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1.
Photobiomodul Photomed Laser Surg ; 42(1): 49-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38150176

RESUMO

Background: The current research extends previous laboratory investigations by investigating the effects of low-level laser irradiation (LLLI) on human blood plasma. Total bilirubin is of special importance because of its potential biostimulatory and modulatory actions. Objective: This study aims to analyze changes in total bilirubin content as a consequence of LLLI on human blood plasma. This study aims to determine how changes in exposure duration and laser wavelength affect these adjustments. Methodology: Plasma was isolated from a healthy adult donor's whole blood using the anticoagulant ethylenediaminetetraacetic acid (EDTA). Plasma samples were exposed to LLLI at 375 and 650 nm for 5, 10, 15, 20, and 25 min. Total bilirubin concentrations were measured both before and after irradiation using spectrophotometric analysis. The difference between 375 and 630 nm lasers was also investigated. Results: Five, 10, 15, 20, and 25 min of exposure to LLLI at 375 and 650 nm wavelengths resulted in statistically significant differences in total bilirubin content (p ˂ 0.05, p ˂ 0.001, p ˂ 0.0001). There was no statistically significant difference in total bilirubin concentration between the 375 and 630 nm lasers. Conclusions: Human blood plasma total bilirubin levels were considerably lower following LLLI at 375 and 630 nm than controls. Multiple exposures provide the same results. These findings demonstrate the role of biostimulation by laser irradiation in blood plasma applications and suggest that low-level laser treatment may control total bilirubin levels, particularly at 375 and 630 nm.


Assuntos
Lasers , Terapia com Luz de Baixa Intensidade , Adulto , Humanos , Plasma
2.
Neurosurgery ; 93(6): 1346-1352, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37530524

RESUMO

BACKGROUND AND OBJECTIVES: Intracranial meningiomas are a diverse group of tumors, which vary by grade, genetic composition, location, and vasculature. Expanding the understanding of the supply of skull base (SBMs) and non-skull base meningiomas (NSBMs) will serve to further inform resection strategies. We sought to delineate the vascular supply of a series of intracranial meningiomas by tumor location. METHODS: A retrospective study of intracranial meningiomas that were studied using preoperative digital subtraction angiograms before surgical resection at a tertiary referral center was performed. Patient, tumor, radiologic, and treatment data were collected, and regression models were developed. RESULTS: One hundred sixty-five patients met inclusion criteria. The mean age was 57.1 years (SD: 12.6). The mean tumor diameter was 4.9 cm (SD: 1.5). One hundred twenty-six were World Health Organization Grade I, 37 Grade II, and 2 Grade III. Arterial feeders were tabulated by Al-Mefty's anatomic designations. SBMs were more likely to derive arterial supply from the anterior circulation, whereas NSBMs were supplied by external carotid branches. NSBMs were larger (5.61 cm vs 4.45 cm, P = <.001), were more often presented with seizure (20% vs 8%, P = .03), were higher grade ( P = <.001) had more frequent peritumoral brain edema (84.6% vs 66%, P = .04), and had more bilateral feeders (47.7% vs 28%, P = .01) compared with SBMs. More arterial feeders were significantly associated with lower tumor grade ( P = .023, OR = 0.59). Higher tumor grade (Grade II/III) was associated with fewer arterial feeders ( P = .017, RR = 0.74). CONCLUSION: Meningioma location is associated with specific vascular supply patterns, grade, and patient outcomes. This information suggests that grade I tumors, especially larger tumors, are more likely to have diverse vascular supply patterns, including internal carotid branches. This study may inform preoperative embolization and surgical considerations, particularly for large skull base tumors.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Humanos , Pessoa de Meia-Idade , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Base do Crânio/patologia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Base do Crânio/patologia
3.
JAMA Surg ; 158(7): 777-778, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36947063
4.
Neurosurgery ; 92(2): 353-362, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36637270

