosis first detected at thoracotomy is relatively favorable. The aim of this study was to describe the results of surgical intervention in NSCLC patients with pleural carcinomatosis in Japan.Methods:In 2010, the Japanese Joint Committee of Lung Cancer Registry conducted a nationwide registration of lung cancer patients who underwent surgery in 2004. Using this database, we performed a retrospective study focused on pleural carcinomatosis. We examined the clinicopathological features, the current status of therapy, and surgical outcomes in patients with pleural carcinomatosis.Results:Among the 11,420 registered NSCLC patients, 329 (2.9%) patients had pleural carcinomatosis. The median survival time and 5-year survival rate of 313 patients without other metastatic disease were 34.0 months and 29.3%, respectively. Primary tumor resection was performed in 256 (81.8%) patients, and macroscopic complete resection was achieved in 152 (48.6%) patients, with 5-year survival rates of 33.1% and 37.1%, respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status (p < 0.001), best stage nodal status (p = 0.002), and the presence or absence of gross residual tumor (p = 0.013) were independent predictors of survival.Conclusion:In our surgical registry for NSCLC, patients with pleural carcinomatosis accounted for 2.9%, and macroscopic complete resection for them was associated with better survival. more...

The kumatakas’ breeding success ratio of the western Hiroshima prefecture has fallen rapidly as another of bird of prey reported since 1990s. The author has studied the relation between the success ratio and the vegetation in the home range for 25 years to make clear the reasons why its ratio have dropped recently. Firstly the author has confirmed that the ratio has kept near 100% in 1980s, and its level have fallen about 50% in 1990s and many kumataka couldn’t breed in 2000s. Secondly the author has confirmed the home range of three site of the kumataka. The area of site A is 635 hectares, site B is 839 hectares and site C is 1,108 hectares. Thirdly vegetation within the range divided 10 categories and data would be related to the success ratio have been collected. The author has analyzed these data and divided the usable vegetation (forest) and un‐usable one. The former categories consisted mainly under 10 years artificial forest, broad leaf forest, harvested area and so on, the latter categories contained mainly over 10 years artificial forest and forest without care. Forest cares, such as thinning, pruning and tending are very important roles to keep their success ratio. Finally the author made clearly conclusion as follow. (1) Wide area of the under 10 year artificial forests and broad‐leaved forests were existed in 1980s. (2) Un‐usable forest area for the kumataka have increased and exceeded usable forest area. (3) Un‐usable area of site A has counted less than 400 hectares since 1990s. (4) Usable area should be kept over 400 hectares for maintenance breeding success ratio. (5) Usable area needs over a half of the home range. (6) If forestry activities, such as harvesting, thinning, pruning and so on, shall be carried out the level of 1980s, its ratio shall go up to higher level like the 1990s. (7) Rehabilitation of forestry is the important matter for the more...

Acupuncture needles can cause non-tuberculosis mycobacteria (NTM) infection on the skin, but there are no reports that acupuncture needles inserted into the lung have caused lung NTM infection. A 63-year-old woman, who underwent removal of a broken acupuncture needle inserted into the lung nine years ago, was admitted with nodules in the right lung. The shadow was positioned where the needle had existed. Partial lung resection of the right lower lobe was performed, and the resected area showed caseous necrosis histopathologically. Furthermore, Mycobacterium avium was cultured from the specimen. When abnormal lung shadows are located where a resected foreign body appeared, NTM infection should be considered. more...

背景. 近年, 悪性腫瘍の診断において, FDG-PETの有用性に関する報告が多数みられるようになっている. 我々は, 原発性肺癌術後の再発例にFDG-PETを施行した症例を経験したので報告する. 症例. 65歳, 女性. 2000年2月, 右原発性肺癌にて右上葉切除術を施行し, 同年9月, 早期胃癌にて手術を行った. 2001年5月頃より, 腫瘍マ-カ-の上昇が明らかとなり, 当科を受診した. 胸部CTでは, 右胸腔内に椎体に接して三日月状の陰影が存在していたが積極的に悪性病変を示唆する所見に乏しく, また, 腹部CT, 腹部超音波検査, 頭部MRI, 骨シンチグラム, 上部消化管内視鏡などの検査を行ったが明らかな異常所見は認められなかった. そこでFDG-PETを施行すると, 右心房背側に強い集積を認め, 胸部CTで認められた陰影が存在する部位と一致していた. 以上より, この陰影が再発病巣と判断し, 手術を施行した. 病巣は肺内に存在し, 病理組織所見は, 2000年2月に切除された右上葉原発の肺癌の組織像と類似しており, 肺癌の再発と診断された. 結論. 原発性肺癌術後の再発に対して; その局在診断にFDG-PETがきわめて有用であった more...

