Search

Published articles support the effect of chemotherapy in the immune environment of tumors, including lung carcinomas. The role of CD4 + T-cells is crucial for expansion and accumulation of other antigen-specific immune cells, and the participation of CD8 + cells in tumor killing activity has been confirmed by many studies. However, little is known about the effect of chemotherapy on the healthy lung parenchyma from lung cancer patients, and whether there are differences between the different chemotherapy compounds used to treat this patient population. The aim of our study was to explore the effect of chemotherapy on CD4 + and CD8 + cells in the bronchoalveolar lavage fluid (BALF) of the healthy lung in patients treated with standard chemotherapy regimens. Fifteen patients underwent BAL, in the healthy lung before and after six chemotherapy courses. Platinum-based regimens included vinolerbine (VN) in 6 patients, gemcitabine (GEM) in 4 patients and etoposide (EP) in 5 patients. All patients but one were males and smokers (93%). The median age of patients was 56 years (42–75). No significant difference was noted in the patients’ age between the three treated groups. Furthermore, between the three groups, no significant changes in the means of CD4 + and CD8 + cells were noted. However, when we compared the mean CD4 + cells before and after chemotherapy within each group, changes were noted when comparing VN before versus after (p = 0.05), GEM before versus after (p = 0.03), and EP before versus after (p = 0.036). In our pilot study, changes were noted in BALF CD4 + cells for the three most applied regimens at the normal lung parenchyma.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive lung scarring due to unknown injurious stimuli ultimately leading to respiratory failure. Diagnosis is complex and requires a combination of clinical, laboratory, radiological, and histological investigations, along with exclusion of known causes of lung fibrosis. The current understanding of the disease etiology suggests an interaction between genetic factors and epigenetic alterations in susceptible, older individuals. Prognosis is dismal and current treatment options include anti-fibrotic agents that only slow down disease progression and carry considerable side effects that hamper patients' quality of life. Therefore, the need for new, more effective treatments, alone or in combination with existing pharmacotherapy, is sorely needed. Regenerative medicine, the potential use of cell therapies to treat destructive diseases that cause architectural distortion to the target organ, has also emerged as an alternative therapeutic for lung diseases with unfavorable prognosis such as IPF. Mesenchymal stem cells (MSCs) and type II alveolar epithelial cells (AEC2s) have been used and their safety has been demonstrated. In the case of MSCs, both homogenic and allogeneic sources have been used and both are considered viable options without immunosuppressive therapy, taking into consideration the absence of immunogenicity and HLA response. AEC2s have been used in one trial with promising results but their use requires a deceased donor and immunosuppressive pre-treatment. In this review, we briefly summarize the current state of knowledge regarding the pathogenesis of IPF, and the background and rationale for using MSCs or AEC2s as potential treatment options. We list and describe the clinical trials completed to date and provide a comparison of their methods and results as well as a possible way forward.

Background Thoracoscopy, either "medical" or "surgical", is the gold standard to reveal the cause of pleural effusion by taking large biopsies. However, in some cases, the histology of pleural biopsies is inconclusive for a specific cause, describing a variable process of inflammation, encompassing for non-specific pleuritis (NSP). Questions are raised whether the surgical (or video-assisted thoracoscopic surgery, VATS) is doing better than the medical thoracoscopy (MT or pleuroscopy), but no direct comparison between the two techniques exist in the current bibliography. The aim of our retrospective study was to compare these two techniques to find whether there is any difference in the false negative cases of NSP. Methods We included in our study 295 patients with NSP, 179 patients who underwent VATS comparing to 116 patients who underwent MT for pleural effusion of initially undetermined cause, having a follow-up of at least one year. Analysis of patients' files, history, clinical examinations, further tests, and follow-up were recorded. Results The mean age of our patients was 58.5±19.1 and M/F gender was 216/79; no difference was observed between the two groups. The mean follow-up period was 47.3±20.7 months. After VATS, only one patient (0.55%) was finally diagnosed with pleural malignancy (false negative) while after MT 2 patients (1.7%). Negative predictive value for pleura-related malignancy for VATS was 0.994 and for MT 0.982. Conclusions In patients with histological diagnosis of NSP both VATS and MT showed similar and excellent results of false negative cases and negative predictive value in excluding malignant pleural disease.

Positron emission tomography/computed tomography (PET/CT) has shown prognostic significance in head and neck cancer patients. The underlying pathologic features that could explain the mechanisms associated with this observation are not clear. To analyze the correlation between 18-F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake assessed by PET/CT in head and neck cancer and histopathologic prognostic factors. Ninety-nine patients with laryngeal and pharyngeal squamous cell carcinoma were retrospectively reviewed for pretreatment PET/CT measurements, namely standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The corresponding histologic material was evaluated for tumor stroma-related prognostic factors such as the amount and type of stroma, lymphocytic response, tumor budding activity, and size of tumor cell nests in the tumor core area and tumor front. TLG and MTV were associated with tumor localization, as they were higher in oropharyngeal tumors. These values were also associated with tumor cell nest size in the tumor core with higher values corresponding to tumors with smaller nests. MTV40% was marginally associated with fibroblastic stroma type and higher budding activity. SUVmax was not associated with the histological factors in the whole sample, but higher values trended with higher tumor budding activity and stroma-rich tumors of the oropharynx. 18F-FDG PET measurements in head and neck squamous cell carcinomas are associated with prognostic histopathologic factors and suggest a possible correlation of glucose metabolism to epithelial-to-mesenchymal transition.

