Publications by authors named "Viharkumar Patel"

8 Publications

  • Page 1 of 1

Immunohistochemical surrogates for molecular alterations for the classification and grading of gliomas.

Semin Diagn Pathol 2022 Jan 24;39(1):78-83. Epub 2021 Nov 24.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115 United States; Department of Pathology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Bader 104, Boston, MA 02467, United States. Electronic address:

Recent advances in molecular diagnostics have led to a better understanding of glioma tumorigenesis, prognosis, and treatment. Therefore, the 2016 WHO Classification of Tumours of the Central Nervous System and more recent literature recommends the incorporation of molecular results in the pathology report. The methods for molecular testing vary among institutions; however, most practicing pathologists utilize a range of immunohistochemical surrogates for molecular alterations in the evaluation of gliomas. This manuscript reviews the clinical aspects and pitfalls of the immunohistochemical stains with diagnostic, prognostic and therapeutic implications in gliomas.
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http://dx.doi.org/10.1053/j.semdp.2021.11.003DOI Listing
January 2022

Integration of Microanatomy, Neuronavigation, Dynamic Neurophysiologic Monitoring, and Intraoperative Multimodality Imaging for the Safe Removal of an Insular Glioma: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 06;21(1):E28-E29

Department of Neurosurgery, Brigham and Women's Hospital, Harvard School of Medicine, Boston, Massachusetts.

Insular gliomas are located amongst myriad critical neurovascular structures, including lenticulostriate vessels, long insular perforators, putamen, internal capsule, frontal and temporal opercula, and key fasciculi.1-6 Each of these critical structures engenders key function of the brain, which must be preserved. Although anatomic knowledge remains the cornerstone of insular glioma surgery, novel tools have been developed to aid the surgeon in identifying and preserving these essential structures. Modern surgery of the insular glioma calls for seamless integration of these techniques to maximize the safety and totality of insular glioma resection, which has been shown to improve length of survival and seizure control, while reducing risk of tumor transformation.7-10 Neuronavigation can be used to help plan the craniotomy to achieve adequate exposure and assist during tumor resection. Brain "shift" can be corrected by re-registration following intraoperative magnetic resonance imaging (MRI). Interval ultrasound imaging reflects real-time progressive tumor resection. Dynamic neurophysiologic monitoring using thresholding techniques guides the surgeon as he resects tumor at its depth and posterior pole-close to the internal capsule. Intraoperative magnetic resonance imaging depicts residual infiltrative tumor that may require additional resection. The patient is a 33-yr-old woman with progressive growth of a right insular tumor and has consented to surgery, photography, and video recording.  Figure at 1:57, © Ossama Al-Mefty, used with permission.
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http://dx.doi.org/10.1093/ons/opab050DOI Listing
June 2021

β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer's disease pathology.

J Neuroinflammation 2020 Sep 21;17(1):280. Epub 2020 Sep 21.

Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.

Alzheimer's disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, β-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD. Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.
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http://dx.doi.org/10.1186/s12974-020-01948-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507727PMC
September 2020

Atypical Teratoid/Rhabdoid Tumor of the Cerebellum in an Adult: Case Report and Literature Review.

World Neurosurg 2021 01 15;145:57-63. Epub 2020 Aug 15.

Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor that is most frequently encountered in the pediatric patient population. AT/RT accounts for approximately 1%-2% of all pediatric central nervous system tumors and roughly 10%-20% of tumors in patients younger than 3 years of age. While AT/RT has been encountered in the adult population, the vast majority of the cases reported occur in the supratentorial space. In the existing literature, only 3 adult cases that arise from the cerebellum have ever been reported.

Case Description: A 38-year-old female presented with 6 months of worsening nausea, emesis, vertigo, diplopia, and coordination difficulty. Magnetic resonance imaging revealed a T1 avidly contrast-enhancing mass, composed of both cystic and solid areas, extending from the cerebellum into the fourth ventricle. Following a gross total resection, surgical pathology was consistent with AT/RT, with tumor cell loss of integrase interactor-1 (INI-1) observed via immunohistochemical staining.

Conclusions: This case represents just the fourth ever reported case of AT/RT arising from the cerebellum in an adult and the oldest reported age to date of a cerebellar AT/RT occurring in a female. Due to the paucity of reported adult AT/RT cases, little is known about adults with AT/RT. Further reports will function to improve the general understanding of AT/RT in the adult population.
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http://dx.doi.org/10.1016/j.wneu.2020.08.079DOI Listing
January 2021

Comparison of two commonly used methods in measurement of cancer volume in prostate biopsy.

