Significance of protein p53 overexpression in the clinical course of high-risk superficial bladder cancer.

OBJECTIVES: This is a retrospective study in which the long-term biological behavior of 67 "high-risk" superficial bladder tumors and the prognostic relevance (prediction of disease recurrence and progression) of the determination of the p53 phenotype in these cases were studied. MATERIAL AND METHODS: 67 tumors with a "high-risk" of progression were selected from the 1,103 transurethral resections for bladder cancer carried out in 640 patients in this center between 1987 and 1992. These included 39 T1G3, 14 Tis (isolated or associated with Ta-T1, non-G3 tumors), and 14 Ta-T1, non-G3 tumors with submucosal lymphatic affection (L+). The median follow-up of these cases was 69.7 months. An immunohistochemical technique with monoclonal antibodies (DO-7) was used to detect the p53 phenotype in paraffin-fixed material. RESULTS: Tumor recurrence occurred in 31 patients (46.3%) and local or distant progression in 14 (20.9%). Radical cystectomy was carried out in 16 (23.9%) cases. p53 overexpression of > or =20% ("p53+") was detected in 40 tumors (59.7%). The rate of recurrence and progression, the disease and progression-free intervals, cancer-specific survival, disease-free survival and progression-free survival were similar in the 3 tumor groups (in all cases, p > 0.05). There were no significant differences in the overexpression of protein p53, using the standard cutoff point of 20% stained nuclei, on comparing the same variables in the whole group of 67 patients (in all cases, p > 0.05). CONCLUSION: The detection of protein p53 was not found to be of use in the retrospective prediction of disease progression or survival in "high-risk" superficial bladder cancer.

Marcadores biológicos en el cáncer de próstata / Biological markers of prostate cancer

En los últimos 20 años se han producido muchos adelantos en el uso clínico de marcadores biológicos en el cáncer de la próstata. El antígeno prostático específico (PSA) se ha consolidado como el más importante de todos los marcadores tumorales humanos. En este artículo se describen las formas moleculares de PSA y sus características, los factores que influyen en los valores séricos de PSA, y los métodos para aumentar la sensibilidad y/o especificidad de PSA total (especialmente en valores entre 4-10 ng/ml), como rangos de PSA específicos de edad, velocidad de PSA, PSA libre, densidad de PSA, densidad de PSA de la zona de la transición; así como el papel de PSA en la monitorización de las diversas formas de tratamiento del cáncer de próstata. Se revisa también el papel de otras formas de calicreínas de las direcciones futuras respecto a marcadores biológicos en el cáncer de la próstata (AU)

The use of neural networks and logistic regression analysis for predicting pathological stage in men undergoing radical prostatectomy: a population based study.

PURPOSE: Clinical under staging occurs in 40% to 60% of patients who undergo radical prostatectomy for prostate cancer. To decrease under staging several methods of predicting pathological stage preoperatively have been developed based on statistical logistic regression analysis and neural networks. To our knowledge none has been validated in our homogeneous regional patient population to date. We created logistic regression and neural network models, and implemented and adapted them into our practice. We also compared the 2 methods to determine their value and practicality in daily clinical practice. We present the results of our novel approach for predicting pathological staging of prostate adenocarcinoma. MATERIALS AND METHODS: Between 1986 and 1999, 600 white men from the Aragon region of Spain underwent surgery for prostate cancer; of whom 468 were selected for study. Predictive study variables included patient age, clinical stage, biopsy Gleason score and preoperative prostate specific antigen (PSA). The predicted result included in analysis was organ confined or nonorgan confined disease. Data were analyzed by multivariate logistic regression and a supervised neural network (multilayer perceptron and radial basis function). Results were compared by comparing the areas under the receiver operating characteristics curves. RESULTS: We generated 5 logistic regression models. The model created with clinical staging, Gleason biopsy score and PSA distributed in 5 categories (p <0.001) with an area under the receiver operating characteristics curve of 0.840 proved to be most predictive of pathological stage. Similarly of the 6 neural network models evaluated the radial basis function model, which included age, clinical stage, Gleason biopsy score and preoperative PSA distributed in 5 categories with an area under the curve of 0.882, proved the most predictive but not superior to the logistic regression model. The difference in the area under the curves in the 2 chosen models was 0.042 (p = 0.1). CONCLUSIONS: It is possible to generate useful predictive models of organ confined disease using logistic regression or neural networks with high indexes of clinical and statistical validity. However, using these variables neural networks did not prove to be better than logistic regression analysis. Therefore, better predictive variables must be identified, preferably nonlinear characteristics with respect to the probability of organ confined tumor, to generate better predictive models using neural networks.

Successful outcome of a cirrhotic patient with postoperative haematuria treated with a single high dose of recombinant factor VIIa.

