Campylobacter jejuni as a Cause of Acute Infectious Thyroiditis, on a Background of SLE-related End Stage Renal Failure and CMV Viraemia: A Case Report and Review of the Literature

<p>Acute suppurative thyroiditis is a rare cause of thyroid disease; however it is capable of causing widespread systemic illness, with catastrophic complications. A large number of causative pathogens have been identified, the most common being Staphylococcus and Streptococcal species. We report a rare case of acute suppurative thyroiditis, caused by Campylobacter jejuni in a patient with systemic lupus erythematosus-related end-stage renal failure and excessive CMV viraemia. She developed severe respiratory compromise and required emergency total thyroidectomy and central neck clearance, which cured the local septic focus. The patient died from refractory sepsis due to E. coli.</p

Oncologic Resection Achieving R0 Margins Improves Disease-Free Survival in Parathyroid Cancer

<p>Parathyroid cancer has a poor mid-term prognosis, often because of local recurrence, observed in half of all patients. Modern diagnostic workup increasingly enables a preoperative diagnosis of parathyroid cancer. There is limited evidence that more comprehensive oncologic surgery can reduce the risk of local recurrence. This study aims to identify the best specific surgical approach in parathyroid cancer.<br>This observational cohort study comprises 19 consecutive patients who had undergone oncologic or nononcologic resection for parathyroid cancer. Baseline parameters were compared by using univariate analysis; outcomes were assessed by χ (2) testing and Kaplan-Meier statistics.<br>Fifteen of 19 patients were primarily operated on in our tertiary center between 1996 and 2013, and four were referred for follow-up because of their cancer diagnosis. Patient cohorts defined by histologic R-status were comparable for established risk factors: sex, calcium levels, low-risk/high-risk status, and presence of vascular invasion. Oncologic resections were performed in 13 of 15 patients primarily treated in the center and 0 of 4 treated elsewhere (χ (2) = 5.6; p < 0.01). R0 margins were achieved in 11 of 13 (85 %) undergoing oncologic resection and 1 of 6 (17 %) undergoing local excision (χ (2) = 8.1; p < 0.01). R0 margins and primary oncologic resection were associated with higher disease-free survival rates (χ (2) = 7.9; p = 0.005 and χ (2) = 4.7; p = 0.03, respectively). Revision surgery achieved R0 margins in only 2 of 4 (50 %) of patients.<br>In parathyroid cancer, a more comprehensive surgery (primary oncologic resection) provides significantly better outcomes than local excision as a result of reduction of R1 margins and locoregional recurrence.</p> <p> </p

A 13-Steroid Serum Panel Based on LC-MS/MS: Use in Detection of Adrenocortical Carcinoma

<h4>BACKGROUND: </h4><p>Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates. Corresponding serum assays for most steroid pathway intermediates are usually unavailable because of low demand or lack of immunoassay specificity. Serum steroid analysis by LC-MS/MS is increasingly replacing immunoassay, in particular for steroids most subject to cross-reaction.</p><h4>METHODS: </h4><p>We developed an LC-MS/MS method for the measurement of serum androstenedione, corticosterone, cortisol, cortisone, 11-deoxycorticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, and testosterone. Assay value in discriminating ACC from other adrenal lesions (phaeochromocytoma/paraganglioma, cortisol-producing adenoma, and lesions demonstrating no hormonal excess) was then investigated.</p><h4>RESULTS: </h4><p>In ACC cases, between 4 and 7 steroids were increased (median = 6), and in the non-ACC groups, up to 2 steroids were increased. 11-Deoxycortisol was markedly increased in all cases of ACC. All steroids except testosterone in males and corticosterone and cortisone in both sexes were of use in discriminating ACC from non-ACC adrenal lesions.</p><h4>CONCLUSIONS: </h4><p>Serum steroid paneling by LC-MS/MS is useful for diagnosing ACC by combining the measurement of steroid hormones and their precursors in a single analysis.</p

Simultaneous targeting PI3K/Akt/mTOR and MEK/RAF/ERK pathways results in a synergis6c an6-prolifera6ve effect in an adrenocor6cal carcinoma model

<p>Introduction:</p> <p>Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options.</p> <p>Aim:</p> <p>The aim of this study was to assess the anti-proliferative effect of combinatorial targeting of the PI3K/Akt/mTOR pathway with different drugs and simultaneous targeting of the MEK/Raf/ERKpathway in H295R adrenocortical cancer cells.</p> <p>Material and Methods:</p> <p>The cytotoxicity of LY294002 (pan-PI3K inhibitor), everolimus (mTOR inhibitor), BEZ235 (dual PI3K/mTOR inhibitor) and U0126 (MEK1/2 inhibitor) was assessed by Alamar blue assay in the H295R cell line. After finding the maximal cytotoxic concentrations for all inhibitors, we used suboptimal concentrations for experiments where multiple agents were used simultaneously. Everolimus and BEZ235 were kindly provided by Novartis, Switzerland; LY294002 and U0126 were commercially available.</p> <p>Results:</p> <p>While everolimus, BEZ235 and LY294002 caused 20±6%, 15.6±6% and 11±1% cytotoxicity when used as single agents, co-treatment of cells with everolimus and BEZ235 showed a synergistic cytotoxic effect of 54±9% (p=0.007) (the strongest effect for combination of two inhibitors in our system, N=3 independent experiments). Addition of LY294002 to everolimus and BEZ235 increased the effect further to 65±7%.</p> <p>We also explored the potential benefit of combined inhibition of PI3K/mTOR and MEK1/2. Addition of U0126 to BEZ235 had a synergistic effect (42±3% vs 14±5% and 15±5.6% alone, respectively, N=3 independent experiments). We observed only an additive effect if the MEK1/2 inhibitor was added to everolimus alone or in combination with BEZ235.</p> <p>Conclusions:</p> <p>The combination of agents inhibiting PI3K/Akt/mTOR and MEK/Raf/ERK pathways results in a synergistic cytotoxic effect. Our results suggest also that multiple mode of inhibition of the same pathway may result in a greater cytotoxic effect in adrenocortical cancer cells which cannot be achieved by simple dose escalation. We suggest that new combinations targeting those pathways require further investigation to improve the treatment of ACC patients.</p