Internal developmental assets and substance use among Hispanic adolescents. A cross-sectional study.

AIMS: To determine the associations between internal assets (planning and decision-making, interpersonal competence and commitment to learning) and substance use (tobacco, alcohol, binge drinking, marijuana use and other drugs). DESIGN: A cross-sectional study was conducted in four countries (Chile, Mexico, Spain and Peru). METHODS: Adolescents aged 12-18 self-completed a multi-purpose questionnaire between 2016 and 2019. Multiple logistic regressions and structural equation models were performed to analyse the association between internal assets (planning and decision-making, interpersonal competence, and commitment to learning) and substance use. RESULTS: The results indicate that planning and decision-making and commitment to learning are conducive to the prevention of substance use. On the contrary, interpersonal competence was not associated with substance use. CONCLUSION: The present study shows that planning and decision-making and commitment to learning can be relevant factors in explaining substance use during adolescence. Internal assets can be an important aspect to include in health promotion interventions with children, youth and families to prevent substance use. These findings may be useful for researchers, schools, paediatric nurse practitioners, and health professionals in general to design health programs focused on children and adolescents. Furthermore, the Developmental Assets framework has been proved as a suitable frame of reference for paediatric nurse practitioners to assess and develop child and adolescent positive development and design health promotion interventions to prevent substance use.

Placing myself in a new normalized life: The process of becoming a first-time father. A grounded theory study.

Becoming a first-time father is an important transition period in men's lives that is frequently accompanied by joy and happiness. Engaging fathers has a broader impact on family and community and on fathers' own well-being. This study explores the process of men becoming first-time fathers and the experiences and challenges involved. Seventeen interviews with men in different stages of pregnancy, childbirth, and the postpartum period were conducted. Through a grounded theory design, a novel four-stage theoretical model emerged that represents the journey to first-time fatherhood. These stages are beginning the journey, fatherhood in limbo, facing reality, and settling down. Participants suggested that achieving a new normality was the final stage where they finally felt located with a sense of mastery in their journey to fatherhood. The novel theoretical approach of addressing the process of men's transition allowed more complete access to their perspectives. Men's needs are different at every phase of the transition to fatherhood, and the use of these findings can help care providers in caring for every man according to the stage he is facing.

Successful pregnancy and follow-up after in vitro fertilization of a kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and hypothyroidism.

This report describes the case of a female kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and postsurgical hypothyroidism due to Grave's disease who had a healthy newborn after in vitro fertilization (IVF). Cases of successful pregnancy involving women who underwent IVF after kidney transplantation have been reported. Normal and stable renal function, adequate immunosuppressant therapy, and well-managed blood pressure are requirements to be eligible for IVF and pregnancy. Primary biliary cholangitis without cirrhosis does not seem to worsen during pregnancy and IVF must be individualized in patients with systemic lupus erythematosus. There are no similar case reports involving kidney transplant patients or individuals with autoimmune disorders, so the decision to perform IVF had to be individualized in order to avoid complications for the mother and fetus.

A valid and reliable scale to assess cultural sensibility in nursing.

BACKGROUND: Cultural sensibility is an important concept linked to the achievement of cultural competence. Health professionals must first improve their cultural sensibility to become culturally competent and to be able to offer competent care to culturally diverse populations. Aim To develop and psychometrically test the Cultural Sensibility Scale for Nursing (CUSNUR), a cultural sensibility scale that can be used in nursing for the achievement of competencies needed to care for culturally diverse populations. DESIGN AND METHODS: The cross-sectional survey was conducted over two stages. The first stage involved the cross-cultural and discipline-specific adaptation of an existing scale addressing this concept in the field of law using the reverse translation method. Second, validation of the scale was carried out from October 2016-June 2017 by studying the psychometric properties of the questionnaire through an analysis of content acceptability and reliability and through exploratory factor analysis (EFA). RESULTS: The questionnaire was designed to be clear, easy to understand, and of adequate length, and experts involved in content validation agreed that the scale meets these criteria. A total of 253 nursing students participated in the validation stage. Four factors were identified from the EFA: (1) patient and health professional behaviours, (2) self-assessments, (3) self-awareness, and (4) cultural influence. Two items were excluded. Factorial saturation is adequate for all factors (>0.30). The Cronbach alpha was measured as 0.75. CONCLUSIONS: This study presents the first version of the CUSNUR and demonstrates that the scale is valid and reliable.

