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症例は71歳女性．他院にてCEA上昇と大動脈傍リンパ節腫大とを指摘され，当科へ紹介となった．全身精査にて大動脈傍リンパ節の腫大以外に異常所見なく，開胸リンパ節生検を施行した．大動脈傍リンパ節1個のみが1×2cm大に腫大し，周囲への浸潤は全くなく，容易に摘出可能だった．その他のリンパ節には腫大を認めず，明らかな肺内・肺門部病変も認めなかった．病理組織学的検査にて未分化癌との診断だった．術後，化学療法2クールと縦隔への同時放射線療法60Gyを追加した．臨床経過や手術所見から，リンパ節が原発の癌である可能性が示唆された．原発不明縦隔リンパ節癌に対しては，診断と治療を兼ねて積極的に手術での完全切除を行い，必要に応じて化学療法・放射線療法を追加することで予後の改善が得られると考えられる．

症例1は19歳女性．動悸を自覚し，甲状腺腫大および前縦隔腫瘤を指摘された．甲状腺腫大は機能検査からバセドウ病と診断され，抗甲状腺剤を開始した．前縦隔腫瘍はCT下吸引細胞診からは胸腺腫も否定できなかったが，画像診断も踏まえ胸腺過形成が強く考えられた．甲状腺機能亢進症に伴う胸腺過形成と判断し経過観察とした．抗甲状腺剤内服から3ヵ月後には胸腺の縮小を認めた．症例2は52歳女性．前縦隔腫瘤を指摘された．画像上，胸腺はびまん性肥大であり，甲状腺の軽度腫大も認めた．甲状腺機能検査を行い，バセドウ病の診断を得た．甲状腺機能亢進症に伴う胸腺肥大と判断し，バセドウ病の治療を開始した．3ヵ月後には胸腺の縮小を認めた．甲状腺機能亢進症に合併した胸腺肥大では，外科的処置の前に抗甲状腺剤の投与による画像上の経過観察も可能と考えられる．無用な手術を回避するためにも呼吸器外科医は，この病態を知っておく必要がある．

当科において非小細胞肺癌に対し施行した肺全摘術について検討した．1993年3月から2003年7月までに肺全摘術を施行した45例を対象とした．患者背景は男性36例，女性9例で，病期はIII期以上が33例であった．また組織型では扁平上皮癌が28例と最も多かった．手術時間は平均281.6分で，術後平均在院期間は46.8日であった．一方術後合併症は12例に認めたが気管支断端瘻はなく，術関連死は1例であった．5年生存率は全体で32.1％で，I期とII期をあわせると22.2％，IIIA期は30.4％であった．肺全摘術において合併症の頻度は許容範囲であり，予後も肺葉切除に対し遜色はなかった．

当科において呼吸リハビリ後に肺切除を施行した低肺機能症例について検討した．2000年11月から2003年8月までに肺切除を施行した術前FEV1.0≦1.0lの症例12例を対象とした．患者背景は男性9例，女性3例で，年齢は65歳以上が11例であった．術前呼吸リハビリは平均14.8±8.7回施行されており，VC，FEV1.0いずれも有意に改善していた（p＝0.0145，p＝0.0112）．術後合併症，術関連死は認められず，在宅酸素療法を必要とした症例もなかった．低肺機能症例において，術前呼吸リハビリは有用である可能性が示唆された．

悪性胸膜中皮腫に対し，GEM＋CDDPの術前化学療法後に胸膜肺全摘術を行った2症例を経験したので報告する．症例1は50歳男性．症例2は52歳男性．2症例ともに組織型は上皮型であり，IMIG病期分類にてc-II期であった．GEM＋CDDPの術前化学療法を行い，評価は症例1がPRで，症例2はSDであった．胸膜肺全摘術を行い2症例とも完全切除であった．術後合併症はなく，現在術後30ヵ月と13ヵ月で無再発生存中である．悪性胸膜中皮腫に対し，GEM＋CDDPによる術前化学療法後に外科療法を加えることで有望な成績が得られる可能性はあると考えられた．

症例は63歳，女性．検診の胸部レントゲンで異常陰影を指摘されたため，近医を受診．胸部CTで右肺S6に径2cm大の辺縁不整な空洞を伴った結節影が認められ，また，FDG-PETで同部位に一致して異常集積像を認めた．原発性肺癌もしくは同じくFDG-PETで異常集積を認め発見された乳癌の肺転移を疑い，診断・治療目的で開胸下肺部分切除術を施行し，術中迅速病理で肺犬糸状虫症と診断された．肺犬糸状虫症では胸部CT所見が肺癌と類似し，またFDG-PETで異常集積像を示すことがあるため，悪性疾患との鑑別が困難となる場合がある．胸部異常陰影の鑑別疾患の1つとして本症の存在を念頭に置くことが重要と考えられた．

We investigated whether beta-amyloid (Abeta)-like immunoreactivity was seen in the brains of newborn piglets. The immunoreactivity for Abeta(1-42) and Abeta(1-40) proteins, but not Abeta precursor protein, was present in CD68-positive perivascular cells of the hippocampus and in parts of the meninges. It was colocalized with immunoreactivity for receptor for advanced glycation end product and tumor necrosis factor-alpha. The protein with a molecular mass of 27 kDa, which was recognized by the Abeta antibodies, was identified as triosephosphate isomerase (TPI) with sequence homology to Abeta peptides by N-terminal amino acid sequencing, mass fingerprint analysis using matrix-associated laser desorption/ionization mass spectrometry, and Western blotting. Western blotting assay also revealed that detectable expression of Abeta proteins were not seen in the piglet brains. These findings indicate that TPI with sequence homology to Abeta peptides accumulates in perivascular cells of the microglia/macrophage lineage located around arterial vessels of the newborn piglet hippocampus.