RESUMO

BACKGROUND: Decompression of the injured spinal cord confers neuroprotection. Compared with timing of surgery, verification of surgical decompression is understudied. OBJECTIVE: To compare the judgment of cervical spinal cord decompression using real-time intraoperative ultrasound (IOUS) following laminectomy with postoperative MRI and CT myelography. METHODS: Fifty-one patients were retrospectively reviewed. Completeness of decompression was evaluated by real-time IOUS and compared with postoperative MRI (47 cases) and CT myelography (4 cases). RESULTS: Five cases (9.8%) underwent additional laminectomy after initial IOUS evaluation to yield a final judgment of adequate decompression using IOUS in all 51 cases (100%). Postoperative MRI/CT myelography showed adequate decompression in 43 cases (84.31%). Six cases had insufficient bony decompression, of which 3 (50%) had cerebrospinal fluid effacement at >1 level. Two cases had severe circumferential intradural swelling despite adequate bony decompression. Between groups with and without adequate decompression on postoperative MRI/CT myelography, there were significant differences for American Spinal Injury Association motor score, American Spinal Injury Association Impairment Scale grade, AO Spine injury morphology, and intramedullary lesion length (IMLL). Multivariate analysis using stepwise variable selection and logistic regression showed that preoperative IMLL was the most significant predictor of inadequate decompression on postoperative imaging (P = .024). CONCLUSION: Patients with severe clinical injury and large IMLL were more likely to have inadequate decompression on postoperative MRI/CT myelography. IOUS can serve as a supplement to postoperative MRI/CT myelography for the assessment of spinal cord decompression. However, further investigation, additional surgeon experience, and anticipation of prolonged swelling after surgery are required.


Assuntos
Medula Cervical , Lesões do Pescoço , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Laminectomia/métodos , Projetos Piloto , Mielografia , Medula Cervical/cirurgia , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/cirurgia , Descompressão Cirúrgica/métodos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Lesões do Pescoço/cirurgia , Traumatismos da Coluna Vertebral/cirurgia , Resultado do Tratamento
5.
JAMA Surg ; 158(1): 6-8, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36197684

RESUMO

This Viewpoint discusses the rising trend in research output among matched US MD seniors in the National Resident Matching Program Main Residency Match from 2009 to 2020.


Assuntos
Internato e Residência , Estudantes de Medicina , Humanos , Estados Unidos/epidemiologia , Escolha da Profissão
6.
J Neurotrauma ; 39(23-24): 1716-1726, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35876459

RESUMO

Expansion duraplasty to reopen effaced subarachnoid space and improve spinal cord perfusion, autoregulation, and spinal pressure reactivity index (sPRX) has been advocated in patients with traumatic cervical spinal cord injury (tCSCI). We designed this study to identify candidates for expansion duraplasty, based on the absence of cerebrospinal fluid (CSF) interface around the spinal cord on magnetic resonance imaging (MRI), in the setting of otherwise adequate bony decompression. Over a 61-month period, 104 consecutive American Spinal Injury Association Impairment Scale (AIS) grades A-C patients with tCSCI had post-operative MRI to assess the adequacy of surgical decompression. Their mean age was 53.4 years, and 89% were male. Sixty-one patients had falls, 31 motor vehicle collisions, 11 sport injuries, and one an assault. The AIS grade was A in 56, B in 18, and C in 30 patients. Fifty-four patients had fracture dislocations; there was no evidence of skeletal injury in 50 patients. Mean intramedullary lesion length (IMLL) was 46.9 (standard deviation = 19.4) mm. Median time from injury to decompression was 17 h (interquartile range 15.2 h). After surgery, 94 patients had adequate decompression as judged by the presence of CSF anterior and posterior to the spinal cord, whereas 10 patients had effacement of the subarachnoid space at the injury epicenter. In two patients whose decompression was not definitive and post-operative MRI indicated inadequate decompression, expansion duraplasty was performed. Candidates for expansion duraplasty (i.e., those with inadequate decompression) were significantly younger (p < 0.0001), were AIS grade A (p < 0.0016), had either sport injuries (six patients) or motor vehicle collisions (three patients) (p < 0.0001), had fracture dislocation (p = 0.00016), and had longer IMLL (p = 0.0097). In regression models, patients with sport injuries and inadequate decompression were suitable candidates for expansion duraplasty (p = 0.03). Further, 9.6% of patients failed bony decompression alone and either did (2) or would have (8) benefited from expansion duraplasty.


