Search

The preoperative assessment of nodal status in lung cancer is complicated and problematic for physicians and surgeons. Although many patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) are candidates for surgical treatment, these patients represent a heterogeneous subgroup with unpredictable survival. We conducted this study to evaluate the surgical results of cN1 disease and to attempt to clarify the delicate issues surrounding its diagnosis and prognosis. The subjects of this study were 187 consecutive patients with cN1 adenocarcinoma or squamous cell carcinoma of the lung, who underwent complete resection without induction therapy. Only 25% of the adenocarcinomas and 54% of the squamous cell carcinomas were correctly diagnosed as N1 disease preoperatively. Multiple logistic regression analyses revealed that adenocarcinoma (P = 0.0141) was a significant predictor of pN2. Multivariate analyses revealed that nodal metastasis (P < 0.0001), large tumor size (P = 0.0079), and high serum carcinoembryonic antigen value (P = 0.0096) were significantly poor prognostic factors in cN1 patients. It is difficult to diagnose nodal status in patients with cN1 disease, which requires various surgical procedures, including plasty, possibly with adjuvant therapy in a defined high-risk subgroup.

症例は65歳，女性．1カ月前より続く咳嗽を主訴に当院受診となった．胸部レントゲン写真にて右下肺野に異常影を認めたため精査目的で入院となった．胸部CTでは右肺S5に8×5cm大の不均一に造影される腫瘤を認め，エコー下針生検にて低分化癌と診断されたため手術となった．手術所見では腫瘍は心嚢に直接浸潤しており術式は右中葉切除術，心嚢合併切除術となった．病理組織学的には肺原発リンパ上皮腫様癌と診断され，病期診断はT3N0M0 stageIIBであった．腫瘍組織のEBER（EB virus encoded RNA) in-situ hybridizationは陽性でありEBウィルスとの関連が示唆された．現在術後5カ月が経過し無再発にて化学療法施行中である．本邦での肺原発リンパ上皮腫様癌の報告は稀であり，若干の文献的考察を加え報告する．

Oxidant injury occurs when an organ is severed from its native blood supply and then reperfused and continues during subsequent periods of immune attack. Experiments here test the hypothesis that an antioxidant given only in the peri-reperfusion period protects against not only oxidative but also nitrosative stress, leading to reduced vasculopathy long after cardiac allotransplantation. Experiments were performed using a murine heterotopic cardiac transplantation model. An antioxidant, in the form of intraperitoneal high-dose riboflavin, was given to recipients during the initial 3 days after transplantation. Antioxidant-treated mice showed significantly longer graft survival than control mice. At 4 h after transplantation, antioxidant treatment significantly reduced graft lipid peroxidation and oxidized DNA and preserved antioxidant enzyme activity. At day 6 posttransplantation, the redox-sensitive transcription factor nuclear factor-κB and inducible nitric oxide synthase were significantly reduced following antioxidant treatment, with concomitant reduction of nitrotyrosine. Despite the limited duration of antioxidant treatment, both acute and chronic rejection were significantly suppressed. In vitro experiments confirmed suppression of nitrosative and oxidative stress and cardiomyocyte damage in antioxidant-treated cardiac allografts. Collectively, antioxidant administration during the initial 3 days after transplantation significantly reduces nitrosative and oxidative stress in cardiac allografts, modulates immune responses, and protects against vasculopathy.

背景．癌性胸膜炎による胸水貯留は胸腔ドレナージ施行後も肺が十分に再膨張しないことがあり，そのコントロールに難渋することがある．今回，我々は癌性胸膜炎による膨張不全肺に対して，ウロキナーゼの胸腔内注入を行い良好な肺の再膨張を得られた症例を経験したので報告する．症例．56歳女性．左乳癌術後経過観察中に左胸水の出現を認めた．その後胸水の著明な増加と労作時の呼吸困難が出現したため，当院乳腺科入院となった．胸腔ドレナージの後に胸膜癒着術が施行されたが，肺の膨張は不十分で胸腔内に多房性の胸水貯留が認められた．フィブリン溶解を目的としてウロキナーゼが胸腔内に投与された．その結果，形成されていた多房性の胸水は消失し良好な肺の再膨張が得られた．その後，再度胸膜癒着術が施行された．患者は約7ヶ月後に癌死となったが，その間胸水の再貯留を認めることなく安定した呼吸状態を保ち，自宅での生活が可能であった．結論．癌性胸膜炎に対するウロキナーゼの胸腔内注入は，trapped lungに対する治療法として有用であった．

Chronic airway rejection, characterized by lymphocytic bronchitis, epithelial cell damage, and obliterative bronchiolitis (OB), limits long-term survival after lung transplantation. The transcription factor early growth response gene-1 (Egr-1) induces diverse inflammatory mediators, some involved in OB pathogenesis. An orthotopic mouse tracheal transplant model was used to determine whether Egr-1 promotes development of airway allograft rejection. Significantly higher Egr-1 mRNA levels were seen in allografts (3.2-fold increase vs. isografts, P = 0.012). Allografts revealed thickening of epithelial and subepithelial airway layers (51 ± 4% luminal encroachment for allografts vs. 20 ± 3% for isografts, P < 0.0001) marked by significant lymphocytic infiltration. Absence of the Egr-1 gene in donor (but not recipient) tissue resulted in significant reduction in luminal narrowing (34 ± 4%, P = 0.0001) with corresponding diminution of T cell infiltration. Egr-1 null allografts exhibited a striking reduction in inducible nitric oxide synthase (iNOS) expression. Effector cytokines previously implicated in OB pathogenesis with known Egr-1 promoter motifs (IL-1β and JE/monocyte chemoattractant protein-1) were reduced in Egr-1 null allografts. These data suggest a paradigm wherein local induction of Egr-1 in tracheal allografts drives expression of inflammatory mediators responsible for lymphocyte recruitment and tissue destruction characteristic of airway rejection.

