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1.
Probl Endokrinol (Mosk) ; 70(1): 100-104, 2024 Feb 28.
Artigo em Russo | MEDLINE | ID: mdl-38433546

RESUMO

The description of the child aged 5 months with the von Hippel-Lindau syndrome without any manifestations of this syndrome is presented. The reason for the molecular genetic examination was the presence of cases of this syndrome in the family (mother and sister). The heterozygous variant c.355T>C p.F119L was found in the VHL gene. An objective examination revealed no pathology. A comprehensive laboratory and instrumental examination aimed at searching for components of the von Hippel-Lindau syndrome, including a blood test for metanephrines and normetanephrines, ultrasound of the abdominal organs, examination of the fundus, also did not reveal any abnormalities. Given the results of molecular genetic diagnosis, the child remains under observation and will undergo regular examinations to identify components of the von Hippel-Lindau syndrome, including blood/urine tests for normetanephrines.


Assuntos
Doença de von Hippel-Lindau , Criança , Animais , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genética , Síndrome , Genes Reguladores , Abomaso , Fundo de Olho , Normetanefrina
2.
Clin Nucl Med ; 49(3): 289-291, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306383

RESUMO

ABSTRACT: Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.


Assuntos
Neoplasias Cerebelares , Radioisótopos de Flúor , Hemangioblastoma , Neoplasias Renais , Octreotida/análogos & derivados , Compostos Organometálicos , Doença de von Hippel-Lindau , Masculino , Humanos , Adulto , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico por imagem , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Renais/patologia
3.
Med Sci (Basel) ; 12(1)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38390862

RESUMO

Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances of RCC predisposition are attributed to the loss-of-function mutations in tumor suppressor genes, which drive the malignant progression via somatic inactivation of the remaining allele. These syndromes almost always have extrarenal manifestations, for example, von Hippel-Lindau (VHL) disease, fumarate hydratase tumor predisposition syndrome (FHTPS), Birt-Hogg-Dubé (BHD) syndrome, tuberous sclerosis (TS), etc. In contrast to the above conditions, hereditary papillary renal cell carcinoma syndrome (HPRCC) is caused by activating mutations in the MET oncogene and affects only the kidneys. Recent years have been characterized by remarkable progress in the development of targeted therapies for hereditary RCCs. The HIF2aplha inhibitor belzutifan demonstrated high clinical efficacy towards VHL-associated RCCs. mTOR downregulation provides significant benefits to patients with tuberous sclerosis. MET inhibitors hold promise for the treatment of HPRCC. Systematic gene sequencing studies have the potential to identify novel RCC-predisposing genes, especially when applied to yet unstudied populations.


Assuntos
Síndrome de Birt-Hogg-Dubé , Carcinoma de Células Renais , Neoplasias Renais , Síndromes Neoplásicas Hereditárias , Esclerose Tuberosa , Doença de von Hippel-Lindau , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Esclerose Tuberosa/genética , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Rim/patologia , Síndrome de Birt-Hogg-Dubé/genética , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/terapia
4.
Medicine (Baltimore) ; 103(6): e37162, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335432

RESUMO

RATIONALE: Hemangioblastomas occur both sporadically and as an important component of von Hippel-Lindau (VHL) disease. The typical MRI features of hemangioblastoma are cysts with enhanced cystic wall nodules in the cerebellum or lesions with uniform enhancement on the surface or inside the spinal cord. If there is edema around hemangioblastoma, it is easy to be misdiagnosed as brain metastasis on MRI. PATIENT CONCERNS: A 41-year-old male patient was found to have a lump in the pancreas during a health examination 3 months ago. Subsequently, the patient underwent surgical treatment. The postoperative pathology suggests that the pancreatic lesion is a neuroendocrine tumor. The patient subsequently came to our hospital for consultation on further treatment plans. Abnormal signals were found in the right cerebellum during pituitary magnetic resonance imaging (MRI) before the development of a treatment plan for neuroendocrine tumors. Subsequently, the patient underwent cerebellar mass resection surgery. The pathological result after the surgery was hemangioblastoma. DIAGNOSIS: The patient underwent surgery to remove the tumor and was diagnosed with hemangioblastoma by pathological examination. Subsequently, the patient's genetic testing results confirmed the diagnosis of VHL syndrome. INTERVENTIONS: The patient underwent cerebellar mass resection surgery. OUTCOMES: The patient recovered after surgical resection. LESSONS: In this report, we emphasize the atypical MRI manifestations of hemangioblastoma. For patients with VHL syndrome-related hemangioblastoma, genetic testing is necessary for the patient and their family members.


