Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

Intellectual disability and the prison setting.

INTRODUCTION: The prevalence of intellectual disability (ID) in the prison setting has scarcely been studied. Although some approximations or estimates regarding people with intellectual disabilities have been performed in Spain, there is little in the way of reliable data. OBJECTIVES: 1) To determine the prevalence of ID in a sample population in the residential modules of a Spanish prison, 2) Obtain data on the prevalence of ID in prison psychiatric units and hospitals. METHODS: 1) A TONI II test was performed on a sub-sample (n = 398) of a prevalence study in Spanish prisons to identify inmates with intellectual disabilities. 2) We reviewed the reports of the psychiatric department of Parc Sanitari Sant Joan de Deu to establish the diagnosis at discharge of patients with a primary diagnosis of intellectual disability 3) Data from the Directorate General of Prisons on the prevalence of ID in Prison Psychiatric Hospitals was reviewed. RESULTS: The data obtained from the TONI II test found 3.77% of the study population has an IQ below 70, and 7.54 % has a borderline IQ rate. Assessment of penitentiary psychiatric hospitalization data showed these figures to be higher. CONCLUSIONS: The data from a Spanish prison population showed that ID levels were higher than those in the community, especially amongst prisoners requiring specialized psychiatric care. What is also evident is that adequate resources are required in prisons and in the community to provide better care for people with intellectual disabilities who are in the pathway of the criminal justice system.

La discapacidad intelectual y el ámbito penitenciario / Intelectural disability and the prison setting

Introducción: La prevalencia de discapacidad intelectual (DI) en el entorno penitenciario ha estado escasamente valorada. En España, a pesar de diversas aproximaciones o estimaciones no existen datos fiables respecto a las personas que sufren de DI. Objetivos: 1) Determinar la prevalencia de DI en una muestra de la población penitenciaria española, ubicada en módulos residenciales 2) Obtener datos sobre la prevalencia de DI en unidades y hospitales psiquiátricos penitenciarios. Métodos: 1) Se realizó una administración del TONI II en una submuestra (n: 398) de un estudio de prevalencia en cárceles españolas para identificar los internos con DI. 2) Se revisaron la memorias del Área Psiquiátrica Penitenciaria del Parc Sanitari Sant Joan de Deu para determinar los pacientes con diagnostico principal de DI. 3) Se revisaron datos de documentos de la Dirección General de Instituciones Penitenciarias para obtener la prevalencia de discapacidad intelectual en los Hospitales Psiquiátricos Penitenciarios. Resultados: Los datos del TONI II fueron que un 3,77% de la población estudiada presenta un Coeficiente Intelectual (CI) por debajo de 70, y un 7,54% presentaba una inteligencia límite. Siendo mayores cuando valoramos la hospitalización psiquiátrica. Conclusiones: Los datos de DI en población penitenciaria presentan unas tasas elevadas, especialmente aquellos que precisan una atención psiquiátrica especializada. Lo que pone de relieve que son necesarios recursos (penitenciarios y comunitarios) para una mayor atención de las personas con DI durante el recorrido en el ámbito penal (AU)

Introduction: The prevalence of intellectual disability (ID) in the prison setting has scarcely been studied. Although some approximations or estimates regarding people with intellectual disabilities have been performed in Spain, there is little in the way of reliable data. Objectives: 1) To determine the prevalence of ID in a sample population in the residential modules of a Spanish prison, 2) Obtain data on the prevalence of ID in prison psychiatric units and hospitals. Methods: 1) A TONI II test was performed on a sub-sample (n = 398) of a prevalence study in Spanish prisons33 to identify inmates with intellectual disabilities. 2) We reviewed the reports of the psychiatric department of Parc Sanitari Sant Joan de Deu to establish the diagnosis at discharge of patients with a primary diagnosis of intellectual disability 3) Data from the Directorate General of Prisons on the prevalence of ID in Prison Psychiatric Hospitals was reviewed. Results: The data obtained from the TONI II test found 3.77% of the study population has an IQ below 70, and 7.54% has a borderline IQ rate. Assessment of penitentiary psychiatric hospitalization data showed these figures to be higher. Conclusions: The data from a Spanish prison population showed that ID levels were higher than those in the community, especially amongst prisoners requiring specialized psychiatric care. What is also evident is that adequate resources are required in prisons and in the community to provide better care for people with intellectual disabilities who are in the pathway of the criminal justice system (AU)

