Percepción de la cultura de seguridad de pacientes en profesionales de una institución argentina / Perception on the culture of patient safety among professionals in an Argentinian health institution / Percepção da cultura de segurança de pacientes em profissionais de uma instituição argentina

Introducción: La cultura de seguridad en instituciones de salud es un tema que viene cobrando gran auge en muchos países desarrollados, e incluso también en algunos países de Latinoamérica. Sin embargo, en Argentina, los estudios sobre la cultura de la seguridad del paciente aún son incipientes. El objetivo de este estudio fue determinar la percepción de cultura de seguridad del paciente en los profesionales de la salud del Hospital Privado de Córdoba en el año 2015. Metodología: Para obtener información acerca de la percepción de cultura de seguridad se aplicó la versión española del instrumento Hospital Survey on Patient Safety Culture adaptado por el grupo de investigación en gestión de calidad de la Universidad de Murcia. La muestra la constituyeron 203 profesionales de la salud que se desempeñan en los servicios de internación (en las áreas clínico-asistenciales) del Hospital Privado de Córdoba. El análisis estadístico fue descriptivo, con medidas de frecuencia para las variables categóricas. Resultados: Las áreas de fortaleza identificadas correspondieron al aprendizaje organizacional/mejora continua y al trabajo en equipo en la unidad/servicio, mientras que la única dimensión evaluada como debilidad fue la referida a la dotación de personal. Conclusión: En términos prácticos de la gestión clínica, este trabajo permitió identificar áreas que indican qué se debe fortalecer dentro de la organización del hospital en materia de cultura de seguridad. En ese sentido, la percepción de que no hay personal suficiente cuando la carga de trabajo es excesiva interfiere para que se brinde atención de una manera óptima a los pacientes del hospital.

Introduction: Safety culture in health institutions is an issue which has been gaining greater importance in many developed countries, as well as in some Latin American countries, however, in Argentina, the studies on patient safety culture are still lacking. The objective of this study was to determine the perception of patient safety culture among health professionals in the Cordoba Private Hospital in 2015. Methodology: In order to obtain the related information, the Spanish version of the instrument Hospital Survey on Patient Safety Culture, adapted by a group of researchers on quality management from the University of Murcia, was applied on a 203 sample health professionals performing roles within the intern services area (clinical and assisting) in the Cordoba Private Hospital. The analysis included descriptive statistics with frequencies of the categorical variables. Results: The areas of strength corresponded to organizational learning/continuous improvement and teamwork in the unit and service; while the only dimension identified as a weakness was that on personnel allotment. Conclusion: This study allowed the identification of areas which need to be improved, in relation to the patient safety culture; in this sense, a perception was that there are not enough health professionals to address excessive workloads, a situation which interferes against the optimal attention of patients.

Introdução: A cultura de segurança de saúde é um tema que vem cobrando grande importância em muitos países desenvolvidos incluindo também alguns países de Latino América, porém na Argentina, os estudos de cultura de segurança de pacientes ainda são incipientes. O objetivo deste estudo foi determinar a percepção de cultura de segurança do paciente nos profissionais da saúde do Hospital Provado de Córdoba no ano 2015. Metodologia: Para obter informação acerca da percepção de cultura de segurança aplicou-se a versão espanhola do instrumento Hospital Survey on Patient Safety Culture adaptado pelo grupo de pesquisa em gestão de qualidade da Universidade de Murcia, a amostra constituiu-se por 203 profissionais de saúde que se desempenham nos serviços de hospitalização (nas áreas clínico assistenciais) do Hospital Privado de Córdoba. A análise estatística foi descritiva com medidas e frequência para variáveis categóricas. Resultados: As áreas de fortaleza identificadas corresponderam à aprendizagem organizacional/melhora contínua e ao trabalho em equipe na unidade/serviço, enquanto que a única dimensão avaliada como debilidade foi a referida à dotação de pessoal. Conclusão: Em termos práticos da gestão clínica, este trabalho permitiu identificar áreas que indicam o que se deve fortalecer dentro da organização do hospital em matéria de cultura de segurança, nesse sentido, a percepção de que não há pessoal suficiente quando a carga de trabalho é excessiva, interfere na atenção de uma maneira ótima aos pacientes do hospital.

