RESUMO
OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.
Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/virologia , Neoplasias Gástricas/patologia , Masculino , Feminino , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Pessoa de Meia-Idade , Herpesvirus Humano 4/genética , Prognóstico , Estudos Retrospectivos , Idoso , Adulto , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antígeno Ki-67/metabolismo , RNA Viral/genética , GastrectomiaRESUMO
Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.
We retrospectively analyzed CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA by mNGS and compared 10-week survival rates among those with and without EBV DNA. Positive CSF-EBV DNA is associated with the increased mortality in HIV-negative CM patients.
Assuntos
DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Meningite Criptocócica , Humanos , Meningite Criptocócica/mortalidade , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/microbiologia , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , DNA Viral/líquido cefalorraquidiano , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/líquido cefalorraquidiano , Idoso , Líquido Cefalorraquidiano/microbiologia , Líquido Cefalorraquidiano/virologia , Cryptococcus neoformans/genética , Cryptococcus neoformans/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Adulto Jovem , China/epidemiologia , Análise de SobrevidaRESUMO
PURPOSE: This study aimed to investigate the latent Epstein-Barr virus (EBV) infection status of patients with newly diagnosed Hodgkin lymphoma (HL) and to discuss the relationship between tumor cell EBV status and the prognosis of HL patients. PATIENTS AND METHODS: A total of 134 previously untreated HL patients were analyzed in the study. Epstein-Barr virus encoded RNAs (EBERs) in situ hybridization was performed to detect the EBV status of tumor cells. RESULTS: EBV positive status correlated with sex (p=0.046) and the proportion of extranodal lesions(p=0.037). There was no obvious correlation between EBV status and overall survival (OS) or failure-free survival (FFS) in all cases, but in cases over 50 years old, EBV positive group had an inferior 5-year FFS compared with EBV negative group (38.5%±13.5% vs 90.9%±8.7%, p=0.012). In FFS multivariate analysis of this age subgroup, EBV positive status was associated with significantly inferior survival (HR, 10.10; 95% CI, 1.26-81.08; p=0.030). CONCLUSION: This study demonstrates positive tumor cell EBV status is an unfavorable prognostic factor in elder HL patients.
Assuntos
Infecções por Vírus Epstein-Barr/mortalidade , Herpesvirus Humano 4/fisiologia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Latência Viral , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/terapia , Feminino , Doença de Hodgkin/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: To analyze the clinical characteristics, prognosis factors and risk factors of chronic active Epstein-Barr virus infection in children. STUDY DESIGN: Observational analysis of baseline data and follow-up evaluation data of children with chronic active Epstein-Barr virus infection in our center between January 1, 2016 and December 31, 2019; they were followed through June 30, 2020. RESULTS: There were 96 children with chronic active Epstein-Barr virus infection (50 male and 46 female children), with the median age of 6.7 years (range from 0.6 to 17.6 years) at diagnosis. The median follow-up time was 16.5 months. The 3 most common clinical manifestations were fever, lymph node enlargement, and hepatomegaly or splenomegaly. Thirty-three patients (36.3%) also had a diagnosis of hemophagocytic lymphohistiocytosis (HLH). Epstein-Barr virus infected only T lymphocytes, natural killer cells, or both T- and natural killer-cell types in 15 (33.3%), 17 (37.8%), and 13 (28.9%), respectively. At the end of follow-up, 26 children had died, 60 survived, and 10 were lost to follow-up. Generally, progression-free survival was 69.8% ± 2.4%. The level of interleukin (IL)-6 and IL-10 and the combination of younger age and lower pathologic grade at diagnosis were independent prognostic factors by Cox regression analysis (P = .009 and .018, respectively). CONCLUSIONS: Children with lower levels of IL-6 and IL-10, or with younger age and lower pathologic grades, generally had favorable outcomes at the terminal point of follow-up, indicating better prognostic signs.
Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Adolescente , Contagem de Células Sanguíneas , Criança , Pré-Escolar , Doença Crônica , Citocinas/sangue , Infecções por Vírus Epstein-Barr/sangue , Feminino , Humanos , Lactente , Masculino , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: To investigate the value of post-induction chemotherapy (IC) cell-free Epstein-Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNApreIC) and at IC completion. CfEBV DNApostIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNApostIC and critical risk factors. RESULTS: We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNApostIC undetectable and detectable respectively. CfEBV DNApostIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNApostIC negative (P < 0.001 for all). Additionally, cfEBV DNApostIC was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40-2.59), DMFS (1.99, 1.45-2.71) and DFS (2.38, 1.86-3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNApostIC or N2-3 and pre-treatment cfEBV DNA [cfEBV DNApreIC] <7000), median-risk (N0-1 and detectable cfEBV DNApostIC or N2-3 and cfEBV DNApreIC ≥7000 with undetectable cfEBV DNApostIC) and high-risk (N2-3 and cfEBV DNApreIC ≥7000 with detectable cfEBV DNApostIC), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004). CONCLUSIONS: CfEBV DNApostIC represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNApostIC, cfEBV DNApreIC and N-stage classification in LA-NPC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Nucleicos Livres/sangue , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Bases de Dados Factuais , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/mortalidade , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/secundário , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Carga ViralRESUMO
Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorder (PTLD) is a serious complication following lung transplant. The extent to which the presence of EBV in PTLD tissue is associated with survival is uncertain. Moreover, whether the heterogeneity in expression of EBV latency programs is related to the timing of PTLD onset remains unexplored. We retrospectively performed a comprehensive histological evaluation of EBV markers at the tissue level in 34 adult lung transplant recipients with early- and late-onset PTLD. Early-onset PTLD, occurring within the first 12 months posttransplant, had higher odds to express EBV markers. The presence of EBV in PTLD was not associated with a difference in survival relative to EBV-negative tumors. However, we found evidence of heterogeneous expression of EBV latency programs, including type III, IIb, IIa, and 0/I. Our study suggests that the heterogeneous expression of EBV latency programs may represent a mechanism for immune evasion in patients with PLTD after lung transplants. The recognition of multiple EBV latency programs can be used in personalized medicine in patients who are nonresponsive to traditional types of chemotherapy and can be potentially evaluated in other types of solid organ transplants.
Assuntos
Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Pulmão/virologia , Transtornos Linfoproliferativos/virologia , Transplante de Órgãos/efeitos adversos , Adulto , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Expressão Gênica , Humanos , Pulmão/metabolismo , Pulmão/cirurgia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/mortalidade , Estudos Retrospectivos , Transplantados , Proteínas Virais/genética , Proteínas Virais/metabolismo , Latência Viral/genéticaRESUMO
Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV-SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post-organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow-up period, a 1-year survival rate of 76.0% and 5-year survival rate of 59.6% may support the indolent and non-deadly nature of EBV-SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV-SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion.
Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Tumor de Músculo Liso/cirurgia , Adulto , Neoplasias do Sistema Nervoso Central/cirurgia , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Infecções por HIV/complicações , Humanos , Hospedeiro Imunocomprometido , Masculino , Invasividade Neoplásica , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias , Tumor de Músculo Liso/mortalidade , Tumor de Músculo Liso/patologia , Tumor de Músculo Liso/virologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with a high mortality rate. Our study aimed to summarize the clinicopathological characteristics of CAEBV infection in adults and improve knowledge of the disease. Data for 19 adult patients with CAEBV confirmed at our hospital from January 2010 to December 2019 were collected retrospectively. There were 14 males and 5 females, and the median age was 33 years (range 14-83). The main clinical manifestations included recurrent fever (84.2%, 16/19), splenomegaly (89.5%, 17/19), hepatomegaly (73.6%, 14/19), lymphadenopathy (42.1%, 8/19), abnormal liver function (78.9%, 15/19), hemopenia (94.7%, 18/19), and hemophagocytosis (52.6%, 10/19). A total of 22 specimens were collected from 19 patients for histopathology. Most of the biopsy specimens showed lymphocyte infiltration. Immunohistochemical staining and EBV-encoded small RNA (EBER) in situ hybridization were performed for 14 of the 22 samples. CD3 and CD20 staining were positive, with more CD3-positive cells than CD20-positive cells (100%, 14/14), and EBER in situ hybridization was positive in most cases (85.7%, 12/14). More than half of TCR gene rearrangement tests showed monoclonal rearrangement (66.6%, 4/6). Mortality was high, with most CAEBV patients dying during the period from diagnosis to the end of follow-up (12/19, 63%); the median survival time was only 20.75 months. Based on limited data, we consider that CAEBV is a disease with different ages of onset and is a complex and heterogeneous syndrome with features of both immunodeficiency and malignant neoplasms. Furthermore, the prognosis of adult-onset CAEBV appears to be very poor.
Assuntos
Antígenos CD20/metabolismo , Complexo CD3/metabolismo , DNA Viral/genética , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , China , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Rearranjo Gênico , Humanos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Receptores de Antígenos de Linfócitos T/genética , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function. AIM: This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival. CONCLUSION: PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases.
Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno CTLA-4/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/fisiologia , Inibidores de Checkpoint Imunológico/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/mortalidade , Antígenos Nucleares do Vírus Epstein-Barr/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.
Assuntos
Infecções por Vírus Epstein-Barr , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Receptores de Somatostatina , Proteínas da Matriz Viral , Animais , Feminino , Humanos , Masculino , Camundongos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Metástase Linfática , Camundongos Nus , Terapia de Alvo Molecular , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/virologia , NF-kappa B/genética , NF-kappa B/metabolismo , Octreotida/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Somatostatina/antagonistas & inibidores , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transdução de Sinais , Análise de Sobrevida , Proteínas da Matriz Viral/antagonistas & inibidores , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Primary pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare non-small cell lung cancer (NSCLC) subtype. Clinical features have been described in our previous report, but molecular characteristics remain unclear. Herein, pLELC genomic features were explored. Among 41,574 lung cancers, 128 pLELCs and 162 non-pLELC NSCLCs were enrolled. Programmed cell death ligand 1 (PD-L1) and protein 53 (p53) expression was detected in 47 surgically resected pLELC samples by immunohistochemical assays. Multiomics genomic analyses, including whole-genome sequencing (WGS), RNA whole-transcriptome sequencing (RNA-seq), and Epstein-Barr virus (EBV) integration analyses, were performed on eight frozen pLELC tissues and compared with 50 lung adenocarcinomas (LUADs) and 50 lung squamous cell carcinomas (LUSCs) from The Cancer Genome Atlas (TCGA) and another 26 EBV-positive nasopharynx cancers (EBV+-NPCs). Progression-free survival (PFS) and overall survival (OS) of pLELC patients were better than those of non-pLELC patients. High PD-L1 or p53 expression was associated with extended disease-free survival (DFS). pLELC had 14 frequently mutated genes (FMGs). Somatically mutated genes and enrichment of genetic lesions were found, which differed from observations in LUAD, LUSC, and