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We previously demonstrated that donor treatment with inhaled hydrogen protects lung grafts from cold ischemia/reperfusion (I/R) injury during lung transplantation. To elucidate the mechanisms underlying hydrogen's protective effects, we conducted a gene array analysis to identify changes in gene expression associated with hydrogen treatment.Donor rats were exposed to mechanical ventilation with 98% oxygen and 2% nitrogen or 2% hydrogen for 3 h before harvest; lung grafts were stored for 4h in cold Perfadex. Affymetrix gene array analysis of mRNA transcripts was performed on the lung tissue prior to implantation.Pretreatment of donor lungs with hydrogen altered the expression of 229 genes represented on the array (182 upregulated; 47 downregulated). Hydrogen treatment induced several lung surfactant-related genes, ATP synthase genes and stress-response genes. The intracellular surfactant pool, tissue adenosine triphosphate (ATP) levels and heat shock protein 70 (HSP70) expression increased in the hydrogen-treated grafts. Hydrogen treatment also induced the transcription factors C/EBPα and C/EBPβ, which are known regulators of surfactant-related genes.Donor ventilation with hydrogen significantly increases expression of surfactant-related molecules, ATP synthases and stress-response molecules in lung grafts. The induction of these molecules may underlie hydrogen's protective effects against I/R injury during transplantation.

Summary Recent evidence suggests that molecular hydrogen has therapeutic value for disease states that involve inflammation. We hypothesized that drinking hydrogen-rich water (HW) daily would protect cardiac and aortic allograft recipients from inflammation-associated deterioration. Heterotopic heart transplantation with short-course tacrolimus immunosuppression and orthotopic aortic transplantation were performed in allogeneic rat strains. HW was generated either by bubbling hydrogen gas through tap water (Bu-HW) or via chemical reaction using a magnesium stick [Mg + 2H2O → Mg (OH)2 + H2] immersed in tap water (Mg-HW). Recipients were given either regular water (RW), Mg-HW, Bu-HW, or Mg-HW that had been subsequently degassed (DW). Graft survival was assessed by daily palpation for a heartbeat. Drinking Mg-HW or Bu-HW was remarkably effective in prolonging heart graft survival and reducing intimal hyperplasia in transplanted aortas as compared with grafts treated with RW or DW. Furthermore, T cell proliferation was significantly inhibited in the presence of hydrogen in vitro, accompanied by less production of interleukin-2 and interferon-γ. Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain. Drinking HW prolongs survival of cardiac allografts and reduces intimal hyperplasia of aortic allografts.

Angiosarcoma is a rare neoplasm, accounting for only 1%-2% of all sarcomas. It occurs most frequently in the skin and soft tissue and rarely in the thoracic region. To our knowledge, a mediastinal angiosarcoma is extremely rare. We report on the surgical resection of a rare case of giant epithelioid angiosarcoma originating in the anterior mediastinum, followed by six courses of adjuvant chemotherapy (doxorubicin + ifosfamide). The patient is alive and asymptomatic 1 year after surgery. As the prognosis for unresectable cases is generally dismal, surgical resection and adjuvant therapy can be an option for mediastinal angiosarcoma.

症例は66歳女性，4年前に原発性食道悪性黒色腫と診断され，胸部食道切除ならびに術後補助化学療法（DAC-tam）を施行した．その後，外来で経過観察中の胸部CTで，左肺門部のリンパ節腫大とPET-CTで同部位に異常集積を認めた．5-S-cysteinyl dopaも上昇し，原発性食道悪性黒色腫のリンパ節転移が疑われ手術となった．完全内臓逆位であり，脈管の走行は左右鏡面像であった．腫大したリンパ節はV1，V3，A3の間に存在し，上葉とも接していた．病変を完全切除するためにV1，V3，A3を結紮切離した．また周囲の肺も一部合併切除した．病理所見は食道悪性黒色腫のリンパ節転移であった．術後補助化学療法（DTIC）を6コース施行し，10ヵ月たった現在，再発無く経過良好である．悪性黒色腫のリンパ節転移に対し，切除が可能であれば手術は有用であると考えられた．

