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• Intracranial hemangioblastoma embolization holds promising results. • Intraoperative blood loss was estimated as 464.29 ml (95% CI: 350.63 ml–614.8 ml). • Major complications occurred in 1% (95% CI: 0% to 3%) of patients. • Minor complications in 1% (95% CI: 0% to 4%) of patients. • Further research is needed to confirm its long-term effectiveness and safety. Hemangioblastomas (HBs) are highly vascular tumors linked to substantial morbidity and mortality. Recently, interventional neuroradiology has evolved rapidly, spurring interest in preoperative embolization as a possible HB treatment. This study evaluates the effectiveness and safety of preoperative embolization in managing HB. Adhering to PRISMA guidelines, this meta-analysis considered randomized and nonrandomized studies meeting specific criteria, encompassing intracranial HB and preoperative embolization. Primary outcomes were preoperative embolization efficacy and safety. Complications were classified as major (cerebellar ischemia, ischemic strokes, intratumoral hemorrhage, subarachnoid hemorrhage) and minor (transient nystagmus, slight facial nerve palsy, nausea, transient dysarthria, hemiparesis, hemisensory impairment, thrombotic complications, extravasation). Thirteen studies involving 166 patients with preoperative embolization before HB resection were included. Two studies using the Glasgow Outcome Scale (GOS) showed 5 patients with good recovery, 6 with moderate disability, and 3 with severe disability. Major complications occurred in 1% (95% CI: 0% to 3%), and minor complications occurred in 1% (95% CI: 0% to 4%). Intraoperative blood loss during resection was estimated at 464.29 ml (95% CI: 350.63 ml to 614.80 ml). Preoperative embolization holds promise in reducing intraoperative bleeding risk in neurosurgical intracranial HB treatment, primarily due to its low complication rates. Nonetheless, additional research and larger-scale studies are essential to establish its long-term efficacy and safety. These findings highlight preoperative embolization as a valuable tool for HB management, potentially enhancing future patient outcomes. [ABSTRACT FROM AUTHOR]

• Hemangioblastoma and radiosurgery. • Cystic Hemangioblastoma and radiosurgery. • Von hipple lindau and radiosurgery. Hemangioblastomas (HB) are benign low grade vascular tumors most frequently occurring in the cerebellum, brain stem, and spinal cord. Often associated with Von Hippel Lindau disease (VHL), the lesions are often multifocal requiring complex resection and are difficult to control. Linear Accelerator (LINAC) Stereotactic Radiosurgery (SRS) has been demonstrated to provide additional tumor control. In this case series, we present our multi-center experience utilizing LINAC SRS in fourteen patients with 23 lesions. We observed a tumor control rate of 87% and found interval changes in the peritumoral enhancement to correlate with treatment outcome. In our study, SRS treatment was also well-tolerated in both cystic and noncystic patients with multifocal disease. Disease control was achieved in all but three patients post-resection and no longitudinal radiation-induced secondary malignancy was observed. SRS response correlated highly with lesion size and radiation dose. We conclude that LINAC SRS is safe and effective for patients with HB and should be considered in addition to surgery in asymptomatic, VHL patients, deep seated lesions and isolated lesions. [ABSTRACT FROM AUTHOR]

