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1.
Artigo em Inglês | MEDLINE | ID: mdl-39122471

RESUMO

BACKGROUND AND PURPOSE: Contrast-enhanced MRI (CEMRI) is a commonly used imaging modality for craniopharyngioma surveillance; however, it carries risks such as allergic reaction and gadolinium deposition. This study evaluates the efficacy of non-contrast enhanced MRI (NCMRI) with a balanced steady state free precession (bSSFP) sequence compared with CEMRI T1-weighted imaging for craniopharyngioma surveillance. MATERIALS AND METHODS: 29 craniopharyngioma patients (16 female/13 male, mean age=21.5± 4.3 years) with CEMRIs including a bSSFP sequence were evaluated. For each patient, 2 blinded neuroradiologists compared the dimensions of residual craniopharyngioma on noncontrast and contrast-enhanced sequences. Tumor volume and solid/cystic component measurements were evaluated using paired t-tests. Diagnostic confidence levels for NC-and CE evaluations were measured using a 3-point scale (2=confident,1=adequate,0=unsure). Analyses of tumor involvement of cranial nerves and adjacent vasculature and diagnostic confidence were performed using Fisher's exact and chi-square tests. RESULTS: No significant difference was observed between residual tumor volumes in both studies (18.86±21.67 cm3 vs 17.64±23.85 cm3, p=0.55) and measurements of dominant solid component volume, number of cystic components, and largest cystic component volume (2.71±3.47 cm3 vs 3.95±5.51 cm3, p=0.10; 2.5±1.5 vs 2.9±1.5, p=0.10; 7.61±13.41 vs 6.84±13.37 cm3, p=0.22, respectively). Tumoral involvement of cranial nerves II (p=0.64), III (p=0.42), and adjacent vasculature (p=0.05) showed no significant differences in detection. Diagnostic confidence was comparable evaluating cranial nerve II, vascular structures, and third ventricle (p>0.05) involvement. Higher levels of confidence were observed with bSSFP sequences for detection of cranial nerve III involvement (p=0.0001) and with ce-T1W for cavernous sinus involvement (p=0.02). CONCLUSIONS: NCMRI techniques using a bSSFP sequence provides similar characterization of craniopharyngiomas as contrast enhanced techniques. ABBREVIATIONS: 3D DRIVE, 3-dimensional driven equilibrium; ACA, anterior cerebral artery; bSSFP, balanced steady-state free precession; ce-T1W, contrast-enhanced T1-weighted imaging; CN, cranial nerve; GTR, gross total resection; STR, subtotal resection.

2.
Oncologist ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066586

RESUMO

BACKGROUND AND AIMS: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). OUTCOMES: After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy. CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

3.
Leukemia ; 38(4): 803-809, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38388646

RESUMO

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18-66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456-9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126-7.874) as poor prognostic factors for EFS. The most common grade 3-4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.


Assuntos
Citarabina , Histiocitose de Células de Langerhans , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/diagnóstico , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
J Neuroimaging ; 34(1): 5-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37872430

RESUMO

The hippocampus is a complex structure located in the mesial temporal lobe that plays a critical role in cognitive and memory-related processes. The hippocampal formation consists of the dentate gyrus, hippocampus proper, and subiculum, and its importance in the neural circuitry makes it a key anatomic structure to evaluate in neuroimaging studies. Advancements in imaging techniques now allow detailed assessment of hippocampus internal architecture and signal features that has improved identification and characterization of hippocampal abnormalities. This review aims to summarize the neuroimaging features of the hippocampus and its common pathologies. It provides an overview of the hippocampal anatomy on magnetic resonance imaging and discusses how various imaging techniques can be used to assess the hippocampus. The review explores neuroimaging findings related to hippocampal variants (incomplete hippocampal inversion, sulcal remnant and choroidal fissure cysts), and pathologies of neoplastic (astrocytoma and glioma, ganglioglioma, dysembryoplastic neuroepithelial tumor, multinodular and vacuolating neuronal tumor, and metastasis), epileptic (mesial temporal sclerosis and focal cortical dysplasia), neurodegenerative (Alzheimer's disease, progressive primary aphasia, and frontotemporal dementia), infectious (Herpes simplex virus and limbic encephalitis), vascular (ischemic stroke, arteriovenous malformation, and cerebral cavernous malformations), and toxic-metabolic (transient global amnesia and opioid-associated amnestic syndrome) etiologies.