Assuntos
Neoplasias Cerebelares , Hemangioblastoma , Tumores Neuroendócrinos , Doença de von Hippel-Lindau , Adulto , Humanos , Masculino , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/cirurgia , Hemangioblastoma/diagnóstico por imagem , Hemangioblastoma/cirurgia , Imageamento por Ressonância Magnética , Tumores Neuroendócrinos/patologia , Medula Espinal/patologia , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/genética
5.
Orphanet J Rare Dis ; 19(1): 73, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365728

RESUMO

BACKGROUND: To date, real-world evidence around the clinical and economic burden related to von Hippel-Lindau (VHL) disease is limited. Therefore, this study characterized the prevalence, healthcare resource utilization (HRU), and economic burden of von Hippel-Lindau-associated central nervous system hemangioblastoma (VHL-CNS-Hb) and pancreatic neuroendocrine tumors (VHL-pNET) in the United States (US). METHODS: Patients with VHL-CNS-Hb or VHL-pNET were identified from Optum's de-identified Clinformatics® Data Mart Database (2007-2020) and matched 1:5 to control patients without VHL disease or CNS-Hb/pNET. Prevalence rates of VHL-CNS-Hb and VHL-pNET (standardized by age and sex) in 2019 were estimated. HRU and healthcare costs (2020 US dollars) were compared between the VHL-CNS-Hb/VHL-pNET and control cohorts. RESULTS: In 2019, US prevalence rates of VHL-CNS-Hb and VHL-pNET were estimated to be 1.12 cases per 100,000 (3,678 patients) and 0.12 cases per 100,000 (389 patients), respectively. Patients with VHL-CNS-Hb (N = 220) had more inpatient, outpatient, and emergency department visits and $49,645 higher annual healthcare costs than controls (N = 1,100). Patients with VHL-pNET (N = 20) had more inpatient and outpatient visits and $56,580 higher annual healthcare costs than controls (N = 100). Costs associated with surgical removal of CNS-Hb and pNET were particularly high. CONCLUSIONS: In this retrospective, claims-based study, both VHL-CNS-Hb and VHL-pNET were associated with substantial HRU and healthcare costs, particularly tumor reduction surgery-related costs. These findings provide important insight for healthcare payers regarding the expected real-world costs that enrollees with VHL-CNS-Hb and VHL-pNET may incur over the course of their disease.


Assuntos
Hemangioblastoma , Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Hemangioblastoma/epidemiologia , Estresse Financeiro , Estudos Retrospectivos , Sistema Nervoso Central/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia
6.
Transl Vis Sci Technol ; 13(2): 8, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345551

RESUMO

Purpose: To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting. Methods: We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods. The underlying causes for the lack of detection were investigated. Results: In 91 eyes (48 patients), 67 RHs were observed (mean, 0.74 ± 1.59 RH per eye). FA was performed in eight eyes. Ophthalmoscopy overlooked 25 of the 35 RHs detected by wOCTA (71.4%) due to the background color of the choroid (n = 5), small tumor size (n = 13), masking by a bright fundus reflex (n = 2), and masking by surrounding retinal scars (n = 5). However, wOCTA missed 29 RHs due to peripheral location (43.3%). The overall detection rates were up to 37% on the basis of ophthalmoscopy alone, up to 52% for wOCTA, and 89% for FA. Within the retinal area covered by wOCTA, the detection rates were up to 46.7% for ophthalmoscopy alone, up to 92.1% for wOCTA, and 73.3% for FA. Conclusions: The overall low detection rate of RHs using wOCTA is almost exclusively caused by its inability to visualize the entire peripheral retina. Therefore, in unclear cases, FA is necessary after ophthalmoscopy. Translational Relevance: Within the imageable retinal area, wOCTA shows a high detection rate of RHs and therefore may be suitable to improve screening for RHs in VHLD.