症例は63歳，男性で検診にて胸部異常陰影を指摘された．胸部CTで前縦隔左側に境界明瞭な腫瘤が認められ，CT下針生検で孤立性線維性腫瘍が疑われた．手術は，胸骨正中切開にてアプローチし，腫瘍摘除ならびに腫瘍浸潤が疑われた心嚢の合併切除が行われた．術後病理で脱分化型脂肪肉腫と診断され，補助化学療法が施行された．今回我々は，極めて稀な前縦隔原発の脱分化型脂肪肉腫を経験したので，若干の文献的考察を含めて報告する．

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive malignant tumor, which was proposed as a novel type of neuroendocrine tumor in 1991. Although it is categorized as a non-small cell lung carcinoma, the precise pathological condition is unknown due to its rare occurrence. The present study outlines the case of a patient presenting with an LCNEC that exhibited pagetoid spread from the region of the primary tumor to the bronchial epithelium (distance, >30 mm). The pagetoid spread was unconfirmed preoperatively, however, was identified by intraoperative rapid diagnosis. This caused us to suffer the perioperative decision of additional resection and resulted in an incomplete resection, as suture of the bronchus was not possible. Pagetoid spread, which is often apparent in the breast, presents as a rare pattern of infiltration of cancer cells when a massive carcinoma is identified beneath the intraepithelial spread. Although preoperative diagnosis of pagetoid spread is difficult due to its rarity and undefined clinical features, it is important for surgeons and pathologists treating lung cancer patients to be aware of potential pagetoid spread in the thoracic region.

Nectin-like molecule-5 (Necl-5) is an immunoglobulin (Ig)-like molecule that is up-regulated in many types of cancer cells. It was shown experimentally that Necl-5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl-5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl-5. The relationship between expression of Necl-5 and clinicopathological features was analyzed, and the influence of Necl-5 expression on outcomes in these patients was assessed. A strong expression of Necl-5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl-5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease-free survival rate in patients with positive Necl-5 overexpression was significantly lower than that in patients with negative Necl-5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl-5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease-free survival rate of the Necl-5-positive group was significantly lower than that of the Necl-5-negative group (P = 0.0192). These results indicate that Necl-5 plays a role in mediating tumor cell invasion and that the overexpression of Necl-5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma. (Cancer Sci 2010; 101: 1326–1330)

The mediastinal mature teratoma is uncommon in adult and sometimes ruptures. We present a case of perforation of mediastinal mature teratoma. A 22-year-old man, who had been scheduled for surgery to resect anterior mediastinal teratoma, was referred to our hospital due to sudden chest pain. The enhanced computed tomography findings suggested a perforation of the teratoma and the emergency surgery was performed. Extirpation of the tumor with partial resection of right upper lung, pericardium, and superior vena cava was performed. The histological diagnosis was mature teratoma and the defect of the mediastinal pleura was found to be the site of perforation. The patient was well and discharged from the hospital without complications.

A thymoma is a neoplasm that arises from the epithelial cells of the thymus, and may cause various signs and symptoms dependent upon its local extent. A non-traumatic hemothorax is extremely rare. The present study reports the case of a 77-year-old female who presented with an acute onset of chest pain. Imaging procedures revealed a mass occupying the anterior mediastinum and left hemithorax, and a left pleural effusion. Progressive anemia was noted following admission. Left hemothorax due to rupture of the anterior mediastinal mass was suspected, and emergency surgery was performed. Hemorrhage was observed on the cut surface of the tumor. An analysis of frozen sections indicated a thymoma, and a thymo-partial thymectomy was subsequently performed to remove as much of the hematoma as possible. The patient was discharged on post-operative day 13 following an uneventful recovery. The present case suggests that in previously healthy individuals, sudden-onset dyspnea and chest pain co-occurring with an acute widening of the mediastinum observed on roentgenograph may be indicative of a ruptured thymoma.

The GINS complex associates with cell division cycle (Cdc) protein 45 and mini-chromosome maintenance (Mcm) proteins 2-7 to form the Cdc45-Mcm-GINS (CMG) complex, which is essential for DNA duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non-small-cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression.