Validity and reliability of the Self-Care Activities Screening Scale (SASS-14) during COVID-19 lockdown.

BACKGROUND: In a context where there is no treatment for the current COVID-19 virus, the combination of self-care behaviours together with confinement, are strategies to decrease the risk of contagion and remain healthy. However, there are no self-care measures to screen self-care activities in general population and which, could be briefly in a lockdown situation. This research aims to build and validate a psychometric tool to screen self-care activities in general population. METHODS: Firstly, an exploratory factor analysis was performed in a sample of 226 participants to discover the underlying factorial structure and to reduce the number of items in the original tool into a significant pool of items related to self-care. Later a confirmatory factor analyses were performed in a new sample of 261 participants to test for the fit and goodness of factor solutions. Internal validity, reliability, and convergent validity between its score with perceived stress and psychological well-being measures were examined on this sample. RESULTS: The exploratory analyses suggested a four-factor solution, corresponding to health consciousness, nutrition and physical activity, sleep, and intra-personal and inter-personal coping skills (14 items). Then, the four-factor structure was confirmed as the best model fit for self-care activities. The tool demonstrated good reliability, predictive validity of individuals' perception of coping with COVID-19 lockdown, and convergent validity with well-being and perceived stress. CONCLUSIONS: This screening tool could be helpful to address future evaluations and interventions to promote healthy behaviours. Likewise, this tool can be targeted to specific population self-care's needs during a scalable situation.

Connections between Family Assets and Positive Youth Development: The Association between Parental Monitoring and Affection with Leisure-Time Activities and Substance Use.

This study aimed to determine the associations between parental monitoring and affection and three adolescent lifestyle aspects: constructive leisure, non-constructive leisure and substance use. A cross-sectional study was conducted in four countries (Chile, Mexico, Spain and Peru). Adolescents aged 12-15 self-completed a multi-purpose questionnaire. Multiple logistic regressions were performed to analyse the association between the parental monitoring and affection variables and the outcomes in terms of the children's lifestyles. The results indicate that parental monitoring is conducive to more constructive leisure and less non-constructive leisure and seems to be conducive to the prevention of substance use. Furthermore, parental affection is conducive to constructive leisure and the prevention of substance use. The discussion focuses on the fact that the family can be a protective resource associated with positive adolescent development.

Effect of ß-catenin alterations in the prognosis of patients with sporadic colorectal cancer.

CONTEXT: Wnt pathway activation represents a critical step in the etiology of most of colorectal cancer (CRC) and it is commonly due to mutations in the APC gene, which originates the loss of ß-catenin regulatory function. It has been suggested that APC inactivation or ß-catenin alteration have similar effects in tumor progression in CRC tumorigenesis. AIMS: The aim of this study was to analyze the frequency of ß-catenin gene mutation in patients with sporadic CRC and to determine its effect in prognosis. MATERIALS AND METHODS: This was a prospective cohort study, which included 345 patients with sporadic CRC. ß-Catenin gene mutations in exon 3 were detected by single strand conformation polymorphism (SSCP). Exon 3 deletion was studied by identifying differences in fragment length of specific amplification products. All the altered samples were confirmed by direct sequencing. RESULTS: In our population, point mutations were detected in 1.8% of the samples and 4.9% of the samples showed deletion. We observed association between exon 3 mutations and increased levels of Carcinoenbryonic Antigen (CEA). In these patients, clinically relevant improvement in overall survival was also observed. CONCLUSION: Frequency of point mutations in exon 3 ß-catenin gene is low in our population. It would be interesting to increase the population size to test the clinically relevant influence in the prognosis found, and to test the relation of these events with Microsatellite Instabillity (MSI) pathway. If these findings were confirmed, ß-catenin determination would help in the selection of patients with different prognosis.

A9 region in EPHB2 mutation is frequent in tumors with microsatellite instability. Analysis of prognosis.