Assuntos
Hemangioblastoma , Neoplasias da Retina , Doença de von Hippel-Lindau , Humanos , Tomografia de Coerência Óptica/métodos , Doença de von Hippel-Lindau/diagnóstico por imagem , Hemangioblastoma/diagnóstico por imagem , Neoplasias da Retina/diagnóstico por imagem , Angiofluoresceinografia/métodos
7.
Int J Hyperthermia ; 41(1): 2308079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346873

RESUMO

BACKGROUND: The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear. OBJECTIVE: To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients. METHODS: Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented. RESULTS: A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively. CONCLUSION: Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Feminino , Adulto , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/cirurgia , Doença de von Hippel-Lindau/patologia , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia
8.
Biochem Biophys Res Commun ; 690: 149250, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039781

RESUMO

The von Hippel-Lindau protein (pVHL) is a tumor suppressor involved in oxygen regulation via dynamic nucleocytoplasmic shuttling. It plays a crucial role in cell survival by degrading hypoxia-inducible factors (HIFs). Mutations in the VHL gene cause angiogenic tumors, characterized as VHL syndrome. However, aggressive tumors involving wild-type pVHL have also been described but the underlying mechanism remains to be revealed. We have previously shown that pVHL possesses several short amyloid-forming motifs, making it aggregation-prone. In this study, using a series of biophysical assays, we demonstrated that a pVHL-derived fragment (pVHL104-140) that harbors the nuclear export motif and HIF binding site, forms amyloid-like fibrillar structures in vitro by following secondary-nucleation-based kinetics. The peptide also formed amyloids at acidic pH that mimics the tumor microenvironment. We, subsequently, validated the amyloid formation by pVHL in vitro. Using the Curli-dependent amyloid generator (C-DAG) expression system, we confirmed the amyloidogenesis of pVHL in bacterial cells. The pVHL amyloids are an attractive target for therapeutics of the VHL syndrome. Accordingly, we demonstrated in vitro that Purpurin is a potent inhibitor of pVHL fibrillation. The amyloidogenic behavior of wild-type pVHL and its inhibition provide novel insights into the molecular underpinning of the VHL syndrome and its possible treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Doença de von Hippel-Lindau/genética , Fatores de Transcrição/metabolismo , Carcinoma de Células Renais/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Genes Supressores de Tumor , Proteínas Amiloidogênicas/genética , Neoplasias Renais/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Microambiente Tumoral
9.
Semin Diagn Pathol ; 41(1): 20-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37980175

RESUMO

von Hippel-Lindau (VHL) disease is characterized by biallelic inactivation of the VHL gene leading to abnormal or absent VHL protein function, and constitutive activation of hypoxia-inducible factors (HIF) that leads to pro-tumorigenic signaling. Individuals with VHL disease develop numerous cysts and tumors involving multiple organs including the kidneys, central nervous system, endolymphatic sac, lungs, pancreatobiliary system, adrenal glands, epididymis, and/or broad ligament. On histologic examination, these lesions show morphologic overlap as they are frequently characterized by cells with clear cytoplasm and prominent vascularity. In addition to distinguishing non-renal tumors from metastatic clear cell renal cell carcinoma, understanding site-specific histopathologic and immunophenotypic features of these tumors has several applications. This includes distinguishing VHL-related tumors from those that arise sporadically and lack VHL gene alterations, guiding further genetic workup, and helping distinguish between different genetic predisposition syndromes. In this context, immunohistochemical studies for markers such as paired box 8 (PAX-8), carbonic anhydrase 9 (CA9), and glucose transporter 1 (GLUT-1) have an important role in routine clinical practice and represent cost-effective diagnostic tools. The recent development of targeted therapeutics directed against HIF-mediated signaling represents a significant milestone in the management of VHL disease and highlights the importance of accurately diagnosing and characterizing the wide spectrum of VHL disease-associated lesions.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Masculino , Feminino , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Rim/patologia
10.
Abdom Radiol (NY) ; 49(2): 542-550, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010527

