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Pubblicazioni recenti - cardiac surgery
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Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.
Cardiol J2020 Oct;():. doi: 10.5603/CJ.a2020.0132.
Kubica Jacek, Adamski Piotr, Niezgoda Piotr, Alexopoulos Dimitrios, Badarien? Jolita, Budaj Andrzej, Buszko Katarzyna, Dudek Dariusz, Fabiszak Tomasz, G?sior Mariusz, Gil Robert, Gorog Diana A, Grajek Stefan, Gurbel Paul A, Grucha?a Marcin, Jaguszewski Mi?osz J, James Stefan, Jeong Young-Hoon, Jilma Bernd, Kasprzak Jaros?aw D, Kleinrok Andrzej, Kubica Aldona, Kuliczkowski Wiktor, Legutko Jacek, Lesiak Maciej, Siller-Matula Jolanta M, Nadolny Klaudiusz, Pstr?gowski Krzysztof, Di Somma Salvatore, Specchia Giuseppe, St?pi?ska Janina, Tantry Udaya, Tyci?ska Agnieszka, Verdoia Monica, Wojakowski Wojciech, Navarese Eliano P,
Abstract
The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the dual antiplatelet therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic treatment (DATT) appear after a longer time from ACS (more than two years) and/or from cessation of DAPT (more than one year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome.
Circulation2020 Oct;():. doi: 10.1161/CIRCULATIONAHA.120.048916.
Dagradi Federica, Spazzolini Carla, Castelletti Silvia, Pedrazzini Matteo, Kotta Maria-Christina, Crotti Lia, Schwartz Peter J,
Abstract
The diagnosis of long QT syndrome (LQTS) is rather straightforward. We were surprised by realizing that, despite long-standing experience, we were making occasional diagnostic errors by considering as affected subjects that, over time, resulted as not affected. These individuals were all actively practicing sports, an observation which helped to design our study. We focused on subjects referred to our Center by Sports Medicine doctors with a suspicion of LQTS because of marked repolarization abnormalities on the ECG performed during the mandatory medical visit necessary in Italy to obtain the certificate of eligibility to practice sports. They all underwent our standard procedures involving both a resting and 12-lead ambulatory ECG, an exercise stress test, and genetic screening. There were 310 such consecutive subjects, all actively practicing sports with many hours of intensive weekly training. Of them, 111 had a normal ECG, different cardiac diseases or were lost to follow-up and exited the study. Of the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities, 121 were diagnosed as affected based on combination of ECG abnormalities with positive genotyping (QTc 482±35 ms). Genetic testing was negative in 78 subjects but 45 were nonetheless diagnosed as affected by LQTS based on unequivocal ECG abnormalities (QTc 472±33 ms). The remaining 33, entirely asymptomatic and with a negative family history, following detraining showed an unexpected and practically complete normalization of the ECG abnormalities (their QTc shortened from 492±37 to 423±25 ms, p<0.001, and their Schwartz score went from 3.0 to 0.06). They were considered not affected by congenital LQTS and are henceforth referred to as "Cases". Furthermore, among them, those who resume a similarly heavy physical training showed reappearance of the repolarization abnormalities. It is not uncommon to suspect LQTS among individuals actively practicing sports, based on marked repolarization abnormalities. Among those who are genotype-negative, >40% normalize their ECG following detraining but the abnormalities tend to recur with resumption of training. These individuals are not affected by LQTS but could have a form of acquired LQTS. Care should be exercised to avoid diagnostic errors.
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SARS-CoV-2-related lung pathology: macroscopic and histologic features and their clinical implications.
Panminerva Med2020 Oct;():. doi: 10.23736/S0031-0808.20.04157-9.
Sanguedolce Francesca, Zanelli Magda, Ascani Stefano, Zizzo Maurizio, Tortorella Simona, Soriano Alessandra, Cavazza Alberto, Sollitto Francesco, Loizzi Domenico,
Abstract
The ongoing global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been posing challenges to proper patients' management. Lungs are the first, and often the most affected organ by SARS-CoV-2; viral infection involves and damages both epithelial and vascular compartments, sometimes leading to severe and even fatal acute respiratory distress syndrome. Histopathological findings, mainly from postmortem examination of COVID-19 deceased patients, have been increasingly published in the last few months, helping to elucidate the sequence of events resulting in organ injury, and the complex multifactorial pathogenesis of this novel disease. A multidisciplinary approach to autopsy, including light microscopy examination along with the detection of viral proteins and/or RNA in tissue samples through ancillary techniques, provided crucial information on the mechanisms underlying the often-heterogeneous clinical picture of COVID-19.