Assuntos
Doença de Alzheimer , Epilepsia do Lobo Temporal , Epilepsia , Glioma , Humanos , Criança , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Epilepsia/patologia , Lobo Temporal/patologia , Imageamento por Ressonância Magnética , Doença de Alzheimer/patologia , Glioma/patologia
5.
Orphanet J Rare Dis ; 18(1): 372, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037140

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. RESULTS: We retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18-69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAFV600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7-211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%. CONCLUSIONS: In our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.


Assuntos
Histiocitose de Células de Langerhans , Fosfatidilinositol 3-Quinases , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Histiocitose de Células de Langerhans/genética , Progressão da Doença , Genômica
6.
J Transl Med ; 21(1): 721, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838657

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) development may be associated with tumor immune escape. This study explores whether the CHI3L1/MAF/CTLA4/S100A4 axis affects immune escape in TNBC through interplay with triple-negative breast cancer stem cells (TN-BCSCs). OBJECTIVE: The aim of this study is to utilize single-cell transcriptome sequencing (scRNA-seq) to uncover the molecular mechanisms by which the CHI3L1/MAF/CTLA4 signaling pathway may mediate immune evasion in triple-negative breast cancer through the interaction between tumor stem cells (CSCs) and immune cells. METHODS: Cell subsets in TNBC tissues were obtained through scRNA-seq, followed by screening differentially expressed genes in TN-BCSCs and B.C.s (CD44+ and CD24-) and predicting the transcription factor regulated by CHI3L1. Effect of CHI3L1 on the stemness phenotype of TNBC cells investigated. Effects of BCSCs-231-derived CHI3L1 on CTLA4 expression in T cells were explored after co-culture of BCSCs-231 cells obtained from microsphere culture of TN-BCSCs with T cells. BCSCs-231-treated T cells were co-cultured with CD8+ T cells to explore the resultant effect on T cell cytotoxicity. An orthotopic B.C. transplanted tumor model in mice with humanized immune systems was constructed, in which the Role of CHI3L1/MAF/CTLA4 in the immune escape of TNBC was explored. RESULTS: Eight cell subsets were found in the TNBC tissues, and the existence of TN-BCSCs was observed in the epithelial cell subset. CHI3L1 was related to the stemness phenotype of TNBC cells. TN-BCSC-derived CHI3L1 increased CTLA4 expression in T cells through MAF, inhibiting CD8+ T cell cytotoxicity and inducing immunosuppression. Furthermore, the CTLA4+ T cells might secrete S100A4 to promote the stemness phenotype of TNBC cells. CONCLUSIONS: TN-BCSC-derived CHI3L1 upregulates CTLA4 expression in T cells through MAF, suppressing the function of CD8+ T cells, which promotes the immune escape of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/genética , Antígeno CTLA-4/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Transdução de Sinais , Células-Tronco Neoplásicas/patologia , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3/metabolismo
8.
Cancer Med ; 12(8): 9902-9911, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36775966

RESUMO

BACKGROUND: This study examines the impact that the COVID-19 pandemic has had on computed tomography (CT)-based oncologic imaging utilization. METHODS: We retrospectively analyzed cancer-related CT scans during four time periods: pre-COVID (1/5/20-3/14/20), COVID peak (3/15/20-5/2/20), post-COVID peak (5/3/20-12/19/20), and vaccination period (12/20/20-10/30/21). We analyzed CTs by imaging indication, setting, and hospital type. Using percentage decrease computation and Student's t-test, we calculated the change in mean number of weekly cancer-related CTs for all periods compared to the baseline pre-COVID period. This study was performed at a single academic medical center and three affiliated hospitals. RESULTS: During the COVID peak, mean CTs decreased (-43.0%, p < 0.001), with CTs for (1) cancer screening, (2) initial workup, (3) cancer follow-up, and (4) scheduled surveillance of previously treated cancer dropping by 81.8%, 56.3%, 31.7%, and 45.8%, respectively (p < 0.001). During the post-COVID peak period, cancer screenings and initial workup CTs did not return to prepandemic imaging volumes (-11.4%, p = 0.028; -20.9%, p = 0.024). The ED saw increases in weekly CTs compared to prepandemic levels (+31.9%, p = 0.008), driven by increases in cancer follow-up CTs (+56.3%, p < 0.001). In the vaccination period, cancer screening CTs did not recover to baseline (-13.5%, p = 0.002) and initial cancer workup CTs doubled (+100.0%, p < 0.001). The ED experienced increased cancer-related CTs (+75.9%, p < 0.001), driven by cancer follow-up CTs (+143.2%, p < 0.001) and initial workups (+46.9%, p = 0.007). CONCLUSIONS AND RELEVANCE: The pandemic continues to impact cancer care. We observed significant declines in cancer screening CTs through the end of 2021. Concurrently, we observed a 2× increase in initial cancer workup CTs and a 2.4× increase in cancer follow-up CTs in the ED during the vaccination period, suggesting a boom of new cancers and more cancer examinations associated with emergency level acute care.