We reviewed our experience in the surgical treatment of 47 patients with colorectal pulmonary metastases and investigated factors affecting their survival.From September 1986 to December 1999, 47 patients underwent 59 thoracotomies for pulmonary metastases from colorectal cancer.The median interval between colorectal resection and lung resection (disease-free interval [DFI]) was 33 months. Overall, 5-year survival was 48%. Five-year survival was 51% for patients with solitary metastasis (n = 30), 47% for patients with ipsilateral multiple metastases (n = 11), and 50% for patients with bilateral metastases (n = 6), and there were no significant differences. Five-year survival was 80.8% for 14 patients with DFI of2 years and 39.7% for 30 patients with a DFI of2 years (p = 0.22). Five-year survival for 11 patients with normal prethoracotomy carcinoembryonic antigen (CEA) levels was 70%, and that for 26 patients with elevated prethoracotomy CEA levels (5 ng/mL) was 36% (p0.05). Eight patients had extrathoracic disease. The median survival time after pulmonary resection was 18.5 months, and the 5-year survival was 60%. A second resection for recurrent metastases was performed in five patients, and a third resection was done in one patient. All six patients are alive. The median survival of five patients who underwent a second thoracotomy was 22 months (range, 2 to 68 months), and one patient is alive 39 months after the third resection.Pulmonary resection for metastases from colorectal cancer may help prolong survival in selected patients, even with bilateral lesions, recurrent metastasectomy, or extrathoracic disease. Prethoracotomy CEA level was found to be a significant prognostic factor.

Background Riboflavin is a well-known nutritional supplement that has been shown to exhibit antioxidant properties and protect tissue from oxidative damage. We hypothesized that riboflavin given during cardiac ischemia-reperfusion (I/R) might reduce subsequent acute rejection, after allotransplantation, and coronary allograft vasculopathy (CAV). Methods A murine heterotopic cardiac transplantation model was used to test whether riboflavin improves I/R injury and acute/chronic rejection. Results Riboflavin significantly reduced oxidant production and inflammatory mediator production induced by I/R injury, as evidenced by decreased levels of malondialdehyde, myeloperoxidase activity, and tumor necrosis factor alpha. Administration of riboflavin also improved graft survival and suppressed T-cell infiltration and donor-reactive alloantibody formation during the early period after allotransplantation. A murine long-term cardiac allograft model using immunosuppression (preoperative anti-murine CD4 and anti-CD8) was employed to investigate the effect of riboflavin against CAV at 60 days. Riboflavin-treated grafts exhibited a significant decrease in the severity of coronary artery luminal occlusion as compared with saline-treated grafts (17.4+/-1.8% vs. 43.5+/-5.6%, P=0.0012). However, there was no significant effect of riboflavin to reduce donor-reactive alloantibodies in this chronic model. Conclusions These data indicate that riboflavin improves early I/R injury and reduces the development of CAV, most likely due to alloantigen-independent effects such as reduced early graft oxidant stress. Riboflavin administered in the setting of cardiac allograft transplantation appears to be a powerful means to reduce early graft lipid peroxidation, leukocytic infiltration, and cytokine production as well as to suppress the late development of cardiac allograft vasculopathy.

SMXA-5 mice are a high-fat diet-induced type 2 diabetes animal model established from non-diabetic SM/J and A/J mice. By using F2 intercross mice between SMXA-5 and SM/J mice under feeding with a high-fat diet, we previously mapped a major diabetogenic QTL (T2dm2sa) on chromosome 2. We then produced the congenic strain (SM.A-T2dm2sa (R0), 20.8-163.0 Mb) and demonstrated that the A/J allele of T2dm2sa impaired glucose tolerance and increased body weight and body mass index in the congenic strain compared to SM/J mice. We also showed that the combination of T2dm2sa and other diabetogenic loci was needed to develop the high-fat diet-induced type 2 diabetes. In this study, to narrow the potential genomic region containing the gene(s) responsible for T2dm2sa, we constructed R1 and R2 congenic strains. Both R1 (69.6-163.0 Mb) and R2 (20.8-128.2 Mb) congenic mice exhibited increases in body weight and abdominal fat weight and impaired glucose tolerance compared to SM/J mice. The R1 and R2 congenic analyses strongly suggested that the responsible genes existed in the overlapping genomic interval (69.6-128.2 Mb) between R1 and R2. In addition, studies using the newly established R1A congenic strain showed that the narrowed genomic region (69.6-75.4 Mb) affected not only obesity but also glucose tolerance. To search for candidate genes within the R1A genomic region, we performed exome sequencing analysis between SM/J and A/J mice and extracted 4 genes (Itga6, Zak, Gpr155, and Mtx2) with non-synonymous coding SNPs. These four genes might be candidate genes for type 2 diabetes caused by gene-gene interactions. This study indicated that one of the genes responsible for high-fat diet-induced diabetes exists in the 5.8 Mb genomic interval on mouse chromosome 2.