Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist

ERS/EACTS statement on the management of malignant pleural effusions

Malignant pleural effusions (MPE) are a common pathology, treated by respiratory physicians and thoracic surgeons alike. In recent years, several well-designed randomized clinical trials have been published that have changed the landscape of MPE management. The European Respiratory Society (ERS) and the European Association for Cardio-Thoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in the management of MPE with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified, including the optimum management of symptomatic MPE, management of trapped lung in MPE, management of loculated MPE, prognostic factors in MPE, whether there is a role for oncological therapies prior to intervention for MPE and whether a histological diagnosis is always required in MPE. The literature revealed that talc pleurodesis and indwelling pleural catheters effectively manage the symptoms of MPE. There was limited evidence regarding the management of trapped lung or loculated MPE. The LENT score was identified as a validated tool for predicting survival in MPE, with Brims' prognostic score demonstrating utility in mesothelioma prognostication. There was no evidence to support the use of oncological therapies as an alternative to MPE drainage, and the literature supported the use of tissue biopsy as the gold standard for diagnosis and treatment planning.Management options for malignant pleural effusions have advanced over the past decade, with high-quality randomized trial evidence informing practice in many areas. However, uncertainties remain and further research is required http://ow.ly/rNt730jOxOS

Levels of Vascular Endothelial Growth Factor in serum and pleural fluid of patients with non-small cell lung carcinoma: their clinical significance

