Publications by authors named "Naris Nilubol"

126 Publications

The Role of Tumor Necrosis Factor in Manipulating the Immunological Response of Tumor Microenvironment.

Front Immunol 2021 27;12:656908. Epub 2021 Apr 27.

Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.

The tumor microenvironment (TME) is an intricate system within solid neoplasms. In this review, we aim to provide an updated insight into the TME with a focus on the effects of tumor necrosis factor-α (TNF-α) on its various components and the use of TNF-α to improve the efficiency of drug delivery. The TME comprises the supporting structure of the tumor, such as its extracellular matrix and vasculature. In addition to cancer cells and cancer stem cells, the TME contains various other cell types, including pericytes, tumor-associated fibroblasts, smooth muscle cells, and immune cells. These cells produce signaling molecules such as growth factors, cytokines, hormones, and extracellular matrix proteins. This review summarizes the intricate balance between pro-oncogenic and tumor-suppressive functions that various non-tumor cells within the TME exert. We focused on the interaction between tumor cells and immune cells in the TME that plays an essential role in regulating the immune response, tumorigenesis, invasion, and metastasis. The multifunctional cytokine, TNF-α, plays essential roles in diverse cellular events within the TME. The uses of TNF-α in cancer treatment and to facilitate cancer drug delivery are discussed. The effects of TNF-α on tumor neovasculature and tumor interstitial fluid pressure that improve treatment efficacy are summarized.
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http://dx.doi.org/10.3389/fimmu.2021.656908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110933PMC
April 2021

Contralateral Suppression Index Does Not Predict Clinical Cure in Patients Undergoing Surgery for Primary Aldosteronism.

Ann Surg Oncol 2021 May 3. Epub 2021 May 3.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Adrenal venous sampling (AVS) is recommended before adrenalectomy for patients with primary aldosteronism (PA) over 35 years old. The literature examining contralateral suppression (CoS) on AVS in predicting surgical outcomes is conflicting. We examined the presence of CoS in patients who underwent adrenalectomy while adjusting for clinical and biochemical factors associated with a clinical cure of hypertension (ccHTN).

Methods: We performed a retrospective review of patients with successful AVS who underwent unilateral adrenalectomy for PA at a quaternary referral center. Patients were excluded if they had overt cortisol co-secretion, or inadequate follow-up. We first evaluated the aldosterone resolution score (ARS) in predicting ccHTN in our cohort. Next, the receiver-operator characteristic analysis (ROC) was used to determine the optimal contralateral suppression index (CSI) cutoff to define CoS. We performed univariable and multivariable analyses of factors associated with ccHTN. The primary outcome was ccHTN defined as blood pressure less than 140/90 mmHg, and off blood pressure medications.

Results: Of the 102 patients on bivariable analysis, age, sex, duration of HTN, number of medications, preoperative systolic blood pressure, and creatinine level were associated with ccHTN. ROC analysis of ARS had an AUC of 0.850 (p < 0.001). On multivariable analysis, only ARS remained associated with ccHTN (OR 3.40, 95% CI 1.20-9.61, p = 0.021). CSI was not significantly associated with ccHTN on ROC, bivariable, or multivariable analyses.

Conclusion: The presence of CoS was not useful in predicting ccHTN following unilateral adrenalectomy for PA in our cohort. After adjusting for clinical and biochemical factors, ARS remains a useful predictor for ccHTN.
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http://dx.doi.org/10.1245/s10434-021-09692-7DOI Listing
May 2021

The impact of level II evidence on surgical practice: Dual agent bowel prep for elective colorectal surgery.

Surgery 2021 Apr 28. Epub 2021 Apr 28.

Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address:

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http://dx.doi.org/10.1016/j.surg.2021.03.037DOI Listing
April 2021

Preoperative serum chromogranin-a is predictive of survival in locoregional jejuno-ileal small bowel neuroendocrine tumors.

Surgery 2021 Jul 2;170(1):106-113. Epub 2021 Apr 2.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address:

Background: Small bowel neuroendocrine tumors (SB-NET) frequently metastasize to regional lymphatic or distant sites. Although most prognostication of SB-NET focuses on lymph node involvement, findings from studies of neuroendocrine tumors from other primary sites have suggested that preoperative serum chromogranin-A (CgA) levels may provide a more accurate metric.

Methods: Using the National Cancer Database (2004-2016), we analyzed patients with locoregional SB-NET who underwent curative resection including an adequate lymphadenectomy (n = 1,274). A statistically optimized cut-point was used to dichotomize CgA cohort based on preoperative serum CgA levels.

Results: We determined that a CgA ≥139 ng/mL identified patients with significantly shorter estimated mean overall survival (6.6 years vs 7.6 years, log-rank P = .00001). These patients were also older (63 vs 57 years, P < .001) and had higher rates of poorly differentiated tumors (2.1% vs 0.7%, P = .04) or primary tumors >1 cm (88.2% vs 79.2%, P = .001). Clinical features associated with shorter overall survival included preoperative CgA ≥139 ng/mL (HR = 2.19, 95% CI 1.22-3.92; P = .009), age at diagnosis (HR = 1.06, 95% CI 1.03-1.09; P < .001), Charlson-Deyo score ≥2 (HR = 3.93, 95% CI 1.71-9.01; P = .001), and poorly differentiated tumors (HR = 11.22, 95% CI 4.16-30.24; P < .001). Neither lymph node metastasis nor T-stage were independently associated with shorter overall survival in patients with locoregional SB-NET.

