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Background: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients., Methods: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed., Results: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%., Conclusions: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

Purpose of the Report: L-type amino acid transporter-1 (LAT1) is a tumor-specific transporter expressed in various tumor types, with minimal expression in normal organs. We previously demonstrated 18F-fluoro-borono-phenylalanine (18F-FBPA) as a selective PET probe for LAT1 in a preclinical study. Herein, we evaluated LAT1 expression in preoperative patients with lung or mediastinal tumors using 18F-FBPA PET and immunofluorescence staining., Patients and Methods: The study population included patients with histopathological diagnosis (n = 55): primary lung cancers (n = 21), lung metastases (n = 6), mediastinal tumors (n = 15), and benign lesion (n = 13). PET scanning was performed 1 hour after the injection of 18F-FBPA (232 ± 32 MBq). Immunofluorescence staining was performed on the resected tumor sections using LAT1 antibody. LAT1 staining was graded on a 4-grade scale and compared with the SUVmax on 18F-FBPA PET., Results: A positive correlation was observed between the SUVmax of 18F-FBPA PET and LAT1 expression by immunofluorescence staining (r = 0.611, P < 0.001). The SUVmax of 18F-FBPA was 3.92 ± 1.46 in grade 3, 3.21 ± 1.82 in grade 2, 2.33 ± 0.93 in grade 1, and 1.50 ± 0.39 in grade 0 of LAT1 expression. Although 18F-FBPA PET showed variable uptake in lung cancers and mediastinal tumors, benign lesions showed significantly lower SUVmax than those in malignant lesions (P < 0.01)., Conclusions: Uptake on 18F-FBPA PET reflected the expression level of LAT1 in lung and mediastinal tumors. It was suggested that 18F-FBPA PET can be used for the precise characterization of the tumor in pretreatment evaluation., Competing Interests: Conflicts of interest and sources of funding: The authors declare no potential conflicts of interest relevant to this study. This study was funded by the QiSS program of OPERA (grant number: JPMJOP1721) from the Japan Science and Technology Agency., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Limited treatment options are available for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). The rationale for immunotherapy and its adverse events for NSCLC with ILD remains unclear. In this study, we examined T cell profiles and functions in the lung tissues of NSCLC patients with or without ILD to provide evidence for the potential mechanism of immune checkpoint inhibitor (ICI)-related pneumonitis in NSCLC patients with ILD., Material and Methods: We investigated T cell immunity in the lung tissues of NSCLC patients with ILD to support the application of immunotherapy for these patients. We analyzed T cell profiles and functions in surgically resected lung tissues from NSCLC patients with and without ILD. The T cell profiles of infiltrating cells in lung tissues were analyzed by flow cytometry. T cell functions were measured based on cytokine production by T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin., Results: The percentages of CD4 +  T cells expressing immune checkpoint molecules (Tim-3, ICOS, and 4-1BB), CD103 + CD8 +  T cells, and regulatory T (Treg) cells were higher in NSCLC patients with than in those without ILD. A functional analysis of T cells in lung tissues indicated that CD103 + CD8 +  T cells positively correlated with IFNγ production, whereas Treg cells negatively correlated with IFNγ and TNFα production. Cytokine production by CD4 +  and CD8 +  T cells did not significantly differ between NSCLC patients with and without ILD, except for TNFα production by CD4 +  T cells being lower in the former than in the latter., Conclusion: In NSCLC patients with ILD stable for surgery, T cells were active participants and balanced in part by Treg cells in lung tissues, suggesting the potential development of ICI-related pneumonitis in NSCLC patients with ILD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

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.