RESUMO

OBJECTIVE: To determine the reliability of an MRI-based qualitative kidney imaging surveillance scoring system (KISSS) and assess which imaging features predict growth rate (GR) of renal tumors in patients with VHL. MATERIALS AND METHODS: We identified 55 patients with VHL with 128 renal tumors who underwent intervention from 2015 to 2020 at the National Cancer Institute. All patients had 2 preoperative MRIs at least 3 months apart. Two fellowship-trained radiologists scored each tumor on location and MR-sequence-specific imaging parameters from the earlier MRI. Weighted kappa was used to determine the degree of agreement between radiologists for each parameter. GR was calculated as the difference in maximum tumor dimension over time (cm/year). Differences in mean growth rate (MGR) within categories of each imaging variable were assessed by ANOVA. RESULTS: Apart from tumor margin and renal sinus, reliability was at least moderate (K > 0.40) for imaging parameters. Median initial tumor size was 2.1 cm, with average follow-up of 1.2 years. Tumor MGR was 0.42 cm/year. T2 hypointense, mixed/predominantly solid, and high restricted diffusion tumors grew faster. When comparing different combinations of these variables, the model with the lowest mean error among both radiologists utilized only solid/cystic and restricted diffusion features. CONCLUSIONS: We demonstrate a novel MR-based scoring system (KISSS) that has good precision with minimal training and can be applied to other qualitative radiology studies. A subset of imaging variables (T2 intensity; restricted diffusion; and solid/cystic) were independently associated with growth rate in VHL renal tumors, with the combination of the latter two most optimal. Additional validation, including in sporadic RCC population, is warranted.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Carcinoma de Células Renais/patologia , Reprodutibilidade dos Testes , Neoplasias Renais/patologia , Rim/diagnóstico por imagem , Rim/patologia , Imageamento por Ressonância Magnética , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico por imagem , Proteína Supressora de Tumor Von Hippel-Lindau
11.
Neurochirurgie ; 70(1): 101513, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37931654

RESUMO

BACKGROUND: Spinal hemangioblastomas (HBs) that involving cauda equina are rare. Data on clinical characteristics and long-term intervention outcomes of patients harboring cauda equina HBs remain lacking due to its scarcity. OBJECTIVE: This study aims to present the clinical-radiological features and treatment results of this rare pathology by using cases from a single center. METHODS: A review of demographic data and intervention outcomes of patients harboring cauda equina HBs in our department between 2009 and 2020 was retrospectively carried out. RESULTS: Ten consecutive adult patients were incorporated, with a slight female predominance (n = 6, 60%). The mean age was 39.9 ± 14.7 (range: 18-58) years. Six patients (60%) had von Hippel‒Lindau (VHL) syndrome and showed multiple symptoms and severe neurological deficits, while 4 (40%) were in the sporadic group and only presented pain symptoms. During follow-up, 3 patients (30%) experienced lesion relapse and underwent repeated surgery. Favorable outcomes were achieved in all patients. CONCLUSION: Cauda equina HBs are rare spinal vascular lesions that should be differentiated from other lumbar canal lesions. Total surgical resection is the main treatment modality and can benefit patients, even recurrent patients. The treatment outcome is usually satisfactory, especially in sporadic cases.