Assuntos
COVID-19 , Neoplasias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias/diagnóstico por imagem , Neoplasias/epidemiologia , Vacinação , Serviço Hospitalar de Emergência
9.
Cancer Med ; 10(18): 6327-6335, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34355873

RESUMO

BACKGROUND: We aimed to investigate the effects of COVID-19 on computed tomography (CT) imaging of cancer. METHODS: Cancer-related CTs performed at one academic hospital and three affiliated community hospitals in Massachusetts were retrospectively analyzed. Three periods of 2020 were considered as follows: pre-COVID-19 (1/5/20-3/14/20), COVID-19 peak (3/15/20-5/2/20), and post-COVID-19 peak (5/3/20-11/14/20). 15 March 2020 was the day a state of emergency was declared in MA; 3 May 2020 was the day our hospitals resumed to non-urgent imaging. The volumes were assessed by (1) Imaging indication: cancer screening, initial workup, active cancer, and surveillance; (2) Care setting: outpatient and inpatient, ED; (3) Hospital type: quaternary academic center (QAC), university-affiliated community hospital (UACH), and sole community hospitals (SCHs). RESULTS: During the COVID-19 peak, a significant drop in CT volumes was observed (-42.2%, p < 0.0001), with cancer screening, initial workup, active cancer, and cancer surveillance declining by 81.7%, 54.8%, 30.7%, and 44.7%, respectively (p < 0.0001). In the post-COVID-19 peak period, cancer screening and initial workup CTs did not recover (-11.7%, p = 0.037; -20.0%, p = 0.031), especially in the outpatient setting. CT volumes for active cancer recovered, but inconsistently across hospital types: the QAC experienced a 9.4% decline (p = 0.022) and the UACH a 41.5% increase (p < 0.001). Outpatient CTs recovered after the COVID-19 peak, but with a shift in utilization away from the QAC (-8.7%, p = 0.020) toward the UACH (+13.3%, p = 0.013). Inpatient and ED-based oncologic CTs increased post-peak (+20.0%, p = 0.004 and +33.2%, p = 0.009, respectively). CONCLUSIONS: Cancer imaging was severely impacted during the COVID-19 pandemic. CTs for cancer screening and initial workup did not recover to pre-COVID-19 levels well into 2020, a finding that suggests more patients with advanced cancers may present in the future. A redistribution of imaging utilization away from the QAC and outpatient settings, toward the community hospitals and inpatient setting/ED was observed.


Assuntos
COVID-19/epidemiologia , Neoplasias/diagnóstico por imagem , Pandemias/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais , Humanos , Pacientes Internados/estatística & dados numéricos , Massachusetts/epidemiologia , Pacientes Ambulatoriais/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Tomografia Computadorizada por Raios X/métodos
10.
AJR Am J Roentgenol ; 217(5): 1093-1102, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33852360

