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In the American Society of Clinical Oncology guideline, it is mentioned that systemic therapy is a standard treatment, but there is no cure for patients with stage IV non-small cell lung cancer (NSCLC). Recent technical advances have facilitated the delivery of curative-intent radiation doses to some stage IV patients. In this report, we introduce a long-term disease-free survivor after concurrent chemoradiotherapy (CRT) and discuss considerations for this treatment. The patient was a 61-year-old woman diagnosed with stage IV adenocarcinoma of the lung classified as cT4N3M1c; the M1c classification was because of multiple synchronous pathologically proven cervical lymph node metastases (CLNM). We administered concurrent CRT to all lesions with a dose of 60 Gy in 30 fractions over 6 weeks. Concurrent chemotherapy consisted of two cycles of carboplatin and pemetrexed. Adjuvant chemotherapy was performed with five cycles of carboplatin and pemetrexed followed by three cycles of pemetrexed alone. As of 43 months after CRT, the patient was still alive without disease. In conclusion, our patient with stage IV NSCLC due to CLNM achieved long-term disease-free survival by concurrent CRT as with patients with locally advanced NSCLC. Patient subgroups should be explored to achieve long-term disease-free survival after definitive CRT in patients with stage IV NSCLC due to CLNM.

A 77-year-old man vomited after alcohol drinking and was sent to our hospital by an ambulance due to sustained chest pain. Chest computed tomography (CT) showed pneumothorax and pleural effusion, and thoracic drainage was performed. Since food residue was found from chest drainage and esophagoscopy and esophagography showed injured potion on the left wall of the lower thoracic esophagus perforating to the left thoracic cavity, a spontaneous esophageal rupture was diagnosed. Establishment of fenestration for open drainage and gastrostomy were performed. After 49 days, the fistula was successfully closed by cleaning of the left thoracic cavity, with application of basic fibroblast growth factor and enteral nutrition through gastrostomy. The fenestration was closed after 53 days and the patient was discharged after 78 days.

A 75-year-old woman was pointed out a mass shadow in the right upper lobe by chest computed tomography (CT) 3 month ago. Bronchoscopic examination revealed adenocarcinoma, and right upper lobectomy was performed. Preoperatively, it was revealed that V1+2 returned to the superior vena cava while V3 returned to the normal position. Postoperative course was uneventful and there has been no recurrence 6 months post-surgery.

A 67-year-old man visited hospital because of prolonged cough. Chest computed tomography (CT) revealed multiple tumors in bilateral lungs. Transbronchial lung biopsy did not reveal malignancy. Because antibiotic treatment was ineffective, partial resection of the right lung was performed for establishing the diagnosis. The pathological diagnosis was inflammatory myofibroblastic tumor. The postoperative course was uneventful. After 6 months postsurgery, he complained of breathing difficulty and exacerbation of the lesions was found by chest CT. By methylprednisolone pulse therapy, the symptom was improved, and the size of lesions reduced. Since this event, he has been administered oral prednisolone (PSL) 10 mg/day, and the exacerbation of the disease has not been noted.

Bronchogenic cyst is not a rare disease, but cases of bronchogenic cyst in the diaphragm are rare. We report a case of intraphrenic bronchogenic cyst. A 68-year-old woman was pointed out a 30 mm tumor on the left diaphragm by chest computed tomography (CT) 12 years ago. Because the size of the tumor had been increasing for 12 years, she was hospitalized for surgery. The tumor in the left diaphragm was removed by thoracotomy. Histologically, the tumor was diagnosed as a intraphrenic bronchogenic cyst.

A 58-year-old woman visited our hospital due to left chest back pain. Chest computed tomography (CT) showed 19 mm nodule in the left lower lobe with the abnormal artery supply from the descending aorta and it was diagnosed as the anomalous systemic arterial supply to the basal segments of the lung. She had undergone partial resection of the left lower lobe by video-assisted thoracoscopic surgery. Histopathology showed the inflammatory change with fibrosis and lymphocites in the nodule, and fungus-like bacterial masses with macrophages and neutrophils. At 7 days after the operation, the patient discharged without any problems. In order to perform less invasive treatment, early surgical intervention should be considered to prevent the spread of inflammation in the thoracic cavity.