Assuntos
Cauda Equina , Hemangioblastoma , Neoplasias da Medula Espinal , Doença de von Hippel-Lindau , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cauda Equina/cirurgia , Cauda Equina/patologia , Hemangioblastoma/diagnóstico , Hemangioblastoma/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/patologia , Resultado do Tratamento , Adolescente , Adulto Jovem
12.
Hum Mol Genet ; 33(3): 224-232, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-37883464

RESUMO

BACKGROUND: Mutations within the Von Hippel-Lindau (VHL) tumor suppressor gene are known to cause VHL disease, which is characterized by the formation of cysts and tumors in multiple organs of the body, particularly clear cell renal cell carcinoma (ccRCC). A major challenge in clinical practice is determining tumor risk from a given mutation in the VHL gene. Previous efforts have been hindered by limited available clinical data and technological constraints. METHODS: To overcome this, we initially manually curated the largest set of clinically validated VHL mutations to date, enabling a robust assessment of existing predictive tools on an independent test set. Additionally, we comprehensively characterized the effects of mutations within VHL using in silico biophysical tools describing changes in protein stability, dynamics and affinity to binding partners to provide insights into the structure-phenotype relationship. These descriptive properties were used as molecular features for the construction of a machine learning model, designed to predict the risk of ccRCC development as a result of a VHL missense mutation. RESULTS: Analysis of our model showed an accuracy of 0.81 in the identification of ccRCC-causing missense mutations, and a Matthew's Correlation Coefficient of 0.44 on a non-redundant blind test, a significant improvement in comparison to the previous available approaches. CONCLUSION: This work highlights the power of using protein 3D structure to fully explore the range of molecular and functional consequences of genomic variants. We believe this optimized model will better enable its clinical implementation and assist guiding patient risk stratification and management.


Assuntos
Aprendizado de Máquina , Mutação de Sentido Incorreto , Doença de von Hippel-Lindau , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Mutação de Sentido Incorreto/genética , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/química , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
13.
Neurosurgery ; 94(3): 630-642, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37967154

RESUMO

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution. METHODS: We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line. RESULTS: At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection. CONCLUSION: SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.


Assuntos
Hemangioblastoma , Radiocirurgia , Neoplasias da Medula Espinal , Doença de von Hippel-Lindau , Humanos , Adulto , Hemangioblastoma/cirurgia , Hemangioblastoma/complicações , Hemangioblastoma/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/cirurgia , Resultado do Tratamento , Neoplasias da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/cirurgia , Seguimentos
14.
Magy Onkol ; 67(4): 279-287, 2023 Dec 18.
Artigo em Húngaro | MEDLINE | ID: mdl-38109507

RESUMO

The occurrence of central nervous system malignancies is relatively low; however, these tumors exhibit poor prognosis and a high mortality rate. On epidemiological grounds, Hungary was placed in the last third among European countries: in the last decade annually 750 to 1000 new cases were diagnosed and the number of deaths was between 550 and 690, without any apparent trends. Age distribution analyses revealed childhood peak and a higher peak at around 65 years of age. Histologically, heterogeneity was apparent, but at least half of the cases were glioblastomas. The exact etiology of adulthood brain tumors is mostly unknown. Among environmental exposures the effect of ionizing radiation was confirmed, the identification of other potential risk factors requires further examinations. 7-10 percent of brain tumors were hereditary tumor syndromes (Li-Fraumeni, neurofibromatosis, sclerosis tuberosa, von Hippel-Lindau, Gorlin- Goltz). Therefore, genetic testing is recommended for families where the diagnosis of brain tumor is suspected.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Síndromes Neoplásicas Hereditárias , Esclerose Tuberosa , Doença de von Hippel-Lindau , Humanos , Adulto , Criança , Idoso , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/epidemiologia , Doença de von Hippel-Lindau/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Esclerose Tuberosa/epidemiologia , Esclerose Tuberosa/patologia
15.
Saudi J Kidney Dis Transpl ; 34(2): 187-190, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38146729