Background Most of the experimental work assessing optimal lung inflation during lung graft preservation was performed in the late 1990s. Since that time, lung preservation before transplantation has been more standardized, and the optimal lung inflation techniques used during lung preservation in the current clinical setting remain undefined. Nonetheless, lung inflation during storage may play a pivotal role in optimal lung preservation. Materials and Methods Lewis rat lungs were perfused with and stored in cold, low-potassium dextran solution (Perfadex, Vitrolife, Goteborg, Sweden) for 6 hours at different levels of lung inflation (25, 50, 75, or 100% of vital capacity [VC]). Orthotopic left lung transplantation using cuff techniques was performed in syngeneic Lewis rats. Posttransplant allograft function, expression of proinflammatory mediators, and expression of lung surfactants were evaluated. Results Lungs inflated to 75 or 100% VC showed a significantly better oxygenation in blood gas analysis than lungs inflated to 25 or 50% VC. The levels of mRNAs for tumor necrosis factor-α, pro-interleukin-1β, intracellular adhesion molecule 1 were attenuated in lungs inflated to 75 or 100% VC as compared with deflated lungs, suggesting reduced ischemia/reperfusion injury. In addition, transmission electron microscopy demonstrated better preserved lung surfactants in the alveolar space in the lungs inflated to 75 or 100% VC. Conclusions Inflating lungs to 75 or 100% VC during preservation may be beneficial and result in better posttransplant allograft function through attenuated reperfusion injury and better preserved lung surfactants.

The Notch signaling pathway enables regulation and control of development, differentiation, and homeostasis through cell-cell communication. Our investigation shows that Notch signaling directly activates the Nrf2 stress adaptive response pathway through recruitment of the Notch intracellular domain (NICD) transcriptosome to a conserved Rbpjκ site in the promoter of Nrf2. Stimulation of Notch signaling through Notch ligand expression in cells and by overexpression of the NICD in Rosa(NICD/-)::AlbCre mice in vivo induces expression of Nrf2 and its target genes. Continuous and transient NICD expression in the liver produces a Notch-dependent cytoprotective response through direct transcriptional activation of Nrf2 signaling to rescue mice from acute acetaminophen toxicity. This response can be reversed upon genetic disruption of Nrf2. Morphological studies showed that the characteristic phenotype of high-density intrahepatic bile ducts and enlarged liver in Rosa(NICD/-)::AlbCre mice could be at least partially reversed after Nrf2 disruption. Furthermore, the liver and bile duct phenotypes could be recapitulated with constitutive activation of Nrf2 signaling in Keap1(F/F)::AlbCre mice. It appears that Notch-to-Nrf2 signaling is another important determinant in liver development and function and promotes cell-cell cytoprotective signaling responses.

OBJECTIVES: Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP. METHODS: The donor heart–lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4°C. And then, the heart–lung blocks were flushed retrogradely and warmed up to 37°C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2 ,8 % CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37°C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR). RESULTS: R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation. CONCLUSIONS: Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.

Recent evidence suggests that molecular hydrogen has therapeutic value for disease states that involve inflammation. We hypothesized that drinking hydrogen-rich water (HW) daily would protect cardiac and aortic allograft recipients from inflammation-associated deterioration. Heterotopic heart transplantation with short-course tacrolimus immunosuppression and orthotopic aortic transplantation were performed in allogeneic rat strains. HW was generated either by bubbling hydrogen gas through tap water (Bu-HW) or via chemical reaction using a magnesium stick [Mg + 2H(2) O → Mg (OH)(2) + H(2) ] immersed in tap water (Mg-HW). Recipients were given either regular water (RW), Mg-HW, Bu-HW, or Mg-HW that had been subsequently degassed (DW). Graft survival was assessed by daily palpation for a heartbeat. Drinking Mg-HW or Bu-HW was remarkably effective in prolonging heart graft survival and reducing intimal hyperplasia in transplanted aortas as compared with grafts treated with RW or DW. Furthermore, T cell proliferation was significantly inhibited in the presence of hydrogen in vitro, accompanied by less production of interleukin-2 and interferon-γ. Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain. Drinking HW prolongs survival of cardiac allografts and reduces intimal hyperplasia of aortic allografts.