A 73-year-old man was injured after crashing his automobile into a concrete wall, and was admitted to our hospital with breathing difficulties. Chest computed tomography showed extensive mediastinal emphysema, right traumatic pneumothorax, and a suspected tracheal injury at the membranous region. Because of the associated tracheomalacia, the site of the tracheal injury was difficult to find by bronchoscopy. In addition, as the patient's respiratory condition was stable, surgical treatment was not chosen. Due to the continuous air leakage from the right lung, the patient underwent surgery after mediastinal and subcutaneous emphysema improved. The postoperative course was uneventful.

A 16-year old young man was referred to our hospital due to abnormal mass of mediastinum on chest radiography. Chest computed tomography scan revealed 45 mm mass in diameter with low density areas and ring shaped calcification at right upper mediastinum. However, chest magnetic resonance imaging showed no existence of fat nor calcification. Although no typical findings was observed, surgical resection was performed because mature cystic teratoma was undeniable. At complete video-assisted thoracoscopic surgery, tumor was found to be in the upper mediastinum covered with mediastinal pleura and with dense fibrous structures around it, and was resected with surrounding fat tissue. Histological diagnosis was hemangioma associated with lymphangiogenesis and arteriovenous malformation-like region in the surrounding fat tissue.

G protein‑coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein‑coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non‑small‑cell lung cancer (NSCLC). We investigated a total of 123 patients with NSCLC who underwent surgery between 1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others). Immunohistochemistry was used to evaluate the intratumoral expression of GPR87 and the Ki‑67 proliferation index. The TUNEL method was also used to investigate tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87‑positive. These tumors were more frequently encountered among squamous cell carcinomas rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and were significantly more frequently poorly and moderately differentiated rather than well differentiated (P=0.029). Moreover, the Ki‑67 index was significantly higher in GPR87‑positive compared to GPR87‑negative tumors (57.0 vs. 40.0%, respectively; P=0.002). The overall survival was significantly worse for patients with GPR87‑positive compared to those with GPR87‑negative tumors (P=0.029). The Cox regression analyses also demonstrated that the GPR87 status was a significant prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present study demonstrated that in NSCLC, the overexpression of GPR87 is significantly associated with poorer differentiation and higher proliferation. During the progression of NSCLC, GPR87 overexpression may be associated with the acquisition of a more aggressive phenotype and, therefore, is a potentially useful target for prognostication and treatment.

Aim Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC. Patients and methods Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS. Results The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0.0011). Conclusion Customized adjuvant chemotherapy based on biomarker examination significantly improved the survival of patients with NSCLC, regardless of p-stage.

Novel colorless polyimides (PIs) derived from 1R, 2S, 4S, 5R-cyclohexane tetracarboxylic dianhydride (a new hydrogenated pyromellitic dianhydride (PMDA) with a controlled steric structure, H"-PMDA) with various aromatic diamines were applied to positive-type photosensitive PI systems. The H"-based PI precursors, poly(amic acid)s (PAAs), were partially imidized with controlled extents of imidization (χI) by adding established amounts of a cyclodehydration reagent (acetic anhydride/pyridine) into the PAA solutions and stirring at room temperature for 24 h while keeping the homogeneity of the reaction mixture except when 4,4'-oxydianiline (4,4'-ODA) was used as a diamine component. A good linear relationship was obtained between the amount of cyclodehydration reagent added and the extent of imidization (%) in the partially imidized PAAs (pi-PAAs) obtained. The pi-PAA cast films (10 μm thick) displayed a considerably high light transmittance at 365 nm (> 85%) in addition to its adequately controlled alkali-solubility. The photosensitive films consisting of the pi-PAAs and diazonaphthoquinone (DNQ) as a photosensitizer provided good positive-tone patterns through uv-irradiation and subsequent development using a 2.38 wt% tetramethylammonium hydroxide (TMAH) aqueous solution. The fully imidized films showed very high glass transition temperatures exceeding 300oC in some cases, sufficient film-forming ability (flexibility), and excellent transparency. The use of a thermally crosslinkable mono-functional end-capper, nadic anhydride (NA), was very effective to inhibit gelation during the chemical imidization process even in the H"-PMDA/4,4'-ODA system owing to its adequately controlled molecular weight. In addition, thermal curing of the NA-terminated system significantly improved the film toughness.

