Priorities and root cause analysis of quality and safety problems in chilean hospitals / Prioridades y análisis de las causas de los problemas de calidad y seguridad en hospitales chilenos

BACKGROUND: Quality improvement is an important component of hospital operations. AIM: To prioritise clinical quality and safety problems in Chilean hospitals according to their severity, frequency, and detectability. MATERIAL AND METHODS: The study was conducted between December 2018 and June 2019. To identify quality and safety problems, an exploratory study was conducted using an online survey aimed to those responsible for clinical quality and safety in Chilean hospitals. The survey was sent to 94 hospitals and completed by quality management personnel at 34 hospitals, yielding a total of 25 valid surveys for analysis. Based on the information gathered, a risk priority score was computed to rank the problems surveyed. Focus groups were held to find the root causes of the quality and safety problem with the highest risk priority score. RESULTS: The three highest risk priorities were:1 ineffective interprofessional communication,2 lack of leadership for addressing frequently recurring safety issues, and3 antimicrobial resistance due to inappropriate use of antibiotics. For the communication problem, the focus group found two main root causes: those due to personnel and those relating to the hospitals themselves. CONCLUSIONS: Hospitals can systematically use the proposed approach to categorize their main clinical quality and safety problems, analyze their causes, and then design solutions.

ANTECEDENTES: La mejora continua de la calidad es un componente importante en las actividades hospitalarias. OBJETIVO: Priorizar los problemas de calidad y seguridad en hospitales chilenos de acuerdo a su severidad, frecuencia y detectabilidad. MATERIAL Y MÉTODOS: Se efectuó un estudio exploratorio con una encuesta en línea para detectar problemas de calidad y seguridad, dirigida a quienes están a cargo de los problemas de calidad y seguridad en los hospitales. La encuesta fue enviada a 94 hospitales y respondida por los encargados de calidad y seguridad en 34 de ellos, lográndose 25 encuestas válidas para análisis. El estudio se llevó a cabo entre diciembre de 2018 y junio de 2019. Se diseñó una escala de prioridades de riesgo para determinar la importancia relativa de los problemas detectados. Se llevaron a cabo grupos focales para determinar las causas del problema más importante. RESULTADOS: En Chile, los problemas de calidad y seguridad más importantes son la falta de comunicación interprofesional, falta de liderazgo para abordar los problemas de seguridad y calidad, y resistencia a antibióticos debido a su uso inapropiado. Problemas relacionados al personal y relacionados al hospital fueron las causas primarias de la falta de comunicación. CONCLUSIONES: Los hospitales podrían utilizar este enfoque de forma sistemática para categorizar sus principales problemas de calidad y seguridad, analizar las causas y diseñar soluciones.

Priorities and root cause analysis of quality and safety problems in chilean hospitals.

BACKGROUND: Quality improvement is an important component of hospital operations. AIM: To prioritise clinical quality and safety problems in Chilean hospitals according to their severity, frequency, and detectability. MATERIAL AND METHODS: The study was conducted between December 2018 and June 2019. To identify quality and safety problems, an exploratory study was conducted using an online survey aimed to those responsible for clinical quality and safety in Chilean hospitals. The survey was sent to 94 hospitals and completed by quality management personnel at 34 hospitals, yielding a total of 25 valid surveys for analysis. Based on the information gathered, a risk priority score was computed to rank the problems surveyed. Focus groups were held to find the root causes of the quality and safety problem with the highest risk priority score. RESULTS: The three highest risk priorities were:1 ineffective interprofessional communication,2 lack of leadership for addressing frequently recurring safety issues, and3 antimicrobial resistance due to inappropriate use of antibiotics. For the communication problem, the focus group found two main root causes: those due to personnel and those relating to the hospitals themselves. CONCLUSIONS: Hospitals can systematically use the proposed approach to categorize their main clinical quality and safety problems, analyze their causes, and then design solutions.

Delphi Project on the trends in Implant Dentistry in the COVID-19 era: Perspectives from Latin America.

AIM: To establish trends in Implant Dentistry in Latin America in the COVID-19 pandemic. MATERIAL AND METHODS: A steering committee and an advisory group of experts in Implant Dentistry were selected among eighteen countries. An open-ended questionnaire by Delphi methodology was validated including 64 questions, divided in 7 topics, concerning the various trends in dental implantology. The survey was conducted in two rounds, which provided the participants in the second round with the results of the first. The questionnaires were completed on August 2020, and the online meeting conference was held on September 2020. The final prediction was developed through consensus by a selected group of experts. RESULTS: A total of 197 experts from Latin America answered the first and second questionnaire. In the first round, the established threshold for consensus (65%) was achieved in 30 questions (46.87%). In the second round, performed on average 45 days later, this level was achieved in 47 questions (73.43%). Consensus was completely reached on the item "Diagnostic" (100%), the field with the lowest consensus was "Demand for treatment with dental implants" (37.5%). CONCLUSIONS: The present study in Latin America has provided relevant and useful information on the predictions in the education and practice of Implant Dentistry in the COVID-19 era. The consensus points toward a great confidence of clinicians in the biosecurity protocols used to minimize the risk of SARS-CoV-2 transmission. It is foreseen as an important change in education, with introduction of virtual reality and other simulation technologies in implant training.