Although bevacizumab has several adverse effects, pneumothorax is rare. This is the first case of initial treatment using an Endobronchial Watanabe Spigot (EWS) for pneumothorax after bevacizumab-containing chemotherapy. A 56-year-old woman with recurrent breast cancer was treated with bevacizumab. Pneumothorax occurred 6 days after the last administration of bevacizumab. The pneumothorax failed to resolve after the chest tube drainage. This was because the bronchopleural fistula formed at the site of the subpleural metastatic lesion. Patient was in need of a surgical repair of the bronchopleural fistula, which could not be carried out due to the recent bevacizumab administration. After the insertion of the EWS, the air leak stopped immediately. A lobectomy was successfully performed for the recurrent pneumothorax and for the resection of the metastatic lung lesion; at a most appropriate duration since the chemotherapy. EWS is useful as the initial palliation of pneumothorax after the treatment with medication causing delayed wound healing.

Video-assisted thoracic surgery( VATS) has been utilized worldwide for treatment of thoracic disease in recent years. Then, in most VATS, the thoracoscope was handled by young surgeons consequently. In VATS, a role of the scopist is very important, because if there is no consensus of verticality and horizontality on the monitor among operator, assistant and scopist, it is difficult to perform the surgery smoothly. Therefore, it is important for young surgeons to improve their skills as scopist. However, there are few models of verticality and horizontality on the monitor and thoracoscope techniques of VATS. We present our consensus of verticality and horizontality on the monitor in the standard 3-ports VATS by right upper lobectomy and left upper lobectomy.

Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides used during DNA synthesis. It is also a cellular target for gemcitabine (GEM). Overexpression of RRM1 is reportedly associated with resistance to GEM and the poor prognosis for many types of malignant tumours. Aim of the present study is to establish gene therapy against RRM1-overexpressing tumours.An adenoviral vector that encoded a short hairpin siRNA targeting the RRM1 gene (Ad-shRRM1) was constructed. Two RRM1-overexpressing non-small cell lung cancer (NSCLC) lines, MAC10 and RERF-LC-MA, were used. Finally, a human tumour xenograft model in nude mice was prepared by subcutaneously implanting tumours derived from RERF-LC-MA cells.Ad-shRRM1 effectively downregulated RRM1 mRNA and protein in both types of NSCLC cells and significantly reduced the percentage of viable cells as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (p0.005). Caspase 3/7 analysis revealed that transfection with Ad-RRM1 increased the percentage of apoptotic cells in culture containing either type of RRM1-overexpressing cell (p0.001). Treatment with Ad-shRRM1 exerted a potent antitumour effect against the RRM1-overexpressing RERF-LC-MA xenografts (p0.05). Furthermore, Ad-shRRM1-mediated inhibition of RRM1 specifically increased sensitivity to gemcitabine of each type of RRM1-overexpressing tumour cell. Combination treatment with Ad-shRRM1 and GEM exerted significantly greater inhibition on cell proliferation than Ad-shRRM1 or GEM treatment alone.RRM1 appeared to be a promising target for gene therapy, and Ad-shRRM1 had strong antitumour effects, specifically anti-proliferative and pro-apoptotic effects, against NSCLC cells that overexpressed RRM1. Combination therapy with Ad-shRRM1 and GEM may become a new treatment option for patients with NSCLC.

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P

Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild-type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53-dependent pathways.

We examined age-related changes in the blood-brain barrier (BBB) of neural cell-specific hypoxia inducible factor-1alpha (HIF-1alpha) deficient mice, which showed hydrocephalus with neuronal cell loss, to investigate an effect of neural cell-specific HIF-1alpha deficiency or hydrocephalus on vascular function. Vascular permeability of horseradish peroxidase (HRP) and binding of cationized ferritin (CF) particles to the endothelial cell luminal surface, as a marker of glycocalyx, were investigated. The thickness of CF-labeled glycocalyx was significantly decreased in the cortex in mutant mice compared with that of control mice, although it was not paralleled by increased vascular permeability. In addition, strong staining for HRP was seen around vessels located along the hippocampal fissure in 24-month-old mutant mice. The reaction product of HRP appeared in an increasing number of the endothelial cell abluminal vesicles and within the thickened basal lamina of arterioles in the hippocampus, showing increased vascular permeability. There were no leaky vessels in 10-week-old mutant mice or 10-week-old and 24-month-old control mice. These findings suggest the necessity of two factors, aging and hydrocephalus, for BBB dysfunction in HIF-1alpha deficient mice.

Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder that is usually diagnosed on the basis of high resolution computed tomography (HRCT) findings. It is unclear whether CPFE is an independent prognostic factor in patients with non-small-cell lung cancer (NSCLC). Therefore, we conducted a retrospective analysis to assess the impact of CPFE on the prognosis of patients with completely resected NSCLC.We retrospectively reviewed 365 patients diagnosed with NSCLC who underwent complete resection at the Tazuke Kofukai Medical Research Institute, Kitano Hospital between January 2007 and December 2012. Patients were classified into four groups according to chest HRCT findings: those with CPFE, those with fibrosis, those with emphysema or those with a normal lung except for the presence of a tumour. We evaluated disease-free survival (DFS) and overall survival (OS) using the two-tailed log-rank test and the Cox proportional hazards model.The two-tailed log-rank test demonstrated that the four groups had significantly different DFS and OS (P0.01). In the multivariate analysis, CPFE was found to be an independent prognostic factor for DFS and OS compared with a normal lung [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.24-5.13; P = 0.01 and HR: 4.53; 95% CI: 1.91-10.7; P0.01, respectively].CPFE is a significant, unfavourable prognostic factor for NSCLC patients after curative resection.

