Comparison of surgical approaches to radical prostatectomy in our series beyond oncological and functional outcomes.

OBJECTIVES: To evaluate the outcomes of robot-assisted radical prostatectomy (RARP) compared to those of open (ORP) and laparoscopic (LRP) surgery. The interest lies fundamentally in the quality-of-life (QoL) evaluation, postoperative recovery, and personal satisfaction of patients with the intervention (PS) beyond oncological and functional outcomes. METHODS: Six hundred eighty-five RPs were performed in our center between 2011-2018 (17,8% ORP, 22,2% LRP and 60% RARP). Patients were prospectively assessed through follow-up until April 2020 and a multiple questionnaire at 12-months post-RP that included ICIQ-SF, SHIM, IPSS, IQL and questions about pain, postoperative recovery and PS. Also baseline and postoperative patient- and treatment-related data were collected, and binomial logistic regressions were performed for the 1 vs.1 comparisons (ORP vs. RARP and LRP vs. RARP). RESULTS: RARP patients have overall fewer comorbidities, less tumor aggressiveness, more operative time requirements and more positive surgical margins than ORP and LRP patients. Nevertheless, RARP outperforms ORP in: hospital stay (days) (OR 0,86; 95% CI: 0,80-0,94), hemoglobin loss (OR 0,38; 95% CI: 0,30-0,47), transfusion rate (OR 0,18; 95% CI: 0,09-0,34), early complications (p = 0,001), IQL (OR 0,82; 95% CI: 0,69-0,98), erectile function (OR 0,41; 95% CI: 0,21-0,79), pain control (OR 0,82; 95% CI: 0,75-0,89), postoperative recovery (p < 0,001) and choice of a different approach (OR 5,55; 95% CI: 3,14-9,80). RARP is superior to LRP in: urinary continence (OR 0,55; 95% CI: 0,37-0,82), IPSS (OR 0,96; 95% CI: 0,93-0,98), IQL (OR 0,76; 95% CI: 0,66-0,88), erectile function (OR 0,52; 95% CI: 0,29-0,93), postoperative recovery (p = 0,02 and 0,004), PS (p = 0,005; 0,002; and 0,03) and choice of a different approach (OR 7,79; 95% CI: 4,63-13,13). CONCLUSIONS: The findings of our study globally endorse a positive effectiveness of RARP over ORP and/or LRP, both on functional issues, postoperative recovery, QoL and PS. Oncologic results should still be improved.

La tromboprofilaxis quirúrgica en el día a día de la cirugía urológica: más allá de la terapia puente / Surgical thromboprophylaxis in daily urologic surgery: Beyond bridge therapy

Introducción: Con el avance de la cirugía laparoscópica y robótica, la profilaxis tromboembólica en los procedimientos urológicos se han basado clásicamente en la experiencia de otras especialidades quirúrgicas. En este trabajo se realiza un análisis de la actualidad de las recomendaciones, basado en un estudio pormenorizado de las guías clínicas europeas y en la bibliografía, aplicando las recomendaciones de tromboprofilaxis a la práctica urológica diaria. Objetivos: Elaborar unas recomendaciones generales aplicables a los pacientes quirúrgicos en urología, evitando la aparición de eventos tromboembólicos en el periodo perioperatorio. Optimizar la medicación y el ajuste en pacientes crónicos y conocer qué pacientes son candidatos a terapias puente. Material y métodos: Se ha realizado una revisión de la literatura disponible y de las guías clínicas europeas. Se analizan los artículos de consenso más recientes realizando una revisión de la bibliografía disponible y los estudios y revisiones en los que se basan las guías europeas de tromboprofilaxis en urología. Resultados: La profilaxis tromboembólica se debe emplear en aquellas cirugías que requieran abordajes abdominales, encamamiento prolongado o enfermedades oncológicas. Las terapias puente con heparinas de bajo peso molecular deben ser reducidas. Los pacientes en tratamiento crónico se pueden beneficiar de terapias puente en casos concretos. Conclusiones: El empleo de heparinas, tan habitual en la práctica clínica, puede ser excesivo según las guías actuales. La aparición de nuevos fármacos anticoagulantes, los cuales poseen antagonistas directos, permiten la reducción de los tiempos de reintroducción de la medicación crónica y un control más eficaz del sangrado