Conclusion: Elevated preoperative serum CgA is an adverse prognostic marker associated with shorter overall survival in patients with locoregional SB-NET.
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http://dx.doi.org/10.1016/j.surg.2021.01.048DOI Listing
July 2021

Current Status and Future Targeted Therapy in Adrenocortical Cancer.

Front Endocrinol (Lausanne) 2021 1;12:613248. Epub 2021 Mar 1.

Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The current treatment standards include complete surgical resection for localized resectable disease and systemic therapy with mitotane alone or in combination with etoposide, doxorubicin, and cisplatin in patients with advanced ACC. However, the efficacy of systemic therapy in ACC is very limited, with high rates of toxicities. The understanding of altered molecular pathways is critically important to identify effective treatment options that currently do not exist. In this review, we discuss the results of recent advanced in molecular profiling of ACC with the focus on dysregulated pathways from various genomic and epigenetic dysregulation. We discuss the potential translational therapeutic implication of molecular alterations. In addition, we review and summarize the results of recent clinical trials and ongoing trials.
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http://dx.doi.org/10.3389/fendo.2021.613248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957049PMC
March 2021

ASO Author Reflections: Predicting Postoperative Resolution of Hypertension in Primary Hyperaldosteronism.

Ann Surg Oncol 2021 Mar 15. Epub 2021 Mar 15.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.1245/s10434-021-09762-wDOI Listing
March 2021

First Somatic Defect Associated With Mosaicism for Another Mutation in a Patient With Cushing Syndrome.

J Endocr Soc 2021 Apr 25;5(4):bvab007. Epub 2021 Jan 25.

Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.

Context: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS) associated mostly with Carney complex (CNC), a rare autosomal dominant multiple neoplasia syndrome. More than two-thirds of familial cases and approximately one-third of sporadic cases of CNC harbor germline inactivating defects. Increasingly sensitive technologies for the detection of genetic defects such as next-generation sequencing (NGS) have further highlighted the importance of mosaicism in human disease.

Case Description: A 33-year-old woman was diagnosed with ACTH-independent CS with abdominal computed tomography showing bilateral micronodular adrenal hyperplasia with a left adrenal adenoma. She underwent left adrenalectomy with pathology demonstrating PPNAD with a 1.5-cm pigmented adenoma. DNA analysis by Sanger sequencing revealed 2 different variants in the adenoma that were absent from DNA extracted from blood and saliva: c.682C > T and c.974-2A > G. "Deep" NGS revealed that 0.31% of DNA copies extracted from blood and saliva did in fact carry the c.682C > T variant, suggesting low-level mosaicism for this defect.

Conclusions: We present a case of PPNAD due to low-level mosaicism for a defect which led to the formation of an adenoma due to a second, adrenal-specific, somatic mutation. The identification of mosaicism for , depending on the number and distribution of cells affected has implications for genetic counseling and tumor surveillance. This is the first recorded case of a patient with mosaicism, PPNAD, and an adenoma forming due to complete inactivation of in adrenal tissue from a second, somatic-only, coding sequence mutation.
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http://dx.doi.org/10.1210/jendso/bvab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885549PMC
April 2021

Volumetric Modeling of Adrenal Gland Size in Primary Bilateral Macronodular Adrenocortical Hyperplasia.

J Endocr Soc 2021 Jan 29;5(1):bvaa162. Epub 2020 Oct 29.

Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.

Context: Radiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated.

Objective: We hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed.

Design: A retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019.

Setting: Tertiary care clinical research center.

Patients: Patients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics.

Intervention: Clinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota).

Main Outcome And Measures: 17-hydroxycorticosteroids (17-OHS), genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume.

Results: A cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ± 11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76,  = 0.028), urinary free cortisol (R = 0.70,  = 0.035), and 17-OHS (R = 0.87,  = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in (R = 0.72,  = 0.018; R = 0.65,  = 0.042; and R = 0.73,  = 0.016, respectively).

Conclusions: Volumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.
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http://dx.doi.org/10.1210/jendso/bvaa162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716656PMC
January 2021

Pancreatic insufficiency following pancreatectomy: Does underlying tumor syndrome confer a greater risk?

Am J Surg 2021 02 5;221(2):465-471. Epub 2020 Sep 5.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Background: The risk of postoperative pancreatic exocrine insufficiency (PPEI) is unknown in patients with multiple endocrine neoplasia type I (MEN1) and von Hippel-Lindau (VHL) who require resection of pancreatic neuroendocrine tumors (PNETs).

Methods: A retrospective review of patients who underwent resection of PNETs at the National Institutes of Health from 2007 to 2019 was performed.

Results: Our cohort included 82 patients (VHL n = 25, MEN1 n = 20, sporadic n = 37), 6 of whom developed PPEI. While VHL compared to all non-VHL patients (p = 0.046), non-functional PNETs (p = 0.050), and pancreaticoduodenectomy (PD) (p=<0.001) were associated with higher rates of PPEI on univariate analysis, only PD was found to be an independent predictor of PPEI on multivariate analysis (OR 14.43, 95% CI 1.43-145.8, p = 0.024).

Conclusions: The rate of PPEI in patients with hereditary tumor syndromes was similar to that of sporadic PNETs. PD was independently associated with PPEI, and this increased risk should be included in preoperative counseling.
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http://dx.doi.org/10.1016/j.amjsurg.2020.08.048DOI Listing
February 2021

Distinct DNA Methylation Signatures in Neuroendocrine Tumors Specific for Primary Site and Inherited Predisposition.