AIM: The aim of the present study was to determine the relation of EPH tyrosine kinase receptor B2 (EPHB2) A9 region mutation and microsatellite instability (MSI); and to analyze their influence in prognosis of patients with sporadic colorectal cancer (CRC). PATIENTS AND METHODS: A total of 481 patients with CRC were examined. MSI (NCI criteria) and EPHB2 were analyzed using PCR and fragment analysis software. RESULTS: EPHB2 mutation was detected in 3.1% of patients. Mutation of EPHB2 was associated with location and with MSI status. We considered low instability (L-MSI) when only one marker showed instability, high instability (H-MSI) when two or more markers were positive and microsatelllite stable (MSS) when no instability was detected. The stratified analysis of overall survival (OS) and disease-free survival (DFS) in MSI according to EPHB2 status revealed no statistically significant differences. However, the risk of recurrence of H-MSI tumors with EPHB2 mutation carriers was 3.6-times higher than in non-mutation carriers. CONCLUSION: The frequency of EPHB2 mutation is higher in patients with H-MSI than MSS tumors. Promising results were found regarding the prognostic influence of EPHB2 in H-MSI.

Influence of vitamin D-related gene polymorphisms (CYP27B and VDR) on the response to interferon/ribavirin therapy in chronic hepatitis C.

BACKGROUND AND AIMS: Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus (HCV). This study was performed to assess the putative influence of polymorphisms in vitamin D-related genes on the response to antiviral therapy in patients with chronic hepatitis C (CHC). METHODS: Single nucleotide polymorphisms (SNPs) in CYP27B-1260 gene promoter (rs10877012AC) and in vitamin D receptor (VDR) gene rs2228570TC, rs1544410CT, rs7975232AC and rs731236AT were analyzed in a cohort of 238 Caucasian CHC patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV). Multivariate analyses were performed to exclude confounding effects of well-known baseline predictors of response to therapy (HCV genotype and load, IL28B genotype, age, and GGT and serum cholesterol). RESULTS: Three SNPs at the VDR gene (rs1544410, rs7975232 and rs731236) were in strong linkage disequilibrium, with the CCA haplotype predicting therapeutic failure [Odds ratio 2.743; (95% C.I. 1.313-5.731), p = 0.007]. The carrier state of the VDR rs2228570 T allele was inversely related to the probability of therapeutic failure [Odds ratio 0.438; 95 C.I. (0.204-0.882), p = 0.021]. No relation existed between CYP27B-1260 rs10877012 polymorphism and response to therapy. The area under the operating curve (AUROC) based on the model including all variables significantly related to the response to therapy was 0.846 (95% confidence interval = 0.793-0.899). CONCLUSION: VDR gene polymorphisms are independently related to the response to Peg-IFN+RBV therapy in chronic hepatitis C and could be used as complementary biomarkers of response when included in a prediction algorithm in association with demographic, virologic, biochemical and genetic traits.

Prognostic value of the combination of circulating tumor cells plus KRAS in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab.

OBJECTIVE: Circulating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) status were identified as prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab in analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer) trial. In this post hoc analysis of the MACRO trial, the potential additive effect of these 2 factors on patient outcomes was explored. METHODS: A total of 158 of the 480 patients involved in the MACRO trial were included in the biological marker substudy. CTC isolation and enumeration were centralized and performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of whole blood. Evaluation of KRAS status was performed retrospectively by the standard method used at each center. PFS and OS were analyzed by the Kaplan-Meier method according to CTC count and KRAS status. RESULTS: Patients with < 3 CTC per 7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2 months compared with 6.2 months in patients with ≥ 3 CTCs and KRAS mutated tumors (P < .0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar findings were observed for OS (28.9 and 13.7 months, respectively, P = .0004; hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed that CTC count ≥ 3 and KRAS status were the only independent prognostic factors for both PFS and OS. CONCLUSIONS: This post hoc analysis showed that CTC count and KRAS status were independent prognostic factors for outcomes in patients with metastatic colorectal cancer treated with bevacizumab ± chemotherapy. These factors should be taken into account in the design of future phase III trials.

Serum level of fibroblast growth factor 23 in maintenance renal transplant patients.