シェーグレン症候群に合併した結節性肺アミロイドーシスの2例を経験した．症例1は67才男性．健診で左肺下葉に石灰化を伴う径15mmの結節影を指摘された．肺過誤種を疑い核出術を施行しAAアミロイドーシスと診断した．元来dry eyeを認めており，抗SS-A抗体陽性，Lip biopsyによりシェーグレン症候群と診断した．症例2は42才女性．健診で胸部異常影と肝機能障害を指摘．シルマーテスト，SAXONテスト，Lip biopsy，抗SS-A, -B抗体陽性よりシェーグレン症候群と診断した．また両肺に多発する結節影を認め小開胸肺生検を施行，ALアミロイドーシスと診断した．2症例とも全身検索で他部位にアミロイド沈着を認めず結節性肺アミロイドーシスと診断した．シェーグレン症候群には種々の肺病変の合併が知られているが，肺アミロイドーシス合併の報告は極めてまれであり文献的考察を加えて報告する．

Within-die parameter variation poses a major challenge to high-performance microprocessor design, negatively impacting a processor's frequency and leakage power. Addressing this problem, this paper proposes a microarchitecture-aware model for process variation-including both random and systematic effects. The model is specified using a small number of highly intuitive parameters. Using the variation model, this paper also proposes a framework to model timing errors caused by parameter variation. The model yields the failure rate of microarchitectural blocks as a function of clock frequency and the amount of variation. With the combination of the variation model and the error model, we have VARIUS, a comprehensive model that is capable of producing detailed statistics of timing errors as a function of different process parameters and operating conditions. We propose possible applications of VARIUS to microarchitectural research.

目的：孤立性肺動静脈瘻に対する外科療法につき検討した．対象と方法：1999年4月から2007年12月までに香川大学医学部付属病院で肺動静脈瘻と診断され，外科的切除を施された6例．男性1例・女性5例．VATSによる切除2例，開胸による切除4例．1例が区域切除，5例が自動縫合器による部分切除であった．結果：5例で肉眼的に異常血管が同定でき，視認できなかった1例は超音波画像診断および触診で同定した．合併症を認めず安全に切除できた．全例で局所再発はみとめなかった．結論：治療適応のある肺動静脈瘻は経カテーテル治療を中心にした治療戦略を立て，全身麻酔可能な治療適応のある孤立性の症例で，より根治性の高い治療法を選択する場合や造影剤アレルギーなどの経カテーテル治療が不可能である場合に外科的治療を選択する必要がある．

Purpose: We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase (TS) and Survivin, in case of non–small-cell lung cancer (NSCLC). Experimental Design: One hundred twenty-seven cases of resected NSCLC were analyzed. Quantitative reverse transcription-PCR was done to evaluate the gene expression of E2F1, TS, and Survivin. Immunohistochemistry was done to investigate the protein expression of E2F1, TS, and Survivin. The Ki-67 proliferation index and the apoptotic index using the terminal deoxyribonucleotidyl transferase–mediated dUTP nick-end labeling method were also evaluated. Results: E2F1 gene expression significantly correlated with the Ki-67 proliferation index (r = 0.487; P < 0.0001), although no correlation was observed between E2F1 gene expression and the apoptotic index. With regard to E2F1 target genes, E2F1 gene expression significantly correlated with TS gene expression (r = 0.709; P < 0.0001) and Survivin gene expression (r = 0.403; P < 0.0001). The overall survival rate was significantly lower in patients with high-E2F1 tumors than in those with low-E2F1 tumors (P = 0.0027), especially among patients with stage II to III NSCLCs (P = 0.0188). A Cox regression analysis showed that the E2F1 status was a significant prognostic factor for NSCLC patients (hazard ratio, 2.052; P = 0.0261). Conclusions: The present study revealed that E2F1 gene expression correlates with TS and Survivin gene expressions and tumor proliferation. During the progression of NSCLC, E2F1 overexpression could produce more aggressive tumors with a high proliferation rate and chemoresistance.