An increased mean platelet volume (MPV) is an early marker of platelet activation. MPV was also shown to be associated with the pathophysiological characteristics of various types of cancer. A previous study demonstrated that MPV was significantly associated with the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC). However, there has been no analysis of the prognostic effect of MPV on patients with resected NSCLC. The aim of this study was to evaluate the contribution of MPV to the survival of patients with completely resected NSCLC. We retrospectively analyzed 308 consecutive patients with NSCLC who underwent curative resection at Kitano Hospital. The associations between MPV and clinicopathological factors were assessed. We also evaluated the effect of MPV on survival, using the two-tailed log-rank test and the Cox proportional hazards model. A MPV value of 8.50 fl was considered to be the optimal cut-off value for prognosis. A low MPV was not associated with any other clinicopathological factors. The two-tailed log-rank test demonstrated that patients with a low MPV experienced a shorter disease-free survival (DFS) and overall survival (OS) (P=0.011 and 0.001, respectively), compared to those with a high MPV. The multivariate analysis demonstrated that a low MPV was an independent unfavorable prognostic factor for DFS and OS [hazard ratio (HR)=1.713; 95% confidence interval (CI): 1.070-2.742, P=0.025; and HR=2.835; 95% CI: 1.304-6.163, P=0.009, respectively)]. Therefore, we demonstrated that a low MPV predicted an unfavorable prognosis in patients with NSCLC following curative resection.

We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P

症例は67歳男性. 右背部腫瘤に気付き, 他院にて生検後, 平滑筋肉腫と診断され, 精査加療目的に当科紹介入院となった. 胸部CT, MRIにて腫瘍の大きさは20×15mmで, 右広背筋に局在すると判明した. 手術は, 頭側に5cm, 尾側に10cmの距離を取り, 広範筋筋膜と前鋸筋を含めて切除した. 術後, 50Gyの放射線療法を追加した.平滑筋肉腫は, 主に後腹膜や腸間膜に発生し, 皮膚や皮下組織に発生するものはまれである. 今回我々は, 広背筋に発生したまれな平滑筋肉腫の1例を経験した.

症例は61歳, 女性. 胸部CTで, 左肺S6に空洞を伴う腫瘤陰影と左肺S10に腫瘤陰影を認め, 肺門リンパ節の腫大も指摘された. PET検査で左下葉及び肺門と縦隔にFDG (fluorodeoxyglucose) の集積を認めた. CEAも高値で, 左下葉の原発性肺癌を疑いTBLBを施行するも悪性所見は認められなかった. 左肺S10の腫瘤陰影に対しCT下肺生検を施行したが確定診断には至らなかった. 消化管内視鏡検査を含む全身精査では他臓器に異常は認めなかった. 診断確定のために開胸肺生検を行い, 左肺S10の腫瘤は術中迅速病理で梗塞巣と診断された. 大動脈下リンパ節と気管分岐部リンパ節をサンプリングしたが, それぞれ低分化癌, 及び中分化腺癌と診断された. 肺門・縦隔リンパ節癌と考え, 術後同時放射線化学療法を施行した. 本症例は肺化膿症と肺梗塞のため画像所見からは左下葉原発の肺癌との鑑別が困難であり, 開胸生検で肺門・縦隔リンパ節癌と診断された.

症例は54歳, 男性. 左上葉原発c-T2N2M0 stage IIIAの扁平上皮癌に対し同時化学・放射線療法後に左上葉切除術 (ND2a) を施行した. 照射範囲であった残存左下葉S6を中心に放射線肺炎が出現し, ステロイドパルス療法を行った. その後病巣は空洞化し, 感染を伴い肺化膿症となった. 感染コントロールのため, 低圧持続胸腔ドレナージを行ったが肺瘻が続くため, 手術を行った. 開胸所見では膿気胸の状態であり, 肺剥皮術と術後胸膜癒着術も施行した. しかし肺瘻及び感染巣の沈静化には至らず, 全膿胸として胸郭形成術, 大網及び腹直筋遊離筋弁充填術を行った. 本症例は, 同時化学・放射線療法に手術を行い, そこに放射線肺炎から肺化膿症を合併し膿胸にまで進展した. ステロイド療法も加わり, 患者本来の治癒力が低下している状態であり, 治療することに難渋した症例であった.

A 64-year-old woman presented with a sessile solitary fibrous tumor in the right thoracic cavity. She had undergone 2 solitary fibrous tumor resections 7 and 20 years previously. The latest histological findings were identical to the previous, and pathologically benign. However, we clinically classified the tumors as malignant because of repeated relapse. The tumor and extrapulmonary structures should be resected at the time of recurrence.

A 47-year-old woman was admitted with recurrent pneumothorax. Preoperative chest computed tomography (CT) showed multiple lung nodules and cysts bilaterally. She had undergone enucleatic myomectomy 12 years earlier. Video-associated thoracoscopic biopsy was performed. Histopathologically, there were bulla-like dilated cystic changes, the walls of which showed spindle cell proliferation, causing pneumothorax. Hormone therapy was started after benign metastasizing leiomyoma resection; pneumothorax has not recurred in 7 months. Multiple residual lung nodules have decreased or disappeared on CT.