J Clin Endocrinol Metab 2020 10;105(10)

Department of Surgery and Stanford Cancer Institute, Stanford University, Stanford, California.

Purpose: To compare the deoxyribonucleic acid (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. Principal components analysis (PCA) and unsupervised hierarchical clustering analyses were used to determine DNA methylome signatures.

Results: Hypomethylated CpGs were significantly more common in VHL-related versus sporadic and MEN1-related NETs (P < .001 for both comparisons). Small-intestinal NETs (SINETs) had the most differentially methylated CpGs, either hyper- or hypomethylated, followed by duodenal NETs (DNETs) and pancreatic NETs (PNETs, P < .001 for all comparisons). There was complete separation of SINETs on PCA, and 3 NETs of unknown origin clustered with the SINET samples. Sporadic, VHL-related, and MEN1-related PNETs formed distinct groups on PCA, and VHL clustered separately, showing pronounced DNA hypomethylation, while sporadic and MEN1-related NETs clustered together. MEN1-related PNETs, DNETs, and gastric NETs each had a distinct DNA methylome signature, with complete separation by PCA and unsupervised clustering. Finally, we identified 12 hypermethylated CpGs in the 1A promoter of the APC (adenomatous polyposis coli) gene, with higher methylation levels in MEN1-related NETs versus VHL-related and sporadic NETs (P < .001 for both comparisons).

Conclusions: DNA CpG methylation profiles are unique in different primary NET types even when occurring in MEN1-related NETs. This tumor DNA methylome signature may be utilized for noninvasive molecular characterization of NETs, through DNA methylation profiling of biopsy samples or even circulating tumor DNA in the near future.
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http://dx.doi.org/10.1210/clinem/dgaa477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456345PMC
October 2020

Epidural anesthesia and hypotension in pheochromocytoma and paraganglioma.

Endocr Relat Cancer 2020 09;27(9):519-527

National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Postoperative hypotension frequently occurs 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 resection of PPGLs. We conducted a retrospective review of patients who underwent open resection of PPGLs at the National Institutes of Health from 2004 to 2019. Clinical and perioperative parameters were analyzed by the use of EA. The primary endpoint was postoperative hypotension. Ninety-seven patients (46 female and 51 male; mean age, 38.5 years) underwent open resection of PPGLs and 69 (71.1%) received EA. Patients with EA had a higher rate beta-blocker use (79.7% vs 57.1%, P = 0.041), metastasis (69.6% vs 39.3%, P = 0.011), and were more frequently hypotensive after surgery (58.8% vs 25.0%, P = 0.003) compared to those without EA. Patients with postoperative hypotension had higher plasma normetanephrines than those without (7.3 fold vs 4.1 fold above the upper limit of normal, P = 0.018). Independent factors associated with postoperative hypotension include the use of beta-blockers (HR = 3.35 (95% CI: 1.16-9.67), P = 0.026) and EA (HR = 3.49 (95% CI: 1.25-9.76), P = 0.017). Data from this retrospective study suggest that, in patients with open resection of PPGLs, EA is an independent risk factor for early postoperative hypotension. Special caution is required in patients on beta-blockade. A prospective evaluation with standardized protocols for the use of EA and management of hemodynamic variability is necessary.
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http://dx.doi.org/10.1530/ERC-20-0139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482424PMC
September 2020

New Therapies for Advanced Thyroid Cancer.

Front Endocrinol (Lausanne) 2020 22;11:82. Epub 2020 May 22.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular pathogenesis of thyroid cancer, thus allowing more personalized treatments for patients with thyroid cancer. Most of the recently discovered targeted therapies inhibit the known oncogenic mechanisms in thyroid cancer initiation and progression such as MAPK pathway, PI3K/Akt-mTOR pathways, or VEGF. Despite the significant advances in molecular testing and the discoveries of new and promising therapeutics, effective treatments for advanced and metastatic, iodine-refractory thyroid cancer are still lacking. Here, we aim to summarize the current understanding of the genetic alterations and the dysregulated pathways in thyroid cancer and to discuss the most recent targeted therapies and immunotherapy for advanced thyroid cancer with a promising anti-tumor activity and clinical benefit.
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http://dx.doi.org/10.3389/fendo.2020.00082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257776PMC
March 2021

Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer.

Cell Rep Med 2020 Apr;1(1)

Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.

Clonal evolution of osimertinib-resistance mechanisms in EGFR mutant lung adenocarcinoma is poorly understood. Using multi-region whole-exome and RNA sequencing of prospectively collected pre- and post-osimertinib-resistant tumors, including at rapid autopsies, we identify a likely mechanism driving osimertinib resistance in all patients analyzed. The majority of patients acquire two or more resistance mechanisms either concurrently or in temporal sequence. Focal copy-number amplifications occur subclonally and are spatially and temporally separated from common resistance mutations such as C797S. amplification occurs in 66% (n = 6/9) of first-line osimertinib-treated patients, albeit spatially heterogeneous, often co-occurs with additional acquired focal copy-number amplifications and is associated with early progression. Noteworthy osimertinib-resistance mechanisms discovered include neuroendocrine differentiation without histologic transformation, amplification, and fusions. The subclonal co-occurrence of acquired genomic alterations upon osimertinib resistance will likely require targeting multiple resistance mechanisms by combination therapies.
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http://dx.doi.org/10.1016/j.xcrm.2020.100007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263628PMC
April 2020

Inhibin A as a tumor marker for primary bilateral macronodular adrenal hyperplasia.