RESUMO

BACKGROUND. Previous studies compared CT findings of COVID-19 pneumonia with those of other infections; however, to our knowledge, no studies to date have included noninfectious organizing pneumonia (OP) for comparison. OBJECTIVE. The objectives of this study were to compare chest CT features of COVID-19, influenza, and OP using a multireader design and to assess the performance of radiologists in distinguishing between these conditions. METHODS. This retrospective study included 150 chest CT examinations in 150 patients (mean [± SD] age, 58 ± 16 years) with a diagnosis of COVID-19, influenza, or non-infectious OP (50 randomly selected abnormal CT examinations per diagnosis). Six thoracic radiologists independently assessed CT examinations for 14 individual CT findings and for Radiological Society of North America (RSNA) COVID-19 category and recorded a favored diagnosis. The CT characteristics of the three diagnoses were compared using random-effects models; the diagnostic performance of the readers was assessed. RESULTS. COVID-19 pneumonia was significantly different (p < .05) from influenza pneumonia for seven of 14 chest CT findings, although it was different (p < .05) from OP for four of 14 findings (central or diffuse distribution was seen in 10% and 7% of COVID-19 cases, respectively, vs 20% and 21% of OP cases, respectively; unilateral distribution was seen in 1% of COVID-19 cases vs 7% of OP cases; non-tree-in-bud nodules was seen in 32% of COVID-19 cases vs 53% of OP cases; tree-in-bud nodules were seen in 6% of COVID-19 cases vs 14% of OP cases). A total of 70% of cases of COVID-19, 33% of influenza cases, and 47% of OP cases had typical findings according to RSNA COVID-19 category assessment (p < .001). The mean percentage of correct favored diagnoses compared with actual diagnoses was 44% for COVID-19, 29% for influenza, and 39% for OP. The mean diagnostic accuracy of favored diagnoses was 70% for COVID-19 pneumonia and 68% for both influenza and OP. CONCLUSION. CT findings of COVID-19 substantially overlap with those of influenza and, to a greater extent, those of OP. The diagnostic accuracy of the radiologists was low in a study sample that contained equal proportions of these three types of pneumonia. CLINICAL IMPACT. Recognized challenges in diagnosing COVID-19 by CT are furthered by the strong overlap observed between the appearances of COVID-19 and OP on CT. This challenge may be particularly evident in clinical settings in which there are substantial proportions of patients with potential causes of OP such as ongoing cancer therapy or autoimmune conditions.


Assuntos
COVID-19/diagnóstico por imagem , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Influenza Humana/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/virologia , Masculino , Massachusetts , Pessoa de Meia-Idade , Variações Dependentes do Observador , Pneumonia Viral/virologia , Radiografia Torácica , Estudos Retrospectivos , SARS-CoV-2
12.
Acad Radiol ; 27(10): 1353-1362, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32830030

RESUMO

RATIONALE AND OBJECTIVES: While affiliated imaging centers play an important role in healthcare systems, little is known of how their operations are impacted by the COVID-19 pandemic. Our goal was to investigate imaging volume trends during the pandemic at our large academic hospital compared to the affiliated imaging centers. MATERIALS AND METHODS: This was a descriptive retrospective study of imaging volume from an academic hospital (main hospital campus) and its affiliated imaging centers from January 1 through May 21, 2020. Imaging volume assessment was separated into prestate of emergency (SOE) period (before SOE in Massachusetts on March 10, 2020), "post-SOE" period (time after "nonessential" services closure on March 24, 2020), and "transition" period (between pre-SOE and post-SOE). RESULTS: Imaging volume began to decrease on March 11, 2020, after hospital policy to delay nonessential studies. The average weekly imaging volume during the post-SOE period declined by 54% at the main hospital campus and 64% at the affiliated imaging centers. The rate of imaging volume recovery was slower for affiliated imaging centers (slope = 6.95 for weekdays) compared to main hospital campus (slope = 7.18 for weekdays). CT, radiography, and ultrasound exhibited the lowest volume loss, with weekly volume decrease of 41%, 49%, and 53%, respectively, at the main hospital campus, and 43%, 61%, and 60%, respectively, at affiliated imaging centers. Mammography had the greatest volume loss of 92% at both the main hospital campus and affiliated imaging centers. CONCLUSION: Affiliated imaging center volume decreased to a greater degree than the main hospital campus and showed a slower rate of recovery. Furthermore, the trend in imaging volume and recovery were temporally related to public health announcements and COVID-19 cases.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Hospitais , Humanos , Massachusetts , Estudos Retrospectivos , SARS-CoV-2 , Serviços Urbanos de Saúde
13.
Respir Med ; 164: 105903, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32217289