Motility-related protein-1 (MRP-1/CD9) is a transmembrane glycoprotein that has been implicated in cell adhesion, motility, proliferation, and differentiation. It has a functional role as a tumor metastatic suppressor. During tumor progression, a reduction of MRP-1/CD9 gene expression results in tumor cells with a high metastatic potential. However, the mechanism of action of MRP-1/CD9 is still unclear. We studied changes of gene expression in relation to MRP-1/CD9 gene transduction into tumor cell lines, HT1080 and A549, using microarray assays and real-time PCR. Consequently, we have demonstrated that MRP-1/CD9 gene transduction can downregulate expression of several Wnt family genes, such as Wnt1, Wnt2b1 and Wnt5a, and their target genes, including WISP-1 (Wnt-1 induced secreted protein 1), WISP-3, c-Myc, vascular endothelial growth factor-A, and matrix metalloproteinase-26. Western blot analyses also showed that MRP-1/CD9 gene transduction downregulated expression of Wnt1 protein and its target proteins. In addition, a neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited the downregulation of Wnt signal pathways in MRP-1/CD9-transfected cells. The present study has revealed that the MRP-1/CD9 signal is located upstream of the Wnt signal pathways. Therefore, MRP-1/CD9 could suppress cell transformation including epithelial to mesenchymal transition through downregulation of Wnt1, and might suppress tumor metastasis through downregulation of Wnt5a.

Objective: The postoperative development or exacerbation of interstitial pneumonia (IP) in lung cancer patients often affects prognoses. We analyzed the patients who suffered from IP after surgery, to determine treatment and prevention of IP. Methods: One hundred and one consecutive patients who underwent resection were enrolled in the study. Clinical background and post-, perioperative course were compared between patients who developed IP and those who did not. Results: If IP developed or was exacerbated, steroid pulse (SP) therapy, immunosuppressant (IS) therapy or nitric oxide (NO) inhalation therapy was employed. Of 101 patients, 20 had suffered from IP before surgery. In four of these 20 (20%), postoperative exacerbation was observed. SP therapy was given to all patients. To one patient, IS and NO therapy were added. Three of the four patients died. 81 patients did not have IP; three of them (3.7%) developed IP after the operation and were treated with SP therapy. To one patient, IS and NO therapy were added. Two of the three patients died. IP development or exacerbation after surgery was observed in seven of 101 patients, and five of them died. It was significantly more frequent in patients with poorly differentiated squamous cell carcinoma, restrictive change in pulmonary function tests, and a low percentage diffusion capacity for carbon monoxide. Postoperative development or exacerbation was observed in patients who had undergone lobectomy or pneumonectomy. Conclusions: Postoperative IP is a serious complication. Further studies are needed to determine definitive therapeutic options. For the patients with the aforementioned risk factors, limited surgery must be considered.

A causative role of blood-brain barrier (BBB) impairment is suggested in the pathogenesis of vascular dementia with leakage of serum components from small vessels leading to neuronal and glial damage. We examined the BBB function of young adult spontaneously hypertensive rats (SHR) in order to determine earlier changes in the BBB in chronic hypertension. SHR and stroke-prone SHR (SHRSP) were injected with horseradish peroxidase (HRP) as an indicator of BBB function and compared with Wistar Kyoto rats (WKY). The brain tissues were further examined with cationized ferritin, a marker for evaluating glycocalyx. The staining for HRP was distributed around the vessels in the hippocampal fissure of SHR and SHRSP, but not in WKY. With electron microscopy, the extravasated reaction product of HRP appeared in abluminal pits of the endothelial cells of arterioles and within the basal lamina in the hippocampus, but not the cerebral cortex, of SHR and SHRSP. On the contrary, the reaction product of HRP was never seen in the abluminal pits of the endothelial cells or the basal lamina of vessels in WKY. The number of cationized ferritin particles binding to the endothelial cells of capillaries was decreased in the hippocampus of SHR and SHRSP, while the number decreased in the cerebral cortex of SHRSP compared with those in WKY. However, the cationized ferritin binding was preserved in the endothelial cells of the arterioles with an increased vascular permeability. These findings suggest that the chronic hypertensive state induces BBB dysfunction in the hippocampus at an early stage.

症例は28歳, 男性.職場健診で胸部異常陰影を指摘された.近医で気管支鏡下肺生検を行うも診断確定には至らず, 精査加療目的で当科紹介入院となった.胸部CT検査では1t.B8aと1t.B8bの間の領域に長径12mm大の腫瘤陰影を認めた.画像上肺過誤腫を疑ったが肺癌も否定できず手術を施行した.腫瘤の位置から部分切除が困難で, 核出術を行った.迅速病理で粘表皮癌と診断され, 引き続き左肺下葉切除術 (ND1) を施行した.本症例は画像所見から肺過誤腫と鑑別を要した点と, 粘表皮癌でも稀な末梢発生であった点で興味ある症例と考え報告した.

症例は66歳女性.気管支喘息の経過中に胸部X線像上, 右下肺野に結節影を指摘され当院を紹介された.胸部CTで右中葉S4からS5にかけて周囲に淡い浸潤影および胸膜嵌入像を伴う境界明瞭な10×8mm大の結節影を認めた.1ヵ月の経過で陰影の縮小傾向はなく悪性腫瘍も否定できなかったため, 胸腔鏡下に肺生検を施行した.胸腔鏡では, 胸膜嵌入を伴う暗赤色の小結節として認めた.術中迅速病理検査では, 中等度のリンパ球浸潤と血管壁の肥厚を指摘され炎症後の瘢痕様の病変が疑われた.切除肺の病理組織検査では, 肺胞壁と血管壁の著明な肥厚, 血管の拡張, 肺胞内出血を認め陳旧性出血性肺梗塞と診断された.気管支喘息を除き基礎疾患の関与が否定的な女性に発症し, 小結節影を呈した陳旧性出血性肺梗塞の一切除例を報告した.