Endocrinol Diabetes Metab Case Rep 2020 Apr 29;2020. Epub 2020 Apr 29.

Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Summary: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS). This condition is characterized by glucocorticoid and/or mineralocorticoid excess, and is commonly regulated by aberrant G-protein coupled receptor expression may be subclinical, allowing the disease to progress for years undetected. Inhibin A is a glycoprotein hormone and tumor marker produced by certain endocrine glands including the adrenal cortex, which has not been previously investigated as a potential tumor marker for PBMAH. In the present report, serum inhibin A levels were evaluated in three patients with PBMAH before and after adrenalectomy. In all cases, serum inhibin A was elevated preoperatively and subsequently fell within the normal range after adrenalectomy. Additionally, adrenal tissues stained positive for inhibin A. We conclude that serum inhibin A levels may be a potential tumor marker for PBMAH.

Learning Points: PBMAH is a rare cause of CS. PBMAH may have an insidious presentation, allowing the disease to progress for years prior to diagnosis. Inhibin A is a heterodimeric glycoprotein hormone expressed in the gonads and adrenal cortex. Inhibin A serum concentrations are elevated in some patients with PBMAH, suggesting the potential use of this hormone as a tumor marker. Further exploration of serum inhibin A concentration, as it relates to PBMAH disease progression, is warranted to determine if this hormone could serve as an early detection marker and/or predictor of successful surgical treatment.
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http://dx.doi.org/10.1530/EDM-20-0006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219132PMC
April 2020

The first pancreatic neuroendocrine tumor in Li-Fraumeni syndrome: a case report.

BMC Cancer 2020 Mar 30;20(1):256. Epub 2020 Mar 30.

Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 4-5952, Bethesda, MD, 20892, USA.

Background: Li-Fraumeni syndrome is a cancer predisposition syndrome caused by germline TP53 tumor suppressor gene mutations, with no previous association with pancreatic neuroendocrine tumors (PNETs). Here we present the first case of PNET associated with Li-Fraumeni syndrome.

Case Presentation: This is a 43-year-old female who underwent laparoscopic distal pancreatectomy at age 39 for a well-differentiated grade 2 cystic PNET. When the patient was 41 years old, her seven-year-old daughter was found to have an astrocytoma and a germline TP53 mutation. While undergoing surveillance with Gallium-DOTATATE positron emission tomography/computed tomography for her PNET, the patient was found to have a large choroid plexus papilloma in her right temporal lobe. She underwent genetic counseling and testing that identified a germline pathogenic variant in TP53, leading to the diagnosis of Li-Fraumeni syndrome. Her PNET had a hemizygous pathogenic TP53 mutation with loss of the wild-type alternate allele, consistent with loss of heterozygosity and the two-hit hypothesis. She was enrolled in a Li-Fraumeni syndrome protocol and continues surveillance screening with our service.

Conclusions: This is the first PNET reported in association with Li-Fraumeni syndrome. Pancreatic cancer risk is elevated in this syndrome, and our case highlights the need for vigilance in screening for pancreatic neoplasms in these patients.
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http://dx.doi.org/10.1186/s12885-020-06723-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106707PMC
March 2020

Wolf in Sheep's Clothing: Papillary Thyroid Microcarcinoma in the US.

J Am Coll Surg 2020 04 6;230(4):484-491. Epub 2020 Mar 6.

Department of Surgery, Tulane University School of Medicine, New Orleans, LA. Electronic address:

Background: The presumptive overdiagnosis of papillary thyroid microcarcinoma (PTMC) has led to an emerging trend of less-extensive operation and an inclination toward active surveillance when possible. In this study, we aimed to examine the risk of advanced PTMC at presentation.

Study Design: We conducted a retrospective analysis using the National Cancer Database (2010 to 2014). Patients with PTMC who underwent surgical intervention were included and patients with a history of any cancer were excluded.

Results: A total of 30,180 adult patients with PTMC were identified; 5,628 patients (18.7%) presented with advanced features, including central lymph node (LN) metastasis (8.0%), lateral LN metastasis (4.4%), microscopic extrathyroidal extension (ETE; 6.7%), gross ETE (0.3%), lymphovascular invasion (LVI; 4.4%), and distant metastasis (0.4%). All of those features were associated with a significantly lower survival rate (p < 0.05 each) except for microscopic ETE and LVI. There was a significant interrelation among those features, distant metastasis was associated with central LN metastasis (odds ratio [OR] 2.44; 95% CI, 1.48 to 4.23; p < 0.001), lateral LN metastasis (OR 3.18; 95% CI, 1.77 to 5.71; p < 0.001), and gross ETE (OR 9.91; 95% Cl, 3.83 to 25.64; p < 0.001). In turn, nodal metastasis was associated with microscopic ETE (OR 4.23; 95% CI, 3.82 to 4.70; p < 0.001) and LVI (OR 7.17; 95% CI, 6.36 to 8.08; p < 0.001).

Conclusions: PTMC could exhibit advanced features in 19% of patients who underwent operation and some of those, such as LVI and microscopic ETE, are undetectable with preoperative workup. Clinicians need to be cognizant of this considerable risk in the era of less-aggressive management of PTMC.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.12.036DOI Listing
April 2020

18F-FDOPA PET/CT accurately identifies MEN1-associated pheochromocytoma.

