RESUMO
OBJECTIVE: Intraventricular metastatic brain tumors account for a small, but challenging, fraction of metastatic brain tumors (0.9%-4.5%). Metastases from renal cell carcinoma (RCC) account for a large portion of these intraventricular tumors. Although patient outcomes have been assumed to be poor, these have not been reported in a modern series with a multimodality treatment paradigm of radiotherapy (RT), resection, and cerebrospinal fluid (CSF) diversion. We have presented the first case series of patients with intraventricular metastatic tumors from RCC. METHODS: We performed a single-institution retrospective review of patients with intraventricular RCC metastases treated from January 2003 to January 2019. Volumetric analysis was used to delineate the tumor size and the Kaplan-Meier method to evaluate the survival data. RESULTS: A total of 22 intraventricular RCC metastases were identified in 19 patients with 61.3 patient-years of follow-up. The median patient age was 64 years, and the median tumor volume was 2.2 cm3. Overall, 19 metastases had been treated initially with RT. Of these, 16 had received stereotactic body RT and 3 had received whole brain RT. Three tumors were surgically excised and had received adjuvant stereotactic body RT in the upfront setting. Although 5 patients had presented with obstructive hydrocephalus, none had required CSF diversion. After treatment, 5 metastases had progressed, resulting in 1- and 3-year progression-free survival rates of 81.6% and 68%, respectively. The median overall survival was 2.8 years, with 1- and 5-year overall survival rates of 76.7% and 28.3%, respectively. Leptomeningeal carcinomatosis was not observed. CONCLUSIONS: Despite the relatively limited overall survival for this population with metastatic cancer, comparable to contemporary parenchymal brain metastasis cohorts, reasonable local central nervous system control was achieved in most patients using a paradigm of focal RT and resection, where indicated. Finally, CSF diversion was not required even in patients presenting with hydrocephalus.
Assuntos
Carcinoma de Células Renais/terapia , Neoplasias do Plexo Corióideo/secundário , Neoplasias do Plexo Corióideo/terapia , Neoplasias Renais/terapia , Procedimentos Neurocirúrgicos/tendências , Radiocirurgia/tendências , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/mortalidade , Neoplasias do Plexo Corióideo/diagnóstico por imagem , Neoplasias do Plexo Corióideo/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Pituitary apoplexy is an uncommon neurosurgical emergency that may be the initial presentation of undiagnosed pituitary adenomas. Though the exact pathogenesis is unclear, there appears to be an association between pituitary apoplexy and medical interventions that disturb the blood supply and venous drainage of the abnormal sellar region. We present the first case of pituitary apoplexy occurring after an endoscopic retrograde cholangiopancreatography (ERCP). CASE DESCRIPTION: A 43-year-old male who was several hours status post ERCP presented with a severe headache, bilateral ptosis, and multidirectional ophthalmoplegia. Computed tomography scan and magnetic resonance imaging of the brain revealed a hemorrhagic and necrotic sellar mass with suprasellar extension compressing the optic chiasm and bilateral extension displacing the cavernous carotid arteries laterally. The patient underwent emergent endoscopic endonasal transsphenoidal resection of the underlying pituitary tumor apoplexy with eventual resolution of his cranial nerve palsies. CONCLUSIONS: Although pituitary apoplexy has been recognized as a sequela of surgical and laparoscopic procedures, it should also be considered in less invasive gastrointestinal procedures which may alter the intraabdominal pressures, such as ERCP. Early detection of this unusual complication allows for rapid diagnosis and timely surgical intervention in select cases to prevent debilitating cranial nerve palsies, preserve visual function, and retain normal pituitary function.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Apoplexia Hipofisária/etiologia , Complicações Pós-Operatórias , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Apoplexia Hipofisária/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagemRESUMO
CONTEXT: Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly. OBJECTIVE: The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin. DESIGN: Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery. SETTING: The study was conducted at tertiary referral centers for pituitary tumors. MAIN OUTCOME MEASURES: Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured. RESULTS: Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment score, triglycerides, and lipoprotein (a) by 6 months and for 32 ± 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin. CONCLUSIONS: Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and long-term implications of the changes that accompany treatment of acromegaly is important to optimizing management because some aspects of the postoperative profile associate with the increased metabolic and CV risk in other populations.
