Genetic Analysis Reveals Dispersal Patterns of Japanese Serow in Two Different Habitats of a Mountainous Region.

Dispersal increases the costs of feeding and predation risk in the new environment and is reported to be biased toward habitats similar to the natal region in some mammals. The benefits and costs of dispersal often differ between sexes, and most mammals show male-biased dispersal in relation to a polygamous mating system. Japanese serow is generally a solitary and monogamous species. However, recent studies have shown that the sociality of serows on Mt. Asama differs between habitat types. In the mountain forests with low forage availability, solitary habits and social monogamy were observed, while, in alpine grasslands, female grouping and social polygyny were observed, which is probably due to abundant forage availability. We investigated the effects of habitat characteristics and sociality on the dispersal of serows using fecal and tissue samples from two different habitats on Mt. Asama. The Fst value between the two areas was significantly positive, and the mean relatedness within areas was significantly higher than that between areas, which suggests limited gene flow and natal habitat-biased dispersal. Bayesian clustering analysis showed unidirectional gene flow from forest to grassland, which was probably due to the high forage availability of the grassland. Analyses of the assignment index and mean relatedness did not show male-biased dispersal, even in the grassland, where serows were polygynous. Thus, polygyny in the grassland is not linked to male-biased dispersal. In summary, our study suggests that dispersal patterns in Japanese serows are affected by habitat rather than social differences.

[A Case of Advanced Gastric Cancer with Preoperative Liver Metastasis and Postoperative Adrenal Metastasis, That Obtained Long-Term Recurrence-Free Survival after Resection and Chemotherapy].

The case was a 70-year-old man of highly advanced gastric cancer with 2 liver metastases(S3, S8)and pancreatic invasion. Three courses of S-1 plus L-OHP(SOX therapy)were performed, and total gastrectomy and combined resection of the spleen and body and tail of the pancreas and partial resection of the liver S3 and S8 were performed after reduction of primary tumor and liver metastasis. S-1 therapy was continued for 1 year as postoperative adjuvant chemotherapy. Left adrenal metastasis was detected by CT, 1 year and 6 months after the operation. PET-CT revealed no other areas suspected of recurrence, so left adrenalectomy was performed through the retroperitoneal space. Radical resection was not achieved because adhesions and scarring from the previous surgery were severe. Paclitaxel plus Ramucirumab was started and after 10 courses, the disappearance of the tumor shadow was observed on enhanced CT, and PET-CT. Three years and 3 months after the initial surgery and 1 year and 8 months after resection of adrenal metastasis, the patient is alive without recurrence.

Prognostic Impact of Number of Organ Invasions in Patients with Surgically Resected Thymoma.

PURPOSE: This study aimed to explore the clinical implications and prognostic value of the number of organ/structure invasions (NOI) in patients with thymoma after curative surgical resection. METHODS: We retrospectively analyzed 306 consecutive Japanese patients with thymoma who underwent curative surgical resection. Tumor invasions of pericardium, mediastinal pleura, phrenic nerve, lung, and venous structures were examined histopathologically. Cases were classified into four subgroups according to NOI: group 0, no tumor invasion; group 1, tumor invasion into single organ/structure; group 2, tumor invasion of two organs/structures; group 3, invasion of three or more organs/structures. Associations with NOI and several clinical characteristics and their prognostic significance were analyzed. RESULTS: Pleural invasion was found in 100 cases (32.7%), lung invasion in 48 cases (15.7%), pericardial invasion in 46 cases (15%), phrenic nerve invasion in 29 (9.5%), and venous invasion in 22 cases (7.2%). NOI was classed as group 0 in 201 cases (65.0%), group 1 in 42 cases (13.7%), group 2 in 20 cases (6.5%), and group 3 in 43 cases (14.1%). Cases with higher NOI showed significantly worse relapse-free survival (RFS) and overall survival (OS). Cox's proportional hazard model analysis also identified NOI as a prognostic factor affecting RFS and OS. CONCLUSIONS: Cases with higher NOI of thymoma after radical surgical resection showed significantly worse recurrence rates and survival.

[Surveillance Bronchoscopy after Lung Transplantation].

