Contaminación de antígeno específico-prostático a largo plazo en la rama española del Estudio Aleatorizado Europeo de Screeningdel Cáncer de Próstata (ERSPC) / Long-term prostate-specific antigen contamination in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC)

Objetivos: Recientemente, el Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata consiguió una reducción de la mortalidad por cáncer de próstata mediante la determinación sérica de antígeno específico-prostático (PSA). Estos resultados no fueron reproducidos en la rama española del Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata. La contaminación de PSA (determinación oportunista fuera del estudio) podría disminuir el poder de contraste del estudio si se lleva a cabo en el brazo control. Hemos calculado la tasa de contaminación de PSA a largo plazo, y su efecto en la realización de biopsia prostática y en la detección de cáncer. Material y métodos: Se aleatorizaron 4.276 varones (2.415 brazo screening, 1.861 brazo control) en la sección española del Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata. No se programó la determinación de PSA en el brazo control. Se indicó biopsia prostática sextante si PSA ≥ 3 ng/ml. Toda determinación de PSA realizada fuera del estudio fue etiquetada como «contaminación de PSA». Se calcularon las tasas de contaminación de PSA, realización de biopsia y detección de cáncer. Resultados: Las medianas de edad y tiempo de seguimiento fueron de 57 y 15,1 años respectivamente. Un total de 2.511 varones se realizó al menos una determinación de PSA fuera del estudio. La contaminación de PSA a los 5, 10 y 15 años fue del 22; 47,1 y 66,3% en el brazo screening, y del 20,8; 43,2 y 58,6 en el brazo control, respectivamente (p < 0,0001). La tasa de biopsia a los 5, 10 y 15 años fue del 19,3; 22,6 y 24,1% (screening) y del 1; 3,6 y 7,1% (control), respectivamente (p < 0,0001). La detección de cáncer de próstata fue del 6,7% (screening) y del 4,3% (control, p = 0,0006). Conclusiones: Aunque la contaminación acumulada de PSA fue notable en los 2 brazos del estudio, la realización de biopsia prostática fue escasa en el brazo control. Por ello, creemos que el impacto de la contaminación de PSA sobre el poder estadístico del estudio debe ser limitado

Objectives: Recently, the European Randomized Study of Screening for Prostate Cancer achieved a reduction in prostate cancer mortality by measuring serum prostate-specific antigen (PSA) levels. These results were not reproduced in the Spanish arm of European Randomized Study of Screening for Prostate Cancer. PSA contamination (opportunistic measurements outside the study) could decrease the study's contrasting power if performed in the control arm. We have calculated the long-term rate of PSA contamination and its effect on performing prostate biopsy and detecting cancer. Material and methods: A total of 4,276 men were randomised (2,415 to the screening arm, 1,861 to the control arm) in the Spanish section of the European Randomized Study of Screening for Prostate Cancer. PSA measurements were not scheduled in the control arm. Sextant prostate biopsy was indicated if PSA levels were ≥ 3 ng/mL. All PSA readings performed outside the study were labelled as "PSA contamination". We calculated the rates of PSA contamination, biopsy implementation and cancer detection. Results: The median age and follow-up time were 57 and 15.1 years, respectively. A total of 2,511 men underwent at least one PSA reading outside the study. PSA contamination at 5, 10 and 15 years was 22.0%, 47.1% and 66.3% in the screening arm, respectively, and 20.8%, 43.2% and 58.6% in the control arm, respectively (P < .0001). The biopsy rate at 5, 10 and 15 years was 19.3%, 22.6% and 24.1% (screening), respectively, and 1.0%, 3.6% and 7.1% (control), respectively (P < .0001). The PC detection rate was 6.7% (screening) and 4.3% (control; P = .0006). Conclusions: Although the cumulative PSA contamination was pronounced in the 2 study arms, the rate of prostate biopsies was low in the control arm. We therefore believe that the effect of PSA contamination on the study's statistical power should be limited

Long-term prostate-specific antigen contamination in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

