Dhaval Patel

National Cancer Institute (USA), National Institutes of Health | NCI · Endocrine Oncology Branch

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can occur in 30-90% of patients with Multiple Endocrine Neoplasia Type 1 (MEN1). However, only 1% of GEP-NETs are Grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs. We report a 43-year...

Von Hippel–Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018‐2020, the VHL Alliance gathered severa...

Purpose To compare the DNA methylation signature of neuroendocrine tumors (NETs) by primary tumor site and inherited predisposition syndromes von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia type 1 (MEN1). Methods Genome-wide DNA methylation (835,424 CpGs) of 96 NET samples. Primary component (PCA) and unsupervised hierarchical clu...

Postoperative hypotension occurs frequently after resection of pheochromocytoma and/or paraganglioma (PPGLs). Epidural anesthesia (EA) is often used for pain control in open resection of these tumors; one of its side effects is hypotension. Our aim is to determine if EA is associated with an increased risk of postoperative hypotension after open re...

Background Prior to thyroidectomy for hyperthyroidism, it is recommended that patients are managed with antithyroid drugs (ATDs) and rendered euthyroid to decrease the risk of thyroid storm. However, not all patients tolerate ATD and the risk of thyroid storm during thyroidectomy in these patients is unclear. Therefore, the aim of this study was to...

Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO. Although the patient was normotensive and asymptomatic, routine screening imaging with CT demonstrated bilateral adrenal...

This first part of a two-part review of pheochromocytoma and paragangliomas (PPGLs) addresses clinical presentation, diagnosis, management, treatment, and outcomes. In this first part, the epidemiology, prevalence, genetic etiology, clinical presentation, and biochemical and radiologic workup are discussed. In particular, recent advances in the gen...

This is the second part of a two-part review on pheochromocytoma and paragangliomas (PPGLs). In this part, perioperative management, including preoperative preparation, intraoperative, and postoperative interventions are reviewed. Current data on outcomes following resection are presented, including outcomes after cortical-sparing adrenalectomy for...

Background: Recurrent adrenocortical carcinoma (ACC) has a poor prognosis with minimal clinical and biochemical factors to guide management. The aim of this study was to evaluate the prognostic significance of systemic inflammatory response in patients with recurrent ACC. Methods: Patients who underwent resection for recurrent ACC were retrospec...

Background: Analysis of plasma circulating cell-free DNA integrity (cfDI) has emerged as a promising tool in the diagnosis of malignant vs. benign tumors. There is limited data on the role of cfDI in thyroid cancer. The goal of this study was to analyze cfDI as a biomarker of malignancy in patients with cytologically indeterminate thyroid nodules....

Background Catecholamine excess in patients with pheochromocytomas or paragangliomas (PPGLs) can lead to hypertension, diabetes and hyperlipidemia. The aim was to investigate the prevalence of hyperlipidemia and the effect of surgical resection. Methods One hundred and thirty-two patients with PPGLs underwent an operation at the National Institute...

Background: Adrenocortical carcinoma is an aggressive malignancy with a low but variable overall survival rate. The role of in adrenocortical carcinoma is poorly understood. Thus, in this study we performed long noncoding RNA expression profiling in adrenocortical carcinomas, adrenocortical adenomas, and normal adrenal cortex. Methods: Long nonc...

BACKGROUND: Gastric neuroendocrine tumors (carcinoid) associated with Zollinger Ellison Syndrome (ZES) induced hypergastrinemia in Multiple Endocrine Neoplasia type 1 (MEN1) occur in 15-50% of patients and are generally thought to be benign. Here we present a case of metastatic grade 3 gastric neuroendocrine tumor in MEN1. CASE: A 41-year male with...

Introduction Adrenocortical carcinoma (ACC) is a rare and aggressive disease with high mortality rate, lack of effective medical therapy, and high recurrence rate even with complete resection. Prognostic biomarkers are needed to guide treatment. The aim of this study was to identify prognostic tissue metabolites and dysregulated pathways to guide t...

Thyroid cancer is the most frequent endocrine tumor. BRAF mutation is the most frequent alteration in thyroid cancer. The metabolic consequences of these mutations is unknown. Recent studies have suggested a pro-metastatic role of the metabolic processes in several solid malignancies. The aim of this study is to identify the metabolic pathways dysr...

Objective: To report the rate of candidate actionable somatic mutations in patients with locally advanced and metastatic gastro-enteropancreatic (GEP) neuroendocrine tumors (NET) and of other genetic alterations that may be associated with tumorigenesis. Methods: A phase II mutation targeted therapy trial was conducted in patients with advanced we...