CTLA-4 is expressed on the surface of activated T cells and negatively regulates T cell activation. Because a low-level expression of CTLA-4 on the cell surface is sufficient to induce negative signals in T cells, the surface expression of CTLA-4 is strictly regulated. We previously demonstrated that the association of CTLA-4 with the clathrin-associated adaptor complex AP-2 induces internalization of CTLA-4 and keeps the surface expression low. However, the mechanism to induce high expression on the cell surface upon stimulation has not yet been clarified. To address this, we investigated the intracellular dynamics of CTLA-4 by analyzing its localization and trafficking in wild-type and mutant CTLA-4-transfected Th1 clones. CTLA-4 is accumulated in intracellular granules, which we identified as lysosomes. CTLA-4 is degraded in lysosomes in a short period, and the degradation process may serve as one of the mechanisms to regulate CTLA-4 expression. Upon TCR stimulation, CTLA-4-containing lysosomes are secreted as proven by the secretion of cathepsin D and β-hexosaminidase in parallel with the increase of surface expression of CTLA-4 and lysosomal glycoprotein 85, a lysosomal marker. These results suggest that the cell surface expression of CTLA-4 is up-regulated upon stimulation by utilizing a mechanism of secretory lysosomes in CD4+T cells. more...

The Japanese Murrelet Synthliboramphus wumizusume breeds in the Japanese islands. Murrelets have been observed around their breeding islands only during the breeding season. Their distribution and ecology during the non-breeding season are not known because the birds are not seen outside the breeding season. I confirmed the presence of several juveniles and adults in the western Seto Inland Sea. There are no previous records of Japanese Murrelets in this area, as the habitat was thought to be unsuitable. The current study provided the first observations of groups of juveniles and the first observation of adults outside the breeding season. The western part of the Seto Inland Sea was therefore confirmed as the habitat of non-breeding Japanese Murrelets. The observations provide information on the ecology and foraging habitat of the Japanese Murrelet during the non-breeding season. This should be valuable when considering ways of conserving the species. more...

Ocean-scale monitoring of pollution is challenging. Seabirds are useful indicators because they travel over a broad foraging range. Nevertheless, this coarse spatial resolution is not fine enough to discriminate pollution in a finer scale. Previous studies have demonstrated that pollution levels are higher in the Sea of Japan and South and East China Seas than the Northen Pacific Ocean. To test these findings in a wide-ranging animal, we tracked streaked shearwaters (Calonectris leucomelas) from four islands in Japan using global positioning system (GPS) and measured persistent organic pollutants (POPs) in the oil of their preen glands. The POPs did not change during 6 to 21 days when birds from Awashima were foraging only in the Sea of Japan, while it increased when they crossed to the Pacific through the Tsugaru Strait and foraged along the eastern coast of Hokkaido where industrial cities occur. These results indicate that POPs in the oil reflect relatively short-term exposure. Concentrations of POPs displayed greater variation among regions. Total polychlorinated biphenyls were highest in birds foraging in a small area of the semiclosed Seto Inland Sea surrounded by urbanized coast, p,p'-dichlorodiphenyltrichloroethane (DDT) was highest in birds foraging in the East China Sea, and total hexachlorocyclohexanes were highest in birds foraging in the Sea of Japan. All were lowest in birds foraging in the Pacific. This distribution of POPs concentration partly agrees with previous findings based on mussels, fish, and seawater and possibly reflects the mobility and emission sources of each type of POP. These results highlight the importance of information on the foraging area of highly mobile top predators to make them more effective monitors of regional marine pollution. more...

術後鎮痛の目的で, バルーンリザーバー式持続法入器による鎖痛薬硬膜外持続投与法の有用性を間欠投与法と比較検討した.対象は当施設において開胸術をうけた患者46例で, A群24例, B群22例に無作為に割り付けた.ブプレノルフィンを生食水にて希釈し硬膜外カテーテルよりA群ではバルーソリザーバー式持続注入器にて持続投与, B群では12時間毎に間欠投与した.ペインスコアの平均ではA群1.62±0.19に対し, B群は1.79±0.24とB群が有意に高かった (p more...