OBJECTIVES: Recently, the European Randomized Study of Screening for Prostate Cancer achieved a reduction in prostate cancer mortality by measuring serum prostate-specific antigen (PSA) levels. These results were not reproduced in the Spanish arm of European Randomized Study of Screening for Prostate Cancer. PSA contamination (opportunistic measurements outside the study) could decrease the study's contrasting power if performed in the control arm. We have calculated the long-term rate of PSA contamination and its effect on performing prostate biopsy and detecting cancer. MATERIAL AND METHODS: A total of 4,276 men were randomised (2,415 to the screening arm, 1,861 to the control arm) in the Spanish section of the European Randomized Study of Screening for Prostate Cancer. PSA measurements were not scheduled in the control arm. Sextant prostate biopsy was indicated if PSA levels were ≥3 ng/mL. All PSA readings performed outside the study were labelled as "PSA contamination". We calculated the rates of PSA contamination, biopsy implementation and cancer detection. RESULTS: The median age and follow-up time were 57 and 15.1 years, respectively. A total of 2,511 men underwent at least one PSA reading outside the study. PSA contamination at 5, 10 and 15 years was 22.0%, 47.1% and 66.3% in the screening arm, respectively, and 20.8%, 43.2% and 58.6% in the control arm, respectively (P<.0001). The biopsy rate at 5, 10 and 15 years was 19.3%, 22.6% and 24.1% (screening), respectively, and 1.0%, 3.6% and 7.1% (control), respectively (P<.0001). The PC detection rate was 6.7% (screening) and 4.3% (control; P=.0006). CONCLUSIONS: Although the cumulative PSA contamination was pronounced in the 2 study arms, the rate of prostate biopsies was low in the control arm. We therefore believe that the effect of PSA contamination on the study's statistical power should be limited.

Actualización de los resultados de la rama española del Estudio aleatorizado europeo de screening del cáncer de próstata (ERSPC) / Update of the results of the Spanish branch of the European randomized study on screening for prostate cancer (ERSPC)

Objetivo: En la actualidad el papel del screening del cáncer de próstata (CaP) está cuestionado. El estudio aleatorizado europeo de screening del cáncer de próstata (ERSPC) tiene como objetivo demostrar si elscreening del CaP reduce la mortalidad por esta enfermedad. Se muestran los resultados en la rama española de este estudio: mortalidad global y cáncer-específica, características de los tumores detectados, de los tratamientos primarios y de la progresión a enfermedad avanzada. Material y métodos: Se invitó a participar a 18.612 varones entre los 45 y 70 años de edad, excluyendo aquellos con una expectativa de vida inferior a 10 años. Se llevó a cabo aleatorización a brazo screening (determinación de PSA sérico) y brazo control (no pruebas diagnósticas). Se indicó biopsia prostática aleatorizada sextante dirigida por ecografía transrectal en los varones del brazo screening con PSA ≥ 3 ng/ml. Se identificaron los CaP detectados (estadio y tratamiento primarios), así como los fallecimientos producidos (fecha y causa de la muerte). Resultados: El estudio se llevó a cabo con 4.276 varones (2.415 brazo screening, 1.861 brazo control). Las medianas de edad y PSA sérico fueron de 57 años y 0,90 ng/ml respectivamente. El tiempo de seguimiento (mediana) fue de 15,8 años. Se diagnosticaron 242 CaP, 162 (6,7%) en el brazo screening y 80 (4,3%) en el control (p < 0,001). De ellos 214 (88,4%) comenzaron con estadio clínico organoconfinado (91,4% brazo screening vs 82,5% control, p = 0,024). Un total de 112 pacientes (46,3%) fue sometido a prostatectomía radical, 53 (21,9%) a radioterapia prostática, 24 (9,9%) a tratamiento hormonal y 47 (19,4%) a observación. Un total de 18 CaP evolucionaron a enfermedad avanzada (M+ o PSA > 100 ng/ml), sin diferencia entre los brazos del estudio (p = 0,938). Un total de 618 (14,5%) fallecieron a lo largo del seguimiento: 340 (14,1%) en el brazo screening y 278 (14,9%) en el control, sin diferencias entre brazos en términos de mortalidad cáncer-específica (p = 0,907) ni por todas las causas (p = 0,399). Las principales causas de muerte encontradas fueron neoplasia (54,0%), cardiovascular (17,6%), respiratoria (8,7%) y digestiva (4,0%), sin diferencia entre brazos. De los 334 pacientes fallecidos por neoplasia tan solo 12 (3,6%) murieron por CaP. Conclusiones: El screening del CaP produce una migración del diagnóstico hacia estadios más precoces. No obstante, no hemos demostrado un beneficio en términos de supervivencia global ni cáncer-específica tras más de 15 años de seguimiento. La baja mortalidad por esta enfermedad en nuestro entorno podría ser uno de los principales factores para explicar estos resultados