Simple Summary Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, with few patients carrying driver mutations in the gene encoding for epidermal growth factor receptor (EGFR). Advances in translational research have established EGFR tyrosine kinase inhibitors (TKIs) as the standard first-line therapy for NSCLC patients with activating EGFR mutations. The aim of our observational study was to assess the frequency of T790M acquired resistance and predictors of its presence, in patients with EGFR-mutated locally advanced or metastatic NSCLC who have progressed in the first-line EGFR-TKI treatment setting with first- or second-generation TKIs and have undergone molecular testing in tissue and/or plasma biopsy. The study highlights the challenges of performing tissue re-biopsy in routine care settings, which can lead to patients considered non-eligible for certain therapies from which they can benefit, and merits further actions from the healthcare community, in order to establish re-biopsy as a standard procedure. Abstract Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Mesothelioma of the tunica vaginalis of the testis (MTVM) is a rare tumor encountering for less than 1% of mesothelioma. Patients suffering from these tumors have poor survival due to local and distant metastasis despite treatment. Actually, no specific treatment recommendations exist for this tumor, yet radical orchidectomy is the gold standard in limited disease. We herein report the case of a 71 patient with MTVM who underwent radical orchidectomy without inguinal lymph node dissection and recurred 2 years later with metastasis in pelvic and mediastinal lymph nodes. Despite systemic chemotherapy combining pemetrexed, bevacizumab and Cisplatinum, the disease relapsed eight months later with multiple metastatic lung nodules leading to a treatment shift. We believe that systematic inguinal-iliac lymph node resection should be included in the initial treatment of this tumor., Highlights • Mesothelioma of the testicular tunica vaginalis. • Actually, no specific treatment recommendations exist for this tumor. • Current local treatment: orchidectomy without systematic inguinal lymph node dissection. • Our suggestion for local treatment: orchidectomy with systematic inguinal lymph node dissection.

INTRODUCTION Accumulating evidence suggests that cardiovascular disease (CVD) is highly prevalent among patients with concurrent obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary disease, otherwise known as overlap syndrome (OS). OBJECTIVES The aim of this study was to investigate the 10-year risk for CVD in OS patients compared with OSAS patients and controls. METHODS Consecutive patients, referred for symptoms suggestive of OSAS, were evaluated with polysomnography and pulmonary function testing. Cardiovascular risk was assessed using the Framingham risk score (FRS) and systematic coronary risk evaluation (SCORE). RESULTS Overall, 244 participants (184 males) without CVD and diabetes were divided into 3 groups: controls (n = 63), OSAS (n = 139) and OS (n = 42). Both FRS and SCORE were found to be elevated in the OS group compared with the OSAS and control groups (P

The pathophysiology and management of primary spontaneous pneumothorax (PSP) are a subject of debate. Despite advances in the understanding of its etiopathogenesis and improvements in its management, implementation in clinical practice is suboptimal. In this manuscript, we review the recent literature with a focus on PSP pathophysiology and management. Blebs and emphysema-like changes (ELC) are thought to contribute to the pathophysiology of PSP but cannot explain all cases. Recent studies emphasize the role of a diffuse porosity of the visceral pleura. Others found a relationship between smoking, occurrence of a PSP and bronchiolitis, which could be the initial pathological process leading to ELC development. Recent or ongoing studies challenge the need to systematically remove air from the pleural cavity of stable patients, introducing conservative management as a valuable therapeutic option. Evidence is growing in favour of needle aspiration instead of chest tube insertion, when air evacuation is needed. In addition, ambulatory management is considered as a successful approach in meta-analyses and is under exploration in a large randomized study. Because of a high recurrence rate of PSP, the benefit of performing a pleurodesis at first occurrence is under evaluation with interesting but not generalizable results. Better identification of 'at risk patients' is needed to improve the investigation strategy. Finally, recent publications confirm the efficacy, security and cost-effectiveness of graded talc poudrage pleurodesis to prevent PSP recurrence. In conclusion, PSP pathophysiology and management are still under investigation. The results of recently published and ongoing studies should be more widely implemented in clinical practice.

