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BACKGROUND: Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed. OBJECTIVES: To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection. METHODS: We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox' regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort. RESULTS: Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density ≥ 20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not. CONCLUSIONS: LN-density ≥ 20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.
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Non-dilated left ventricular cardiomyopathy (NDLVC) is a newly categorized cardiomyopathy phenotype includingseveral aetiologies with a linking characteristic represented by the normal left ventricular volume. Inflammatory heart disease (InHD) is a heterogeneous process with variegate clinical manifestations, sometimes in overlap with NDLVC. A 26-year-old woman was admitted forcomplete heart block (CHB) and persistently raised troponin. Echocardiography and coronary angiography were normal. Extensive oedema and late gadolinium enhancement was found at cardiac magnetic resonance. Endomyocardial biopsy showed no signs of active myocarditis. Steroid therapy was started with restoration of atrioventricular conduction but subsequently the patient experienced a mild recurrence with a new troponin relapse. Genetic test was negative for mutations related with the clinical scenario. In this case of NDLVC with InHD the precise diagnostic work-up, including genetic test, was crucial for diagnostic, prognostic andtherapeutic purposes. Multimodality approach is crucial to detect and treat possible recurrences.
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Forensic pathologists are frequently asked to investigate cases of sudden death (SD), and identifying the cause of death can be of particular importance, especially where it may be necessary to perform family screening among the relatives of the victim. A multidisciplinary approach inclusive of genetic analysis is therefore strongly recommended. According to forensic practice, arrhythmogenic cardiomyopathy (ACM) is a well-known cause of SD. However, cases of SD caused by a left ventricular pattern of ACM diagnosed at autopsy are rarely reported in the literature. We present the case of an apparently healthy, 37-year-old male found dead at his home. At autopsy, multiple foci of epicardial and mid-wall fibrous and fibro-adipose tissue were observed within the left ventricle and, to a lesser extent, within the interventricular septum. Toxicology was negative, whereas a filamin C truncating mutation was detected through genetic analysis. To our knowledge, this is the first instance of arrhythmogenic left ventricular cardiomyopathy being diagnosed at autopsy.
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Filaminas , Mutação , Humanos , Masculino , Adulto , Filaminas/genética , Autopsia , Displasia Arritmogênica Ventricular Direita/genética , Ventrículos do Coração/patologia , Patologia Legal/métodos , Morte Súbita Cardíaca/etiologiaRESUMO
AIMS: 'Hot phases', characterized by chest pain and troponin release, may represent the first clinical presentation of arrhythmogenic cardiomyopathies. Differential diagnosis with acute myocarditis is an unmet challenge for the clinicians. We sought to investigate histological and genetic features in patients with cardiomyopathy presenting with hot phases. METHODS AND RESULTS: We evaluated a case series of consecutive patients hospitalized for suspected 'hot-phase cardiomyopathy' in two Italian centres from June 2017 to March 2022 (median follow-up 18 months) that underwent both endomyocardial biopsy (EMB) and genetic testing. Apoptosis was confirmed with TUNEL assay. Among the 17 enrolled patients (mean age 34 ± 15 years, 76% male), only six patients (35%) presented standard histological and immunohistochemical markers for significant cardiac inflammation at EMB. Conversely, apoptosis was found in 13 patients (77%). Genetic testing was positive for a pathogenic/likely pathogenic (P/LP) variant in genes involved in cardiomyopathies (most frequently in DSP) in eight patients (48%), rising to 62% among patients with apoptosis on EMB. Notably, all patients without apoptosis tested negative for P/LP disease-related variants. Left ventricular ejection fraction was lower in patients showing apoptosis at EMB compared to those without (p = 0.003). CONCLUSIONS: Apoptosis, rather than significant inflammation, was mostly prevalent in this case series of patients with 'hot-phase' presentation, especially in carriers of variants in cardiomyopathy-related genes. Detecting apoptosis on EMB might guide clinicians in performing genetic testing and in more tailored therapeutic choices in 'hot-phase cardiomyopathy'.