Objectives: The surgical Apgar score (SAS) is a simple score that predicts postoperative complications based on 3 intraoperative valuables. The present study evaluated the association between the SAS and postoperative outcomes in non-small-cell lung cancer patients who underwent surgery., Methods: A total of 585 patients who underwent lung resection were enrolled in the present study. We calculated the SAS of each patient and investigated its influence on the short- and long-term outcomes., Results: Postoperative complications of any grade were detected in 164 cases (28%). The morbidity rate increased with decreasing SAS. When all the patients were divided into 2 groups (SAS <7 vs ≥7), postoperative complications were observed more frequently in the SAS <7 group than in the SAS ≥7 group (41% vs 25%, P < 0.001). In the multivariate analysis, the SAS was an independent risk factor for postoperative complications (odds ratio: 1.64 [1.03-2.61], P = 0.036). In terms of long-term outcomes, the 5-year disease-free survival (54.1% vs 73.2%, P < 0.001) and overall survival (73.8% vs 83.0%, P = 0.031) were significantly worse in the SAS <7 group than in the SAS ≥7 group. In a multivariate analysis, however, the SAS was not found to be an independent prognostic factor for either disease-free survival (hazard ratio: 1.39 [0.97-2.00], P = 0.075) or overall survival (hazard ratio: 0.90 [0.57-1.42], P = 0.642)., Conclusions: The SAS reflected preoperative and intraoperative characteristics and was able to stratify the morbidity rate, suggesting it to be a useful predictor of short-term outcomes in non-small-cell lung cancer patients who undergo surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Introduction: The prognosis of non-small cell lung cancer greatly depends on the presence of lymph node metastasis, which limits the need for surgery and adjuvant therapy for advanced cancer. One-step nucleic acid amplification of cytokeratin19 (CK19) mRNA was used to detect lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of the new one-step nucleic acid amplification system, which has increased gene amplification efficiency by improving the reagent composition, have shorter preprocessing and measurement times than conventional systems. We aimed to compare the clinical performance of the new system with that of histopathology and the conventional system., Materials and Methods: 199 lymph nodes from 58 non-small cell lung cancer patients who underwent lymph node dissection were examined intraoperatively using the new system, conventional system, and histopathology., Results: Lymph node metastasis was diagnosed in 32, 42, and 44 patients using histopathological analysis, the new system, and the conventional system, respectively. Compared with histopathological analysis, the concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value of the new system were 92.0%, 90.6%, 92.2%, 69.0%, and 98.1%, respectively, and compared with the conventional system, the values were 95.0%, 86.4%, 97.4%, 90.5%, and 96.2%, respectively., Conclusion: The clinical performance of the new one-step nucleic acid amplification system in detecting lymph node metastasis of lung cancer is comparable to that of histopathology and the conventional system; its performance was sufficient for determining the appropriate clinical treatment. The new rapid system can be effectively utilized during lung cancer treatment intraoperatively and postoperatively., Competing Interests: Naoko Ose, Yasushi Shintani, Yukiyasu Takeuchi, Yasushi Sakamaki and Yoshihisa Kadota had grant support from Sysmex Corp. and Mayuko Noguchi is an employee of Sysmex Corp. Hiromi Tsuji, Kunimitsu Kawahara and Kenji Urasaki declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Non-small cell lung cancer (NSCLC) patients with idiopathic pulmonary fibrosis (IPF) show poor prognosis. Periostin is an extracellular matrix protein highly expressed in the lung tissues of IPF. This study aimed to investigate the possibility that periostin secreted by fibroblasts derived from IPF lung might affect proliferation of NSCLC cells. Periostin was more highly expressed and secreted by fibroblasts from diseased human lung with IPF (DIPF) than by normal human lung fibroblasts (NHLF). Cocultivation of NSCLC cells with conditioned media (CM) from DIPF increased proliferation of NSCLC cells through pErk signaling, with this proliferation attenuated by periostin-neutralizing antibodies. Knockdown of integrin β3, a subunit of the periostin receptor, in NSCLC cells suppressed proliferation of NSCLC cells promoted by recombinant human periostin and CM of DIPF. On in vivo examination, DIPF promoted tumor progression more than NHLF, and knockdown of integrin β3 in NSCLC cells suppressed tumor progression promoted by DIPF. Fibroblasts derived from surgical specimens from IPF patients also increased secretion of periostin compared to those from non-IPF patients. Periostin secreted from IPF-activated fibroblasts plays critical roles in the proliferation of NSCLC cells. The present study provides a solid basis for considering periostin-targeted therapy for NSCLC patients with IPF., (© 2021. The Author(s).)