The primary objective of the present study was to prospectively evaluate the potential prognostic value of pretreatment vascular endothelial growth factor (VEGF) levels in serum and pleural fluid from patients with non-small cell lung carcinoma (NSCLC) presenting with malignant pleural effusion (MPE). We also aimed to investigate the diagnostic utility of serum VEGF levels in discriminating between patients with NSCLC and healthy individuals. Forty consecutive newly diagnosed NSCLC patients with MPE at presentation but without distant metastases, who were referred to the Oncology Unit G’PP of “Sotiria” General Hospital, Athens, Greece, between September 2009 and September 2013, were prospectively enrolled. Serum and pleural fluid VEGF levels were assayed by enzyme-linked immunoassay (ELISA). Serum VEGF levels were also measured in 50 controls with similar age and sex distribution (p=0.517 and p=0.795, respectively). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for serum VEGF to discriminate between patients and healthy subjects. Serum and pleural fluid VEGF levels were correlated with standard clinicopathological parameters, including gender, age, smoking history, performance status (PS), histological type of tumor and treatment response. The prognostic value of each variable for overall survival (OS) and progression-free survival (PFS) was assessed by univariate and multivariate Cox regression analysis.The median serum VEGF levels were significantly higher in patients as compared to healthy controls (p<0.001), while the optimal cut-off of serum VEGF was 375 pg/ml, with a sensitivity and specificity of 76.9% and 98.0%, respectively. Serum VEGF more than 375 pg/ml, pleural fluid VEGF over the median value and the presence of progressive disease, were all significantly associated with reduced OS and PFS, both in univariate and in multivariate analysis. A statistically significant correlation was also observed between serum and pleural fluid VEGF levels (p<0.001).The results of the present study suggest that serum VEGF levels may be useful in discriminating between patients with NSCLC and healthy individuals, and that increased pretreatment serum and pleural fluid levels of VEGF may be independent predictors of a worse survival in advanced-stage NSCLC patients. Future prospective studies are nevertheless needed to confirm these findings in larger patient cohorts and to further explore the potential value of these candidate biomarkers in predicting not only survival, but also response to targeted anti-angiogenic therapies.Ο πρωταρχικός σκοπός της παρούσας μελέτης ήταν η προοπτική διερεύνηση της δυνητικής προγνωστικής αξίας των προθεραπευτικών επιπέδων VEGF ορού και πλευριτικού υγρού σε ασθενείς με μη μικροκυτταρικό καρκίνο πνεύμονα (ΜΜΚΠ) που παρουσιάζονται με κακοήθη πλευριτική συλλογή. Επιπρόσθετος στόχος ήταν η διαλεύκανση της διαγνωστικής χρησιμότητας των προθεραπευτικών επιπέδων VEGF ορού για τη διάκριση μεταξύ ασθενών με ΜΜΚΠ και υγιών ατόμων. Στο παρόν ερευνητικό έργο μελετήσαμε προοπτικά 40 συνεχόμενους νεοδιαγνωσθέντες ασθενείς με ΜΜΚΠ, με κακοήθη πλευριτική συλλογή χωρίς απομακρυσμένες μεταστάσεις, που παραπέμφθηκαν για ογκολογική θεραπεία και αντιμετωπίστηκαν στην Ογκολογική Μονάδα της 3ης Πανεπιστημιακής Παθολογικής Κλινικής του Γενικού Νοσοκομείου Αθηνών «Η Σωτηρία», μεταξύ Σεπτεμβρίου 2009 και Σεπτεμβρίου 2013. Τα επίπεδα VEGF ορού και πλευριτικού υγρού μετρήθηκαν με τη χρήση ανοσοενζυμικής μεθόδου (ELISA). Τα επίπεδα VEGF ορού μετρήθηκαν επίσης σε πενήντα υγιείς μάρτυρες, εξομοιωμένους ως προς το φύλο και την ηλικία με τους ασθενείς (p=0.517 και p=0.795, αντιστοίχως). Η διαγνωστική ακρίβεια των επιπέδων VEGF ορού για τη διάκριση μεταξύ ασθενών με ΜΜΚΠ και υγιών μαρτύρων υπολογίστηκε με τη χρήση καμπυλών λειτουργικού χαρακτηριστικού δέκτη (Receiver operating characteristic curves, ROC curves). Τα επίπεδα VEGF ορού και πλευριτικού υγρού συσχετίσθηκαν με δημογραφικές και κλινικοπαθολογοανατομικές παραμέτρους, συμπεριλαμβανομένου του φύλου, της ηλικίας, του ιστορικού καπνίσματος, του performance status,του ιστολογικού τύπου του όγκου και της ανταπόκρισης στη θεραπεία. Η προγνωστική αξία κάθε μεταβλητής για τη συνολική επιβίωση και το διάστημα ελεύθερο προόδου νόσου αξιολογήθηκε με μονοπαραγοντική και πολυπαραγοντική ανάλυση παλινδρόμησης του Cox (univariate and multivariate Cox regression analysis). Οι διάμεσες τιμές VEGF ορού ήταν στατιστικώς σημαντικά υψηλότερες στους ασθενείς σε σύγκριση με τους υγιείς μάρτυρες (p<0.001), ενώ το βέλτιστο διαχωριστικό όριο όσον αφορά στις τιμές VEGF ορού για τη διάκριση μεταξύ ασθενών και μαρτύρων ήταν 375 pg/ml, με τιμές ευαισθησίας και ειδικότητας 76.9% και 98.0%, αντιστοίχως. Επίπεδα VEGF ορού μεγαλύτερα απο 375 pg/ml και επίπεδα VEGF πλευριτικού υγρού μεγαλύτερα από τη διάμεση τιμή, καθώς και η παρουσία προόδου νόσου, συσχετίσθηκαν με χαμηλότερο διάστημα PFS και χαμηλότερη συνολική επιβίωση, τόσο στη μονοπαραγοντική όσο και στην πολυπαραγοντική ανάλυση επιβίωσης. Στατιστικά σημαντική συσχέτιση παρατηρήθηκε επίσης μεταξύ των επιπέδων VEGF ορού και πλευριτικού υγρού (p<0.001).Τα αποτελέσματα της μελέτης μας υποδεικνύουν ότι τα επίπεδα VEGF ορού μπορεί να χρησιμεύουν για τη διάκριση μεταξύ ασθενών με ΜΜΚΠ και υγιών, καθώς και ότι τα αυξημένα προθεραπευτικά επίπεδα VEGF τόσο στον ορό και στο πλευριτικό υγρό ασθενών με ΜΚΚΠ προχωρημένου σταδίου μπορεί να αντιπροσωπεύουν ανεξάρτητους δείκτες δυσμενούς πρόγνωσης σε αυτή την υποομάδα των ασθενών. Για την επιβεβαίωση των ευρημάτων του παρόντος ερευνητικού έργου και την περαιτέρω διερεύνηση της πιθανής αξίας των ως άνω βιοδεικτών ως δεικτών πρόβλεψης όχι μόνο της επιβίωσης των ασθενών αυτών αλλά και της ανταπόκρισής τους στις στοχευμένες αντι-αγγειογενετικές θεραπείες, απαιτείται η διενέργεια μελλοντικών προοπτικών ερευνών σε μεγαλύτερες σειρές ασθενών

Clinical and surgical-pathological staging in early non-small cell lung cancer

Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC) because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC), a tumor, node, and metastases (TNM) staging system is currently used for NSCLC. Clinical staging (c-TNM) is achieved via non-invasive modalities such as examination of case history, clinical assessment and radiological tests. Pathological staging (p-TNM) is based on histological examination of tissue specimens obtained with the aid of invasive techniques, either non-surgical or during the intervention. This review is a critical evaluation of the roles of current pre-operative staging modalities, both invasive and non-invasive. In particular, it focuses on new techniques and their role in providing accurate confirmation of patient TNM status. It also evaluates the surgical-pathological staging modalities used to obtain the true-pathological staging for NSCLC

Histones and lung cancer: are the histone deacetylases a promising therapeutic target?