OBJECTIVES: Biliverdin (BV), one of the byproducts of heme catalysis through the heme oxygenase system, is a known scavenger of the reactive oxygen species. We hypothesized that adding BV to the perfusate and cold storage solution could protect rat lung grafts from oxidative injuries via its antioxidant efficacies. METHODS: Orthotopic left lung transplantation was performed in a syngenic Lewis-to-Lewis rat combination under 100% oxygen. Grafts were preserved in low-potassium dextran (LPD; Perfadex) at 4°C for 6 h with or without supplementation of 1 or 10 μ Mo f BV into LPD. RESULTS: Prolonged cold storage and reperfusion resulted in a considerable deterioration of graft functions associated with massive apoptosis in the grafts after reperfusion. The untreated grafts exhibited the early up-regulations of mRNA for inflammatory mediators and an increase in a marker of lipid peroxidation, showing oxidative injuries. Although BV supplementation of LPD at a lower concentration (1 μM) did not improve the graft gas exchange, the grafts treated with BV (10 μM) showed a significant improvement of oxygenation and less inflammatory responses as well as reduced lipid peroxidation and apoptosis. Although the rapid activations of mitogenactivated protein kinases (MAPKs) were seen 30 min after reperfusion in the grafts stored in control LPD, BV treatment significantly reduced phosphorylated-MAPK protein expression. CONCLUSIONS: This study demonstrates that the exposure of the lung grafts to BV during cold storage can impart potent cytoprotective effects to lung cold ischaemia/reperfusion injury and significantly improve the lung graft function following extended cold preservation and transplantation by the mechanism of a reduction in oxidative injury and following inflammatory events.

Background Exogenously administered hydrogen exerts cytoprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in various disease settings, including organ transplantation. Our objective in this study was to evaluate the efficacy of a novel cold storage device equipped with a hydrogen-rich water bath. Methods The study used an established rat heterotopic transplantation model. Syngeneic heart grafts from elderly donors (60- to 70-week-old Lewis rats) or allografts from adult donors (12-week-old Brown Norway rats) were exposed to prolonged cold preservation. The cardiac grafts were stored in plastic bags containing Celsior, which were immersed in the cold water bath equipped with an electrolyzer to saturate the water with hydrogen. The cardiac grafts then were heterotopically engrafted into Lewis rat recipients. Results In both experimental settings, serum troponin I and creatine phosphokinase were markedly elevated 3 hours after reperfusion in the control grafts without hydrogen treatment. The grafts exhibited prominent inflammatory responses, including neutrophil infiltration and the upregulation of messenger RNAs for pro-inflammatory cytokines and chemokines. Myocardial injury and inflammatory events were significantly attenuated by organ storage in the hydrogen-rich water bath. The grafts stored using the hydrogen-rich water bath also exhibited less mitochondrial damage and a higher adenosine triphosphate content. Conclusions Hydrogen delivery to cardiac grafts during cold preservation using a novel hydrogen-supplemented water bath efficiently ameliorated myocardial injury due to cold ischemia and reperfusion. This new device to saturate organs with hydrogen during cold storage merits further investigation for possible therapeutic and preventative use during transplantation.

Descending necrotizing mediastinitis is a critical infection and the mortality rate remains high. Early aggressive surgical drainage and antibiotic therapy are essential for treatment. We evaluated the efficiency of transthoracic drainage using a minimally invasive technique in 11 cases of descending necrotizing mediastinitis between May 2002 and March 2008. Weperformed a right-side minithoracotomy with thoracoscopic assistance, and the mediastinum was thoroughly drained. The length of hospitalization ranged from 30 to 117 days. The postoperative course was good in all patients, and the outcome was favorable. All patients were discharged without major complications. We recommend employing a minithoracotomy with thoracoscopic assistance for aggressive treatment of descending necrotizing mediastinitis.

UV laser photodissociation of trimethylgallium (TMG) in the gas phase and on a quartz surface at 110 K was studied with multiphoton ionization (MPI)-time of flight mass spectroscopy. A series of ions, Ga(CH 3 ) n + (n=1-3), Ga + , and CH n + (n=1-3), were observed in the photolysis in the gas phase. The dependence of ion signal intensitics on photodissociation/photoionization laser wavelength and on laser power was studied, and its implication in the reaction mechanism is discussed. The parent ion Ga(CH 3 ) 3 + was observed for the first time. Its depletion at ∼215 and ∼220 nm indicates the presence of a metastable species which absorbs light in the ionization step of excited TMG

Malignant pleural mesothelioma (MPM) has a poor prognosis and is a treatment resistant tumor, which is increasing in frequency throughout the world. The poor prognosis is due to the aggressive local invasiveness rather than distant metastasis. In this study, we established a cell line of malignant mesothelioma from a clinical specimen and assessed the relationship between the expression of MT1-MMP and the invasion ability of that line, as well as the cultured cells of several other lines, using the simple method that we created previously. We established a cell line from a clinical specimen from a patient with malignant mesothelioma. We assessed the invasive activities of MPM cells in an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) system that enabled us to visualize cell movements during invasion. To assess the role of MT1-MMP in the invasive activity of MPM cells, we knocked down its expression by RNA interference (RNAi). The invasion assay with DL-CGH revealed that a high expression of MT1-MMP in MPM cells was associated with aggressive invasive activity. The RNAi of MT1-MMP indicated that the expression of MT1-MMP might have a crucial role in the invasiveness of MPM cells. The MT1-MMP expression in MPM cells is related to their capacity for locally aggressive spreading into the pleura and the surrounding tissues, and MT1-MMP should be a suitable molecular target for the suppression of the invasiveness of MPM.