Abstract Increasing data implicate iron accumulation in tumorigenesis of the kidney, particularly the clear cell renal cell carcinoma (ccRCC) subtype. The von Hippel Lindau (VHL)/hypoxia inducible factor-α (HIF-α) axis is uniquely dysregulated in ccRCC and is a major regulator and regulatory target of iron metabolism, yet the role of iron in ccRCC tumorigenesis and its potential interplay with VHL inactivation remains unclear. We investigated whether ccRCC iron accumulation occurs due to increased cell dependency on iron for growth and survival as a result of VHL inactivation. Free iron levels were compared between four VHL-mutant ccRCC cell lines (786-0, A704, 769-P, RCC4) and two benign renal tubule epithelial cell lines (RPTEC, HRCEp) using the Phen Green SK fluorescent iron stain. Intracellular iron deprivation was achieved using two clinical iron chelator drugs, deferasirox (DFX) and deferoxamine (DFO), and chelator effects were measured on cell line growth, cell cycle phase, apoptosis, HIF-1α and HIF-2α protein levels and HIF-α transcriptional activity based on expression of target genes CA9 , OCT4 / POU5F1 and PDGFβ/PDGFB. Similar assays were performed in VHL-mutant ccRCC cells with and without ectopic wild-type VHL expression. Baseline free iron levels were significantly higher in ccRCC cell lines than benign renal cell lines. DFX depleted cellular free iron more rapidly than DFO and led to greater growth suppression of ccRCC cell lines (>90% at ~30–150 µM) than benign renal cell lines (~10–50% at up to 250 µM). Similar growth responses were observed using DFO, with the exception that a prolonged treatment duration was necessary to deplete cellular iron adequately for differential growth suppression of the less susceptible A704 ccRCC cell line relative to benign renal cell lines. Apoptosis and G1-phase cell cycle arrest were identified as potential mechanisms of chelator growth suppression based on their induction in ccRCC cell lines but not benign renal cell lines. Iron chelation in ccRCC cells but not benign renal cells suppressed HIF-1α and HIF-2α protein levels and transcriptional activity, and the degree and timing of HIF-2α suppression correlated with the onset of apoptosis. Restoration of wild-type VHL function in ccRCC cells was sufficient to prevent chelator-induced apoptosis and G1 cell cycle arrest, indicating that ccRCC susceptibility to iron deprivation is VHL inactivation-dependent. In conclusion, ccRCC cells are characterized by high free iron levels and a cancer-specific dependency on iron for HIF-α overexpression, cell cycle progression and apoptotic escape. This iron dependency is introduced by VHL inactivation, revealing a novel interplay between VHL/HIF-α dysregulation and ccRCC iron metabolism. Future study is warranted to determine if iron deprivation using chelator drugs provides an effective therapeutic strategy for targeting HIF-2α and suppressing tumor progression in ccRCC patients. Graphical abstract fx1 Highlights • Free iron levels are elevated in clear cell renal cell carcinoma (ccRCC) cells. • ccRCC cells depend on iron to escape apoptosis and cell cycle arrest. • ccRCC cells depend on iron for HIF-2α protein overexpression and activity. • Clinical iron chelator drugs suppress HIF-2α activity and growth of ccRCC cells. • ccRCC iron dependency is mediated by von Hippel Lindau (VHL) gene inactivation. [ABSTRACT FROM AUTHOR]

Haemangioblastoma is a rare benign tumour which is known to occur in association with von Hippel Lindau disease in approximately 25% of cases. Occurrence outside the central nervous system is exceptionally rare. This is a case report of a sporadic renal haemangioblastoma occurring in a 32 year old woman. She presented with post-partum fatigue and was found to be polycythaemic with haemoglobin of 19.8 g/dl as well as hypothyroidism. Microscopically this was a highly vascular tumour consisting of densely packed capillary sized blood vessels. Between these were single rows and sheets of polygonal tumour cells with abundant eosinophilic cytoplasm. On immunohistochemistry the tumour cells were positive for S100, CD10, NSE and alpha inhibin and negative for CD34, HMB45, AE1/AE3, MNF116, CAM5.2, RCC, Chromogranin, CD117, synaptophysin, desmin, and melanA. This case also showed focal rhabdoid features and CD10 positivity described only in one other case report in the literature. The differential diagnosis is extensive and includes a variant of renal cell carcinoma, melanoma, paraganglioma, epithelioid leiomyosarcoma and epithelioid angiomyolipoma/PEComa. This is a rare tumour with pseudomalignant appearances and a potential diagnostic pitfall. We have included a literature review of other sporadic haemangioblastomas to characterise the typical immunological and morphological profile of sporadic haemangioblastomas occurring outside the central nervous system. Also of note is the clinical presentation with polycythaemia which has been documented with cases of cerebellar haemangioblastoma and is thought to be a secondary polycythaemia as a result of erythropoietin produced by stromal cells within the tumour. [ABSTRACT FROM AUTHOR]