Objective: The role of prostate cancer (PC) screening is currently being questioned. The objective of the European Randomized Study of Screening for Prostate Cancer (ERSPC) was to demonstrate whether PC screening reduced mortality from this disease. The results from the Spanish branch of this study are presented: all-cause and cancer-specific mortality, the characteristics of the detected tumors, primary treatments and progression to advanced disease. Material and methods: A total of 18,612 men, between the ages of 45 and 70, were invited to participate in the study, excluding those with a life expectancy of less than 10 years. The men were randomized to the screening arm (serum prostate-specific antigen [PSA] reading) or the control arm (no diagnostic tests). Randomized transrectal ultrasound-guided sextant prostate biopsies were indicated for the men in the screening arm with PSA levels ≥ 3 ng/ml. The detected PCs were identified (stage and primary treatment), as well as the deaths that occurred (date and cause of death). Results: The study was performed with 4276 men (2415 in the screening arm and 1861 in the control arm). The median age and serum PSA level were 57 years and 0.90 ng/mL, respectively. The median follow-up time was 15.8 years. A total of 242 PCs were diagnosed, 162 (6.7%) in the screening arm and 80 (4.3%) in the control arm (P < .001). Of these, 214 (88.4%) had an organ-confined clinical stage at onset (91.4% in the screening arm vs. 82.5% in the control arm; P = .024). A total of 112 patients (46.3%) underwent radical prostatectomy, 53 (21.9%) underwent prostate radiation therapy, 24 (9.9%) underwent hormone therapy and 47 (19.4%) were kept under observation. A total of 18 PCs progressed to advanced disease (M+ or PSA levels > 100 ng/mL), with no differences between the study arms (P = .938). A total of 618 (14.5%) patients died during follow-up: 340 (14.1%) in the screening arm and 278 (14.9%) in the control arm, with no differences between the arms in terms of cancer-specific (P = .907) or all-cause (P = .399) mortality. The main causes of death were neoplasia (54.0%), cardiovascular (17.6%), respiratory (8.7%) and gastrointestinal (4.0%), with no difference between study arms. Of the 334 patients who died from neoplasia, only 12 (3.6%) died from PC. Conclusions: PC screening results in a shifting of the diagnosis towards earlier stages. Nevertheless, we have not demonstrated a benefit in terms of overall or cancer-specific survival after more than 15 years of follow-up. The low mortality from this disease in our community could be one of the main factors that explain these results

Update of the results of the Spanish branch of the European Randomized Study on Screening for Prostate Cancer (ERSPC).

OBJECTIVE: The role of prostate cancer (PC) screening is currently being questioned. The objective of the European Randomized Study of Screening for Prostate Cancer (ERSPC) was to demonstrate whether PC screening reduced mortality from this disease. The results from the Spanish branch of this study are presented: all-cause and cancer-specific mortality, the characteristics of the detected tumors, primary treatments and progression to advanced disease. MATERIAL AND METHODS: A total of 18,612 men, between the ages of 45 and 70, were invited to participate in the study, excluding those with a life expectancy of less than 10 years. The men were randomized to the screening arm (serum prostate-specific antigen [PSA] reading) or the control arm (no diagnostic tests). Randomized transrectal ultrasound-guided sextant prostate biopsies were indicated for the men in the screening arm with PSA levels ≥3ng/ml. The detected PCs were identified (stage and primary treatment), as well as the deaths that occurred (date and cause of death). RESULTS: The study was performed with 4276 men (2415 in the screening arm and 1861 in the control arm). The median age and serum PSA level were 57 years and 0.90ng/mL, respectively. The median follow-up time was 15.8 years. A total of 242 PCs were diagnosed, 162 (6.7%) in the screening arm and 80 (4.3%) in the control arm (P<.001). Of these, 214 (88.4%) had an organ-confined clinical stage at onset (91.4% in the screening arm vs. 82.5% in the control arm; P=.024). A total of 112 patients (46.3%) underwent radical prostatectomy, 53 (21.9%) underwent prostate radiation therapy, 24 (9.9%) underwent hormone therapy and 47 (19.4%) were kept under observation. A total of 18 PCs progressed to advanced disease (M+ or PSA levels >100ng/mL), with no differences between the study arms (P=.938). A total of 618 (14.5%) patients died during follow-up: 340 (14.1%) in the screening arm and 278 (14.9%) in the control arm, with no differences between the arms in terms of cancer-specific (P=.907) or all-cause (P=.399) mortality. The main causes of death were neoplasia (54.0%), cardiovascular (17.6%), respiratory (8.7%) and gastrointestinal (4.0%), with no difference between study arms. Of the 334 patients who died from neoplasia, only 12 (3.6%) died from PC. CONCLUSIONS: PC screening results in a shifting of the diagnosis towards earlier stages. Nevertheless, we have not demonstrated a benefit in terms of overall or cancer-specific survival after more than 15 years of follow-up. The low mortality from this disease in our community could be one of the main factors that explain these results.

