Adenomatoid tumor of the genital tract: evidence of mesenchymal cell origin.

The objective of this study was to re-examine the histogenesis of adenomatoid tumors. This benign neoplasm is characterized by gland-like structures with a pseudodinfiltrative pattern, usually involving fibromuscular tissue at a certain distance from an overlying surface mesothelium. Twenty cases of adenomatoid tumors and four cases of reactive submesothelial lesions, characterized by marked proliferation of subserosal mesenchymal cells, were reviewed. Nineteen of twenty adenomatoid tumors, including lesions with ill-defined borders, showed no connection with surface mesothelium. At the periphery of small tumors, isolated glands, clusters of epithelioid cells and single epithelioid, and spindled cells showing no connection to adjacent glands or cell clusters were identified. The tumor cells shared features with reactive subserosal stromal cells including an infiltrative pattern and histochemical and immunohistochemical properties. The differences between adenomatoid tumors and reactive submesothelial tissue are quantitative in nature: predominant amount of spindled cells in reactive submesothelial lesions, and predominant amount of gland-like structures in adenomatoid tumors. It is proposed that adenomatoid tumors arise from pluripotent mesenchymal cells that differentiate toward submesothelial cells and eventually mesothelial cells. This differentiation is probably induced by the adjacent submesothelial cells.     

Complex Vertebral Arteriovenous Fistula and Ruptured Aneurysm in Neurofibromatosis: A Therapeutically Challenging Case

The objective and importance of this study was to describe the challenges encountered with treating a high-flow vertebral arteriovenous fistula (AVF) and ruptured aneurysm in a patient with life-threatening hemorrhage. A 36-year-old female with Neurofibromatosis type 1 (NF1) presented 2 weeks after uneventful cesarean section with a rapidly expanding pulsatile neck mass. Angiography demonstrated a complex left vertebral AVF and multiple associated vertebral artery aneurysms. Emergent endovascular coil embolization was performed using a retrograde and antegrade approach to occlude the fistulas and trap the ruptured aneurysm, successfully treating the acute hemorrhage. Subsequent definitive therapy was accomplished utilizing a combined neurointerventional and neurosurgical strategy of direct-puncture acrylic embolization and ligation of the vertebral artery. Recent advances in neurointerventional technology allow novel approaches in the primary and/or preoperative treatment of complex vascular lesions such as those seen in NF1.     

Restless legs syndrome in psoriasis: an unexpected comorbidity

Background

Restless legs syndrome (RLS) is characterized by unpleasant sensations in the legs and an uncontrollable urge to move them in order to gain relief. Higher frequencies of RLS have been reported in systemic lupus, multiple sclerosis, rheumatoid arthritis and atopic dermatitis.

Objectives

Since the disease-related stress present in psoriasis is similar to the stress of those diseases, we aimed to study the frequency of RLS in a German cohort of patients with psoriasis.

Methods

300 patients with psoriasis and 300 healthy controls were evaluated for RLS symptoms in this study.

Results

While 17% (n = 51) of patients with psoriasis reported symptoms of RLS, only 4% (n = 12) of individuals without psoriasis suffered from RLS symptoms (95% confidence interval: 0.08–0.18, p<0.01). In patients with psoriasis and RLS the average RLS score was 16.0 ± 9.2 whereas individuals with RLS in the control group had an average RLS score of 13.5 ± 7.1.

Conclusions

Our findings indicate an increased frequency of RLS in patients with psoriasis, suggesting screening patients with psoriasis for the presence of RLS as a well-treatable co-morbidity.

     

Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers

Objective Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, is metabolized primarily by cytochrome P450 (CYP) 3A with minor contributions from CYP1A2, CYP2C19, and glucuronidation. Co-administration with CYP inhibitors may increase systemic exposure to axitinib and alter its safety profile. This study evaluated changes in axitinib plasma pharmacokinetic parameters and assessed safety and tolerability in healthy subjects, following axitinib co-administration with the potent CYP3A inhibitor ketoconazole. Methods In this randomized, single-blind, two-way crossover study, 32 healthy volunteers received placebo, followed by a single 5-mg oral dose of axitinib, administered either alone or on the fourth day of dosing with oral ketoconazole (400 mg/day for 7 days). Results Axitinib exposure was significantly increased in the presence of ketoconazole, with a geometric mean ratio for area under the plasma concentration–time curve from time zero to infinity of 2.06 (90% confidence interval [CI]: 1.84–2.30) and a geometric mean ratio for maximum plasma concentration (C_max) of 1.50 (90% CI: 1.33–1.70). For axitinib alone or with ketoconazole, C_max occurred 1.5 and 2.0 h after dosing, respectively. Adverse events were predominantly mild; the most commonly reported treatment-related adverse events were headache and nausea. Conclusions Axitinib plasma exposures and peak concentrations were increased following concurrent administration of axitinib and ketoconazole in healthy volunteers. Axitinib alone and in combination with ketoconazole was well tolerated. These findings provide an upper exposure for expected axitinib plasma concentrations in the presence of potent metabolic inhibition.     

A review on dural tail sign

"Dural tail sign" (DTS) which is a thickening of the dura adjacent to an intracranial pathology on contrast-enhanced T1 MR Images, was first thought to be pathognomonic of meningioma, however, many subsequent studies demonstrated this sign adjacent to various intra- and extra-cranial pathologies and in spinal lesions. In this paper we outline the history, accompanying pathologies and the differentiation and probable pathophysiology of DTS. We also discuss whether we can predict tumoral involvement of the dural tail before surgery and whether the dural tail adjacent to a tumor should be resected.     

Auraptene Induces Apoptosis via Myeloid Cell Leukemia 1‐Mediated Activation of Caspases in PC3 and DU145 Prostate Cancer Cells

Although auraptene, a prenyloxy coumarin from Citrus species, was known to have anti‐oxidant, anti‐bacterial, antiinflammatory, and anti‐tumor activities, the underlying anti‐tumor mechanism of auraptene in prostate cancers is not fully understood to date. Thus, in the present study, we have investigated the anti‐tumor mechanism of auraptene mainly in PC3 and DU145 prostate cancer cells, because auraptene suppressed the viability of androgen‐independent PC3 and DU145 prostate cancer cells better than androgen‐sensitive LNCaP cells. Also, auraptene notably increased sub‐G1 cell population and terminal deoxynucleotidyl transferase dUTP nick end labeling‐positive cells as features of apoptosis in two prostate cancer cells compared with untreated control. Consistently, auraptene cleaved poly(ADP‐ribose) polymerase, activated caspase‐9 and caspase‐3, suppressed the expression of anti‐apoptotic proteins, including Bcl‐2 and myeloid cell leukemia 1 (Mcl‐1), and also activated pro‐apoptotic protein Bax in both prostate cancer cells. However, Mcl‐1 overexpression reversed the apoptotic effect of auraptene to increase sub‐G1 population and induce caspase‐9/3 in both prostate cancer cells. Taken together, the results support scientific evidences that auraptene induces apoptosis in PC3 and DU145 prostate cancer cells via Mcl‐1‐mediated activation of caspases as a potent chemopreventive agent for prostate cancer prevention and treatment. Copyright © 2017 John Wiley & Sons, Ltd.