Gabriel Zada

Keck School of Medicine USC, Los Angeles, California, United States

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Publications (81)186.72 Total impact

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    ABSTRACT: A 38-year-old female with metastatic brain cancer developed non-enhancing, diffusion restricted lesions following bevacizumab treatment. From our review of the literature, this is the first reported case of this type of lesion. Clinicians should be wary of these lesions, as they can represent either tumor progression or necrosis/effects of chronic hypoxia from anti-angiogenic therapy. Further investigation is necessary to determine the biological mechanism and clinical significance of this type of imaging appearance.
    Clinical imaging. 05/2014;
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    ABSTRACT: The intranasal route for drug delivery is rapidly evolving as a viable means for treating selected central nervous system (CNS) conditions. We aimed to identify studies pertaining to the application of intranasal drug administration for the treatment of primary CNS tumors. A systematic literature review was conducted to identify all studies published in the English language pertaining to intranasal therapy for CNS neoplasms, and/or general mechanisms and pharmacokinetics regarding targeted intranasal CNS drug delivery. A total of 194 abstracts were identified and screened. Thirty-seven studies met inclusion criteria. Of these, 21 focused on intranasal treatment of specific primary CNS tumors, including gliomas (11), meningiomas (1), and pituitary adenomas (4). An additional 16 studies focused on general mechanisms of intranasal therapy and drug delivery to the CNS using copolymer micelles, viral vectors, and nanoparticles. Inhaled compounds/substances investigated included perillyl alcohol, vesicular stomatitis virus, parvovirus, telomerase inhibitors, neural stem and progenitor cells, antimetabolites, somatostatin analogues, and dopamine agonists. Radiolabeling, CSF concentration measurement, imaging studies, and histological examination were utilized to clarify the mechanism and distribution by which drugs were delivered to the CNS. Successful drug delivery and tumor/symptom response was reported in all 21 tumor-specific studies. The intranasal route holds tremendous potential as a viable option for drug delivery for CNS neoplasms. A variety of antitumoral agents may be delivered via this route, thereby potentially offering a more direct delivery approach and ameliorating the adverse effects associated with systemic drug delivery.
    Journal of Neuro-Oncology 01/2014; · 3.12 Impact Factor
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    ABSTRACT: Pituitary adenomas (PAs) are neoplasms that may cause a variety of neurological and endocrine effects. Although known causal contributors include heredity, hormonal influence and somatic mutations, the pathophysiologic mechanisms driving tumorigenesis and invasion of sporadic PAs remain unknown. We hypothesized that alterations in DNA methylation are associated with PA invasion and histopathology subtype, and that genome-scale methylation analysis may complement current classification methods for sporadic PAs. Twenty-four surgically-resected sporadic PAs with varying histopathological subtypes were assigned dichotomized Knosp invasion scores and examined using genome-wide DNA methylation profiling and RNA sequencing. PA samples clustered into subgroups according to functional status. Compared with hormonally-active PAs, nonfunctional PAs exhibited global DNA hypermethylation (mean beta-value 0.47 versus 0.42, P = 0.005); the most significant site of differential DNA methylation was within the promoter region of the potassium voltage-gated channel KCNAB2 (FDR = 5.11×10-10). Pathway analysis of promoter-associated CpGs showed that nonfunctional PAs are potentially associated with the ion-channel activity signal pathway. DNA hypermethylation tended to be negatively correlated with gene expression. DNA methylation analysis may be used to identify candidate genes involved in PA function and may potentially complement current standard immunostaining classification in sporadic PAs. DNA hypermethylation of KCNAB2 and downstream ion-channel activity signal pathways may contribute to the endocrine-inactive status of nonfunctional PAs.