Endocrinol Diabetes Metab Case Rep 2020 Mar 3;2020. Epub 2020 Mar 3.

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK).

Summary: 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 masses. The left adrenal mass grew from 2.5 to 3.9 cm over 4 years with attenuation values of 9 Hounsfield units (HU) pre-contrast and 15 HU post-contrast washout. Laboratory evaluation demonstrated an adrenergic biochemical phenotype. Both 18F-fluorodeoxyglucose (18F-FDG) PET/CT and 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy demonstrated bilateral adrenal uptake. In contrast, 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT demonstrated unilateral left adrenal uptake (28.7 standardized uptake value (SUV)) and physiologic right adrenal uptake. The patient underwent an uneventful left adrenalectomy with pathology consistent for PHEO. Post-operatively, he had biochemical normalization. A review of the literature suggests that adrenal tumors >2 cm may be at higher risk for pheochromocytoma in patients with MEN1. Despite a lack of symptoms related to catecholamine excess, enlarging adrenal nodules should be biochemically screened for PHEO. 18F-FDOPA PET/CT may be beneficial for localization in these patients.

Learning Points: 18F-FDOPA PET/CT is a beneficial imaging modality for identifying pheochromocytoma in MEN1 patients. Adrenal adenomas should undergo routine biochemical workup for PHEO in MEN1 and can have serious peri-operative complications if not recognized, given that MEN1 patients undergo frequent surgical interventions. MEN1 is implicated in the tumorigenesis of PHEO in this patient.
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http://dx.doi.org/10.1530/EDM-19-0156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077596PMC
March 2020

Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents.

J Cancer Res Clin Oncol 2020 Apr 15;146(4):1051-1063. Epub 2020 Feb 15.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.

Purpose: Pheochromocytomas/paragangliomas (PHEOs/PGLs) are rare in children with only a few SDHB mutation-related cases. Previous studies on children were conducted in small cohorts. This large set of pediatric patients provides robust data in the evaluation of clinical outcomes.

Methods: Sixty-four pediatric PHEO/PGL patients with SDHB germline mutations were included in the present study. The clinical presentation, disease course, and survival rate were evaluated.

Results: Thirty-eight males and 26 females were diagnosed with PHEO/PGL at a median age of 13 years. The majority of patients displayed norepinephrine hypersecretion and 73.44% initially presented with a solitary tumor. Metastases developed in 70% of patients at the median age of 16 years and were mostly diagnosed first 2 years and in years 12-18 post-diagnosis. The presence of metastases at the time of diagnosis had a strong negative impact on survival in males but not in females. The estimated 5-, 10-, and 20-year survival rates were 100%, 97.14%, and 77.71%, respectively.

Conclusion: The present report has highlighted several important aspects in the management of pediatric patients with SDHB mutations associated-PHEO/PGL. Initial diagnostic evaluation of SDHB mutation carriers should be started at age of 5-6 years with initial work-up focusing on abdominal region. Thorough follow-up is crucial first 2 years post-diagnosis and more frequent follow-ups are needed in years 10-20 post-diagnosis due to the increased risk of metastases. Although this age group developed metastasis as early as 5 years from diagnosis, we have shown that the overall 20-year prognosis and survival are good.
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http://dx.doi.org/10.1007/s00432-020-03138-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388579PMC
April 2020

Multi-omics Signatures and Translational Potential to Improve Thyroid Cancer Patient Outcome.

Cancers (Basel) 2019 Dec 10;11(12). Epub 2019 Dec 10.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20817, USA.

Recent advances in high-throughput molecular and multi-omics technologies have improved our understanding of the molecular changes associated with thyroid cancer initiation and progression. The translation into clinical use based on molecular profiling of thyroid tumors has allowed a significant improvement in patient risk stratification and in the identification of targeted therapies, and thereby better personalized disease management and outcome. This review compiles the following: (1) the major molecular alterations of the genome, epigenome, transcriptome, proteome, and metabolome found in all subtypes of thyroid cancer, thus demonstrating the complexity of these tumors and (2) the great translational potential of multi-omics studies to improve patient outcome.
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http://dx.doi.org/10.3390/cancers11121988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966476PMC
December 2019

Adrenocortical carcinoma and pulmonary embolism from tumoral extension.

Endocrinol Diabetes Metab Case Rep 2019 Nov 25;2019. Epub 2019 Nov 25.

Section on Endocrinology & Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Summary: Adrenococortical carcinoma (ACC) is a rare cancer, occurring at the rate of one case in two million person years. Cushing syndrome or a mixed picture of excess androgen and glucocorticoid production are the most common presentations of ACC. Other uncommon presentations include abdominal pain and adrenal incidentalomas. In the present report, a 71-year-old male presented with abdominal pain and was eventually diagnosed with ACC. He was found to have pulmonary thromboembolism following an investigation for hypoxemia, with the tumor thrombus extending upto the right atrium. This interesting case represents the unique presentation of a rare tumor, which if detected late or left untreated is associated with poor outcomes, highlighting the need for a low index of suspicion for ACC when similar presentations are encountered in clinical practice.