Recurrencia de oligodendroglioma luego de cirugía, quimioterapia y radioterapia / Recurrence of oligodendroglioma after surgery, chemotherapy and radiotherapy

Introducción: Los gliomas conforman la mayoría de los tumores primarios que surgen del parénquima cerebral. Reporte de caso: varón de 39 años, con antecedente de hace 08 años de oligodendroglioma grado II sometido a cirugía para exéresis completa, más quimioterapia y radioterapia; que se presentó con 6 semanas de enfermedad caracterizada por crisis convulsivas tónico clónicas generalizadas, adormecimiento y disminución de fuerza de hemicuerpo derecho. El examen clínico revelo hemiparesia derecha a predominio braquial 2/5, Glasgow 15 puntos. En la resonancia cerebral se encontró extenso realce nodular de 4.8 cm localizado en región fronto-parietal izquierda, con abundante edema vasogénico ejerciendo efecto de masa. Se realiza segunda cirugía encontrando en anatomía patología un glioma de IV grado OMS. Conclusión: Los oligodendrogliomas son tumores de crecimiento lento, cuyo tratamiento es conjunto, cirugía, quimioterapia y radioterapia. La recurrencia generalmente se da con un grado más elevado, disminuye la esperanza de vida del paciente.

Estilos de crianza como predictores del comportamiento tabáquico adolescente / Parenting Styles of Father and Mother as Predictors of Adolescents' Smoking Behavior / Estilos de criação como preditores do comportamento do consumo de tabaco em adolescentes

Objetivo. Evaluar la asociación de cada uno de los componentes de los estilos de crianza del padre y de la madre sobre la susceptibilidad a fumar, la experimentación con los cigarros y el consumo actual de tabaco de los hombres y las mujeres adolescentes. Método. La muestra fue no aleatoria de una población de estudiantes de secundaria pública de la Ciudad de México. Estuvo constituida por 253 adolescentes, quienes respondieron un cuestionario demográfico y las escalas de Estilos Crianza de Steinberg y de Susceptibilidad Tabáquica. Resultados. Los análisis de regresión múltiple efectuados permitieron identificar el cuidado del padre como el principal predictor de la susceptibilidad y la experimentación en los hijos hombres, y la supervisión y el cuidado de las madres, como los componentes que más varianza explicaron en el caso de las mujeres. Conclusión. Cada uno de los componentes de los estilos de crianza del padre y de la madre afecta de manera diferenciada el comportamiento tabáquico de los adolescentes.

Objective. Research on adolescent tobacco use has shown the significant influence of family variables, particularly, parenting style. The purpose of this study was to evaluate the association of each component of fathers' and mothers' parenting styles on smoking susceptibility, cigarette experimentation and the current tobacco use of boys and girls. Method. A non-probabilistic sample of 253 adolescent public high school students in Mexico City answered a demographic questionnaire and the Steinberg's Parenting Styles Scale and Tobacco Susceptibility Scale. Results. Multiple regression analyses made it apparent that the father's care is the main predictor of susceptibility and experimentation in boys, and supervision and care from the mother are the components that explained most variance for girls. Conclusion. Each of the components of the parenting styles of fathers and mothers differently affects the smoking behavior of boys and girls.

Escopo. A pesquisa sobre o consumo de tabaco em adolescentes tem mostrado a influência negativa significativa das variáveis familiares, em particular, dos estilos de criação dos pais. O propósito do presente estudo foi avaliar a associação de cada um dos componentes dos estilos de criação do pai e da mãe sobre a susceptibilidade para fumar, a experimentação com os cigarros e o consumo atual de tabaco dos homens e mulheres adolescentes. Metodologia. A amostra foi não aleatória de uma população de estudantes de uma escola de ensino médio pública da Cidade do México, esteve constituída por 253 adolescentes, os quais responderam um questionário demográfico e as escadas de Estilos Criação de Steinberg e de Susceptibilidade para o Tabaco. Resultados. A análise de regressão múltipla efetuada permitiu identificar o cuidado do pai como o principal preditor da susceptibilidade e a experimentação em filhos homens, e a supervisão e o cuidado das mães, como os componentes que com mais variação explicaram o caso das mulheres. Conclusão. Cada um dos componentes dos estilos de criação do pai e da mãe afeta de jeito diferente o comportamento de uso de tabaco nos adolescentes.

Células prostáticas circulantes para la detección de cáncer / Circulating prostate cells for cancer detection