We aimed to identify prognostic factors after pulmonary metastasectomy for colorectal cancer and propose the clinical application of them. Furthermore, we endeavored to provide a rationale for pulmonary metastasesectomy.Several prognostic factors have been proposed, but clinical application of them remains unclear. Moreover, there is no theoretical evidence that pulmonary metastasectomy is indicated for colorectal cancer.We retrospectively analyzed 1030 patients who underwent pulmonary metastasectomy for colorectal cancer from 1990 to 2008. Prognostic factors were identified and the relationship of recurrent sites after pulmonary resection to pulmonary tumor size was assessed.Overall 5-year survival was 53.5%. Median survival time was 69.5 months. Univariate analysis showed tumor number (P0.0001), tumor size (P0.0001), prethoracotomy serum carcinoembryonic antigen (CEA) level (P0.0001), lymph node involvement (P0.0001), and completeness of resection (P0.0001) to significantly influence survival. In multivariate analysis, all remained independent predictors of outcome. In patients whose recurrent sites extended downstream from the lung via hematogenous colorectal cancer spread, pulmonary tumor size was significantly larger than in those with recurrent sites confined to the lung and regions upstream from the lung.We should utilize these prognostic factors to detect patients who might benefit from surgery. Therefore, we should periodically follow up advanced colorectal cancer patients by chest computed tomography to detect small pulmonary metastases before serum CEA elevation. Metastases to the lung or organs upstream from the lung are regarded as semi-local for colorectal cancer. This concept provides a rationale for validating surgical indications for pulmonary metastases from colorectal cancer. more...

Castleman’s disease (CD) is rare and difficult to diagnose preoperatively. We report two similar cases of hyaline vascular type CD diagnosed preoperatively using different modalities. In the first case, a biopsy specimen taken during diagnostic thoracoscopy revealed lymphatic structure suggestive of CD. In the second case, endobronchial ultrasound-guided transbronchial needle aspiration enabled sampling of histological cores for histological diagnosis. In both cases, the final diagnosis was established by surgical resection. more...

Aberrant methylation of promoter CpG that causes silencing of tumor suppressor genes (TSGs) may play a key role in the carcinogenesis of many cancer types. RASSF1A, regarded as a TSG, has been extensively studied in lung cancer and other malignant tumors, whereas RASGRF2 has only been reported to possibly play a role in the pathogenesis of pancreatic cancer cell lines. The aims of our study were to i) determine the methylation profile of RASGRF2 and ii) compare the methylation profiles of RASGRF2 with RASSF1A in lung cancer. We examined RASGRF2 expression by reverse transcription PCR and aberrant methylation of RASGRF2 by methylation-specific PCR in lung cancer cell lines. Loss of RASGRF2 expression was presented in 36% lung cancer cell lines while aberrant methylation of RASGRF2 was present in 30% (3/10) non-small cell lung cancer (NSCLC) cell lines and in 25% (1/4) small cell lung cancer (SCLC) cell lines. The concordance between loss of expression and aberrant methylation of RASGRF2 was 86% (12/14). RASGRF2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all four cell lines tested that downregulated RASGRF2 expression. Among primary NSCLC, RASGRF2 and RASSF1A methylation was observed in 34% (39/114) and 39% (44/114) of cases respectively, while it was observed in only 7% (4/57) and none of the corresponding non-malignant lung tissue. There is no correlation between RASGRF2 and RASSF1A methyl-ation status. Both RASGRF2 and RASSF1A methylation did not associate with clinical characteristics. Frequent methylation and silencing of RASGRF2 in tumor cells may play an important role, different from that of RASSF1A, in the carcinogenesis of NSCLC. more...

Thymic carcinoma, which is a rare epithelial neoplasm of the thymus gland, is different from thymoma in its clinical and pathological features. To clarify the mechanism underlying the aggressive behavior of thymic carcinoma, we examined the clinicopathologic features, aberrant methylation patterns of the tumor suppressor genes, and epidermal growth factor receptor (EGFRs) mutation in both thymic carcinomas and thymomas. Clinical data of 11 thymic cancers and 13 thymomas were reviewed. Resected samples of 5 thymic cancers and 6 thymomas selected from 24 cases were used for methylation and mutation studies. Positive tumor markers were more frequent in thymic cancers than in thymomas (p=0.0233), and the methylation index, which reflects the overall methylation pattern, was significantly higher in thymic carcinomas (p=0.0053). No tumors showed a mutation of EGFR, KRAS, and HER2. Thymic carcinoma is distinct from thymoma not only with respect to clinicopathological features, but also aberrant methylation patterns of the tumor suppressor genes. more...