Learning Points: ACC is a rare but aggressive tumor. ACC commonly presents with rapid onset of hypercortisolism, combined hyperandrogenism and hypercortisolism, or uncommonly with compressive symptoms. Clinicians should have a low index of suspicion for ACC in patients presenting with rapid onset of symptoms related to hypercortisolism and/or hyperandrogenism. Venous thromboembolism and extension of the tumor thrombus to the right side of the heart is a very rare but serious complication of ACC that clinicans should be wary of. The increased risk of venous thromboembolism in ACC could be explained by direct tumor invasion, tumor thrombi or hypercoagulability secondary to hypercortisolism. Early diagnosis and prompt treatment can improve the long-term survival of patients with ACC.
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http://dx.doi.org/10.1530/EDM-19-0095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893304PMC
November 2019

Preoperative systemic inflammatory markers are prognostic indicators in recurrent adrenocortical carcinoma.

J Surg Oncol 2019 Dec 16;120(8):1450-1455. Epub 2019 Nov 16.

Surgical Oncology Program, National Cancer Institute, Bethesda, Maryland.

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 retrospectively analyzed. Preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), and mean platelet volume were calculated.

Results: Twenty-five patients (age at operation 52.2 ± 9.5 years) were identified. We observed a statistically significant shorter disease-specific survival (DSS) in patients with LMR less than 4 (41 ± 7.4 months vs 71 ± 12.3, P = .023) and male sex (26.6 ± 4.2 months vs 57.6 ± 9.5 months, P = .079), while time-to-recurrence (TTR) less than 12 months (40 ± 7.7 months vs 70.3 ± 13.1 months, P = .059) had a trend on univariate analysis for worse DSS. On multivariable analysis, LMR < 4 (hazard ratio [HR] 4.18; 95% confidence interval [CI]: 1.18-14.76; P = .027) and TTR less than 12 months (HR 2.77 95% CI: 1-7.62; P = .049) were found to be significantly associated with worse DSS.

Conclusion: Preoperative LMR greater than 4 and TTR greater than 12 months are associated with longer DSS. Patients with LMR greater than 4 and TTR greater than 12 months may benefit from a more aggressive therapeutic approach and may require less frequent surveillance.
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http://dx.doi.org/10.1002/jso.25760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192065PMC
December 2019

Some Considerations in Treating Malignant Head and Neck Paragangliomas.

JAMA Otolaryngol Head Neck Surg 2020 02;146(2):209-210

Section on Medical Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1001/jamaoto.2019.3444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685196PMC
February 2020

Limited Utility of Circulating Cell-Free DNA Integrity as a Diagnostic Tool for Differentiating Between Malignant and Benign Thyroid Nodules With Indeterminate Cytology (Bethesda Category III).

Front Oncol 2019 18;9:905. Epub 2019 Sep 18.

Metabolic Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

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. The cfDI was measured in the plasma of patients with cytologically indeterminate thyroid nodules. All patients underwent plasma collection within 24-72 h before surgical treatment for thyroid nodules. Additionally, samples were collected from seven patients via the vein draining the thyroid and peripheral vein during surgery. Quantitative real-time PCR was performed on the isolated cell-free DNA using two different primer sets (115 and 247 bp) to amplify consensus ALU sequences. The cfDI was calculated as the ratio of ALU247 to ALU115. All data are given as median [25th-75th percentile]. The study group consisted of 67 patients with 100 nodules, 80.6% (54/67) women, aged 43 [33-60] years. There was no difference in cfDI between 29 patients with benign nodules (0.49 [0.41-0.59]) and 38 patients with malignant lesions (0.45 [0.36-0.57], = 0.19). There was no difference in cfDI in the vein draining the thyroid (0.47 [0.24-1.05]) and peripheral vein (0.48 [0.36-0.56], = 0.44). In comparison to thyroid cancer patients, patients with benign nodules were characterized by significantly higher concentrations of ALU115 (1,064 [529-2,960] vs. 411 [27-1,049] ng/ml; = 0.002) and ALU247 (548 [276-1,894] vs. 170 [17-540] ng/ml; = 0.0005), most likely because benign tumors were larger (3, [1.8-4.1 cm]) than malignant lesions (0.7 [0.23-1.45], < 0.0001). Women had significantly lower cfDI (0.45 [0.27-0.54]) than men (0.56 [0.44-0.8], = 0.011). The cfDI measured in the vein draining the thyroid is similar to the cfDI measured in the antecubital vein, validating cfDI measurements by peripheral liquid biopsy. Analysis of cfDI needs to be stratified by patients gender. In contrast to its diagnostic utility in aggressive cancers, cfDI has limited utility as a biomarker of malignancy in cytologically indeterminate thyroid nodules.
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http://dx.doi.org/10.3389/fonc.2019.00905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759775PMC
September 2019

Surgical Resection of Pheochromocytomas and Paragangliomas is Associated with Lower Cholesterol Levels.

World J Surg 2020 02;44(2):552-560

Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.

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 Institutes of Health from 2009 to 2016, of which 54 patients met the inclusion criteria. Clinical demographics, BMI, genetic mutations, tumor size, perioperative catecholamine levels and perioperative lipid panels were retrospectively reviewed. Spearman correlation between catecholamines and lipid levels was evaluated. Paired Wilcoxon and paired t test were used to analyze differences in pre- and postoperative lipid levels.

Results: Preoperatively, 51 patients (94.4%) had elevated catecholamines, thirteen (24.1%) had elevated total cholesterol (TC) (>200 mg/dL), nine (16.6%) had elevated LDL (>130 mg/dL) and ten (18.5%) had elevated triglycerides (>150 mg/dL). Serum and urinary metanephrine levels were positively associated with TC (r = 0.2792, p = 0.0372 and r = 0.4146, p = 0.0031, respectively) and LDL levels (r = 0.2977, p = 0.0259 and r = 0.4434, p = 0.0014, respectively). Mean TC decreased from 176.4 to 166.3 mg/dL (p = 0.0064) and mean HDL decreased from 56.7 to 53.2 mg/dL (p = 0.0253) after PPGL resection (median 3.1 months (range 1.3-50.2) between lipid panels). Most patients with elevated TC (76.9%) had improvement with mean TC decreasing from 225 to 200.2 mg/dL (p = 0.0230). Of patients with elevated LDL, 66.7% had improvement with mean LDL decreasing from 149 to 131.1 mg/dL (p = 0.0313).

Conclusions: The prevalence of hyperlipidemia in patients with PPGLs is 46%. Future prospective studies are needed to determine whether surgical resection improves TC and/or LDL levels.
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http://dx.doi.org/10.1007/s00268-019-05175-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442156PMC
February 2020

Precision Surgery for Pheochromocytomas and Paragangliomas.

Horm Metab Res 2019 Jul 15;51(7):470-482. Epub 2019 Jul 15.

Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Since Felix Fränkel's account of pheochromocytoma in 1886, great discoveries and vast advancements in the diagnosis, genetics, anatomical and functional imaging techniques, and surgical management of pheochromcytoma and paraganglioma (P-PGL) have been made. The improved insight in the pathophysiology of P-PGL and more accurate detection methods enable physicians to tailor the treatment plan to an individual based on the genetic profile and tumor behavior. This review will cover briefly the clinical features, diagnosis, genetic mutations, and imaging modalities that are used to guide current surgical management of these rare and interesting endocrinopathies.
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http://dx.doi.org/10.1055/a-0926-3618DOI Listing
July 2019

Postoperative Management in Patients with Pheochromocytoma and Paraganglioma.

Cancers (Basel) 2019 07 3;11(7). Epub 2019 Jul 3.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla and sympathetic/parasympathetic ganglion cells, respectively. Excessive release of catecholamines leads to episodic symptoms and signs of PPGL, which include hypertension, headache, palpitations, and diaphoresis. Intraoperatively, large amounts of catecholamines are released into the bloodstream through handling and manipulation of the tumor(s). In contrast, there could also be an abrupt decline in catecholamine levels after tumor resection. Because of such binary manifestations of PPGL, patients may develop perplexing and substantially devastating cardiovascular complications during the perioperative period. These complications include hypertension, hypotension, arrhythmias, myocardial infarction, heart failure, and cerebrovascular accident. Other complications seen in the postoperative period include fever, hypoglycemia, cortisol deficiency, urinary retention, etc. In the interest of safe patient care, such emergencies require precise diagnosis and treatment. Surgeons, anesthesiologists, and intensivists must be aware of the clinical manifestations and complications associated with a sudden increase or decrease in catecholamine levels and should work closely together to be able to provide appropriate management to minimize morbidity and mortality associated with PPGLs.
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http://dx.doi.org/10.3390/cancers11070936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678461PMC
July 2019

MicroRNA-210 May Be a Preoperative Biomarker of Malignant Pheochromocytomas and Paragangliomas.

J Surg Res 2019 11 27;243:1-7. Epub 2019 May 27.

Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Background: Currently, no reliable predictive clinical or laboratory tests exist that can accurately distinguish between benign and malignant pheochromocytomas or paragangliomas (PPGLs). The aim of this study was to investigate if serum microRNA-210 (miR-210) levels could be a marker of malignancy in patients with PPGLs.

Methods: Preoperative serum from patients with PPGLs was collected on the day of surgery. Clinical demographics, germline mutation status, primary tumor size, postoperative biochemical response, and the development of malignant disease were prospectively collected. Total microRNA was extracted from preoperative serum samples, and miR-210 levels were measured by quantitative real-time reverse transcription-polymerase chain reaction and normalized to miR-16. Prognostic variables were compared using univariable and multivariable analyses.

Results: Of the 35 patients, 10 (29%) were diagnosed with malignant PPGLs and 25 patients (71%) were diagnosed with benign PPGLs (median follow-up 72.5 mo). Sixty-nine percent of patients had a pheochromocytoma (n = 24/35) compared with 31% of patients with paraganglioma (n = 11/35). The most common germline mutation was succinate dehydrogenase complex subunit B (SDHB) (n = 10). On univariable analysis, lower serum miR-210 expression level (2.3 ± 0.5 versus 3.1 ± 1.2, P = 0.013) and larger primary tumor size (6.7 ± 5.0 cm versus 4.1 ± 2.3 cm, P = 0.043) were significantly associated with malignant disease. No significant prognostic variables were found on multivariable analysis.

Conclusions: In this pilot study, low serum miR-210 expression levels and large primary tumors were identified to be markers of PPGL malignancy on univariable analysis. Given the initial encouraging results in a small cohort, further investigation is warranted to determine if serum miR-210 levels are prognostic.
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http://dx.doi.org/10.1016/j.jss.2019.04.086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478339PMC
November 2019

ONCOGENE PANEL SEQUENCING ANALYSIS IDENTIFIES CANDIDATE ACTIONABLE GENES IN ADVANCED WELL-DIFFERENTIATED GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS.

Endocr Pract 2019 Jun 13;25(6):580-588. Epub 2019 Mar 13.