Prostate cancer incidence and mortality in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

BACKGROUND: To present the long-term results of a prostate cancer (PC) screening trial conducted in a Mediterranean setting. METHODS: A total of 4276 men aged 45-70 years were randomized to screening arm (PSA test performed) and control arm (no tests). Transrectal ultrasonography-guided sextant prostate biopsy was conducted when PSA > or = 3 ng ml(-1). Date and cause of death were retrieved from death certificates. PC incidence, and disease-specific and overall mortality curves were plotted and comparison between arms was made. Analysis of causes of death was also performed. RESULTS: Median age at randomization was 57.0 years. Median follow-up time was 15.2 years. A total of 241 men were diagnosed with PC, 161 (6.7%) in the screening arm and 80 (4.3%) in the control arm (P<0.01). Eventually, 554 men (13%) died. No difference in all-cause mortality was found between arms (P=0.34). Only 10 men (10/4276, 0.23%) died from PC, no differences between arms (P=0.67). Overall, the main causes of death were malignancy (54.2%), cardiovascular (17.9%) and respiratory (9.2%) diseases. Main cancer causes of death were lung and bronchus cancer (37.2%), colorectum (15.0%) and stomach (9.0%) cancer. PC only accounted for 3.0% of all malignant causes of death (ranked 10th). CONCLUSIONS: Our study failed to demonstrate benefits of PC screening in terms of all-cause and PC-specific mortality after a median follow-up of 15 years. The limited sample size and the low long-term PC mortality observed in our setting were probably the most important factors to explain these results.

Mortalidad por cáncer de próstata en la rama española del European Randomized Study of Screening for Prostate Cancer (ERSPC). Resultados tras 15 años de seguimiento / Mortality Due to Prostate Cancer in the Spanish Arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Results After a 15-Year Follow-Up

Objetivo: Estudiar si el screening del cáncer de próstata (CaP) reduce la mortalidad por esta enfermedad en la población asintomática, dentro del ámbito de la rama española del European Randomized Study of Screening for Prostate Cancer (ERSPC). Material y métodos: Entre 1996 y 1999 fueron reclutados 4.278 varones con edades comprendida sentre los 45 y los 70 años. Fueron aleatorizados a brazo screening (PSA cada 4 años, con biopsia prostática si PSA≥3 ng/ml) y brazo control (no tests). De modo anual se registraron fechas y causas de mortalidad. Se realizó un análisis Kaplan-Meier para calcular la supervivencia global y cáncer-específica. Resultados: Se reclutaron 2.416 sujetos en el brazo screening y 1.862 en el control. La edad media fue de 57,8 años y la mediana del tiempo de seguimiento de 13,3 años. Al finalizar el seguimiento se registraron 427 fallecimientos (9 por CaP). El análisis de supervivencia no mostró diferencia entre los brazos del estudio con respecto a la mortalidad global ni cáncer-específica (p = 0,939 y p = 0,544 respectivamente). Las causas principales de muerte fueron los tumores malignos (52,9%), las enfermedades cardiovasculares (17,3%) y respiratorias (8,9%). Solo un 2,1% de las muertes (0,2% de todos los reclutados) fueron causadas por CaP (2,5% screening, 1,6%control). Conclusiones: La rama española del ERSPC no ha reproducido los resultados a largo plazo del estudio principal, no observándose diferencias en la mortalidad (global o cáncer-específica)después de 15 años de seguimiento. La mortalidad por CaP fue muy limitada (inferior al 1%).Estos resultados apoyan el escaso rendimiento del screening del CaP en nuestro entorno (AU)

Objective: To address if prostate cancer (PCa) screening decreases PCa mortality in the asymptomatic population, within the setting of the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Material and methods: From 1996 to 1999, 4,278 men aged 45-70 years were recruited and randomized to the screening arm (PSA every 4 years, prostate biopsy when PSA≥3 ng/ml)and control arm (no tests). Dates and causes of death were collected on an annual basis. A Kaplan-Meier analysis was used to calculate overall and cancer-specific survival. Results: A total of 2,416 men were recruited in the screening arm and 1,862 in the control arm. Mean age was 57.8 years, median follow-up was 13.3 years. At the end of the follow-up period, 427 deaths (9 from PCa) were observed. Survival analysis did not show any difference between the study arms with respect to overall and cancer-specific survival (p = 0.939 and p = 0.544respectively). Most relevant causes of death were malignant tumors (52.9%), cardiovascular disease (17.3%) and respiratory (8.9%). Only 2.1% of deaths (0.2% of all recruited men) were due to PCa (2.5% screening, 1.6% control).Conclusions: The Spanish arm of ERSPC failed to reproduce the long-term results shown in the whole study. No differences in mortality (overall or cancer-specific) were observed after15 years of follow-up. PCa mortality was infrequent (less than 1%). These results suggest limited yield of PCa screening in our setting (AU)

[Mortality due to prostate cancer in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Results after a 15-year follow-up]. / Mortalidad por cáncer de próstata en la rama española del European Randomized Study of Screening for Prostate Cancer (ERSPC). Resultados tras 15 años de seguimiento.

