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Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-death due to early metastatic spread, in many cases primarily to the brain. Organ-specific pattern of spread of disease might be driven by the activity of a specific signaling pathway within the primary tumors. We aimed to identify an expression signature of genes and the relevant signaling associated with the development of brain metastasis (BM) after surgical resection of NSCLC., Methods: Rapidly frozen NSCLC surgical specimens were procured from tumor banks. RNA was extracted and analyzed by RNA-sequencing (Illumina HiSeq 2500). Clinical parameters and gene expression were examined for differentiating between patients with BM, patients with metastases to sites other than brain, and patients who did not develop metastatic disease at a clinically significant follow up. Principal component analysis and pathway enrichments studies were done., Results: A total of 91 patients were included in this study, 32 of which developed BM. Stage of disease at diagnosis (P=0.004) and level of differentiation (P=0.007) were significantly different between BM and control group. We identified a set of 22 genes which correlated specifically with BM, and not with metastasis to other sites. This set achieved 93.4% accuracy (95% CI: 86.2-97.5%), 96.6% specificity and 87.5% sensitivity of correctly identifying BM patients in a leave-one-out internal validation analysis. The oxidative phosphorylation pathway was strongly correlated with BM risk., Conclusions: Expression level of a small set of genes from primary tumors was found to predict BM development, distinctly from metastasis to other organs. These genes and the correlated oxidative phosphorylation pathway require further validation as potentially clinically useful predictors of BM and possibly as novel therapeutic targets for BM prevention., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-477). IK has a patent Gene signature prognostic of brain metastasis in NSCLC. 62/879,716 pending. ID has a patent Gene signature prognostic of brain metastasis in NSCLC. 62/879,716 pending. AO reports and honoraria from BI, MSD, Roche, AstraZeneca in Israel. JB has a patent Gene signature prognostic of brain metastasis in NSCLC. 62/879,716 pending and consultant fees from Roche, Boehringer Ingelheim, Novartis, BMS, Pfizer, AstraZeneca, Takada, MSD, VBL, Abbvie, Bayer, Lilly, grant support (to the institute) from MSD, Boehringer Ingelheim, AstraZeneca, Pfizer, Roche, Abbvie, BMS, Takeda. The other authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Background: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy)., Objectives: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery., Methods: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method., Results: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01)., Conclusions: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer., Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009., Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009-2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method., Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78-94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%., Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

Objectives: Patients with breast cancer following mastectomy and silicone implant reconstruction may have enlarged internal mammary lymph nodes with pathological uptake on positron emission tomography with (18)F-fluorodeoxyglucose. This lymphadenopathy is usually considered as metastatic in nature, but has also been reported to be related to other conditions, including silicon migration. The purpose of this study was to determine the rate of metastatic disease in this unique group of patients., Methods: A retrospective comparative study of 12 female patients with breast cancer with silicone implants referred for biopsy due to isolated internal mammary lymph node fluorodeoxyglucose uptake on positron emission tomography., Results: Five patients (41.6%) had histological findings related to silicone (n = 4) or non-specific inflammation (n = 1). The remaining 7 (58.3%) had histological evidence of cancer recurrence. There was no significant difference in the fluorodeoxyglucose-standardized uptake value between the two groups., Conclusions: Fluorodeoxyglucose-positive mammary lymph nodes in patients with breast cancer following silicone implant reconstruction may be due to metastatic deposits, non-specific inflammation or silicone migration. Clinical and imaging characteristics are insufficient in differentiating between these conditions. Biopsy is recommended prior to initiation of further treatment.