Acute cellular rejection( ACR) is one of the major complications of the acute phase after lung transplantation. In addition, ACR is considered to be a major cause of chronic lung allograft dysfunction (CLAD). Therefore, the diagnosis and treatment for ACR are major issues at transplantation facilities. Surveillance bronchoscopy( SB) is performed at many institutions as the golden standard for ACR diagnosis, and our hospital also implements long-term post-transplant monitoring of ACR as a preventive measure for CLAD. However, the suitability of SB may be questioned due to the risk of complications such as bleeding and pneumothorax. Here, we would like to report the results of SB in our department and discuss future diagnosis and treatment policy for ACR.

Hepatocyte growth factor ameliorates methylglyoxal-induced peritoneal inflammation and fibrosis in mouse model.

BACKGROUND: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. METHODS: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. RESULTS: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-ß, TNF-α, IL-1ß) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. CONCLUSION: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.

Importance of the preoperative prognostic nutritional index score as a predictor of chronic lung allograft dysfunction after lung transplantation: a Japanese single-institution study.

PURPOSES: Numerous indicators have been discussed as predictive markers for the incidence of chronic allograft dysfunction (CLAD) after lung transplantation (LTX). The aim of this study was to evaluate whether or not the preoperative prognostic nutrition index (PNI) correlated with the development of CLAD. METHOD: This study is a single-center and retrospective cohort study. Forty-six patients underwent cadaveric lung transplantation between 2000 and 2016 at our institution. The primary endpoint of this study was the CLAD-free survival of the patients. RESULT: CLAD was diagnosed in 11 patients (23%) during the follow-up period. Potential risk factors included recipient factors, donor factors, number of HLA mismatches, operation-related factors, and preoperative blood test results, including the preoperative PNI. The patients with a higher PNI showed a longer CLAD-free survival after LTX than those with lower values according to univariate and multivariate analyses (p = 0.01, 0.04, respectively). The 5-year CLAD-free survival rates in the higher-PNI patients and lower-PNI patients were 94% and 62%, respectively. CONCLUSION: We found that a lower preoperative PNI of the recipient was significantly associated with a higher incidence rate of CLAD. The preoperative PNI may, therefore, be useful as a predictor of the development of CLAD.

Surgical management of thymic epithelial tumors.

Resection is the mainstay of treatment for thymic epithelial tumors (TETs), with complete removal of the tumor and involved organs being the ultimate aim. The choice of surgical approach plays a major role in defining treatment success, and the optimal choice of method should thus provide an adequate surgical view to achieve complete tumor resection. While median sternotomy is considered the gold standard for access to the mediastinum, several minimally invasive approaches to thymectomy have been described, including video-assisted robotic-assisted thymectomy, although the oncological outcomes of that procedure remain unclear. A multimodal approach incorporating chemotherapy or chemoradiotherapy followed by extended surgery may improve resectability and outcomes for patients with advanced TETs. Surgical debulking is also reportedly acceptable for invasive thymoma because of its potential for achieving favorable outcomes. Re-resection is an acceptable option for patients with recurrent thymoma after initial resection, and repeat resection for recurrent pleural dissemination seems effective. Here, the literature on current clinical practices in the surgical management and treatment of TETs is reviewed.

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis.

PURPOSE: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. RESULTS: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). CONCLUSIONS: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

Genetic Variation in Y-Chromosome Genes of Sika Deer (Cervus nippon) in Japan.

Sika deer (Cervus nippon) in Japan are classified into southern and northern groups. However, previous studies primarily relied on maternally inherited mitochondrial DNA (mtDNA). The paternally inherited Y-chromosome is useful for analyzing the contribution of males to the population genetic history of sika deer. In total, approximately 16 kb of partial sequences of four Y-chromosomal genes, Y-linked, sex-determining region Y, DEAD-box helicase 3 Y-linked, and Zinc finger protein Y-linked, were sequenced to investigate intraspecific variation. As a result, we identified nine intronic single nucleotide polymorphisms (SNPs) in 478 sika deer samples collected over the entire Japanese archipelago from Hokkaido to Kyushu. SNP genotyping revealed 10 distinct haplotypes (SYH1-SYH10). The most common haplotype (SYH1) was present in all populations and was the most abundant haplotype, identified in 80.3% of the sampled individuals. The remaining haplotypes were unique to a single locality. SYH1 was also central to all other haplotypes that diverged by a SNP, resulting in this haplotype being the core of a star-like cluster topography. We found that contrary to mtDNA patterns, there was no clear differentiation of Y-chromosome markers between the southern and the northern populations. Due to the female philopatry of sika deer, mtDNA may provide a highly structured differentiation of populations. On the other hand, the male-biased gene flow may provide a reduced differentiation of populations. Our findings revealed that the genetic structure of the Japanese sika deer is more complex than previously thought based on mtDNA-based phylogeographic studies.