Consideraciones clínicas de la expresión 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 / 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

OBJETIVO: la manipulación quirúrgica del cáncer tiene la potencialidad de aumentar la diseminación de células cancerosas al torrente sanguíneo y con esto el riesgo de metástasis. Presentamos el efecto de la biopsia prostática en la diseminación de estas células así como sus características fenotípicas. MÉTODOS: Se incluyeron cincuenta hombres que fueron sometidos a una biopsia prostática trans rectal como sospecha de cáncer de próstata en nuestro estudio. Se recolectaron muestras sanguíneas inmediatamente antes de la biopsia, una hora y 24 horas posterior a la misma, para detección de células prostáticas en sangre (CPC) así como para determinar sus características fenotípicas utilizando inmunocitoquímica estándar con anti PSA y luego caracterizarlas utilizando anti P504S y anti matriz de metaloproteinasa 2 (MMP-2). RESULTADOS: Catorce hombres (28%) tuvieron cáncer de próstata en la biopsia, 13 de estos fueron P504S + y MMP-2 + previo a la biopsia. Una hora posterior a la biopsia existió una mezcla de P504S + y P504S - así como de MMP2 + y MMP2 - en pacientes con biopsia positiva para cáncer, niveles que se igualaron a los pre biopsia luego de 24 horas. En pacientes negativos para cáncer, se detectaron células circulantes P504S - y MMP-2 -, algunas de ellas se mantuvieron por más de 24 horas. CONCLUSIONES: La biopsia prostática puede causar diseminación de células prostáticas malignas y benignas a la circulación y la mayoría son eliminadas dentro de las primeras 24 horas. No existió conversión de pacientes con cáncer de CPCs negativos a positivos lo que sugiere que la capacidad inherente de las células prostáticas de diseminar es más importante que el efecto de la biopsia prostática

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 prebiopsy 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

Panitumumab and irinotecan very 3 weeks is an active and convenient regimen for secondline treatment of patients with wild-type K-RAS metastatic colorectal cancer

PURPOSE: To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). METHODS: Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). CONCLUSION: This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC (AU)

Effect of androgen blockade on HER-2 and matrix metalloproteinase-2 expression on bone marrow micrometastasis and stromal cells in men with prostate cancer.

INTRODUCTION: HER-2 has been associated with castrate resistant prostate cancer and matrix metalloproteinase-2 (MMP-2) in the dissemination and invasion of tumor cells as well as activating angiogenesis. We present an immunocytochemical study of the effect of androgen blockade on the expression of HER-2 and MMP-2 in bone marrow micrometastasis and the surrounding stromal cells in men with prostate cancer. METHODS AND PATIENTS: A cross-sectional study of men with prostate cancer. Touch preps were obtained from bone marrow biopsies of men with prostate cancer, before and after radical prostatectomy and during androgen blockade. Micrometastasis detected with anti-PSA immunocytochemistry underwent processing with anti-HER-2 and anti-MMP-2 immunocytochemistry. Patients were defined as HER-2 positive or negative, MMP-2 negative or an MMP-2 pattern described as border or central and stromal MMP-2 defined as positive or negative. The expression of the biomarkers was compared before and after primary treatment and during androgen blockade in relation to the serum PSA at the time of sampling and duration of androgen blockade. RESULTS: 191 men participated, 35 men before surgery and 43 after surgery; there were no significant differences in HER-2 expression between groups, there was no MMP-2 expression centrally or stromal expression of MMP-2. In men with androgen blockade, HER-2 expression was significantly higher; there was a trend for increasing HER-2 expression up to 5 years; central MMP-2 expression significantly increased after 3 years, while stromal MMP-2 significantly increased after 6 years. MMP-2 expression both in micrometastasis and stroma was significantly associated with HER-2 expression. Expression of MMP-2 at the border of the micrometastasis was not associated with HER-2 expression and occurred in the absence of androgen blockade. CONCLUSIONS: Androgen blockade decreases serum PSA by eliminating HER-2 negative prostate cancer cells. However, there is early selection of HER-2 positive cancer cells which leads to androgen independence and to increased expression of MMP-2 activity in the micrometastasis. The increased MMP-2 activity in the micrometastasis increases the expression of MMP-2 in the surrounding stromal cells and thus could promote angiogenesis and tumor growth resulting in macrometastatic androgen independent disease.