Obstructive sleep apnea syndrome (OSAS) is a multifactorial and common disorder affecting 10-17% of men and 3-9% of women. A low vitamin D serum concentration has been reportedly linked to OSAS susceptibility, but the underlying molecular genetic mechanisms are poorly understood thus far. We report here original findings on the ways in which vitamin D receptor (VDR) gene polymorphic variation (FokI, BsmI, ApaI, and TaqI polymorphisms) impacts serum vitamin D concentration and, additionally, susceptibility to OSAS. In a sample of 176 consecutive subjects (144 patients with OSAS and 32 healthy controls) phenotyped by full polysomnography (PSG), we characterized human genetic variation in VDR using the Sequenom MassARRAY iPLEX platform. A logistic regression analysis was employed to account and correct for covariates such as sex, age, body mass index, and comorbidities. Importantly, we observed that the FokI CC genotype frequency was markedly higher in patients with OSAS compared with controls (50.7% vs. 28.1%; p = 0.027). VDR FokI polymorphism explained 14.5% of vitamin D serum concentration variability. Moreover, the VDR FokI polymorphism was also associated with excessive daytime sleepiness (p = 0.016). To the best of our knowledge, this is the first clinical genetics study examining the role of VDR polymorphic variation on OSAS as phenotyped using full PSG. We call for further studies of vitamin D-related mechanisms that might contribute to OSAS risk in independent populations.

Background/aim In metastatic head and neck squamous cell carcinoma (HNSCC) the metastatic tumor does not always keep the same gene expression profile as the parental tumor, which may influence the course of the disease. The aim of this study was to compare the expression of genes implicated in HNSCC carcinogenesis between the primary tumor and the corresponding lymph node metastasis. Materials and methods Eighteen HNSCC, their corresponding node metastases and non-neoplastic tissues were studied by RT-qPCR for the expression of EGFR, VEGF, claudin7, maspin, survivin and SCCA. The levels of expression were correlated with histological characteristics and patients' prognosis. Results All genes except for survivin displayed different expression in node metastasis compared to the primary tumor. The expression of EGFR, survivin, maspin, and claudin7 in node metastasis and SSCA in the primary tumor affected the prognosis. SCCA expression is associated with the expression of claudin7 and maspin. P16-positive tumors expressed low levels of VEGF and SCCA, while keratinizing tumors over-expressed VEGF. Conclusion Differential gene expression levels in node metastases compared to the primary tumor is linked to the prognosis of HNSCC patients. The histological/immunohisto-chemical characteristics of the tumor are associated with these genes expression changes.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Endobronchial masses such as mucoepidermoid carcinomas or carcinoid tumors are extremely rare in children and they usually originate from large bronchi. These lesions may cause wheezing and dyspnea with poor response to bronchodilators and mimic the airway obstruction caused by asthma.We present the case of an 8-year-old girl with tracheal mucoepidermoid carcinoma who was treated as a difficult asthma case with high dose of inhaled corticosteroids.The characteristic stridor, the lack of response to bronchodilators and to inhaled corticosteroid treatment, combined with the characteristic flow loop in spirometry and the hyperinflation seen on the chest radiograph, all raised the clinical suspicion of a tracheal lesion and indicated the need for flexible bronchoscopy. The bronchoscopy revealed a large lesion obstructing totally the trachea lumen. The latter finding was confirmed by chest high resolution CT. The mass was completely excised via sternotomy under cardiopulmonary bypass, and the pathologic examination showed a low-grade mucoepidermoid carcinoma of the trachea. One month after the surgery she was free of symptoms and her spirometry was normal.Tracheal lesions mimic the symptoms of airway obstruction caused by asthma and should be always be part of the differential diagnosis in young patients with no response to asthma treatment.

Background: Thoracoscopy, either “medical” or “surgical”, is the gold standard to reveal the cause of pleural effusion by taking large biopsies. However, in some cases, the histology of pleural biopsies is inconclusive describing a variable process of inflammation, encompassing for non-specific pleuritis (NSP). Questions are raised whether the surgical (or VATS) is doing better than the medical thoracoscopy (MT), but no direct comparison between the two techniques exist in the current bibliography. The Aim: of our retrospective study was to compare these two techniques to find whether there is any difference in the false negative cases of NSP. Methods: We included in our study 295 patients with NSP, 179 patients who underwent VATS comparing to 116 patients who underwent MT for pleural effusion of initially undetermined cause, having a follow-up of at least one year. Analysis of patients’ files, history, clinical examinations, further tests, and follow-up were recorded. Results: The mean age of our patients was 58.5±19.1 and M/F gender was 216/79; no difference was observed between the two groups. A previous history of cancer was noted in 36 patients (12.2%). The mean follow-up period was 47.3±20.7 months. 3 patients were diagnosed with mesothelioma during the follow-up: with VATS, only one patient (0.55%) (false negative), while with MT 2 patients (1.7%). Negative predictive value for pleura-related malignancy for VATS was 0.994 and for MT 0.982. Conclusion: In patients with histological diagnosis of NSP both VATS and MT showed similar and excellent results of false negative cases and negative predictive value in excluding malignant pleural disease.