Introduction: With the advanced laparoscopic and robotic surgery, thromboembolic prophylaxis in urologic procedures has traditionally been based on the experience of other surgical specialties. This paper aims to analyze the current recommendations, through a detailed study of the European clinical guidelines and bibliography, applying the recommendations of thromboprophylaxis to the daily urological practice. Objectives: To elaborate general recommendations to surgical patients in Urology, avoiding the risk of perioperative thromboembolic events. Optimize medication in chronic patients and accurately classify who are eligible for bridge therapy. Material and methods: A review of the available literature and the European clinical guidelines was carried out. We analyzed the most recent consensus articles by studying the available bibliography, trials and reviews on which the European guidelines for thromboprophylaxis in urology are based. Results: Thromboembolic prophylaxis should be targeted towards surgeries that require abdominal approaches, prolonged bed rest or oncological pathologies. Bridge therapies with low molecular weight heparins should be limited. Patients undergoing treatment for chronic conditions can benefit from bridge therapies in specific cases

Surgical thromboprophylaxis in daily urologic surgery: Beyond bridge therapy. / La tromboprofilaxis quirúrgica en el día a día de la cirugía urológica: más allá de la terapia puente.

INTRODUCTION: With the advanced laparoscopic and robotic surgery, thromboembolic prophylaxis in urologic procedures has traditionally been based on the experience of other surgical specialties. This paper aims to analyze the current recommendations, through a detailed study of the European clinical guidelines and bibliography, applying the recommendations of thromboprophylaxis to the daily urological practice. OBJECTIVES: To elaborate general recommendations to surgical patients in Urology, avoiding the risk of perioperative thromboembolic events. Optimize medication in chronic patients and accurately classify who are eligible for bridge therapy. MATERIAL AND METHODS: A review of the available literature and the European clinical guidelines was carried out. We analyzed the most recent consensus articles by studying the available bibliography, trials and reviews on which the European guidelines for thromboprophylaxis in urology are based. RESULTS: Thromboembolic prophylaxis should be targeted towards surgeries that require abdominal approaches, prolonged bed rest or oncological pathologies. Bridge therapies with low molecular weight heparins should be limited. Patients undergoing treatment for chronic conditions can benefit from bridge therapies in specific cases. CONCLUSIONS: According to the current guidelines, there might be an overuse of heparins in the daily clinical practice. The development of -direct oral- anticoagulants have shown to reduce the time to reintroduction of medication for chronic conditions as well as a more effective bleeding management.

Respuesta y supervivencia libre de progresión en tumores vesicales en estadios T2-T4 tratados con tratamiento trimodal de conservación vesical / Response and Progression-Free Survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation

Objetivo: Evaluar la respuesta y la supervivencia libre de progresión (SLP) en pacientes diagnosticados de carcinoma vesical infiltrante tratados con RTU-quimioterapia-radioterapia y compararlos con una serie no aleatorizada de pacientes tratados con cistectomía radical. Material y métodos: Análisis retrospectivo de 43 pacientes con carcinoma vesical infiltrante tratados entre 1994–2007 con dos pautas de conservación vesical y estudio comparativo con pacientes sometidos a cistectomía radical (145 casos) en el mismo periodo. Las variables pronósticas para estudio fueron estadio y grado clínico, presencia o no de hidronefrosis, tratamiento quimioterapéutico recibido, dosis de radioterapia y alteraciones en p53 y Ki67. Resultados: La media y la mediana de los pacientes sometidos a conservación vesical fueron de 51 y de 39 meses, respectivamente. El 72% de los pacientes con conservación vesical obtuvo respuesta completa (RC) al finalizar el tratamiento. Solo la hidronefrosis tuvo influencia pronóstica (OR: 7,3; p=0,02). Al final del estudio, el 74% de los que obtuvieron RC mantenía la respuesta. Ninguna de las variables analizadas fueron predictoras del mantenimiento de la respuesta. La SLP en el grupo fue del 69±7 y del 61±7% a 3 y a 5 años. La dosis de radioterapia >60Gy (OR: 6,1; p=0,001) y la ausencia de hidronefrosis (OR 7,5; p=0,02) fueron las únicas variables influyentes. La SLP del grupo con RC fue del 80±7 y del 58±10% a 3 y a 5 años. Al concluir el estudio, 23/43 (53,5%) conservaban la vejiga y estaban libres de enfermedad. Se realizaron 145 cistectomías radicales a pacientes diagnosticados de carcinoma vesical infiltrante. La media y la mediana de seguimiento de este grupo fueron de 29 y 18 meses, respectivamente. El análisis estadístico reflejó que los pacientes que se habían sometido a conservación vesical presentaban únicamente peor estadio clínico que los pacientes sometidos a cistectomía radical (p=0,17).La SLP a 3 y a 5 años de los pacientes sometidos a cistectomía radical fue del 72±5 y del 63±7%, no evidenciando diferencias estadísticamente significativas (p=0,83) con respecto a los pacientes sometidos a pauta de conservación vesical. Conclusiones: Los pacientes sometidos a conservación vesical obtienen una supervivencia similar a la de los pacientes a los que se les ha realizado cistectomía radical. La dosis de radioterapia >60Gy y la ausencia de hidronefrosis son factores de influencia independiente en la SLP (AU)