OBJECTIVE: To address if prostate cancer (PCa) screening decreases PCa mortality in the asymptomatic population, within the setting of the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC). MATERIAL AND METHODS: From 1996 to 1999, 4,278 men aged 45-70 years were recruited and randomized to the screening arm (PSA every 4 years, prostate biopsy when PSA ≥3 ng/ml) and control arm (no tests). Dates and causes of death were collected on an annual basis. A Kaplan-Meier analysis was used to calculate overall and cancer-specific survival. RESULTS: A total of 2,416 men were recruited in the screening arm and 1,862 in the control arm. Mean age was 57.8 years, median follow-up was 13.3 years. At the end of the follow-up period, 427 deaths (9 from PCa) were observed. Survival analysis did not show any difference between the study arms with respect to overall and cancer-specific survival (p=0.939 and p=0.544 respectively). Most relevant causes of death were malignant tumors (52.9%), cardiovascular disease (17.3%) and respiratory (8.9%). Only 2.1% of deaths (0.2% of all recruited men) were due to PCa (2.5% screening, 1.6% control). CONCLUSIONS: The Spanish arm of ERSPC failed to reproduce the long-term results shown in the whole study. No differences in mortality (overall or cancer-specific) were observed after 15 years of follow-up. PCa mortality was infrequent (less than 1%). These results suggest limited yield of PCa screening in our setting.

Tools for protein-protein interaction network analysis in cancer research

As cancer is a complex disease, the representation of a malignant cell as a protein-protein interaction network (PPIN) and its subsequent analysis can provide insight into the behaviour of cancer cells and lead to the discovery of new biomarkers. The aim of this review is to help life-science researchers without previous computer programming skills to extract meaningful biological information from such networks, taking advantage of easy-to-use, public bioinformatics tools. It is structured in four parts: the first section describes the pipeline of consecutive steps from network construction to biological hypothesis generation. The second part provides a repository of public, user-friendly tools for network construction, visualisation and analysis. Two different and complementary approaches of network analysis are presented: the topological approach studies the network as a whole by means of structural graph theory, whereas the global approach divides the PPIN into sub-graphs, or modules. In section three, some concepts and tools regarding heterogeneous molecular data integration through a PPIN are described. Finally, the fourth part is an example of how to extract meaningful biological information from a colorectal cancer PPIN using some of the described tools (AU)

Tratamiento farmacológico de la hepatitis B / Drugs treatment of hepatitis B

Objetivo: Definir el papel de los fármacos disponibles para el tratamiento de la hepatitis B y analizar las actuales guías de tratamiento de las principales sociedades científicas relacionadas. Método: Se realizaron sendas búsquedas bibliográficas en las bases de datos PubMed y EMBASE con el término hepatitis B, limitado a drug therapy y clinical trial, metaanálisis o guidelines, en el período 1991-2007. Resultados: Actualmente son 6 los fármacos disponibles: interferón alfa (convencional o pegilado), lamivudina, adefovir, entecavir y telbivudina. En la práctica habitual, el interferón pegilado ha desplazado casi completamente al convencional. Los pacientes con antígeno E del virus de la hepatitis B (VHB) positivo (HBeAg+) con concentraciones elevadas de alaninotransferasa (ALT), cifras bajas de ADN-VHB y genotipos A y B son los que mejor responden al interferón. Lamivudina consigue una supresión viral más rápida y potente que adefovir; su principal problema es la resistencia que genera. Probablemente, su papel disminuirá con la incorporación de entecavir y telbivudina, asociados con menores resistencias. Adefovir es útil en los pacientes descompensados y/o resistentes a lamivudina. Debido a las tasas de respuestas obtenidas, entecavir podría ser el fármaco de elección en pacientes HBeAg+, fundamentalmente en los que tienen cargas virales más altas. En HBeAg¬, cualquier fármaco podría ser utilizado como primera opción. Las guías difieren, principalmente, en la definición de la enfermedad y los marcadores séricos que indican replicación activa: cargas virales y positividad del HBeAg. Conclusiones: Todos los fármacos son capaces de alcanzar los objetivos bioquímicos, virales e histológicos a corto plazo. No hay unanimidad acerca de qué pacientes tratar, con qué fármacos, durante cuánto tiempo y cuáles son los objetivos perseguidos (AU)