Objective Clinical characteristics and management of hemangioblastomas of the spinal cord associated with von Hippel-Lindau syndrome have been extensively covered in the literature. This report aims to analyze the characteristics and surgical treatment results of sporadic spinal hemangioblastomas (SSHB). Methods This is a retrospective analysis of 14 patients with SSHB (8 men and 6 women) operated on during a span of 23 years. The median age was 41.5 years (24–70 years). von Hippel Lindau syndrome was excluded by imaging in all patients. The median follow-up was 4 years (1–23 years). We also conducted a meta-analysis of all 271 SSHB cases reported in the English-speaking language literature from 1967 to 2011. Results Nine (64.3%) lesions were cervical, 3 (28.5%) were thoracic, and 1 (7.1%) was lumbar. Eight (57.1%) tumors were dorsal intramedullary, 4 (28.6%) were exophytic, 1 (7.1%) was intradural extramedullary, and 1 (7.1%) was completely extradural. Diffuse segmental cord enlargement was present in 7 patients (50%) and a cyst/syrinx was present in 7 (50%). These 14 patients underwent 15 operations, and gross total resection was achieved in all operations. There was no mortality. Symptoms improved after 8 (53.3%) of 15 operations, remained the same after 5 (33.3%), and worsened after 2 (13.3%). The mean Karnofsky performance score improved from 79.3 (± 17.5) to 87.3 (± 12.2) after 6 months of follow-up. There was one recurrence 15 years after magnetic resonance imaging confirmed total resection. Conclusions The SSHBs occur most often in the upper spinal cord. Excellent surgical results and long-term outcome can be achieved using microsurgery alone with only rare recurrences. [ABSTRACT FROM AUTHOR]

Abstract: Management of pediatric patients with pheochromocytomas associated with genetic syndromes, such as Von Hippel-Lindau (VHL) disease, is complex owing to the need for continuous surveillance, high rates of recurrence, multiple operations during childhood, and the possibility of lifelong exogenous steroid replacement. We report the successful treatment of two siblings with VHL who underwent a total of six cortical-sparing procedures without requiring steroid therapy. [Copyright &y& Elsevier]

Gastric bypass and vertical sleeve gastrectomy (VSG) remain the most potent and durable treatments for obesity and type 2 diabetes but are also associated with iron deficiency. The transcription factor HIF2α, which regulates iron absorption in the duodenum, increases following these surgeries. Increasing iron levels by means of dietary supplementation or hepatic hepcidin knockdown does not undermine the effects of VSG, indicating that metabolic improvements following VSG are not secondary to lower iron levels. Gut-specific deletion of Vhl results in increased constitutive duodenal HIF2α signaling and produces a profound lean, glucose-tolerant phenotype that mimics key effects of VSG. Interestingly, intestinal Vhl deletion also results in increased intestinal secretion of GLP-1, which is essential for these metabolic benefits. These data demonstrate a role for increased duodenal HIF2α signaling in regulating crosstalk between iron-regulatory systems and other aspects of systemic physiology important for metabolic regulation. [Display omitted] • Bariatric surgeries result in reduced iron despite upregulation of absorption pathways • Dietary or genetic manipulation to increase iron does not affect VSG effectiveness • Genetic activation of intestinal HIF2α results in improved body fat glucose tolerance • Intestinal HIF2α activation increases GLP-1 secretion, which mediates effects Bariatric surgery remains the most potent treatment for obesity and type 2 diabetes but also reduces iron levels. Evers et al. find that the machinery for absorbing iron is activated after VSG. Activation of this machinery recapitulates multiple effects of VSG. These findings may lead to less invasive therapies. [ABSTRACT FROM AUTHOR]