Long-Term Outcomes After Surgical Resection for Pleural Dissemination of Thymoma.

BACKGROUND: Cases of thymoma with pleural dissemination are occasionally encountered, and their management is difficult. Some reports have noted that surgical treatment for dissemination is effective, although the long-term results and clinical course details remain unclear. The current study investigated the short- and long-term outcomes of surgical resection of pleural dissemination. METHODS: A retrospective review examined the medical records for 38 patients who underwent surgical resection for pleural dissemination occurring synchronously with a primary thymoma or metachronously after complete surgical resection of a primary thymoma between 1996 and 2017 at the authors' institution. Clinical characteristics and prognostic factors were analyzed. RESULTS: The patients were classified into synchronous (n = 21) and metachronous (n = 17) groups. The 10-year overall survival rate was 59% for the synchronous group and 88% for the metachronous group. The median follow-up period for all the patients was 61 months (range 4-225 months). No perioperative deaths occurred. For all the patients, the 5- and 10-year overall survival rates were respectively 91% and 82%, and the 5- and 10-year relapse-free survival rates were respectively 29% and 19%. A significantly worse prognosis was observed for patients 50 years of age or older than for those younger than 50 years (p = 0.02). For 13 patients who underwent repeat resection for pleural dissemination, the prognosis was better than for those without repeat resection (p < 0.01). CONCLUSION: Surgical resection of thymoma with pleural disseminated nodules can be safely performed and provides a favorable long-term outcome. Repeat resection is considered to be effective for achieving a good prognosis.

Long-Term Outcomes of Pulmonary Resection for Lung Cancer Patients with Chronic Kidney Disease.

BACKGROUND: The survival outcome in lung cancer patients with chronic kidney disease (CKD) has not been well evaluated. The aim of this study was to evaluate the survival outcomes following non-small cell lung cancer (NSCLC) surgery in patients with CKD as a preoperative comorbidity. METHODS: Among 671 patients who underwent surgery for NSCLC between 2007 and 2014 at our hospital, 55 (8%) had CKD and we retrospectively analyzed the survival outcomes of these patients. RESULTS: Most patients with CKD were elderly and male. Patients with CKD had a higher frequency of smoking habit, cardiovascular disease, and pulmonary diseases, and a notably lower pulmonary function, resulting in receiving limited pulmonary resection. There were no marked differences in the frequency of surgical complications between patients with and without CKD (p = 0.16). Squamous cell carcinoma was more frequently diagnosed in patients with CKD than in those without it. The 5-year disease-free survival rates in patients with and without CKD were 60.0% and 69.7% (p = 0.06), respectively, and the 5-year overall survival rates were 68.9% and 80.0%, respectively, showing significant differences (p = 0.01). The rate of receiving supportive care was higher in patients with CKD when recurrence observed. CONCLUSION: CKD is associated with a poorer overall survival in patients who undergo lung cancer resection for recurrent disease. As patients with CKD tend to have a poor respiratory function, thoracic surgeons should carefully select the resection type to balance the therapeutic benefit and invasiveness.

Proposal of a Useful Surrogate Endpoint of the Overall Survival in Patients Undergoing Pulmonary Metastasectomy: The Time to Local Therapy Failure.