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Apoptose , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Miocárdio/patologia , Biomarcadores , Biópsia/métodos , Diagnóstico Diferencial , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Miocardite/diagnóstico , Cardiomiopatias/diagnóstico , Itália/epidemiologia , Troponina/sangueRESUMO
Pulmonary fibrosis is a devastating disease, in which fibrotic tissue progressively replaces lung alveolar structure, resulting in chronic respiratory failure. Alveolar type II cells act as epithelial stem cells, being able to transdifferentiate into alveolar type I cells, which mediate gas exchange, thus contributing to lung homeostasis and repair after damage. Impaired epithelial transdifferentiation is emerging as a major pathogenetic mechanism driving both onset and progression of fibrosis in the lung. Here, we show that lung endothelial cells secrete angiocrine factors that regulate alveolar cell differentiation. Specifically, we build on our previous data on the anti-fibrotic microRNA-200c and identify the Vascular Endothelial Growth Factor receptor 1, also named Flt1, as its main functional target in endothelial cells. Endothelial-specific knockout of Flt1 reproduces the anti-fibrotic effect of microRNA-200c against pulmonary fibrosis and results in the secretion of a pool of soluble factors and matrix components able to promote epithelial transdifferentiation in a paracrine manner. Collectively, these data indicate the existence of a complex endothelial-epithelial paracrine crosstalk in vitro and in vivo and position lung endothelial cells as a relevant therapeutic target in the fight against pulmonary fibrosis.
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MicroRNAs , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/metabolismo , Transdiferenciação Celular , Células Endoteliais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Pulmão/metabolismo , Células Epiteliais Alveolares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
OBJECTIVE: The septum pellucidum is a virtual cavity located at the anterior part of the brain midline, which only in fetal life has a certain amount of fluid inside. The presence of an obliterated cavum septi pellucidi (oCSP) in the prenatal period is poorly described in the literature but, nevertheless, it constitutes an important clinical dilemma for the fetal medicine specialist in terms of significance and prognosis. Moreover, its occurrence is increasing maybe because of the widespread of high-resolution ultrasound machine. The aim of this work is to review the available literature regarding the oCSP along with the description of a case-report of oCSP with an unexpected outcome. METHODS: A search of the literature through Pubmed was performed up to December 2022 with the aim to identify all cases of oCSP previously described, using as keywords "cavum septi pellucidi," "abnormal cavum septi pellucidi," "fetus," and "septum pellucidum." Along with the narrative review, we describe a case-report of oCSP. RESULTS: A 39 years old woman was diagnosed with a nuchal translucency between the 95° and 99° centile in the first trimester and an oCSP and "hookshaped" gallbladder at 20 weeks. Left polymicrogyria was found at fetal magnetic resonance imaging (MRI). Standard karyotype and chromosomal microarray analysis (CMA) were normal. After birth, the newborn presented signs of severe acidosis, untreatable seizures and multiorgan failure leading to death. A targeted gene analysis of the epilepsy panel revealed the presence of a de novo pathogenic variant involving the PTEN gene. The literature review identified four articles reporting on the oCSP of which three were case report and one was a case-series. The reported rate of associated cerebral findings is around 20% and the rate of adverse neurological outcome is around 6%, which is higher than the background risk of the general population. CONCLUSIONS: This case-report and review of the literature shows that oCSP is a clinical entity poorly described so far and that, despite the generally good prognosis, it requires caution in counseling. The diagnostic work-up should include neurosonography while fetal MRI may be always indicated for non-isolated cases only, depending on local facilities. Targeted gene analysis or whole exome sequencing may be indicated for non-isolated cases.
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Epilepsia , Septo Pelúcido , Gravidez , Recém-Nascido , Feminino , Humanos , Adulto , Septo Pelúcido/diagnóstico por imagem , Encéfalo , Feto , Cuidado Pré-Natal , Imageamento por Ressonância MagnéticaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively. CHK1 loss leads to deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, DNA damage, pro-inflammatory pathways activation and cellular senescence. Supplementation of deoxynucleosides reduces that. Furthermore, SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing DNA repair. Key observations are recapitulated in SARS-CoV-2-infected mice and patients with COVID-19. We propose that SARS-CoV-2, by boosting ribonucleoside triphosphate levels to promote its replication at the expense of dNTPs and by hijacking damage-induced long non-coding RNAs' biology, threatens genome integrity and causes altered DNA damage response activation, induction of inflammation and cellular senescence.
