Utilità della biopsia epatica nella valutazione d'idoneità al trapianto di rene del paziente con infezione da virus C

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Lung carcinoid tumours: histology and Ki-67, the eternal rivalry

WHO classification of Thoracic Tumours defines lung carcinoid tumours (LCTs) as well-differentiated neuroendocrine neoplasms (NENs) classified in low grade typical (TC) and intermediate grade atypical carcinoids (AC). Limited data exist concerning protein expression and morphologic factors able to predict disease aggressiveness. Though Ki-67 has proved to be a powerful diagnostic and prognostic factor for Gastro-entero-pancreatic NENs, its role in lung NENs is still debated. A retrospective series of 370 LCT from two oncology centers was centrally reviewed. Morphology and immunohistochemical markers (Ki-67, TTF-1, CD44, OTP, SSTR-2A, Ascl1, and p53) were studied and correlated with Overall Survival (OS), Cancer-specific survival (CSS) and Disease-free survival (DFS). Carcinoid histology was confirmed in 355 patients: 297 (83.7%) TC and 58 (16.3%) AC. Ki-67 at 3% was the best value in predicting DFS. Ki-67 ≥ 3% tumours were significantly associated with AC histology, stage III-IV, smoking, vascular invasion, tumour spread through air spaces OTP negativity, and TTF-1, Ascl1 and p53 positivity. After adjustment for center and period of diagnosis, both Ki-67 (≥3 versus <3) and histology (AC versus TC) alone significantly added prognostic information to OS and CSS multivariable model with age, stage and OTP; addition of both variables did not provide further prognostic information. Conversely, an improved significance of the DFS prediction model at multivariate analysis was seen by adding Ki-67 (≥3 versus <3, P adj = 0.01) to TC and AC histological distinction, age, lymph node involvement, residual tumour and OTP. Ki-67 ≥ 3% plays a potentially pivotal role in LCT prognosis, irrespective of histological grade

Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications

Simple Summary In this manuscript, we offer an integrated molecular analysis of 44 combined large cell neuroendocrine carcinomas (CoLCNECs) in order to deepen the knowledge about these rare histotypes and to clarify their relationship with lung cancers. In the present state of research, molecular studies are still scant, consisting of small and heterogeneous cohorts, and the genomic landscape is poorly characterized. This study shows that CoLCNECs constitute a standalone group of neuroendocrine neoplasm, with three different molecular profiles, two of which overlap with pure LCNEC or adenocarcinoma. CoLCNECs can be considered an independent histologic category with specific genomic and transcriptomic features, different and therefore not comparable to other lung cancers. Indeed, in addition to a histological re-evaluation of lung cancer classification, our study may help to develop a new diagnostic approach for novel and personalized treatments in CoLCNECs. Background: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. Methods: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQC), 3 with small cell carcinoma (CoSCLC), 4 with atypical carcinoid (CoAC) and 4 napsin-A positive LCNEC (NapA+), were assessed for alterations in 409 genes and transcriptomic profiling of 20,815 genes. Results: Genes altered included TP53 (n = 30), RB1 (n = 14) and KRAS (n = 13). Targetable alterations included six KRAS G12C mutations and ALK-EML4 fusion gene. Comparison of CoLCNEC transcriptomes with 86 lung cancers of pure histology (8 AC, 19 ADC, 19 LCNEC, 11 SCLC and 29 SQC) identified CoLCNEC as a separate entity of neuroendocrine tumours with three different molecular profiles, two of which showed a non-neuroendocrine lineage. Hypomethylation, activation of MAPK signalling and association to immunotherapy signature specifically characterized each of three CoLCNEC molecular clusters. Prognostic stratification was also provided. Conclusions: CoLCNECs are an independent histologic category. Our findings support the extension of routine evaluation of KRAS mutations, fusion genes and immune-related markers to offer new perspectives in the therapeutic management of CoLCNEC

Need for Developing a Collapsible and Inexpensive Spacer Device for Use with Metered Dose Inhalers

Most of the patients with asthma or COPD (Chronic Obstructive Pulmonary Disease) in the United States require the use of metered dose inhalers (MDIs) to control their symptoms. Over the past three decades, metered dose inhalers have become a mainstay of asthma therapy. (Mayo Clinic Institution-1, 2000) These aerosolized/pressurized canisters of medication are efficacious in that the medication is delivered directly to the lung tissue. This is where the therapeutic effect takes place. However, many patients cannot coordinate the hand and breath skills necessary to deliver an optimal dose of the medicine. Medical professionals teach techniques to these particular patients. Even after the education of using a MDI properly, some patients maintain difficulty in the proper use of the metered-dose-inhaler. At this point, many physicians and respiratory therapists will advise the patient to use some type of an aerosol spacer device. These devices allow the patient to lesson the critical timing of activation of the MDI with the inhalation of the aerosolized medication into their lungs. There are many aerosol MDIs on the market today with varying features and advantages. Further, these bronchodilators and inhaled corticosteroids come structured in plastic holders. These plastic holders are used to hold the canister in place while the patient is using the medication. The mouthpiece of each MDI will vary in shapes and lengths, however, approximately 90% of the MDIs on the market share one of two distinct shapes that will be discussed later in this synthesis project. The purpose of this study is to determine the feasibility of introducing a new portable and collapsible spacer device into the medical market place that is currently under development. It is hypothesized that the need for expensive and complicated spacer devices may not be necessary in order to allow a patient the needed space between the MDI easement and their mouth. Therefore, this paper will examine the medical literature and survey medical professionals to determine the rational uses of spacer devices when treating patients on MDIs. This paper will also examine what products are popular spacer devices in the medical community. This will serve to determine the logical methodology that medical professionals use when selecting a particular spacer device. The outcome of this study speculates that a simple portable spacer device of optimal and medically documented dimensions, will serve as a logical alternative when the need for a spacer device has been determined by a health care professional