RESUMO

Management of renal malignancies in Von Hippel-Lindau (VHL) is challenging. We present six patients [mean age = 35.1 years (range: 24-54), males = 5] with VHL syndrome with multiple bilateral renal malignancies and the lessons learned during their management. The number of tumors at the time of presentation ranged from 1 to 6, while the number of new lesions varied from 1 to 3. Different combinations of radical nephrectomy (n = 2), partial nephrectomy (n = 7), and focal therapy (n = 6) were used appropriately. Median follow-up was 36 months (range: 12-72). Two patients developed new lesions which were managed with focal therapy. Nephron-sparing approaches are successful even in bilateral, multifocal, large, and recurring renal tumors associated with VHL. Awareness about the availability of efficacious surgical and minimally invasive measures would reduce psychosocial problems faced by patients and their families due to the social stigma associated with malignancies running in a family and burden of renal replacement therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias da Próstata , Doença de von Hippel-Lindau , Masculino , Humanos , Adulto , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/cirurgia , Sri Lanka/epidemiologia , Recidiva Local de Neoplasia/complicações , Neoplasias Renais/cirurgia , Neoplasias Renais/complicações , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/complicações , Neoplasias da Próstata/complicações
16.
Probl Endokrinol (Mosk) ; 69(5): 39-44, 2023 Nov 11.
Artigo em Russo | MEDLINE | ID: mdl-37968950

RESUMO

This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The main component of preoperative preparation is the use of alpha-blockers. The need to prescribe them to all patients is increasingly disputed, especially for patients without severe hypertension. An increasing number of publications demonstrate positive results of treatment without the use of alpha-blockers, advocating an individual approach and the use of the drug according to certain indications. Minimally invasive endoscopic techniques of adrenalectomy have become widespread in surgical treatment. They are represented by laparoscopic and retroperitonescopic technic, including using their single-port modifications. The earliest possible intersection of the central vein in the past was considered the most important aspect of adrenalectomy for pheochromocytoma, currently, due to the development of surgical techniques and anesthesiological manuals, this has ceased to be a mandatory rule of successful surgery. Despite the significant influence of the intersection of this vessel on intraoperative hemodynamics, surgical tactics with its later intersection have their own justifications and do not lead to a deterioration in treatment results. The standard volume of surgical intervention for pheochromocytomas is total adrenalectomy, however, in the presence of hereditary syndromes, such as multiple endocrine neoplasia type 2 syndrome, neurofibomatosis type 1, von Hippel-Lindau syndrome, it is possible to perform cortical-sparing adrenalectomy.


Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasia Endócrina Múltipla Tipo 2a , Feocromocitoma , Doença de von Hippel-Lindau , Humanos , Feocromocitoma/cirurgia , Doença de von Hippel-Lindau/etiologia , Doença de von Hippel-Lindau/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasia Endócrina Múltipla Tipo 2a/etiologia , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Adrenalectomia/efeitos adversos , Adrenalectomia/métodos , Síndrome
17.
Obstet Gynecol Surv ; 78(10): 606-619, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37976316

RESUMO

Importance: Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population. Objective: This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient. Evidence Acquisition: A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms "pregnancy," "Sturge -Weber," "Neurofibromatosis Type 1," "neurofibromatosis type 2," "von Hippel Lindau," "Tuberous Sclerosis," "neurocutaneous disorder," "treatment," "congenital malformations," "neurodevelopmental defects," "miscarriage," "breastfeeding," "autoimmune," "pathophysiology," and "management." References of included articles were searched to identify any articles that may have been missed after the above method was used. Results: Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder. Conclusion and Relevance: Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients.


