An Overview of Epigenetics in Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents a heterogenous group of cancers with complex genetic background and histological varieties, which require various clinical therapies. Clear cell RCC represents the most common form of RCC that accounts for 3 out of 4 RCC cases. Screening methods for RCC lack sensitivity and specificity, and thus biomarkers that will allow early diagnosis are crucial. The impact of epigenetics in the development and progression of cancer, including RCC, is significant. Noncoding RNAs, histone modifications and DNA methylation represent fundamental epigenetic mechanisms and have been proved to be promising biomarkers. MicroRNAs have advantageous properties that facilitate early diagnosis of RCC, while their expression profiles have been assessed in renal cancer samples (tissue, blood, and urine). Current literature reports the up-regulation of mir122, mir1271 and mir15b in RCC specimens, which induces cell proliferation via FOXP-1 and PTEN genes. However, it should be noted that conflicting results are found in urine and serum patient samples. Moreover, promoters of at least 200 genes are methylated in renal cancers leading to epigenetic dysregulation. In this review, we analyze the vast plethora of studies that have evaluated the role of epigenetic mechanisms in RCC patients and their clinical importance.

Treatment Adherence in Patients with Lung Cancer from Prospects of Patients and Physicians.

PURPOSE: Adherence to treatment can be defined as the degree to which a patient's behavior is consonant with medical or health advice he or she receive as part of his treatment regimen. The aim of this study was:  1) to measure the rate of treatment adherence to among patients with lung cancer from the prospect of both patients and physicians, 2) to measure the degree of concordance between the two prospect, and 3) to identify factors related to adherence for both prospect (patients and physicians). MATERIALS AND METHODS: A total of 250 patients were included in this study. Information about socio-economic characteristics, depressive and anxiety symptoms (Hospital Anxiety and Depression scale), nicotine dependence (Fagerstrom scale), barriers to accessing care, and the level of treatment adherence was collected through interview. Physicians were enquired about disease and treatment variables as well as patients' level of adherence. RESULTS: From the patient perspective, only 1.2% of patients displayed poor adherence; whereas the corresponding percentage among physicians was 12.4%. The concordance between the two was low: 0.244. The correlation of measurements made on the same individual was found to be equal to 0.14. Barriers to accessing medication (O.R.=2.82, 95% C.I.: 1.01-8.09) was the only risk factor when adherence was self-rated; barriers to accessing medication (O.R.=2.45, 95% C.I.: 1.03-5.86), education equal to 12 years (O.R.=0.33, 95% C.I.: 0.13-0.82) or higher than 12 years (O.R.=0.28, 95% C.I.: 0.08-0.96), nicotine dependence (O.R.=1.41, 95% C.I. 1.17-1.69) and HADS anxiety score (O.R.=1.15, 95% C.I. 1.03-1.30) were the predictors in physicians' rating. CONCLUSIONS: Differences in rating adherence may underpin communication gaps between patients and physicians. Systemic determinants of poor adherence should not be overlooked. A concerted effort by researchers, physicians and policy makers in defining as well as communicating adherence, while removing its barriers should be made.
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Biological acellular pericardial mesh regulated tissue integration and remodeling in a rat model of breast prosthetic implantation.

The use of biological meshes has proven beneficial in surgical restriction and periprosthetic capsular contracture following breast prosthetic-reconstruction. Three different types (smooth, texturized, and polyurethane) of silicone round mini prostheses were implanted under rat skin with or without two different bovine acellular pericardial biological meshes (APMs, BioRipar, and Tutomesh). One hundred eighty-six female rats were divided into 12 groups, sacrificed after 3, 6, and 24 weeks and tissue samples investigated by histology and immunohistochemistry. Implantation of both APMs, with or without prostheses, reduced capsular α-SMA expression and CD3+ inflammatory cell infiltration, increasing capillary density and cell proliferation, with some differences. In particular, Tutomesh was associated with higher peri-APM CD3+ inflammation, prosthetic capsular dermal α-SMA expression and less CD31+ vessels and cell proliferation compared with BioRipar. None differences were observed in tissue integration and remodeling following the APM + prostheses implantation; the different prostheses did not influence tissue remodeling. The aim of our study was to investigate if/how the use of different APMs, with peculiar intrinsic characteristics, may influence tissue integration. The structure of APMs critically influenced tissue remodeling after implantation. Further studies are needed to develop new APMs able to optimize tissue integration and neoangiogenesis minimizing periprosthetic inflammation and fibrosis.

Cancer patients' organisation participation in heath policy decision-making: a snapshot/cluster analysis of the EU-28 countries.

OBJECTIVES: Even though patient involvement in health policy decision-making is well documented, studies evaluating the degree and impact of this participation are scarce. This is even more conspicuous in the case of cancer. There is evidence showing that patients with the same type of cancer and at the same stage of the disease will receive different treatments in different countries. Therefore, it is crucial to assess the degree of patient participation in health policy decision-making across Europe, as it may result in health inequalities across countries. In a response to this research call, the present study aimed to provide a snapshot of cancer patients' organisation (CPO) participation in health policy processes in European Union (EU)-28 countries. SETTING: CPOs from the EU-28 countries. PARTICIPANTS: Primary and secondary outcome measures: information about participants' sociodemographic characteristics and their involvement in their CPO was collected as well as data about the CPO. A 17-item index containing questions about the type and impact of participation in various facets of health policy decision-making was used to assess the degree of CPOs participation in health policy decision-making processes and its impact.

Assessing Patient Organization Participation in Health Policy: A Comparative Study in France and Italy.

BACKGROUND: Even though there are many patient organizations across Europe, their role in impacting health policy decisions and reforms has not been well documented. In line with this, the present study endeavours to fill this gap in the international literature. To this end, it aims to validate further a previously developed instrument (the Health Democracy Index - HDI) measuring patient organization participation in health policy decision-making. In addition, by utilizing this tool, it aims to provide a snapshot of the degree and impact of cancer patient organization (CPO) participation in Italy and France. METHODS: A convenient sample of 188 members of CPOs participated in the study (95 respondents from 10 CPOs in Italy and 93 from 12 CPOs in France). Participants completed online a self-reported questionnaire, encompassing the 9-item index and questions enquiring about the type and impact of participation in various facets of health policy decisionmaking. The psychometric properties of the scale were explored by performing factor analysis (construct validity) and by computing Cronbach α (internal consistency). RESULTS: Findings indicate that the index has good internal consistency and the construct it taps is unidimensional. The degree and impact of CPO participation in health policy decision-making were found to be low in both countries; however in Italy they were comparatively lower than in France. CONCLUSION: In conclusion, the HDI can be effectively used in international policy and research contexts. CPOs participation is low in Italy and France and concerted efforts should be made on upgrading their role in health policy decision-making.

Characterization of a new decellularized bovine pericardial biological mesh: Structural and mechanical properties.

Implants made from naturally-derived biomaterials, also called biological meshes or biomeshes, typically derive from decellularized extracellular matrix of either animal or human tissue. Biomeshes have many biomedical applications such as ligament repair, bone and cartilage regeneration and soft tissue replacement. Bovine collagen is one of the most widely used and abundantly available xenogenic materials. In particular, bovine pericardium is widely used as extracellular matrix bioprosthetic tissue. The efficiency of a pericardial mesh to function as scaffold depends on the quality of the decellularization protocol used. Moreover, the biomesh mechanical features are critical for a successful surgical repair process, as they must reproduce the biological properties of the autologous tissue. Different methods of physical, chemical, or enzymatic decellularization exist, but no one has proved to be ideal. Therefore, in the present study, we developed a novel decellularization protocol for a bovine pericardium-derived biomesh. We characterized the biomesh obtained by comparing some ultrastructural, physical and mechanical features to a reference commercial biomesh. Quantification revealed that our novel decellularization process removed about 90% of the native pericardial DNA. Microscopic and ultrastructural analysis documented the maintenance of the physiological structure of the pericardial collagen. Moreover, mechanical tests showed that both the extension and resilience of the new biomesh were statistically higher than the commercial control ones. The results presented in this study demonstrate that our protocol is promising in preparing high quality bovine pericardial biomeshes, encouraging further studies to validate its use in tissue engineering and regenerative medicine protocols.

Can psychobiotics intake modulate psychological profile and body composition of women affected by normal weight obese syndrome and obesity? A double blind randomized clinical trial.

BACKGROUND: Evidence of probiotics effects on gut function, brain activity and emotional behaviour were provided. Probiotics can have dramatic effects on behaviour through the microbiome-gut-brain axis, through vagus nerve. We investigated whether chronic probiotic intake could modulate psychological state, eating behaviour and body composition of normal weight obese (NWO) and preobese-obese (PreOB/OB) compared to normal weight lean women (NWL). METHODS: 60 women were enrolled. At baseline and after a 3-week probiotic oral suspension (POS) intake, all subjects underwent evaluation of body composition by anthropometry and dual X-ray absorptiometry, and psychological profile assessment by self-report questionnaires (i.e. EDI-2, SCL90R and BUT). Statistical analysis was carried out using paired t test or a non-parametric Wilcoxon test to evaluate differences between baseline and after POS intake, one-way ANOVA to compare all three groups and, where applicable, Chi square or t test were used to assess symptoms. RESULTS: Of the 48 women that concluded the study, 24% were NWO, 26% were NWL and 50% were PreOB/OB. Significant differences in body composition were highlighted among groups both at baseline and after a POS (p < 0.05). After POS intake, a significant reduction of BMI, resistance, FM (kg and %) (p < 0.05), and a significant increase of FFM (kg and  %) (p < 0.05) were observed in all subjects in NOW and PreOB/OB. After POS intake, reduction of bacterial overgrowth syndrome (p < 0.05) and lower psychopathological scores (p < 0.05) were observed in NWO and PreOB/OB women. At baseline and after POS intake, all subjects tested were negative to SCL90R_GSI scale, but after treatment subjects positive to BUT_GSI scale were significantly reduced (8.33%) (p < 0.05) compared to the baseline (33.30%). In NWO and PreOB/OB groups significant differences (p < 0.05) in response to the subscales of the EDI-2 were observed. Significant improvement of the orocecal transit time was observed (p < 0.05) after POS intake. Furthermore, significant differences were observed for meteorism (p < 0.05) and defecation frequency (p < 0.05). CONCLUSIONS: A 3-week intake of selected psychobiotics modulated body composition, bacterial contamination, psychopathological scores of NWO and PreOB/OB women. Further research is needed on a larger population and for a longer period of treatment before definitive conclusions can be made. Trial registration ClinicalTrials.gov Id: NCT01890070.

PET Probe-Guided Surgery in Patients with Breast Cancer: Proposal for a Methodological Approach.

BACKGROUND: Although it is valuable for detecting distant metastases, identifying recurrence, and evaluating responses to chemotherapy, the role of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) in assessing locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. In the current report, we describe a new PET probe-based clinical approach, with evaluation of the technical performance of a handheld high-energy gamma probe for intraoperative localization of breast carcinomas, and evaluation of lymph node metastases during radio-guided oncological surgery. PATIENTS AND METHODS: Three patients underwent a PET/CT scan immediately prior to surgery following the standard clinical protocol. Intraoperatively, tumors were localized and resected with the assistance of a hand-held gamma probe. PET-guided assessment of the presence or absence of regional nodal spread of malignancy was compared with the reference standard of histopathological examination. RESULTS: In all three cases, perioperative 18F-FDG PET/CT imaging and intraoperative gamma probe detection verified complete resection of the hypermetabolic lesions and demonstrated no additional suspicious occult disease. CONCLUSION: This innovative approach demonstrates great promise for providing real-time access to metabolic and morphological tumor information that may lead to an optimal disease-tailored approach. In carefully selected indications, a PET probe can be a useful adjunct in surgical practice, but further trials with a larger number of patients need to be performed to verify these findings.

Catamenial pneumothorax due to solitary localization of diaphragmatic endometriosis.

INTRODUCTION: Catamenial pneumothorax (CP) is a spontaneous recurrent pneumothorax occurring in women in reproductive age. The etiology of CP has been associated with thoracic endometriosis and is its most common presentation. PRESENTATION OF CASE: A case of right catamenial pneumothorax in a 38 year old woman is presented in which three episodes of CP occurred within 72h of menses in a 6 month period. The patient underwent videothoracoscopy that revealed a solitary localization of diaphragmatic endometriosis. After surgical pleurodesis and based on final pathology of resected lesion, hormonal treatment was started. The outcome was uneventful and the patients is symptom-free at 6 months. DISCUSSION: Catamenial pneumothorax (CP) is a rare clinical entity characterized by lung collapse during menstruation, believed to be secondary to pleural endometriosis. Nearly all catamenial pneumothorax occur on the right side as pleural lesions are almost exclusively right-sided. Diagnostic imaging is based on high resolution computed tomography (HRCT) and, preferably, magnetic resonance imaging (MRI) since it is able to detect the blood products in the endometrial deposits. However the lack of macroscopic findings at surgery makes this condition still under-diagnosed. Based on the solitary diaphragmatic localization of endometriosis in our case we preferred to limit surgery to videothoracoscopic pleurodesis and start hormonal treatment with successful outcome. CONCLUSION: Catamenial pneumothorax is the most common presentation of thoracic endometriosis syndrome and should always be suspected in women in childbearing age. Treatment option are still debated but best results are achieved by videothoracoscopic pleurodesis combined with hormonal therapy.

Nodal status assessment in breast cancer: strategies of clinical grounds and quality of life implications.

Even in the era of gene-expression profiling, the nodal status still remains the primary prognostic discriminant in breast cancer patients. The exclusion of node involvement using noninvasive methods could reduce the rate of axillary surgery, thereby preventing from suffering complications. However, lymphatic mapping with sentinel node biopsy (SNB) is one of the most interesting recent developments in surgical oncology. Optimization of procedure could be implemented by dual mapping injection site skills, resection of all hot or blue nodes through tracer combination, and improvement in atypical drainage patterns mapping. This anatomical analysis suggests safety measures in patients with high probability of node metastasis through a renewed interest in surgical management. The perspective of a guided axillary sampling (GAS) could represent a potential development of recent anatomical and functional acquisitions, offering a dynamic technique shared according to clinical and anatomical disease parameters. Furthermore, the surgical staging procedures may adopt a conservative approach through the evaluation of upper arm lymphatics, thus defining a functional model aimed at the reduction of short- and long-term adverse events. Quality results in breast cancer surgery need to generate oncological safety devoid of complications through renewed clinical experience.

Lung volume reduction reoperations.

BACKGROUND: Optimal management of emphysematous patients who have lost the benefits achieved after lung volume reduction surgery is a clinical dilemma. We have hypothesized that in stringently selected instances, lung volume reduction reoperations might be considered as a salvage surgical treatment. We sought to analyze the results of a series of patients undergoing lung volume reduction reoperations after successful bilateral lung volume reduction surgery. METHODS: Between January 2000 and April 2006, 17 patients (mean age, 66 +/- 3 years) with radiologic evidence of distinct regional lung hyperinflation underwent lung volume reduction reoperations. Surgical procedures entailed completion lobectomy in 7 patients, nonanatomic resection of lung target areas were performed in 5 patients under general anesthesia with one-lung ventilation, and awake lung plication was performed in 5 patients under sole epidural anesthesia. Follow-up at 6 and 12 months was complete in all survivors. RESULTS: Mean operative time was 100 +/- 12 minutes. Two patients (11.7%) died perioperatively of adult respiratory distress syndrome. Hospital stay was 9 +/- 2 days. Significant improvements occurred for up to 12 months in forced expiratory volume in 1 second (FEV(1); p < 0.001), forced vital capacity (p < 0.002), residual volume (p < 0.001), 6-minute walk test (p < 0.001), and modified Medical Research Council dyspnea index (p < 0.001). At 6-months, improvements in FEV(1) were greater than 200 mL in 11 patients and correlated with the postoperative reduction in residual volume (r = -0.62, p = 0.01); baseline residual volume was inversely correlated with the degree of improvement in the dyspnea index (r = -0.54, p = 0.03). CONCLUSIONS: Lung volume reduction reoperations can offer significant clinical improvement to stringently selected patients who have lost the clinical benefit achieved after lung volume reduction surgery.