Objectives: With improvements in the outcome of treatment for non-small-cell lung cancer (NSCLC), other diseases may account for a high death rate after surgery in patients with stage I NSCLC. In the present study, we analysed the associations between the clinical factors and non-cancer death after surgery in these patients., Methods: The records of 514 patients with stage I NSCLC who underwent surgery were retrospectively reviewed; a proportional hazards model for the subdistribution of a competing risk was conducted to define the risk factors for non-cancer death., Results: The mean patient age was 67 years. A total of 367 patients (71%) underwent bilobectomy or lobectomy while 147 (29%) underwent sublobar resection. The pathological stage was IA in 386 (75%) and IB in 128 (25%) patients. Three patients (0.6%) died within 90 days after surgery, and 108 (21%) experienced postoperative complications. Until the time of writing this report, 83 patients had died during the follow-up. The cause of death was primary lung cancer in 38 (46%) patients and other diseases in 45 (54%) patients, including non-cancer causes in 29 patients, such as pneumonia, cardiac death and cerebral stroke. According to a multivariable competing risk analysis for non-cancer death age (≥70 years), sex (male), body mass index (BMI <18.5), postoperative complications and % forced expiratory volume in 1 s (<80) were identified as risk factors for postoperative non-cancer death., Conclusions: Advanced age (≥70 years), male sex, low BMI (<18.5), postoperative complications and low preoperative % forced expiratory volume in 1 s (<80) were found to be the risk factors for postoperative non-cancer death after surgery in patients with stage I NSCLC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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.

Background: Due to its rarity, information on pulmonary metastasectomy for pulmonary metastasis from ovarian cancer is limited., Methods: Cases of pulmonary metastasectomy for ovarian cancer were collected in a multi-institutional setting and the outcomes were analyzed., Results: Among 1508 cases in which pulmonary resection was performed to treat pulmonary metastasis from tumors of various organs, 6 cases (0.4%) involved pulmonary metastasis from ovarian cancer. The mean age was 61 years (range, 39-75 years). The histological types were undifferentiated carcinoma in 2 patients, and clear cell adenocarcinoma, serous papillary cystadenocarcinoma, serous adenocarcinoma, and endometroid adenocarcinoma in 1 patient each. One patient (17%) had a history of liver metastasis at the time of pulmonary resection. The median disease-free interval was 22 months (range, 0 [synchronous]-188 months). The tumor was solitary in 5 patients (83%). The mean tumor size was 15 mm (range, 5-23 mm). All 6 patients underwent complete resection. The type of resection was wide wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 1 patient. Four patients (67%) received postoperative chemotherapy. Thus far, 4 patients (67%) have experienced recurrence after pulmonary resection. In terms of outcomes, 1 patient who had synchronous pulmonary metastasis with the primary tumor died in the early period after pulmonary resection, 1 patient is alive without recurrence after a short follow-up period (5 months), 3 patients have achieved mid- to long-term survival and are alive with disease (38-61 months), and 1 patient achieved long-term (61 months) disease-free survival., Conclusions: Patients with pulmonary metastasis from ovarian cancer who fulfill the eligibility criteria for pulmonary metastasectomy are rare. Pulmonary metastasectomy for ovarian cancer can provide favorable outcomes in highly selected patients. Patients with synchronous pulmonary metastasis from ovarian cancer are not good candidates for pulmonary metastasectomy.

Targeting cancer-associated fibroblasts (CAFs), as well as the crosstalk between stroma and cancer cells, could be of value in managing cancers. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of fibroblast activation and the tumor-stroma interaction in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. PFD significantly inhibited myofibroblast differentiation and activation of both primary cultured normal human lung fibroblasts and CAFs. Cocultivation of NSCLC cells with conditioned media (CM) of fibroblasts changed the morphology or epithelial to mesenchymal transition (EMT) status, and PFD suppressed these changes. Cocultivation of CAFs with CM of NSCLC cells also induced activation of CAFs, and these changes were suppressed by PFD. On in vivo examination, CAFs promoted tumor progression, and PFD suppressed tumor progression with an inhibitory effect on tumor-stroma crosstalk. PFD might inhibit not only fibroblast activity, but also the crosstalk between cancer cells and fibroblasts. PFD may have great potential as a novel treatment for NSCLC from multiple perspectives.

