Accuracy of endometrial sampling in the diagnosis of endometrial cancer: a multicenter retrospective analysis of the JAGO-NOGGO.

BACKGROUND: Accurate preoperative molecular and histological risk stratification is essential for effective treatment planning in endometrial cancer. However, inconsistencies between pre- and postoperative tumor histology have been reported in previous studies. To address this issue and identify risk factors related to inaccurate histologic diagnosis after preoperative endometrial evaluation, we conducted this retrospective analysis. METHODS: We conducted a retrospective analysis involving 375 patients treated for primary endometrial cancer in five different gynaecological departments in Germany. Histological assessments of curettage and hysterectomy specimens were collected and evaluated. RESULTS: Preoperative histologic subtype was confirmed in 89.5% of cases and preoperative tumor grading in 75.2% of cases. Higher rates of histologic subtype variations (36.84%) were observed for non-endometrioid carcinomas. Non-endometrioid (OR 4.41) histology and high-grade (OR 8.37) carcinomas were identified as predictors of diverging histologic subtypes, while intermediate (OR 5.04) and high grading (OR 3.94) predicted diverging tumor grading. CONCLUSION: When planning therapy for endometrial cancer, the limited accuracy of endometrial sampling, especially in case of non-endometrioid histology or high tumor grading, should be carefully considered.

A Randomized Clinical Trial of Elemental Zinc Add-on Therapy on Clinical Outcomes of Patients with Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP).

Recent studies suggest a relationship between zinc deficiency and inflammation. In the present study, we studied the effect of oral zinc supplementation on clinical improvement of chronic rhinosinusitis with nasal polyposis. In this single-blind randomized controlled trial, 44 patients with chronic rhinosinusitis with polyposis referring to ENT clinic of the Loghman Hakim hospital during 2013-2014 were randomly allocated in two groups. The treatment group (n = 28) was treated with a four-drug fixed-dose regimen (FD_FDR) consisting of oral dexamethasone (0.02 mg/kg), fluticasone nasal spray, fexophenadine 60 mg daily, montelukast 10 mg daily plus 220mg zinc sulfate capsules containing 55 mg elemental zinc, b.d., and the control group (n = 16) received the FD_FDR without supplemental zinc, for six weeks. After sixth week, two groups were compared regarding clinical outcomes based on theSNOT20 (Sinonasal outcome test) questionnaire, the general health questionnaire (SF12), the Lund-Mackay, and the Lund-Kennedy scoring systems. In the treatment group, serum zinc levels were significantly increased compared to those at the baseline (1.33 fold-increase; p = 0.0002). Within groups analysis revealed a significant reduction (p < 0.01) in LM and LK in both treatment (55% LM; 50% LK) and control groups (45% LM; 53% LK). Incontrast, between groups analysis revealed no significant differences in the LM and LK. The treatment group showed a mild superiority in general health improvement compared to that of the control group. Add-on therapy with supplemental zinc sulfate was not associated with significant improvement in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). The advantage of zinc supplementation on the general health improvement of the patients with CRSwNP requires further assessments.

Lipophilicity but not stereospecificity is a major determinant of local anaesthetic-induced cytotoxicity in human T-lymphoma cells.

BACKGROUND AND OBJECTIVES: Local neurotoxicity of local anaesthetics is a well known phenomenon which is determined by lipophilicity. Recent reports have indicated the relevance of local anaesthetic-induced cytotoxicity also in nonneuronal tissues. This study re-evaluates the role of lipophilicity in local anaesthetic cytotoxicity in nonneuronal cells. In addition, the toxicities of pipecoloxylidine S(-) enantiomers were investigated. METHODS: Local anaesthetic-induced cytotoxicity was investigated in vitro in T-lymphoma cells (Jurkat). Cells were incubated with each of eight different local anaesthetics, two esters and six amides. Annexin V-fluorescein isothiocyanate and 7-aminoactinomycin D double staining followed by flow cytometry were used to investigate the fraction of early apoptotic cells as well as the overall cell death. The concentrations leading to 50% cell death (LC50) were calculated and compared. In a second step, we compared the toxicities of S(-) bupivacaine and the racemate as well as R(+) and S(-) ropivacaine. RESULTS: Concentration-dependent cytotoxicity was observed for all investigated local anaesthetics. Apoptosis was seen at low concentrations, whereas necrosis was observed at higher concentrations. LC50 values of the different local anaesthetics yielded the following decreasing order of toxicity: tetracaine, bupivacaine, ropivacaine, prilocaine, procaine, lidocaine, articaine and mepivacaine. Toxicity correlated with octanol/buffer partition coefficients, but was independent of the ester or amide linkage. There was no effect of stereoisomerism on apoptosis and necrosis. CONCLUSION: Moderate correlations for cytotoxicity with lipophilicity and clinical potency of local anaesthetics can be found in nonneuronal cells that are less than those reported previously with neuronal cells. Structural factors such as ester or amide linkage or stereospecificity do not have any influence on cytotoxicity. Although S(-) enantiomers may be advantageous with regard to systemic toxicity, they have no advantage in respect of local cytotoxicity in vitro.