Background Aberrant methylation is a known cause of cancer initiation and/or progression. There are scant data on the genome‐wide methylation pattern of nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and sporadic and hereditary NFPanNETs. Methods Thirty‐three tissue samples were analyzed: they included samples from sporadic (n = 9), v...

Background: The BRAFV600E mutation is the most common somatic mutation in thyroid cancer. The mechanism associated with BRAF-mutant tumor aggressiveness remains unclear. Lysyl oxidase (LOX) is highly expressed in aggressive thyroid cancers, and involved in cancer metastasis. The objective was to determine whether LOX mediates the effect of the act...

Background: Because chronic kidney disease is an important comorbidity associated with primary hyperparathyroidism, we sought to evaluate the prevalence of chronic kidney disease and effects of parathyroidectomy on kidney function in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism. Methods: We performed a...

Purpose Patients with von Hippel-Lindau (VHL) disease may develop various tumors, including neuroendocrine tumors of the pancreas (PNETs) and adrenal, central nervous system and retinal hemangioblastomas, kidney tumors and more. ⁶⁸Ga-DOTATATE positron emission tomography (PET)/computerized tomography (CT) has been shown to be highly accurate for tu...

Background: There are conflicting reports on whether familial nonmedullary thyroid cancer is more aggressive than sporadic nonmedullary thyroid cancer. Our aim was to determine if the clinical and pathologic characteristics of familial nonmedullary thyroid cancer are different than nonmedullary thyroid cancer. Methods: We compared patients with...

Importance Neuroendocrine tumors (NETs) express somatostatin receptors, which can be targeted with radiolabeled peptides. In a variety of solid tumors, radioguided surgery (RGS) has been used to guide surgical resection. Gallium 68 (⁶⁸Ga) dota peptides have been shown to be more accurate than other radioisotopes for detecting NETs. A pilot study pr...

Primary hyperparathyroidism, a common endocrine disorder, is associated with familial disease in about 10% of cases. These syndromes include multiple endocrine neoplasia types 1, 2A and 4 (MEN1, MEN2A, MEN4), familial isolated hyperparathyroidism (FIHP), and the hyperparathyroidism jaw tumor (HPT-JT) syndrome. HPT-JT syndrome, an autosomal dominant...

Purpose: It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However, there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hypergly...

Objective: New clinical prognostic tools are needed to select the population of patients with neuroendocrine tumors (NETs) that have a high risk of disease progression and disease-specific mortality (DSM). Biochemical biomarker doubling time (DT) is used clinically for prognosis prediction in several solid malignancies. The aim of the current stud...

Background: The incidence of parathyroid carcinoma is reported to be rising. There is minimal data on prognostic variables associated with cancer-specific survival. The objectives of this study were to evaluate the trends in incidence and assess prognostic factors. Methods: A retrospective review of the SEER database between 1973 and 2014 was pe...

Purpose: Mitochondrial glycerophosphate dehydrogenase (mGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin (MF) in the liver. There are no data on the expression and role of mGPDH as a metformin target in cancer. In this study, we evaluated mGPDH as a potential...

Aim The study's aim was to determine the utility of 68-Gallium DOTATATE positron emission tomography (PET)-CT scanning in patients with carcinoid-like symptoms and negative anatomical imaging. Methods Retrospective analysis of 22 of 196 patients with carcinoid-like symptoms and no evidence of primary neuroendocrine tumor (NET) based on anatomical...

Background: Approximately 10% of patients with primary hyperparathyroidism (PHPT) have hereditary disease. Hereditary PHPT may be syndromic (multiple endocrine neoplasia (MEN1, 2, 4), hyperparathyroidism-jaw tumor syndrome) or non-syndromic (familial isolated primary hyperparathyroidism). There are limited data on the probability of testing positi...

Background: Fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging is recommended in patients with metastatic pheochromocytoma (PC) and paraganglioma (PGL). There are no data on whether routine preoperative F-FDG PET/CT in all patients with PC/PGL impacts surgical management. Objective: The aim of this study...

Context Patients with vHL disease caused by a missense VHL mutation have a more severe phenotype compared with other VHL mutation types. Objective To define PNET aggressiveness according to VHL genotype. Design A prospective natural history study. Setting The NIH clinical center. Patients Patients with vHL disease, pancreatic manifestations, an...

Background: The prognosis and behavior of pancreatic neuroendocrine tumors (PNETs) vary and may be divergent even at the same stage or tumor grade. Markers of systemic inflammatory response are readily available and are inexpensive, and have been shown to be prognostic factors in several cancers. Objective: The aim of this study was to evaluate...