BACKGROUND: Several reports have revealed the association between single nucleotide polymorphisms (SNPs) and the development of cancer. Although many SNPs have been investigated, they were tested individually. In this study, nonsynonymous SNPs present in DNA damage response genes were comprehensively analyzed for lung cancer susceptibility. METHODS: The authors selected 37 nonsynonymous SNPs in 23 genes involved in DNA damage repair pathways. Fifty lung adenocarcinoma patients resected at their institution between 2002 and 2005 and 50 individuals without any known history of cancer were recruited for a case-control study. RESULTS: Three variants (XRCC1 194Trp homozygotes, POLδ1 119His homozygotes, and RAD9 239Arg heterozygotes) tended to coassociate with lung cancer risk. The authors analyzed and calculated whether the association between combinations of these 3 SNPs significantly affected the risk of lung cancer. Compared with carriers of either XRCC1 194Trp homozygote or RAD9 239Arg heterozygote variants, noncarriers were at a significantly decreased risk for lung cancer (odds ratio [OR], 0.282; confidence interval [CI], 0.089-0.893). The same results were found for the combination of POLδ1 119His homozygotes and RAD9 239Arg heterozygotes (OR, 0.277; CI, 0.077-0.993). Moreover, compared with carriers that had at least 1 of the 3 variants, noncarriers showed a more significant decrease in risk (OR, 0.263; CI, 0.090-0.767). CONCLUSIONS: Analysis of the presence of XRCC1 194Trp homozygote, POLδ1 119His homozygote, and RAD9 239Arg heterozygote variants revealed that their coassociation leads to a significant risk for the development of lung adenocarcinoma. Inclusive analyses of different SNPs were important in this cancer risk study. Cancer 2010. © 2010 American Cancer Society.

Descending necrotizing mediastinitis (DNM) is a fatal disease that is caused by a cervical or odontogenical infection spreading downward to the mediastinum through anatomical cervical spaces. The mortality rate of DNM is still high. We have experience of 2 cases of DNM. In case 1 patient, a cervical abscess expanded to the esophageal hiatus through the superior and posterior mediastinum. A right minithoracotomy on the triangle of auscultation was performed with a thoracoscope in order to dissect the necrotic materials and drain the abscess. In case 2 patient, a left second costal cartilage resection was performed to approach the anterior mediastinal abscess. Both patients recovered well.