A performance analysis of the presence of malignant circulating prostate cells as a predictive factor for the detection of prostate cancer in the first, second and third prostate biopsy.

OBJECTIVES: Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. This may be more so in subsequent biopsies where serum PSA has a decreased diagnostic yield. To evaluate the diagnostic yield of the detection of CPCs as a complementary PC screening test in a population fulfilling criteria for an initial, second and third prostate biopsy for suspicion of PC. METHODS: A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0 ng/ml, PSA velocity >0.35 ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for CPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-his-tochemical staining with anti-PSA and anti-P504S was used to detect CPCs. Both cytologist and pathologist were blinded to the results of the biopsy, CPC results and clinical details. The diagnostic yield of the presence or absence of CPC was evaluated; the prostate biopsy was classified as cancer or no-cancer. RESULTS: 282 men participated, 83 undergoing of these undergoing a second and 38 a third biopsy, with a mean age of 66.2 ± 8.9 years and a median serum PSA of 5.10 ng/ml, 5.45 ng/ml and 6.45 ng/ml for first, second and third biopsies. Cancer was detected in 33,6%, 10.8% and 29.0% of first, second and third biopsies respectively, CPCs were detected in 36.9%, 21.7% and 36.8% of the patients. Sensibility, specificity and negative predictive value were 86% ,91% and 94% for the first biopsy, 89%, 87% and 99% for the second and 100% , 89% and 100% for third biopsy respectively. All the CPC determinations were interpretable. There were 11 false negative cases, all with small low grade tumors. Of the 29 men with a false positive CPC, 8/10 had cancer detected in the subsequent biopsy. CONCLUSIONS: The use of CPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, and including patients with indications for repeat biopsies. Men with a false positive CPC detection had a high risk of detecting cancer in the succeeding biopsy.

Análisis del desempeño de la presencia de células prostáticas malignas circulantes como factor predictivo para la detección de cáncer de próstata en la primera, segunda y tercera biopsia prostática / A performance analysis of the presence of malignant circulating prostate cells as a predictive factor for the detection of prostate cancer in the first, second and third prostate biopsy

OBJETIVO: El PSA en conjunto con el tacto rectal son los exámenes más utilizados para el cribado de cáncer de próstata (CP), sin embargo, en solo el 30% de estos pacientes se confirma el diagnóstico. En el presente estudio evaluamos el rendimiento diagnóstico de la detección de células prostáticas circulantes malignas (mCPC) para la detección precoz del CP en pacientes que cumplen con los criterios para realización de una o más biopsias prostáticas. MÉTODO: Estudio prospectivo, ciego, con reclutamiento consecutivo de pacientes entre 45-80 años, con sospecha de CP. Criterios de inclusión: PSA sérico >4,0 ng/ml, elevación >0,75 ng/ml/año, tacto rectal sospechoso de cáncer. La detección de mCPC fue realizada por inmunohistoquímica con doble marcación hacia el PSA y P504S. Se evalúo el rendimiento diagnóstico de la presencia o ausencia de mCPC comparándolos con los resultados de la biopsia prostática, la cual se clasificó como cáncer o no cáncer. RESULTADOS: Participaron 282 hombres; 83 de los cuales fueron sometidos a una segunda biopsia y 38 a una tercera. La edad media fue 66.2 ± 8.9 años; una media de PSA de 5,10, 5,45 y 6,45 ng/dl para la primera, segunda y tercera biopsia respectivamente. Se diagnosticó CP en 33.6%, 10,8% y 29,0% y las mCPC se detectaron en 36,9%, 21,7% y 36,8% de la primera, segunda y tercera biopsia respectivamente. Con una sensibilidad, especificidad y valor predictivo negativo de 86.2%, 90.8% y 94.3% para la primera biopsia; 89%, 87% y 99% para la segunda y 100%, 89% y 100% para la tercera biopsia respectivamente. Ocurrieron 11 casos de falsos negativos, con un CP pequeño y de bajo grado. De los 29 pacientes con un falso positivo para CPC, 8/10 tuvieron un cáncer detectado en la siguiente biopsia. CONCLUSIÓN: El uso de la detección de mCPC puede ser un método útil como examen complementario a los actualmente en uso para la detección de cáncer prostático, y durante el seguimiento de pacientes con PSA persistentemente elevado para determinar la necesidad de una re biopsia. Las mCPCs tienen un especial valor por su alto valor predictivo negativo en pacientes con un PSA ≥4.0ng/ml (AU)