Objective: To define the role of those drugs available for hepatitis Btreatment and analyse current treatment guides prepared by the leading scientific societies in the field. Methods: Bibliographic searches were carried out in the databases PubMed and EMBASE, using the search word «hepatitis B», limited by «drug therapy» plus «clinical trial», «meta-analysis» or «guidelines», within the period 1991-2007. Results: Six drugs are currently available: interferon alpha (conventional or pegylated), lamivudine, adefovir, entecavir and telbivudine. In normal practice, pegylated interferon has almost completely displaced the conventional variety. HBeAg+ patients with high ALT levels, low HBV DNA counts and genotypes A and B show the best response to interferon. Lamivudine achieves faster and more potent viral suppression thanadefovir; its principal drawback is the resistance that some patients develop. Its role will probably decrease as entecavir and telbivudine become more widespread, as they are associated with less resistance. Adefovir is useful in decompensated patients and/or those resistant to lamivudine. Because of the response rates it obtains, entecavir could be the drug of choice for HBeAG+ patients, particularly those with higher viral loads. For HBeAg– cases, any drug can be used as a first-choice drug. The main difference between the treatment guides lies in the way they define the illness and the serum markers that indicate active replication: viral loads and HBeAG positivity. Conclusions: All of the drugs are capable of accomplishing short term biochemical, viral and histological objectives. There is no unanimous opinion on which patients should be treated with which drugs, during what length of time, and what objectives are to be reached (AU)

[Drugs treatment of hepatitis B]. / Tratamiento farmacológico de la hepatitis B.

OBJECTIVE: To define the role of those drugs available for hepatitis B treatment and analyse current treatment guides prepared by the leading scientific societies in the field. METHODS: Bibliographic searches were carried out in the databases PubMed and EMBASE, using the search word <>, limited by <> plus <>, <> or <>, within the period 1991-2007. RESULTS: Six drugs are currently available: interferon alpha (conventional or pegylated), lamivudine, adefovir, entecavir and telbivudine. In normal practice, pegylated interferon has almost completely displaced the conventional variety. HBeAg+ patients with high ALT levels, low HBV DNA counts and genotypes A and B show the best response to interferon. Lamivudine achieves faster and more potent viral suppression than adefovir; its principal drawback is the resistance that some patients develop. Its role will probably decrease as entecavir and telbivudine become more widespread, as they are associated with less resistance. Adefovir is useful in decompensated patients and/or those resistant to lamivudine. Because of the response rates it obtains, entecavir could be the drug of choice for HBeAG+ patients, particularly those with higher viral loads. For HBeAg- cases, any drug can be used as a first-choice drug. The main difference between the treatment guides lies in the way they define the illness and the serum markers that indicate active replication: viral loads and HBeAG positivity. CONCLUSIONS: All of the drugs are capable of accomplishing short-term biochemical, viral and histological objectives. There is no unanimous opinion on which patients should be treated with which drugs, during what length of time, and what objectives are to be reached.

Consumption of cruciferous vegetables and glucosinolates in a Spanish adult population.

OBJECTIVE: To assess the intake of glucosinolates and cruciferous vegetables among Spanish adults. DESIGN: Cross-sectional analysis of a prospective cohort study. SETTING: The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: We analysed data from 40 684 men and women aged 35-64 years from the EPIC-Spain cohort. The usual diet was assessed by means of the dietary history method, and glucosinolate intake was calculated using a published food composition database. RESULTS: The average intake of cruciferous vegetables was 11.3 g/day, accounting for about 5% of total vegetable consumption, whereas the daily intake of total glucosinolates was 6.5 mg, among which 35% were of indole type. The absolute intake of glucosinolates was in average higher in men than in women (6.8 vs 6.2 mg/day), whereas glucosinolate density per energy unit was higher in women's diet (3.4 vs 2.7 mg/4200 kJ). Northern regions consumed in average 36% more glucosinolates than Southern regions (7.3 vs 5.4 mg/day). There was a positive association of glucosinolate intake with body mass index, physical activity, educational level and an inverse relationship with alcohol consumption. CONCLUSIONS: Contrary to the pattern seen for total vegetable intake, our estimate of consumption of cruciferous vegetables, and hence of glucosinolates, is relatively low within Europe, which in turn is lower than in North America and several Asian populations.

Validity of self reported diagnoses of cancer in a major Spanish prospective cohort study.

INTRODUCTION: This study aims to assess the validity of self reported diagnoses of cancer by persons recruited for the Spanish EPIC (European prospective investigation into cancer and nutrition) cohort study and to identify variables associated with correctly reporting a diagnosis of cancer. METHODS: 41 440 members of EPIC were asked at the time of recruitment whether they had been diagnosed with cancer and the year of diagnosis and site. The process of validating self reported diagnoses of cancer included comparison of the cohort database with the data from the population based cancer registries. Cancer diagnostic validity tests were calculated. The association between a correct report and certain sociodemographic, tumour related, or health related variables were analysed by logistic regression. RESULTS: The overall sensitivity of self reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest values being shown by persons with a higher level of education or with a family history of cancer and the lowest values by smokers. Breast and thyroid cancers are those with the highest diagnostic validity and uterus, bladder, and colon-rectum those with the lowest. In both sexes the variables showing a significant association with a correct report of cancer are: higher education level, number of previous pathologies, invasive tumour, and, in women, a history of gynaecological surgery. CONCLUSIONS: The overall sensitivity of self reported diagnoses of cancer is comparatively low and it is not recommended in epidemiological studies for identifying tumours. However, self reported diagnoses might be highly valid for certain tumour sites, malignant behaviour, and average to high levels of education.