Background Tumors lymphocytic infiltration has prognostic and predictive value. However, the mechanisms involved in lymphocyte recruitment remain poorly characterized. High endothelial venules (HEV) are blood vessels specialized in lymphocyte recruitment, recently showing prognostic significance in some types of cancer. Their implications in laryngeal or pharyngeal cancer is largely unknown. Aim of the study To investigate the possible presence of HEVs in head and neck cancer. Material and Methods Oropharyngeal (n = 61), hypopharyngeal (n = 53) and laryngeal (n = 21) squamous cell carcinomas were immunohistochemically studied with the MECA-79 antibody, which specifically recognizes HEVs. Histological and clinical factors were correlated with HEVs’ presence. Results HEVs were present in 34% of tumors, showing significant correlations with oropharyngeal localization, higher lymphocytic response, lower tumor budding, lower T status, absence of distant metastases and better overall and progression-free survival. Conclusion HEVs represent an important prognostic factor in head and neck cancer.

Background: Medical thoracoscopy (MT) is an important procedure in the management of patients with pleural diseases. Objectives: We designed a survey to explore whether the participants of our courses implement MT at their hospital after attending the course as no real-life data exist. Methods: We distributed by e-mail a questionnaire to the participants of the courses. The questionnaire included general information about the participants, the precourse experience on MT, the postcourse implementation of the technique, and the reasons for failure. Results: Responses were obtained from 104 of 324 (32.3%) identified emails. Responders were males (76%), seniors (59.7%), respiratory physicians (91.3%), working in a public/university hospital (78.8%), and mostly beginners (65.3%) from 41 countries. Following the course, 58.6% of responders either created or modified a MT program in their workplace. The reasons for not performing MT before the course were as follows: patients’ referral to a thoracic surgeon, not enough training, lack of funding, department understaffed, and refusal by the hospital/department. Overall, these reasons were significantly decreased (p = 0.002) after the course. Conclusions: Real-life data of our survey suggest that more than half of the responders have implemented the technique or modified their practice according to the skills they got from the course.

Background: Evidence suggests that metabolic syndrome (MetS) is highly prevalent in patients with obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD). However, ...

Bronchiolitis obliterans is a clinical entity which results from a variety of etiologies and has a detrimental impact on patients' quality of life when it remains undiagnosed and untreated. Due to its non-pathognomic clinical symptoms and signs, physicians often proceed to radiological examination, especially with high resolution chest tomography. Histological examination reveals constrictive bronchiolitis, the pathological definition of bronchiolitis obliterans. Due to an almost normal aspect of the lung parenchyma this condition can be missed. However, its recognition and the identification of a possible exposure are important for removing the patient from the incriminating agent. We present a case of constrictive bronchiolitis in a metal-cutting worker, highlighting the principal findings of this disease.

Background: Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects. Objective: The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects. Methods: We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (n = 40) versus lidocaine and midazolam (n = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients’ quality of life (QoL) as assessed by a visual analog scale (VAS). Results: The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS. Conclusion: Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients’ QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.

Background Solitary papillomas of the lung are rare. One of their subtypes is glandular papilloma with only a very few cases described in the literature. We describe a case of pulmonary glandular papilloma with emphasis in its differential diagnosis and its molecular analysis. Case description A 64-years old former smoker was incidentally found to have an endobronchial tumor of the right main bronchus. Microscopic and immunohistochemical findings revealed a glandular papilloma. EGFR, KRAS and BRAF V600E mutation analysis, as well as HPV detection analysis revealed no mutation or HPV infection. Detailed differential diagnosis and literature review are presented. Conclusion Glandular papillomas of the lung are usually central, affecting older patients than squamous or mixed squamous cell and glandular papillomas. In previously reported cases, one glandular papilloma with KRAS mutation and another one with BRAF mutation have been reported. The present case harbored no mutation or HPV infection.

Background: Reports point out lung toxicity of chemotherapeutic agents and radiation therapy in cancer patients. The aim of our study was to assess lung function after sequential chemoradiation therapy in patients with lung cancer Methods: Fifteen lung cancer patients participated the study and underwent lung function assessment before and after sequential treatment of chemotherapy with the 3 most applied platinum-based combinations: of vinorelbine (VN) 6 patients, gemcitabine (GEM) 4 patients and etoposide (EP) 5 patients and radiation therapy. Lung function tests were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO) and carbon monoxide transfer coefficient (Kco). Results: Mean patients’ age was 58±9.4 years (42–75 years). Male patients were 14 (93.3%), all smokers. Overall, after chemoradiation treatment significant changes were noted in FEV1 (P=0.012), FVC (P=0.046), TLC (P=0.04) from baseline. The drop from baseline was more significant after chemoradiation therapy in DLCO (P=0.002) and KCO (P=0.008). Conclusions: According to our results, sequential chemoradiation causes significant changes in lung function parameters in patients with lung cancer.