Assuntos
Medula Cervical , Lesões do Pescoço , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Medula Cervical/lesões , Traumatismos da Medula Espinal/cirurgia , Traumatismos da Medula Espinal/patologia , Descompressão Cirúrgica/métodos , Traumatismos da Coluna Vertebral/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
7.
Sci Rep ; 11(1): 23182, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848729

RESUMO

Previous study has shown the antimicrobial activities of mucus protein extracted from Anabas testudineus. In this study, we are interested in characterizing the anticancer activity of the A. testudineus antimicrobial peptides (AMPs). The mucus was extracted, fractioned, and subjected to antibacterial activity testing to confirm the fish's AMPs production. The cytotoxic activity of each fraction was also identified. Fraction 2 (F2), which shows toxicity against MCF7 and MDA-MB-231 were sent for peptide sequencing to identify the bioactive peptide. The two peptides were then synthetically produced and subjected to cytotoxic assay to prove their efficacy against cancer cell lines. The IC50 for AtMP1 against MCF7 and MDA-MB-231 were 8.25 ± 0.14 µg/ml and 9.35 ± 0.25 µg/ml respectively, while for AtMP2 it is 5.89 ± 0.14 µg/ml and 6.97 ± 0.24 µg/ml respectively. AtMP1 and AtMP2 treatment for 48 h induced breast cancer cell cycle arrest and apoptosis by upregulating the p53, which lead to upregulate pro-apoptotic BAX gene and downregulate the anti-apoptotic BCL-2 gene, consequently, trigger the activation of the caspase-3. This interaction was supported by docking analysis (QuickDBD, HPEPDOCK, and ZDOCK) and immunoprecipitation. This study provided new prospects in the development of highly effective and selective cancer therapeutics based on antimicrobial peptides.


Assuntos
Peptídeos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Peixes/metabolismo , Muco/metabolismo , Peptídeos/farmacologia , Animais , Apoptose , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Biologia Computacional/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Concentração Inibidora 50 , Células MCF-7 , Peptídeos/química , Mapeamento de Interação de Proteínas
8.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34504017

RESUMO

Pharmacological treatment of gliomas and other brain-infiltrating tumors remains challenging due to limited delivery of most therapeutics across the blood-brain barrier (BBB). Transcranial MRI-guided focused ultrasound (FUS), an emerging technology for noninvasive brain treatments, enables transient opening of the BBB through acoustic activation of circulating microbubbles. Here, we evaluate the safety and utility of transcranial microbubble-enhanced FUS (MB-FUS) for spatially targeted BBB opening in patients with infiltrating gliomas. In this Phase 0 clinical trial (NCT03322813), we conducted comparative and quantitative analyses of FUS exposures (sonications) and their effects on gliomas using MRI, histopathology, microbubble acoustic emissions (harmonic dose [HD]), and fluorescence-guided surgery metrics. Contrast-enhanced MRI and histopathology indicated safe and reproducible BBB opening in all patients. These observations occurred using a power cycling closed feedback loop controller, with the power varying by nearly an order of magnitude on average. This range underscores the need for monitoring and titrating the exposure on a patient-by-patient basis. We found a positive correlation between microbubble acoustic emissions (HD) and MR-evident BBB opening (P = 0.07) and associated interstitial changes (P < 0.01), demonstrating the unique capability to titrate the MB-FUS effects in gliomas. Importantly, we identified a 2.2-fold increase of fluorescein accumulation in MB-FUS-treated compared to untreated nonenhancing tumor tissues (P < 0.01) while accounting for vascular density. Collectively, this study demonstrates the capabilities of MB-FUS for safe, localized, controlled BBB opening and highlights the potential of this technology to improve the surgical and pharmacologic treatment of brain tumors.