Estimacion pronostica en enfermos criticos. Validacion de un nuevo y muy sencillo sistema de estimación pronóstica de supervivencia en pacientes ingresados en una Unidad de Cuidados Intensivos / Prognostic estimation in critical patients. Validation of a new and very simple system of prognostic estimation of survival in an Intensive Care Unit

Objetivo. Realizar la validación de un nuevo sistema de estimación pronóstica de supervivencia de enfermos críticos (EPEC) atendidos en una Unidad de Cuidados Intensivos (UCI) polivalente. Diseño y ámbito. Análisis prospectivo de una cohorte de pacientes atendidos en la UCI de un Servicio de Medicina Intensiva polivalente de un hospital docente de referencia, dotado de 19 camas. Pacientes y método. Cuatrocientos ochenta y cuatro pacientes ingresados consecutivamente durante 6 meses de 2003. Recogida de datos de un conjunto mínimo básico de datos (CMBD) propio que incluye datos de identificación de pacientes (género, edad, etc.), motivo de ingreso y procedencia del mismo, estimación pronóstica de supervivencia mediante EPEC, MPM II 0 y SAPS II (considerados estos dos como gold standard). La mortalidad fue evaluada al alta hospitalaria. La validación de EPEC fue realizada mediante análisis de su capacidad discriminante (curvas ROC); la calibración de su capacidad pronóstica (test de Hosmer Lemeshow C) y resolución de las tablas de contingencia 2 x 2 alrededor de distintos valores de probabilidad (20, 50, 70 y valor medio de la estimación pronóstica). Se calculó la tasa estandarizada de mortalidad (SMR) para cada uno de los métodos. Se estableció la regresión lineal de EPEC respecto de MPM II 0 y SAPS II y se realizaron análisis de concordancia (test de Bland-Altman) de la predicción de mortalidad por los tres sistemas. Resultados. A pesar de una aparentemente buena correlación lineal, una exactitud de predicción y una capacidad de discriminación similares, EPEC no está bien calibrado (ninguna probabilidad de muerte superior al 50%) y los análisis de concordancia demuestran que más del 10% de los pares están fuera del intervalo de confianza del 95%. Conclusión. A pesar de su sencillez de aplicación y cálculo y de incorporar como variable el retraso de ingreso en UCI, EPEC no ofrece ninguna ventaja predictiva sobre MPM II 0 o SAPS II, y sus predicciones se ajustan peor a la realidad

Objective. To make the validation of a new system of prognostic estimation of survival in critical patients (EPEC) seen in a multidisciplinar Intensive care unit (ICU). Design and scope. Prospective analysis of a patient cohort seen in the ICU of a multidisciplinar Intensive Medicine Service of a reference teaching hospital with 19 beds. Patients and method. Four hundred eighty four patients admitted consecutively over 6 months in 2003. Data collection of a basic minimum data set that includes patient identification data (gender, age), reason for admission and their origin, prognostic estimation of survival by EPEC, MPM II 0 and SAPS II (the latter two considered as gold standard). Mortality was evaluated on hospital discharge. EPEC validation was done with analysis of its discriminating capacity (ROC curve), calibration of its prognostic capacity (Hosmer Lemeshow C test), resolution of the 2 x 2 Contingency tables around different probability values (20, 50, 70 and mean value of prognostic estimation). The standardized mortality rate (SMR) for each one of the methods was calculated. Linear regression of the EPEC regarding the MPM II 0 and SAPS II was established and concordance analyses were done (Bland-Altman test) of the prediction of mortality by the three systems. Results. In spite of an apparently good linear correlation, similar accuracy of prediction and discrimination capacity, EPEC is not well-calibrated (no likelihood of death greater than 50%) and the concordance analyses show that more than 10% of the pairs were outside the 95% confidence interval. Conclusion. In spite of its ease of application and calculation and of incorporating delay of admission in ICU as a variable, EPEC does not offer any predictive advantage on MPM II 0 or SAPS II, and its predictions adapt to reality worse

Reliability of bulky DNA adducts measurement by the nuclease P1 32P-post-labelling technique.