OBJECTIVES: Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. This may be more so in subsequent biopsies where serum PSA has a decreased diagnostic yield. To evaluate the diagnostic yield of the detection of CPCs as a complementary PC screening test in a population fulfilling criteria for an initial, second and third prostate biopsy for suspicion of PC. METHODS: A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0ng/ml, PSA velocity >0.35ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for CPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-his-to chemical staining with anti-PSA and anti-P504S was used to detect CPCs. Both cytologist and pathologist were blinded to the results of the biopsy, CPC results and clinical details. The diagnostic yield of the presence or absence of CPC was evaluated; the prostate biopsy was classified as cancer or no-cancer. RESULTS: 282 men participated, 83 undergoing of these undergoing a second and 38 a third biopsy, with a mean age of 66.2 ± 8.9 years and a median serum PSA of 5.10ng/ml, 5.45ng/ml and 6.45ng/ml for first, second and third biopsies. Cancer was detected in 33,6%, 10.8% and 29.0% of first, second and third biopsies respectively, CPCs were detected in 36.9%, 21.7% and 36.8% of the patients. Sensibility, specificity and negative predictive value were 86%, 91% and 94% for the first biopsy, 89%, 87% and 99% for the second and 100%, 89% and 100% for third biopsy respectively. All the CPC determinations were interpretable. There were 11 false negative cases, all with small low grade tumors. Of the 29 men with a false positive CPC, 8/10 had cancer detected in the subsequent biopsy. CONCLUSIONS: The use of CPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, and including patients with indications for repeat biopsies. Men with a false positive CPC detection had a high risk of detecting cancer in the succeeding biopsy (AU)

Association of formal thought disorder in schizophrenia with structural brain abnormalities in language-related cortical regions.

BACKGROUND: Formal thought disorder (FTD) in schizophrenia has been found to be associated with volume reductions in the left superior temporal cortex. However, there have been negative findings and some studies have also found associations in other cortical regions. METHOD: Fifty-one schizophrenic patients were evaluated for presence of FTD with the Thought, Language and Communication (TLC) scale and underwent whole-brain structural MRI using optimized voxel-based morphometry (VBM). Fifty-nine matched healthy controls were also scanned. RESULTS: Compared to 31 patients without FTD (global TLC rating 0 or 1), 20 patients with FTD (global TLC rating 2-5) showed clusters of volume reduction in the medial frontal and orbitofrontal cortex bilaterally, and in two left-sided areas approximating to Broca's and Wernicke's areas. The pattern of FTD-associated volume reductions was largely different from that found in a comparison between the healthy controls and the patients without FTD. Analysis of correlations within regions-of-interest based on the above clusters indicated that the 'fluent disorganization' component of FTD was correlated with volume reductions in both Broca's and Wernicke's areas, whereas poverty of content of speech was correlated with reductions in the medial frontal/orbitofrontal cortex. CONCLUSIONS: The findings point to a relationship between FTD in schizophrenia and structural brain pathology in brain areas involved in language and executive function.

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer.

PURPOSE: To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). METHODS: Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). CONCLUSION: This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-linetreatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile (AU)

Redefining micrometastasis in prostate cancer - a comparison of circulating prostate cells, bone marrow disseminated tumor cells and micrometastasis: Implications in determining local or systemic treatment for biochemical failure after radical prostatectomy.

The presence of cells positive for cytokeratins or prostate-specific antigen (PSA) in bone marrow aspirates (BMAs) has been used to indicate the presence of micrometastasis. The aim of this prospective study of prostate cancer patients was to determine the presence of prostate cells in blood and BMAs and to compare them with bone marrow biopsy touch prep samples. The results indicated that there was a satisfactory concordance between circulating prostate cells (CPCs) in blood and disseminated tumor cells (DTCs) in BMAs for all Gleason scores (κ>0.50). However, neither were concordant with the presence of prostate cells in bone marrow biopsies except for high-grade tumors, Gleason 8 and 9. Phenotypic characteristics of CPCs and DTCs were identical (κ>0.9) but were different than cells detected in bone marrow biopsies (κ<0.2). The expression of matrix metalloproteinase-2 (MMP-2) in bone marrow biopsies was positively associated with the Gleason score (trend Chi-squared <0.05) and may explain the differences between the presence of DTCs and the presence of prostate cells in bone marrow biopsies. If the presence of DTCs was used to indicate micrometastatic disease, 20% of patients would be misclassified compared to micrometastasis defined as patients with a positive biopsy. This may have clinical implications for patients with low-grade tumors.