RESUMO

Aspergilloma, also known as mycetoma or fungus ball, is the most common manifestation of pulmonary involvement by Aspergillus species. The fungal ball typically forms within preexisting cavities of the lungs. Diagnosis requires both radiographic evidence along with serologic or microbiologic evidence of Aspergillus species involvement. While clinical features such as hemoptysis, chest pain, shortness of breath, cough, and fever are helpful in diagnosis, they are non-specific symptoms. Surgery is currently the mainstay of treatment for aspergilloma but is associated with considerable mortality and morbidity. Alternative options exist for patients who are poor surgical candidates and for those who prefer a less invasive treatment modality. Systemic treatment with amphotericin B is ineffective and is not recommended as a monotherapy, but systemic azoles is effective in approximately 50-80% of patients. Potential alternatives to surgery include intracavitary instillation or endobronchial administration of antifungal medication, as well as direct transbronchial aspergilloma removal. Bronchial artery embolization and radiotherapy are options to manage hemoptysis until definite eradication of the aspergilloma. More rigorous studies are needed to better establish non-surgical treatment paradigm for inoperable patients.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Azóis/administração & dosagem , Tratamento Conservador/métodos , Aspergilose Pulmonar/terapia , Artérias Brônquicas , Embolização Terapêutica/métodos , Feminino , Hemoptise/etiologia , Hemoptise/terapia , Humanos , Instilação de Medicamentos , Masculino , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/radioterapia
14.
J Cell Physiol ; 235(9): 6167-6182, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31975386

RESUMO

Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy.


Assuntos
Fator de Indução de Apoptose/genética , Carcinoma Hepatocelular/tratamento farmacológico , Células Estreladas do Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Caspases/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Fragmentação do DNA/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Células Estreladas do Fígado/química , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Microambiente Tumoral
15.
J Neurosurg Spine ; : 1-6, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881538

RESUMO

OBJECTIVE: Spinal schwannoma remains the third most common intradural spinal tumor following spinal meningioma and ependymoma. The available literature is generally limited to single-institution reports rather than epidemiological investigations. As of 1/1/2004, registration of all benign central nervous system tumors in the United States became mandatory after the Benign Brain Tumor Cancer Registries Amendment Act took action, which provided massive resources for United States population-based epidemiological studies. This article describes the epidemiology of spinal schwannoma in the United States from January 1, 2006, through December 31, 2014. METHODS: In this study, the authors utilized the Central Brain Tumor Registry of the United States, which corresponds to 100% of the American population. The Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance Epidemiology and End Results program provide the resource for this data registry. The authors included diagnosis years 2006 to 2014. They used the codes per the International Coding of Diseases for Oncology, 3rd Edition: histology code 9560/0 and site codes C72.0 (spinal cord), C70.1 (spinal meninges), and C72.1 (cauda equina). Rates are per 100,000 persons and are age-adjusted to the 2000 United States standard population. The age-adjusted incidence rates and 95% confidence intervals are calculated by age, sex, race, and ethnicity. RESULTS: There were 6989 spinal schwannoma cases between the years 2006 and 2014. The yearly incidence eminently increased between 2010 and 2014. Total incidence rate was 0.24 (95% CI 0.23-0.24) per 100,000 persons. The peak adjusted incidence rate was seen in patients who ranged in age from 65 to 74 years. Spinal schwannomas were less common in females than they were in males (incidence rate ratio = 0.85; p < 0.001), and they were less common in blacks than they were in whites (IRR = 0.52; p < 0.001) and American Indians/Alaska Natives (IRR = 0.50; p < 0.001) compared to whites. There was no statistically significant difference in incidence rate between whites and Asian or Pacific Islanders (IRR = 0.92; p = 0.16). CONCLUSIONS: The authors' study results demonstrated a steady increase in the incidence of spinal schwannomas between 2010 and 2014. Male sex and the age range 65-74 years were associated with higher incidence rates of spinal schwannomas, whereas black and American Indian/Alaska Native races were associated with lower incidence rates. The present study represents the most thorough assessment of spinal schwannoma epidemiology in the American population.