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Efficacy and safety of bevacizumab in advanced lung adenocarcinoma patients with stable disease after two cycles of first-line chemotherapy: A multicenter prospective cohort study.
Thorac Cancer2020 Oct;():. doi: 10.1111/1759-7714.13687.
Ai Bin, Zhang Li, Huang Dingzhi, Chen Jun, Liu Zhe, Hu Xingsheng, Zhou Shengyu, Hu Yi, Zhao Jun, Yang Fan,
Abstract
Bevacizumab is the first antiangiogenetic monoclonal antibody, combined with platinum-based double agent chemotherapy, which has been reported to improve the objective response rate (ORR) and progression-free survival (PFS) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC), and to improve overall survival (OS) in patients when combined with carboplatin and paclitaxel. However, serious adverse effects have been reported to be associated with bevacizumab therapy. In this multicenter prospective cohort study of advanced lung adenocarcinoma patients with stable disease after two cycles of platinum-based double agent chemotherapy, we will compare the ORR between the group who continued with their original chemotherapy regimen and the group in which bevacizumab was added to the original regimen. It is expected that there will be an ORR improvement of 20% in patients in the bevacizumab group plus chemotherapy, compared with those in the original chemotherapy group. This study has been registered as Clinical Trial NCT03240549.
© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
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Preoperative echocardiographic parameters predict primary graft dysfunction following pediatric lung transplantation.
Pediatr Transplant2020 Oct;():e13858. doi: 10.1111/petr.13858.
Himebauch Adam S, Wong Wai, Wang Yan, McGowan Francis X, Berg Robert A, Mascio Christopher E, Kilbaugh Todd J, Lin Kimberly Y, Goldfarb Samuel B, Kawut Steven M, Mercer-Rosa Laura, Yehya Nadir,
Abstract
The importance of preoperative cardiac function in pediatric lung transplantation is unknown. We hypothesized that worse preoperative right ventricular (RV) systolic and worse left ventricular (LV) diastolic function would be associated with a higher risk of primary graft dysfunction grade 3 (PGD 3) between 48 and 72 hours. We performed a single center, retrospective pilot study of children (<18 years) who had echocardiograms <1 year prior to lung transplantation between 2006 and 2019. Conventional and strain echocardiography parameters were measured, and PGD was graded. Area under the receiver operating characteristic (AUROC) curves and logistic regression were performed. Forty-one patients were included; 14 (34%) developed PGD 3 and were more likely to have pulmonary hypertension (PH) as the indication for transplant (P = .005). PGD 3 patients had worse RV global longitudinal strain (P = .01), RV free wall strain (FWS) (P = .003), RV fractional area change (P = .005), E/e' (P = .01) and lateral e' velocity (P = .004) but not tricuspid annular plane systolic excursion (P = .61). RV FWS (AUROC 0.79, 95% CI 0.62-0.95) and lateral e' velocity (AUROC 0.87, 95% CI 0.68-1.00) best discriminated PGD 3 development and showed the strongest association with PGD 3 (RV FWS OR 3.87 [95% CI 1.59-9.43], P = .003; lateral e' velocity OR 0.10 [95% CI 0.01-0.70], P = .02). These associations remained when separately adjusting for age, weight, primary PH diagnosis, ischemic time, and bypass time. In this pilot study, worse preoperative RV systolic and worse LV diastolic function were associated with PGD 3 and may be modifiable recipient risk factors in pediatric lung transplantation.
© 2020 Wiley Periodicals LLC.
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'Surgery first' if cure is your aim in CTEPH.
Respirology -
Candida spp. Infective Endocarditis: Characteristics and Outcomes of Twenty Patients with a Focus on Injection Drug use as a Predisposing Risk Factor.
Mycoses2020 Oct;():. doi: 10.1111/myc.13200.