BACKGROUND: The discovery of fibroblast growth factor 23 (FGF23) provides a new conceptual framework that improves our understanding of the pathogenesis of post-transplant bone disease. Excess FGF23 is produced in the early post-transplant period; levels return to normal in the months following transplant. However, few manuscripts discuss FGF23 levels in stable long-term renal transplant recipients. METHODS: We performed a cross-sectional observational study of 279 maintenance kidney recipients with chronic kidney disease (CKD) Stages 1-4 and stable allograft function who had received their transplant at least 12 months previously. We calculated the estimated GFR (eGFR) using the MDRD4 equation. RESULTS: FGF23, parathyroid hormone (PTH) and phosphorus values were higher in more advanced stages, while the serum calcitriol levels and the phosphate reabsorption rate were lower. A significant inverse correlation was found between eGFR and FGF23 (r = -0.487; P < 0.001), PTH (r = -0.444; P < 0.001), serum phosphate levels (r = -0.315; P < 0.001) and fractional excretion of magnesium (r = -0.503; P < 0.001). Multivariable analysis showed that increased time on corticosteroids (P < 0.001), PTH (P < 0.001), serum phosphate (P = 0.003), decreased serum calcitriol (P = 0.049) and estimated glomerular filtration (P = 0.003) rate were associated with high FGF23 levels. In contrast with pre-transplant patients and first year post-transplant patients, higher FGF23 values were not correlated with increased phosphate excretion. An elevated phosphate reabsorption rate was associated with decreased PTH (P < 0.001) and calciuria (P = 0.028) and increased serum calcitriol (P = 0.009), plasma bicarbonate (P = 0.024) and estimated glomerular filtration (P = 0.003). CONCLUSIONS: Serum FGF23 concentrations remain increased in long-term kidney graft recipients, even in the early stages of CKD. It remains to be seen whether measures aimed at reducing serum levels of PTH and phosphate and/or corticosteroid doses might help to lower serum FGF23 and whether this will improve kidney recipient outcomes.

Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease.

BACKGROUND/AIMS: Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma. METHODS: We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards. RESULTS: In multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053-2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients. CONCLUSION: The IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C.

Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study.

BACKGROUND: The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints. PATIENTS AND METHODS: One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment. RESULTS: The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095). CONCLUSIONS: The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients.

Diagnostic and prognostic utility of methylation and protein expression patterns of myopodin in colon cancer.

Myopodin is an actin-binding protein believed to play a tumor suppressor role in several solid neoplasias. We evaluated the potential differential myopodin methylation and expression and their clinical relevance in colon cancer. The epigenetic silencing of myopodin by hypermethylation was tested in colon cancer cells (n = 5) before and after azacitidine treatment. Myopodin methylation status was evaluated by methylation-specific PCR in colon cancer cells and colorectal tissues (n = 210) grouped in a training set (n = 62) and two independent validation series (n = 100 and n = 48) collected at independent clinical settings. Myopodin expression patterns were analyzed by immunohistochemistry on tissue arrays. Myopodin hypermethylation correlated with gene and protein expression loss, being increased in vitro by azacitidine. Myopodin was frequently methylated in colon cancer cells (four out of five). Methylation rates were 90.3%, 70.0%, and 47.8% in the training and validation sets, respectively. Myopodin methylation rendered a diagnostic accuracy of 83.9% (p < 0.0005). Cytoplasmic myopodin expression was significantly higher in non-neoplastic biopsies compared to colon tumors (p < 0.0005). Loss of myopodin expression correlated with increasing tumor stage (p = 0.011), methylation (p = 0.005), and poor overall survival (p = 0.003). In the first validation set (n = 100), myopodin methylation predicted disease-free (p = 0.046) and overall survival (p = 0.031). In the second validation cohort, myopodin methylation and protein expression patterns predicted disease-specific (p = 0.012 and p = 0.001, respectively) and overall survival (p = 0.009 and p = 0.043, respectively). Thus, myopodin was revealed to be epigenetically modified in colon cancer. The diagnostic and prognostic clinical utility of myopodin methylation and expression patterns suggest considering their assessment for the clinical management of colon cancer patients.