Crustáceos decápodos asociados a ensamblajes macroalgales en el litoral rocoso de Córdoba, Caribe colombiano / Decapod crustaceans associated with macroalgae assemblages on the rocky coastline of Córdoba, Colombian Caribbean

Objetivo. Determinar la estructura de las poblaciones de crustáceos decápodos asociados a ensamblajes algales en el litoral rocoso del departamento de Córdoba. Materiales y métodos. Para la recolección de los especímenes se delimitó con un cuadrante de 625 cm2, un área con cinco repeticiones dispuestas al azar en cada estación. Para la separación de las macroalgas desde su disco de fijación en el sustrato, se empleó una espátula metálica. En un recipiente plástico se separaron los crustáceos decápodos del resto del material y se conservaron en alcohol al 70%. Resultados. Se identificaron representantes de 50 especies asociadas a los céspedes algales, agrupadas en 16 familias y 29 géneros. Especies como Acanthonyx petiverii, Epialtus bituberculatus, Eurypanopeus abbreviatus y Pachycheles serratus, presentaron un rango amplio de distribución, siendo características en las dos ecorregiones de estudio. Los cambios en cobertura de algas rojas como Gracilaria mammillaris, Hypnea musciformis y Acanthophora muscoides, determinaron la mayor asociación de crustáceos decápodos en la ecorregión Morrosquillo, mientras que los cambios en cobertura de G. damaecornis y Padina gymnospora, fueron las que determinaron la mayor asociación de crustáceos decápodos en el Darién cordobés. Conclusiones. Los resultados indicaron que las especies de crustáceos decápodos asociados a ensamblajes macroalgales, no se encontraron distribuidas de forma similar en las dos ecorregiones estudiadas, siendo P. armatus la especie con mayor porcentaje de abundancia en la ecorregión Morrosquillo, y E. bituberculatus en el sector comprendido entre los municipios de Moñitos y Los Córdobas.

Rendimiento diagnóstico de la detección de células prostáticas malignas en la circulación sanguínea para la detección précoz del cáncer prostático: una comparación con la biopsia prostática / Diagnostic performance of malignant prostatic cells detection in blood for early detection of prostate cancer: comparison to prostatic biopsy

OBJETIVO: El PSA y el tacto rectal son los exámenes utilizados para el tamizaje de cáncer prostático (CP), pero solo en el 30% de los pacientes con sospecha de cáncer prostático se confirma el diagnóstico. La detección de células prostáticas circulantes en sangre puede ser una herramienta útil para la detección de cáncer prostático en estos pacientes.Evaluar el rendimiento diagnóstico de la detección de CPCm para la detección precoz del CP, en una población que cumple los criterios para la realización de una biopsia prostática por sospecha de CP.MÉTODO: Estudio prospectivo, con reclutamiento consecutivo de pacientes entre 45-80 años, con sospecho de CP. Criterios de inclusión: PSA sérico >4,0 ng/ml, elevación >0,35 ng/ml/año, tacto rectal sospechoso de cáncer. Pacientes con alguno de estos criterios fue sometido a una biopsia prostática transrectal y a la determinación de CPCm en sangre. La detección de CPCm fue realizada por inmunohistoquímica con doble marcación hacia el PSA y P504S. Tanto el citólogo como el patólogo fueron ciegos al resultado de las CPCm y la BP, así como a los datos clínicos. Se evalúo el rendimiento diagnóstico de la presencia o ausencia de CPCm. La biopsia se clasificó como cáncer o no cáncer. Los pacientes fueron divididos entre 1) PSA ≥4,0ng/ml y 2) PSA <4,0ng/ml y cumple con otro criterio para una BP.RESULTADOS: Participaron 228 hombres; edad media de 66.8 ± 8.8 años; PSA mediana de 5.15 ng/dl. Se diagnosticó CP en 28.6% de los casos mediante la BP y las CPCm se detectaron en 31% de todos los pacientes. Con una sensibilidad, especificidad y valor predictivo negativo de 86.2%, 90.8% y 94.3%, respectivamente. Razón de verosimilitud negativa y positiva de 0,15 y 9,36. En hombres con un PSA <4,0ng/ml, hubo 13,3% con CP, una sensibilidad y especificidad de 83,3% y 84,6% y valor predictivo negativo de 97,1%. Ocurrieron 9 casos de falsos negativos, con un CP pequeño y de bajo grado(AU)