Introducción: El antígeno prostático específico (APE) es el marcador en suero más utilizado para la patología prostática, y el único empleado para la detección del cáncer de próstata. Si bien el APE es sumamente específico para tejido prostático, un nivel elevado no lo es para cáncer de próstata, ya que se puede ver elevado también en la enfermedad prostática benigna. Existe la necesidad de un examen simple para definir la necesidad de una biopsia prostática en hombres con un APE alterado. El examen de detección de células prostáticas malignas en sangre (CPMs) puede ser un candidato para la detección precoz del cáncer de próstata (CP). Métodos y pacientes: Analizamos de manera prospectiva un grupo de pacientes que fueron sometidos a una biopsia inicial por sospecha de cáncer de próstata y también a una segunda biopsia en el seguimiento posterior. Los resultados de la biopsia fueron comparados con las células prostáticas malignas circulantes (CPMC), las cuales fueron identificadas en muestras de sangre tomadas antes de la realización de la biopsia utilizando inmunocitoquímica estándar. El objetivo fue determinar la capacidad diagnóstica de las CPMC antes de la primera, la segunda y la tercera biopsia prostática. Resultados: En total, 423 pacientes consecutivos participaron en el estudio, con una edad promedio de 65.3 ± 8.9 años y un APE (mediana) de 5.28 ng/ml (RIQ 4.36-7.94 ng/ml). De ellos, 138 (32.6%) tuvieron un cáncer detectado en la biopsia inicial. La prueba de la detección de CPCs tuvo una sensibilidad de 0.89 (IC 95%: 0.82 a 0.94) y una especificidad de 0.89 (IC 95%: 0.84 a 0.92). De los 423 pacientes, a 125 se les reallizó una segunda biopsia, y a 57, una tercera, las CPCs lograron una sensibilidad y especificidad de 0.89/0.87 y 0.88/0.96 en la segunda y tercera biopsia, respectivamente, con un valor predictivo negativo y positivo de 0,65 / 0,97 y 0,88 / 0,95 en la segunda y tercera biopsia, en ese orden. Conclusiones: Las CPCs utilizadas en conjunto con las pruebas de tamizaje actuales, APE y tacto rectal, pueden mejorar la efectividad del tamizaje, reduciendo la frecuencia de biopsias negativas, así como su número total y sus complicaciones. Además, el costo-beneficio para el sistema de salud público en términos de utilización de recursos es positivo

Introduction: The prostate-specific antigen (PSA) is the most frequently used serum marker for the detection of prostatic disease, and the only marker used for the detection of prostate cancer. While PSA is highly specific for prostatic tissue, a high PSA serum level is not specific for prostate cancer, since it can be high even in benign prostatic disease. There is a need for a simple exam to define the opportunity of a prostate biopsy in men with an altered PSA levels. Detection of malignant prostatic cells (mCPC) in blood may be a candidate for early detection of prostate cancer (PC). Patients and methods: a group of patients, who underwent an initial prostate biopsy -and also a second one during a follow up - due to suspicion of prostate cancer, were assessed prospectively. The results of the biopsy were compared with malignant circulating prostate cells (mCPC) levels, identified in blood samples drawn prior to the biopsy, using standard immunocytochemistry methods. The objective was to determine the diagnostic ability of mCPC before the first, the second and the third prostate biopsies. Results: In total, 423 consecutive patients participated in the study, with an average age of 65.3 ± 8.9 years and a PSA (median) of 5.28 ng/ml (interquartile range [IQR] 4.36-7.94 ng/ml). Of them, 138 (32.6%) had a prostate cancer detected in the initial biopsy. Tests for the detection of circulating prostatic cells in blood (CPCs) had a sensitivity of 0.89 (95% confidence interval [95% CI: 0.82-0.94) and a specificity of 0.89 (95% CI: 0.84 to 0.92). Of the 423 patients, 125 had a second biopsy, and 57 had a third biopsy. CPCs attained a sensitivity and specificity of 0.89/0.87 and 0.88/0.96 for the second and third biopsy, respectively, with a positive and negative predictive value of 0.65 / 0.97 and 0.88 / 0.95 in the second and third biopsy, in that order. Conclusions: CPCs used in combination with current screening tests -PSA and digital rectal exam- can improve screening effectiveness by reducing the frequency of negative biopsies, as well as the total number of biopsies and their complications. In addition, profitability for the public health system in terms of resource utilization, is positive

[Expression of P504S and matrix metalloproteinase-2 in circulating prostate cells disseminated as a result of transrectal ultrasound guided biopsy as determined by immunocytochemistry: Clinical implications]. / Condideraciones clínicas de la expressión de P504S y metaloproteinasa de matriz 2 en células prostáticas circulantes en sangre diseminadas como resultado de una biopsia prostática trans-rectal guiada por ecografía.

OBJECTIVES: Surgical manipulation of cancer has been shown to increase blood borne cancer cell dissemination and increase the risk of metastasis. We present the effect of prostate biopsy on prostate cell dissemination and the phenotypic characteristics of these cells. METHODS: 50 men undergoing initial prostate biopsy for suspicion of prostate cancer were studied. Blood samples were taken immediately before, and 1 and 24 hours after biopsy for circulating prostate cells (CPC) determination and phenotypic characterization. CPCs were detected and counted using standard immunocytochemistry using anti-PSA and then characterized using anti-P504S and anti-matrix metalloproteinase-2 (MMP-2). RESULTS: 14 (28%) men had cancer detected on biopsy. 13/14 had P504S (+) and MMP-2 (+) cells detected prior to biopsy. One hour after biopsy there was a mixture of P504S (+) and P504S (-) cells detected, as well as MMP-2 (+) and MMP-2 (-) cells detected. 24 hours after biopsy the same 13/14 men remained positive, although the number of CPCs increased 1 hour after biopsy and then the numbers decreased to pre-biopsy levels after 24 hours. In cancer negative men, P504S (-) and MMP-2 (-) cells were detected, some of these cells persisted 24 hours after biopsy. CONCLUSIONS: Prostate biopsy causes dissemination of prostate cells into the circulation, both malignant and benign; the majority of them are cleared within 24 hours. There was no conversion of negative to positive result in men with cancer, this suggests that the inherent capacity of malignant CPCs to disseminate is more important than the effect of dissemination caused by prostate biopsy.

Elimination of primary circulating prostate cells after radical prostatectomy for prostate cancer decreases the risk of future biochemical failure.