BackgroundThe surgeon must use the results of preoperative computed tomography findings and scintigraphic studies to make a subjective decision during lung volume reduction surgery with regard to the best incision line.ObjectivesOur purpose was to develop an objective and real-time method of detecting areas of pulmonary emphysema by using infrared thoracoscopy.MethodsPulmonary emphysema was developed in various lobes of the lung in the dog by injecting porcine pancreatic elastase through the bronchi. One month after the injection, chest computed tomography and lung biopsy were performed. Infrared thoracoscopic study was then performed to reveal the presence of the emphysematous lung tissue. Simultaneously, indocyanine green was injected intravenously, and the time taken for each type of lung tissue to stain blue was measured.ResultsChest computed tomography and histologic examinations revealed pulmonary emphysema-like areas in the porcine pancreatic elastase-injected lung. The computed tomography numbers of the porcine pancreatic elastase-injected lung tissue, normal lung tissue, and the tracheal lumen were −868.8 ± 18.6, −752.2 ± 32.5, and −1013 ± 27.1, respectively. There were significant differences between the porcine pancreatic elastase-injected lung and the normal lung (P < .0001). The time for staining to begin was 10.7 ± 4.8 seconds for normal lung tissue and 25.8 ± 9.4 seconds for the emphysematous tissue; the onset of staining emphysematous lung tissue was significantly delayed (P = .003).ConclusionsWe developed a successful canine model of pulmonary emphysema by injecting porcine pancreatic elastase. Infrared thoracoscopic examination revealed that the staining of emphysematous lung using indocyanine green injection was significantly greater than of normal lung.

We investigated whether saber sheath-type tracheomalacia could be treated by the slow release of bone morphogenetic protein (BMP)-2 from a gelatin sponge. A 1 cm gap was made in the middle portion of each of 10 consecutive tracheal cartilage rings in the canine cervix (control group, n = 3), then a gelatin sponge containing 12 microg of BMP-2 solution was implanted in the gap (12 microg group, n = 3). In another group (120 microg + P group, n = 3), the implanted gelatin sponge contained 120 microg of BMP-2 solution, and the gap was covered with periosteum. All of the control dogs developed saber sheath-type tracheomalacia, whereas tracheomalacia was not observed in the 12 microg and 120 microg + P groups. In the 12 microg group, fibrous cartilage was observed at the ends of the cartilage stumps. In the 120 microg + P group, newly formed bone and cartilage were observed to form a bridge between the cartilage stumps. The regeneration of cartilage or bone induced by the slow release of BMP-2 from a gelatin sponge might be useful for treatment of tracheomalacia.

症例は59歳男性.1999年1月に左下葉原発肺扁平上皮癌に対し下葉管状切除術および有茎のpericardial fat padによる吻合部被覆を施行した.術後1年9ヵ月目の胸部CTで術側前縦隔に腫瘤影が出現し, その後増大傾向を認めた.2000年12月にCT下に腫瘤生検を施行したが, 悪性所見は認めなかった.2001年2月に胸骨縦切開下に手術を行った.周囲臓器への浸潤は認めず, 腫瘤および胸腺摘出術を施行した.腫瘤は, 胸腺左葉下極に存在, 大きさは2.0×2.0cm, 弾性軟で薄い被膜に覆われ肉眼的に単房性の胸腺嚢胞であった.病理学的には, 嚢胞壁が単層立方上皮の他, リンパ球浸潤と過形成を伴う扁平上皮化生からなり, 組織球の集簇と線維性結合組織の増生を伴う上皮の脱落も認められた.周囲の胸腺組織内に小嚢胞も認め, 肺癌手術時のpericardial fat pad作成あるいはこれによる気管支吻合部被覆が誘因と考えられる後天性の多房性胸腺嚢胞と診断し報告した.

We reviewed ten patients with resected thymic carcinoma. The mean age was 55.0 years, ranging from 36 to 71 years, with five males and five females. The histological types were squamous cell carcinoma in 9 cases, and squamous cell carcinoma combined with small cell carcinoma in one case. One of the 10 patients was in stage I, 7 were in stage III, one was in stage IVa, and one was in stage IVb. Eight of the ten patients underwent complete resection, and induction chemotherapy was performed in one of the 8 cases, while induction chemoradiotherapy was performed in two of the 8 cases. Postoperative radiotherapy was performed in all cases (20-50Gy). In recurrence cases, operation was positively performed for resectable cases. The five-year and ten-year survival rates were 78.7%, 52.5%, respectively. We expect that patients with thymic carcinoma can be cured completely or survive for long periods with multimodal therapy and resection of recurrences.

肺リンパ脈管筋腫症 (Pulmonary lymphangioleiomyomatosis: LAM) は, 妊娠可能な女性の肺に平滑筋が異常に増殖する疾患であり, 診断は胸部CT, 胸腔鏡下肺生検, 剖検, 経気管支肺生検で行われてきた.症例は36歳, 女性.胸痛を自覚し, 近医を受診した.胸部X線写真で気胸と診断され当院紹介となった.胸腔ドレナージ後の胸部CTで肺野の多発性嚢胞陰影の散在, 血管気管支壁の不整は認めなかったが, リークは止まらず月経随伴性気胸も考慮し胸腔鏡を施行した.右上葉に微小嚢胞および細血管の増生を認め, 胸腔鏡下肺部分切除を施行した.病理学的には, 肺胞壁の破壊と平滑筋の異常な増生を認めた.SMAは陽性, HMB-45, エストロゲン・プロゲステロンレセプターは陰性であった.胸腔鏡所見と病理学的所見より, LAMの早期例として矛盾しないと考えられた.LAMの早期診断に胸腔鏡下肺生検は有用であった.

