Marios Froudarakis - Academia.edu (original) (raw)

Papers by Marios Froudarakis

Cancers

Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologie... more Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they can be associated with poor survival; thus, it is important to understand their pathophysiology. Furthermore, diagnosing a benign pleural pathology always harbors the uncertainty of a false-negative diagnosis for physicians and pathologists, especially for the group of non-specific pleuritis. This review aims to present the role of the inflammation in the development of benign pleural effusions, with a special interest in their pathophysiology and their association with malignancy.

Annals of Translational Medicine, 2021

Background: Pleural metastatic disease is a common disease with dismal prognosis. The immune micr... more Background: Pleural metastatic disease is a common disease with dismal prognosis. The immune microenvironment of metastatic pleural tissue remains largely unknown. Thus, we aimed to investigate the presence of different immune cell populations, and to compare them with clinical characteristics. Methods: We included 70 patients with lung and breast adenocarcinoma (ADC) diagnosed with pleural metastasis during a 2-year period with the primary endpoint to investigate if the main immune cell populations are present in pleural metastases and if they have any prognostic role. Secondary endpoints were to detect any differences in their presence between lung and breast primaries and to search for any correlation with the macroscopic (thoracoscopic) findings. We used immunohistochemical techniques for the detection of CD4 + , CD8 + , CD20 + , CD163 + and S100 + cells in whole tissue pleural biopsies of lung and breast metastases. Results: Primary endpoint: all these populations are present in the biopsies from lung and higher stromal and intratumoral CD4 counts, as well as higher stromal CD20 cells were positive prognostic factors for lung cancer metastases, while higher S100 intratumoral counts were positive prognostic factors in lung and marginally breast cancer metastases. Secondary endpoints: significant higher values for the stromal CD163 group (P=0.04) and for the intratumoral S100 group (P=0.006) were seen in lung compared to breast metastases. Interesting correlations were also noted between thoracoscopic findings (nodules, masses, pachypleuritis) and the different factors studied. Conclusions: Our data show that the immune microenvironment may be important in this advanced tumoral setting and that possible targets of the nowadays numerous treatment strategies implicating the immune system may merit further exploration in this poor prognosis disease.

Journal of Thoracic Disease, 2019

Journal for ImmunoTherapy of Cancer, 2020

BackgroundBrain metastases (Bmets) are frequent; however, limited data exist on the efficacy of i... more BackgroundBrain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.MethodsThis is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ2 test, Cramer’s V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.ResultsPD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary ...

Journal of Thoracic Disease, 2020

Background: Thoracoscopy, either "medical" or "surgical", is the gold standard to reveal the caus... more 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.

Annals of Medicine and Surgery, 2019

Mesothelioma of the tunica vaginalis of the testis (MTVM) is a rare tumor encountering for less t... more 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.

Cancer Genomics - Proteomics, 2019

Background/Aim: In metastatic head and neck squamous cell carcinoma (HNSCC) the metastatic tumor ... more 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.

Medicine, 2017

Rationale: Endobronchial melanoma metastases are rare, comprising 4.5% of all endobronchial metas... more Rationale: Endobronchial melanoma metastases are rare, comprising 4.5% of all endobronchial metastases. They are diagnosed at a median time of 48 months from primary tumor presentation, and survival of these patients is poorer when accompanied by other metastatic sites or malignant pleural effusion. We present a case of endobronchial melanoma metastasis happening 40 years after the initial diagnosis. The need of adjuvant techniques in the diagnosis of this tumor is highlighted and a short review on this rare phenomenon is provided. Patients concerns: An 83-year old nonsmoking woman, presented with dyspnea. Diagnoses: Left lung atelectasis was found. Interventions: Endobronchial resection of a tumor of the left main stem bronchus was achieved by rigid bronchoscopy under general anesthesia with complete reventilation of the left lung. Outcomes: Histopathological, immunohistochemical and molecular diagnostics of the resected tumor led to a diagnosis of an endobronchial melanoma metastasis. Lessons: Melanoma is a type of tumor that cannot be regarded as cured even after long disease-free periods, and thus, any new symptomatology in these patients warrants stringent work up. Abbreviations: AE1/AE3 = cytokeratin AE1/AE3, BRAF = v-raf murine sarcoma viral oncogene homolog B1, CD34 = cluster of differentiation 34, CT = computed tomography, CTLA-4 = cytotoxic T lymphocyte-associated antigen 4, DAB = 3,3 0diaminobenzidine, EMA = epithelial membrane antigen, GFAP = glial fibrillary acidic protein, HES = hematoxylin, eosin, saffran, HMB-45 = human melanoma black-45, KL1 = cytokeratin KL1, MDM2 = mouse double minute 2 homolog, MEK = mitogen-activated protein kinase, MiTF = microphthalmia-associated transcription factor, p40 = DNp63 isoform, PD-1 = programmed-death 1, PEC = perivascular epithelioid cell, PET = positron emission tomography, S100 = S100 protein, STAT6 = signal transducer and activator of transcription 6, TTF1 = thyroid transcription factor 1.

The Clinical Respiratory Journal, 2017

ObjectivesTo describe the technique of pleuroscopy, its clinical uses such as diagnosis of exudat... more ObjectivesTo 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 sourceWe 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.ConclusionMedical 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.