EBV+-nasopharyngeal carcinoma (NPC). Three tumor-associated genes, zinc finger and BTB domain-containing 16 (ZBTB16), peroxisome proliferator activated receptor gamma (PPARG), and transforming growth factor beta receptor 2 (TGFBR2), were downregulated with copy number variation (CNV) loss. EBV was prone to integrating into intergenic and intronic regions with two upregulated miR-BamH1-A rightward transcripts (BARTs), BART5-3P and BART20-3P. Our findings reveal that pLELC has a distinct genomic signature. Three tumor-associated genes with CNV loss and two miR-BARTs might be involved in pLELC tumorigenesis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Infecções por Vírus Epstein-Barr , Genômica , Herpesvirus Humano 4/genética , Neoplasias Pulmonares , Mutação , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Intervalo Livre de Progressão , RNA-SeqRESUMO
Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare peripheral T-cell lymphoma that predominantly occurs in Asian and South American populations. The treatment of ENKL has been a challenge for a long time. This study was conducted to compare the clinical efficacy and safety of cisplatin, dexamethasone, gemcitabine, and pegaspargase (DDGP) and methotrexate, dexamethasone, ifosfamide, L-asparaginase, and etoposide (SMILE) regimens for relapsed/refractory ENKL and explore the prognostic factors. From October 2014 to July 2019, 54 patients with relapsed/refractory ENKL who received DDGP or SMILE chemotherapy were retrospectively assessed in this study. Thirty-one patients received DDGP chemotherapy and 23 patients received SMILE chemotherapy. A higher complete response rate was observed in patients treated with DDGP regimen (61.3% vs. 30.4%, P = 0.025). The DDGP group (95% confidence interval (CI) of 5-year progression-free survival (PFS): 24.6-66.2%; 95% CI of 5-year overall survival (OS): 8.5-91.7%) was also significantly associated with longer 5-year PFS and 5-year OS (P = 0.008 for 5-year PFS, P = 0.023 for 5-year OS). More serious leucopenia (P = 0.021), neutropenia (P = 0.041), and allergy (P = 0.040) were observed in the SMILE group. Post-treatment Epstein-Barr virus (EBV)-DNA status (P = 0.001 for PFS, P = 0.018 for OS) was identified as a significant prognostic factor for PFS and OS in multivariate analysis. The present research suggested that compared with SMILE chemotherapy, DDGP chemotherapy can significantly improve the response and survival of relapsed/refractory ENKL with better tolerance. Post-treatment EBV-DNA status was identified as a significant prognostic factor for PFS and OS in relapsed/refractory ENKL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , DNA Viral/isolamento & purificação , Resistencia a Medicamentos Antineoplásicos , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) associated with B-cell lymphoma is a highly aggressive disease with unclear clinical features and has no standard treatment. PATIENTS AND METHODS: We analyzed the clinical characteristics of 31 patients from two individual centers. RESULTS: The median overall survival was only 1.5 months. Both univariate and multivariate analyses, based on lymphoma or HLH-related characteristics, revealed that patients with high Epstein-Barr virus (EBV) DNA load and ≥ 2 extranodal lesions, or hypofibrinogenemia, respectively, showed significantly poorer overall survival. Interestingly, some patients with high EBV DNA load had EBV-positive natural killer (NK) and/or T cells, which may be related to the coexistence of immunodeficiency and/or chronic active EBV infection. Molecular genetics examination confirmed that 47.4% (9/19) of patients had complex karyotypes, 37.5% (3/8) of patients had TP53 deletions, and 21.34% (3/14) of patients had TP53 mutation or alteration of malignancy-related pathways, including BCR/NF-κB, JAK-STAT, and epigenetic regulatory pathways, which may provide clues to choose targets for therapy. Treatment regimens containing etoposide, anti-CD20 monoclonal antibodies, or anthracyclines improved patient prognosis (P = .0183, .025, and .0436, respectively). Patients with infections had significantly shorter survival than those without infections (P = .00019). CONCLUSION: The patients' performance status, number of extranodal lesions, high EBV DNA load, and hypofibrinogenemia are poor prognostic factors for HLH associated with B-cell lymphoma. Molecular genetic high-risk factors are of particular importance because these factors can provide information for prognosis prediction, treatment decisions, and disease surveillance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfoma de Células B/complicações , Adulto , Idoso , Biomarcadores Tumorais/genética , Biópsia , Medula Óssea/patologia , DNA Viral/isolamento & purificação , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Cariotipagem , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Linfoma de Células B/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Carga ViralRESUMO