OBJECTIVES: Primary CPCs are those detected in the blood of prostate cancer patients before radical treatment; secondary CPCs are those detected afterwards. Although primary CPCs are frequently found, it has been suggested that only a few will survive and go on to form metastasis. We evaluate the frequency of primary and secondary CPC detection and the association with biochemical failure, relation with clinical-pathological parameters and clinical implications in men treated by radical prostatectomy (RP) for prostate cancer. METHODS: Serial blood samples were taken before surgery and during follow up after RP. Mononuclear cells were obtained by differential gel centrifugation, and CPCs were identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, non organ confined), pathological grade, margin status (positive, negative), extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative) were compared with the presence/absence of CPCs in patients with and without biochemical failure. Kaplan Meier method was used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. RESULTS: 138 of 423 (32.6%) men undergoing prostate biopsy for an elevated serum PSA were diagnosed of prostate cancer. Of these men 15 (10.9%) were CPC negative. 95 CPC positive men underwent RP. There was no relation between primary CPC detection and clinical-pathological parameters; however, secondary CPCs were associated both with clinical-pathological parameters and biochemical failure. CONCLUSIONS: Primary CPCs are frequently detected in men with prostate cancer, but they are not associated with biochemical failure, so that they may be useful for prostate cancer detection but not for prognosis. The persistence of CPCs after surgery is associated with increased biochemical failure.

La eliminación de células prostáticas circulantes primarias en sangre posterior a la prostatectomía radical disminuye el riesgo de recidiva bioquímica / Elimination of primary circulating prostate cells after radical prostatectomy for prostate cancer decreases the risk of future biochemical failure

OBJETIVO: Las células prostáticas circulantes en sangre (CPCs) primarias son aquellas células prostáticas detectadas en pacientes con cáncer de próstata antes del tratamiento quirúrgico radical, por el contrario, las CPCs secundarias son aquellas detectadas posterior a este tratamiento. Pese a que las CPCs primarias son encontradas frecuentemente en pacientes con cáncer de próstata, solo unas pocas sobreviven y formarán metástasis. Evaluamos la asociación de las CPCs primarias y secundarias con la recidiva bioquímica en hombres con cáncer de próstata tratados con prostatectomía radical. MÉTODOS: Se tomaron muestras de sangre seriadas antes y después del tratamiento quirúrgico, se obtuvieron células mononucleares por centrifugación diferencial y se identificaron las CPCs utilizando inmunocitoquímica. Los datos de edad, estadio patológico, grado patológico, márgenes quirúrgicos, extensión extracapsular, perineural, vascular e infiltración linfática fueron comparados con la presencia o ausencia de CPCs en pacientes con o sin recidiva bioquímica. Se utilizo el método de Kaplan Meyer para comparar la sobrevida libre de enfermedad de los pacientes con o sin CPCs. RESULTADOS: 138 de 423 (32,6%) de los hombres que fueron sometidos a una biopsia prostática por un PSA elevado tuvieron cáncer de próstata, de estos hombres, 15 (10,9%) fueron negativos para CPCs. De los hombres positivos, 95 fueron sometidos a una prostatectomía radical, no existió relación entre la detección de CPCs primarias y los parámetros clínico - patológicos del cáncer, sin embargo, los pacientes con CPCs secundarias se asociaron con mayor tasa de recidiva bioquímica. CONCLUSIONES: Las CPCs primarias son frecuentemente detectadas en hombres con cáncer de próstata, pero no se asocian con recidiva bioquímica, por lo tanto pueden ser útiles para la detección de cáncer de próstata pero no para su pronóstico. La detección de CPCs posterior a la cirugía se asocia con mayores posibilidades de recidiva bioquímica

OBJECTIVES: Primary CPCs are those detected in the blood of prostate cancer patients before radical treatment; secondary CPCs are those detected afterwards. Although primary CPCs are frequently found, it has been suggested that only a few will survive and go on to form metastasis. We evaluate the frequency of primary and secondary CPC detection and the association with biochemical failure, relation with clinical-pathological parameters and clinical implications in men treated by radical prostatectomy (RP) for prostate cancer. METHODS: Serial blood samples were taken before surgery and during follow up after RP. Mononuclear cells were obtained by differential gel centrifugation, and CPCs were identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, non organ confined), pathological grade, margin status (positive, negative), extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative) were compared with the presence/absence of CPCs in patients with and without biochemical failure. Kaplan Meier method was used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. RESULTS: 138 of 423 (32.6%) men undergoing prostate biopsy for an elevated serum PSA were diagnosed of prostate cancer. Of these men 15 (10.9%) were CPC negative. 95 CPC positive men underwent RP. There was no relation between primary CPC detection and clinical-pathological parameters; however, secondary CPCs were associated both with clinical-pathological parameters and biochemical failure. CONCLUSIONS: Primary CPCs are frequently detected in men with prostate cancer, but they are not associated with biochemical failure, so that they may be useful for prostate cancer detection but not for prognosis. The persistence of CPCs after surgery is associated with increased biochemical failure

A comparative performance analysis of total PSA, percentage free PSA, PSA velocity, and PSA density versus the detection of primary circulating prostate cells in predicting initial prostate biopsy findings in Chilean men.