The aim was to assess the reliability of bulky DNA adducts measurement by means of the 32P-post-labelling assay. The research design consisted of an intramethod reliability study. Buffy coats from 41 subjects were used to obtain two aliquots of 1-5 microg DNA for each subject; bulky DNA adducts were measured using the nuclease P1 32P-post-labelling technique. The reliability of the measurement was assessed by means of the intraclass correlation coefficient (ICC), the distribution of the differences between the two measurements and the limits of agreement. The estimated ICC was 0.977, with a 95% confidence interval between 0.921 and 0.977. The limits of agreement were +/- 0.44 (DNA adducts per 10(8) nucleotides). Only three subjects had differences lying out of such limits. Bulky DNA adduct levels measured by the 32P-post-labelling technique showed good reliability. Only one measurement is needed to use DNA adducts as a biomarker of exposure and, possibly, cancer risk. Besides, as a validation analysis, 32P-post-labelling measurements can be repeated in only 20-30% of samples.

Quantitative real-time reverse transcription: polymerase chain reaction of prostate-specific antigen (PSA) for detection of circulating prostatic cells in patients with clinically localized prostate cancer.

OBJECTIVE: To evaluate the clinical utility of using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify prostate-specific antigen (PSA) mRNA in peripheral blood samples from patients with prostate cancer as a predictor of extraprostatic extension of the disease and to assess any correlations with known predictive markers of this condition. METHODS: Immediately before radical prostatectomy, peripheral blood samples were taken from 42 men with clinically localized prostate cancer and analysed for PSA and 18S ribosomal (endogenous control) genes using real-time RT-PCR (with gene expression assays and the comparative CT-cycle threshold-method for quantifying). A total of 30 healthy male blood donors aged <50 y was taken as a control group. The relationships between PSA mRNA values, pathological and clinical features were analysed. PSA mRNA value, PSA level and biopsy Gleason score were then compared as predictors of extraprostatic extension. RESULTS: PSA gene expression was 3.73 times significantly higher in patients with clinically localized prostate cancer than in healthy men (P<0.05). There was no relationship between PSA real-time RT-PCR values and pathological stage pT2 or pT3 (P=0.5), and no association between PSA mRNA value and serum PSA level (P=0.9) or the Gleason score of the preoperative biopsy (P=0.9). CONCLUSION: There was no significant advantage in using the real-time RT-PCR assay of PSA mRNA before surgery to stage prostate cancer and to discriminate between organ-confined and extraprostatic extension.

Prostate cancer detection and tumor characteristics in men with multiple biopsy sessions.

PURPOSES: To address prostate cancer (PCa) detection with respect to the number of biopsy sessions performed, to identify risk factors for detection after a negative biopsy, and to analyze the clinical characteristics of the detected tumors. SCOPE: Only biopsied men (sextant) were included. A total of 1011 biopsy sessions were carried out in 770 men; 172 underwent a second prostate biopsy and 51 a third biopsy. During the first biopsy round, 111 cancers were found (14.4%), 27 in the second (15.7%), and five during the third round (9.8%), P=0.156. Only high-grade PIN or atypia were identified as independent predictors or PCa detection in subsequent biopsies (P=0.008). A nonsignificant increase of clinically localized tumors, and a decrease of metastatic and poorly differentiated cases were found when more biopsy sessions were needed for detection. CONCLUSIONS: A nonsignificant trend to lower cancer detection rates and less clinical relevance of the tumors detected can be observed when more biopsy rounds are needed for detection.

Prostate apoptosis after doxazosin treatment in the spontaneous hypertensive rat model.

OBJECTIVE: To validate the spontaneous hypertensive rat (SHR) model for basic research into benign prostate hyperplasia (BPH), and to assess doxazosin-induced changes in prostatic structure and apoptotic status. MATERIALS AND METHODS: Four groups of rats were assessed: group 1, 15 SHRs treated with doxazosin; group 2, 14 SHRs with unilateral excision of the major pelvic ganglion; group 3, 14 untreated SHRs; and group 4, 16 intact Wistar-Kyoto (WKY) rats. The doxazosin mesylate (0.03 mg daily) was given compacted in rat food for 3 months. The prostatic ventral lobe (VL) was excised and weighed. Stereological light microscopy, multiplex reverse transcription-polymerase chain reaction of prostate caspases, and caspase-3 activity (cellular enzymatic assay) were assessed. RESULTS: There was more development of the glandular epithelium (P < 0.001) in SHR rats than in controls, which was even greater after doxazosin exposure (P = 0.027). SHR animals had higher caspase expression (P < 0.05) and activity (P = 0.008) than WKY rats, but both were reduced after doxazosin therapy (P < 0.01 and 0.028, respectively). CONCLUSIONS: This study confirmed prostate hyperplasia in the SHR model. Doxazosin exposure did not reduce the volume of glandular epithelium and contributed to protecting against caspase-induced apoptosis. The SHR model may be not a valid option to study doxazosin-induced apoptosis in BPH.