Objective: To evaluate the response and the free-survival progression in pacients diagnosed of invasive bladder cancer who have been treated with transurethral resection, chemotherapy and radiotherapy. This multimodal treatment is compared with a not random serie of patients treated by radical cistectomy. Material and methods: Retrospective analysis of 43 cases of invasive bladder cancer treated with two schemes of bladder preservation between 1994–2007. They are compared with 145 cases treated with radical cistectomy in the same period of time. Pronostic variables included in the study are clinical stage, grade of differentiation, presence of ureteral obstruction, chemotherapy modality, radiotherapy doses and p53 and ki-67 expression. Results: Mean and median time are 51 and 39 months in patients with multimodal treatment. Complete response is achieved in 72% of cases treated with bladder preservation. Ureteral obstruction is a prognostic factor (OR: 7,3;p:0,02). 72% patients with complete response mantain it at the end of the study. None of analyzed variables are predictors of maintenance of the response. Survival rates with a intact bladder were 69±7% and 61±7% at three and five years. Radiotherapy doses greater than 60Gy (OR: 6,1; p<0,001) and the absence of ureteral obstruction (OR: 7,5; p<0,002) were pronostic variables. Free-survival in patients with complete response was 80±7% and 58±10% at three and five years. At the end of the study, 53,5% of patients had a intact bladder and free-disease. In the same period of time, 145 radical cistectomies were performed due to muscle invasive bladder cancer. Mean and median time in this group were 29 and 18 months respectively. Stadistical analysis reveals a worse clinical stage in the group of patients treated with multimodal treatment (p:0.01). Free-survival was 72±5% and 63±7% at 3 and 5 years in the group of radical cistectomies. There was not stadistical significant differences between cistectomies and bladder preservation. Conclusions: Patients treated with bladder preservation have a free-survival similar to those treted with radical cistectomy. Radiotherapy doses greater than 60Gy and absence of ureteral obstruction were free-survival prognostic variables (AU)

[Response and progression-free survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation]. / Respuesta y supervivencia libre de progresión en tumores vesicales en estadios T2-T4 tratados con tratamiento trimodal de conservación vesical.

OBJECTIVE: To evaluate the response and the free-survival progression in patients diagnosed of invasive bladder cancer who have been treated with transurethral resection, chemotherapy and radiotherapy. This multimodal treatment is compared with a not random serie of patients treated by radical cistectomy. MATERIAL AND METHODS: Retrospective analysis of 43 cases of invasive bladder cancer treated with two schemes of bladder preservation between 1994-2007. They are compared with 145 cases treated with radical cistectomy in the same period of time. Pronostic variables included in the study are clinical stage, grade of differentiation, presence of ureteral obstruction, chemotherapy modality, radiotherapy doses and p53 and ki-67 expression. RESULTS: Mean and median time are 51 and 39 months in patients with multimodal treatment. Complete response is achieved in 72% of cases treated with bladder preservation. Ureteral obstruction is a prognostic factor (OR: 7,3;p:0,02). 72% patients with complete response mantain it at the end of the study. None of analyzed variables are predictors of maintenance of the response. Survival rates with a intact bladder were 69±7% and 61±7% at three and five years. Radiotherapy doses greater than 60Gy (OR: 6,1; p<0,001) and the absence of ureteral obstruction (OR: 7,5; p<0,002) were pronostic variables. Free-survival in patients with complete response was 80±7% and 58±10% at three and five years. At the end of the study, 53,5% of patients had a intact bladder and free-disease.In the same period of time, 145 radical cistectomies were performed due to muscle invasive bladder cancer. Mean and median time in this group were 29 and 18 months respectively. Stadistical analysis reveals a worse clinical stage in the group of patients treated with multimodal treatment (p:0.01). Free-survival was 72±5% and 63±7% at 3 and 5 years in the group of radical cistectomies. There was not statistical significant differences between cistectomies and bladder preservation. CONCLUSIONS: Patients treated with bladder preservation have a free-survival similar to those treated with radical cistectomy. Radiotherapy doses greater than 60Gy and absence of ureteral obstruction were free-survival prognostic variables.