Assuntos
Barreira Hematoencefálica/fisiologia , Sistemas de Liberação de Medicamentos/métodos , Terapia por Ultrassom/métodos , Adulto , Transporte Biológico/fisiologia , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/fisiologia , Estudos de Viabilidade , Feminino , Glioma/fisiopatologia , Glioma/terapia , Humanos , Masculino , Microbolhas , Sonicação/métodos
9.
J Neurotrauma ; 38(15): 2073-2083, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33726507

RESUMO

The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the t test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. During a 19-year period, 101 patients with ATCCS, admission ASIA Impairment Scale (AIS) grades C and D, and an admission AMS of ≤95 were surgically decompressed. Twenty-four of 101 patients had an AIS grade C injury. Eighty-two patients were males, the mean age of patients was 57.9 years, and 69 patients had had a fall. AMS at admission was 68.3 (standard deviation [SD] 23.4); upper extremities (UE) 28.6 (SD 14.7), and lower extremities (LE) 41.0 (SD 12.7). AMS at the latest follow-up was 93.1 (SD 12.8), UE 45.4 (SD 7.6), and LE 47.9 (SD 6.6). Mean number of stenotic segments was 2.8, mean canal compromise was 38.6% (SD 8.7%), and mean intramedullary lesion length (IMLL) was 23 mm (SD 11). Thirty-six of 101 patients had decompression within 24 h, 38 patients had decompression between 25 and 72 h, and 27 patients had decompression >72 h after injury. Demographics, etiology, AMS, AIS grade, morphometry, lesion length, surgical technique, steroid protocol, and follow-up AMS were not statistically different between groups treated at different times. We analyzed the effect size of timing of decompression categorically and in a continuous fashion. There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21; p = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.


Assuntos
Síndrome Medular Central/diagnóstico por imagem , Síndrome Medular Central/cirurgia , Descompressão Cirúrgica , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Tempo para o Tratamento , Idoso , Síndrome Medular Central/etiologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atividade Motora , Recuperação de Função Fisiológica , Estudos Retrospectivos , Estenose Espinal/complicações , Resultado do Tratamento
10.
Pituitary ; 22(6): 633-639, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31620953

RESUMO

PURPOSE: This case series evaluates the surgical management of granular cell tumor (GCT) of the sellar region. This rare entity presents a unique diagnostic and surgical challenge. METHODS: Institutional neuropathology databases at Brigham and Women's Hospital and Massachusetts General Hospital were searched for cases with a tissue diagnosis of GCT, and with a location in the sellar region. Patient, treatment, tumor, and follow-up data were extracted. RESULTS: Three patients had a diagnosis of GCT of the sellar region occurring over an 18-year period. All three patients were followed postoperatively at our multidisciplinary pituitary center (median follow-up = 30 months; range 12-30 months). Hormonal disturbances, an incidental lesion requiring diagnosis, and neurological symptoms were indications for surgery in these patients. Two patients underwent a craniotomy and one underwent endoscopic transsphenoidal surgery. All three patients were free of tumor recurrence at last follow-up. In one case tested, positive thyroid transcription factor-1 (TTF-1) immunohistochemistry was observed. CONCLUSION: GCT is generally a benign tumor of the sellar region. Surgical resection is the standard treatment, more recently with transsphenoidal surgery when indicated. Surgical resection results in optimal outcome for patients.