Tasas y causas de suspensión de cirugías en un hospital público durante el año 2014 / Rates and causes of suspended surgeries in a public hospital during 2014 / Taxas e causas de suspensão de cirurgias em um hospital público no ano 2014

Objetivo Analizar la suspensión de cirugías en el Hospital de Trauma Dr. Federico Abete en el año 2014. Método Se analizaron datos de 441 cirugías suspendidas en la Unidad de Quirófano del Hospital de Trauma Dr. Federico Abete entre el 1 de enero y el 31 de diciembre de 2014. Se definió como suspensión de cirugía programada toda aquella programación de procedimientos quirúrgicos que por cualquier razón no se realizó en el día y la hora programados en el centro quirúrgico del hospital. Resultados La tasa de suspensión de cirugías fue del 7.6%. La tasa más baja fue registrada en el mes de diciembre (4.3%), mientras que noviembre registró la mayor tasa (11.1%). Las causas relacionadas con la logística o las de tipo administrativo correspondieron al 44.2% de las causas de suspensión, mientras que las causas médicas (no quirúrgicas) tuvieron una frecuencia del 40.8%. Las causas relacionadas con la anestesia representaron el 5.4% del total de las suspensiones de cirugías. Conclusiones Estos hallazgos permiten disponer de un insumo importante para gestionar los recursos de manera eficiente.

Objective To analyze the surgeries which were suspended in the Dr. Federico Abete hospital during the year of 2014. Method Data from 441 suspended surgeries in the Surgery Unit of the Dr. Federico Abete hospital, between January 1st and December 31st 2014, were analyzed. A suspended surgery was defined as any surgery procedure which, due to any cause, was not performed on the day and at the time which was programmed by the hospital surgery center. Results The overall rate of suspended surgeries was 7.6%. The lowest rate was registered during December (4.3%), while the highest in November (11.1%). Logistic or administration related causes represented 44.2%, while medical, but not surgical, causes represented 40.8%. Specifically anesthesia related causes represented 5.4%. Conclusions These findings suggest that it is important to address this issue managing the resources in an efficient manner.

Objetivo Analisar a suspensão de cirurgias no Hospital de Trauma Dr. Federico Abete no ano 2014. Método Analisaram-se dados de 441 cirurgias suspendidas na sala de operações do Hospital de Trauma Dr. Federico Abete entre 1 de janeiro e 31 de dezembro de 2014. Definiu-se como suspensão de cirurgia programada a toda aquela programação de procedimentos cirúrgicos que por qualquer motivo não se realizou no dia e na hora programada na sala de operações do hospital. Resultados A taxa de suspensão de cirurgias foi de 7.6%. A taxa mais baixa foi registrada no mês de dezembro (4.3%), enquanto que novembro registrou a maior taxa (11.1%). As causas relacionadas com a logística o causas administrativas corresponderam a 44.2% das causas de suspensão, enquanto que as causas médicas (não cirúrgicas) tiveram a frequência de 40.8%. As causas relacionadas com a anestesia representaram o 5.4% do total das suspensões de cirurgias. Conclusões Estes achados permitem dispor de um insumo importante para gerenciar os recursos de maneira eficiente.

Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.

Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4,603,718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51,434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection.

Clinical Behavior in Metastatic Brain Disease Is Not Influenced by the Immunological Defense Mediated by CD57 NK-Cells.

Objectives. The purpose of the present study is to verify if the degree of immunological response against metastatic tumors, measured by the number of CD57(+) NK-cells in the tissue of a brain metastasis, influences the later development of new brain metastases or tumor recurrence. Patients and Methods. CD57(+) NK-cells were immunohistochemically identified in the resected tumor, in a series of twenty patients operated on by a single brain metastasis secondary to lung adenocarcinoma. In each case, the degree of CD57(+) NK-cells infiltration within the tumor tissue and the period free of new intracranial disease after brain surgery were recorded. Results. All the studied tumors showed variable number of CD57(+) NK-cells (mean ± standard deviation: 8.4 ± 4.8 per microscopical field, at 200x). The period free of intracranial disease ranged between 10 and 52 weeks (mean ± standard deviation: 22.7 ± 11.9). Statistical analysis showed that there was no correlation between the degree of NK-cells infiltration within the resected tumor and the period free of intracranial disease after surgery (P > 0.05). Conclusion. This finding supports that clinical behavior in metastatic brain disease is not influenced by the immunological response mediated by CD57(+) NK-cells.

Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review.

The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, but such measurements are a poor marker of acute deterioration in kidney function. We performed a systematic review of publications that evaluated the accuracy and reliability of serum and urinary biomarkers in human subjects when used for the diagnosis of established AKI or early AKI, or to risk stratify patients with AKI. Two reviewers independently searched the MEDLINE and EMBASE databases (January 2000-March 2007) for studies pertaining to biomarkers for AKI. Studies were assessed for methodologic quality. In total, 31 studies evaluated 21 unique serum and urine biomarkers. Twenty-five of the 31 studies were scored as having 'good' quality. The results of the studies indicated that serum cystatin C, urine interleukin-18 (IL-18), and urine kidney injury molecule-1 (KIM-1) performed best for the differential diagnosis of established AKI. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin, IL-18, glutathione-S-transferase-pi, and gamma-glutathione-S-transferase performed best for early diagnosis of AKI. Urine N-acetyl-beta-D-glucosaminidase, KIM-1, and IL-18 performed the best for mortality risk prediction after AKI. In conclusion, published data from studies of serum and urinary biomarkers suggest that biomarkers may have great potential to advance the fields of nephrology and critical care. These biomarkers need validation in larger studies, and the generalizability of biomarkers to different types of AKI as well as the incremental prognostic value over traditional clinical variables needs to be determined.

[Parathyroid cancer in a patient with previous history of hypernephroma: a clinical case]. / Cáncer de paratiroides en paciente con antecedentes de hipernefroma, a propósito de un caso.

We report the clinical case of a 55 year-old male patient, with a previous history of nephrectomy by hypernephroma sixteen years ago, first presenting hypercalcemia and rising of intact parathyroid hormone (iPTH) levels. A localization study revealed an intrathyroid nodule with cystic appearance. After undergoing a hemi-thyroidectomy, the patient is diagnosed with parathyroid carcinoma. This article analyzes previously published cases presenting parathyroidal pathologies associated with hypernephroma. A broader differential diagnosis--including the screening of parathyroidal pathologies should be considered in patients with hypercalcemia and hypernephroma.

Cáncer de paratiroides en paciente con antecedentes de hipernefroma a propósito de un caso / Parathyroid cancer in a patient with previous history of hypernephroma: a clinical case

Presentamos el caso de un varón de 55 años con antecedentes de nefrectomía por hipernefroma dieciseis años antes que debuta con hipercalcemia y aumento de parathormona intacta (PTHi 1-84). En el estudio de localización se identifica un nódulo intratiroideo de apariencia quística. Tras hemitiroidectomía, se llega al diagnóstico anatomopatológico de carcinoma paratiroideo. En este artículo se analizan los casos publicados con anterioridad con asociación entre patología paratiroidea e hipernefroma. En pacientes con hipercalcemia e hipernefroma debe considerarse la realización de un diagnóstico diferencial más amplio que incluya el despistaje de patología paratiroidea

We report the clinical case of a 55 year-old male patient, with a previous history of nephrectomy by hypernephroma sixteen years ago, first presenting hypercalcemia and rising of intact parathyroid hormone (iPTH) levels. A localization study revealed an intrathyroid nodule with cystic appearance. After undergoing a hemi-thyroidectomy, the patient is diagnosed with parathyroid carcinoma.This article analyzes previously published cases presenting parathyroidal pathologies associated with hypernephroma. A broader differential diagnosis- including the screening of parathyroidal pathologies- should be considered in patients with hypercalcemia and hypernephroma

Acute renal failure in hematopoietic cell transplantation.