Background: The clinical outcome of patients undergoing hemodialysis (HD) has not yet been clarified in lung cancer surgery. The aims of this study were to assess the clinical features, outcomes, and main cause of death after lung cancer surgery in patients undergoing HD and to evaluate the risk factors for postoperative complications., Methods: The study identified 39 patients undergoing HD who had lung cancer surgery in 9 institutions under the Thoracic Surgery Study Group of Osaka University in Japan between 2007 and 2016. Study investigators retrospectively analyzed the surgical outcomes of these patients., Results: Most patients were male and were smokers. Diabetes mellitus was the most common cause of primary renal disease. Lobectomy with systemic lymph node dissection was performed in 16 patients, and an extended operation was performed in 6 patients. Most patients had a diagnosis of pathologic stage IA (69.2%) lung cancer. The overall complication and mortality rates were 30.8% and 7.7%, respectively. Pneumonia was the most frequently observed complication. Extended operation was significantly associated with complications (P = .04). The 5-year overall survival rate was 57.9%, and the most common cause of death was not primary lung cancer but was a disease related to HD., Conclusions: Lung cancer surgery for patients undergoing HD provides favorable long-term outcomes despite higher postoperative mortality and morbidity rates. Because an extended operation is significantly associated with postoperative complications, thoracic surgeons should carefully select the type of resection on the basis of a balance between therapeutic benefit and invasiveness in these patients., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Stereotactic body radiation therapy (SBRT) has recently been widely performed for relatively small-volume tumors. We analyzed the short-term outcomes of pulmonary metastasectomy (PM) or SBRT for pulmonary metastases., Methods: This study was a retrospective analysis of 82 patients with pulmonary metastasis from epithelial tumors who underwent PM or SBRT between 2013 and 2016., Results: Fifty-nine patients underwent PM, 21 patients underwent SBRT, and 2 patients underwent combined PM and SBRT. The mean age of the PM group was significantly lower than that of the SBRT group (60.6 vs 67.4 years, p = 0.03). The most frequent types of primary tumor in the PM and SBRT groups were colorectal cancer (n = 27, 46%) and head and neck squamous cell carcinoma (n = 8, 38%), respectively. The rate of treatment-associated complications did not differ between the two groups to a statistically significant extent (20% vs 24%, p = 0.76). The 3-year local control rates of the two groups were similar (PM group, 88%; SBRT group, 92%; p = 0.48). The 3-year progression-free survival (PFS) rate of the PM group were better than that of SBRT groups (42% vs 11%, p = 0.01). The 3-year overall survival (OS) rates of the PM and SBRT groups were 77 and 52% respectively; although the rate of the PM group was higher, the difference was not statistically significant (p = 0.10)., Conclusions: SBRT provides a favorable 3-year local control rate. The 3-year OS rate of the SBRT group tended to be lower than that of the PM group, despite the difference was not statistically significant. PM and SBRT play complementary roles in patients with pulmonary metastases.

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.

Objectives: The objective of this study was to evaluate the validity of Eurolung risk models in a Japanese population and assess their utility as predictive indicators for the prognosis., Methods: Between 2007 and 2014, 612 anatomic lung resections were performed among 694 lung cancer patients in our institution. We analysed the cardiopulmonary morbidity and mortality and compared them with the predicted results. We also investigated the association between the Eurolung aggregate risk scores and the long-term outcomes using the Kaplan-Meier method and a multivariable analysis., Results: The percentage of cardiopulmonary complications was lower than that predicted by Eurolung 1 (22.4% vs 24.6%). The mortality rate was significantly lower than predicted by Eurolung 2 (0.7% vs 3.0%). The morbidity rate was stratified by Aggregate Eurolung 1. The stratification of the mortality rate by the Eurolung 2 aggregate score was also in line with the increase in score, although the observed number of deaths was quite small (4 cases). The 5-year overall survival was clearly separated according to the stratified Aggregate Eurolung 1 and 2 (P < 0.01 and P < 0.01, respectively). Besides pathological stage, both the Aggregate Eurolung 1 (score 0-7 vs 8-20) and 2 (score 0-8 vs 9-19) scores were shown to be independently associated with overall survival on multivariable., Conclusions: Eurolung risk models cannot be directly applied to the patients in our institution. However, Eurolung aggregate risk scores were helpful not only for stratifying morbidity and mortality after anatomic lung resection but also for predicting the long-term outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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.

Feasibility is one of the major concerns during adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. A phase II clinical trial of adjuvant chemotherapy with four courses of carboplatin (AUC 5 at day 1) and S-1 (80 mg/m 2 /day for 2 weeks followed by a 2-week rest) was performed to evaluate the feasibility (UMIN 9101). The primary endpoint was the completion rate and the secondary endpoints were adverse events, 2-year overall survival and disease-free rates. Thirty-five non-small cell lung cancer patients were enrolled. The adjuvant chemotherapy completion rate was 85.3% (29/34); 17/34 (50%) patients completed 4 courses without dose reduction. There were no treatment-related deaths, and Grade 3/4 adverse events included neutropenia (38.2%), leukocytopenia (14.7%), anemia (20.6%), thrombocytopenia (20.6%), anorexia (5.9%), fatigue (5.9%), and oral mucositis (2.9%). Two-year overall and disease-free survival rates were 96.3% and 53.3%, respectively. Adjuvant chemotherapy with carboplatin plus S-1 is safe and feasible.