Edad del donante y su influencia en la supervivencia del injerto / Influence of donor age on graft survival

Introducción: En 2007 en España el 43% de los donantes tuvo más de 60 años, lo que supone peor calidad del injerto y probablemente peor supervivencia. Objetivo: Nuestro objetivo es analizar la influencia de la edad del donante en la supervivencia del injerto. Material y métodos: Analizamos retrospectivamente 216 trasplantes renales consecutivos realizados entre 2000–2008. Valoramos la influencia de la edad del donante sobre la supervivencia del injerto y buscamos el mejor punto de corte. Para el estudio de la supervivencia actuarial del injerto se ha utilizado el método de Kaplan Meyer. Para la comparación de curvas de supervivencia utilizamos el test de log-rank. Para el estudio de los factores influyentes en la supervivencia hemos utilizado los modelos de regresión de Cox en forma de estudio univariado y multivariado. Resultados: La media de seguimiento fue de 48 meses (±33,4 DE) y la mediana de seguimiento fue de 48 meses (rango de 0–166 meses).El análisis univariado de la supervivencia del injerto nos mostró que la edad del donante como variable continua influye significativamente en la supervivencia del injerto (odds ratio: 1,03; 95% intervalo de confianza [IC]: 1,01–1,05; p=0,009).Al estudiar la relación entre la edad del donante y el receptor evidenciamos una correlación inversa significativa (correlación de Pearson: 0,55; p<0,0001), pero a pesar de esto, la significación se mantiene si se ajusta con la edad de los receptores (odds ratio: 1,02; 95% IC: 1,01–1,04) (p=0,04). El mejor punto de corte corresponde a 60 años. La supervivencia actuarial del injerto en donantes mayores de 60 años es del 79 (95% IC: 74–84) y del 71% (95% IC: 65–77) en 3 y 5 años frente al 94 (95% IC: 94–96%) y al 90% (95% IC: 88–92) en los receptores de riñones de donantes menores de 60 años (p=0,002).El estudio multivariado de los factores influyentes en la supervivencia del injerto revela que la edad del donante dicotomizada en mayor y menor de 60 años, la presencia de reintervenciones quirúrgicas inmediatas y la función diferida eran los factores de influencia independiente en la supervivencia del injerto. Conclusiones: La edad del donante mayor de 60 años influye negativamente en la supervivencia del injerto renal con valor pronóstico independiente (AU)

Introduction: In 2007 in Spain 43% of donors were older than 60 years. This produces a worse graft quality and probably a worse survival. Objective: Our objective is to analyze the influence of donor age on graft survival. Material and methods: We analyze retrospectively 216 renal consecutive transplants realized between 2000 and 2008. A univaried and multivaried study (Cox regression) was performed and Kaplan-Meyer test with log rank for graft survival. Results: Follow-up mean of 40 months (±33,4 SD). The univaried analysis of graft survival showed that donor age had a significative influence on graft survival. (OR=1,03; 95% CI 1,01–1,05) (p: 0,009). Studying the relation between donor and recipient age we find an inverse correlation (Pearson's Correlation: 0,55. p<0,0001), but there are significative differences after the adjustment for recipient age. (OR: 1,02; 95% CI 1,01–1,04) (p: 0,04). Optimal cut-point value determined by the ROC analysis was 60 years. The graft survival of donors over 60 years is 79% (95% CI; 74–84%) and 71%(95% CI; 65–77%) at 3 and 5 years in contrast with 94% (95% CI; 94–96%) and 90% (95% CI; 88–92 in donors under 60. (p: 0,002). The multivaried study of the influential factors on graft survival reveals that donor age dichotomized in older or younger than 60, the presence of a surgical immediate reintervention and a delayed graft function were independent influence factors. Conclusions: Donor age over 60 years has a negative and independent prognostic influence on graft survival (AU)

[Influence of donor age on graft survival]. / Edad del donante y su influencia en la supervivencia del injerto.