    PLoS ONE 01/2014; 9(4):e96178. · 3.73 Impact Factor
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    ABSTRACT: Object Meningiomas are among the most common primary adult brain tumors. Although typically benign, roughly 2%-5% display malignant pathological features. The key molecular pathways involved in malignant transformation remain to be determined. Methods Illumina expression microarrays were used to assess gene expression levels, and Illumina single-nucleotide polymorphism arrays were used to identify copy number variants in benign, atypical, and malignant meningiomas (19 tumors, including 4 malignant ones). The authors also reanalyzed 2 expression data sets generated on Affymetrix microarrays (n = 68, including 6 malignant ones; n = 56, including 3 malignant ones). A weighted gene coexpression network approach was used to identify coexpression modules associated with malignancy. Results At the genomic level, malignant meningiomas had more chromosomal losses than atypical and benign meningiomas, with average length of 528, 203, and 34 megabases, respectively. Monosomic loss of chromosome 22 was confirmed to be one of the primary chromosomal level abnormalities in all subtypes of meningiomas. At the transcriptome level, the authors identified 23 coexpression modules from the weighted gene coexpression network. Gene functional enrichment analysis highlighted a module with 356 genes that was highly related to tumorigenesis. Four intramodular hubs within the module (GAB2, KLF2, ID1, and CTF1) were oncogenic in other cancers such as leukemia. A putative meningioma tumor suppressor MN1 was also identified in this module with differential expression between malignant and benign meningiomas. Conclusions The authors' genomic and transcriptome analysis of meningiomas provides novel insights into the molecular pathways involved in malignant transformation of meningiomas, with implications for molecular heterogeneity of the disease.
    Neurosurgical FOCUS 12/2013; 35(6):E3. · 2.49 Impact Factor
  • Alan A Moazzam, Naveed Wagle, Gabriel Zada
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    ABSTRACT: Object Currently, few medical options exist for refractory and atypical/anaplastic meningiomas. New developments in chemotherapeutic options for meningiomas have been explored over the past decade. The authors review these recent developments, with an emphasis on emerging avenues for therapy, clinical efficacy, and adverse effects. Methods A review of the literature was performed to identify any studies exploring recent medical and chemotherapeutic agents that have been or are currently being tested for meningiomas. Results from included preclinical and human clinical trials were reviewed and summarized. Results Current guidelines recommend only 3 drugs that can be used to treat patients with refractory and highgrade meningiomas: hydroxyurea, interferon-α 2B, and Sandostatin long-acting release. Recent developments in the medical treatment of meningiomas have been made across a variety of pharmacological classes, including cytotoxic agents, hormonal agents, immunomodulators, and targeted agents toward a variety of growth factors and their signaling cascades. Promising avenues of therapy that are being evaluated for efficacy and safety include antagonists of platelet-derived growth factor receptor, epidermal growth factor receptor, vascular endothelial growth factor receptor, and mammalian target of rapamycin. Because malignant transformation in meningiomas is likely to be mediated by numerous processes interacting via a complex matrix of signals, combination therapies affecting multiple molecular targets are currently being explored and hold significant promise as adjuvant therapy options. Conclusions Improved understanding of the molecular mechanisms driving meningioma tumorigenesis and malignant transformation has resulted in the targeted development of more specific agents for chemotherapeutic intervention in patients with nonresectable, aggressive, and malignant meningiomas.
    Neurosurgical FOCUS 12/2013; 35(6):E18. · 2.49 Impact Factor
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    ABSTRACT: Object A more comprehensive understanding of the epigenetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide useful targets for molecular classification and development of targeted therapies for meningiomas. Methods The authors performed a review of the current literature to identify the epigenetic modifications associated with the formation and/or progression of meningiomas. Results Several epigenomic alterations, mainly pertaining to DNA methylation, have been associated with meningiomas. Hypermethylation of TIMP3 inactivates its tumor suppression activity while CDKN2 (p14[ARF]) and TP73 gene hypermethylation and HIST1H1c upregulation interact with the p53 regulation of cell cycle control. Other factors such as HOX, IGF, WNK2, and TGF-β epigenetic modifications allow either upregulation or downregulation of critical pathways for meningioma development, progression, and recurrence. Conclusions Genome-wide methylation profiling demonstrated that global hypomethylation correlates with tumor grades and severity. Identification of additional epigenetic changes, such as histone modification and higher-order chromosomal structure, may allow for a more thorough understanding of tumorigenesis and enable future individualized treatment strategies for meningiomas.