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COVID-19 , Animais , Camundongos , SARS-CoV-2 , Senescência Celular , Dano ao DNARESUMO
Background: Cardiac involvement in amyloid light-chain (AL) amyloidosis usually represents a brick in the wall of a multi-system disease. The presence of cardiac deposition of free light chains (FLCs) is the main determinant of survival. Isolated cardiac AL is an uncommon scenario characterized by a challenging diagnostic and therapeutic workup. Case summary: A 57-year-old asymptomatic man was presented for an incidental finding of myocardial necrosis at the electrocardiogram (ECG) performed for newly diagnosed arterial hypertension. Alongside signs of previous myocardial infarction, transthoracic echocardiography showed a severely increased left ventricular (LV) wall thickness not consistent with ECG voltages, segmental akinaesia with normal LV systolic function with 'apical sparing' pattern. Laboratory assessment showed an unexpectedly high level of natriuretic peptide and persistently abnormal troponin in the absence of symptoms or signs of heart failure or ongoing ischaemia. Coronary angiogram confirmed the coronary artery disease. Before revascularization, a complete diagnostic workup was carried. Serum electrophoresis detected a monoclonal gammopathy that was further investigated by serum immunofixation, revealing high lambda FLCs concentration. Fat pad, bone marrow, and salivary glands biopsies resulted negative for amyloid deposition. Finally, endomyocardial biopsy was consistent with AL amyloidosis. Urgent percutaneous revascularization was performed, and the patients was timely started on chemotherapy. Discussion: The diagnosis of isolated cardiac AL amyloidosis is challenging and carries important therapeutic implications. As the short-term prognosis might be severely compromised, an accurate diagnostic flowchart has to be systematically pursued to obtain a precise diagnosis and address the optimal, tailored management.
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OBJECTIVES: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). MATERIALS AND METHODS: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3). RESULTS: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P = 0.015) and small-cell (P = 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively. CONCLUSIONS: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Prognóstico , Cistectomia , Estudos RetrospectivosRESUMO
SARS-CoV-2 infection is clinically heterogeneous, ranging from asymptomatic to deadly. A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11-300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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COVID-19 , Humanos , SARS-CoV-2 , RNA Viral/genética , Células Endoteliais , Síndrome de COVID-19 Pós-AgudaRESUMO
Cardiac hamartoma is a rare benign tumor of the heart, and the vascular type is an extremely rare histologic diagnosis. A small number of cases have previously been described in childhood. We report the case of a 63-year-old woman with an incidentally detected cardiac mass that was finally diagnosed as vascular hamartoma. Approval for publication was obtained from the patient.
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Hamartoma , Procedimentos de Cirurgia Plástica , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Coração , Tomografia Computadorizada por Raios X , Hamartoma/diagnóstico , TóraxRESUMO
Endomyocardial biopsy (EMB) is an invasive procedure originally developed for the monitoring of heart transplant rejection. Over the year, this procedure has gained a fundamental complementary role in the diagnostic work-up of several cardiac disorders, including cardiomyopathies, myocarditis, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Major advances in EMB equipment and techniques for histological analysis have significantly improved diagnostic accuracy of EMB. In recent years, advanced imaging modalities such as echocardiography with three-dimensional and myocardial strain analysis, cardiac magnetic resonance and bone scintigraphy have transformed the non-invasive approach to diagnosis and prognostic stratification of several cardiac diseases. Therefore, it emerges the need to re-define the current role of EMB for diagnostic work-up and management of cardiovascular diseases. The aim of this review is to summarize current knowledge on EMB in light of the most recent evidences and to discuss current indications, including challenging scenarios encountered in clinical practice.