Pericardial and pleural cavities produce effusions with important clinical consequences. Metastases are one of the most common etiologies of both serosal effusions. However, data regarding the type of metastatic involvement of the pleura and the pericardium are lacking. This study investigated the histologic patterns of tumors involving the two cavities to better define their pathophysiology and possible consequences in molecular diagnostics.This was a retrospective study of patients diagnosed with pericardial (n = 75) and pleural (n = 70) metastases. Patterns of metastasis were characterized as (1) tumor cells floating inside the cavity (2) as lymphatic emboli and (3) as tumor cells frankly invading underlying fibrous tissue. Molecular analysis (EGFR, KRAS, BRAF, ALK, HER2) was performed in 44 metastases of lung adenocarcinomas.The two serosal membranes differed significantly (p0.0001) in the pattern of metastasis. The pleura showed predominantly an invasive pattern (67 [95.7%]), whereas most pericardial metastases consisted of tumor cells floating inside the cavity or as lymphatic emboli (44 [58.6%]). The origin of the primary differed marginally between the two organs. Time to diagnosis of metastasis differed between the two organs, with pleural metastases presenting later than the pericardial ones. Molecular analysis failed more often in pericardial biopsy specimens and in specimens with emboli or surface involvement.Although pericardium and pleura share common embryologic and histologic features and are often regarded as giving similar effusions, they differ significantly in the type of metastases involving them. This can have important consequences in histologic, cytologic, and molecular diagnostics.

Evidence suggests that there is platelet activation in obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD). Our objective is to evaluate mean platelet volume (MPV) and platelet distribution width (PDW) in patients with overlap syndrome (OS), that is, concurrent COPD with OSAS. Mean platelet volume and PDW were assessed in consecutive patients who had undergone polysomnography and pulmonary function testing. They were divided into the following groups: controls (apnea–hypopnea index [AHI] 1]/forced vital capacity [FVC] >70%), OSAS group (AHI ≥5/hour and FEV1/FVC >70%), and OS group (AHI ≥5/hour and FEV1/FVC

Numerous studies have indicated that obstructive sleep apnea syndrome (OSAS), may contribute to the development of metabolic syndrome (MetS) and diabetes. Moreover, OSAS has been associated with lowered vitamin D (Vit D) levels, but reports are inconclusive. Aim of the study was to compare Vit D levels according to the presence of MetS and its components in OSAS patients.The presence of MetS was evaluated and serum 25-hydroxy vitamin D [25(OH)D] levels were measured in consecutive newly diagnosed, by polysomnography, subjects with OSAS.A total of 107 subjects (88 men) with OSAS were included in the study. Patients were divided into group A (OSAS with MetS group: 55 subjects) and group B (OSAS without MetS: 52 subjects). There were no differences between the two groups in terms of age, body mass index, and sleep parameters. Patients in group A exhibited higher levels of daytime sleepiness, as expressed by Epworth Sleepiness Scale score (12 ± 5.5 vs. 9.3 ± 4.8 for groups A vs. B, p = 0.008). Serum 25(OH)D levels were significantly decreased in group A, as compared with group B (18 ± 8.6 ng/mL vs. 23.9 ± 14.1 ng/mL, respectively, p = 0.012). Group A was then subdivided in two smaller groups, according to patients' metabolic index: OSAS patients with metabolic score = 3 and OSAS patients with metabolic score3. Serum 25(OH)D levels were higher in OSAS patients with metabolic score = 3 compared with OSAS patients with metabolic score3 (19.8 ± 8.9 ng/mL vs. 15.1 ± 7.3 ng/mL respectively, p = 0.038).OSAS patients with concurrent MetS exhibit lower serum Vit D levels, as compared with those without MetS.

BACKGROUND AND OBJECTIVE Cell-based therapies have been used for the management of several diseases, holding promising results. Few studies have evaluated their use in chronic lung diseases. Idiopathic pulmonary fibrosis (IPF) remains a lethal disease although new therapies have emerged the recent years. We have recently published a phase I study of 14 patients receiving endobronchially adipose-derived stem cells (ADSCs). The aim of this report is to assess the outcome for our patients' population. PATIENTS AND METHODS Patients who originally participated in this phase I study were followed up until the time of death. Pulmonary function tests as well as disease progression and survival time points were recorded. RESULTS After first administration, a significant functional decline was observed as assessed by the changes (delta-Δ) of diffusion capacity for carbon monoxide (DLco) (mean ΔDLco = 6.2%, P = .04) and forced vital capacity (FVC) (mean ΔFVC = 6%, P = .029) at 18 and at 24 months, respectively. Median overall progression-free survival was 26 months and median overall survival was 32 months. All patients were alive for at least 2 years (survival rate, 100%) after first administration. Twelve patients (85.7%) died owing to disease progression. None of the patients experienced tumor development. CONCLUSIONS Significant functional decline occurred at 24 months after first administration. The median survival and time to progression are in line with the published epidemiologic data. Further clinical trials complemented by mechanistic studies are sorely needed to delineate the role of ADSCs in IPF pathogenesis and treatment.