    Neurosurgical FOCUS 12/2013; 35(6):E5. · 2.49 Impact Factor
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    ABSTRACT: Object Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as "hard" or "soft," no objective criteria exist for grading, studying, and conveying the consistency of meningiomas. Methods The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability. Results Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency grade was 0.87 (SE 0.06, 95% CI 0.76-0.99), with 90% user agreement. Kappa analysis scores for minimum and maximum grades of tumor regions were 0.69 (agreement 72%) and 0.75 (agreement 78%), respectively. The kappa analysis score for tumor vascularity grading was 0.56 (agreement 76%). Overall consistency did not correlate with patient age, tumor location, or tumor size. A higher tumor vascularity grade was associated with a larger tumor diameter (p = 0.045) and with skull base location (p = 0.02). Conclusions The proposed grading system provides a reliable, practical, and objective assessment of meningioma consistency and facilitates communication among providers. This system also accounts for heterogeneity in tumor consistency. With the proposed scale, meningioma consistency can be standardized as groundwork for future studies relating to surgical outcomes, predictability of consistency and vascularity using neuroimaging techniques, and effectiveness of various surgical instruments.
    Neurosurgical FOCUS 12/2013; 35(6):E1. · 2.49 Impact Factor
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    ABSTRACT: Background:Meningiomas are the most common primary intracranial tumours, with ∼3% meeting current histopathologic criteria for malignancy.Methods:In this study, we explored the transcriptome of meningiomas using RNA-Seq.Results:Inversion-mediated fusions between two adjacent genes, NAB2 and STAT6, were detected in one malignant tumour, creating two novel in-frame transcripts that were validated by RT-PCR and Sanger sequencing.Conclusion:Gene fusions of NAB2-STAT6 were recently implicated in the pathogenesis of solitary fibrous tumours; our study suggested that similar fusions may also have a role in a malignant meningioma with unusual histopathologic features.British Journal of Cancer advance online publication, 16 July 2013; doi:10.1038/bjc.2013.395 www.bjcancer.com.
    British Journal of Cancer 07/2013; · 5.08 Impact Factor
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    ABSTRACT: Over the last decade, endoscopic intraventricular and skull base operations have become widely used for a variety of evolving indications. The authors performed a global survey of practicing endoscopic neurosurgeons to characterize patters of usage regarding endoscopy equipment, instrumentation, and the indications for using image-guided surgery systems (IGSS). An online survey consisting of 8 questions was completed by 235 neurosurgeons with endoscopic surgical experience. Responses were entered into a database and subsequently analyzed. The median number of operations performed per year by intraventricular and skull base endoscopic surgeons was 27 and 25, respectively. Data regarding endoscopic equipment brand, diameter, and length are presented. The most commonly reported indications for IGSS during intraventricular endoscopic surgery were: tumor biopsy/resection, intraventricular cyst fenestration, septostomy/pellucidotomy, endoscopic third ventriculostomy (ETV), and aqueductal stent placement. Intraventricular surgeons reported using IGSS for all cases in 16.6% and never in 24.4%. Overall, endoscopic skull base surgeons reported using IGSS for all cases in 23.9% and never in 18.9%. The most commonly reported indications for IGSS during endoscopic skull base operations were: complex sinus/skull base anatomy, extended approaches, and reoperation. Many variations and permutations for performing intraventricular and skull base endoscopic surgery exist worldwide. Much can be learned by studying the patterns and indications for using various types of equipment and operative adjuncts such as IGSS.
    World Neurosurgery 07/2013; · 1.77 Impact Factor
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    ABSTRACT: Background Bioabsorbable plates are frequently utilized in the repair of skull base defects following transsphenoidal operations. Traumatic intracranial pseudoaneurysms are a rare complication of transsphenoidal surgery. To date, iatrogenic carotid pseudoaneurysm associated with the use of an absorbable plate has been reported once. Results A 57-year-old man with a large nonfunctional pituitary macroadenoma underwent an endoscopic transsphenoidal operation with gross total resection. An absorbable plate was placed extradurally to reconstruct the sellar floor. He experienced delayed repeated epistaxis, followed by a right middle cerebral artery distribution embolic stroke. Computed tomorgraphy (CT) angiogram 6 weeks postoperatively revealed a 6 × 4 mm pseudoaneurysm located on the medial wall of the right cavernous internal carotid artery. Stent coiling was used to successfully obliterate the pseudoaneurysm, and the patient fully recovered. Conclusion Delayed erosion of the carotid artery wall caused by a plate used to reconstruct the sellar floor may manifest with epistaxis or embolic stroke. The authors' preference is to avoid insertion of a rigid plate for sellar floor reconstruction in the absence of intraoperative cerebrospinal fluid (CSF) leaks, unless it is required to buttress a large skull base defect. Short-segment embolization with stent coiling is the preferred treatment option for carotid pseudoaneurysms following transsphenoidal operations.