World journal of surgical oncology, Jan 26, 2005

The incidence of multiple primary malignant neoplasms increases with age and they are encountered... more The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90-100 packets per year). The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. It is important for the clinicians to keep in mind the possibility of a metachronous (successive) or a synchronous (simultaneous) malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous) is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas...

Military Medicine, 2004

Pulmonary toxicity, as an adverse effect of methotrexate (MTX) therapy, is uncommon in psoriatics... more Pulmonary toxicity, as an adverse effect of methotrexate (MTX) therapy, is uncommon in psoriatics. This report concerns a patient with psoriatic arthritis who developed fatal pneumonitis with a histopathological pattern of the organizing stage of diffuse alveolar damage and who was receiving MTX at a dose of 15 mg weekly for 1 month. The patient died despite the immediate withdrawal of MTX, the administration of corticosteroids, and adequate supportive care. Since MTX pneumonitis is a potentially fatal complication, new pulmonary symptoms, even in patients on low-dose MTX treatment, should be appropriately investigated.

Respiratory Research, 2009

Background: Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogene... more Background: Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP). Methods: Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6-to 8wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects. Results: A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients. Conclusion: Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.

Respiratory Medicine, 2007

Background: Thoracoscopic talc poudrage induces peripheral blood granulocytosis and lymphopenia. ... more Background: Thoracoscopic talc poudrage induces peripheral blood granulocytosis and lymphopenia. The aim of this study is to investigate the type of lymphopenia in patients undergoing thoracoscopic talc poudrage. Methods: We have measured peripheral blood lymphocyte subsets in 11 patients undergoing thoracoscopic talc poudrage, before (baseline), at 24 and 48 h after the procedure. Lymphocyte numbers were analysed by flow cytometry for the evaluation of the CD3+, CD4+, CD8+ cells (total T-lymphocytes, helper T-lymphocytes, cytotoxic Tlymphocytes, respectively), the CD19+ cells (B-lymphocytes), and the CD16+, CD56+ and CD57+ cells (NK-cells). No anti-inflammatory medication was permitted before, during or after the procedure. Results: Absolute peripheral blood lymphocyte count significantly decreased following thoracoscopic talc poudrage compared to baseline values (p ¼ 0:007). Similarly, peripheral blood CD3+, CD4+ and CD8+ lymphocyte counts significantly decreased compared to baseline (p ¼ 0:005, 0.02 and 0.03, respectively) with a more prominent reduction of CD3/ CD45RO memory cells. No significant difference was found in the absolute number of CD19+, CD16+, CD56+, and CD57+ cells before and after thoracoscopic talc poudrage.

Respiration, 2011

Thoracoscopy is currently the gold standard for the diagnosis and treatment of pleural diseases. ... more Thoracoscopy is currently the gold standard for the diagnosis and treatment of pleural diseases. Its diagnostic yield is 95% in patients with malignant pleural disease, with approximately 90% successful pleurodesis for malignant pleural effusion and 95% for pneumothorax. At the same time, thoracoscopy constitutes an important tool in the research of pleural pathophysiology and molecular biology. The improvement of technology has provided important tools to thoracoscopy, such as autofluorescence, narrow band imaging, and infrared light, used in clinical and basic research in many disorders involving the pleura. For these reasons, training in thoracoscopy should be considered equally important as training in bronchoscopy for residents in respiratory medicine.

Respiration, 2010

The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the t... more The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the treatment of pleural infection may increase pleural fluid drainage associated with a clinical and imaging improvement, leading to a faster resolution. The use of r-tPA is generally well tolerated. Here we report 2 cases of massive pleural hemorrhage resulting in life-threatening hypovolemia, in 2 patients treated with intrapleural r-tPA for a pleural infection, who were simultaneously receiving systemic anticoagulation (1 therapeutic, the second prophylactic) with low-molecular weight heparin. It appears that the decision of treating pleural infection with r-tPA in patients receiving therapeutic or prophylactic systemic anticoagulation must be well balanced and in case of association of these compounds, close monitoring is necessary.

Respiration, 2008

A wide range of diseases may be the cause of an accumulation of fluid in the pleural space. Pleur... more A wide range of diseases may be the cause of an accumulation of fluid in the pleural space. Pleural effusion is a major diagnostic problem, since the pleura is an inner cavity with no direct access. The aim of this review is to provide a practical approach to the investigation of the patient presenting with pleural effusion. This should help to accurately diagnose pleural effusion and keep time-consuming, but necessary, invasive investigations to the minimum.

$Research paper thumbnail of A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis$

Journal of Translational Medicine, 2013

Introduction Regenerative medicine and particular adult stem cells represent an alternative optio... more Introduction Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease. Patients and methods To this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity –FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events ...

Respiration; international review of thoracic diseases, 2010

Medical thoracoscopy (MT) is a procedure considered as minimally invasive. The safety of the proc... more Medical thoracoscopy (MT) is a procedure considered as minimally invasive. The safety of the procedure has been questioned recently in fragile patients, but no explanation of the pathophysiologic mechanism has been given. Although MT is applied by respiratory physicians who are also dealing with patients with impairment of lung function, it is surprising that there are no data concerning lung mechanics and function in this patient population.