Objectives. Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. The aim of this study was to assess whether the 10-year risk for cardiovascular disease in newly diagnosed patients with OSAS is increased. Materials and Methods. Recently diagnosed, with polysomnography, consecutive OSAS patients were included. The Systematic Coronary Risk Evaluation (SCORE) and the Framingham Risk Score (FRS) were used to estimate the 10-year risk for cardiovascular disease. Results. Totally, 393 individuals (73.3% males), scheduled to undergo a polysomnographic study with symptoms indicative of OSAS, were enrolled. According to apnea-hypopnea index (AHI), subjects were divided in four groups: mild OSAS (AHI 5–14.9/h) was diagnosed in 91 patients (23.2%), moderate OSAS (AHI 15–29.9/h) in 58 patients (14.8%), severe OSAS (AHI > 30/h) in 167 patients (42.5%), while 77 individuals (19.6%) had an AHI p<0.001 and FRS values p<0.001. More specifically, a significant correlation was observed both between AHI and SCORE r=0.251, p<0.001 and AHI and FRS values r=0.291, p<0.001. Furthermore, a negative correlation was observed between FRS values and sleep efficiency r=−0.224, p=0.006. Conclusions. The 10-year risk for cardiovascular morbidity and mortality seems to increase with severity of OSAS. Physicians should bear this finding in mind, in order to seek for and consecutively eliminate risk factors for cardiovascular disease and to prevent future cardiovascular events in OSAS patients.

Background: Obstructive sleep apnoea syndrome (OSAS) has been linked with abnormal glucose metabolism, insulin resistance (IR) and development of diabetes mellitus. Methods: Non-diabetic patients (n=69) with OSAS, diagnosed by polysomnography, were prospectively recruited. To evaluate IR among OSAS patients, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Insulin sensitivity by Quantitative Insulin sensitivity Check Index (QUICKI) were used. Results: HOMA-IR was positively associated with body-mass index (BMI) (ρ=0.364, p=0.002), time with oxyhaemoglobin saturation Conclusions: An independent association between OSAS and IR in patients without pre-existing diabetes mellitus was observed. Recurrent hypoxia and sleep fragmentation in OSAS are associated with IR in these patients.

Background Pirfenidone is a novel anti-fibrotic drug that has shown efficacy in five randomized multicenter clinical trials enrolling patients with Idiopathic Pulmonary Fibrosis of mild-to-moderate disease severity. Scarce data supports the use of pirfenidone in IPF patients with more advanced disease. Objective To investigate the safety and efficacy profile of pirfenidone in IPF patients with severe lung function impairment. Patients and methods This was a retrospective study enrolling patients with advanced IPF (FVC%predicted Results Between September 2011 and March 2013, we identified 43 patients with severe IPF (baseline meanFVC%predicted±SD: 63.8 ± 20.3, meanDL CO %predicted: 27.3 ± 8.2), of mean age±SD: 66.3 + 9.7, 34 males (81%) that received pirfenidone (2.403 mg/daily) for one year. Pirfenidone treatment was associated with a trend towards decrease in functional decline compared to 6-months before treatment initiation but failed to show any benefit after one year of treatment (ΔFVC: −3.3 ± 4.6 vs 0.49 ± 11.4 and vs. −5.8 ± 11.8, p = 0.06 and p = 0.04, respectively and ΔDL CO : −13.3 ± 15.2 vs. −10.1 ± 16.6 and vs. 28.3 ± 19.2, p = 0.39 and p = 0.002, respectively). Gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%) were the most common adverse events. Adverse events led to treatment discontinuation in 9 patients (20.9%) and dose reduction in 14 (32.5%). Conclusion Pirfenidone appears to be safe when administered in patients with advanced IPF. Pirfenidone efficacy in IPF patients with severe lung function impairment may diminish after 6 months of treatment.

Objectives To describe the technique of pleuroscopy, its clinical uses such as diagnosis of exudative pleural effusion, treatment of pleural infection, treatment of pneumothorax, and diagnosis and pleurodesis of malignant pleural mesothelioma. Also to describe the newer techniques developed such as minothoracoscopy, semirigid thoracoscopy, narrow band imaging pleuroscopy, infrared pleuroscopy, autofluorescence pleuroscopy. Data source We searched the pubmed the last decade for publications with the key words pleuroscopy, medical thoracoscopy, pneumothorax and pleuroscopy, malignant pleural mesothelioma, minothoracoscopy, semirigid thoracoscopy, autofluorescence pleuroscopy. Conclusion Medical thoracoscopy is the method of choice for investigation of the undiagnosed exudative pleural effusions. Newer techniques, such as narrow band imaging thoracoscopy, infrared thoracoscopy, autofluorescence thoracoscopy are offering a promising future for medical thoracoscopy.

