ACTN4 is associated with the malignant potential of thymic epithelial tumors through the ß-catenin/Slug pathway.

Thymic epithelial tumors (TETs) are rare tumors arising from the mediastinum. Among TETs, thymoma type B2, B3 and thymic carcinoma are highly malignant and often present invasion and dissemination. However, the biological characteristics of TETs have not been thoroughly studied, and their mechanisms of invasion and dissemination are largely unknown. α-Actinin 4 (ACTN4) is a member of actin-binding proteins and reportedly plays important roles in the progression of several cancers. In this study, we investigated the relationship between ACTN4 and characteristics of the malignant potential of TETs, such as invasion and dissemination. In vitro experiments using Ty-82 thymic carcinoma cells revealed that overexpression of ACTN4 enhanced the proliferative and invasive ability of Ty-82 cells; conversely, knockdown of ACTN4 attenuated the proliferative and invasive potential of Ty-82 cells. In western blotting (WB) experiments, ACTN4 induced the phosphorylation of extracellular signal-regulated kinase and glycogen synthase kinase 3ß to regulate the ß-catenin/Slug pathway. Furthermore, WB analysis of cancer tissue-origin spheroids from patients with TETs showed results similar to those for Ty-82 cells. In vivo experiments showed that the knockdown of ACTN4 significantly suppressed the dissemination of Ty-82 cells. A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, ß-catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the ß-catenin/Slug pathway.

Native lung surgery after single lung transplantation: clinical characteristics and outcomes.

PURPOSE: Single lung transplantation (SLT) is a viable option for patients with end-stage pulmonary parenchymal and vascular diseases. However, various diseases can occur in native lungs after SLT. METHODS: Between January 2000 and December 2021, 35 patients underwent cadaveric SLT and survived for more than 30 days in our hospital. Among these 35 patients, 10 required surgery for diseases that developed in their native lungs. The clinical characteristics of these 10 patients and the outcomes of native lung surgery (NLS) were investigated. RESULTS: Among these ten patients, the indications for lung transplantation were chronic obstructive pulmonary disease and idiopathic interstitial pneumonia in three patients each, and lymphangioleiomyomatosis and collagen vascular disease-related interstitial pneumoniain two patients each. The causes of NLS included pneumothorax (n = 4), primary lung cancer (n = 2), native lung hyperinflation (n = 2), and pulmonary aspergilloma (n = 2). The surgical procedures were pneumonectomy (n = 7), lobectomy (n = 2), and alveolar-pleural fistula repair (n = 1). Only one postoperative complication, empyema, was treated with antibiotics. The 5-year overall survival rates after transplantation with and without NLS were 70.0% and 80.0%, respectively, and did not differ to a statistically extent (p = 0.56). CONCLUSION: NLS is an effective treatment option for diseases that develop in the native lungs after SLT.

Surgical resection of advanced intrathoracic tumors through a combination of the hemiclamshell and transmanubrial approaches.

PURPOSE: The hemiclamshell (HCS) approach provides a comprehensive view of the anterior mediastinum, whereas the transmanubrial osteomuscular sparing approach (TMA) allows sufficient exposure of the cervico-thoracic transition. We assessed the effectiveness and the outcomes of the combined HCS plus TMA approach to resect thoracic malignant tumors. METHODS: We reviewed five patients with thoracic malignant tumors invading the thoracic outlet who underwent surgery using an HCS and TMA approach between 2018 and 2021. RESULTS: The preoperative diagnosis was myxofibrosarcoma, lung cancer, thymic cancer, thymoma, and neurofibromatosis type1 in one patient each, respectively. Cardiovascular reconstruction was done on the aortic arch in two patients, on the descending aorta in one, and on the superior vena cava in one, combined with resection of the vagus nerve in three patients, of the phrenic nerve in two, and of vertebra in one, with overlap in some cases. The TMA was added because all patients required dissection of the periphery of the subclavian artery, and two had tumor extension to the neck. Macroscopic complete resection was achieved in four patients. There was no postoperative mortality. CONCLUSION: The combination of the HCS and TMA approaches at the same operation provides a comprehensive view of the mediastinum, lung, and cervico-thoracic transition and allows safe access to the thoracic great vessels and subclavian vessels.

Stereotactic ablative body radiotherapy with a central high dose using CyberKnife for metastatic lung tumors.