16.
J Neurol Surg B Skull Base ; 79(6): 593-598, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30456030

RESUMO

Background T1-weighted magnetic resonance imaging (MRI) remains the standard pituitary imaging sequence. However, up to 50% of pituitary adenomas are missed with standard imaging in Cushing's disease (CD) patients. Utility of other imaging sequences needs be explored. Objective To compare a T2-gradient echo sequence, constructive interference in steady state (CISS), with a contrast-enhanced (CE) T1-weighted sequence, volume-interpolated breath-hold examination (VIBE), in the detection of pituitary adenomas in CD patients. Design Retrospective analysis of CD patients who underwent endoscopic transsphenoidal pituitary adenomectomy at our institution. Patients and Measurement Twelve patients were included in the study. Two neuroradiologists, who were blinded to the patients' clinical and surgical findings, independently reviewed the CE-VIBE and CISS images. Localization of pituitary adenoma from imaging was compared with intraoperative localization. Results The averaged sensitivity of detecting pituitary adenoma in CD patients was not significantly different between CE-VIBE sequence (63%) and CISS sequence (54%). The positive predictive value was 75% (Observer A) and 100% (Observer B) with CE-VIBE sequence, and 64% (Observer A) and 100% (Observer B) with CISS sequence. In two patients, pituitary adenoma was easily localized with CISS sequence but hard to detect with CE-VIBE sequence. In two other patients, the adenoma was much better delineated on CE-VIBE sequence. Conclusion In our series, the addition of CISS sequence to T1-weighted MRI imaging protocols improved the detection of pituitary adenomas in CD patients. CISS sequence may be a useful adjunct to T1-weighted pituitary MRI protocols and an appropriate alternative for patients with gadolinium contraindications.

17.
J Neurosurg ; : 1-8, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29570007

RESUMO

OBJECTIVEPreoperatively determining the extent of parasellar invasion of pituitary macroadenomas is useful for surgical planning and patient counseling. Here, the authors compared constructive interference in steady state (CISS), a T2-weighted gradient-echo MRI sequence, to volume-interpolated breath-hold examination (VIBE), a T1-weighted gradient-echo MRI sequence, for evaluation of cavernous sinus invasion (CSI) by pituitary macroadenomas.METHODSVIBE and CISS images of 98 patients with pituitary macroadenoma were retrospectively analyzed and graded using the modified Knosp classification. The Knosp grades were correlated to surgical findings of CSI, which were determined intraoperatively using 0° and 30° endoscopes. The predictive accuracies for CSI according to the Knosp grades derived from the CISS and VIBE images were compared using receiver operating characteristic (ROC) curves. Postoperative MRI was used to evaluate the gross-total resection (GTR) rates.RESULTSThe CSI rate by pituitary macroadenomas was 27.6% (27 of 98 cases). Of 196 assessments (left and right sides of 98 macroadenomas), 45 (23.0%) had different Knosp grades when scored using VIBE versus CISS images. For the VIBE images, 0% of Knosp grade 0, 4.5% of grade 1, 23.8% of grade 2, 42.1% of grade 3A, 100% of grade 3B, and 83.3% of grade 4 macroadenomas were found to have CSI intraoperatively. For the CISS images, 0% of Knosp grade 0, 2.1% of grade 1, 31.3% of grade 2, 56.3% of grade 3A, 100% of grade 3B, and 100% of grade 4 macroadenomas were found to have CSI intraoperatively. Two pituitary macroadenomas were classified as grade 4 on VIBE sequences but grades 3A and 2 on CISS sequences; CSI was not observed intraoperatively in both cases. The GTR rate was 64.3% and 60.0% for high-grade (3A, 3B, and 4) macroadenomas classified using VIBE and CISS sequences, respectively. The areas under the ROC curves were 0.94 and 0.97 for VIBE- and CISS-derived Knosp grades (p = 0.007), respectively.CONCLUSIONSKnosp grades determined using CISS sequence images are better correlated with intraoperative CSI than those determined using VIBE sequence images. CISS sequences may be valuable for the preoperative assessment of pituitary macroadenomas.