Background: Knowledge of pleural malignancy can lead to immediate pleurodesis during thoracoscopy. However, the accuracy of pleural frozen sections is largely unknown. Objectives: To investigate the accuracy of frozen sections in pleural tumor pathology. Methods: A total of 156 frozen pleural sections performed with the question of malignancy were retrospectively reviewed. The original frozen sections were compared to the permanent section slides which were considered as the gold standard. The influence of the following parameters on the frozen section response was evaluated: specimen size, clinical information, as well as the processing by a specialized pulmonary pathologist or not. The reasons of discrepancies were categorized as sampling errors or interpretation errors. Results: Frozen sections made up 16.4% of 951 pleural biopsies performed in the same time period. Accurate diagnosis was feasible in 92.3% of the cases. There were 7 (4.5%) deferred (inconclusive) cases and 5 (3.2%) discrepant cases. Sensitivity of the method was 96.26%, specificity 97.87%, the positive predictive value was 99.04%, and the negative predictive value was 92%. There was no association between the responses given during frozen section and specimen size, clinical information, or the evaluation by a specialized pulmonary pathologist. Four of the 12 cases were sampling errors, while 8 cases were interpretation errors mostly made in the absence of fat tissue invasion. Thus, paucicellular lesions without prominent invasion - fat invasion or haphazardly invading cellular proliferation - were those posing most of the difficulties during frozen section. Conclusions: Frozen sections are a highly accurate tool in pleural pathology. Thus, they can be used when an immediate pleurodesis is requested.

// Georgia Karpathiou 1 , Francois Casteillo 1 , Jean-Baptiste Giroult 2 , Fabien Forest 1 , Pierre Fournel 4 , Alessandra Monaya 1 , Marios Froudarakis 3 , Jean Marc Dumollard 1 , Jean Michel Prades 2 , Michel Peoc'h 1 1 Department of Pathology, North Hospital, University Hospital of St-Etienne, St-Etienne, France 2 Department of Head and Neck Surgery, North Hospital, University Hospital of St-Etienne, St-Etienne, France 3 Department of Pneumonology, North Hospital, University Hospital of St-Etienne, St-Etienne, France 4 Oncology Institute Lucien Neuwirth, St-Etienne, France Correspondence to: Georgia Karpathiou, email: gakarpath@yahoo.gr Keywords: PD-L1, CTLA4, macrophages, dendritic cells Received: July 15, 2016 Accepted: December 02, 2016 Published: December 27, 2016 ABSTRACT Background: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. Patients and Methods: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4. Results: CD3, CD8, CD57 and stromal S100 higher density is a good prognostic factor (p=0.02, 0.01, 0.02, 0.03 respectively). CTLA4 tumor expression is a poor prognostic factor (p=0.05). The rest immune cells do not affect prognosis. CD3 and CD8 density does not correlate with clinicopathological factors or p16/p53 expression, while CD57 and CD4 higher density is associated with the absence of distant metastases (p=0.03 and 0.07, respectively). Higher CD20 and S100 density is associated with lower T stage (p=0.04 and 0.03, respectively). PD-L1 expression is higher in CD3, CD8, and CD163 infiltrated tumors and in histologically more aggressive tumors. Response to neoadjuvant chemotherapy is better in highly CD3 infiltrated tumors and in tumors with less intraepithelial macrophages. Conclusion: Rich T-lympocytic and dendritic cell response is a good prognostic factor in SCCHN, whereas tumors expressing CTLA4 show poor prognosis. PDL1 expression does not affect prognosis, but it is expressed in histologically more aggressive tumors and in T-cells rich tumors. Response to induction chemotherapy is better in tumors less infiltrated by macrophages and mostly infiltrated by T cells.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] &ge, 2) and without insulin resistance (HOMA-IR &lt, 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 &plusmn, 5.8 compared to 32 &plusmn, 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 &plusmn, 28.9 compared to 40.9 &plusmn, 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 &plusmn, 11.5 vs 26.7 &plusmn, 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (&beta, = &minus, 0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913&ndash, 0.995, p = 0.030) and a positive association of BMI (&beta, = 0.110, OR: 1.116, 95% CI: 1.007&ndash, 1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

A pleural biopsy without granulomatous inflammation or tumour cells is interpreted as 'non-specific pleuritis' (NSP), a diagnosis without any specificity, often frustrating for physicians. However, varying histological features are found in NSPs with unknown significance. The aim of this study was to describe the detailed microscopic features of NSP and correlate them with the underlying aetiology. One hundred patients diagnosed with NSP after pleural biopsy were retrospectively evaluated. A benign cause of pleural effusion was attributed. Histological features evaluated were inflammation, fibrosis, vascular proliferation, haemorrhage, fibrin, oedema and mesothelial hyperplasia. A semi-quantitative scoring was applied. Bacterial-caused and autoimmune disease-associated NSPs showed a higher score followed by viral and drug-induced conditions, while pneumothorax and cardiac-induced NSPs showed a lower score (p