    Journal of neurological surgery reports. 06/2013; 74(1):10-6.
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    ABSTRACT: Background Oculorrhea, or cerebrospinal fluid leakage developing from a cranio-orbital fistula, is a rare development following traumatic injury. Case Report A 22-year-old man involved in a motor vehicle accident developed a blowout fracture of the left orbital roof penetrating the frontal lobe, inducing oculorrhea. He underwent a supraorbital craniotomy for removal of the bony fragment and skull base reconstruction using a pericranial flap. Methods A systematic review of the database was performed to identify all prior cases of traumatic oculorrhea. Results Twenty-two reported cases met inclusion criteria for subsequent analysis. Oculorrhea developed due to blunt and penetrating head injury in 14 (64%) and 8 patients (36%), respectively. The most common mechanisms were car accidents, stab wounds, falls, and gunshot wounds. Ocular signs and symptoms-including visual loss, ophthalmoplegia, and pupillary dysfunction-were commonly associated findings. Initial conservative management was successful in four patients. Thirteen patients underwent initial surgical intervention, and three additional patients required operative intervention following failed conservative treatment. Conclusion Although oculorrhea rarely develops following severe orbital trauma, suspicion should nevertheless be maintained to facilitate more prompt diagnosis and management. The decision for conservative versus surgical management often depends on the severity of the fracture and dural injury.
    Journal of neurological surgery reports. 06/2013; 74(1):57-66.
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    ABSTRACT: OBJECTIVE: Intracranial epidermoid tumors are epithelially derived lesions that may present particular challenges to neurosurgeons, often encasing critical neurovascular structures and extending into multiple subarachnoid cisterns. We aimed to evaluate our recent experience with endoscopic assistance to craniotomy with microsurgical resection of these lesions. METHODS: A retrospective review of patients undergoing endoscopic-assisted craniotomy for resection of an epidermoid tumor at the Keck School of Medicine of USC between 2009-2012 was conducted. In all patients, the surgical approach and tumor resection were first performed microscopically. This was followed by use of an angled endoscope to facilitate further inspection and additional resection of tumor using a two-surgeon technique. RESULTS: Twelve patients undergoing 13 consecutive endoscopic-assisted craniotomies were included in the analysis. The mean patient age was 45 years. The mean maximal tumor diameter was 4.0 cm (range 2.4-5.8 cm). Surgery was for recurrent epidermoid in 6 of 13 cases (46%). Epidermoid tumor location included the cerebellopontine angle (9 patients, 75%), fourth ventricle (2 patients, 17%), and third ventricle (1 patient, 8%). Surgical approaches included retro-sigmoid craniotomy (8 patients), sub-occipital craniotomy (1 patient), sub-occipital craniotomy with supra-cerebellar approach (1 patient), extradural temporopolar approach (1 patient), and subtemporal approach (1 patient). In 11 of 13 cases (85%), additional tumor was identified upon inspection with an angled endoscope, facilitating additional tumor resection in each case. Gross or deliberate near total resection was achieved in 7 of 13 cases (54%). Four patients (31%) had improvement of cranial nerve function. Post-operative neurological deficits included transient abducens and oculomotor nerve paresis in 1 patient each. CONCLUSION: The endoscope is a safe and effective adjunct to the microscope in facilitating additional inspection and further resection of epidermoid tumors. Endoscopic-assisted surgery is particularly useful for identifying and removing additional tumor located around surgical corners.
    World Neurosurgery 03/2013; · 1.77 Impact Factor
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    ABSTRACT: BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is an uncommon neoplasm characterized by local extension and an aggressive course. Treatment often includes a combination of chemotherapy, radiation therapy, and surgery, although the optimal strategy remains unclear. Here, we present the first reported case of leptomeningeal carcinomatosis from SNUC. METHODS AND RESULTS: A 28-year-old man with rapidly progressive headaches, congestion, and exophthalmos was found to have a nasal mass. Biopsy revealed sinonasal undifferentiated carcinoma. He had a transient response to chemotherapy followed by a sustained response to concurrent chemoradiation. At the completion of radiation, he developed subtle neurologic findings and MRI revealed diffuse, bulky leptomeningeal spread. He was able to receive only a single fraction of external beam radiation to his spinal axis before his disease rapidly progressed, leading to respiratory failure and death. CONCLUSIONS: Sinonasal undifferentiated carcinoma can be associated with leptomeningeal carcinomatosis, which can lead to a fulminant clinical course. Head Neck, 2012.
