Anna Aronova

Management of hypertension in primary aldosteronism

Hypertension causes significant morbidity and mortality worldwide, owing to its deleterious effects on the cardiovascular and renal systems. Primary hyperaldosteronism (PA) is the most common cause of reversible hypertension, affecting 5%-18% of adults with hypertension. PA is estimated to result from bilateral adrenal hyperplasia in two-thirds of patients, and from unilateral aldosterone-secreting adenoma in approximately one-third. Suspected cases are initially screened by measurement of the plasma aldosterone-renin-ratio, and may be confirmed by additional noninvasive tests. Localization of aldostosterone hypersecretion is then determined by computed tomography imaging, and in selective cases with adrenal vein sampling. Solitary adenomas are managed by laparoscopic or robotic resection, while bilateral hyperplasia is treated with mineralocorticoid antagonists. Biochemical cure following adrenalectomy occurs in 99% of patients, and hemodynamic improvement is seen in over 90%, prompting a reduction in quantity of anti-hypertensive medications in most patients. End-organ damage secondary to hypertension and excess aldosterone is significantly improved by both surgical and medical treatment, as manifested by decreased left ventricular hypertrophy, arterial stiffness, and proteinuria, highlighting the importance of proper diagnosis and treatment of primary hyperaldosteronism. Although numerous independent predictors of resolution of hypertension after adrenalectomy for unilateral adenomas have been described, the Aldosteronoma Resolution Score is a validated multifactorial model convenient for use in daily clinical practice.

Aldosteronoma resolution score predicts long-term resolution of hypertension

BACKGROUND The Aldosteronoma Resolution Score (ARS) takes into consideration four, readily available, preoperative clinical parameters in predicting the likelihood of resolution of hypertension in patients 6 months after undergoing unilateral adrenalectomy for aldosterone-producing adenoma (APA). We sought to determine the durability of this predictive model after 1 year. METHODS Sixty patients who underwent unilateral adrenalectomy for APA at a single institution between 2004 and 2013 were reviewed retrospectively. Patients who were normotensive without any antihypertensive medication requirement at greater than 1-year follow-up were considered to have complete resolution of hypertension. RESULTS Forty-seven patients had data available for analysis. Median follow-up was 1,135 days (371-3,202). Forty-five percent of patients had complete resolution, 45% had improvement, and 10% had no improvement in hypertension. Applying the ARS, we found there was complete resolution of hypertension in 73% of patients with ARS 4-5, 53% of patients with ARS 2-3, and 24% of patients with ARS 0-1 compared with 75% (P = .9), 46% (P = .66), and 28% (P = .76), respectively, in the original cohort used to create the ARS. CONCLUSION Most patients (90%) have long-term improvement or complete resolution of hypertension after unilateral adrenalectomy for APA. The ARS predicts accurately a patients likelihood of complete resolution of hypertension beyond 1 year.

Prostate-Specific Membrane Antigen Is a Potential Antiangiogenic Target in Adrenocortical Carcinoma.

CONTEXT Adrenocortical carcinoma (ACC) is a rare tumor type with a poor prognosis and few therapeutic options. OBJECTIVE Assess prostate-specific membrane antigen (PSMA) expression as a potential novel therapeutic target for ACC. DESIGN Expression of PSMA was evaluated in benign and malignant adrenal tumors and 1 patient with metastatic ACC. SETTING This study took place at a tertiary referral center. PATIENTS Fifty adrenal samples were evaluated, including 16 normal adrenal glands, 16 adrenocortical adenomas, 15 primary ACC, and 3 ACC metastases. MAIN OUTCOME MEASURES Demographics, PSMA expression levels via real-time quantitative polymerase chain reaction and immunohistochemistry and whole-body positron emission tomography-computed tomography standardized uptake values for 1 patient. RESULTS qPCR demonstrated an elevated level of PSMA in ACC relative to all benign tissues (P < .05). Immunohistochemistry localized PSMA expression to the neovasculature of ACC and confirmed overexpression of PSMA in ACC relative to benign tissues both in intensity and percentage of vessels stained (78% of ACC, 0% of normal adrenal, and 3.27% of adenoma-associated neovasculature; P < .001). Those with more than 25% PSMA-positive vessels were 33 times more likely to be malignant than benign (odds ratio, P < .001). Whole-body positron emission tomography-computed tomography imaging showed targeting of anti-PSMA Zr89-J591 to 5/5 of the patients multiple lung masses with an average measurement of 3.49 ± 1.86 cm and a standardized uptake value of 1.4 ± 0.65 relative to blood pool at 0.8 standardized uptake value. CONCLUSIONS PSMA is significantly overexpressed in ACC neovasculature when compared with normal and benign adrenal tumors. PSMA expression can be used to image ACC metastases in vivo and may be considered as a potential diagnostic and therapeutic target in ACC.

Cost disparity between health care systems--it's not the surgeons: A cost analysis of thyroid cancer care between the United States and France.