Hematopoietic cell transplantation is a common procedure for the treatment of malignancies and some non-malignant hematologic disorders. In addition to other transplant-related organ toxicities, acute renal failure is a common complication following transplantation. This review discusses the incidence, timing, etiologies, risk factors, and prognosis of renal failure associated with three commonly used transplantation procedures - myeloablative autologous, myeloablative allogeneic, and non-myeloablative allogeneic transplantation. It is important to note that the epidemiology and prognosis of renal failure are distinct with these three transplantation procedures. However, the common theme is that mortality increases with worsening renal failure with all three procedures. Moreover, mortality is >80% for patients with renal failure requiring dialysis. It also appears that surviving patients have an increased risk of chronic kidney disease after renal failure. The reduction of acute renal failure will have several advantages, including reducing mortality and the burden of chronic kidney disease following transplantation.

Evaluation of the antitumor activity of interleukin-12 in an experimental murine model of colorectal cancer induced by 1,2 dimethyl-hydrazine (DMH).

OBJECTIVE: Interleukin 12 (IL-12) is a cytokine that may enhance the proliferation and cytotoxic activity of T lymphocytes and natural killer (NK) cells. A relationship between extensive intratumoral infiltration of NK cells and longer survival rates in colorectal cancer (CRC) patients was previously noted. Preliminary evidence suggests that the combined administration of IL-12 and IL-2 may produce additive immunomodulatory activity. The purpose of this study was to determine whether the systemic administration of IL-12 (+/- IL-2) may induce an immune response against CRC as induced by 1,2-dimethylhydrazine (DMH). METHODS: Sixty-five 6-week-old Wistar rats were treated with weekly subcutaneous injections of DMH for 26 weeks at a dose of 20 mg/kg of body weight. Once tumoral induction was over, the animals were randomly allocated to one of three groups: I, control; II, intraperitoneal injections of IL-12; III, intraperitoneal injections of IL-12 combined with IL-2. At 30 weeks, all surviving animals were sacrificed. We studied the following parameters in each rat--number of tumors, size of tumors, and total tumoral volume. Tumor samples were studied using the monoclonal antibody CD 57 for the detection of NK cells. The extent of NK infiltration was classified as small, less than 50 NK cells/50 high-power field (HPF); moderate, 50 to 150 NK cells/50 HPF, and extensive, more than 150 NK cells/50 HPF. RESULTS: Thirty-five rats died before completion of the carcinogen exposure, and 30 rats were randomized (10 each group). In group II, 2 animals died during treatment. All rats in groups I and III developed tumors, while in group II two rats (25%) were tumor-free. Moreover, only one rat in group II developed multiple neoplasms, in contrast with group I and group III, where six rats (60%) and seven rats (70%), respectively, had more than one tumor. We found statistically significant differences in the mean number of tumors found in group II when compared to group I (p = 0.028) and group III (p = 0.019). Other parameters measured, such as biggest tumor size and total tumoral volume were found to be lower in group II, although no statistical differences were found between groups. Only 10% of rats in group I showed moderated/extensive NK cell infiltration, vs. 60% of rats in group II (p = 0.077) and 70% in group III (p = 0.02). CONCLUSION: The administration of DMH to rodents provides a reliable and consistent means of inducing CRC that may be suitable for the evaluation of anti-cancer therapies. Our findings suggest that IL-12 is effective against the development of experimental CRC. Its antineoplastic effect could be attributed to the stimulus of this cytokine on the intratumoral infiltration of NK cells.

Estudio de la respuesta antitumoral de la interleucina- 12 en cáncer de colon inducido mediante 1, 2-dimetilhidracina (DMH) / Evaluation of the antitumor activity of interleukin-12 in an experimental murine model of colorectal cancer induced by 1, 2 dimethyl-hydrazine (DMH)