Background: Cryptogenic organizing pneumonia is increasingly being recognized as a major cause of diffuse infiltrative lung disease. The differential diagnosis of non-infectious diseases that resemble pneumonia should include this entity. Understanding the radiologic features of this entity will help in defining the correct diagnosis, although lung biopsy is needed to provide histopathologic confirmation. Treatment with steroids achieves an excellent response., Objectives: To present a variety of radiologic findings on high resolution computerized tomography in eight sequential patients with COP, together with clinical and pathologic correlation., Methods: Sequential HRCT examinations of eight patients (four males) aged 53-80 years (mean 65.5 years) with pathologcally proven COP were retrospectively analyzed by a consensus of two experienced chest radiologists for the existence and distribution of airspace consolidation, ground-glass opacities, nodular thickening along bronchovascular bundles and small (<1 cm) and large (>1 cm) nodules. The distribution of radiologic findings was classified as unilateral or bilateral, located in the upper, lower or middle lobe, and central or peripheral. Also recorded was the presence or absence of mediastinal lymphadenopathy and pleural effusion. Correlation with clinical symptoms was analyzed., Results: All eight patients had bilateral airspace consolidations. in two cases consolidations were limited to central fields, in four they were peripheral, and in the remaining two cases they were both central and peripheral. Small nodules were noted in six cases and large nodules in three. Ground-glass opacities were found ln four cases. All patients had enlarged lymph nodes (1-1.5 cm) in the mediastinum. Radiologic abnormalities resolved or improved after steroid treatment in all patients., Conclusions: HRCT findings of bilateral multiple heterogenic lung infiltrates and nodules associated with mild mediastinal lymphadenopathy in a patient with non-specific clinical symptoms are suggestive of COP; in such cases lung biopsy is indicated. Radiologic resolution of abnormalities correlates well with clinical improvement under adequate steroid treatment.

Objectives: This study was undertaken to determine the incidence and outcome of major bleeding complicating deep sternal infection after cardiac surgery, to identify predisposing factors and means of prevention, and to clarify management options., Methods: This was a retrospective study of 10,863 consecutive patients, of whom 213 (2.18%) acquired deep sternal infection. With 43 additional referrals, the total number of patients with deep sternal infection was 280. Deep sternal infection was managed by a two-stage scheme. Major bleeding was considered to be bleeding that occurred during or after operation for deep sternal infection from the heart, great vessels, or grafts, or bleeding requiring urgent exploration., Results: Fifteen patients (5.36%) had major bleeding. The incidences of deep sternal infection and bleeding were highest among patients undergoing coronary artery bypass grafting. Thirteen patients had underlying diseases (type 2 diabetes in 9 cases). Deep sternal infection was diagnosed a median of 15 days after reoperation. Bleeding originated from the right ventricle in 9 patients. In 4 patients bleeding was iatrogenic during surgery for wire removal (n = 2) or reconstruction (n = 2). In 11 it occurred 15 minutes to 15 days (median 2 days) after wire removal, as a result of shearing forces in 7 cases and of infection only in 4 cases. Three patients died immediately. The other 12 were operated on, 6 with complete cardiopulmonary bypass, 2 with femoral cannulation, and 4 without cardiopulmonary bypass. The immediate mortality was 26.7%; the overall mortality was 53.3%. The median length of hospitalization of surviving patients was 38 days., Conclusions: The probability of development of major bleeding in patients with deep sternal infection was unrelated to the primary operation. The mortality associated with this complication was high. Meticulous technique during wire removal may decrease the risk of major bleeding. The impacts of cardiopulmonary bypass and of the technique and timing of sternal reconstruction remain undetermined.

A 17-year-old boy presented with spontaneous hemothorax due to a puncture wound of the diaphragm by an inward facing exostosis of the rib. Diagnosis was made by computed tomographic scan, and the patient underwent a video-assisted thoracoscopic procedure to remove the exostosis. This is only the eighth reported case of an exostosis causing hemothorax.

Re-expansion pulmonary oedema may occur after chest tube drainage of pneumothorax and can give rise to cardiopulmonary manifestations which range from the mild to the severe. In order to evaluate the prevalence and the clinical manifestations of this complication, all patients with spontaneous pneumothorax managed with chest tube drainage were evaluated over an 8-yr period (1986-1994). A chest radiograph was performed routinely in all patients within 4 h of tube insertion. Lung expansion and the appearance of infiltrates within the lungs were investigated specifically. Re-expansion oedema was noted in three of 320 episodes (0.9%). Two of the three patients needed rapid and extensive clinical treatment.