Abstract: Herein, we review the associations between the kidney, renal cancers, and the eye. Renal cancers have been reported to metastasize to the eye and the orbit. As these tumors can be confused with other amelanotic or vascular tumors, a high index of suspicion is required for early detection and management of the primary tumor. We discuss the physiology of metastases, clinical features and management of metastatic disease. A variety of ocular anomalies have been associated with renal disease. Wilms tumor, a renal tumor of childhood, can present with aniridia, which may be the first clue leading to the diagnosis of the primary tumor. Paraneoplastic syndromes are common manifestations of renal cancers and can present as retinopathies and neuro-ophthalmic disorders. Multiple cancer syndromes involve both the eye and the kidney. For example, the diagnosis of von Hippel retinal tumors can lead to a systemic evaluation and discovery of associated visceral tumors. The prognosis, screening, and counseling of such patients is discussed. Newer systemic treatments available for renal tumors, such as interferon alfa, may lead to ocular side effects including retinopathy. These patients require periodic ophthalmic examinations. This review demonstrates the essential role of the ophthalmologist, for early diagnosis and treatment that can help reduce the morbidity and mortality associated with kidney tumors and renal-associated disease. [Copyright &y& Elsevier]

This survey reviews selected medical disorders in which the ophthalmologist has a unique opportunity of anticipating the existence of asymptomatic, life-threatening disease simply by recognizing that certain benign conditions involving the eye or adnexa represent clues to occult non-ocular cancer and other neoplasias. Having knowledge that these clues are associated with specific types of neoplasia, the ophthalmologist can then initiate a goal-directed oncologic investigation designed to identify the underlying neoplasm with the hope of providing potentially life-saving therapy. The survey is organized to feature each clue separately. The clinical characteristics of the clue are described and illustrated with color photographs when possible. A discussion reviews associated malignancies and other important medical features. The survey begins with clues expressed anteriorly in the lids, progressively reviewing those clues located more posteriorly, concluding with clues involving the retinal pigment epithelium and choroid. [Copyright &y& Elsevier]

Renal cell carcinoma incidence is rising worldwide with increasing subtype stratification by the World Health Organization. Each subtype has unique genetic alterations, cell biology changes and clinical findings. Such genetic alterations offer the potential for individualized therapeutic approaches that are rapidly progressing. This review highlights the most common subtypes of renal cell carcinoma, including both hereditary and sporadic forms, with a focus on genetic changes, clinical findings and ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Patients with a confirmed germline mutation in the von Hippel-Lindau (VHL) tumor suppressor gene have been followed at the National Cancer Institute since the 1980s. In this study, we identify VHL patients with pheochromocytoma and long-term follow-up to determine the best candidates for active surveillance and surgical resection.Methods: A prospectively collected database of patients with a confirmed germline VHL mutation was reviewed to identify patients with a history of pheochromocytoma and at least 10 years of follow up. The presence of symptoms was assessed at the time of resection. Imaging data obtained at each clinic visit was reviewed to evaluate mass size and annual growth rate. Catecholamine data were reviewed to evaluate for data above the upper limit of the reference range. Masses that underwent imaging at least 3 months apart were considered in our surveillance cohort.Results: Median follow up was 16.7 years. There was a size-dependent increase in catecholamine production (P<0.05). For 36 masses on active surveillance, growth rate increased exponentially from 0.03 cm/y when masses were <1 cm to 0.32 cm/y when masses were greater than 2 cm. Approximately 1/3 of patients developed another pheochromocytoma after initial resection with a median time of 7.9 years. Partial adrenalectomy was associated with no metastatic events and a steroid-free rate of 97%.Conclusion: Active surveillance is a safe strategy for management of VHL associated pheochromocytoma in masses less than 2 cm. [ABSTRACT FROM AUTHOR]