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Cardiomiopatias , Cardiopatias , Miocardite , Humanos , Coração , Miocárdio/patologia , Cardiomiopatias/diagnóstico , Miocardite/patologia , Cardiopatias/patologia , Biópsia/métodosRESUMO
OBJECTIVE: To better characterize the histopathology of oral lichen planus and oral lichenoid lesions and to highlight the differences between them in order to support the clinician in the diagnostic and therapeutic management of such conditions. SUBJECTS AND METHODS: Fifty-five patients, clinically diagnosed with oral lichen planus (n = 25) or oral lichenoid lesions (n = 30), were consecutively enrolled in the present study. Subsequently, one blind pathologist reviewed all the biopsy specimens of enrolled subjects following a specific protocol to provide a detailed histopathological description. Demographic, anamnestic, and clinical data were also recorded from all the participants. Patients' data were analysed and compared using the chi-squared test, to provide distinguishing features between the studied conditions. RESULTS: We found a higher and statistically significant number of eosinophils in the oral lichenoid lesions compared with the oral lichen planus group (p < 0.01), an equally promising result was seen regarding plasma cells, which were more represented (p = 0.05) in the oral lichenoid lesions than in the oral lichen planus cases. No statistically significant differences were detected in demographic, anamnestic and clinical data. CONCLUSION: A mixed lichenoid inflammatory infiltrate, consisting of eosinophils and plasma cells, could be used as reliable histological features for the diagnosis of oral lichenoid lesions, as long as compared with findings obtained from the patients' history and clinical examination.
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Líquen Plano Bucal , Erupções Liquenoides , Humanos , Líquen Plano Bucal/patologia , Estudos TransversaisRESUMO
The sequencing of cell-free fetal DNA in the maternal plasma through non-invasive prenatal testing (NIPT) is an accurate genetic screening test to detect the most common fetal aneuploidies during pregnancy. The extensive use of NIPT, as a screening method, has highlighted the limits of the technique, including false positive and negative results. Feto-placental mosaicism is a challenging biological issue and is the most frequent cause of false positive and negative results in NIPT screening, and of discrepancy between NIPT and invasive test results. We are reporting on two cases of feto-placental mosaicism of trisomy 21, both with a low-risk NIPT result, identified by ultrasound signs and a subsequent amniocentesis consistent with a trisomy 21. In both cases, after the pregnancy termination, cytogenetic and/or cytogenomic analyses were performed on the placenta and fetal tissues, showing in the first case a mosaicism of trisomy 21 in both the placenta and the fetus, but a mosaicism in the placenta and a complete trisomy 21 in the fetus in the second case. These cases emphasize the need for accurate and complete pre-test NIPT counselling, as well as to identify situations at risk for a possible false negative NIPT result, which may underestimate a potential pathological condition, such as feto-placental mosaicism or fetal trisomy. Post-mortem molecular autopsy may discriminate between placental, fetal and feto-placental mosaicism, and between complete or mosaic fetal chromosomal anomalies. A multidisciplinary approach in counselling, as well as in the interpretation of biological events, is essential for the clarification of complex cases, such as feto-placental mosaicisms.
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Objective: Natural history of cardiac amyloidosis (CA) is poorly understood. We aimed to examine the changing mortality of different types of CA over a 30-year period. Patients and methods: Consecutive patients included in the "Trieste CA Registry" from January 1, 1990 through December 31, 2021 were divided into a historical cohort (diagnosed before 2016) and a contemporary cohort (diagnosed after 2016). Light chain (AL), transthyretin (ATTR) and other forms of CA were defined according to international recommendations. The primary and secondary outcome measures were all-cause mortality and cardiac death, respectively. Results: We enrolled 182 patients: 47.3% AL-CA, 44.5% ATTR-CA, 8.2% other etiologies. The number of patients diagnosed with AL and ATTR-CA progressively increased over time, mostly ATTR-CA patients (from 21% before 2016 to 67% after 2016) diagnosed non-invasively. The more consistent increase in event-rate was observed in the long-term (after 50 months) in ATTR-CA compared to the early increase in mortality in AL-CA. In the contemporary cohort, during a median follow up of 16 [4-30] months, ATTR-CA was associated with improved overall and cardiac survival compared to AL-CA. At multivariable analysis, ATTR-CA (HR 0.42, p = 0.03), eGFR (HR 0.98, p = 0.033) and ACE-inhibitor therapy (HR 0.24, p < 0.001) predicted overall survival in the contemporary cohort. Conclusion: Incidence and prevalence rates of ATTR-CA and, to a less extent, of AL-CA have been increasing over time, with significant improvements in 2-year survival of ATTR-CA patients from the contemporary cohort. Reaching an early diagnosis and starting disease-modifying treatments will improve long-term survival in CA.