近年, CTの性能の向上により, 小さなスリガラス様陰影を見つける機会が増した.早期の同時性両側性多発肺癌の3症例を経験し, 各症例とも病巣の陰影は1cm以下で臨床病期はIA期であった.1cm以下の早期腺癌にリンパ節転移がみられないことや, 呼吸機能の温存を考慮し, 積極的縮小手術として3例全例に, 両側の拡大部分切除あるいは区域切除を施行した.病理組織診断は3例とも高分化型腺癌 (bronchiolo-alveolar carcinoma) で, 2例にはAAH (atypical adenomatous hyperplasia) も認められた.現在まで20～27ヵ月が経過したが, 3例とも再発を認めていない.同時性両側性多発肺癌に対する標準的治療は確立されていないが, 早期の同時性両側性多発肺癌に対して, 積極的縮小手術が適切と考えられた.

Objective: Many reports have raised certain problems concerning the current TNM classification of lung cancer, namely that there is no sufficient difference in prognosis between patients with pathologic stage IIIA and IIIB disease. For clarifying this problem, the present study was constructed in light of T3 and T4 classifications. Methods: Among 429 patients with non-small cell lung cancer who underwent resection, those with stage IIIA (n = 73) and stage IIIB (n = 79) disease were enrolled in this study, and their prognostic factors were compared. Results: No difference in the survivals between patients with T3 and T4 disease was observed, and this seemed to affect the prognoses of patients with stage IIIA and IIIB disease. However, when those with T3 and T4 disease were classified into different groups on the basis of TNM descriptors, differences in the survivals became evident. The T3 bronchial invasion group showed a better prognosis than the T3 extrapulmonary invasion group. The T4 tracheal invasion group and T4 pulmonary metastasis group showed a significantly better prognosis than that in the T4 extrapulmonary invasion group and the T4 malignant pleural exudate group. The surgical curativity of patients with T3 disease was evaluated as curative resection or noncurative resection, and the surgical curativity of T4 was evaluated as R0 resection or R1 or R2 resection. The T3 bronchial invasion group included more curative resection cases. The T4 tracheal invasion group and T4 pulmonary metastasis group included more R0 resection cases. Furthermore, when patients with T3 to T2 bronchial invasion and patients with T4 tracheal invasion and T4 pulmonary metastasis were reclassified as having T3 disease, the survivals of the patients reclassified as having T3 and T4 disease, as well as the resultant subsets having stage IIIA and IIIB disease, were significantly different. Conclusion: Tumor status should be reviewed by taking into account the surgical curativity. J Thorac Cardiovasc Surg 2002;124:503-10

症例は46歳男性.アスベスト暴露歴あり.人間ドックにて左肺に胸膜肥厚を伴う異常結節影を指摘された.その後経過観察していたが, 4ヵ月後のCT検査で増大傾向を認めたため, TBLB, CTガイド下経皮的針生検を施行したが悪性所見は得られなかった.画像上は円形無気肺を最も疑ったが, 悪性腫瘍の存在を完全には否定しきれず審査開胸術を施行した.術中針生検による病理組織所見では炎症所見のみで悪性所見は得られず, 円形無気肺と診断した.本症例のごとく増大傾向を示し悪性疾患が否定できない円形無気肺では, 審査開胸術が必要と考えられた.

今回我々は脳膿瘍を合併した肺動静脈瘻の一手術例を経験したので報告する.症例は38歳男性.健診で胸部異常を指摘されていた.発熱に続く頭痛・意識混濁を主訴に近医受診し, 精査の結果脳膿瘍と診断され治療を受けた.脳膿瘍の原因が肺動静脈痩と診断されたため根治目的で当科紹介された.入院時, 体動時呼吸困難および低酸素血症を認めた.造影剤アレルギーがみられ, 経カテーテルによる治療は適応外と判断し, 肺区域切除術を施行した.術後経過は良好で術後14日に退院した.術後, 呼吸困難および低酸素血症の改善が見られた.当症例は外科的切除が有効な治療方法であったと考えられた.

Objective: Peritoneal disseminated ovarian and pancreatic cancers are the most difficult to be treated with conventional cytotoxic or molecular targeted drugs. The treatment option is very limited although an intraperitoneal (IP) paclitaxel has been available and shown to improve a prognosis in patients. Therefore, it is urgent to develop a new IP chemotherapeutic drug regulating the fast DNA synthesis in peritoneal disseminated tumors originated commonly from the ovary, pancreas and stomach. We have developed a unique RNAi molecule consisting of shRNA (55-mer) against TS and a cationic liposome (DFP-10825) and tested its anti-tumor activity and PK profile in peritoneal disseminated ascetic tumor models. Methods: We developed luciferase gene-transfected ovarian cancer (SKOV3-luc) and pancreatic cancer (PANC-1-luc) models in mice. After IP injection of 5x106 cells, DFP-10825 containing 20 µg TS shRNA (20 mg/mouse) was administered in an IP route (q3d x 4) to the tumor-bearing mice. In combination therapy, paclitaxel (10 mg/kg) was also IP administered to SKOV3-luc model to which the treatment was performed in the same schedule. The anti-tumor effect was assessed by measuring luciferase activity and tumor volume. Furthermore, the TS expression level in both ascetic tumor cells and solid tumors was measured by conventional RT-PCR. For PK study with DFP-10825 (especially TS shRNA), total RNAs were isolated at various time points from ascetic tumor cells and disseminated SKOV3-luc solid tumor models treated with DFP-10825 and TS shRNA levels were determined by Stem-loop RT-PCR. Results: IP DFP-10825 delivery significantly suppressed the growth of ascetic SKOV3-luc and PANC-1-luc tumor cells and extended the survival time of these tumor-bearing mice compared with that of control group. Combination with the IP paclitaxel augmented the efficacy of DFP-10825. After the IP administration, TS shRNA levels derived from DFP-10825 in ascetic fluid were maintained at nM range (0.7 - 4.3-nM) across 24 hours but not detected (below 5 pM) in the plasma, suggesting that TS shRNA be relatively stable in the peritoneal cavity to be able to exert its anti-tumor activity but not in blood. Also, TS expression (TS mRNA) in ascetic tumor cells was significantly suppressed, supporting the notion that the anti-tumor activity and host survival benefit by DFP-10825 in tumor-bearing mice are through MOA to knock down the TS level in tumors specifically. Conclusion: IP administration of newly developed DFP-10825, the TS shRNA conjugated with cationic liposome is localized stably in the peritoneal cavity and provides a new effective treatment option to the intractable peritoneal disseminated ovarian and pancreatic cancers without any systemic adverse events. Citation Format: Cheng Jin, Kenzo Iizuka, Kokoro Eshima, Masakazu Fukushima, Tatsuhiro Ishida, Cheng-Long Huang, Hiromi Wada, Kiyoshi Eshima. DFP-10825 IP delivery provides a new effective treatment option to peritoneal-disseminated cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2192. doi:10.1158/1538-7445.AM2017-2192