INTRODUCTION: PSA parameters have been used in an attempt to improve the diagnostic yield of prostate screening tests; the detection of primary malignant circulating prostate cells (CPCs) may improve the diagnostic yield of screening and therefore avoid unnecessary biopsies. PATIENTS AND METHODS: Prospective study of all men undergoing initial prostate biopsy due to an elevated total serum PSA. Free percent PSA, PSA velocity, and PSA density were determined. Primary CPCs were detected using standard immunocytochemistry. A positive test for CPCs was defined as one cell PSA (+) P504S (+) in an 8 ml blood sample. Positive predictive and negative predictive values, specificity, and sensitivity were calculated for each test as well as the number of biopsies avoided and cancers missed. RESULTS: 303 men participated in the study of whom 113/303 (37.3%) men had prostate cancer. Of the three PSA based parameters, free percent PSA was superior, sensitivity 70.8%, and specificity 67.4%. Primary CPCs detection had a sensitivity of 88.5% and a specificity of 88.4% avoiding 181 (59.7%) biopsies, detecting 93/95 (98%) of clinically significant cancers, and missing 13 (11.5%) low grade, small volume tumors. CONCLUSIONS: The use of primary CPCs as a sequential test could decrease the number of initial prostate biopsies missing those cancers which are treated by active observation.

Circulating Prostate Cells Found in Men with Benign Prostate Disease Are P504S Negative: Clinical Implications.

Introduction. Developments in immunological and quantitative real-time PCR-based analysis have enabled the detection, enumeration, and characterization of circulating tumor cells (CTCs). It is assumed that the detection of CTCs is associated with cancer, based on the finding that CTCs can be detected in all major cancer and not in healthy subjects or those with benign disease. Methods and Patients. Consecutive men, with suspicion of prostate cancer, had blood samples taken before prostate biopsy; mononuclear cells were obtained using differential gel centrifugation and CPCs detecting using anti-PSA immunocytochemistry. Positive samples underwent further classification with anti-P504S. Results. 329 men underwent prostate biopsy; of these men 83 underwent a second biopsy and 44 a third one. Of those with a biopsy negative for cancer, 19/226 (8.4%) had CPCs PSA (+) P504S (-) detected at first biopsy, 6/74 (8.1%) at second biopsy, and 5/33 (15.2%) at third biopsy. Men with cancer-positive biopsies did not have PSA (+) P504S (-) CPCs detected. These benign cells were associated with chronic prostatitis. Conclusions. Patients with chronic prostatitis may have circulating prostate cells detected in blood, which do not express the enzyme P504S and should be thought of as benign in nature.

Secondary circulating prostate cells predict biochemical failure in prostate cancer patients after radical prostatectomy and without evidence of disease.

INTRODUCTION: Although 90% of prostate cancer is considered to be localized, 20%-30% of patients will experience biochemical failure (BF), defined as serum PSA >0.2 ng/mL, after radical prostatectomy (RP). The presence of circulating prostate cells (CPCs) in men without evidence of BF may be useful to predict patients at risk for BF. We describe the frequency of CPCs detected after RP, relation with clinicopathological parameters, and association with biochemical failure. METHODS AND PATIENTS: Serial blood samples were taken during followup after RP, mononuclear cells were obtained by differential gel centrifugation, and CPCs identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, nonorgan confined), pathological grade, margin status (positive, negative), extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative) were compared with the presence/absence of CPCs and with and without biochemical failure. Kaplan Meier methods were used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. RESULTS: 114 men participated, and secondary CPCs were detected more frequently in patients with positive margins, extracapsular extension, and vascular and lymphatic infiltration and were associated with biochemical failure independent of these clinicopathological variables, and with a shorter time to BF. CONCLUSIONS: Secondary CPCs are an independent risk factor associated with increased BF in men with a PSA <0.2 ng/mL after radical prostatectomy, but do not determine if the recurrence is due to local or systemic disease. These results warrant larger studies to confirm the findings.

Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol.

INTRODUCTION: HER-2 expression in prostate cancer is associated with a worse prognosis and is suggested to play a role in androgen resistance. We present a study of HER-2 expression in circulating tumor cells and micrometastasis in bone marrow and the effect of androgen blockage or DES in the presence of HER-2 expressing cells. PATIENTS AND METHODS: A multicenter study of men with prostate cancer, treated with surgery, radiotherapy, or observation, and with or without hormone therapy. Mononuclear cells were separated from blood and bone marrow aspirate by differential centrifugation, touch preps were made from bone marrow biopsy samples. Prostate cells were detected using anti-PSA monoclonal antibody and standard immunocytochemistry. Positive samples were processed using Herceptest® to determine HER-2 expression. After 1 year, patients were re-evaluated and the findings of HER-2 expression and PSA change compared with treatment. RESULTS: Total 199 men participated, and 97 had a second evaluation 1 year later, frequency of HER-2 expression in circulating tumor cells and micrometastasis was 18% and 21%, respectively. There was no significant difference in HER-2 expression in the pretreatment group, after radical surgery or radiotherapy or with biochemical failure. Men with androgen blockade had a significantly higher expression of HER-2 (58%) (P =0.001). Of the 97 men with a second evaluation, 56 were in the observation arm, 27 androgen blockade, and 14 DES. Use of androgen blockade or DES significantly reduced serum PSA levels in comparison with observation (P =0.001). However, there was a significant increase in HER-2 expression in patients with androgen blockade (P =0.05) en comparison with observation or DES treatment. No patient with observation or DES became HER-2 positive, en comparison 4/22 patients initially HER-2 negative became HER-2 positive with androgen blockade. CONCLUSIONS: The results suggest that HER-2 positive cells are resistant to androgen blockade. In an environment lacking androgens, HER-2 positive cells are selected and survive, while HER-2 negative cells are eliminated thus decreasing the serum PSA. The population of HER-2 positive cells proliferate producing androgen-independent disease. DES does not increase HER-2 expression possibly by stimulating beta-estrogen receptors and blocking HER-2 androgen receptor activation.