Detección inmunomagnética de células tumorales circulantes en cáncer de mama metastásico: nuevas tecnologías / Inmunomagnetic detection of circulating tumor cells in metastatic breast cancer: new technologies

Las metástasis hematógenas son la mayor causa de mortalidad en el cáncer de mama. Está documentado que una vez las células tumorales se diseminan el resultado es, generalmente, letal. Las células tumorales circulantes han sido consideradas por largo tiempo un reflejo de la agresividad de los tumores, y entre ellos uno de los más agresivos es el cáncer de mama metastásico. Los primeros resultados clínicos han permitido determinar una fuerte relación entre la detección y el número de las células tumorales circulantes, como un valor pronóstico y como marcador de la actividad antitumoral del tratamiento. El análisis inmunomagnético utilizando una nueva metodología permite determinar que un recuento de 5 células tumorales circulantes o más en 7,5 ml de sangre, en cualquier fase de la enfermedad, se asocia a un mal pronóstico, y es predictivo de una supervivencia global más corta.

Hematogenous metastasis is the major cause of mortality in breast cancer. Evidence indicates that tumor cells escape from the primary tumor mass into the blood stream and that these disseminated cells are the source of increased lethality. Circulating or metastatic tumour cells have been considered as useful indicators of the aggressiveness of breast cancer tumours. The first clinical results obtained with such assays strongly suggest that in metastatic breast cancer, circulating tumour cells detection and enumeration can be used to estimate prognosis and may serve as an early marker to assess anti-tumour activity of a treatment. Immunomagnetic analysis using a new methodology, determine that a circulating tumour cells count of 5 or more per 7,5 ml of blood, at any time during the course of the disease is associated with a poor prognosis and is predictive of shorter progression and overall survival.

Circulating tumor cells in solid tumor in metastatic and localized stages.

UNLABELLED: The aim of this study was the detection of circulating tumor cells (CTC) in three tumor types of epithelial origin. PATIENTS AND METHODS: Four hundred and thirty-eight patients with breast cancer (56.2% localized and 43.8% metastatic), 195 with colorectal tumors (84.1% localized and 15.9% metastatic) and 50 with prostate cancer (52% localized and 48% metastatic) took part in this study. CTC quantification was performed using the CellSpotter Analyzer (Veridex LLC). RESULTS: 31.5% of patients with cancer had > or =2 CTCs/7.5 mL but none of the healthy volunteers were above this level (p<0.001). Among patients with metastatic disease, 62.3% of them had > or =2 CTCs/7.5 mL but only 14.0% of those with localized disease were above this level (p<0.001). The presence of CTCs were correlated to stage in the three studied tumor types and no differences in the number of cells were found between them. CONCLUSION: The presence of more than 2 CTCs/7.5 ml is a frequent event in metastatic cases. In particular, patients with localized disease who have more than 2 CTCs/7.5 ml should be carefully studied to determine the possible prognostic and predictive value of this finding.

Circulating tumor cells in metastatic breast cancer: timing of blood extraction for analysis.

PURPOSE: Circulating tumor cells (CTCs) can be detected in the peripheral blood of around 50% of patients with metastatic breast cancer. Their numbers are an independent predictor of the patient's progression-free survival (PFS) and of overall survival (OS). However, to date, none of the studies carried out with the most commonly used system of CTC determination (the CellSearch System, approved by the US Food and Drug Administration) has examined the intra-patient variation in CTC numbers, a variation that could impact on prognosis assessment. EXPERIMENTAL DESIGN: To evaluate possible circadian variations in the number of CTCs in patients with breast cancer a pilot study was conducted in which these cells were quantified 12 h apart (at 8:00 a.m. and 8:00 p.m. of the same day) in a cohort of hospitalized patients with metastatic breast cancer. RESULTS: Out of the 58 patients included in the study, 51 were evaluable. No statistically significant differences between day-time and night-time CTC numbers were observed (p=0.8427, Wilcoxon matched pair test). Only two of the patients were classified in different prognostic categories in the morning and night determinations (5 or more CTCs=poor prognosis group; <5 CTCs=good prognosis group). The prognostic classification of the remaining 49 patients was the same at 8:00 a.m. and 8:00 p.m. CONCLUSION: The number of peripheral blood CTCs in metastatic breast cancer patients is not significantly different at 8:00 a.m. from that at 8:00 p.m. and, as such, indicates a lack of circadian rhythm with respect to CTC numbers in these patients.

Circulating tumour cells in locally advanced breast cancer.