Assuntos
Síndromes Neurocutâneas , Neurofibromatose 1 , Esclerose Tuberosa , Doença de von Hippel-Lindau , Recém-Nascido , Humanos , Gravidez , Feminino , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/terapia , Síndromes Neurocutâneas/complicações , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico , Neurofibromatose 1/complicações
18.
J Neurooncol ; 165(2): 373-379, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37955759

RESUMO

PURPOSE: Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience. METHODS: We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD). RESULTS: Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10-17). Median follow up time was 15 months (range 10-24). An ORR of 71% was observed. The median TTR was 5 months (range: 1-10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3-4 CTCAE). CONCLUSION: Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.


Assuntos
Carcinoma de Células Renais , Neoplasias do Sistema Nervoso Central , Hemangioblastoma , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Hemangioblastoma/tratamento farmacológico , Hemangioblastoma/patologia , Estudos Retrospectivos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/tratamento farmacológico , Doença de von Hippel-Lindau/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Sistema Nervoso Central/patologia , Proteína Supressora de Tumor Von Hippel-Lindau
19.
Neurosurg Rev ; 46(1): 281, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37875641

RESUMO

Supratentorial hemangioblastomas are rare, vascular lesions. The presence of peri-tumoral cysts and edema has meaningful clinical, diagnostic and therapeutic implications. Nevertheless, the pathogenesis of both cyst and edema formation is not fully understood. This study sought to determine if the radiologic phenotype of supratentorial hemangioblastoma is affected by the different cerebral arterial circulations. Review of the English-language literature from 1973 to 2023 yielded 53 cases of parenchymal supratentorial hemangioblastomas eligible for analysis. Patients were divided by the vascular territorial distribution of the lesions: anterior circulation (n = 36) or posterior circulation (n = 17), and the groups were compared for demographic, clinical, radiologic and molecular variables. Univariate analyses yielded a significant difference between the groups in five variables. Cystic changes and "classic" radiological phenotype were associated with hemangioblastomas of the posterior circulation (OR = 0.19, p = 0.045 and OR = 0.287, p = 0.048, respectively), while female gender, significant peritumoral edema and purely solid phenotype were associated with hemangioblastomas of the anterior circulation (OR = 3.384, p = 0.045 and OR = 5.25, p = 0.05 and OR = 14.0, p = 0.015; respectively). On multivariate analysis, solid phenotype and female gender remained significantly associated with the anterior circulation (OR = 36.04, p = 0.014 and OR = 4.45, p = 0.045). The incidence of von-Hippel Lindau disease was higher in the anterior-circulation group. Cystic tumors were present in all females in the posterior-circulation group compared to 43.4% in the anterior-circulation group (OR = 20.714, 95% CI 1.061 to 404.122; p = 0.045). Based on historical cases of supratentorial hemangioblastoma, this study shows that different tumor phenotypes are associated with the different cerebral circulations. Gender was also associated with differences in tumor distribution and radiologic phenotype. These novel data may improve our understanding of unique vascular diseases of the central nervous system.


Assuntos
Cistos , Hemangioblastoma , Doença de von Hippel-Lindau , Humanos , Feminino , Hemangioblastoma/complicações , Doença de von Hippel-Lindau/complicações , Cistos/complicações , Cistos/patologia , Edema , Sistema Nervoso Central
20.
Clin Nucl Med ; 48(12): e600-e602, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37844561

RESUMO

ABSTRACT: We describe 18 F-PSMA-1007 PET/CT findings in case of von Hippel-Lindau syndrome with a cerebellar hemangioblastoma, 6 renal cell carcinomas in the bilateral kidneys, cystic lesions in the pancreas and left adrenal gland, and solid lesions in the bilateral epididymides. 18 F-PSMA-1007 PET/CT showed intense activity with SUV max of 111.3 of the cerebellar hemangioblastoma, variable activity with SUV max range of 6.4-37.6 of the renal cell carcinomas, and increased activity of the bilateral epididymal lesions (SUV max of 5.1 and 8.2 for the left and right epididymal lesions, respectively).


Assuntos
Carcinoma de Células Renais , Neoplasias Cerebelares , Hemangioblastoma , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hemangioblastoma/patologia
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