P504S expressing circulating prostate cells as a marker for prostate cancer.

Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer deaths. The serum prostate specific antigen (PSA) is the only biomarker routinely used in screening. The aim of this study was to develop a system to test the presence of circulating prostate cells in men without a diagnosis of prostate cancer in relation with age, serum PSA levels and prostate biopsy by determining the co-expression of several markers such as CD82, HER-2 and matrix metalloproteinase 2 (MMP-2). For this purpose mononuclear cells were separated from blood using differential centrifugation and then prostate cells were identified by using standard immunocytochemical method. Results indicated that among 409 men screened for prostate cancer 16.6% were positive for circulating prostate cells. Cells were positive for MMP-2 and HER-2 in 100 and 14.3% of cases, respectively, without an association with age or PSA levels. However, CD82 protein expression was associated with older age and low grade tumors. It can be concluded that the study of circulating prostate cells with various markers could be a useful complementary screening test for prostate cancer in men with increased PSA level.

Detection and characteristics of primary circulating prostate cells; association with micrometastasis and implications for surgical treatment of men with prostate cancer.

OBJECTIVES: To determine the frequency of primary circulating prostate cells in men with prostate cancer at the time of diagnosis, the association with micrometastasis, sub-classification for CD82 and the relation with pathological stage. To determine their clinical usefulness to identify patients in whom radical prostatectomy would be first choice therapy. METHODS: Men with the diagnosis of prostate cancer before definitive therapy. Blood and bone marrow samples were taken, mononuclear cells separated by differential centrifugation and prostate cells identified with immunocytochemistry using anti-PSA. Positive samples were sub-classified with anti-CD82. Details of serum PSA, Gleason score and pathological stage were registered. RESULTS: Of 77 men 58 (75.3%) had primary CPCs detected, there was an association with stage but not Gleason. 31 (40.3%) had micrometastasis with an association with stage and Gleason score. CPC-negative patients had fewer micrometastasis detected, 1/19 versus 30/58 (p<0.003). There was an inverse relation between CD82 expression and Gleason score, men with CPCs expressing CD82 had fewer micrometastasis. The combined group of CPC negative and CPC positive CD82 positive men showed a sensitivity of 87%and specificity of 73.9% for the absence of micrometastasis. CONCLUSIONS: The detection of CPCs and sub-classification with CD82 could be clinically useful to identify men with a significantly lower risk of micrometastais and as a consequence to identify men in whom radical prostatectomy could be the best initial treatment.

Deteccion y características de células prostáticas circulantes primarias, asociación con la presencia de micrometástasis y las implicaciones para el tratamiento quirúrgico en hombres con cáncer prostático. El estudio ProTECT (Prostate Tumor Early Cancer Test) / Detection and characteristics of primary circulating prostate cells; association with micrometastasis and implications for surgical treatment of men with prostate cáncer

OBJETIVO: Determinar la frecuencia de células prostáticas circulantes (CPCs) primaria en hombres con cáncer de próstata en el momento del diagnóstico, la asociación con micrometástasis ósea y subclasificación por CD82. Determinar la relación con la estadio patológica y la eficacia para seleccionar pacientes para la prostatectomía radical.MÉTODOS: Se incluyeron hombres con diagnóstico de cáncer de próstata previo a tratamiento definitivo. Se obtuvieron muestras de sangre y de médula ósea, las células mononucleares separadas por centrifugación diferencial y células prostáticas identificadas con inmumocitoquímica con anti-APE, las muestras positivas fueron sub-clasificadas con anti-CD82. Se registraron también los detalles de APE sérico, Índice de Gleason y estadio patológica.RESULTADOS: De 77 hombres, 58 (75,3%) tuvieron 1° CPCs detectadas. Hubo una asociación con estadio pero no con el Índice de Gleason, 31 (40,3%) tuvieron micrometástasis. Hubo una asociación significativa con la estadio patológica y Índice de Gleason. Pacientes CPC negativa tuvieron una menor frecuencia de micrometástasis que los hombres CPC positiva 1/19 versus 30/58 (p<0,0003).Hubo una relación inversa significativa entre la expresión de CD82 en CPCs y el índice de Gleason y menor frecuencia de micrometástasis en comparación con hombres CPC CD82 positivos (p<0,0005).En el grupo de combinación de hombres CPC negativa y CPC positiva CD82 positivo la frecuencia de micrometastasis fue significativamente menor que el grupo CPC (+) CD82 (-) 5/39 versus 26/38 respectivamente(p<0,0000007), con una sensibilidad de 87% y especificidad de 73,9% para la ausencia de micrometástasis(AU)

CONCLUSIONES: La presencia de CPCs implica un riesgo mayor de desarrollar micrometástasis, la co-expresión del CD82 es asociada con tumores de bajo grado, un riesgo disminuido del desarrollo de micrometástasis óseas. Como consecuencia, el uso de la detección de CPCs primarias y su sub-clasificación podrían ser clínicamente útiles para identificar los pacientes los cuales beneficiarán de una prostatectomía radical como tratamiento de primera línea(AU)