MATERIAL AND METHODS: A prospective study was conducted to determine the value of changes in circulating tumour cell (CTC) levels prior to and after the first cycle of neoadjuvant treatment in early prediction of pathologic response in locally advanced breast cancer (LABC). Two blood samples were obtained from 72 eligible LABC patients to isolate and enumerate CTCs before neoadjuvant chemotherapy started on day 1, and on day 21, immediately before second cycle administration. RESULTS: Sixty patients (83.3%) had <1 CTC in the first sample and response rates in this cohort were pathologic complete response (PCR) in 2 patients (5%), partial response (PR) in 35 (87.5%), stable disease (SD) in 2 (5%) and progressive disease (PD) in 1 (2.5%). Twelve patients (16.7%) had >2 CTCs in the first sample; these patients were more likely to have triple negative tumours. All 12 had fewer CTCs in the second sample. Response rates in this second cohort of 12 patients were PCR in 4 (34%), PR in 6 (50%), SD in 1 (8%) and PD in 1 (8%). PCR rate was markedly better in this second cohort (p<0.0042; OR 14.5, 95% CI 2.3-92). DISCUSSION: This study suggests that the presence of CTCs prior to neoadjuvant therapy might be a predictor of response to this therapy.

Carcinoma invasor de la mama: estadificación molecular del ganglio centinela / Breast invasive carcinoma: the molecular stratification of sentinel node

Demostrar que existe un grupo de pacientes estadios patológicos N0 que presentan metástasis en el estudio del ganglio centinela no diagnosticados por métodos de rutina. El estudio del análisis molecular nos informa o no sobre el pronóstico, y podría considerarse como factor independiente. Se observó una relación agrupando los casos de mayor riesgo conocido, detectándose una población de bajo riesgo en la que se obviaría la quimioterapia. Observamos, que si agrupamos las pacientes con Ki-67 mayor de 5 por ciento, la mayoría de los casos en las que se observaron micro metástasis estaban en este grupo; aceptamos una relación entre los dos factores pronóstico. Algo similar sucede con pacientes grado II y III; la relación con la existencia de micrometástasis es evidente, pudiendo aceptarse que existe un grupo de carcinomas de mama de menor agresividad; se plantea que estas pacientes no reciban tratamiento adyuvante, y no planificar tratamientos quirúrgicos agresivos.

Demonstrated that exist a group of patients with pathological stage No who present metastases in the study of sentinel nodule no diagnostic for routine method. The study of molecular analysis inform or not about the prognosis and be considered a prognosis independent factor. We observed a relation between the mayor risk known cases and detected a low risk population in which obviated the chemotherapy. We observed that grouped patients with Ki-67 raised of 5 % the majority of the cases in which observed micro metastases were in these group; we accepted a relationship between this two prognosis factors. Some similar occur with patient’s grade II and grade III; the relation with the existence of micro metastases is evident, and we accepted that exist a group of breast carcinoma of less aggressive; for these reason we planted that these patient does not receive adjuvant treatment, and no planned surgical aggressive treatment.

Inactivation of p16 by CpG hypermethylation in renal cell carcinoma.

OBJECTIVE: Renal carcinoma develops as a consequence of the accumulation of several genetic aberrations. Alterations in the p16 gene have been described in many tumors. Methylation of its promoter in CpG islands is the most common mechanism of inactivation of this gene. The aim of this study was to establish whether p16 gene methylation leads to a loss of the encoded protein in 57 patients with renal carcinoma, and if this aberration has any value in predicting disease progression in these patients. METHODS: Gene promoter methylation was determined by deoxyribonucleic acid treated with sodium bisulfite to subsequently amplify methylated and unmethylated regions rich in CpG islands. The p16 protein product was detected for immunohistochemical examination. RESULTS: Hypermethylation of the p16 gene was detected in 22.9% of the patients, none of whom had the protein product. A lack of p16 protein was confirmed in 52.9% of the tumors, indicating another genetic alteration or posttranscriptional modifications preventing the codification of this protein. Through multivariate analysis of overall survival, gene methylation was found to have independent prognostic value: the absence of alteration confers an undefined risk of death. CONCLUSIONS: Of the molecular modifications described for renal carcinoma, aberrations in the p16 gene are frequent. In these patients, methylation of the p16 gene promoter seems to afford a protective effect against the risk of death.