BACKGROUND: A recent study demonstrated remarkable discrepancy between the relapse-free survival (RFS) and overall survival (OS) after pulmonary metastasectomy (PM) in the current era. As the RFS may not be a suitable parameter after PM, a more suitable parameter is needed for PM as a surrogate marker for OS. METHODS: A total of 134 consecutive patients who underwent PM were retrospectively analyzed. In the present study, we introduced a new endpoint, time to local treatment failure (TLTF). This endpoint was defined as the time interval between the first PM and the first untreatable recurrence by local treatment with curative intent or death due to any cause. We analyzed the correlation between the RFS and OS and between the TLTF and OS to validate whether or not the TLTF is a better parameter than the RFS after PM. RESULTS: Thus far, 78 patients have experienced relapse. Of these, 37 patients (47%) underwent local therapy with curative intent, 29 of whom are alive without local treatment failure. The 5-year OS, RFS and TLTF were 70.9%, 36.5%, and 57.6%, respectively. The concordance proportions for the RFS and OS and for the TLTF and OS were 0.634 and 0.851 for all patients, respectively. The Spearman's rank correlation coefficient for the RFS and OS was 0.639, while that for the TLTF and OS was 0.875. CONCLUSIONS: The TLTF may be a good surrogate parameter for the OS after PM in the current era.

Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma.

BACKGROUND: The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan-Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses. RESULTS: There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively. CONCLUSION: The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.

Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide.

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.

Stromal PDGFR-ß Expression is Associated with Postoperative Survival of Non-Small Cell Lung Cancer Patients Receiving Preoperative Chemo- or Chemoradiotherapy Followed by Surgery.

BACKGROUND: PDGFR-ß is used as a stromal biomarker and is functional in mesenchymal cells of the tumor microenvironment. The significance of stromal PDGFR-ß expression in non-small cell lung cancer (NSCLC) in patients undergoing preoperative chemo- or chemoradiotherapy had not been determined. METHODS: Patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy between 1996 and 2014 were assessed for expression of stromal PDGFR-ß by immunohistochemistry using resected specimens. Relationships between stromal PDGFR-ß expression and survival after operation were analyzed. Forty-three patients who underwent surgery without preoperative treatment in 2005 were also analyzed as a chemo-naïve control group. RESULTS: The mean age of the 92 patients was 60.2 years. Seventy-eight (85%) were male, and 14 (15%) were female. Fifty-four patients (59%) underwent preoperative chemoradiotherapy, and 38 patients (41%) underwent preoperative chemotherapy. Regimens for preoperative chemotherapy were cisplatin (CDDP) based in 48 patients (52%) and carboplatin (CBDCA) based in 43 (42%). While stromal cells expressed PDGFR-ß in 21 chemo-naïve patients (49%), stromal cells expressed PDGFR-ß in 65 patients who underwent preoperative therapy (p = 0.02). The 5-year disease-free survival rate (DFS) of the PDGFR-ß-positive group was significantly worse than that of the negative group (27 vs. 48%, p = 0.04). The 5-year disease-specific survival rate (DSS) in the stromal PDGFR-ß-positive group was also significantly worse than in the negative group (43 vs. 70%, p = 0.01). On the other hand, stromal PDGFR-ß expression did not influence survival in chemo-naïve patients. CONCLUSIONS: Stromal PDGFR-ß expression is negatively associated with DFS and DSS in patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy.

Interleukin-6/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension.

IL-6 is a multifunctional proinflammatory cytokine that is elevated in the serum of patients with pulmonary arterial hypertension (PAH) and can predict the survival of patients with idiopathic PAH (IPAH). Previous animal experiments and clinical human studies indicate that IL-6 is important in PAH; however, the molecular mechanisms of IL-6-mediated pathogenesis of PAH have been elusive. Here we identified IL-21 as a downstream target of IL-6 signaling in PAH. First, we found that IL-6 blockade by the monoclonal anti-IL-6 receptor antibody, MR16-1, ameliorated hypoxia-induced pulmonary hypertension (HPH) and prevented the hypoxia-induced accumulation of Th17 cells and M2 macrophages in the lungs. Consistently, the expression levels of IL-17 and IL-21 genes, one of the signature genes for Th17 cells, were significantly up-regulated after hypoxia exposure in the lungs of mice treated with control antibody but not in the lungs of mice treated with MR16-1. Although IL-17 blockade with an anti-IL-17A neutralizing antibody had no effect on HPH, IL-21 receptor-deficient mice were resistant to HPH and exhibited no significant accumulation of M2 macrophages in the lungs. In accordance with these findings, IL-21 promoted the polarization of primary alveolar macrophages toward the M2 phenotype. Of note, significantly enhanced expressions of IL-21 and M2 macrophage markers were detected in the lungs of IPAH patients who underwent lung transplantation. Collectively, these findings suggest that IL-21 promotes PAH in association with M2 macrophage polarization, downstream of IL-6-signaling. The IL-6/IL-21-signaling axis may be a potential target for treating PAH.

Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

Podocalyxin influences malignant potential by controlling epithelial-mesenchymal transition in lung adenocarcinoma.

Epithelial-mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of PODXL overexpression in EMT in lung cancer, and to determine the prognostic value of PODXL overexpression in tumors from lung cancer patients. The morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL-knockdown (KD) or PODXL-overexpression (OE) lung adenocarcinoma cells were examined. PODXL expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. PODXL-KD cells were epithelial in shape, whereas PODXL-OE cells displayed mesenchymal morphology. Epithelial markers were upregulated in PODXL-KD cells and downregulated in PODXL-OE cells, whereas mesenchymal markers were downregulated in the former and upregulated in the latter. A highly selective inhibitor of phosphatidylinositol 3-kinase-Akt signaling attenuated EMT of PODXL-OE cells, while a transforming growth factor inhibitor did not, suggesting that PODXL induces EMT of lung adenocarcinoma cells via the phosphatidylinositol 3-kinase pathway. In lung adenocarcinoma clinical specimens, PODXL expression was detected in minimally invasive and invasive adenocarcinoma, but not in non-invasive adenocarcinoma. Disease free survival and cancer-specific survival were significantly worse for patients whose tumors overexpressed PODXL. PODXL overexpression induces EMT in lung adenocarcinoma and contributes to tumor progression.

Outcomes of lung cancer surgery in patients with coronary artery disease: a decade of experience at a single institution.

PURPOSE: The aim of this study is to investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with coronary artery disease (CAD). METHODS: Among 805 patients who underwent surgery for NSCLC at our hospital within a recent 10-year period, 43 (5.3 %) had a history of CAD. We analyzed the surgical outcomes and risk factors for postoperative complications in these 43 patients. RESULTS: The postoperative mortality and morbidity rates were 2 and 42 %, respectively. The morbidity rate was significantly higher in the patients with CAD than in those without CAD (P < 0.01). Postoperative cerebrovascular or cardiovascular events occurred in four patients (9 %). Having two of the following was significantly associated with the development of postoperative complications: decreased cardiac function, respiratory dysfunction, or deteriorated renal function (p = 0.04). The 5-year overall and disease-free survival rates of the patients with CAD were 75.6 and 64.5 %, respectively; comparable with those of the patients without CAD; at 77.9 % and 72.5 %, respectively (p = 0.46 and 0.69). CONCLUSIONS: Patients with NSCLC and a history of CAD are at higher risk of complications after pulmonary resection. Combined decreased organ function is a risk factor for postoperative complications. CAD did not influence the long-term outcomes of patients after pulmonary resection for NSCLC.

Outcomes of surgery for lung cancer in patients with atrial fibrillation as a preoperative comorbidity: a decade of experience at a single institution in Japan.

PURPOSE: To investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with atrial fibrillation (AF) as a preoperative comorbidity. METHODS: Among 805 patients who underwent surgery for NSCLC, 27 (3.4%) had a history of AF. We analyzed the perioperative and long-term outcomes of these 27 patients. RESULTS: Fourteen patients (52%) had chronic AF and 13 (48%) had paroxysmal AF; being high rates of a comorbid illness. Nineteen patients (70%) underwent lobectomy, and 8 (30%) underwent sublobar resection. Ten patients (37%) received perioperative heparinization. There was no mortality. Other non-AF postoperative complications developed in 8 patients (30%), this incidence being higher than among the patients without AF (16%, 127 out of 778, p = 0.09). A thromboembolic event occurred in one patient (4%). With respect to the long-term outcomes, the 5-year overall survival and disease-free survival rates among the patients with AF were 70.3 and 60.8%, respectively, which were similar to those in the patients without AF (79.8 and 72.6%, p = 0.30 and 0.31). CONCLUSIONS: Lung cancer surgery in patients with AF is safe and provides favorable long-term outcomes; however, thoracic surgeons should monitor these patients carefully for postoperative thromboembolic events.