BACKGROUND: The CyberKnife system features a robotically-positioned linear accelerator to deliver real-time image-guided stereotactic ablative body radiotherapy (SABR). It achieves steep dose gradients using irradiation from hundreds of different directions and increases the central dose of the gross tumor volume (GTV) without increasing the marginal dose to the planning target volume. We evaluated the effectiveness and safety of SABR with a central high dose using CyberKnife for metastatic lung tumors. METHODS: A total of 73 patients with 112 metastatic lung tumors treated with CyberKnife were retrospectively analyzed. Local control, progression-free survival, and overall survival were calculated using the Kaplan-Meier method. The median age was 69.2 years. The most common primary sites were the uterus (n = 34), colorectum (n = 24), head and neck (n = 17), and esophagus (n = 16). For peripheral lung tumors, the median radiation dose was 52 Gy in 4 fractions, whereas for centrally located lung tumors, it was 60 Gy in 8-10 fractions. The dose prescription was defined as 99% of the solid tumor components of the GTV. The median maximum dose within the GTV was 61.0 Gy. The GTV and planning target volume were enclosed conformally by the 80% and 70% isodose lines of the maximum dose, respectively. The median follow-up period was extended to 24.7 months; it was 33.0 months for survivors. RESULTS: The 2-year local control, progression-free survival, and overall survival rates were 89.1%, 37.1%, and 71.3%, respectively. Toxicities of grade ≥ 2 were noted as grade 2 and 3 radiation pneumonitis in one patient each. The two patients with grade 2 or higher radiation pneumonitis had both received simultaneous irradiation at two or three metastatic lung tumor sites. No toxicity of grade ≥ 2 was observed in patients with metastasis in one lung only. CONCLUSIONS: SABR with a central high dose using CyberKnife for metastatic lung tumors is effective with acceptable toxicity. TRIAL REGISTRATION: Number: 20557, Name: Stereotactic ablative radiotherapy using CyberKnife for metastatic lung tumor, URL: http://www.radonc.med.osaka-u.ac.jp/pdf/SBRT.pdf , Date of registration: April 1, 2021 (retrospectively registered), Date of enrollment: May 1, 2014.

Association of the psoas muscle index with the survival of patients on a waiting list for lung transplantation: a Japanese single-institution study.

PURPOSES: Some predictive markers of death have been reported for patients on the waiting list for lung transplantation (LTx). We assessed whether or not the preoperative psoas muscle index (PMI) correlates with waitlist mortality. METHODS: In 81 patients with end-stage lung disease on the waiting list for LTx between 2011 and 2020 at Osaka University Hospital, we examined the association between baseline characteristics, including the diagnosis, respiratory function test results, blood collection items, steroid use, and psoas muscle mass on computed tomography, and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: Thirty-three patients (41%) died during follow-up. Univariate and multivariate analyses showed that patients with a low PMI had a higher rate of death during follow-up than those with a high PMI (p < 0.0001 and 0.0002, respectively). In addition, a diagnosis of interstitial pneumonia (hazard ratio 3.30, 95% confidence interval 1.52-7.17, p = 0.0025) and low albumin level (hazard ratio 2.21, 95% confidence interval 1.02-4.80, p = 0.0449) were also significant predictors of survival. CONCLUSION: A low PMI at registration is associated with a decreased survival time among LTx candidates and it may be a predictive factor of mortality in patients waiting for LTx.

Outcomes of surgical resection for pulmonary metastasis from pancreatic cancer.

PURPOSE: As the number of long-term survivors of pancreatic cancer is expected to increase thanks to recent advances in multidisciplinary treatment and earlier diagnoses of pancreatic cancer, we are likely to encounter more cases of postoperative pulmonary nodules. We analyzed the clinical course and prognosis of resection of pulmonary metastases from pancreatic cancer to clarify the prognostic implication of pulmonary metastasectomy for pancreatic cancer. METHOD: We retrospectively analyzed 35 patients who underwent resection of lung metastases after pancreatic cancer surgery. Short- and long-term outcomes and factors associated with the prognosis were analyzed. RESULTS: The observation period was 20 (range, 1-101) months, with 3- and 5-year survival rates of 88.3% and 64.5% from pancreatectomy and 44.1% and 28.3% from lung resection, respectively. A univariate analysis revealed that a period from pancreatic cancer resection to pulmonary nodule shadow detection of < 15 months was associated with a significantly lower overall survival from pancreatic resection than a longer period. Conversely, histological type, stage, size of lung metastases, and resection technique were not associated with the overall survival. CONCLUSION: A long-term prognosis may be expected in some cases with a disease-free interval of ≥ 15 months. Our findings suggest that the disease-free interval may influence the prognosis.