Morelli Morgan K, Veve Michael P, Lorson William, Shorman Mahmoud A,
Abstract
BACKGROUND:
Candida spp. infective endocarditis (CIE) although rare is associated with high morbidity and mortality. Risk factors include prosthetic heart valves and injection drug use (IDU). We reviewed all cases of CIE at our institution to describe the microbiology, treatment, and outcomes of patients focusing on IDU as a predisposing factor.
METHODS:
Retrospective cohort of patients with definite CIE between 2013-2019 at a university hospital was analyzed. Demographic data collected included IDU, microbiologic, treatment, and mortality. The primary outcome of interest was 12-month, all-cause mortality.
RESULTS:
20 patients were included (one had two separate episodes of CIE); CIE accounted for 4% of total infective endocarditis (IE) cases during the study period. The median (IQR) age was 38 (30-58) years, 10 (50%) had a previous history of IE, and 4 (20%) patients had prosthetic heart valves or an implanted cardiac device. Thirteen (65%) patients were IDU. The tricuspid valve was the primary valve involved (8/18, 44%), and C. albicans was the most frequently isolated organism (8, 36%). Echinocandin was the most common treatment strategy (8, 40%). Only three (15%) patients underwent valve replacement during hospitalization. There were no in-hospital fatalities, and 5 (25%) patients died at one-year; all were IDU (39% to 0%, P=0.11).
CONCLUSION:
CIE is a rare infectious disease seen more commonly in the IDU population. Cardiac surgery was rarely performed, and long-term mortality was 25%. Additional data are needed to identify ideal management strategies in this population.
This article is protected by copyright. All rights reserved.
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Ginsenoside Rb2 alleviates myocardial ischemia/reperfusion injury in rats through SIRT1 activation.
J Food Sci2020 Oct;():. doi: 10.1111/1750-3841.15505.
Xue Yan, Fu Wenwen, Liu Yanzhe, Yu Ping, Sun Mingyang, Li Xin, Yu Xiaofeng, Sui Dayun,
Abstract
The cardioprotective effects of ginsenoside Rb2 on oxidative stress, which is induced by hydrogen peroxide and myocardial ischemia/reperfusion (MI/R) injury, have been studied. The mechanisms were associated with the inhibition of cardiomyocyte apoptosis, a high concentration of antioxidant defense enzymes, and scavenging oxidative stress products. Because of the association with oxidative reaction and cardioprotection, sirtuin-1 (SIRT1) was selected as a promising target for investigating whether MI/R injury can be alleviated by ginsenoside Rb2 pretreatment through SIRT1 activation. The rats were exposed to ginsenoside Rb2 with or without SIRT1 inhibitor EX527 before ligation of coronary artery. Ginsenoside Rb2 reduced myocardial superoxide generation; downregulated gp91 expression; and decreased the mRNA expression levels and activities of interleukin-1?, interleukin-6, and tumor necrosis factor-?. The results demonstrated that ginsenoside Rb2 significantly attenuated oxidative stress and inflammation induced by MI/R injury. In addition, ginsenoside Rb2 upregulated SIRT1 expression and downregulated Ac-p53 expression. However, EX527 blocked the protective effects, indicating that the pharmacological action of ginsenoside Rb2 involves SIRT1. Our results thus revealed that ginsenoside Rb2 alleviated MI/R injury in rats by inhibiting oxidative stress and inflammatory response through SIRT1 activation. PRACTICAL APPLICATION: Ginsenoside Rb2 has a protective effect on MI/R injury by activating SIRT1 expression, reducing myocardium inflammation, and alleviating oxidative stress. Thus, ginsenoside Rb2 is a promising novel agent for ameliorating MI/R injury in ischemic heart diseases and cardiac surgery.
© 2020 Institute of Food Technologists®.
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Impact of Examined Lymph Node Count for Esophageal Squamous Cell Carcinoma in Patients who Underwent Right Transthoracic Esophagectomy.
Ann Surg Oncol2020 Oct;():. doi: 10.1245/s10434-020-09217-8.
Zheng Yu-Zhen, Li Xiao-Qiang, Wang Jun-Ye, Yang Hong, Wen Jing, Zhai Wen-Yu, Yuan Lian-Xiong, Fu Shen-Shen, Liao Hong-Ying, Fu Jian-Hua,
Abstract
BACKGROUND:
The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who underwent right transthoracic esophagectomy is still unclear.