OBJECTIVES: To determine the frequency of primary circulating prostate cells in men with prostate cancer at the time of diagnosis, the association with micrometastasis, sub-classification for CD82 and the relation with pathological stage. To determine their clinical usefulness to identify patients in whom radical prostatectomy would be first choice therapy.METHODS: Men with the diagnosis of prostate cancer before definitive therapy. Blood and bone marrow samples were taken, mononuclear cells separated by differential centrifugation and prostate cells identified with immunocytochemistry using anti-PSA. Positive samples were sub-classified with anti-CD82. Details of serum PSA, Gleason score and pathological stage were registered.RESULTS: Of 77 men 58 (75.3%) had primary CPCs detected, there was an association with stage but not Gleason. 31 (40.3%) had micrometastasis with an association with stage and Gleason score. CPC-negative patients had fewer micrometastasis detected, 1/19 versus 30/58 (p<0.003).There was an inverse relation between CD82 expression and Gleason score, men with CPCs expressing CD82 had fewer micrometastasis. The combined group of CPC negative and CPC positive CD82 positive men showed a sensitivity of 87% and specificity of 73.9% for the absence of micrometastasis.CONCLUSIONS: The detection of CPCs and sub-classification with CD82 could be clinically useful to identify men with a significantly lower risk of micrometastais and as a consequence to identify men in whom radical prostatectomy could be the best initial treatment(AU)

Espresión de enzima metalproteinasa de matriz 2 (MPM-2) en células prostáticas en circulación sanguínea (CPCS) en pacientes con cáncer prostático: estudio utilizando inmunocitoquímica / Expression of matrix metalproteinasa enzyme 2 (MPM-2) in prostate cells in blood circulation (CPCS) in men with prostate cancer: an immunocytochemistry study

La metaloproteinasa de matriz-2 (MPM-2) es una gelatinasa implicada en el proceso de metástasis. Las células que expresan MPM-2pueden cruzar la matriz extracelular y diseminarse a los tejidos distantes. Presentamos un estudio de la detección de células prostáticas en la circulación sanguínea y la expresión de MPM-2 en varones con cáncer prostático antes y después de una prostatectomía radical. Método y pacientes: Estudio prospectivo, multicéntrico, de pacientes atendidos en el Hospital de Carabineros de Chile, INRAD y el Instituto de Bío-Oncología, entre los años 2006 y 2008. Después de un consentimiento informado por escrito, 4 ml de sangre venosa fueron obtenidos. Las células mononucleares fueron aisladas por centrifugación diferencial y la CPCs detectadas con anti-PSA e identificadas mediante inmunocitoquímica con un sistema basado en fosfatasa alcalina con neofuscina como cromógeno. Las muestras positivas tuvieron un segundo proceso con anti-MPM-2, un sistema de detección basado en peroxidasa y Vector VIP como cromogen. Detalles de la etapa, la edad y nivel de APE sérico fueron registrados. Resultados: 105 pacientes participaron, 30 pretratamiento y 75 postratamiento, con una edad promedio de 71,3 +/- 8,4 años. Existió una asociación entre la frecuencia de detección de CPCs, la etapa clínica y el índice de Gleason. Todas las CPCs expresaron MPM-2. Conclusiones: Los resultados confirman que la expresión de MPM-2 tiene un papel importante en la 1a y 2a diseminación de células cancerosas y no hay una asociación de los otros factores pronóstico. La presencia de las CPCs no implica la presencia de micrometástasis ni su origen de diseminación en el 2o caso de CPCs, pero implica un riesgo más elevado de la enfermedad micrometastásica. Su detección podría ser útil durante el seguimiento para la detección precoz de estos pacientes.

Objective: Matrix metalloproteinase-2 is a gelatinase implicated in the metastatic process. Cells expressing MMP-2 can cross the extracellular matrix and disseminate to other tissues. We present a study of MMP-2 express of circulating prostate cells in men with prostate cancer. Methods and Patients: A prospective, multicenter study of men with prostate cancer attending the Hospital de Carabineros de Chile, INRAD and the Instituto de BioOncología between 2006 and 2008. After written informed consent a 4 ml blood sample was taken, mononuclear cells were obtained using differential centrifugation and CPCs identified using immunocytochemistry. Positive samples with PSA staining cells underwent a second process with anti-MPM-2. Age, clinical stage, serum PSA were noted for each patient. Results: 105 patients entered the study, 30 pre-treatment and 75 post treatment, with an average age of 71.3 +/- 8.4 years. There was an association with CPC detection frequency with clinical stage and Gleason score. All CPCs expressed MMP-2. Conclusions: The results indicate that MMP-2 expression is important in the dissemination of primary and secondary prostate cancer cells, that there is no association between prognostic factors and MMP-2 expression in CPCs. The presence of CPCs does not imply the presence of micrometastasis nor origin of dissemination in the case of 2nd CPCs but the presence implies a higher risk of micrometastasis. The detection of these cells could be a useful tool in the follow up of patients with prostate cancer.