We experienced an extremely rare case of a thymoma in the middle mediastinum. A 42-year-old woman presented with a 4-cm-sized abnormal mass in the middle mediastinum by chest computed tomography. To resect this tumor, we performed surgery using the thoracoscopic lateral approach from the right side subsequently followed by a median sternotomy. After the resection of this tumor, the intraoperative quick pathological examination diagnosed this tumor as a thymoma. An extended thymectomy was performed additionally.

BACKGROUND Angiogenesis has important effects on tumor growth and metastasis. It is regulated by a variety of angiogenic and angiostatic factors. METHODS To evaluate the effects of tumor cell-derived angiogenic factors, we performed an immunohistochemic study to evaluate the intratumoral expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in relation to intratumoral microvessel density (IMD) in tumors from 104 nonsmall cell lung carcinoma (NSCLC)patients. RESULTS Fifty-four carcinomas were VEGF-positive, 47 carcinomas were IL-8-positive, and 53 carcinomas were hypervascular tumors. There was no significant correlation between the percentages of positive VEGF-staining and positive IL-8-staining in NSCLCs (ρ = 0.174, P = 0.080). The IMD of VEGF-positive carcinomas was significantly greater than that of VEGF-negative carcinomas (P = 0.023). In addition, the IMD of IL-8-positive carcinomas was significantly greater than that of IL-8-negative carcinomas (P =0.013). The overall survival rate of patients with hypervascular tumors was significantly lower than that of patients with hypovascular tumors (41.0% versus 67.0%, P = 0.004). Cox proportional-hazards regression model also demonstrated that angiogenesis was one of the significant factors in predicting the survival of NSCLC patients (relative risk = 1.944, P = 0.041). CONCLUSIONS Intratumoral expression of VEGF and IL-8 was associated with angiogenesis in NSCLCs. Tumor angiogenesis significantly affected the prognosis of NSCLC patients. Cancer 2001;92:2628–38. © 2001 American Cancer Society.

BACKGROUND Previously, the authors reported the role of the vascular endothelial growth factor (VEGF) as an angiogenic factor in 40 patients with pancreatic carcinoma. In this study, they investigated the mechanism underlying the regulation of VEGF gene expression and evaluated VEGF expression and K-ras gene status in 48 patients with pancreatic carcinoma. METHODS The authors used quantitative reverse transcriptase-polymerase chain reaction analysis and direct sequencing techniques for a retrospective study of VEGF gene expression and K-ras gene status in tumor tissue samples from 48 patients with pancreatic carcinoma. Immunohistochemistry also was used to investigate VEGF protein expression. RESULTS Thirty-one tumors (64.6%) were evaluated with high VEGF expression, and 17 tumors (35.4%) were evaluated with low VEGF expression. Of the 48 primary pancreatic tumors studied, 33 tumors (68.8%) contained mutations of the K-ras gene. There was a significant correlation between VEGF expression and K-ras status. Twenty-five of 33 tumors (75.8%) with mutant K-ras genes showed high VEGF expression, whereas only 6 of 15 tumors with the wild type K-ras (40.0%) showed high VEGF expression (P = 0.038). The mean (± standard error) VEGF conservation rate for the 33 tumors with mutant K-ras was 1.839 ± 1.241, and that for the 15 tumors with wild type K-ras was 1.057 ± 0.983 (P = 0.037). Furthermore, the median survival for patients with mutant K-ras was shorter than for those with wild type K-ras (10.6 months vs. 27.6 months, respectively; P = 0.026), whereas the median survival for patients with high VEGF expression was shorter compared with that for patients with low VEGF expression (9.5 months vs. 26.4 months, respectively; P = 0.002). Cox regression model analysis indicated that only the VEGF status was a significant factor for prognosis (P = 0.024). Other variables, i.e., K-ras status, histopathologic tumor grade, tumor status, lymph node status, metastatic status, gender, and age at surgery, were not significant. CONCLUSIONS The results of this study suggest that K-ras oncogene mutation may be associated with VEGF expression and that patients with pancreatic carcinoma who have high VEGF expression are associated with a poor prognosis. Cancer 2001;92:488–99. © 2001 American Cancer Society.