METHODS:
Patients with ESCC who underwent right transthoracic esophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem and ?-binomial distribution estimation, respectively. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression.
RESULTS:
Among the 875 included patients, greater ELNs were associated with a higher rate of nodal metastasis. Significant association between staging bias and the number of ELNs is only observed through the Bayes method. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted hazard ratio [aHR] 0.986), especially in those patients with node-negative disease (aHR 0.972). In patients with node-negative disease, cut-point analysis showed a threshold ELN count of 21.
CONCLUSIONS:
A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 21 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease using the right thoracic approach.
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The effect of COVID-19 lockdown on acute type A aortic dissection: insights from Bologna.
JTCVS Tech2020 Oct;():. doi: 10.1016/j.xjtc.2020.10.002.
Murana Giacomo, Folesani Gianluca, Botta Luca, Di Marco Luca, Leone Alessandro, Loforte Antonino, Pacini Davide,
Abstract
This document is intended to provide an overview of the incidence and characteristics of acute type A aortic dissection in Bologna during the month of severe restrictions imposed by the National Italian government due to COVID-19 pandemic. Aspects on management and time to intervention are outlined.
© 2020 The Authors.
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Evaluation of PEEP and prone positioning in early COVID-19 ARDS.
EClinicalMedicine2020 Oct;():100579. doi: 10.1016/j.eclinm.2020.100579.
Mittermaier Mirja, Pickerodt Philipp, Kurth Florian, de Jarcy Laure Bosquillon, Uhrig Alexander, Garcia Carmen, Machleidt Felix, Pergantis Panagiotis, Weber Susanne, Li Yaosi, Breitbart Astrid, Bremer Felix, Knape Philipp, Dewey Marc, Doellinger Felix, Weber-Carstens Steffen, Slutsky Arthur S, Kuebler Wolfgang M, Suttorp Norbert, Müller-Redetzky Holger,
Abstract
Background:
In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned.
Methods:
The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study.
Findings:
Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (<0.01).
Interpretation:
In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume.
Funding:
German Research Foundation, German Federal Ministry of Education and Research.
© 2020 The Author(s).
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Prevalence, Predictors, and Early Outcomes of Post-operative Delirium in Patients With Type A Aortic Dissection During Intensive Care Unit Stay.
Front Med (Lausanne)2020 ;7():572581. doi: 10.3389/fmed.2020.572581.
Cai Shining, Zhang Xiaomin, Pan Wenyan, Latour Jos M, Zheng Jili, Zhong Jun, Gao Jian, Lv Minzhi, Luo Zhe, Wang Chunsheng, Zhang Yuxia,
Abstract
The aim of this study was to investigate the prevalence and explore the predictors and early outcomes of post-operative delirium (POD) in patients with type A aortic dissection (AAD) during intensive care unit (ICU) stays. We retrospectively reviewed the records of 301 patients with AAD who underwent surgical treatment in our institution from January 2017 to December 2018. Delirium developed in 73 patients (24.25%) during the ICU stay. Patients with lower estimated glomerular filtration rates [odds ratio (OR) 0.84, 95% CI 0.74-0.94, = 0.003], post-operative midazolam use (OR 2.37, 95% CI 1.33-4.23, = 0.004), and post-operative morphine use (OR 1.87, 95% CI 1.07-3.29, = 0.029) were more susceptible to developing POD. Patients who developed POD had a longer ICU stay (11.52 vs. 7.22 days, < 0.001) and hospital stay (23.99 vs. 18.91, = 0.007) with higher hospitalization costs (48.82 vs. 37.66 thousand dollars, < 0.001) than those without POD. The in-hospital mortality rate was higher in the delirium group, but the difference was not significant (6.85 vs. 4.82%, = 0.502). The incidence of POD in patients with AAD was high and was associated with renal dysfunction and the use of midazolam and morphine. POD was associated with poor early outcomes, suggesting the importance of early screening, such as for renal dysfunction, and prevention by using sedation scales to minimize the use of midazolam and morphine in these patients.
Copyright © 2020 Cai, Zhang, Pan, Latour, Zheng, Zhong, Gao, Lv, Luo, Wang and Zhang.