BACKGROUND: Graft survival in pediatric kidney transplant recipients has increased in the last decades. Determining prognostic factors for graft function over time allows the identification of patients at risk for graft loss and could lead to improvement of current guidelines. METHODS: Data were collected among pediatric kidney transplant recipients in a single center during the first 5 years after transplantation. Mixed model analysis was used to indicate possible prognostic factors for the loss of graft function. RESULTS: A total of 100 pediatric kidney transplant recipients were analyzed. Negative prognostics of graft function are higher donor age and higher recipient age, presence of obstructive uropathology, re-transplant, and occurrence of BK viremia. The negative influence on graft function of both donor age and presence of obstructive uropathology increased over time. In this study, the factors that did not influence graft function over time were the number of HLA mismatches, pre-transplant dialysis, intra-abdominal graft placement, ischemia time, occurrence of acute rejection, presence of lower urinary tract dysfunction, occurrence of urinary tract infections, and infections with cytomegalovirus and Epstein-Barr virus. CONCLUSIONS: This study showed that a higher donor age and higher recipient age, presence of obstructive uropathology, a re-transplant, and the occurrence of BK viremia were negative prognostic factors of graft function over time, in the first 5 years after transplant. Graft function was comparable between steroid-sparing regimens (preferable in low-risk patients) and regimens including steroids (for special reasons).
Assuntos
Rejeição de Enxerto/etiologia , Transplante de Rim/mortalidade , Complicações Pós-Operatórias/mortalidade , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Citomegalovirus , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Herpesvirus Humano 4 , Humanos , Rim/fisiopatologia , Masculino , Complicações Pós-Operatórias/etiologia , Prognóstico , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Viremia/etiologia , Viremia/mortalidadeRESUMO
Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of EBV-related tumors. This study aimed to explore the inner relationship and regulatory mechanism among oxidative stress, EBV reactivation, and radioresistance and to identify new molecular subtyping models and treatment strategies to improve the therapeutic effects of radiotherapy. Methods: ROS, NADP+/NADPH, and GSSG/GSH were detected to evaluate the oxidative stress of cells. 8-OHdG is a reliable oxidative stress marker to evaluate the oxidative stress in patients. Its concentration in serum was detected using an ELISA method and in biopsies was detected using IHC. qPCR array was performed to evaluate the expression of essential oxidative stress genes. qPCR, Western blot, and IHC were used to measure the level of EBV reactivation in vitro and in vivo. A Rta-IgG ELISA kit and EBV DNA detection kit were used to analyze the reactivation of EBV in serum from NPC patients. NPC tumor tissue microarrays was used to investigate the prognostic role of oxidative stress and EBV reactivation. Radiation resistance was evaluated by a colony formation assay. Xenografts were treated with NAC, radiation, or a combination of NAC and radiation. EBV DNA load of tumor tissue was evaluated using an EBV DNA detection kit. Oxidative stress, EBV reactivation, and the apoptosis rate in tumor tissues were detected by using 8-OHdG, EAD, and TUNEL assays, respectively. Results: We found that EBV can induce high oxidative stress, which promotes its reactivation and thus leads to radioresistance. Basically, EBV caused NPC cells to undergo a process of 'Redox Resetting' to acquire a new redox status with higher levels of ROS accumulation and stronger antioxidant systems by increasing the expression of the ROS-producing enzyme, NOX2, and the cellular master antioxidant regulator, Nrf2. Also, EBV encoded driving protein LMP1 promotes EBV reactivation through production of ROS. Furthermore, high oxidative stress and EBV reactivation were positively associated with poor overall survival of patients following radiation therapy and were significant related to NPC patients' recurrence and clinical stage. By decreasing oxidative stress using an FDA approved antioxidant drug, NAC, sensitivity of tumors to radiation was increased. Additionally, 8-OHdG and EBV DNA could be dual prognostic markers for NPC patients. Conclusions: Oxidative stress mediates EBV reactivation and leads to radioresistance. Targeting oxidative stress can provide therapeutic benefits to cancer patients with radiation resistance. Clinically, we, for the first time, generated a molecular subtyping model for NPC relying on 8-OHdG and EBV DNA level. These dual markers could identify patients who are at a high risk of poor outcomes but who might benefit from the sequential therapy of reactive oxygen blockade followed by radiation therapy, which provides novel perspectives for the precise treatment of NPC.