Assuntos
Tumor de Células Granulares/diagnóstico , Tumor de Células Granulares/cirurgia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/cirurgia
11.
World Neurosurg ; 121: e223-e229, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30261394

RESUMO

OBJECTIVE: Readmission and reoperation are risks in the resection of benign cranial nerve tumors (BCNTs). This report analyzes the impact of patient-level and surgical factors on these adverse outcomes. METHODS: This retrospective cohort review comprised patients with a diagnosis of BCNT enrolled in the American College of Surgeons National Surgical Quality Improvement Program registry from 2011 to 2015. Multivariate logistic regression was used to determine the impact of select medical and operative factors on the primary outcomes of readmission and reoperation within 30 days, adjusted for relevant covariates. RESULTS: We identified 996 patients who underwent resection of a BCNT. The most frequent major complications were readmission (11%), reoperation (8%), surgical site infections (2.6%), and venous thromboembolism (1.5%). The most frequent indications for readmission were management of infection (2.5%), cerebrospinal fluid leak (2.3%), and hydrocephalus (0.5%). Repair of cranial and meningeal defects (3.0%), correction of lagophthalmos (1.2%), and repair of middle ear defects (1.0%) were the most common indications for reoperation. Logistic regression revealed that extremes of age were associated with readmission, whereas preoperative steroid usage, long operative time, and postoperative length of stay >3 days were associated with reoperation (P < 0.05). Obesity trended toward an association with readmission and reoperation. CONCLUSIONS: Extremes of age were associated with readmission; preoperative steroid use, long operative time, and postoperative length of stay >3 days were associated with reoperation. Surgeons should consider these factors when assessing risk of postoperative complications for BCNTs.


Assuntos
Neoplasias dos Nervos Cranianos/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Adulto , Neoplasias dos Nervos Cranianos/epidemiologia , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/epidemiologia , Neuroma Acústico/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação/estatística & dados numéricos , Fatores de Risco , Esteroides/uso terapêutico , Estados Unidos/epidemiologia
12.
J Neurosurg Pediatr ; 21(4): 434-438, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29350592

RESUMO

OBJECTIVE Absent from an analysis of supply is consideration of the geographic distribution of pediatric neurosurgeons. Several patient socioeconomic metrics are known to be associated with outcome in pediatric neurosurgical diseases, such as hydrocephalus. The purpose of this study was to determine current geographic proximity to pediatric neurosurgical care using professional society databases. This study also sought to establish how socioeconomic factors are related to distance to care, using federal government-collected data. METHODS A list of currently practicing American Board of Pediatric Neurological Surgery (ABPNS)-certified neurosurgeons was compiled (ABPNS group). A separate list of practicing members of the Joint Pediatric Section (JPS) of the American Association of Neurological Surgeons/Congress of Neurological Surgeons was prepared (JPS group). Current primary practice locations were collected from each professional society database for each ABPNS or JPS neurosurgeon and were charted using ArcGIS mapping software (ESRI, version 10.3) on a United States Census Bureau map. The straight distance from the centroid of each zip code tabulation area (ZCTA) to the nearest neurosurgeon was determined by group type of neurosurgeon (ABPNS vs ABPNS + JPS). ZCTA-level data on demographic and socioeconomic factors were acquired from the American Community Survey, including data in children and young adults (0-18 or 0-24 years old) and the general population. These data were compared by distance to care and by groups of neurosurgeons (Pearson's chi-square analysis; the threshold of significance was set at 0.05). RESULTS Three hundred fifty-five practicing neurosurgeons providing pediatric care were located, of whom 215 surgeons were certified by the ABPNS and 140 were JPS members only. The analysis showed that 1 pediatric neurosurgeon is in practice for every 289,799 persons up to the age of 24 years. The average distance between a ZCTA and the nearest pediatric neurosurgeon is 63.3 miles (SE 0.3, range 0.0-499.7 miles). Geographic analysis showed that 27.1% of children live farther than 60 miles from an ABPNS-certified neurosurgeon and 19.7% from either an ABPNS-certified neurosurgeon or a JPS member. ZCTAs with children who live farther than 60 miles from a neurosurgeon providing pediatric care had a marginally higher rate of uninsured children, a higher percentage of families with children living below the federal poverty level, and a higher proportion of persons living in rural areas compared with ZCTAs with children who live within 60 miles of care (p < 0.005 for each finding). CONCLUSIONS The results of this study indicate that there is considerable variation in proximity to pediatric neurosurgical subspecialty care by geographic region. In addition, there is a relationship between distance to neurosurgical care and socioeconomic indicators. Optimization of access to pediatric neurosurgical care may involve strategies to overcome long geographic distances, particularly in rural and underserved areas. Such areas may have disproportionately lower socioeconomic levels, which may further limit access to care and affect outcomes. Both the total number of pediatric neurosurgeons per pediatric population and their geographic distribution could be important in determining appropriate subspecialty supply factors (e.g., the number of accredited pediatric neurosurgical fellowship training programs), as well as being important drivers of neurosurgical patient outcomes.