CONCLUSIÓN: La detección de CPCm podría ser útil como examen complementario en la detección de cáncer prostático, en especial para su exclusión, incluido pacientes con PSA < de 4 ng/ml(AU)

OBJECTIVES: Serum prostate specific an-tigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of can-cer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable re-sults, but it could be a useful complementa-ry screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy.To evaluate the diagnostic yield of the detection of mCPC as a complementary PC screening test in a po-pulation fulfilling criteria for a prostate biopsy for sus-picion of PC.METHODS: A prospective screening study of consecuti-ve patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0ng/ml, PSA velocity >0.35ng/ml/year and/or DRE suspi-cious for cancer. Patients fulfilling inclusion criteria had blood taken for mCPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-histochemical staining with anti-PSA and anti-P504S was used to detect mCPC. Both cytologist and pathologist were blinded to the results of the biopsy, mCPC results and clinical de-tails. The diagnostic yield of the presence or absence of mCPC was evaluated; the prostate biopsy was classi-fied as cancer or no-cancer(AU)

RESULTS: 228 men participated, with a mean age of 66.8 ± 8.8 years and a median serum PSA of 5.15ng/ml. 28.6% of the biopsies were positive for PC, and mCPC were detected in 31.0% of all cases. Sensibility, specifici-ty and negative predictive value were 86.2%, 90.8% and 94.3% respectively. The negative and positive like-lihood ratios were 9.36 and 0.15. In men with a PSA <4.0ngml, 13.3% had cancer detected on biopsy, with a sensibility and specificity for mCPC detection of 83.3% and 84.6% and negative predictive value of 97.1%. All the mCPC determinations were interpretable. There were 9 false negative cases, all with small low grade tumors.CONCLUSIONS: The use of mCPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, including patients with a serum PSA <4.0ng/ml(AU)

Diagnostic performance of malignant prostatic cells detection in blood for early detection of prostate cancer: comparison to prostatic biopsy.

OBJECTIVES: Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. To evaluate the diagnostic yield of the detection of mCPC as a complementary PC screening test in a population fulfilling criteria for a prostate biopsy for suspicion of PC. METHODS: A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0 ng/ml, PSA velocity >0.35 ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for mCPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-histochemical staining with anti-PSA and anti-P504S was used to detect mCPC. Both cytologist and pathologist were blinded to the results of the biopsy, mCPC results and clinical details. The diagnostic yield of the presence or absence of mCPC was evaluated; the prostate biopsy was classified as cancer or no -cancer. RESULTS: 228 men participated, with a mean age of 66.8 ± 8.8 years and a median serum PSA of 5.15 ng/ml. 28.6% of the biopsies were positive for PC, and mCPC were detected in 31.0%of all cases. Sensibility, specificity and negative predictive value were 86.2%, 90.8% and 94.3% respectively. The negative and positive like-lihood ratios were 9.36 and 0.15. In men with a PSA <4.0ngml, 13.3% had cancer detected on biopsy, with a sensibility and specificity for mCPC detection of 83.3% and 84.6% and negative predictive value of 97.1%. All the mCPC determinations were interpretable. There were 9 false negative cases, all with small low grade tumors. CONCLUSIONS: The use of mCPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, including patients with a serum PSA <4.0 ng/ml.

Expresion de la proteína P504S en las células prostáticas en la circulación sanguínea (CPCS) en pacientes con cáncer prostático y el efecto de la supresión adrogénica: estudio inmunocitoquímico / Circulating prostate cells(CPCS)in patient with prostate cancer express P504S and androgen blockage effect: an immunocytochemical based study

Determinar la presencia de CPCS en pacientes con cáncer prostático, la expresión de p504 S yel efecto de la supresión androgénica. Pacientes, materiales y método: en muestras de sangre venosa de 92 pacientes portadores de cáncer a la prostáta se separaron las células mononucleares por centrifugación diferencial. Las cpcs fueron identificadas utilizando anticuerpos monoclonales contra APE y P504S. Muestras de sangre de 10 mujeres fueron usadas como controles. Resultados: En ninguna de las muestras utilizadas como control y en el 68 por ciento de los hombres estudiados se detectaron CPCS. Todas las células detectadas fueron positivas para la expresión de P504S. Los pacientes con supresión androgénica, DES o después de una orquidectomía, tuvieron un nivel de P504S promedio menor que aquellos sin terapia sistémica p menor que 0,03. Conclusiones: la detección de CPCS P504S positivas en biopsias de prostáta es utilizada para el diagnóstico de cáncer, las celulas benignas no expresan este antígeno. Este estudio pionero demuestra que la expresión de P504S en CPCS es menor eb hombres con tratamiento hormonal sistémico.