Assuntos
Quimiorradioterapia/métodos , Infecções por Vírus Epstein-Barr/terapia , Sequestradores de Radicais Livres/administração & dosagem , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Acetilcisteína/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia , Linhagem Celular Tumoral , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/patogenicidade , Humanos , Infecção Latente/sangue , Infecção Latente/patologia , Infecção Latente/terapia , Infecção Latente/virologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Nasofaringe/patologia , Nasofaringe/virologia , Estresse Oxidativo/efeitos dos fármacos , Seleção de Pacientes , Prognóstico , Intervalo Livre de Progressão , Tolerância a Radiação/efeitos dos fármacos , Espécies Reativas de Oxigênio , Carga Viral , Proteínas da Matriz Viral/metabolismo , Ativação Viral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto JovemRESUMO
Epstein-Barr virus is an etiologic agent of several malignancies. In this study, we explored the association of Epstein-Barr virus-encoded RNA1 and Epstein-Barr virus latent membrane protein 1 co-expression with osteosarcoma. Epstein-Barr virus-encoded RNA1 expression in tumor cells was quantified using reverse transcriptase polymerase chain reaction and in situ hybridization and Epstein-Barr virus latent membrane protein 1 expression was measured using immunohistochemistry staining. There was a statistically significant association between Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus-encoded RNA1 co-expression and characteristics of osteosarcoma such as nodal stage (p < 0.04), metastasis (p < 0.04), Ki67 index (p < 0.03), and tumor stage (p < 0.05). Co-expression of Epstein-Barr virus-encoded RNA1 and Epstein-Barr virus latent membrane protein 1 in tumors correlated with advanced osteosarcoma and indicated the aggressiveness of bone sarcoma.
Assuntos
Osteossarcoma/virologia , RNA Viral/metabolismo , Proteínas da Matriz Viral/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Criança , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/fisiologia , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Osteossarcoma/mortalidade , Osteossarcoma/patologia , RNA Viral/genética , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
Some patients diagnosed with methotrexate-associated lymphoproliferative disorder (MTX-LPD) develop spontaneous regression upon the discontinuation of MTX, whereas others require chemotherapy. The mechanisms underlying this differential response and the capacity to spontaneously regress are not clearly understood. We evaluated numerous clinicopathological features in 63 patients diagnosed with MTX-LPD, with a special focus on those with Epstein-Barr virus (EBV)-positive mucocutaneous lesions (EBVMCL). The diagnosis of EBVMCL included cases of both EBV-positive mucocutaneous ulcers (EBVMCU) and diffuse gingival swelling associated with proliferation of EBV-positive large B-cells. Of the four subgroups of MTX-LPD, one-year treatment-free survival (TFS) after the discontinuation of MTX was achieved among those with EBVMCL (100%), diffuse large B-cell lymphoma (57%), Hodgkin-like lesions (60%), or classical Hodgkin lymphoma (29%); a significant difference in TFS was observed when comparing the responses of patients with EBVMCL to the those diagnosed with other subtypes. Multivariate analysis revealed predictive factors for prolonged TFS that included EBV-positive lesions and comparatively low levels of serum LDH. Taken together, our study suggests that a diagnosis of EBVMCL is related to the overall clinical outcome after the discontinuation of MTX.
Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4/metabolismo , Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Metotrexato/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Feminino , Doença de Hodgkin/induzido quimicamente , Doença de Hodgkin/metabolismo , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Linfoma Difuso de Grandes Células B/induzido quimicamente , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Objective: Malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) in children is a relatively rare but life-threatening secondary hemophagocytic lymphohistiocytosis (sHLH). Until now, only a limited number of cases regarding children with M-HLH has been reported. Methods: We conducted a retrospective study of 27 children with M-HLH, who admitted to our center between July 2007 and October 2019. The clinical data and laboratory data were analyzed. Results: The median age of the children with M-HLH was 7 years. Underlying diseases included myeloid malignancy (n = 6), lymphoid malignancy (n = 18) and unknown type lymphoma (n = 3). The one-year mortality rate was 56%. All patients had persistent fever. The clinical manifestations included hepatomegaly (89%), splenomegaly (67%) and central nervous system symptoms (56%). Thirteen children (48%) had Epstein-Barr virus (EBV) infection. No significant differences were observed between EBV-positive and negative M-HLH patients in terms of most clinical indicators. However, EBV-positive M-HLH patients showed prolonged activated partial thromboplastin time (APTT) and more hemophagocytosis in the bone marrow (BM) in contrast to EBV-negative patients. Eighteen patients (67%) received the HLH-94/04 regimen as the initial treatment. There were no significant differences in the overall survival (OS) between EBV-positive and negative patients. Patients with prolonged APTT had a significantly poorer OS than other patients (p = 0.012). Conclusions: The M-HLH children with EBV infection are more likely to have prolonged APTT and more hemophagocytosis in BM. The M-HLH children had a poor prognosis, especially those with prolonged APTT.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Hospitais Pediátricos , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. PATIENTS AND MATERIALS: A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. RESULTS: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high-risk patients, while no survival difference was found between CCRT and IC+CCRT in low-risk patients. CONCLUSIONS: Our study can help clinicians select stage II-IVa NPC patients who benefit from IC, which is important in guiding individual treatment.
Assuntos
DNA Viral/genética , Infecções por Vírus Epstein-Barr/diagnóstico , Fluordesoxiglucose F18 , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomada de Decisão Clínica , Progressão da Doença , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de TempoRESUMO
Background There is scarce data about the long-term mortality as well as the prognostic value of cardiovascular magnetic resonance and late gadolinium enhancement (LGE) in patients with biopsy-proven viral myocarditis. We sought to investigate: (1) mortality and (2) prognostic value of LGEcardiovascular magnetic resonance (location, pattern, extent, and distribution) in a >10-year follow-up in patients with biopsy-proven myocarditis. Methods and Results Two-hundred three consecutive patients with biopsy-proven viral myocarditis and cardiovascular magnetic resonance were enrolled; 183 patients were eligible for standardized follow-up. The median follow-up was 10.1 years. End points were all-cause death, cardiac death, and sudden cardiac death (SCD). We found substantial long-term mortality in patients with biopsy-proven myocarditis (39.3% all cause, 27.3% cardiac, and 10.9% SCD); 101 patients (55.2%) demonstrated LGE. The presence of LGE was associated with a more than a doubled risk of death (hazard ratio [HR], 2.40; 95% CI], 1.30-4.43), escalating to a HR of 3.00 (95% CI, 1.41-6.42) for cardiac death, and a HR of 14.79 (95% CI, 1.95-112.00) for SCD; all P≤0.009. Specifically, midwall, (antero-) septal LGE, and extent of LGE were highly associated with death, all P<0.001. Septal LGE was the best independent predictor for SCD (HR, 4.59; 95% CI, 1.38-15.24; P=0.01). Conclusions In patients with biopsy-proven viral myocarditis, the presence of midwall LGE in the (antero-) septal segments is associated with a higher rate of mortality (including SCD) compared with absent LGE or other LGE patterns, underlining the prognostic benefit of a distinct LGE analysis in these patients.