Advanced craniofacial juvenile nasopharyngeal angiofibroma. Description of surgical series,case report,and review of literature

Background  

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor occurring almost exclusively in adolescent and young adult males. The tumor is characterized by slow progression, aggressive growth, high vascularization, and increased rate of persistence and recurrence. The aim of this study was to describe a case of giant JNA from our practice and discuss the controversies of surgical treatment of advanced JNA.     

Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study

Purpose

To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients.

Methods

Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %).

Results

Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15–57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses.

Conclusion

In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin’s association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

     

Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats

This study was conducted to define the regulatory mechanisms underlying stress-induced decreases in food intake and weight gain. Rats received a single or 4 daily injections of dexamethasone (0.1 or 1 mg/kg). Food intake and weight gain were recorded, and plasma leptin, brain contents of serotonin (5-hydroxytryptamine; 5-HT), 5-hydroxy-indole-acetic acid (5-HIAA) and the raphe expression of tryptophan hydroxylase (TPH), monoamine oxidase A (MAO-A) and 5-HT reuptake transporter (5-HTT) genes were examined. A single injection of dexamethasone did not acutely affect food intake, but cumulative food intake and weight gain were suppressed dose-dependently by daily injections of dexamethasone. Both a single and repeated injections of dexamethasone elevated plasma leptin in a dose dependent manner. 5-HT contents in the hypothalamus was decreased, but 5-HIAA increased, both by a single and repeated dexamethasone. A single injection of dexamethasone did not affect mRNA expressions of TPH, MAO-A and 5-HTT genes, but repeated dexamethasone increased them in the dorsal raphe nucleus. These results suggest that plasma leptin may play a role in dexamethasone-induced anorexia. Additionally, increased expression of MAO-A and 5-HTT genes by repeated dexamethasone appears to be implicated in decreases of the brain 5-HT contents.     

Synthesis and biological evaluation of 2‐acylbenzofuranes as novel α‐glucosidase inhibitors with hypoglycemic activity

A series of benzofuran derivatives was synthesized as analogues of known natural α‐glucosidase inhibitors. Their activity was evaluated in enzymatic assay and in rat model of diabetes mellitus. Newly identified inhibitors demonstrate significant potency with IC₅₀ values ranging from 6.50 to 722.2 μm , as well as hypoglycemic activity exceeding the reference drug acarbose. Docking simulations provided insight into structure‐activity relationships to direct further development of these novel hypoglycemic agents.     

Increasing chronic subdural hematoma after endoscopic III ventriculostomy

Object: Endoscopic III ventriculostomy (ETV) is an effective and a rather safe treatment for noncommunicating hydrocephalus secondary to aqueductal stenosis and other obstructive pathologies. Though not devoid of risk, ETV is increasingly replacing shunt operations, and it prevents related complications, including overdrainage. Methods: We report a rare case of a large chronic subdural hematoma (ChSDH) after ETV in a patient with aqueductal stenosis. Three weeks after he was shunted elsewhere, he presented to us with clinical symptoms of intracranial hypotension and overdrainage. ETV was performed and the shunt removed uneventfully. On routine postoperative MRI a few weeks later, a large ChSDH was noted, the patient being totally asymptomatic. Since the ChSDH grew significantly, causing a mass effect on the follow-up MRI, it was finally drained. Large and increasing ChSDHs have previously been reported secondary to overdrainage after shunt placement, but not after ETV. Conclusions: We conclude that though rare, a ChSDH may evolve even after ETV, if there is a substantial decrease in previously elevated intracranial pressure. Received: 28 December 1999     

Effect of filler on kinetics and energy of activation of phase separation in poly(methyl methacrylate)/poly(vinyl acetate) blend

The effect of a filler on the rate and energy of activation of phase separation was studied for binary poly(methyl methacrylate)/poly(vinyl acetate) blends (system with LCST) using light scattering. It was found that the rate of phase separation of the filled blends at close quench depth ΔT = T–T_s is much lower as compared with the unfilled one at close quench depth. The activation energy for the filled blends is lower than that of unfilled blends. The drop of the rate of phase separation and of the activation energy in filled systems is explained by the formation of a border layer at the interface with solid where molecular packing is less dense and molecular mobility is restricted in comparison with unfilled polymer. Equal rates of phase separation or the equilibrium state may be achieved at higher quench depth for the filled blend.     

Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin

The ability of albumin to bind drugs and other lipophilic organic acids is decreased in chronic renal failure by the accumulation of albumin-bound uraemic toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not removed by haemodialysis. The inhibitory effects of these three uraemic toxins on the interaction of three marker ligands sodium octanoate (for medium chain fatty acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have been investigated by differential scanning microcalorimetry and flow microcalorimetry. CMPF was the most potent inhibitor and its binding site coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest inhibitor, inhibited binding to the salicylic acid site.     

Systems Medicine: from molecular features and models to the clinic in COPD

Background and hypothesis

Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.

Objective and method

Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework.

Results

In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.

Conclusions

The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them.