Objective To determine the effect of androgen blockage on the expression of P504S en circulating prostate cells (CPCs) in men with prostate cancer. Patients, material and method: mononuclear cells were separated from venous blood using differential centrifugation and identification fied using monoclonal antibodies against PSA and P504S. 10 women were used as controls and 92 men with prostate cancer formesd the study group. Results: 64,8 percent of men were positive for CPCs, all the CPCs detected expressed the antigen P504S. No controls were positive. Conclusions. The detection of P504S postive cells in prostate biopsies is used to determine whether they are malignant or not, benign cells P504S negative. This is pioner study to show that CPCs are P504S positive, with the implication that they are malignant cells.

Randomized study of weekly irinotecan plus high-dose 5-fluorouracil (FUIRI) versus biweekly irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as first-line chemotherapy for patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors Study.

BACKGROUND: Irinotecan plus infusional 5-fluorouracil/leucovorin (FOLFIRI) is accepted as a reference treatment for the first-line treatment of patients with metastatic colorectal cancer (MCRC). The aim of this study was to demonstrate that a regimen without leucovorin (LV) (FUIRI) is not inferior to the standard FOLFIRI (response rate). PATIENTS AND METHODS: Chemotherapy-naive patients with MCRC were randomized to receive either irinotecan (180 mg/m(2) on day 1) + 5-fluorouracil (5-FU) (400 mg/m(2) bolus and 600 mg/m(2) 22-h infusion) + LV (200 mg/m(2) on days 1-2) (FOLFIRI) every 2 weeks or irinotecan (80 mg/m(2)) + 5-FU (2.250 mg/m(2) 48-h infusion) (FUIRI) weekly. RESULTS: In all, 346 patients were included, 173 in each arm. In the intention-to-treat analysis, the response rates for FOLFIRI and FUIRI were 57% [95% confidence interval (CI) 49% to 64%] and 51% (95% CI 43% to 59%), respectively (P = 0.2809). No statistically significant differences were observed between FOLFIRI and FUIRI regarding median progression-free survival (8.3 versus 8.4 months; P = 0.4339) nor median overall survival (21.6 versus 19.2 months; log-rank test P = 0.2941). Grade 3/4 neutropenia was significantly more frequent on FOLFIRI arm (27% versus 9%), while the proportion of diarrhea was higher on FUIRI arm (21% versus 42%). CONCLUSION: FUIRI represents a valid alternative without LV to the FOLFIRI regimen as MCRC first-line treatment.

Clinical and serotonergic predictors of non-affective acute remitting psychosis in patients with a first-episode psychosis.

OBJECTIVE: The study aimed to establish clinical predictors of non-affective acute remitting psychosis (NARP) and assess whether these patients showed a distinct serotonergic profile. METHOD: First-episode never treated psychotic patients diagnosed of paranoid schizophrenia (n=35; 21 men and 14 women) or NARP (n=28; 15 men and 13 women) were included. RESULTS: NARP patients showed significantly lower negative symptomatology, better premorbid adjustment, shorter duration of untreated psychosis, more depressive symptomatology and a lower number of 5-HT2A receptors than the paranoid schizophrenia patients. In the logistic regression, the four variables associated with the presence of NARP were: low number of 5-HT2A receptors; good premorbid adjustment; low score in the item 'hallucinatory behaviour' and reduced duration of untreated psychosis. CONCLUSION: Our findings support the view that NARP is a highly distinctive condition different from either affective psychosis or other non-affective psychosis such as schizophrenia, and highlight the need for its validation.