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BACKGROUND: Lightning strike is a rare but dramatic cause of injury. Patients admitted to intensive care units (ICUs) with lightning strike frequently have a high mortality and significant long-term morbidity related to a direct brain injury or induced cardiac arrest (CA). CASE PRESENTATION: A 50-year-old Caucasian man was admitted to our hospital after being struck by lightning resulting in immediate CA. Spontaneous circulation was initially restored, and the man was admitted to the ICU, but ultimately died while in hospital due to neurological injury. The computer tomography scan revealed a massive loss of grey-white matter differentiation at the fronto-temporal lobes bilaterally. Somatosensory-evoked potentials demonstrated bilateral absence of the cortical somatosensory N20-potential, and the electroencephalogram recorded minimal cerebral electrical activity. The patient died on day 10 and a post-mortem study revealed a widespread loss of neurons. CONCLUSION: This case study illustrates severe brain injury caused by a direct lighting strike, with the patient presenting an extraordinary microscopic pattern of neuronal desertification.
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Lesões Encefálicas , Lesões Provocadas por Raio , Raio , Humanos , Pessoa de Meia-Idade , Lesões Provocadas por Raio/complicações , Conservação dos Recursos Naturais , NeurôniosRESUMO
With the regional law n. 26 of December 30, 2020, the Friuli Venezia Giulia Region wanted to promote the establishment of the Regional Register of Sudden Cardiac Death, with the aim of favoring the study of all those deaths that occurred suddenly and unexpectedly under the age of 50 years in which it is not possible to trace the cause of death with certainty. Such dramatic events, difficult to quantify considering the complexity of data collection, are often accepted with resignation without any further investigation of the possible causes. The Regional Register of Sudden Cardiac Deaths of Friuli Venezia Giulia was born from this premise and from the awareness of the importance of going back with a rigorous scientific methodology and through a multidisciplinary approach, to the diagnosis of hereditary heart diseases which, when determined, allow the enrollment of relatives in a cardiological screening process and, therefore, primary prevention of potentially fatal events. The authors describe the operating procedures feeding the Regional Register and present the results of the first year of activity on 26 cases.
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Morte Súbita Cardíaca , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Itália/epidemiologiaRESUMO
INTRODUCTION: Cardiac tumors are rare and heterogeneous entities which still remain a diagnostic and therapeutic challenge. The treatment for most cardiac tumors is prompt surgical resection. We sought to provide an overview of surgical results from a series of consecutive patients treated at our tertiary care center during almost a 20-year experience. METHODS AND RESULTS: In this single center study, 55 consecutive patients with diagnosis of cardiac tumor underwent surgical treatment from January 2002 to April 2021. Of these, 23 (42%) were male and the mean age was 62â±â12âyears. Fifteen (27%) patients were symptomatic at the time of the diagnosis, mostly for dyspnea and palpitations. The most frequent benign cardiac tumor was myxoma (32; 58%), occurring mainly in the left atrium (31; 97%). Pleomorphic sarcoma was the most frequent primary malignant cardiac tumor (4; 7%), mainly located in the ventricles (1; 25% in the left ventricle; 2; 50% in the right ventricle). In all cases of benign tumors surgery was successful with no relapses. Two (50%) pleomorphic sarcomas showed subsequent relapses. After a median follow-up of 44âmonths, 15 (27%) patients died. Although malignant tumors presented a limited survival, benign tumors showed a very good prognosis. CONCLUSION: Cardiac tumors require a multidisciplinary approach to guarantee a prompt diagnosis and appropriate treatment. In our surgical experience, outcome after surgery of benign tumors was excellent, while malignant tumors had poor prognosis despite radical surgery.
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Neoplasias Cardíacas , Mixoma , Sarcoma , Idoso , Feminino , Átrios do Coração/patologia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/patologia , Mixoma/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/cirurgiaRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15-20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME). METHODS: Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients. CONCLUSIONS: Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the "cold" OPSCC counterparts.