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Polarized Light Imaging of the Myoarchitecture in Tetralogy of Fallot in the Perinatal Period.
Front Pediatr2020 ;8():503054. doi: 10.3389/fped.2020.503054.
Truong Ba Luu, Jouk Pierre-Simon, Auriau Johanne, Michalowicz Gabrielle, Usson Yves,
Abstract
The pathognomonic feature of tetralogy of Fallot (ToF) is the antero-cephalad deviation of the outlet septum in combination with an abnormal arrangement of the septoparietal trabeculations. The aim of this article was to study perinatal hearts using Polarized Light Imaging (PLI) in order to investigate the deep alignment of cardiomyocytes that bond the different components of the ventricular outflow tracts both together and to the rest of the ventricular mass, thus furthering the classic description of ToF. 10 perinatal hearts with ToF and 10 perinatal hearts with no detectable cardiac anomalies (control) were studied using PLI. The orientation of the myocardial cells was extracted and studied at high resolution. Virtual dissections in multiple section planes were used to explore each ventricular structure. Contrary to the specimens of the control group, for all ToF specimens studied, the deep latitudinal alignment of the cardiomyocytes bonds together the left part of the Outlet septum (OS) S to the anterior wall of the left ventricle. In addition, the right end of the muscular OS bonds directly on the right ventricular wall (RVW) superior to the attachment of the ventriculo infundibular fold (VIF). Thus, the OS is a bridge between the lateral RVW and the anterior left ventricular wall. The VIF, RVW, and OS define an "inverted U" that roofs the cone between the interventricular communication and the overriding aorta. The opening angle and the length of the branches of this "inverted U" depend however on three components: the size of the OS, the size of the VIF, and the distance between the points of insertion of the OS and VIF into the RVW. The variation of these three components accounts for a significant part of the diversity observed in the anatomical presentations of ToF in the perinatal period.
Copyright © 2020 Truong, Jouk, Auriau, Michalowicz and Usson.
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SABR-BRIDGE: tereotactic lative adiotherapy efore esection to Avod elay for Early-Stage Lun Cancer or Oligomts During the COVID-19 Pandemic.
Front Oncol2020 ;10():580189. doi: 10.3389/fonc.2020.580189.
Kidane Biniam, Spicer Jonathan, Kim Julian O, Fiset Pierre-Olivier, Abdulkarim Bassam, Malthaner Richard, Palma David,
Abstract
Surgical resection is the standard-of-care approach for early-stage non-small cell lung cancer (NSCLC). Surgery is also considered an acceptable standard infit patients with oligometastatic lesions in the lungs. The COVID-19 pandemic has led to worldwide issues with access to operating room time, with patients and physicians facing uncertainty as to when surgical resection will be available, with likely delays of months. Further compounding this are concerns about increased risks of respiratory complications with lung cancer surgery during active phases of the pandemic. In this setting, many thoracic oncology teams are embracing a paradigm where stereotactic ablative radiotherapy (SABR) is used as a bridge, to provide radical-intent treatment based on a combination of immediate SABR followed by planned surgery in 3-6 months. This pragmatic approach to treatment has been named SABR-BRIDGE (Stereotactic ABlative Radiotherapy Before Resection to avoId Delay for early-stage lunG cancer or oligomEts). This term has also been applied to the pragmatic study of the outcomes of this approach. In this paper, we discuss the standards of care in treatment of early-stage (NSCLC) and pulmonary oligometastases, the impetus for the SABR-BRIDGE approach, and the controversies surrounding assessment of pathological response to neo-adjuvant radiation therapy.
Copyright © 2020 Kidane, Spicer, Kim, Fiset, Abdulkarim, Malthaner and Palma.
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Therapeutic Landscape of Malignant Pleural Mesothelioma: Collateral Vulnerabilities and Evolutionary Dependencies in the Spotlight.
Front Oncol2020 ;10():579464. doi: 10.3389/fonc.2020.579464.