El uso de la detección de células prostáticas en la circulación sanguínea podría disminuir el número de biopsias prostáticas necesarias para detectar cáncer prostático / Detection of circulating prostate cells could avoid prostate biopsies

Introducción: El uso del antígeno prostático específico como pesquisa para cáncer prostático ha significado según algunos estudios una disminución en la mortalidad y un cambio hacia las etapas más precoces. Pero, implica también que aproximadamente70 por ciento de los hombres con un APE elevado tendrán una biopsia negativa para cáncer, asumiéndose los riesgos de hemorragia e infección del procedimiento. Presentamos un estudio sobre la detección de células prostáticas en la circulación sanguínea como examen complementario y los resultados de la biopsia prostática. Método y pacientes: A hombres que cumplían con los criterios para someterse a una biopsia prostática, se les tomó una muestra de sangre. Las células mononucleares fueron separadas usando centrifugación diferencial y las células prostáticas detectadas usando anticuerpos monoclonales contra el APE y identificadas con inmunocitoquímica. Los resultados de la presencia o ausencia de las CPCs fueron comparados con los resultados de la biopsia. La biopsia fue dirigida por ecografía y tomada siguiendo la norma estándar en sextante. Resultados: Participaron 358 hombres, de éstos, 91 pacientes cumplieron con los criterios para una biopsia, de los cuales 86 se les tomó una biopsia. La ausencia de CPCs fue asociada con una biopsia negativa en 94,7 por ciento (54/57) y hubo CPCs detectadas en 24/27 (89 por ciento) de los casos con una biopsia positiva para cáncer. En 3 casos biopsia positiva CPC negativa el cáncer fue de bajo grado y localizado. Hubo una sensibilidad de 91,5 por ciento y una especificad de 89,0 por ciento. Conclusiones: Hombres negativo para CPCs tienen una alta posibilidad de una biopsia prostática negativa (94,7 por ciento), en estos hombres es posible postergar la biopsia con un monitoreo cuidadoso del APE sérico. Evitando biopsias no necesarias disminuirán los riesgos asociados al paciente sin aumentar los riesgos de no detectar un cáncer agresivo.

Introduction: The widespread use of PSA screening for prostate cancer has decreased mortality and increased early stage detection. However, approximately 70 percent of biopsies will be negative in men with an increased PSA, incurring in the associated risks of haemorrhage and infection. We report the use of circulating prostate cells (CPCs) as a complementary test and compare the results with the associated prostate biopsy. Patients and Methods: Men fulfilling biopsy criteria had a blood sample taken, the mononuclear cells were separated using differential centrifugation and detected using monoclonal antibodies against PSA and identified using monoclonal antibodies against PSA and identified using immunocytochemistry. Standard ultrasound guided sextant biopsy was used. The presence or absence of CPCs was compared with prostate biopsy results. Results: Of 358 men participating in the study 91 fulfilled biopsy criteria of which 86underwent biopsy. The absence of CPCs was seen in 94.7 percent of cases (54/57) with a negative biopsy. In the 3 remaining cases the CPC negative patient had a low grade local cancer. Overall there was a sensitivity of 91.5 percent and specificity of 89.0 percent. Conclusions: Men with negative CPC have a high probability of a negative biopsy, in these patients the biopsy could be deferred with close monitoring of PSA levels, thus avoiding biopsy complications. This would avoid unnecessary risks without jeopardizing early stage cancer detection.

A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression.

Capecitabine is a drug that requires the consecutive action of three enzymes: carboxylesterase 2 (CES 2), cytidine deaminase (CDD), and thymidine phosphorylase (TP) for transformation into 5-fluorouracil (5FU). The metabolism of 5FU requires the activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) among other enzymes. The present study prospectively examined the possible relationship between the toxicity and efficacy of capecitabine and 14 different polymorphisms in CES 2, CDD, TS and DPD. Between 2003 and 2005, a total of 136 patients with advanced breast or colorectal cancer treated with capecitabine were prospectively enrolled. The presence of two polymorphisms (CDD 943insC and CES 2 Exon3 6046 G/A) were associated with a non-statistically significant higher incidence of grade 3 hand-foot syndrome (HFS) (p=0.07) and grade 3-4 diarrhoea (p=0.09), respectively. Patients heterozygous or homozygous for the polymorphism CES 2 5'UTR 823 C/G exhibited a significantly greater response rate to capecitabine, and time to progression of disease (59%, 8.7 months) than patients with the wild type gene sequence (32%, p=0.015; 5.3 months, p=0.014). For the first time, an association between a polymorphism in the CES2 gene and the efficacy of capecitabine has been described, providing preliminary evidence of its predictive and prognostic value.