Background: Hereditary primary hyperparathyroidism may be syndromic or nonsyndromic (familial isolated hyperparathyroidism). Recently, germline activating mutations in the GCM2 gene were identified in a subset of familial isolated hyperparathyroidism. This study examined the clinical and biochemical characteristics and the treatment outcomes of GC...

Background: Our knowledge of the susceptibility genes for pheochromocytomas/paragangliomas has increased; however, data on its impact on surgical decision-making has not been described. The aim of this study was to determine the effect of routine preoperative genetic testing on the operative intervention in patients with pheochromocytomas/paragang...

Background & aims: Survival times vary among patients with neuroendocrine tumors (NETs)-even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs, because some patients can survive decades without treatment. (68)Gallium-DOTATATE positron emission tomograp...

Von Hippel–Lindau (VHL) disease is a familial cancer syndrome caused by a germline mutation in the VHL tumor suppressor gene (OMIM 193300).¹ The prevalence of pancreatic neuroendocrine tumors (PNETs) in VHL disease ranges from 9% to 17% and is characterized by a better prognosis compared with sporadic PNETs.²,3 Several risk factors for PNET metasta...

Context The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing. Current staging systems include nodal positivity, but the association of lymph node status and worse survival is controversial. Objective The study aim was to determine the prognostic significance of lymph node ratio (LNR) and compare it to nodal positivity for PNET....

Adrenal masses require a stepwise approach to determine whether surgical or medical intervention or no intervention is warranted. Patients with adrenal masses may have functional tumors that hypersecrete cortisol, aldosterone, virilizing/feminizing hormones, or vasoactive catecholamines. Nonfunctional adrenal masses, however, may harbor either a pr...

Multiple endocrine neoplasia type 1 (MEN1) and Von Hippel Lindau (VHL) disease are autosomal-dominant diseases caused by germline mutations in tumor-suppressor genes. A patient with a germline MEN1 mutation and a somatic VHL mutation in their tumor has not been reported. Herein, we report MEN1 patient with metastatic nonfunctioning pancreatic neuro...

Background: Although a family history of thyroid cancer is one of the main risk factors for thyroid cancer, the benefit of screening individuals with a family history of thyroid cancer is not known. Methods: We performed a prospective cohort study with yearly screening using neck ultrasound and fine needle aspiration biopsy (FNAB) of the thyroid...

Background: Patients with neuroendocrine tumors (NETs) have divergent survival, even when having the same site of primary tumor, and tumor stage and grade. 68Gallium (68Ga)-DOTATATE positron emission tomography (PET)/computed tomography (CT) is a sensitive imaging modality for detecting NETs. The purpose of this study was to determine whether 68Ga-...

Background: About 8–20% of patients with von Hippel-Lindau disease (vHLd) develop pancreatic neuroendocrine tumors (PNETs). However, prognostic markers for these tumors are lacking. The VHL gene mutation type is associated with the clinical phenotype of vHLd. Hence, we aimed to determine whether VHL mutation characteristics may be associated with P...

Objective: To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by (68)Ga DOTATATE PET/CT imaging. Design: A retrospective analysis of a prospective database of patients with NETs. Methods: Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, va...

Aim: We aimed to compare the performance of nine adrenal steroids in confirming the correct catheter position during adrenal venous sampling (AVS) without cosyntropin in patients with primary hyperaldosteronism. Materials & methods: A successful adrenal vein catheterization without cosyntropin was defined as the ratio of steroids from adrenal to...

Purpose: Adrenal incidentalomas must be differentiated from adrenocortical cancer (ACC). Currently, size, growth, and imaging characteristics determine the potential for malignancy but are imperfect. The aim was to evaluate whether urinary small molecules (<800 Da) are associated with ACC. Experimental Design: Preoperative fasting urine specimen...

Context: The reliable localization of insulinoma is critical for the successful surgical treatment. Objective: This study compared the accuracy of (68)Gallium (Ga)-DOTATATE PET/CT to anatomic imaging modalities, selective arterial secretagogue injection (SASI), and intraoperative ultrasound (IOUS) and palpation for localizing insulinoma in patie...

Background: A staging/prognostic system has long been desired to better categorize pheochromocytoma/paraganglioma which can be very aggressive in the setting of SDHB mutations. Methods: A retrospective analysis was conducted of clinical characteristics and outcomes including results of genetic testing, tumor recurrence/metastasis, Ki67/MIB1% sta...

Background: Pediatric pheochromocytomas and paragangliomas are rare with limited data on the optimal management approach. The aim of this study was to determine the role of genetic testing and imaging to detect extra-adrenal and/or metastatic tumors in pediatric pheochromocytomas and paragangliomas. Methods: We performed a retrospective study of...