18.
Neurosurgery ; 83(3): 548-555, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040773

RESUMO

BACKGROUND: The guideline for treating unruptured brain arteriovenous malformations (ubAVMs) remains controversial. A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) reported lower risk of stroke or death with conservative management compared to interventional treatment. There were numerous limitations to the study, including short follow-up period and disproportionate number of patients treated with surgery and embolization. OBJECTIVE: To evaluate whether treatment of ARUBA-eligible patients have acceptable outcomes at our institution. METHODS: Retrospective analysis was performed on 673 patients with brain AVMs treated at our institution between 2001 and 2014. One hundred five patients were ARUBA eligible and included in the study. Patients were divided into the microsurgery or Gamma Knife Radiosurgery (GKS; Elekta, Stockholm, Sweden) arm depending on their final treatment. Mean follow-up period was 43 mo (range 4-136 mo). Primary outcome was stroke or death. RESULTS: A total of 8 (7.6%) patients had a stroke or died. The overall risk of stroke or death was 11.4% (5 of 44 patients) for the microsurgery arm and 4.9% (3 of 61 patients) for the GKS arm. The annual rates of stroke or death were 2.1%, 4.0%, and 1.2% for the entire patient cohort, microsurgery arm, and GKS arm, respectively. AVM obliteration rates at the end of the follow-up period were 95.5% and 47.5% for the microsurgery and GKS arms, respectively. CONCLUSION: We report a lower overall risk of stroke or death in our ARUBA-eligible patients following treatment than ARUBA. Our results suggest that microsurgery and GKS may be appropriate treatments for patients with ubAVM.


Assuntos
Tratamento Conservador/tendências , Malformações Arteriovenosas Intracranianas/mortalidade , Malformações Arteriovenosas Intracranianas/terapia , Microcirurgia/tendências , Procedimentos Neurocirúrgicos/tendências , Radiocirurgia/tendências , Adulto , Idoso , Estudos de Coortes , Tratamento Conservador/mortalidade , Embolização Terapêutica/mortalidade , Embolização Terapêutica/tendências , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Masculino , Microcirurgia/mortalidade , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/mortalidade , Radiocirurgia/mortalidade , Estudos Retrospectivos , Suécia/epidemiologia , Resultado do Tratamento
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(10): 1337-1344, 2017 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-29070463

RESUMO

OBJECTIVE: To investigate the structural changes inintestinal flora and metabolic changes in type 2 diabetic patients with obesity(BMI≥40 kg/m2)by sequencing the 16S rRNA genes. METHODS: Stool samples were collected from 4 diabetic patients before and after gastric bypass surgery for extraction of the total DNA. The diversity of the intestinal flora in the samples was investigated by 16S rRNA sequencing. After surgery, the changes in glucose and lipid metabolism were evaluated in the patients, and the changesin body mass index (BMI) and waist to hip ratio were assessed at 3 month intervals. RESULTS: After gastric bypass, the patient's BMI, waist to hip ratio, glucose metabolism and lipid metabolism gradually recovered the normal levels. The proportion of Bacteroidetesis increased and the proportions of Firmicutes and Proteobacteria decreased in the intestinal bacteria after the surgery. CONCLUSION: Gastric bypass surgery can effectively alleviate the condition of obese patients with type 2 diabetes and improve the composition of the intestinal flora.


Assuntos
Bactérias/classificação , Diabetes Mellitus Tipo 2/microbiologia , Derivação Gástrica , Microbioma Gastrointestinal , Obesidade/cirurgia , Diabetes Mellitus Tipo 2/complicações , Humanos , Obesidade/complicações , Obesidade/microbiologia , RNA Ribossômico 16S/genética
20.
J Clin Neurosci ; 24: 28-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26498091

RESUMO

Tuberous sclerosis and hippocampal sclerosis are both well-defined entities associated with medically intractable epilepsy. To our knowledge, there has been only one prior case of these two pathologies being co-existent. We report a 7-month-old boy who presented with intractable seizures at 2 months of age. MRI studies showed diffuse volume loss in the brain with bilateral, multiple cortical tubers and subcortical migration abnormalities. Subependymal nodules were noted without subependymal giant cell astrocytoma. Genetic testing revealed TSC2 and PRD gene deletions. Histopathology of the hippocampus showed CA1 sclerosis marked by loss of neurons in the CA1 region. Sections from the temporal, parietal and occipital lobes showed multiple cortical tubers characterized by cortical architectural disorganization, gliosis, calcifications and increased number of large balloon cells. Focal white matter balloon cells and spongiform changes were also present. The patient underwent resection of the right fronto-parietal lobe and a subsequent resection of the right temporal, parietal and occipital lobes. The patient is free of seizures on anti-epileptic medication 69 months after surgery. Although hippocampal sclerosis is well documented to be associated with coexistent focal cortical dysplasia, the specific co-existence of cortical tubers and hippocampal sclerosis appears to be rare.


Assuntos
Hipocampo/patologia , Esclerose Tuberosa/complicações , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Esclerose/patologia , Convulsões/etiologia
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