Objetivo: la interleucina (IL-12) es una citocina que estimulala proliferación y la actividad citotóxica de los linfocito T y las célulasnatural killer (NK). En trabajos previos se ha observado unarelación entre la infiltración intratumoral de células NK y una mayorsupervivencia en carcinomas colorrectales (CCR). Existen evidenciasde un efecto aditivo en la actividad inmunomoduladora dela asociación de IL-12 con IL-2. Así, nos hemos propuesto el estudiode la capacidad de respuesta inmune antitumoral, tras la administraciónsistémica de IL-12 sola o combinada con IL-2, en unmodelo experimental de CCR inducidos mediante la administraciónde 1,2-dimetilhidracina (DMH).Método: sesenta y cinco ratas Wistar de 6 semanas a las quese administró en inyección subcutánea una dosis semanal deDMH a razón de 20 mg/kg de peso durante 26 semanas. Finalizadoel periodo de inducción, los animales se distribuyeron aleatoriamenteen tres grupos. I: grupo control. Grupo II, se administróIL-12 recombinante murina. Grupo III: se administró IL-12, combinadacon IL-2. Las ratas se sacrificaron en la semana 30, estudiándoselos siguientes parámetros: número y localización de tumores,tamaño y carga tumoral. Se realizó inmunotinción paracélulas NK con anticuerpo monoclonal CD 57. Se establecierontres grupos según la cuantía del infiltrado: leve, menos 50 células/50 campos de gran aumento (CGA), moderado, entre 50 y150/células/50 CGA y elevado, más de 150 células/50 CGA.Resultados: durante la inducción tumoral fallecieron 35 ratas.Las 30 restantes fueron distribuidas aleatoriamente en 3 gruposde 10. Durante las 2 semanas de tratamiento fallecieron 2 ratas,del grupo II. Todas las ratas de los grupos I y III desarrollaronCCR. En el grupo II, dos animales (25%) no desarrollaron tumor.Sólo una rata del grupo II desarrolló neoplasias múltiples en contrastecon el grupo I en el que esto ocurrió en 6 ratas (60%) y siete(70%) en el grupo III. Se hallaron diferencias estadísticamentesignificativas en el número de tumores desarrollados entre el grupoII respecto al I (p = 0,028) y al grupo III (p = 0,019). El mayortamaño tumoral o el volumen tumoral total fueron menores en elgrupo II pero no se obtuvieron diferencias estadísticamente significativascon los restantes grupos. Un 10% de las ratas del grupo Ipresentó moderada o extensa infiltración, frente al 60% del grupoII (p = 0,077) y al 70% del grupo III (p = 0,02). Entre los grupos IIy III no se encontró ninguna diferencia estadística (p = 1).Conclusión: El modelo usado de inducción tumoral es un modeloútil para el estudio de la eficacia de distintos tratamientos antitumorales.Pensamos que la IL-12 tiene un efecto antineoplásicofrente al desarrollo de tumores experimentales, lo que puede seratribuido, al menos en parte, al estímulo ejercido por esta citocinasobre los infiltrados intratumorales de células NK

Objective: interlukin 12 (IL-12) is a cytokine that may enhancethe proliferation and cytotoxic activity of T lymphocytesand natural killer (NK) cells. A relationship between extensive intratumoralinfiltration of NK cells and longer survival rates in colorectalcancer (CRC) patients was previously noted. Preliminaryevidence suggests that the combined administration of IL-12 andIL-2 may produce additive immunomodulatory activity. The purposeof this study was to determine whether the systemic administrationof IL-12 (+/- IL-2) may induce an immune responseagainst CRC as induced by 1,2-dimethylhydrazine (DMH).Methods: sixty-five 6-week-old Wistar rats were treated withweekly subcutaneous injections of DMH for 26 weeks at a dose of20 mg/kg of body weight. Once tumoral induction was over, theanimals were randomly allocated to one of three groups: I, control;II, intraperitoneal injections of IL-12; III, intraperitoneal injectionsof IL-12 combined with IL-2. At 30 weeks, all surviving animalswere sacrificed. We studied the following parameters in eachrat – number of tumors, size of tumors, and total tumoral volume.Tumor samples were studied using the monoclonal antibodyCD 57 for the detection of NK cells. The extent of NK infiltrationwas classified as small, less than 50 NK cells/50 high-power field(HPF); moderate, 50 to 150 NK cells/50 HPF, and extensive,more than 150 NK cells/50 HPF.Results: thirty-five rats died before completion of the carcinogenexposure, and 30 rats were randomized (10 each group). Ingroup II, 2 animals died during treatment. All rats in groups I andIII developed tumors, while in group II two rats (25%) were tumorfree.Moreover, only one rat in group II developed multiple neoplasms,in contrast with group I and group III, where six rats(60%) and seven rats (70%), respectively, had more than one tumor.We found statistically significant differences in the meannumber of tumors found in group II when compared to group I(p=0.028) and group III (p = 0.019). Other parameters measured,such as biggest tumor size and total tumoral volume were found tobe lower in group II, although no statistical differences were foundbetween groups. Only 10% of rats in group I showed moderated/extensive NK cell infiltration, vs. 60% of rats in group II (p =0.077) and 70% in group III (p = 0.02).Conclusion: The administration of DMH to rodents provides areliable and consistent means of inducing CRC that may be suitablefor the evaluation of anti-cancer therapies. Our findings suggest thatIL-12 is effective against the development of experimental CRC. Itsantineoplastic effect could be attributed to the stimulus of this cytokineon the intratumoral infiltration of NK cells