Xu Duo, Yang Haitang, Schmid Ralph A, Peng Ren-Wang,
Abstract
Malignant pleural mesothelioma (MPM) is the epitome of a recalcitrant cancer driven by pharmacologically intractable tumor suppressor proteins. A significant but largely unmet challenge in the field is the translation of genetic information on alterations in tumor suppressor genes (TSGs) into effective cancer-specific therapies. The notion that abnormal tumor genome subverts physiological cellular processes, which creates collateral vulnerabilities contextually related to specific genetic alterations, offers a promising strategy to target TSG-driven MPM. Moreover, emerging evidence has increasingly appreciated the therapeutic potential of genetic and pharmacological dependencies acquired en route to cancer development and drug resistance. Here, we review the most recent progress on vulnerabilities co-selected by functional loss of major TSGs and dependencies evolving out of cancer development and resistance to cisplatin based chemotherapy, the only first-line regimen approved by the US Food and Drug Administration (FDA). Finally, we highlight CRISPR-based functional genomics that has emerged as a powerful platform for cancer drug discovery in MPM. The repertoire of MPM-specific "Achilles heel" rises on the horizon, which holds the promise to elucidate therapeutic landscape and may promote precision oncology for MPM.
Copyright © 2020 Xu, Yang, Schmid and Peng.
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Combined Immunoscore for Prognostic Stratification of Early Stage Non-Small-Cell Lung Cancer.
Front Oncol2020 ;10():564915. doi: 10.3389/fonc.2020.564915.
Boscolo Alice, Fortarezza Francesco, Lunardi Francesca, Comacchio Giovanni, Urso Loredana, Frega Stefano, Menis Jessica, Bonanno Laura, Guarneri Valentina, Rea Federico, Conte PierFranco, Calabrese Fiorella, Pasello Giulia,
Abstract
Background:
To date, no combined immunoscore has been evaluated for prognostic stratification of early stage non-small-cell lung cancer (NSCLC). The main goal of this study was to investigate the prognostic impact of programmed death ligand 1 (PD-L1) expression and different immune cell components (CD4+, CD8+ T-lymphocytes, and CD68+ macrophages) in early stage NSCLC patients, distinguishing peritumoral (PT) and intratumoral (IT) localizations. The secondary aim was to identify a combined immunoscore to optimize the prognostic stratification of NSCLC patients.
Methods:
This retrospective study included surgical specimens from consecutive chemo-naive stage II-III radically resected NSCLC patients. Immunohistochemistry was carried out to evaluate PD-L1 expression and to quantify IT and PT CD4+, CD8+ T-lymphocytes, and CD68+ macrophages. The impact of a single marker and of a combination of multiple markers on overall survival (OS) was investigated.
Results:
Seventy-nine patients were included in the study. PD-L1 expression was associated with worse prognosis (3 years OS: 58% in high- compared with 67% in low-expressing tumors), even though without statistical significance. When integrating PT CD8+, CD4+, and CD68 into a combined PT immunoscore, a significant prognostic stratification of patients was obtained and confirmed at multivariate analysis (3 years OS: 86% in patients with low PT immunoscore vs. 59% in patients with high PT immunoscore, = 0.018). The integration of derived neutrophil/lymphocyte ratio (dNLR) with combined PT immunoscore improved prognostic stratification, with longer OS in patients with low PT immunoscore and low dNLR ( = 0.002).
Conclusion:
The combined PT immunoscore (CD8+, CD4+, and CD68) integrated with dNLR may be a promising marker for the development of an integrated Tumor, Node, Metastasis (TNM) immunoscore.
Copyright © 2020 Boscolo, Fortarezza, Lunardi, Comacchio, Urso, Frega, Menis, Bonanno, Guarneri, Rea, Conte, Calabrese and Pasello.
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Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy.
Front Oncol2020 ;10():1775. doi: 10.3389/fonc.2020.01775.