Impacto del índice de masa corporal en la nefrectomía radical laparoscópica por cáncer de riñón / Impact of body mass index in laparoscopic radical nephrectomy for renal cell carcinoma

Introducción: La obesidad es causa de aumento de complicaciones intra y post operatorias en pacientes sometidos a cirugía convencional. La Nefrectomía Radical Laparoscópica (NRL) es hoy la técnica de elección para el tratamiento del carcinoma de células renales. Nuestro objetivo es evaluar el impacto de la obesidad representado por el Índice de Masa Corporal (IMC) en pacientes sometidos a NRL por cáncer renal. Material y Método: Estudio prospectivo aleatorio de 82 NRL consecutivas, en pacientes con sospecha de cáncer renal, realizadas entre julio del 2001 y agosto del 2005. Los pacientes fueron analizados en 3 grupos según su IMC: Grupo 1: No obesos (IMC menor a 30), Grupo 2: obesos (IMC entre 30 y 35), y Grupo 3: obesos mórbidos (IMC mayor a 35). Correspondieron a 60 hombres y 20 mujeres, con una edad promedio de 60,59 años. Se realizaron 17 NRL mano asistidas y 65 NRL puras. Resultados: El grupo 1 (No obesos) se compone de 55 (67,07 por ciento) pacientes, el grupo 2 (Obesos) de 17 (20,73 por ciento) pacientes, y el grupo 3 (Obesos Mórbidos) de 10 (12,19 por ciento) pacientes. El tiempo operatorio promedio fue de 131,63 minutos, 138,88 minutos, y 141 minutos respectivamente no habiendo diferencias estadísticamente significativas. En cuanto al sangrado promedio, los valores fueron 139,09ml. para el grupo 1, 254 ml. para el grupo 2 y a 137 ml. para el grupo 3; sin diferencias estadísticamente significativas. En 78 pacientes el diagnóstico histológico fue de Hipernefroma, en 4 pacientes no se encontró neoplasia. Todos se encuentran sin progresión de la enfermedad con un seguimiento promedio de 18 meses. Conclusión: No existen diferencias significativas entre pacientes no obesos, obesos y obesos mórbidos con esta técnica. Nuestro estudio demuestra que la NRL es el abordaje de elección en pacientes obesos con cáncer renal.

Introduction: Obesity caused an increased of intra-and post-operative complications in patients undergoing conventional surgery. Laparoscopic radical nephrectomy (LRN) is currently the technique of choice for the treatment of renal cell carcinoma. Our goal is to evaluate the impact of obesity represented by body mass index (BMI) in patients undergoing LRN for renal cancer. Material and Methods: Prospective randomized study of 82 consecutives LRN in patients with suspected renal masses, conducted between July 2001 and August 2005. Patients were analyzed in 3 groups according to their BMI: Group 1: Non-obese (BMI less than 30), Group 2: obese (BMI between 30 and 35) and Group 3: morbidly obese (BMI greater than 35). There was 60 males and 20 females with a mean age of 60.59 years. We make 17 hand assisted LRN and 65 pure LRN. Results: Group 1 (not obese) is composed of 55 (67.07 percent) patients in group 2 (obese) 17 (20.73 percent)patients, and group 3 (morbidly obese) 10 (12, 19 percent) patients. Medium operative time was 131.63 minutes, 138.88 minutes and 141 minutes respectively, no statistically significant differences. As the average bleeding, the values were 139.09 ml. for group 1, 254 ml. for group 2 and 137 ml. For group 3, no statistically significant difference. In 78 patients the histological diagnosis was Hypernephroma and in 4 patients no tumor was found. All patients are free of disease progression with an average of 18 months. Conclusion: No significant differences exist between non-obese patients, obese and morbidly obese with this technique. Our study shows that LRN is the approach of choice in obese patients with kidney cancer.

Relative proportions of T-cell subpopulations and cytokines that mediate and regulate the adaptive immune response in patients with aggressive periodontitis.

BACKGROUND: Both the virulence factors of periodontopathic bacteria and the immune response against them have been involved in tissue destruction observed in periodontal disease. Considering the regulatory role of cytokines produced by T cells, the purpose of this study was to compare the CD3+, CD4+, and CD8+ subpopulations of T cells, and to characterize the mRNA of cytokines involved in the adaptive immune response in a group of healthy/gingivitis 1 (HI/G1) individuals and aggressive periodontitis (AgP) patients. METHODS: The percentages of T-cell subpopulations were analyzed in 10 gingival samples of HI/G1 individuals and 10 gingival samples of AgP patients by immunohistochemistry. The presence of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL- 13, and transforming growth factor (TGF)-beta was measured by reverse transcription polymerase chain reaction (RT-PCR) of mRNA extracted from complete gingival biopsies. RESULTS: Significant differences were found in CD3+ and CD4+ cell counts between both groups. The parameters were lower in the gingival biopsies from AgP patients while CD8+ counts were similar in both groups. The cytokine mRNA analysis showed constant expression of IL-2 and IFN-gamma in all cases. The mRNA of IL-5 and IL-10 was present in the majority of HI/G1 (N = 10, N = 9, respectively) but was not in the AgP group (N = 2, N = 1). IL-13 and TGF-beta were only detected in HI/G1 (N = 2, N = 3) and IL-4 was not detected in any of the individuals. CONCLUSIONS: These results indicate that the role of the CD8+ subpopulation in aggressive periodontitis lesions is limited. On the other hand, cytokines IL-2 and IFN-gamma may not be relevant in the progression of aggressive periodontitis.