BACKGROUND The cost disparity between the United States and other advanced health care systems, including France, is expanding. In this report we identified the management of papillary thyroid cancer (PTC) that contribute to reimbursement disparity. METHODS A tri-institutional, retrospective review included 200 patients with PTC (100 from the United States, 100 from France) treated by total thyroidectomy with/without central neck dissection. A cost model was generated incorporating perioperative management variables (within 1 year) and their reimbursement rates according to the 2014 US Medicare and French government fee-schedules. RESULTS In the United States, total thyroidectomy with central neck dissection was more frequent (92% vs 35%, P < .001), median duration of stay was less (1 vs 3 days, P < .001), and use of radioactive iodine was less (66% vs 93%, P < .001), although Thyrogen stimulation was more prevalent (100% vs 43%, P < .001). Overall, the median cost per patient was greater in the United States (

Genomic medicine for cancer diagnosis: Genomic Medicine for Cancer Diagnosis

14,069 vs

CHL1 expression differentiates Hürthle cell carcinoma from benign Hürthle cell nodules: LI et al.

4,590, P < .001). Reimbursements to the hospital facility accounted for 70% of the disparity, despite lesser durations of stay. Nuclear medicine accounted for 19%, mostly from Thyrogen reimbursement despite less use of radioactive iodine. Surgeon fees accounted for 6%, followed by office visits, laboratory/imaging, anesthesia/pathology fees, and medications. CONCLUSION The costs of management of PTC are substantially greater in the US compared with France. Efforts to decrease this disparity should focus on reimbursements for hospital facility and use of nuclear medicine imaging.

STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive Phenotype In Vitro

Genomic diagnostics in cancer has evolved since the completion of the Human Genome Project and the advancements made in diagnosis and therapy in chronic myelogenous leukemia. Among the diseases to achieve limited success or potentially benefit from diagnostic genetic testing are thyroid cancer, Burkitts lymphoma, gastrointestinal stromal tumors, adrenocortical carcinoma, and colorectal cancer. With increased understanding of genomics, genetic tests should improve diagnosis and help guide medical and surgical management. J. Surg. Oncol. 2015 111:24–30.

991 Esophageal Dysmotility and the Utility of Barium Swallow: An Opaque Diagnosis

Hürthle cell carcinoma (HCC) is an unusual and relatively rare type of differentiated thyroid cancer. Currently, cytologic analysis of fine‐needle aspiration biopsy is limited in distinguishing benign Hürthle cell neoplasms from malignant ones. The aim of this study was to determine whether differences in the expression of specific genes could differentiate HCC from benign Hürthle cell nodules by evaluating differential gene expression in Hürthle cell disease.

Navigating the Management of Follicular Variant Papillary Thyroid Carcinoma Subtypes: A Classic PTC Comparison

BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and few therapeutic options. Stathmin1 (STMN1) is a cytosolic protein involved in microtubule dynamics through inhibition of tubulin polymerization and promotion of microtubule depolymerization, which has been implicated in carcinogenesis and aggressive behavior in multiple epithelial malignancies. We aimed to evaluate expression of STMN1 in ACC and to elucidate how this may contribute to its malignant phenotype.MethodsSTMN1 was identified by RNA sequencing as a highly differentially expressed gene in human ACC samples compared with benign adrenal tumors. Expression was confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical (IHC) staining of a tissue microarray (TMA) from two independent cohorts. The biologic relevance of STMN1 was investigated in NCI-H295R cells by lentivirus-mediated silencing.ResultsDifferential gene expression demonstrated an eightfold increase in STMN1 messenger RNA (mRNA) in malignant compared with benign adrenal tissue. IHC showed significantly higher expression of STMN1 protein in ACC compared with normal and benign tissues. STMN1 knockdown in an ACC cell line resulted in decreased cell viability, cell-cycle arrest at G0/G1, and increased apoptosis in serum-starved conditions compared with scramble short hairpin RNA (shRNA) controls. STMN1 knockdown also decreased migration, invasion, and anchorage-independent growth compared with controls.ConclusionsSTMN1 is overexpressed in human ACC samples, and knockdown of this target in vitro resulted in a less aggressive phenotype of ACC, particularly under serum-starved conditions. Further study is needed to investigate the feasibility of interfering with STMN1 as a potential therapeutic target.

Use of hybrid vascular grafts in failing access for hemodialysis: Report of two cases

Background: The gold standard for diagnosis of esophageal dysmotility is high-resolution manometry (HRM); however, barium swallow studies are still routinely incorporated in the diagnostic algorithm by clinicians. We aim to assess the sensitivity of barium swallow to diagnose esophageal dysmotility using HRM for comparison. Methods: We retrospectively reviewed 100 consecutive patients evaluated for esophageal dysmotility by both barium swallow and HRM. Dysmotility on barium swallow was graded as mild, moderate or severe. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated, including an achalasia subset analysis. Results: Compared to HRM, barium swallow had an overall sensitivity, specificity, NPV, and PPV of 88%, 35%, 80%, and 51%, respectively, for detecting esophageal dysmotility. In achalasia patients (N=17), it detected dysmotility with 100% sensitivity and 30% specificity. Excluding achalasia patients, barium swallow had 81% sensitivity and 35% specificity; in other words, 65% of patients with normal HRM were misdiagnosed with dysmotility on barium swallow. For patients who exhibited normal, mild, moderate, and severe dysmotility as diagnosed on barium swallow, the concordance rates compared with HRM were 80%, 22%, 27%, and 89%, respectively. Conclusion: Compared to the gold standard using high-resolution manometry, barium swallow accurately rules out patients with achalasia and is reliable in evaluating patients with severe dysmotility. However, it is a poor testing modality for diagnosis of esophageal dysmotility in patients without achalasia, especially in mild or moderate disease. As such, careful consideration of the diagnosis of esophageal dysmotility should be taken when using this technique.