Increasing evidence suggests that an elevated peripheral monocyte count at presentation predicts a poor prognosis in various types of malignancy, including malignant lymphoma. In lung adenocarcinoma, tumor-associated macrophages (TAMs) were reported to be associated with a poor prognosis. However, it is unknown if an elevated peripheral monocyte count is associated with a poor prognosis in lung adenocarcinoma. This study assessed the prognostic impact of the preoperative peripheral monocyte count in lung adenocarcinoma.We retrospectively analyzed 302 consecutive patients with lung adenocarcinoma who received curative resection at Kitano Hospital. The receiver operating characteristic (ROC) curve for the peripheral monocyte count was used to determine the cut-off value. The relations between peripheral monocyte counts and clinicopathological factors were assessed. We also evaluated the impacts of possible prognostic factors including the preoperative peripheral monocyte count on survival, using the two-tailed log-rank test and Cox proportional hazards model. In addition, immunohistochemical staining for CD68 was performed to evaluate the monocytes in primary tumors.A peripheral monocyte count of 430mm(-3) was the optimal cut-off value for prognosis. An elevated peripheral monocyte count was significantly associated with sex, performance status, smoking history, chronic obstructive pulmonary disease and interstitial lung disease. The two-tailed log-rank test demonstrated that patients with an elevated peripheral monocyte count experienced a poorer recurrence-free survival (RFS) and overall survival (OS) (P=0.0063, P0.0001, respectively). In the multivariate analysis an elevated peripheral monocyte count was shown to be an independent prognostic factor for the RFS and OS (HR: 1.765; 95% CI: 1.071-2.910; P=0.0258, HR: 4.339; 95% CI: 2.032-9.263; P=0.0001, respectively). Furthermore, numbers of the monocytes in primary tumors significantly correlated with peripheral monocyte counts (r=0.627, P0.0001).The preoperative peripheral monocyte count is an important prognostic factor for patients with lung adenocarcinoma after curative resection.

Azygos vein aneurysm is very rare and most cases are detected incidentally. We report a safe resection of azygos vein aneurysm by video-assisted thoracoscopic surgery (VATS) under preoperative evaluation of thrombus by multidetector computed tomography (MDCT). A 60-year old woman presented to our department due to a mediastinal mass revealed by enhanced CT. A dynamic enhanced-CT scan showed a dilated azygos vein with great enhancement in the early phase. Under the diagnosis of azygos vein aneurysm, we analysed the aneurysm by MDCT and confirmed that there was no thrombus within the aneurysm. The resection of the aneurysm by VATS was performed safely. She was discharged 4 days after surgery.

We present the establishment of a natural killer (NK) leukemia cell line, designated KHYG-1, from the blood of a patient with aggressive NK leukemia, which both possessed the same p53 point mutation. The immunophenotype of the primary leukemia cells was CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16+, CD56+, CD57+ and HLA-DR+. A new cell line (KHYG-1) was established by culturing peripheral leukemia cells with 100 units of recombinant interleukin (IL)-2. The KHYG-1 cells showed LGL morphology with a large nucleus, coarse chromatin, conspicuous nucleoli, and abundant basophilic cytoplasm with many azurophilic granules. The immunophenotype of KHYG-1 cells was CD1-, CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16-, CD25-, CD33+, CD34-, CD56+, CD57-, CD122+, CD132+, and TdT-. Southern blot analysis of these cells revealed a normal germline configuration for the beta, delta, and gamma chains of the T cell receptor and the immunoglobulin heavy-chain genes. Moreover, the KHYG-1 cells displayed NK cell activity and IL-2-dependent proliferation in vitro, suggesting that they are of NK cell origin. Epstein-Barr virus (EBV) DNA was not detected in KHYG-1 cells by Southern blot analysis with a terminal repeat probe from an EBV genome. A point mutation in exon 7 of the p53 gene was detected in the KHYG-1 cells by PCR/SSCP analysis, and direct sequencing revealed the conversion of C to T at nucleotide 877 in codon 248. The primary leukemia cells also carried the same point mutation. Although the precise role of the p53 point mutation in leukemogenesis remains to be clarified, the establishment of an NK leukemia cell line with a p53 point mutation could be valuable in the study of leukemogenesis.

An immunohistochemical analysis for p16 protein was performed in 171 patients with non-small-cell lung cancer (NSCLC). Sixty-two carcinomas (36.3%) were classified as p16-negative. p16-negative tumours in squamous cell carcinomas (SCCs) were significantly more than those in adenocarcinomas (P = 0.039). There was no significant difference in survival according to tumour p16 status in patients with NSCLCs or in patients with adenocarcinomas. In contrast, of patients with SCCs, the 5-year survival rate of patients with p16-negative tumours was significantly lower than those with p16-positive tumours (P = 0.001). Especially, the survival of patients with p16-negative tumours was significantly worse than that of patients with p16-positive tumours in the early stage of the SCC, e.g. stage I (P = 0.005). Multivariate analysis showed that p16 status and nodal status were significant prognostic factors for the survival of patients with SCCs of the lung (P = 0.024 and P = 0.008 respectively). In conclusion, our study showed that alteration of p16 was one of the significant factors of a poor prognosis in SCCs of the lung, and that p16 might play an important role in some SCCs of the lung due to its high prevalence and prognostic value. © 2000 Cancer Research Campaign

A molecular staging protocol using reliable markers is of importance in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) and for instituting their appropriate post-surgical treatment. We analysed tumor tissues from 187 NSCLC patients. The DNA and mRNA were extracted from frozen specimens, and then polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exons 5-8, and mutations of K-ras at exon 1. To determine MRP-1/CD9 gene and KA11/CD82 gene expression, which have been postulated to be metastasis suppressor genes, we have applied quantitative RT-PCR. A Cox multivariate regression analysis showed that nodal status, MRP-1/CD9 and K-ras status were significant factors for prognosis (P