[Ingenuities of Segmentectomy for Small Lung Cancer in Uniportal Video-assisted Thoracic Surgery].

Our department has been performing uniportal thoracoscopic lobectomy since April 2019 and now also performs segmentectomy for small malignant tumors. A skin incision of approximately 4 cm is created between the anterior fifth intercostal space on the left and right sides. Based on our experience, uniportal segmentectomy does not follow the learning curve unique to segmentectomy. For dissection of segmental surface, an automatic suture is used to prevent pulmonary fistulas. If the cutting line between the segments is straight, dissection can be performed easily even in uniportal surgery, in which the automatic suturing device is inserted from one direction. For inter-area identification, we use an air-containing collapsed line with normal ventilation, after which thoracoscopic indocyanine green( ICG) imaging is introduced. However, there have been cases in which a difference in inter-area identification occurred between ICG identification and the air-containing collapsed line. As such, it is better to utilize both methods in cases with masses close to the inter-areas.

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.

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.

Long-Term Outcomes of Pulmonary Metastasectomy for Uterine Malignancies: A Multi-institutional Study in the Current Era.

BACKGROUND: Information on pulmonary metastasectomy (PM) for uterine malignancies in the current era is limited. In the present study, we analyzed the clinical course and results of PM for uterine malignancies in the era of modern imaging diagnostics to clarify the role of PM in the current era in a multi-institutional setting. METHODS: Fifty-seven patients who underwent PM for uterine malignancies between 2006 and 2015 were retrospectively reviewed. The short- and long-term outcomes, along with factors associated with the prognosis, were analyzed. Details of the clinical course after PM were described. RESULTS: The mean age of patients was 59.4 years. The primary tumor was located in the uterus corpus in 34 cases (60%) and in the uterus cervix in 23 cases (40%). The median disease-free interval (DFI) was 32 months. Forty patients (70%) received fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography before PM, and complete resection was achieved in 52 patients (91%). Postoperative complications occurred in 4 patients (7%). Of the 52 patients who underwent complete resection of pulmonary metastases, 28 experienced recurrence, and among these, 17 (60%) underwent local therapy, including six repeat PMs. Among the 52 patients who underwent complete resection, the 5-year relapse-free survival rate was 40.7% and the 5-year overall survival (OS) rate was 68.8%. The univariate analysis revealed that a DFI of ≤ 24 months was associated with significantly poorer OS. CONCLUSIONS: PM for uterine malignancies is safe and provides favorable long-term outcomes in selected patients. Patients with a DFI of > 24 months have better OS and are good candidates for PM.

Host Immune Response and Novel Diagnostic Approach to NTM Infections.

The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species.

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.

Association of cigarette smoking with the expression of nuclear survivin in pathological Stage IA lung adenocarcinomas.

Survivin is expressed in the cytoplasm and/or nucleus of various types of malignant tumor cells. Cytoplasmic survivin functions as an apoptosis inhibitor, while nuclear survivin is indispensable for complete mitosis completion. To investigate the effect of cigarette smoking on the survivin expression in lung adenocarcinomas at the early developmental stage, we examined the expression of nuclear and cytoplasmic survivin in pathological Stage IA lung adenocarcinomas resected from 38 non-smokers and 44 smokers (current smokers and ex-smokers) using an immunohistochemical method. Labeling indices of nuclear survivin in tumors of smokers were significantly greater than those of non-smokers. The labeling index of nuclear survivin was above 3 % in only 1 (2.6 %) of the 38 tumors of the non-smokers, while the labeling indices in 19 (43.2 %) of 44 tumors of the smokers were above 3 % with a significantly greater frequency. There was no significant difference in the labeling index of nuclear survivin between current smokers and ex-smokers. There was no significant difference in the labeling index of cytoplasmic survivin between tumors of the non-smokers and the smokers. The present results show that cigarette smoking is associated with the higher nuclear surviving expression in lung adenocarcinomas at the early stage, suggesting that cigarette smoking affects the nuclear survivin expression in lung adenocarcinomas at the early developmental stage.