Background Approximately 8–17 % of patients with von Hippel–Lindau (VHL) syndrome develop pancreatic neuroendocrine tumors (PNETs), with 11–20 % developing metastases. Tumor grade is predictive of prognosis. Objective The aim of this study was to determine if preoperative metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associate...

Context: The vasoactive intestinal peptide secreting neuroendocrine tumor (VIPoma) is a very rare pancreatic tumor. We report the first case of a patient with VIPoma that co-secreted dopamine and had pulmonary emboli. Case description: A case of 67-year-old woman presented with 2 months of watery diarrhea, severe generalized weakness, and 15 lbs...

Context: Insulinomas are usually due to a solitary tumor but can be challenging to localize. Case description: A 66-year old woman presented with a one-year history of episodic neuroglycopenic hypoglycemia and was suspected of having an insulinoma. On a supervised fasting, she was found to be hypoglycemic at 39 mg/dL with an insulin of 40 mcU /m...

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Unequivocally, cumulative mutations are required for the development of cancer and many sources of mutagenic activity contribute to tumorigenesis. Recent evidence has implicated that a member of cytidine deaminase family, APOBEC3B (Apolipoprotein B mRNA editing enzyme,...

Objective: Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to as...

Context: Retinoic acid receptor responder protein 2 (RARRES2) is a small secreted protein involved in multiple cancers, including adrenocortical carcinoma (ACC). However, discordant tumor and serum RARRES2 levels have been reported in various cancers. The etiology of this discordance is unknown and has not been studied in pair-matched tumor and se...

Background: Gallium-68 (Ga-68) DOTATATE is a radiolabeled peptide-imaging modality that targets the somatostatin receptor (SSTR), especially subtype 2 (SSTR2). Benign and malignant thyroid tumors have been observed to express SSTR. The objective of this study was to evaluate the frequency and clinical significance of incidental atypical thyroid up...

Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer, and no current effective therapy is available for locally advanced and metastatic ACC. Drug repurposing is an emerging approach for identifying new indications for existing drugs, especially for rare cancers such as ACC. The objective of this study was to use quantitative hig...

Background: A recent study suggested a survival benefit in patients with adrenocortical carcinoma (ACC) who had undergone lymphadenectomy. The objective of this study was to study the effect of lymphadenectomy on the survival rates of patients with ACC. Methods: Data from adult patients with histology-proven ACC from the National Cancer Institut...

To gain insight into the pathogenesis of adrenocortical carcinoma (ACC) and whether there is progression from normal-to-adenoma-to-carcinoma, we performed genome-wide gene expression, gene methylation, microRNA expression and comparative genomic hybridization (CGH) analysis in human adrenocortical tissue (normal, adrenocortical adenomas and ACC) sa...

Background: Patients with Cushing's Syndrome (CS) and Conn's Syndrome with bilateral adrenal masses pose a dilemma. Uptake of 18F-FDG by hyperfunctioning adrenal glands has not been previously reported and may help lateralize. The aim was to determine if 18F-FDG PET/CT scan could identify hyperfunctioning adrenal masses and determine a biological...

Background: Adrenocortical carcinoma (ACC) is a rare but lethal malignancy with few reliable prognostic markers. FDG-PET metabolic parameters have been shown to predict survival in several cancers. The objective was to determine if metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) could ser...

Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased...

Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies. Currently, there is no standard or effective therapy for ATC. Drug repurposing for cancer treatment is an emerging approach for identifying compounds that may have antineoplastic effects. The aim of this study was to use high-throughput drug library screening to ident...

Purpose: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy without any effective therapy. The aim of this study is to use a high-throughput drug library screening to identify a novel therapeutic agent that targets dysregulated genes/pathways in ATC. Experimentaldesign: We performed quantitative high-throughput screening (qHTS) in A...

Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated do...

Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castr...

Background: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare, autosomal-dominant disease secondary to germline-inactivating mutations of the tumor suppressor gene HRPT2/CDC73. The aim of the present study was to determine the optimal operative approach to parathyroid disease in patients with HPT-JT. Methods: A retrospective analysis of...

The aim of this pilot study was to determine if metabolic tumor volume (MTV) and total lesion glycolysis (TLG) could serve as predictors of biochemical remission and pharmacotherapy-free interval in patients with metastatic pheochromocytomas (PCCs) and paragangliomas (PGLs). Patients with metastatic PCCs/PGLs have a high rate of biochemical recurre...

Adrenocortical carcinoma (ACC) lacks diagnostic and prognostic biomarkers to guide treatment. A consistently dysregulated pathway in ACC is the IGF signaling pathway, specifically overexpression of IGF2, IGF-I-receptor, and IGFBP2. The objective of this study was to perform a comprehensive analysis of serum IGF and IGFBP levels and to determine the...