Abstract
BACKGROUND
to assess the long-term benefit associated with supramarginal CE resection and to apply ReSECT criteria for extent of resection in patients with primary glioblastoma IDH ...wild-type.
MATERIAL AND METHODS
We performed a retrospective search in the institutional of Livorno Hospital for adult patients with primary GBM IDH wild-type. We assess residual tumor volumetry in the early post-operative magnetic resonance imaging by the 3dslicer software. We attributed EOR classes according to ReSECT criteria based on residual contrast and non-contrast enhancing tumor volumes. We performed multivariate analysis by Cox regression including main known prognostic factors and MGMT promoter status assessed by pyrosequencing. IDH wild-type status was defined on both IDH1 and IDH2 genes.
RESULTS
We identified 173 patients who underwent surgery for confirmed primary glioblastoma IDH wild-type in our institutions from 2016 and 2022. Male/female ratio was 1.6, median age at diagnosis 68 years old (yo) (range 30-83), median KPS before surgery was 80 (range 30-100) with no significant variation at the post-operative stage. Forty out of 173 (23%) patients received a supramarginal CE resection (class 1) in the whole cohort; prevalence of class 1 resection was the highest in the subgroup of patients aged ≤ 65 yo (27%) than the subgroup of >65 ≤ 75 yo (22%) and the subgroup of >75 yo (14%). The rate of class 1 resection was not different between patients with tumors located in the right and in left hemisphere (24% and 23% respectively). We analysed survival in patients treated with adjuvant RT-TMZ and found a significant longer OS in patients operated with resection class 1 (16.7 months) than other classes (p<0.0001). Long term benefit resulted the strongest in the subgroup of patients aged ≤ 65 yo (median OS 23.8 months). Multivariate analysis confirmed EOR according to the ReSECT criteria as the strongest independent predictor factor of OS (HR 0.6, p=0.004).
CONCLUSION
We efficiently implemented ReSECT criteria for EOR in our retrospective cohort of patients with primary GBM IDH wild-type. Supramarginal CE resection defined as no residual CE and ≤ 5 cm of nCE on the post-operative imaging emerged as the strongest predictive factor of survival.
Abstract Drospirenone (DRSP) is an antialdosterone agent with progestogenic and antiandrogenic effects. This compound, has been recently used in combination with 17β-estradiol (E2) as hormonal ...therapy in postmenopausal women and has been shown to exert a significant antihypertensive effect in hypertensive post-menopausal women. Aim of the present study was to compare the effect of DRSP/E2 with those of Tibolone (T) on endothelial function, arterial stiffness, and lipid profile of early postmenopausal women naïve on post-menopausal hormonal therapy. Twenty-four women met the inclusion criteria and entered the study. Women were randomized to receive either DRSP/E2 or T for 6 months. Blood pressure and heart rate were similar in both groups at baseline and at the end of the study. Compared to baseline, endothelial function assessed by Reactive Hyperemia (RH) significantly improved in women receiving E2/DRSP, whereas no significant differences between baseline and follow up were detected in women receiving Tibolone. Women receiving E2/DRSP showed a significant decrease in pulse wave velocity and Augmentation Index compared to baseline while no changes were observed in women receiving Tibolone. The capacity of sera to trigger endothelial cells apoptosis in vitro measured by cell death assay was significantly reduced by E/DRSP but not by T (HFA-E 70 ± 5,6% vs HFD-E 41 ± 4,5%, p < 0,001). In conclusion, the present study shows that the association of Estradiol and Drospirenone as hormonal replacement therapy significantly improves vascular parameters and the composition of sera relevant for vascular protection in early post-menopausal normotensive women. These effects are not shared by Tibolone.
Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the ...Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.
Colon carcinogenesis induced in rats by azoxymethane (AOM) is a useful experimental model as it mimics the human adenoma–carcinoma sequence and allows the study of dietary variation and of the ...effects of chemopreventive substances. Alterations of specific oncogenes and tumor suppressor genes (APC and K-ras) play roles at different stages of this carcinogenesis process. Recently, it has been suggested that genomic instability is the necessary step for the generation of multiple mutations underlying the occurrence of cancer. We studied the frequency of K-ras and microsatellite instability (MSI) in 30 colorectal tumors induced by AOM (30 mg/kg) in F344 rats. We also used the random amplified polymorphic DNA (RAPD) method to identify genomic alterations in chemically induced aberrant crypt foci (ACF), adenomas and adenocarcinomas. K-ras mutations were identified in 16.7% of the cases (5/30; 9% in adenomas and 37.5% in adenocarcinomas) and MSI in 20% (6/30) of the tumors (only one sample exhibited instability at more than one locus). Of 21 primers used for the RAPD assay, six were very informative. All the analyzed tumors (16/16) showed at least one RAPD profile with lost or additional bands compared with the normal mucosa. A lower level of genomic alteration was present in the ACF analyzed (7/10). In conclusion, K-ras and MSI are not often involved in the AOM carcinogenesis in the rat, whereas extensive genomic instability is always present and can be detected using the RAPD analysis.
Cardiovascular disease is the leading cause of death in women in Western countries. Despite preventive strategies, in the past decades the incidence of cardiovascular events has shown a decline in ...men but a rise in women, matching the growth of the population of postmenopausal women. Several epidemiological findings suggest the causative pathophysiological role of ovarian hormone deficiency in the development of cardiovascular disease in women. Observational and randomized studies have suggested that hormone replacement therapy in early postmenopause could be beneficial from a cardiovascular point of view. Conversely, aging, time since menopause and presence of cardiovascular risk factors or cardiovascular disease may decrease its efficacy and increase the risk of cardiovascular events. It is plausible that the unfavorable effects of the estrogen/progestin combination used in the randomized studies are not related to the hormone preparation per se but rather to the use of hormones in the less receptive group of women, older and with cardiovascular risk factors. Clinical judgment, choice of the right dose and estrogen/progestin combination are of pivotal importance to maximize the beneficial effect of estrogen replacement therapy/hormone replacement therapy, especially if given within a reasonable time after the menopause to women who need the therapy for the relief of menopausal symptoms.
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