Recombinant factor VIIa (rfVIIa) has been widely used for the treatment and prevention of bleeding episodes in haemophiliacs with high-titre inhibitors. High single doses are the treatment of choice for joint and muscle bleeds in those patients. There are only a few reports on the value of rfVIIa in cirrhotic patients with haemostatic impairment but this drug can consistently correct the prothrombin time in these individuals. We report a case of a good response to a single high dose of rfVIIa in a patient with advanced liver disease who suffered from severe refractory postoperative haematuria.

[Why evidence-based medicine? 20 years of meta-analysis]. / Por qué la medicina basada en la evidencia? 20 años de metaanálisis.

BACKGROUND: Meta-analysis, described within evidence-based medicine, has become a frequent issue in recent medical literature. An exhaustive search of reported meta-analysis from any medical specialty is described. MATERIAL AND METHODS: Search of papers included in Medline or Embase between 1973-1998. A study of intra and inter-reviewers liability about selection and classification have been performed. A descriptive analysis of the reported papers (frequency tables and graphics) is described, including differences of mean of reported meta-analysis papers by medical specialty and year. RESULTS: 1,518 papers were selected and classified. Most frequently found (45.91%) were: methodology (15.7%), psychiatry (11.79%), cardiology (10.01%) and oncology (8.36%). Inter personal agreement was 0.93 in selecting papers and 0.72 in classifying them. Between 1977-1987 overall mean of reported studies of meta-analysis (1.67 + 4.10) was significatively inferior to the 1988-1998 (49.54 + 56.55) (p < 0.001). Global number of meta-analysis was positively correlated (p < 0.05) with the number of studies about fundamentals and methodology during the study period. CONCLUSIONS: The method used to identify meta-analysis reports can be considered to be adequate; however, the agreement in classifying them in medical specialties was inferior. A progressive increase in the number of reported meta-analysis since 1977 can be demonstrated. Specialties with a greater number of meta-analysis published in the literature were: psychiatry, oncology and cardiology. Diffusion of knowledge about fundamentals and methodology of meta-analysis seems to have drawn and increase in performing and reporting this kind of analysis.

¿Por qué la medicina basada en la evidencia? 20 años de metaanálisis / Why evidence based medicine? 20 years of experience

Fundamento: El metaanálisis, introducido a partir de la Medicina Basada en la Evidencia, se ha convertido en un tema habitual de la bibliografía en los últimos años. Se describe una búsqueda exhaustiva de publicaciones de metaanálisis de todas las especialidades médicas, su número y evolución temporal. Material y métodos: Búsqueda de artículos de metaanálisis en Medline y Embase entre 1973-1998. Estudio de fiabilidad interobservadores e intraobservador de la estrategia de selección y clasificación. Análisis descriptivo de las publicaciones (tablas de frecuencia y gráficos). Análisis de las diferencias de medias del número de publicaciones por especialidad y año. Resultados: Resultaron seleccionados y clasificados 1.518 artículos. Los más frecuentes (45,91 porciento) englobaban: metodología (15,7 porciento), psiquiatría (11,79 porciento), cardiología (10,01 porciento) y oncología (8,36 porciento). El acuerdo interobservadores en la selección fue de 0,93; en la clasificación fue 0,72. Entre 1977-1987 la media de estudios de metaanálisis de cualquier disciplina (1,67+4,10) es significativamente inferior a la 1988-1998 (49,54+56,55) (p<0,001). El total de metaanálisis se correlaciona positivamente (p<0,05) con el número de estudios sobre bases y metodología realizados durante el periodo estudiado. Conclusiones: Se puede considerar adecuado el método de identificación de estudios de metaanálisis, aunque ha existido un menor grado de acuerdo para clasificarlos según la especialidad correspondiente. Se constata una progresión en la publicación de metaanálisis desde 1977. Las disciplinas con más metaanálisis publicados en los últimos 20 años han sido psiquiatría, oncología y cardiología. La difusión del conocimiento de las bases y metodología del metaanálisis ha repercutido positivamente sobre la frecuencia de realización de estos análisis (AU)

Value of PSA (prostate-specific antigen) in the detection of prostate cancer in patients with urological symptoms. Results of a multicentre study.

The aim of this multicentre study was to assess the usefulness of prostate-specific antigen (PSA) as a diagnostic procedure for prostate cancer in patients with urological symptoms, and compare it with digital rectal examination (DRE). The study included 2054 urological patients, aged over 50 years, and PSA levels were measured using an automated enzyme immunoassay. In the 680 cases with PSA levels > 3 micrograms/l and/or suspect DRE, transrectal ultrasound and prostate biopsy were also performed, leading to a diagnosis of cancer in 131 cases. The sensitivity of PSA was higher (95% and 73% for the cut-off values of 3 and 10 micrograms/l, respectively) than DRE (69%), both parameters being complementary. When DRE and PSA (> 10 micrograms/l) were combined, 118 cancers were diagnosed, with a PPV of 37%. We recommend using PSA and DRE in combination as a diagnostic procedure for prostate cancer in urological patients, since both methods are complementary.