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. A phase II mutation targeted therapy trial was conducted in patients with advanced well-differentiated G1/G2 GEP-NET. Mutations found in the mTOR pathway-associated genes led to treatment with the mTOR inhibitor everolimus, and were defined as actionable. Tumor deoxyribonucleic acid (DNA) from GEP-NET were sequenced and compared with germline DNA, using the OncoVAR-NET assay, designed for hybrid capture sequencing of 500 tumor suppressor genes and oncogenes. Somatic variants were called and copy-number (CN) variant analysis was performed. Thirty patients (14 small-intestine, 8 pancreatic, 3 unknown primary NET, and 5 of other primary sites) harbored 37 lesions (4 patients had DNA of multiple lesions sequenced). Only 2 patients with sporadic NET (n = 26) had an actionable mutation leading to treatment with everolimus. Driver somatic mutations were detected in 18 of 30 patients (21/37 lesions sequenced). In the remaining samples without a driver mutation, CN alterations were found in 11/16 tumors (10/12 patients), including CN loss of chromosome (Chr) 18 (<.05), CN gain of Chr 5, and loss of Chr 13. CN losses in Chr 18 were more common in patients without driver mutations detected. Pronounced genetic heterogeneity was detected in patients with multiple lesions sequenced. Genome-wide DNA sequencing may identify candidate actionable genes and lead to the identification of novel target genes for advanced well-differentiated GEP-NET. = chromosome; = copy number; = deoxyribonucleic acid; = Food and Drug Administration; = gastro-enteropancreatic; = multiple endocrine neoplasia syndrome type 1; = mammalian target of rapamycin; = neuroendocrine tumor; = progression-free survival; = pancreatic neuroendocrine tumors; = small-intestine neuroendocrine tumor.
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http://dx.doi.org/10.4158/EP-2018-0603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170837PMC
June 2019

The utility of Gallium-DOTATATE PET/CT in the detection of von Hippel-Lindau disease associated tumors.

Eur J Radiol 2019 Mar 22;112:130-135. Epub 2018 Nov 22.

Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States; Department of Surgery, The George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, United States.

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. Ga-DOTATATE positron emission tomography (PET)/computerized tomography (CT) has been shown to be highly accurate for tumors with cells expressing somatostatin receptors. We aimed to assess the performance of Ga-DOTATATE PET/CT in patients with VHL disease.

Methods: Patients with a diagnosis of VHL were enrolled in a prospective study and underwent surveillance imaging for pancreatic lesions (n = 301). The current analysis includes 73 evaluations with multiple imaging modalities of 36 patients (2.1 ± 0.8 evaluations/patient, range 1-4) for a head-to-head comparison of Ga-DOTATATE PET/CT, CT and/or MRI. In this post-hoc analysis we compared the detection rates of various imaging modalities for PNETs and for any extrapancreatic tumors located within the scan field of CT/MRI of the abdomen.

Results: Ga-DOTATATE PET/CT detected a total of 206 lesions, CT detected 208 lesions and MRI detected 94 lesions in 61, 66 and 33 scans, respectively. Ga-DOTATATE PET/CT (3.4 ± 0.1 per scan) was superior than CT (3.2 ± 0.1 per scan, p = 0.02) with a similar trend when comparing with MRI (2.8 ± 0.1 per scan, p = 0.03) in detecting lesions in any anatomic locations.

Conclusions: Ga-DOTATATE PET/CT had a significantly higher detection rate when compared with anatomic imaging for all lesions, and comparable detection rate for pancreatic lesions in VHL patients. Hence, given the higher accuracy and lower radiation exposure associated with Ga-DOTATATE PET/CT, its potential role in the surveillance of VHL-associated lesions should be further studied.
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http://dx.doi.org/10.1016/j.ejrad.2018.11.023DOI Listing
March 2019

Is VTE Prophylaxis Necessary on Discharge for Patients Undergoing Adrenalectomy for Cushing Syndrome?

J Endocr Soc 2019 Feb 12;3(2):304-313. Epub 2018 Dec 12.

Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: Patients with Cushing syndrome (CS) have an increased risk for venous thromboembolism (VTE). However, it is unclear whether patients undergoing adrenalectomy for CS are at increased risk for postoperative VTE. The aim of this study was to determine the rate of postoperative VTE in patients undergoing adrenalectomy for CS.

Methods: A retrospective analysis of patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent adrenalectomy from 2005 to 2016 was performed. We compared the clinical characteristics and 30-day postoperative VTE occurrence in patients with and without CS.

Results: A total of 4217 patients were analyzed; 2607 (61.8%) were female and 310 (7.4%) had CS. The overall prevalence of postoperative VTE was 1.0% (n = 45). The rates of VTE were higher in patients with CS (2.6% vs 0.9%; = 0.007). In the two groups, CS was associated with younger age, increased body mass index, and diabetes mellitus ( < 0.001). CS was also associated with longer length of operation and longer hospital length of stay ( < 0.001). In the subgroup of patients who had diagnosed VTE, CS was associated with longer length of operation ( < 0.001). Rates of laparoscopic vs open surgery were equivalent between patients with and without CS, and VTE events did not differ. The median time to VTE event was 14.5 days (range, 1 to 23 days) in the CS group and 4 days (range, 2 to 25 days) in the group without CS.

Conclusions: The prevalence of postoperative VTE was increased in patients undergoing adrenalectomy for CS. In patients with CS undergoing adrenalectomy, VTE prophylaxis for 28 days should be considered upon discharge.
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http://dx.doi.org/10.1210/js.2018-00278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330172PMC
February 2019