Matrix metalloporteinase-7 (MMP-7) is a member of the MMP family, and it has been reported to play an important role in tumorigenesis, invasion and metastasis. We performed a retrospective study on the MMP-7 expression in non-small cell lung cancer (NSCLC) according to the clinical characteristics, biological markers and the Wnt1 expression.One hundred forty-seven postsurgical NSCLC patients were investigated. Immunohistochemistry was performed to evaluate the MMP-7 expression, the Ki-67 proliferation index, tumor angiogenesis and the Wnt1 expression. The TUNEL method was performed to investigate tumor apoptosis.Seventy-six carcinomas (51.7%) were MMP-7-positive. The MMP-7 expression was significantly higher in squamous cell carcinomas than in adenocarcinomas (P0.0001). The Ki-67 proliferation index was significantly higher in MMP-7-positvie tumors than in MMP-7-negative tumors (P=0.0003). However, there was no difference in the MMP-7 expression in relation to apoptosis or angiogenesis. Regarding its regulation, the MMP-7 expression significantly correlated with the Wnt1 expression (r=0.426, P0.0001). The overall survival was significantly lower in patients with MMP-7-positive NSCLCs than in those with MMP-7-negative NSCLCs (P=0.0018). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 2.187; P=0.0023).The overexpression of MMP-7 was associated with tumor proliferation, and a poor prognosis in NSCLCs. In addition, Wnt1 may play a critical role in regulating the intratumoral MMP-7 expression.

The nucleoside analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-(18)F-fluoro-D-glucose (FDG).A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs.The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p0.0002) and for FDG SUV (r = 0.81; p0.0001).The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.

Chemical syntheses of complex-type glycans derived from the eggs of parasitic helminths, Schistosoma mansoni and Schistosoma japonicum were achieved. In addition, their analogs, which lack xylose and/or fucose residue(s), are described. These branched sugar chains were synthesized regio- and stereoselectively by using beta-mannosylation, desilylation under high-pressure and glycosylation in frozen solvent as key transformations.

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．

A hydroxyamide-containing tetracarboxylic dianhydride was synthesized from trimellitic anhydride chloride and bis(3-amino-4-hydroxyphenyl)sulfone. Poly(amic acid)s (PAAs) were prepared from this dianhydride with several diamines in N-methyl-2-pyrrolidone (NMP). The reflux of the PAA solutions at 160°C for 3 h allowed to form hydroxyamide-containing polyimides (PHAIs) highly soluble in common organic solvents such as NMP. The PHAI films could be completely converted to poly(benzoxazole imide)s (PBOIs) through cyclodehydration of the hydroxyamide groups upon heat treatment at 300°C. The thermally cured PBOI films showed a high Tg ranging 298-323&degC. Other PBOI film properties are also discussed in this paper. The PHAI films were highly transparent at 435 nm but not at 365 nm. This is a problem to be solved for high sensitivity patterning at i-line. The solubility of the PHAI films in TMAH could be controlled by copolymerization using different diamines. The PHAI copolymer films dispersing diazonaphthoquinone (DNQ) as a photosensitizer were uv-irradiated through a photo-mask. Development using a 2.38 wt% TMAH aqueous solution containing 2-propanol gave a fine positive-type pattern with L&S = 20 μm.

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．

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．

In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.

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.

Existing cache-level checkpointing schemes do not continuously support a large rollback window. Immediately after a checkpoint, the number of instructions that the processor can undo falls to zero. To address this problem, we introduce Swich, an FPGA-based prototype of a new cache-level scheme that keeps two live checkpoints at all times, forming a sliding rollback window that maintains a large minimum and average length

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

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.