Assuntos
Neurocirurgiões/provisão & distribuição , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Saúde da População Rural , Centros Cirúrgicos/provisão & distribuição , Estados Unidos , Adulto Jovem
13.
World Neurosurg ; 109: e676-e683, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29061463

RESUMO

BACKGROUND: Chordoma that occurs primarily in the sella turcica is rare and presents unique treatment challenges. OBJECTIVE: The purpose of this study was to determine common features, treatment approaches, and survival characteristics of intrasellar chordoma. METHODS: Institutional databases, the SEER (Surveillance Epidemiology and End Results) database, and PubMed/EMBASE were queried for chordoma with a primarily intrasellar component. The SEER database was also queried for adult skull base chordoma. Patient-level data were extracted where available. Kaplan-Meier survival analyses were conducted. RESULTS: Among 80 cases, the mean age at presentation was 55.6 (standard deviation, 15.9), with a female predominance (1.16:1.00). Patients experienced symptoms for a mean duration of 19.0 months, including cranial nerve deficits, hypopituitarism, and hyperprolactinemia. Among patients receiving treatment, 77.5% underwent surgery. In addition, less than half of the patients (n = 34, 47.3%) received adjuvant radiation therapy. The 5-year overall survival (OS) of intrasellar chordoma was 60.0% (standard error [SE], 6.9). Patients aged 40 years and younger had a 5-year OS of 80.8% (SE, 12.2), compared with patients older than 40 years, who had an OS of 55.4% (SE, 7.7) (Mantel-Cox, P = 0.044). Males experienced a lower 5-year OS (44.0; SE, 9.7) than did females (76.8; SE, 8.5), (Mantel-Cox, P = 0.003). Median OS was greater in patients with skull base chordoma than in patients with intrasellar chordoma (Mantel-Cox, P = 0.046). CONCLUSIONS: Intrasellar chordoma presents frequently with visual disturbances and hyperprolactinemia and has a slightly higher incidence in females. Young age predicts a better prognosis. Intrasellar chordoma has a lower overall survival than has skull base chordoma.


Assuntos
Cordoma/diagnóstico , Programa de SEER/tendências , Neoplasias da Base do Crânio/diagnóstico , Estatística como Assunto/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Cordoma/mortalidade , Cordoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Base do Crânio/mortalidade , Neoplasias da Base do Crânio/cirurgia , Estatística como Assunto/métodos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Neuro Oncol ; 20(2): 225-235, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29016938