Esser Laura K, Branchi Vittorio, Leonardelli Sonia, Pelusi Natalie, Simon Adrian G, Klümper Niklas, Ellinger Jörg, Hauser Stefan, Gonzalez-Carmona Maria A, Ritter Manuel, Kristiansen Glen, Schorle Hubert, Hölzel Michael, Toma Marieta I,
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer accounting for 80% of all renal cancers as well as the majority of renal cancer-associated deaths. During the last decade, the treatment paradigm for ccRCC has radically changed. In particular, the recent development of immune checkpoint inhibitors (ICI) has led to an increased overall survival in the metastatic setting. Moreover, novel immune therapies targeting the tumor microenvironment have been developed. In this rapidly evolving treatment landscape, precise tools for personalized cancer therapy are needed. Here, we collected fresh tissue from 42 patients who underwent surgical resection for renal cell carcinoma. Part of the tissue was used to obtain formalin-fixed, paraffin-embedded samples or RNA. The remaining tissue was minced and cultured in a collagen-based three-dimensional, air-liquid interface (ALI) culture system. The generated patient-derived tumor organoids (ALI PDOs) were characterized by immunohistochemistry staining and RNA sequencing to validate their close similarity to the matched tumor. Immune cells and stromal cells within the microenvironment could be identified. Finally, we treated 10 ALI PDOs with the commonly used targeted cancer drug cabozantinib or the ICI nivolumab. Interestingly, we observed varying responses of ALI PDOs to these treatments and future studies are needed to investigate whether the ALI PDO approach could inform about treatment responses in patients. In conclusion, this three-dimensional ccRCC culture model represents a promising, facile tool for monitoring tumor responses to different types of therapies in a controlled manner, yet, still preserves the key features of the tumor of origin.
Copyright © 2020 Esser, Branchi, Leonardelli, Pelusi, Simon, Klümper, Ellinger, Hauser, Gonzalez-Carmona, Ritter, Kristiansen, Schorle, Hölzel and Toma.
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Exosome-Derived LncRNAs in Lung Cancer.
Front Oncol2020 ;10():1728. doi: 10.3389/fonc.2020.01728.
Fan Tao, Sun Nan, He Jie,
Abstract
As extracellular vesicles, exosomes are released from most cells to perform cell-cell communication. Recent studies have shown that exosomes could be released into tumor microenvironment and blood to promote tumor progression through packaging and transmitting various bioactive molecules, such as cholesterol, proteins, lipids, miRNAs, mRNAs, and long non-coding RNAs (lncRNAs) to distant cells. LncRNAs have emerged as a major class of non-coding transcripts. A lot of LncRNAs have been discovered during the past few years of research on genomics. They have been proven to participate in various biological functions and disease processes through multiple mechanisms. In this review, we analyzed the role of exosome-derived lncRNAs in lung carcinogenesis and metastasis. We also highlight opportunities for the clinical potential of exosomes with specific lncRNAs as biomarkers and therapeutic intervention in lung cancer.
Copyright © 2020 Fan, Sun and He.
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Commentary: The Incidence of Node-Positive Non-small-Cell Lung Cancer Undergoing Sublobar Resection and the Role of Radiation in Its Management.
Front Oncol -
Malignant lymphoma mimics miliary tuberculosis by diffuse micronodular radiographic findings.
Respir Med Case Rep2020 ;31():101239. doi: 10.1016/j.rmcr.2020.101239.
Yagyu Kyoko, Kobayashi Masaaki, Ueda Takahiro, Uenishi Riki, Nakatsuji Yuko, Matsushita Haruhiko,
Abstract
This case reports rare findings on computed tomography of a manifestation of malignant lymphoma, in which diffuse lung shadows appeared as miliary nodules distributed throughout the lungs bilaterally. The patient had a history of surgical treatment of rectal cancer and had received chemotherapy for suspicious liver metastasis. At her current presentation for evaluation suspected miliary tuberculosis on chest radiography, subsequent liver biopsy revealed a mass infiltration of atypical lymphocytes, which was diagnosed as follicular lymphoma. The miliary tuberculosis was suspected more than neoplastic lesions, such as metastatic rectal cancer or malignant lymphoma. Despite repeated bacteriologic tests of various samples, including sputum, urine, bronchial secretion, peripheral blood, bone marrow aspiration, and gastric lavage, all results were negative for mycobacterium tuberculosis. Finally, multiple, small, mass lesions of lymphocytes were demonstrated in the lung obtained from video-assisted thoracic surgery, and a diagnosis of follicular lymphoma was given. The final interpretations of liver mass and military lung lesions were tumor involvement by the follicular lymphoma. This radiologic findings of multiple miliary opacities throughout the whole lungs confused definite diagnosis because these images were remarkably similar with miliary tuberculous. This case reminds us to consider a wide variety of differential diagnoses even we assumed to be familiar with radiographic imaging at first glance.
© 2020 The Author(s).
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