Infiltrados linfocitarios de células NK y apoptosis en tumores cerebrales metastásicos / Lymphocytary infiltrates of NK-cells and apoptosis in metastatic brain tumors

Introducción: El desarrollo de fenómenos de apoptosis en las células de los tumores sólidos se ha tratado de relacionar con un ataque inmunológico a cargo de células linfocitarias tipo Natural Killer (NK).Objetivo: Teniendo en cuenta que los tumores cerebrales metastásicos se caracterizan por una intensa infiltración linfocitaria, el propósito del presente trabajo es verificar si existe una correlación entre la presencia de linfocitos tipo NK en el estroma de estos tumores y el desarrollo de fenómenos de apoptosis. Material y métodos: Se ha estudiado una serie de 20 metástasis cerebrales obtenidas tras su extirpación quirúrgica, marcándose las células NK del estroma tumoral mediante el anticuerpo monoclonal CD57. Igualmente, se marcaron las células tumorales en apoptosis mediante el anticuerpo monoclonal F7-26. Se utilizó el test de Spearman para conocer si existía una correlación entre presencia de células NK en el estroma tumoral y presencia de células tumorales apoptóticas. Resultados: En todos los tumores estudiados existían células en apoptosis, pero en número variable, con un índice de marcaje promedio de 11,48 por ciento. En todos los casos se observó, igualmente, que existían células linfocitarias tipo NK en el estroma tumoral, también en proporción variable, oscilando entre 4 y 20 por campo, a un aumento de 200x (valor medio de 8,4 células/campo). El estudio estadístico efectuado en esta serie de tumores no demostró que existiera una correlación entre presencia de células NK y número de células en apoptosis. Este hallazgo sugiere que, al menos en el caso de las metástasis cerebrales, las células NK no desempeñan un papel significativo en los mecanismos de defensa inmunológica (AU)

Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer.

BACKGROUND: Survival at the intermediate stage of colorectal cancer (CRC) is less predictable than in the early and advanced stages. Several genetic markers possibly involved in growth and progression of CRC can be used for prognosis. AIMS: This study investigated the proportion of allelic loss (loss of heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient prognosis. PATIENTS AND METHODS: A total of 314 patients were investigated for LOH at the BRCA1 locus using polymerase chain reaction by means of three intragenic polymorphic microsatellite markers. Allelic losses were compared with clinicopathological characteristics of patients, recurrence rate, disease free survival (DFS), and overall survival. RESULTS: Twenty six patients were excluded because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%) were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was higher in patients with LOH (p=0.0003), and DFS was 73.3% (SEM 5.7) at five years in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss (p=0.0004). Retention of alleles at the BRCA1 locus was associated with a favourable DFS in stages I and II (p<0.05). The presence of LOH was also significantly associated with short overall survival (p=0.02). Multivariate analysis in the complete series showed that stage (p=0.006) and lymph node metastases (> or =4 nodes, p=0.0001; 1-3 nodes, p=0.038) were independent prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH was an independent prognostic factor in stages I and II (p=0.001). CONCLUSIONS: BRCA1 LOH is a molecular alteration present in CRC, with unfavourable repercussions for overall survival, that could be considered as an outstanding independent prognostic factor in stages I and II.

Apoptosis is not correlated with the presence of CD57+ NK-cells in brain metastases.