    Head & Neck 03/2013; · 2.83 Impact Factor
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    ABSTRACT: Although the concept of endoscopy has existed for centuries, a practical working neuro-endoscopic system did not emerge until last century, as a result of numerous contributions and refinements in optical technology, illumination sources, and instrumentation. Modern neuro-endoscopy would not be a flourishing field, as it is today, without the dedication, innovation, and implementation of emerging technology by key contributors including Maximilian Nitze, Walter Dandy, and Harold Hopkins. Despite several inherent and unique limitations, neuro-endoscopic surgery is now performed for a variety of intraventricular, skull base, and spinal operations. In this review, the history of neuro-endoscopy, the key players who envisioned how the inner workings of the human body could be visualized "through the looking glass", and the current state and future potential for neuro-endoscopic surgery, are discussed. Future directions of neuro-endoscopic surgery are likely to be guided by further miniaturization in camera and optical technology, innovations in surgical instrumentation design, the introduction of robotics, multi-port minimally invasive surgery, and an enhanced ability to perform bimanual microdissection.
    World Neurosurgery 02/2013; · 1.77 Impact Factor
  • Ifije Ohiorhenuan, Gabriel Zada
    World Neurosurgery 01/2013; · 1.77 Impact Factor
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    ABSTRACT: Craniopharyngiomas (CP) are locally invasive and frequently recurring neoplasms often resulting in neurological and endocrinological dysfunction in children. In addition, social-behavioral impairment is commonly reported following treatment for childhood CP, yet remains to be fully understood. The authors aimed to further characterize the prevalence of neurobehavioral, social, and emotional dysfunction in survivors of childhood craniopharyngiomas. A systematic literature review was conducted in PubMed to identify studies formally assessing neurobehavioral, social, and emotional outcomes in patients treated for CP prior to 18 years of age. Studies published between the years 1990-2012 that reported the primary outcome (prevalence of neurobehavioral, social, emotional/affective dysfunction, and/or impaired quality of life (QoL)) in ≥10 patients were included. Of the 471 studies screened, 11 met inclusion criteria. Overall neurobehavioral dysfunction was reported in 51 of 90 patients (57%) with available data. Social impairment (i.e. withdrawal, internalizing behavior) was reported in 91 of 222 cases (41%). School dysfunction was reported in 48 of 136 patients (35%). Emotional/affective dysfunction was reported in 58 of 146 patients (40%), primarily consisting of depressive symptoms. Health related quality of life was affected in 49 of 95 patients (52%). Common descriptors of behavior in affected children included irritability, impulsivity, aggressiveness, and emotional outbursts. Neurobehavioral, social, and emotional impairment is highly prevalent in survivors of childhood craniopharyngioma, and often affects quality of life. Thorough neurobehavioral/emotional screening and appropriate counseling is recommended in this population. Additional research is warranted to identify risk factors and treatment strategies for these disorders.
    PLoS ONE 01/2013; 8(11):e76562. · 3.73 Impact Factor
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    ABSTRACT: Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3-5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as diagnostic biomarkers or candidate causal genes for malignant transformation.
    PLoS ONE 01/2013; 8(1):e54114. · 3.73 Impact Factor
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    Gabriel Zada
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    ABSTRACT: Cushing's Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing's Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing's Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing's Disease are discussed.
    International Journal of Endocrinology 01/2013; 2013:893781. · 2.52 Impact Factor
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    ABSTRACT: Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression. A systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed. Of the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1). Epigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.
    PLoS ONE 01/2013; 8(12):e82619. · 3.73 Impact Factor
  • Surgical Neurology International 01/2013; 4:35. · 1.18 Impact Factor

Publication Stats

506 Citations
186.72 Total Impact Points

Institutions

  • 2012–2014
    • Keck School of Medicine USC
      Los Angeles, California, United States
    • George Washington University
      Washington, Washington, D.C., United States
  • 2013
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 2010–2011
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2007–2011
    • University of Southern California
      • • Keck School of Medicine
      • • Department of Neurological Surgery
      Los Angeles, California, United States
    • Children's Hospital Los Angeles
      • Division of Neurosurgery
      Los Angeles, California, United States