Assuntos
Acromegalia/cirurgia , Adiposidade/fisiologia , Peso Corporal/fisiologia , Doenças Cardiovasculares/etiologia , Grelina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/complicações , Acromegalia/metabolismo , Adenoma/complicações , Adenoma/metabolismo , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/metabolismo , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Estudos Prospectivos , Risco , Resultado do Tratamento , Circunferência da Cintura/fisiologia , Adulto JovemRESUMO
Molecular subtypes of glioblastoma (GBM) with distinct alterations have been identified. There is need for reproducible, versatile preclinical models that resemble specific GBM phenotypes to facilitate preclinical testing of novel therapies. We present a cell line-based murine proneural GBM model and characterize its response to radiation therapy. Proneural gliomas were generated by injecting PDGF-IRES-Cre retrovirus into the subcortical white matter of adult mice that harbor floxed tumor suppressors (Pten and p53) and stop-floxed reporters. Primary cell cultures were generated from the retrovirus induced tumors and maintained in vitro for multiple passages. RNA sequencing-based expression profiling of the resulting cell lines was performed. The tumorigenic potential of the cells was assessed by intracranial injection into adult naïve mice from different strains. Tumor growth was assessed by bioluminescence imaging (BLI). BLI for tumor cells and brain slices were obtained and compared to in vivo BLI. Response to whole-brain radiation was assessed in glioma-bearing animals. Intracranial injection of Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) glioma cells led to formation of GBM-like tumors with 100 % efficiency (n = 48) and tumorigenesis was retained for more than 3 generations. The cell lines specifically resembled proneural GBM based on expression profiling by RNA-Seq. Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) cell number correlated with BLI signal. Serial BLI measured tumor growth and correlated with size and location by ex vivo imaging. Moreover, BLI predicted tumor-related mortality with a 93 % risk of death within 5 days following a BLI signal between 1 × 10(8) and 5 × 10(8) photons/s cm(2). BLI signal had transient but significant response following radiotherapy, which corresponded to a modest survival benefit for radiated mice (p < 0.05). Intracranial injection of Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) cells constitutes a novel and highly reproducible model, recapitulating key features of human proneural GBM, and can be used to evaluate tumor-growth and response to therapy.
Assuntos
Neoplasias Encefálicas , Modelos Animais de Doenças , Glioma , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Genes Supressores de Tumor , Glioma/genética , Glioma/patologia , Glioma/radioterapia , Camundongos , Camundongos Knockout , Transplante de Neoplasias , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/genética , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVES: Recent preclinical studies suggest that treating glioblastoma (GBM) with a combination of targeted chemotherapy and radiotherapy may enhance the anti-tumor effects of both therapies. However, the effects of these treatments on glioma growth and progression are poorly understood. METHODS: In this study, we have tested the effects of combination therapy in a mouse glioma model that utilizes a PDGF-IRES-Cre-expressing retrovirus to infect adult glial progenitors in mice carrying conditional deletions of Pten and p53. This model produces tumors with the histological features of GBM with 100% penetrance, making it a powerful system to test novel treatments. Sunitinib is an orally active, small molecule inhibitor of multiple receptor tyrosine kinases critical for tumor growth and angiogenesis, including PDGF receptors. We investigate the addition of Sunitinib to radiotherapy, and use bioluminescence imaging to characterize the effects of treatment on glioma growth and progression. RESULTS: Treating our PDGF-driven mouse model with either Sunitinib or high-dose radiation alone delayed tumor growth and had a modest but significant effect on survival, while treating with low-dose radiation alone failed to control glioma growth and progression. The addition of Sunitinib to low-dose radiation caused a modest, but significant delay in tumor growth. However, no significant survival benefit was seen as tumors progressed in 100% of animals. Histological analysis revealed a reduction in vascular proliferation and a marked increase in brain invasion. An additional study combining Sunitinib with high-dose radiation revealed a fatal toxicity despite individual monotherapies being well tolerated. DISCUSSION: These results show that the addition of Sunitinib to radiotherapy fails to significantly alter survival in GBM despite enhancement of the effects of radiation. Furthermore, an enhanced risk of toxicity associated with combined therapy must be considered in the design of future clinical studies.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Indóis/administração & dosagem , Pirróis/administração & dosagem , Animais , Neoplasias Encefálicas/patologia , Quimiorradioterapia , Terapia Combinada , Modelos Animais de Doenças , Progressão da Doença , Glioblastoma/patologia , Camundongos , Camundongos Transgênicos , Doses de Radiação , SunitinibeRESUMO
BACKGROUND: Ventriculostomy-related infection (VRI) is a severe complication of external ventricular drain use, occurring in 5% to 23% of patients. Preventive measures for VRI include prolonged prophylactic systemic antibiotics (PSAs) and an antibiotic-coated external ventricular drains (ac-EVDs). OBJECTIVE: We performed a systematic review of all studies evaluating PSAs and ac-EVD for VRI prevention through July 2010. METHODS: Two reviewers independently assessed eligibility and evaluated study quality based on pre-established criteria. Observational studies and randomized clinical trials (RCTs) that fulfilled inclusion criteria were included in the meta-analysis. RESULTS: Three RCTs and 7 observational studies met our inclusion criteria and were included in the analysis. The type of antibiotics and VRI definitions varied among these studies. Pooled analysis showed a protective effect of PSAs and ac-EVDs for VRI (risk ratio: 0.32; 95% CI: 0.18-0.56). Results showed moderate heterogeneity (I(2) = 53%) explained by the difference in quality among the studies and the inclusion of 1 large positive cohort study. The effect of PSAs and ac-EVDs was unrelated to the type of study (RCT or observational, P for interaction = .55), the route of antibiotic administration (PSAs or ac-EVDs, P = .13), or the quality of the studies (suboptimal vs good/excellent, P = .55). CONCLUSION: RCTs and observational-derived evidence support the use of PSAs throughout the duration of external ventricular drainage; similarly, the use of ac-EVDs to prevent VRI seems to be beneficial. Available data are heterogeneous and of suboptimal quality. Further research is needed to confirm the findings of this meta-analysis. There are not sufficient data to compare the protective effect of ac-EVDs and PSAs.