High CTLA-4 expression correlates with poor prognosis in thymoma patients

Thymomas, tumors that arise from epithelial cells of the thymus gland, are the most common neoplasms of the anterior mediastinum, with an incidence rate of approximately 2.5 per million/year. Cytotoxic T Lymphocyte Antigen 4 (CTLA-4 or CD152) exerts inhibitory activity on T cells, and since its oncogenic role in the progression of different types of tumors, it has emerged as a potential therapeutic target in cancer patients. In this study, we assessed the expression of CTLA-4 both at mRNA and protein levels in paraffin embedded-tissues from patients with thymomas. Furthermore, we evaluated the relationship between CTLA-4 expression and the clinical-pathologic characteristics and prognosis in patients with thymomas. Sixty-eight patients with median age corresponding to 62 years were included in this analysis. Thymomas were classified accordingly to the WHO and Masaoka-Koga for histochemical analysis and for prognostic significance. A statistical difference was found between CTLA-4 mRNA levels in human normal thymus compared with thymoma specimens. CTLA-4 expression was statistically found to progressively increase in A, B1, B2, AB and it was maximal in B3 thymomas. According to Masaoka-Koga pathological classification, CTLA-4 expression was lower in I, IIA and IIB, and higher in invasive III and IV stages. By confocal microscopy analysis we identified the expression of CTLA-4 both in tumor cells and in CD45+ tumor-infiltrating leukocytes, mainly in B3 and AB thymomas. Finally, CTLA-4 overexpression significantly correlates with reduced overall survival in thymoma patients and in atypical thymoma subgroup, suggesting that it represents a negative prognostic factor

Gastro-entero-pancreatic neuroendocrine tumors: Is now time for a new approach?

Gastro-entero-pancreatic tumors (GEP-NETs) are rare neoplasms often characterized by an overexpression of somatostatin receptors. Thus, radiolabeled somatostatin analogues have showed an increasing relevance both in diagnosis and treatment, especially in low- And intermediate- differentiated GEP-NETs. These evidences have led to a growing development of new functional imaging techniques as 68Ga-DOTATATE positron emission tomography/ computed tomography (PET/CT) proved useful in the management of these neoplasms. However these tumors have a heterogeneous behavior also modifying their aggressiveness through time. Therefore sometimes 18F-fluorodeoxyglucose PET/CT appears to be more appropriate to obtain a better assessment of the disease. According to these considerations, the combination of different functional imaging techniques should be considered in the management of GEP-NETs patients allowing clinicians to choose the tailored therapeutic approach among available options

Electrolyte disorders in cancer patients: a systematic review

Electrolyte disorders are very common complications in cancer patients. They might be associated to a worsening outcome, influencing quality of life, possibility to receive anticancer drugs, and conditioning survival. In fact, they might provoke important morbidity, with dysfunction of multiple organs and rarely causing life-threatening conditions. Moreover, recent studies showed that they might worsen cancer patients’ outcome, while a prompt correction seems to have a positive impact. Furthermore, there is evidence of a correlation between electrolyte alterations and poorer performance status, delays in therapy commencement and continuation, and negative treatment outcomes. These alterations usually involve sodium, potassium, calcium, and magnesium serum levels. Several causes might contribute to electrolyte disorders in cancer patients: cancer effects, such as paraneoplastic syndrome of inappropriate antidiuresis and tumor lysis syndrome; anti-cancer therapies; and other concomitant clinical conditions or treatments. However, the origin of the electrolyte disorder is often multifactorial, thus identifying and correcting the causes is not always feasible. Furthermore, they are often not recognized or not considered in clinical practice, worsening these alterations and patient condition. An improvement of knowledge about the physiological mechanisms underlying electrolyte disorders is necessary to strengthen their identification and set up a prompt, adequate, and effective treatment. The aim of this systematic review is to provide an analysis of the pathophysiological mechanisms of electrolyte abnormalities in cancer patients to facilitate their identification, management, and therapy to improve patient outcome

Medical therapy for advanced gastro-entero-pancreatic and bronchopulmonary neuroendocrine tumors

Neuroendocrine tumors (NETs) represent a spectrum of rare neoplasms arising in different organism sites. Depending on the site of onset, they also can be distinguished using lab exams (secreting vs. nonsecreting), clinical symptoms (functioning vs. nonfunctioning), behavioral, morphological characteristics (tumor cells’ architectural growth patterns, mitotic and Ki-67 index, presence of necrosis), and grade of cellular differentiation. The aim of this review is to focus on the main signaling pathways targeted by medical treatments of advanced sporadic gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) neuroendocrine neoplasms. The scientific literature regarding treatment of advanced GEP and BP-NETs has been extensively reviewed using MEDLINE and PubMed databases, selecting principal and more recent research articles, clinical trials, and updated guidelines. Somatostatin analogues represent a valid approach to control symptoms in functioning tumors and to inhibit tumor progression in certain categories on the basis of the typical somatostatin receptor expression observed in NETs. The pathogenesis of NETs has been the subject of increased interest in recent years. Many driver mutations pathway genes have been identified as important factors in the carcinogenesis process and, therefore, as potential targets for new anticancer therapies. Activating mutations have been shown in epidermal growth factor receptor, stem cell factor receptor, platelet-derived growth factor receptor, vascular endothelial growth factor, basic-fibroblastic growth factor, transforming growth factor, insulin-like growth factor-1, and their receptors. Effective M-Tor inhibition pathway modulation has led to the approval of drugs in this field such as everolimus. New drugs and several combination regimens with targeted and newer biological agents are being developed and tested in recently conducted and ongoing trials

Management of lung cancer patients during COVID-19 pandemic: dos, don'ts and don't knows

Aim: During the coronavirus disease 2019 (COVID-19) pandemic two needs have overlapped: on one hand continuing to provide the best care for patients with lung cancer and preventing the spread of the virus between patients and healthcare professionals on the other hand. Due to the pandemic's unpredictable duration, physicians had to evaluate the risk/benefit ratio of anti-cancer therapeutic strategy to do the best for their patients and to protect patients themselves, as well as healthcare workers. Methods: Systematic literature research was performed with the aim to assess the available guidelines for the management of lung cancer patients during the COVID-19 pandemic. Thirteen potentially relevant articles were selected and recommendations have been divided into three main categories: dos, don'ts and don't knows. Results: All guidelines and recommendations highlighted the relevance of being able to delay, if possible and based on risk stratification, and curative interventions. The selected recommendations should be considered adaptable and flexible because they might be contextualized on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and the availability of diagnostic-therapeutic resources. Conclusions: It remains of fundamental importance to discuss each diagnostic and therapeutic decision with the patient taking into account risks and benefits that might vary from case to case