BACKGROUND: Cell apoptosis in solid tumours has been related to immunological attack by NK-cells. The purpose of the present study is to verify in the tissue of brain metastases a possible relationship among the degree of NK-cell infiltration and the number of apoptotic tumour cells. METHODS: Twenty brain metastases whose tumour cells expressed CD95 (Fas/APO1) have been studied. NK-cells were identified by using the monoclonal antibody to CD57, and apoptotic tumour cells by means of the immunostain with the anti-ssDNA monoclonal antibody F7-26. The Spearman rank correlation test was used to study the relationship between the degree of CD57-NK-cell infiltration and the apoptosis labelling-index. FINDINGS: Positivity to F7-26 was present in all tumour samples, but the number of immunostained cells showed a wide variability, with a mean apoptosis labelling-index of 11.48%. All the studied tumours showed CD57 immunostained cells, with a number that ranged between 4 and 20 per microscopical field at 200x (mean+/-standard deviation: 8.4+/-3.7). Statistical studies showed that there was no correlation between the number of CD57 immunostained NK-cells and the apoptosis labelling-index (p>0.05). INTERPRETATION: These findings suggest that in brain metastases, apoptosis related to immune response is mainly mediated by activated tumour-infiltrating mononuclear cells other than CD57(+) NK-cells.

Apoptosis y proliferación en metástasis cerebrales / Apoptosis and proliferation in brain metastases

Introducción: La proliferación celular y la muerte celular programada (apoptosis) en tumores sólidos determinan, en gran medida, la progresión neoplásica. Existen observaciones previas en la literatura que muestran una clara correlación entre proliferación y apoptosis en tumores cerebrales primarios, tales como los astrocitomas y oligodendrogliomas, pero no en glioblastomas. Objetivo: El propósito del presente estudio es verificar una posible correlación entre expresión de marcadores de proliferación y marcadores de apoptosis en metástasis cerebrales. Material y métodos: Se ha estudiado una serie de 20 tumores cerebrales metastásicos. Tras marcaje inmunohistoquímico con F7-26 y MIB1/Ki-67 se determinó en cada tumor un índice de apoptosis (IA) y un índice de proliferación (IP). En la totalidad de la serie se estudió una posible relación directa entre estos parámetros, utilizando el test de correlación de Spearman. Resultados: Todas las muestras tumorales mostraron positividad en grado variable a los marcadores F7-26 y MIB1/Ki-67. Los índices de apoptosis y de proliferación mostraron valores que oscilaron entre el 1 y el 78 por ciento para el índice de apoptosis (valor medio: 11,48 por ciento) y entre el 2,4 y el 21 por ciento (valor medio: 8,23 por ciento) para el índice de proliferación. Cuando se estudió la relación entre ambos parámetros para la totalidad de la serie se observó una estrecha correlación, estadísticamente significativa (p < 0,0001). Este resultado sugiere que, en pacientes con tumores cerebrales metastásicos, proliferación y apoptosis muestran una estrecha correlación y que, al contrario de lo que ocurre en algunos casos de gliomas malignos primarios, no es posible predecir el ritmo de crecimiento de una metástasis cerebral analizando el balance entre apoptosis y proliferación (AU)

Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma.

OBJECTIVE: To study the prognostic significance of angiogenesis and enhancement on contrast-enhanced computerized tomography (CT) in oligodendrogliomas. MATERIAL AND METHODS: CD34 immunostaining was employed in samples of 26 low-grade oligodendrogliomas from patients treated by extensive resection and radiotherapy to determine the tumor angiogenesis index (TAI), calculated by measuring the immunostained endothelial surface area, in microm(2), per 1000 tumor cells. Preoperative CT scan was evaluated in each case, and the absence or presence of tumor enhancement after contrast administration was recorded. Survival was analyzed and statistically compared for subgroups of patients with lesions in which the TAI was less than or greater than 15, and for subgroups of patients having tumors showing presence or absence of enhancement on contrast-enhanced CT. RESULTS: Survival of patients with tumors showing a TAI of less than 15 was 100% and 71% at 5 and 10 years, respectively, vs a survival of 50% and 0% for patients showing a TAI of more than 15 (P < 0.05). The 14 patients whose tumors showed enhancement in preoperative contrast-enhanced CT had 5- and 10-year survival rates of 57% and 14%, respectively, vs 100% and 83% for the 12 patients whose tumors presented no enhancement (P < 0.05). Moreover, 79% of the tumors showing contrast enhancement had a TAI greater than 15, while 92% of those exhibiting no enhancement had a TAI of less than 15. CONCLUSION: These findings indicate a relationship between enhancement on preoperative CT scan and endothelial surface area in oligodendrogliomas, and suggest that this enhancement and the TAI may be considered angiogenesis-related factors with similar prognostic significance in terms of survival.