活性化自己リンパ球移入療法は自己のリンパ球をex vivoで増殖活性化し再びこれを癌患者の体内に戻すことによって癌の消退をはかる免疫治療である. 我々は再発転移肺癌患者に対して, 癌抗原MUC1を標的とした活性化自己リンパ球移入療法を施行した. 3例の治療患者のうち1例は治療後に抗原特異的細胞性免疫を獲得していた. 同患者は治療後, 全身倦怠感と食欲不振の症状軽減が認められた. いずれの患者においても, 腫瘍縮小や腫瘍マーカー値低下などの治療効果は認められなかった. 副作用として, 治療患者2例に発熱が, 1例に呼吸苦が出現したがいずれも軽度でかつ一過性であった.本治療は低侵襲であること, 癌患者に抗腫瘍免疫誘導が可能であることなどを考慮すると, 治療適応の見直しや培養技術のさらなる改良は必要と思われるが, 新しい分子標的治療として将来広く臨床応用されるものと期待できる.

背景. 限局性胸膜線維腫 (localized fibrous tumor of the pleura; 以下LFTP) の多発症例は世界的にも報告が少ない. 今回我々は同側胸腔内に多発した1症例を経験した. 症例. 患者は54歳女性, 検診時の胸部X線写真にて, 右下肺野に類円形の異常陰影を指摘された. 胸部CTにて右胸膜腫瘍を疑われ, CTガイド下穿刺吸引細胞診が行われた. この結果Class IIIのため確定診断できず, 胸腔鏡下摘出術が行われた. 胸腔内には, 長径5cm大の有茎性肺外腫瘍が右横隔膜上に存在し, 近傍の壁側胸膜にも1cm大の腫瘤が2個認められた. 術後, 病理組織学的に検索した結果, 良性のLFTPと診断された. 結論. 自験例のような多発したLFTPの報告は稀であり, その多発原因は未だ不明である. 一方で良性のLFTPと診断され根治術が施行されたうちの数%に再発が報告されており, 術後長期の経過観察が必要と考えられる.

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.64歳時に右乳癌にて右胸筋温存乳房切除術を受けた.病理病期はstage IIで, 術後DMpC療法 (5'-DFUR: 800mg, MPA: 800mg, CPA: 100mg) を施行中であった.2003年1月16日, 胸部CTで左S8にspicula, notchを伴う小結節陰影の出現を認めた.結節陰影の増大を認め, またFDG-PETで, 左S8の結節陰影に一致して集積を認め, 精査目的で, 2003年3月24日当科へ入院した.CT下肺生検では確定診断に至らず, 2003年4月23日, 胸腔鏡補助下肺生検を施行し肺クリプトコッカス症と診断された.腫瘤陰影を呈する肺クリプトコッカス症のCT所見は肺癌と類似し, PETでも陽性を示すことがあるため画像上の鑑別は困難である.

In the joint experimental and computational efforts reported here to obtain novel chemical entities as growth hormone secretagogues (GHSs), a small database of peptides and non-peptides known to have GHS activity was used to generate and assess a 3D pharmacophore for this activity. This pharmacophore was obtained using a systematic and efficient procedure, "DistComp", developed in our laboratory. The 3D pharmacophore identified was then used to search 3D databases to explore chemical structures that could be novel GHSs. A number of these were chosen for synthesis and assessment of their ability to release growth hormone (GH) from rat pituitary cells. Among the compounds tested, those with a benzothiazepin scaffold were discovered with micromolar activity. To facilitate lead optimization, a second program, a site-dependent fragment QSAR procedure was developed. This program calculates a library of chemical and physical properties of "fragments" or chemical components in a known pharmacophore and determines which, if any, of these properties are important for the observed activity. The combined use of the 3D pharmacophore and the results of the site-dependent fragment QSAR analysis led to the discovery and synthesis of a novel series of potent GHSs, a number of which had nanomolar in vitro activity.