RESUMO

Background: Combined immunotherapy approaches are promising cancer treatments. We evaluated anti-programmed cell death protein 1 (PD-1) treatment combined with gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection of a prodrug metabolizing nonreplicating adenovirus (AdV-tk), providing in situ chemotherapy and immune stimulation. Methods: The effects of GMCI on PD ligand 1 (PD-L1) expression in glioblastoma were investigated in vitro and in vivo. The efficacy of the combination was investigated in 2 syngeneic mouse glioblastoma models (GL261 and CT-2A). Immune infiltrates were analyzed by flow cytometry. Results: GMCI upregulated PD-L1 expression in vitro and in vivo. Both GMCI and anti-PD-1 increased intratumoral T-cell infiltration. A higher percentage of long-term survivors was observed in mice treated with combined GMCI/anti-PD-1 relative to single treatments. Long-term survivors were protected from tumor rechallenge, demonstrating durable memory antitumor immunity. GMCI led to elevated interferon gamma positive T cells and a lower proportion of exhausted double positive PD1+TIM+CD8+ T cells. GMCI also increased PD-L1 levels on tumor cells and infiltrating macrophages/microglia. Our data suggest that anti-PD-1 treatment improves the effectiveness of GMCI by overcoming interferon-induced PD-L1-mediated inhibitory signals, and GMCI improves anti-PD-1 efficacy by increasing tumor-infiltrating T-cell activation. Conclusions: Our data show that the GMCI/anti-PD-1 combination is well tolerated and effective in glioblastoma mouse models. These results support evaluation of this combination in glioblastoma patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Encefálicas , Terapia Combinada , Glioblastoma , Imunoterapia , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Terapia Combinada/métodos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/imunologia , Humanos , Imunoterapia/métodos , Camundongos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
15.
Acta Neurochir (Wien) ; 159(11): 2209-2216, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28948361

RESUMO

BACKGROUND: Rarely, granular cell tumor (GCT) occurs in the sellar region. The natural history of this clinical entity is not well known. This study sought to determine the clinical features and long-term outcome of GCT of the sellar region. METHODS: Institutional databases, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, and PubMed/EMBASE were searched for GCT of the sellar region. Patient-level data were extracted where available, including age, sex, symptoms, tumor size and location, presumed diagnosis, surgical approach and result, subtotal resection (STR) and gross-total resection (GTR), use of radiation, and outcome. The primary endpoints of recurrence and survival were determined. RESULTS: A total of 141 cases were analyzed. The mean age at diagnosis was 48.9 (SD 15.3) with a female predominance (sex ratio 1.49:1). Almost all patients experienced either or both neurological and endocrine symptoms. The most common pre-operative diagnosis was pituitary adenoma. Approximately 60% of patients were treated with surgery, 57.7% with a craniotomy, and 39.7% with a transsphenoidal approach. The 5-year overall survival (OS) was 84.7% (standard error, SE 4.2). Patients with tumors less than 2.5 cm experienced a greater 5-year OS (100.0%) than patients with tumors 2.5 cm or larger (74.0%, SE: 11.7), (Mantel-Cox, p = 0.024). GTR resulted in a greater 5-year OS (95.7%, SE 4.3) than STR (88.8%, SE 5.5) and no surgery or biopsy alone (75.0%, SE 15.3) (Mantel-Cox, p = 0.016). The use of radiation therapy did not improve OS. The 5-year progression-free survival rate was 80.8% (SE 9.2). CONCLUSIONS: Granular cell tumor of the sellar region is a relatively benign neoplasm with neurological and endocrine clinical manifestations. Surgical resection is appropriate for management. Tumor size and extent of resection influence overall survival.


Assuntos
Neoplasias Encefálicas/cirurgia , Tumor de Células Granulares/cirurgia , Sela Túrcica , Adenoma/diagnóstico , Adolescente , Adulto , Distribuição por Idade , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Craniotomia , Bases de Dados Factuais , Diagnóstico Diferencial , Intervalo Livre de Doença , Feminino , Tumor de Células Granulares/diagnóstico , Tumor de Células Granulares/epidemiologia , Tumor de Células Granulares/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/diagnóstico , Prognóstico , Estudos Retrospectivos , Distribuição por Sexo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
16.
World Neurosurg ; 107: 534-541, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28823671