Objective: There is no criterion for the timing of surgical resection of pulmonary metastasis. In this study, we investigated the optimal period for pulmonary metastasectomy. Methods: Between 2000 and 2005, 68 patients underwent complete pulmonary resection of metastatic cancer. Clinical prognostic factor in multivariate analysis was examined. Results: The interval from pulmonary metastasectomy until subsequent recurrence and the interval from detection of pulmonary metastasis until pulmonary metastasectomy were independent prognostic factors. To investigate the relationship between the two characteristics, the 68 patients were divided into two groups according to the interval from lung metastasectomy until subsequent recurrence. Nineteen patients relapsed within 1 year after pulmonary metastasectomy (group A), while 49 patients did not relapse within 1 year (group B). The interval from detection of pulmonary metastasis until pulmonary metastasectomy was significantly shorter in group A than in group B (2.9 months vs 7.1 months, p = 0.01). Based on these results, we divided the patients into two different groups and survival was compared. Significantly shorter survival was observed in the patients who underwent pulmonary metastasectomy within 3 months after detection of pulmonary metastasis (group X, n = 35) than in those who underwent the surgery beyond 3 months (group Y, n = 33). Conclusions: There were many cases of early relapse after metastasectomy when the interval from detection of pulmonary metastasis until pulmonary metastasectomy was short. Performing metastasectomy at least three months after detection of pulmonary metastasis may significantly improve the prognosis of patients. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Purpose Hydrogen (H 2 ) has a high potential as a safe and multi-potent therapeutic gas. We have recently reported inhaled H 2 could prevent acute lung injury through anti-inflammatory and anti-apoptotic effects in lung injury animal models. We hypothesized that H 2 inhalation during ex-vivo lung perfusion (EVLP) that is a novel strategy for donor lung preservation, optimizes the opportunity and contributes to further refinement in the current EVLP strategy. Methods and Materials Using heart-lung blocks harvested from Lewis rats, our rat EVLP system was established in a stable and reliable fashion where rat lungs after 1hr cold preservation, perfused with acellular Steen solution and ventilated at 37°C on EVLP for 4hrs were evaluated. In the H 2 -treated group, lungs were ventilated with 2% H 2 during EVLP and their results were compared with those from lungs ventilated with air on EVLP as the control group. Results H 2 inhalation was associated with significantly better preserved graft function in terms of oxygenation, lung compliance and reduced pulmonary vascular resistance. In addition, H 2 -treated lungs exhibited significantly reduced proinflammatory cytokine (IL-6, IL-1β, TNF-α) mRNA levels in the allografts. Interestingly, H 2 -treated lungs resulted in significantly reduced elevation of lactate levels as well as hypoxia-inducible factor 1 (HIF-1) levels in lung tissues as compared to the control group, suggesting the contribution of H 2 to improve metabolism in lung grafts during EVLP. [ figure 1 ] Conclusions H 2 inhalation during EVLP may play a pivotal role in preserving better graft function through promotion of anti-inflammatory and cytoprotective effects as well as activation of mitochondrial biogenesis in lungs.

Purpose Historically, most of experimental work to seek for the optimal lung inflation techniques during lung preservation was performed in the late 1990s. Currently clinical lung preservation protocol has been more standardized; however, the optimal lung inflation techniques under the current lung preservation setting remain to be defined while those techniques play a pivotal role in the optimal lung preservation. Methods and Materials Lewis rat lungs were perfused with and stored in cold Perfadex for 6 hours at different levels of lung inflation defined by total lung capacity (25%, 50%, 75% or 100% of total lung capacity (TLC)) ( Fig. 1 A). Then orthotopic left lung transplantation using cuff techniques was performed in syngenic Lewis rats. Two hours after reperfusion, posttransplant allograft function, pro-inflammatory and lung surfactant profiles were evaluated and compared among the groups. Results Lungs with 75% or 100% TLC inflation showed a significantly better oxygenation in blood gas than 25% and 50% inflated lungs ( Fig 1 B). Lungs with 75% or 100% TLC exhibited attenuated serum TNF-α, IL-1β, ICAM-1 mRNA levels as compared to those with the deflated lungs, suggesting reduced ischemic reperfusion injury. In addition, transmission electron microscopy investigation confirmed better preserved lung surfactants in the alveolar space in the lungs with 75% or 100% TLC. Conclusions Lungs with 75% or 100% TLC inflation during preservation appear to be more beneficial with better posttransplant allograft function through attenuated reperfusion injury and better preserved lung surfactants.

Purpose Airway hypoxia due to microvascular loss may be a predisposing factor for subsequent fibrotic remodeling in allografts, resulting in suboptimal transplant outcomes in lung transplantation. Ex-vivo lung perfusion (EVLP) is a novel strategy for lung allograft preservation that keeps the organs at physiological protective conditions. Modifying EVLP strategy, we have developed a new lung preservation technique focusing on airway protection through bronchial artery perfusion. Methods and Materials Using heart-lung blocks harvested from Lewis rats, we have developed a model where bronchial circulation (using another cannula from descending aorta, retrogradely) was synchronously perfused in addition to pulmonary circulation with acellular Steen solution on EVLP (the scheme of the model is shown in Fig 1 ). Rat lungs after 1 hour cold preservation, perfused and ventilated on EVLP for 4 hours were evaluated and lungs with bronchial artery perfusion were compared with those without bronchial perfusion on EVLP. The studies were performed based on our rat EVLP protocol that has proven to be reliable with at least 4 hours of duration with stable results. Results At 4 hours on EVLP, bronchial artery perfusion was associated with significantly better preserved oxygenation and better compliance in lung allografts through reduced glucose consumption and increased ATP level as compared to the control group. Conclusions Bronchial artery perfusion on EVLP may be a new lung preservation strategy that breaks through the current major limitation in hypoxic transplant airways after lung transplantation.