Int J Clin Exp Pathol 2020 1;13(4):664-674. Epub 2020 Apr 1.

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison Madison, WI, USA.

Currently, cancer volume in prostate biopsy samples is commonly calculated as linear length of carcinoma divided by total core length and reported as percentage involvement. The measurement of the linear length of carcinoma can be problematic particularly when there are two or more separate foci of carcinoma in a single core. There are two most methods commonly used by practicing pathologists. One method is to measure the exact linear extent of each discrete carcinoma foci in millimeters and then add up the linear length (the exact method, E method). The other method is to measure the core length encompassing all carcinoma foci including the intervening benign prostate tissue (glands and/or stroma) (the scattered method, S method). In this study, we used digital pathology to compare the site-specific and overall cancer volumes measured with the E and S methods and analyzed their correlation with the cancer volume in the corresponding prostatectomy specimens. Our results showed that prostate-cancer volumes estimated with both E and S methods on biopsy samples positively correlate with cancer volume at radical prostatectomy. However, the cancer volumes measured with both E and S methods in the majority of biopsy samples were significantly larger than that in prostatectomy (P<0.001). The E method more closely predicts the cancer volume compared to the S method. The overall cancer volume is better than site-specific cancer volume at biopsy in predicting cancer volume at prostatectomy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191135PMC
April 2020

Outcome-Related Signatures Identified by Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated after Starting Hu14.18-IL2.

Clin Cancer Res 2020 07 9;26(13):3296-3306. Epub 2020 Mar 9.

Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin.

Purpose: We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers in patients with melanoma at high risk for recurrence.

Experimental Design: Patients were randomly assigned to receive the first of three monthly courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known diseases. Tumors were evaluated by histology and whole transcriptome sequencing.

Results: Tumor-infiltrating lymphocyte (TIL) levels directly associated with relapse-free survival (RFS) and overall survival (OS) in resected tumors from Group A, where early responses to the immunotherapy agent could be assessed. TIL levels directly associated with a previously reported immune signature, which associated with RFS and OS, particularly in Group A tumors. In Group A tumors, there were decreased cell-cycling gene RNA transcripts, but increased RNA transcripts for repair and growth genes. We found that outcome (RFS and OS) was directly associated with several immune signatures and immune-related RNA transcripts and inversely associated with several tumor growth-associated transcripts, particularly in Group A tumors. Most of these associations were not seen in Group B tumors.

Conclusions: We interpret these data to signify that both immunologic and tumoral cell processes, as measured by RNA-sequencing analyses detected shortly after initiation of hu14.18-IL2 therapy, are associated with long-term survival and could potentially be used as prognostic biomarkers in tumor resection specimens obtained after initiating neoadjuvant immunotherapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334053PMC
July 2020

Tectal region papillary neuroglial tumour: a case report.

Br J Neurosurg 2019 Feb 11:1-3. Epub 2019 Feb 11.

a Department of Neurological Surgery , University of Wisconsin Hospitals and Clinics , Madison , WI, USA.

Papillary glioneuronal tumor (PGNT) is a rare central nervous system neoplasm. Of reported cases, the vast majority are located in the frontal and temporal lobes. We present the case of a 39-year-old male who presented with a one day history of gait disturbance following chemotherapy treatment for metastatic rectal adenocarcinoma. Following MRI of the head showed a tectal mass. Following an occipital interhemispheric craniotomy for tumor resection, final pathology was diagnostic of a papillary neuroglial tumor, WHO grade I. To the best or out knowledge this is the only report of it arising from the tectal plate.
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http://dx.doi.org/10.1080/02688697.2018.1562035DOI Listing
February 2019

Small molecules and Alzheimer's disease: misfolding, metabolism and imaging.

Curr Alzheimer Res 2015 ;12(5):445-61

Department of Physiology and Neuroscience, P.O Box 7, St. George's University, St Georges, Grenada, West Indies.

Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (Aβ), with specific attention on recent developments to further improve contrast, specificity, and sensitivity. With advances in imaging technologies, such fluorescent imaging probes will open new diagnostic avenues.
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http://dx.doi.org/10.2174/1567205012666150504145646DOI Listing
February 2016
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