RESUMO

BACKGROUND: Although the World Health Organization classifies papillary glioneuronal tumor (PGNT) as a grade I tumor, several malignant cases have been reported. In this study, we examined the clinical and prognostic characteristics of PGNT. METHODS: PubMed, Embase, and institutional databases were queried for patient-level reports of PGNT, resulting in identification of 138 cases. Descriptive and Kaplan-Meier survival analyses were conducted. The threshold of significance was 0.05. RESULTS: The mean age at presentation was 26.9 ± 16.3 years, and the incidence was higher in males (1.42:1). Tumors with a high Ki-67 index (≥5) were more likely to exhibit perilesional edema and ring enhancement on magnetic resonance imaging, trending toward significance (P = 0.114 and 0.113, respectively). Compared with tumors with a low Ki-67 index (<5), those with a high Ki-67 index were more likely to be treated with subtotal resection (STR) than with gross total resection (GTR) (Kruskal-Wallis test, P = 0.006) and with radiation therapy (χ2 test, P = 0.010). At 5 years post-treatment, PGNT had a mean progression-free survival (PFS) of 85.9 ± 3.9%. Males had a better 5-year PFS than females (94.0 ± 3.4% vs. 74.8 ± 7.8%; Mantel-Cox test, P = 0.002). Two-year PFS was higher after GTR than after STR (91.9 ± 3.6% vs. 46.7 ± 21.4%; Mantel-Cox test, P < 0.001). A low Ki-67 index was associated with a higher 5-year PFS compared with a high Ki-67 index (94.8 ± 3.6% vs. 55.6 ± 12.9%; Mantel-Cox test, P < 0.001). CONCLUSIONS: PGNT is a benign tumor of young adults, but can present atypically as high grade. Male sex, low cellular proliferation, and maximal surgical resection are positive prognostic indicators for PGNT.


Assuntos
Neoplasias Encefálicas/cirurgia , Carcinoma Papilar/cirurgia , Doenças Raras/cirurgia , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Proliferação de Células , Intervalo Livre de Doença , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Prognóstico , Doenças Raras/mortalidade , Doenças Raras/patologia , Resultado do Tratamento
17.
Clin Spine Surg ; 30(9): E1206-E1210, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27906741

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the utilization and effectiveness of halo-vest (HV) immobilization for type II odontoid fractures from 2004 to 2014. SUMMARY OF BACKGROUND DATA: Controversy persists regarding the optimal treatment method for odontoid fractures in the elderly. Management options include immobilization in a cervical orthosis, HV immobilization, and operative intervention. Over the past decade, high mortality and morbidity rates have been reported following HV immobilization in this patient population. MATERIALS AND METHODS: In a retrospective study, patient demographics, presentation, Charlson comorbidity index, treatment method, and outcome data for patients over 65 who had suffered type II odontoid fractures from 2004 to 2014 were compared with a historical cohort from 1997 to 2004. RESULTS: One hundred twenty-six patients met inclusion criteria. The mean age was 82.7±8.8 compared with 80.7±0.9 in the 1997-2004 cohort. The in-hospital mortality rate from 2004 to 2014 was 11.1% (14/126) compared with 31% in the historical cohort, and 10 (7.9%) patients were treated with HV compared with 49%. Mortality in the HV group was higher than the surgical group (P=0.01) but no different from the orthosis group (P=0.63).There were no differences in injury severity score, Charlson comorbidity index, or complications between treatment groups. CONCLUSIONS: Over the past decade, HV use for elderly odontoid fractures has decreased at our institution. Mortality and morbidity of elderly patients treated with HV has also decreased. These findings are likely the result of improved patient selection and greater attention to respiratory care. This study demonstrates that HV immobilization of odontoid fractures in elderly patients can be as safe as cervical orthosis treatment in select patients.


Assuntos
Hospitais , Imobilização , Processo Odontoide/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Humanos , Complicações Pós-Operatórias/etiologia , Sobreviventes , Resultado do Tratamento
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