Deoxyribonucleic acid is wrapped around an octamer of core histone proteins to form a nucleosome, the basic structure of chromatin. Two main families of enzymes maintain the equilibrium of acetyl groups added to or removed from lysine residues. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues in histone amino termini and non-histone proteins also, leading to chromatin condensation and transcriptional repression. HDAC overexpression, resulting in tumor suppressor genes silencing, has been found in several human cancer tissues, indicating that aberrant epigenetic activity is associated with cancer development. Therefore, inhibitors of these enzymes are emerging anticancer agents and there is evidence supporting their role in hematological malignancies. The minimal efficacy of conventional chemotherapy has prompted a renewed focus on targeted therapy based on pathways altered during the pathogenesis of lung cancer. We identify the pleiotropic antitumor effects of HDAC inhibitors in lung cancer, focusing on the result caused by their use individually, as well as in combination with other chemotherapeutic agents, in lung cancer cell lines and in clinical trials. We searched reviews and original papers in Pubmed over the last 10 years. We identified 76 original papers on this topic. Numerous preclinical studies have shown that HDAC inhibitors exhibit impressive antitumor activity in lung cancer cell lines. Nevertheless, Phase III randomized studies do not support HDAC inhibitors use in lung cancer patients in everyday practice. Ongoing and future studies would help determine their role in lung cancer treatment

Giant Tuberculin Reaction Associated With the Homeopathic Drug Tuberculinum: A Case Report

Giant reactions to the tuberculin skin test are extremely rare and have been previously reported almost exclusively in patients with lepromatous leprosy. We herein report a giant tuberculin reaction associated with the homeopathic drug Tuberculinum in a patient with no evidence of active tuberculosis or leprosy

Artificial Intelligence-Based Treatment Decisions: A New Era for NSCLC

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable

Sampling versus systematic full lymphatic dissection in surgical treatment of non-small cell lung cancer

The extent of mediastinal lymph node assessment during surgery for non-small cell cancer remains controversial. Different techniques are used, ranging from simple visual inspection of the unopened mediastinum to an extended bilateral lymph node dissection. Furthermore, different terms are used to define these techniques. Sampling is the removal of one or more lymph nodes under the guidance of pre-operative findings. Systematic (full) nodal dissection is the removal of all mediastinal tissue containing the lymph nodes systematically within anatomical landmarks. A Medline search was conducted to identify articles in the English language that addressed the role of mediastinal lymph node resection in the treatment of non-small cell lung cancer. Opinions as to the reasons for favoring full lymphatic dissection include complete resection, improved nodal staging and better local control due to resection of undetected micrometastasis. Arguments against routine full lymphatic dissection are increased morbidity, increase in operative time, and lack of evidence of improved survival. For complete resection of non-small cell lung cancer, many authors recommend a systematic nodal dissection as the standard approach during surgery, and suggest that this provides both adequate nodal staging and guarantees complete resection. Whether extending the lymph node dissection influences survival or recurrence rate is still not known. There are valid arguments in favor in terms not only of an improved local control but also of an improved long-term survival. However, the impact of lymph node dissection on long-term survival should be further assessed by large-scale multicenter randomized trials

Pleural lavage cytology: Where do we stand?

Although a malignant pleural effusion is considered a manifestation of an advanced stage disease not amenable to curative resection in patients with non-small cell lung cancer, the same is not true in the case of the presence of malignant cells in the pleural cavity without an accompanying effusion, discovered incidentally during the operation with pleural lavage cytology (PLC). PLC is a diagnostic technique used to detect tumor cells and translate this finding to a prognostic index. Various reports have attempted to utilize the results of PLC and draw inferences regarding the origins of malignant cells in the pleural cavity, the association of these results with various disease characteristics and, most importantly, their impact on disease recurrence and survival. However, due to non-consistent techniques and protocols used to acquire the samples for cytological evaluation and assess their significance, results are inhomogeneous. Nevertheless, the entrance of malignant cells in the pleural cavity follows the rules posed by the natural disease process when discovered before pulmonary resection takes place, while surgical manipulations certainly play an important role in the case malignant cells are checked over after pulmonary resection. In addition, although the prognostic significance of a positive PLC result is indisputable and significantly decreases long-term survival in the majority of studies, this factor has not yet been incorporated into the TNM staging system. Lastly, some authors have advocated the use of some form of adjuvant treatment for those patients found with positive PLC results, based on the assumption that a curative resection followed by multiple pleural washings will not remove the entirety of the population of malignant cells present in the pleural space. (C) 2013 Published by Elsevier Ireland Ltd