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.

Background: PDGFR-β is used as a stromal biomarker and is functional in mesenchymal cells of the tumor microenvironment. The significance of stromal PDGFR-β 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-β by immunohistochemistry using resected specimens. Relationships between stromal PDGFR-β 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-β in 21 chemo-naïve patients (49%), stromal cells expressed PDGFR-β in 65 patients who underwent preoperative therapy (p = 0.02). The 5-year disease-free survival rate (DFS) of the PDGFR-β-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-β-positive group was also significantly worse than in the negative group (43 vs. 70%, p = 0.01). On the other hand, stromal PDGFR-β expression did not influence survival in chemo-naïve patients., Conclusions: Stromal PDGFR-β expression is negatively associated with DFS and DSS in patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy.

Background: We previously reported that patients with elevated preoperative B-type natriuretic peptide (BNP) levels have an increased risk for postoperative atrial fibrillation following lung cancer surgery. The present study evaluated whether the specific phosphodiesterase III inhibitor olprinone can reduce the incidence of postoperative atrial fibrillation in patients with elevated BNP levels undergoing pulmonary resection for lung cancer., Methods: A prospective randomized study was conducted with 40 patients who had elevated preoperative BNP levels (≥ 30 pg/mL) and underwent scheduled lung cancer surgery. All patients were in sinus rhythm at surgery. Low-dose olprinone or placebo was continuously infused for 24 h and started just before anesthesia induction. The primary end point was the incidence of postoperative atrial fibrillation. The secondary end points were perioperative hemodynamics and levels of BNP, WBC counts, and C-reactive protein., Results: The incidence of postoperative atrial fibrillation was significantly lower in the olprinone group than in the placebo group (10% vs 60%, P < .001). Patients in the olprinone group showed significantly lower BNP, WBC counts, and C-reactive protein levels after surgery., Conclusions: Continuous infusion of olprinone during lung cancer surgery was safe and reduced the incidence of postoperative atrial fibrillation following pulmonary resection in patients with elevated preoperative BNP levels., Trial Registry: Japan Primary Registries Network; No.: JPRN-UMIN2404; URL: http://www.umin.ac.jp/ctr/.

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.

Objectives: Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer and computed tomography (FDG-PET/CT) are utilized for the diagnosis of lymph node (LN) metastasis from lung cancer. In this study, we analyzed the diagnostic ability of FDG-PET for N staging by focusing on the clinical features of false-positive (FP) and false-negative (FN) cases., Methods: From March 2006 to February 2010, 112 patients underwent preoperative examinations using FDG-PET/CT followed by radical resection with hilar and mediastinal dissection. We analyzed their clinicopathological characteristics based on preoperative FDG-PET/CT findings and post-operative histopathological diagnosis of resected LNs., Results: Based on the PET/CT results, 17 patients were misdiagnosed (9 FN and 8 FP). The sensitivity, specificity, accuracy and negative and positive predictive values for N1/N2 were 50.0, 94.5, 84.0, 93.0 and 58.3%, respectively, whereas those for N2 were 57.8, 90.3, 84.8, 90.3 and 61.1%, respectively. FP findings more frequently occurred in cases with elevated white blood cell (WBC) count (P=0.015) and smokers (P=0.04). In the FN group, the maximum standardized uptake value for the primary tumour was lower than that in the true-positive (TP) group (P=0.01). The short-axis sizes of 71 LNs differently diagnosed by PET/CT and histopathology findings were significantly smaller in the FN group than the TP group (P<0.001), whereas there was no difference between TP and FP. As for FN LNs in the TP group, there was no significant difference., Conclusions: PET/CT showed a good ability to detect metastatic LNs, especially for N2 diagnosis. However, there were some limitations, especially in cases with elevated peripheral WBC count and/or smoking history.

A 64-year-old man, who had received chemoradiation therapy for stage IIIB non-small-cell lung cancer, underwent stent insertion with a covered expandable metallic stent for post-radiation bronchial stenosis. Stenosis due to formation of granulation tissue at the distal stent site resulted in critical respiratory failure. The stent was removed after 43 months, using rigid bronchoscopy.