For non-small cell lung cancer (NSCLC), which is refractory for both platinum-based chemotherapy and docetaxel, no standard regimen has yet been established. We conducted a phase I study of a combination of vinorelbine and gemcitabine as third-line chemotherapy for refractory NSCLC to determine both the maximum tolerated dose (MTD) and the recommended dose (RD). Twenty patients with NSCLC refractory for both platinum and docetaxel were enrolled, and all patients were eligible for this phase I study. Cohorts of three to seven patients received vinorelbine at doses ranging from 20 to 25 mg/m(2), and gemcitabine at doses ranging from 600 to 1000 mg/m(2), on days 1 and 8 every 3 weeks. The dose-limiting toxicities were treatment delay, serum gammaGTP elevation, diarrhea and cerebral infarction, which were resolved without serious sequela, and there was no treatment-related death. The MTD was vinorelbine at 25 mg/m(2) and gemcitabine at 1000 mg/m(2) and the RD was vinorelbine at 25 mg/m(2) and gemcitabine at 800 mg/m(2). The median overall survival time was 6.8 months for all 20 patients eligible. As third-line chemotherapy, the combination of vinorelbine and gemcitabine was feasible and promising for NSCLC which is refractory for both platinum and docetaxel. more...

Thymic carcinoma is a rare mediastinal neoplasm with a poor prognosis due to delayed diagnosis and highly malignant behavior. To evaluate 7 serum tumor markers and the outcome of treatment, 11 stage III-IVb thymic carcinomas undergoing multimodality treatment were reviewed. High levels of serum CYFRA21-1 were detected in 5 patients (45%) and correlated with the progression of disease. Of the patients, 6 underwent surgery. The median survival time was 38.4 months, and the 5-year survival rate was 15.6%. The metastatic stage (IVb) and treatment without resection were significantly associated with poorer overall survival (p=0.0034 and p=0.0041, respectively). Our data demonstrated that serum CYFRA21-1 may represent a potential new biomarker in thymic carcinoma. Stage may provide a basis for prognosis in stage III-IVb thymic carcinoma, and resection is one of the most important parts of multimodality treatment for advanced thymic carcinoma. Effective neoadjuvant treatment is therefore essential. more...

The tumor-draining lymph node tissue (TDLT) of lung cancer patients generated killer cells specific to autologous tumor cells when cultured with low dose IL-2. This production of killer cells lasted as long as 2 months after the initiation of the culture (productive phase). Even after this productive phase, TDLT supported the generation of the killer cells when these were co-cultured with peripheral blood lymphocytes (PBL) from the same patients. We tried to analyze the mechanisms of this production of killer cells from TDLT.TDLT, tumor tissues as well as PBL were obtained from primary lung cancer patients and cultured in vitro. Cell growth, cell surface markers and specific cytotoxic activity of the lymphocytes were examined.The majority of the cells from TDLT or TDLT+ PBL co-culture (TDL-Pb) were CD3-positive T cells (89-99%) and a 51Cr-releasing assay showed that these cells had a stronger cytotoxic activity against autologous tumor cells than cells from PBL cultured with IL-2. Their activity against allogeneic MHC incompatible target cells was not, however, elevated. Cytotoxic activity against autologous tumor cells was blocked by anti-HLA class 1 (52.0%), class 11 (47.9%) and CD8 (46.8%) antibodies, but not by anti-CD56 antibody. The treatment of TDLT with anti-CD8, CD4, CD80 and CD83 all together completely abrogated the ability of TDLT to generate killer cells, with one of these antibodies it did so partially, while treatment with anti-CD56 antibody failed to do so at all.These results collectively suggest that TDLT contains tumor antigen-pulsed DCs as well as precursors of specific killer T cells and gives rise to the generation of killer cells when cultured in a low dose of IL-2. more...

Background Spontaneous regression of metastatic renal cell carcinoma is rarely observed. Case presentation Metastatic renal cell carcinoma was identified in a 70-year-old male using computed tomography-guided percutaneous needle biopsy. Two months after the diagnosis, a partial resection of the sternal bone was performed. Pathological examination revealed granulated tissue with bleeding and necrosis but no carcinogenic cells. Conclusion We report a pathologically identified case in which a sternal bone metastasis that was noticed two years after radical nephrectomy regressed completely and spontaneously. more...

FBN2, a large modular extracellular matrix glycoprotein, is known to be a key component of human elastic fiber. A loss of FBN2 expression due to promoter methylation was recently identified in pancreatic cancer. We examined FBN2 expression by reverse transcription PCR and aberrant methylation of FBN2 by methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2 was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines, but it absent in small cell lung cancer cell lines. The concordance between loss of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell lines. FBN2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression. Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7% (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2 methylation was detected even in patients with early stage disease, it occurred frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis, invasion, and metastasis of NSCLC. more...