Angiogénesis en glioblastomas: significado biológico de la expresión del factor de crecimiento endotelial vascular / Angiogenesis in glioblastomas: biological significance of the expression of vascular endothelial growth factor

Introducción: La angiogénesis es un fenómeno por el cual las células tumorales forman un lecho vascular que les permite su nutrición. En el caso de los tumores malignos, el conocimiento de este fenómeno puede ir seguido de estrategias terapéuticas destinadas a inhibir el crecimiento tumoral. Objetivo: Estudiar la expresión de proteínas inductoras de angiogénesis (VEGF) en glioblastomas y analizar su relación con la formación del lecho vascular, formación de edema peritumoral y supervivencia. Material y método: Se ha estudiado el grado de expresión de VEGF en 38 glioblastomas de los hemisferios cerebrales por técnicas inmunohistoquímicas y se ha analizado estadísticamente la posible correlación entre expresión de VEGF y factores como son la presencia de edema peritumoral, el grado de superficie endotelial vascular, medido morfométricamente tras marcaje inmunohistoquímico del antígeno CD-34 de las células endoteliales y la mayor o menor supervivencia de los pacientes. Resultados: Al menos el 95 per cent de los glioblastomas expresan VEGF en mayor o menor grado. Esta expresión se correlaciona estrechamente con la angiogénesis intratumoral, pero no con el desarrollo de edema adyacente al tumor. En cuanto al significado pronóstico de la angiogénesis VEGF-dependiente, nuestros resultados sugieren que la determinación del índice de angiogénesis, en relación con el número de células tumorales, puede tener significación en estos tumores (AU)

Imbalance between apostain expression and proliferative index can predict survival in primary glioblastoma.

BACKGROUND: Cell proliferation and cell death are opposing processes in tumour growth, with tumour progression reflecting the balance between proliferating and apoptotic cells. The purpose of the present study is to verify the hypothesis that an imbalance between apoptosis and proliferation can predict survival in patients with primary glioblastoma. METHODS: After the immunohistochemical study of Apostain and MIB-1 expression, the index of apoptosis (AI), the index of proliferation (PI), and the ratio AI/PI was recorded for each tumour specimen, in a series of 32 primary glioblastomas. Studies of correlation between AI and PI, between AI and survival, between PI and survival, and between the ratio AI/PI and survival, were performed using the Spearman rank correlation test. Furthermore, a comparative study of survival was performed for subgroups of patients with ratio AI/PI greater or lesser than 1, using the log rank test. FINDINGS: In the present series, values of AI and PI showed a wide distribution, with a mean +/- SD of 8.16 +/- 7.2, and of 12.69 +/- 21.1, respectively. The values for the ratio AI/PI ranged between 0.01 and 6.03 (mean +/- SD: 1.44 +/- 1.60). Statistical study failed to obtain correlation between AI and PI. Survival of patients not correlated with AI neither with PI. The ratio between AI and PI did not correlate with survival either. Nevertheless, when survival for the subgroups of patients showing a ratio AI/PI greater or lesser than 1 was compared, a significant difference was found (p: 0.02). Survival ranged between 50 and 81 weeks (mean of 58.5 +/- 11.05 weeks) for the 12 cases showing a ratio AI/PI greater than 1, and it ranged between 8 and 85 weeks (mean: 38.20 +/- 25.37 weeks) for the 20 cases showing a ratio AI/PI lesser than 1. INTERPRETATION: Our present results suggest that a clear imbalance between cell proliferation and apoptosis can predict outcome in patients operated on for a primary glioblastoma.

Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.

The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p < 0.05). Our present findings suggest the usefulness of VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma.