Toxicity results after treatment with Electronic Brachytherapy in patients with endometrial cancer

Poster Session [EP-2226] Purpose or Objective To analyse the toxicity outcomes after treatment with Electronic Brachytherapy (XB) in postsurgical endometrial cancer patients treated at our medical centre. Material and Methods Prospective study in which we selected 94 patients, between September/2015 and September/2017, that received treatment with XB administered twice a week after endometrial cancer surgery, with IMRT planificati on. The patients were divided in two groups: Group 1 (57/94) considered high risk received external beam radiotherapy (46Gy) followed by XB (15Gy in 5Gy fractions) and group 2 (37/94) considered intermediate risk received exclusive XB (25Gy in 5Gy fraction s). We analysed the median dose in bladder, rectum and sigmoid D2cc, V50, V35 with XB comparing the doses with Ir192. The vaginal mucosa, gastrointestinal (GI) and genitourinary (GU) toxicities were analysed with the Common Terminology Criteria for Adverse Events (CTCAE 4.0) scale. Results The median dose in bladder with XB vs. Ir192 was: 2cc 62.9 vs. 69.9%, V50 7.1 vs. 12.6Gy, V35 15 vs. 28.1. In rectum XB vs. Ir192 was: D 2cc 64.01% vs. 67.7%, V50 7.8 vs. 10.9Gy, V35 16.5 vs. 31.8Gy. In sigmoid XB vs. Ir 192 was: D 50.37%vs. 58.0%, V50 8.8 vs. 16.2Gy, V35 21.2 vs. 37.5Gy. The median follow- up was 11 months (range 1 - 23, 9 months). In group 1, acute vaginal mucositis (G1) was observed in 35.08% of the patients, GI toxicity (G1) in 5.26% and GU toxicity (G1) in 10.52%. In group 2, we observed acute vaginal mucositis G1 in 45% of the patients and G2 in 10.81%, GI toxicity (G1) occurred in 2.7% and GU toxicity (G1) was present in 16.21%. There was no grade 3 or greater toxicity in any of the groups. Late toxici ty was observed in only 4 patients: Mucositis (G1) in 3 patients and GU toxicity (G1) in 1 patient. Conclusion The dose received by the organs at risk with the XB is less compared to Ir192, with a good coverage of the PTV. The greater toxicity was observe d immediately after the treatment was finished with an important reduction of the symptoms after 6 months. This technique shows excellent results as for toxicity

Epidemiología, carga de la enfermedad y tendencias de tratamiento de la enfermedad inflamatoria intestinal en México

Introducción y objetivos: En México no existe información sistematizada para determinar/ monitorizar la carga de la enfermedad inflamatoria intestinal (EII). El objetivo del estudio fue estimar la carga anual de la EII en el Sistema Nacional de Salud por número de pacientes atendidos, hospitalizaciones y muertes y por grupos de edad. Material y métodos: Utilizando registros específicos de bases de datos del Sistema Nacional de Salud codificados por CIE-10: K50 y K51, obtuvimos y analizamos datos correspondientes a los pacientes atendidos y hospitalizados por grupo etario, así como muertes específicas durante el año 2015. Asimismo, se exploró la tendencia de tratamiento entre médicos. Resultados: En 2015, el número total de casos atendidos (prevalencia de casos atendidos) fue: enfermedad de Crohn en mujeres 5,009 (8.1), en hombres 4,944 (8.4). Los pacientes ≥ 50 años representaron el 35.1% del total; colitis ulcerosa crónica idiopática en mujeres 17,177 (27.7), en hombres 15,883 (26.9). Los ≥ 50 años representaron el 31.6% del total. Los casos hospitalizados fueron (prevalencia de casos hospitalizados): enfermedad de Crohn 1,097 (0.91). Los pacientes≥ 50 años representaron el 43.7% del total; colitis ulcerosa crónica idiopática 5,345 (4.42). Los enfermos ≥ 50 años representaron el 47.6% del total. Las defunciones fueron (tasa de muertes específicas): en enfermedad de Crohn: mujeres 32 (0.52), hombres 36 (0.50); colitis ulcerosacrónica idiopática en mujeres 267 (4.31), en hombres 186 (3.15).Conclusiones: La EII representa una carga para la salud de los adultos mexicanos y el Sistema de Salud, y se espera que aumente en los próximos 15 años

Inflammatory bowel disease in Mexico: Epidemiology, burden of disease, and treatment trends

Introduction and aims: There is no systematized information for determining/monitoring the burden of inflammatory bowel disease in Mexico. The aim of the present study was to estimate the annual burden of inflammatory bowel disease on the Mexican National Healthcare System, by number of patients seen, hospitalizations, and specific deaths, stratified into age groups. Materials and methods: Utilizing specific databases of the Mexican National Healthcare System registries coded as ICD-10: K50 and K51, we retrieved and analyzed the data corresponding to the patients seen and hospitalized in 2015, stratified by age group, as well as the specific deaths. Treatment trends among physicians were also examined. Results: In 2015, 5009 women (8.1) and 4944 men (8.4) with Crohn’s disease received medical attention (prevalence of cases seen) and 35.1% of those patients were ≥50 years of age. In that same period, 17,177 women (27.7) and 15,883 men (26.9) with ulcerative colitis wereseen and 31.6% of those patients were ≥50 years of age. The hospitalized cases (prevalence ofhospitalized cases) were 1097 patients (0.91) with Crohn’s disease and 43.7% of those patientswere ≥50 years of age; and 5345 patients (4.42) with ulcerative colitis and 47.6% of thosepatients were ≥50 years of age. Deaths (specific mortality rate) were: 32 women (0.52) and 36men (0.50) due to Crohn’s disease, and 267 women (4.31) and 186 men (3.15) due to ulcerativecolitis.Conclusions: Inflammatory bowel disease is a burden on the health of Mexican adults and theMexican National Healthcare System, and it is expected to increase over the next 15 year

Epstein-Barr-virus-positive large B-cell lymphoma associated with breast implants: an analysis of eight patients suggesting a possible pathogenetic relationship.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting

Incretins in patients with rheumatoid arthritis

Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.This work was supported by grants from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of MAGG was also partially supported by RETICS Programs RD12/0009 (RIER) and RD12/0009/0013 from the ISCIII (Spanish Health Ministry)

Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alvolar bone resorption by mitochondrial-related mechanisms

Background/Objectives: Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats.Methods/Findings: Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations.Conclusions: The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.This study was supported by I+D grants from the Spanish Ministry of Education and Science (AGL2008-01057) and the Autonomous Government of Andalusia (AGR832)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field