Objectives: Induction chemotherapy (IC) is occasionally used in head and neck cancer, leading to less extensive surgery and reduced need for irradiation. Factors predicting the response to IC have not been determined. In this study, we investigated the clinical and histopathologic factors that predict the response to IC. Methods: Head and neck squamous cell carcinomas from 81 patients were analyzed; clinical factors, histologic parameters, and expression of p16 and p53 were correlated with response to chemotherapy and prognosis. Results: Factors predicting a good response to IC were the nonoropharyngeal localization, a rich lymphocytic tissue response, and a low platelet-to-lymphocyte blood ratio before treatment. Response to IC did not correlate with prognosis, whereas a low neutrophil-to-lymphocyte ratio (NLR), the absence of a desmoplastic reaction, a rich lymphocytic tissue response, and the overexpression of p53 were associated with better prognosis. Conclusions: Lymphocytic tissue response, NLR, and nonoropharyngeal localization are factors predictive of response to IC.

Background Metastatic spread to the tracheobronchial tree from other than bronchopulmonary tumors is a common clinical problem. However, malignant melanoma, a highly metastatic potential tumor, is rarely metastasing in the airways. Therefore little is known about survival of patients with endobronchial metastasis from melanoma. Objectives The aim of our study was to assess survival of patients with endobronchial metastasis of melanomas according to clinical and radiological features, to determine any possible factor affecting survival. Methods This retrospective study included 19 patients who underwent a bronchoscopy from 11 different hospitals. Data about patients' demographics, symptoms, radiographic, endoscopic findings and treatment were investigated to evaluate any possible impact on survival. Results Endobronchial metastases occurred at a median of 48 months (range 0-120) following the diagnosis of the primary tumor. About 73.7% of patients had other proven metastases when the endobronchial involvement was diagnosed. Symptoms are not specific as well as radiological features. Median overall survival of the studied population was 6 months (range 1-46). Factors of poor survival were multiple metastatic sites (P = 0.019), pleural (P = 0.0014) and soft tissue metastasis (P = 0.024). Different treatment modalities applied in our patients showed no effect on survival. Conclusion Patients with endobronchial metastasis have overall poor survival, affected by multiple organ involvement, the presence of pleural and soft tissue disease, while no impact on survival has been shown by any treatment applied.

Background: Idiopathic pulmonary fibrosis (IPF) is associated with a prothrombotic state. Aim: To study mean platelet volume (MPV) and Platelet Distribution Width (PDW) as markers of platelet activation and their potential association with lung function in patients with recently diagnosed IPF. Materials and Methods: This study included 56 patients with IPF (age 64.9±7.4 years) and 79 controls (age 64.2 ± 5.9 years). Results: An inverse relation was demonstrated between platelet count and MPV in the control group but not among patients with IPF. Platelet count was significantly lower in patients with IPF compared with controls (230 ± 60 vs 256 ± 75 × 103/μL, P = .038). Conversely, MPV was higher in patients versus controls (10.3 ± 1.2 vs 9.8 ± 1.2 fl, P = .024), while there was no difference between the groups in PDW. Respiratory function was, as expected, significantly impaired in patients with IPF versus controls in terms of forced expiratory volume in first second (FEV1; 67.2 ± 23.1 vs 102.6 ± 15.9% of predicted value, P < .001), forced vital capacity (FVC; 65.3 ± 21 vs 95.2 ± 16.1% of predicted value, P < .001), FEV1/FVC (83.1 ± 15 vs 87.5 ± 6.4%, P = .041) and partial pressure of oxygen in arterial blood (PaO2; 67.1 ± 10.3 vs 81.5 ± 15.2 mm Hg, P < .001). No significant correlation was seen between MPV and FVC ( r = −.1497, P = .275), MPV and lung diffusion capacity for carbon monoxide ( r = .035, P = .798) and total lung capacity ( r = .032, P = .820). Conclusions: Patients with IPF exhibit higher MPV values and lower platelet count. Further studies are needed to assess the clinical implications of these findings.

Background and Aim:Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels.Materials and Methods:Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use.Results:At baseline, serum VEGF levels in OSA patients were higher compared with controls (pConclusion:In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy.

Gestational choriocarcinomas are highly malignant tumors with elevated serum human chorionic gonadotropin (hCG) levels. We report an extremely rare case of a 27-year-old woman who presented 4 months after normal delivery, with pulmonary, renal and intracardiac metastases of a choriocarcinoma. No primary uterine tumor was found. She was surgically treated for the renal and cardiac metastases as well as with cisplatin-etoposide chemotherapy. No recurrence has been observed 16 years after initial diagnosis, and the patient was able to have a second child. This case report shows that appropriate treatment of metastatic gestational choriocarcinoma can cure the patient without compromising her fertility.