INTRODUCTION: In 2007 in Spain 43% of donors were older than 60 years. This produces a worse graft quality and probably a worse survival. OBJECTIVE: Our objective is to analyze the influence of donor age on graft survival. MATERIAL AND METHODS: We analyze retrospectively 216 renal consecutive transplants realized between 2000 and 2008. A univaried and multivaried study (Cox regression) was performed and Kaplan-Meyer test with log rank for graft survival. RESULTS: Follow-up mean of 40 months (+/-33,4 SD). The univaried analysis of graft survival showed that donor age had a significative influence on graft survival. (OR=1,03; 95% CI 1,01-1,05) (p: 0,009). Studying the relation between donor and recipient age we find an inverse correlation (Pearson's Correlation: 0,55. p<0,0001), but there are significative differences after the adjustment for recipient age. (OR: 1,02; 95% CI 1,01-1,04) (p: 0,04). Optimal cut-point value determined by the ROC analysis was 60 years. The graft survival of donors over 60 years is 79% (95% CI; 74-84%) and 71% (95% CI; 65-77%) at 3 and 5 years in contrast with 94% (95% CI; 94-96%) and 90% (95% CI; 88-92 in donors under 60. (p: 0,002). The multivaried study of the influential factors on graft survival reveals that donor age dichotomized in older or younger than 60, the presence of a surgical immediate reintervention and a delayed graft function were independent influence factors. CONCLUSIONS: Donor age over 60 years has a negative and independent prognostic influence on graft survival.

[Laparoscopic adrenalectomy for metachronous metastasis. Experience in 12 cases]. / Adrenalectomía laparoscópica por metástasis metácrona. Experiencia en 12 casos.

OBJECTIVE: To assess the peroperative and oncological results of laparoscopic adrenalectomy for an isolated metastasis. MATERIAL AND METHODS: A retrospective, descriptive study was conducted of 12 laparoscopic adrenalectomies performed for metastases out of a total of 40 adrenalectomies performed from May 1998 to April 2009. The primary tumor was pulmonary in 7 patients, renal in 3, and colonic in 2. Demographic data collected included median age, operating time, blood loss, complications, tumor size, and length of hospital stay. The Kaplan-Meier method was used to analyze survival. RESULTS: Operating time was 150 min (range, 90-206). Peroperative bleeding was 60 ml (range, 15-150). Peroperative complications occurred in 3% of patients. Tumor size was 4.5 cm (range, 1.3-8.5). No positive margins were seen in the resected specimens. Hospital stay was 3 days (range 3-5). Actuarial survival was 55.6% at 23 months (range, 2-38) with mean and median follow-up times of 20.9 and 23 months. CONCLUSIONS: In selected patients, laparoscopic adrenalectomy for metastasis is a safe procedure with oncological results superimposable to those of open surgery.

[Surgical complications in kidney transplantation and their influence on graft survival]. / Complicaciones quirúrgicas en el trasplante renal y su influencia en la supervivencia del injerto.

OBJECTIVES: To analyze surgical complications in kidney transplantation and their influence on graft survival. MATERIALS AND METHODS: A retrospective analysis was made of the early and late surgical complications occurring in 216 consecutive kidney transplants performed at our institution and their influence on graft survival. RESULTS: At least one surgical complication occurred in 82 (38%) of the 216 transplantations, and 68 (31%) required some type of repeat surgery, 23 in the early postoperative period and 45 more than 3 months after surgery. Mean follow-up was 48 months (SD +/-33.4), and median follow-up 48 months (range, 0-166 months). No recipient or donor factors predisposing to surgical complications were found. Graft survival was significantly shorter in patients with surgical complications [3- and 5-year survival rates of 86% (95% CI 83-89) and 78% (95% CI 73-82) as compared to 92% (95% CI 90-94) and 88% (95% CI 85-91), p=0.004]. Early repeat surgery, venous thrombosis, and wound infection were among the complications having an independent influence on graft survival. A multivariate analysis of graft survival in the whole group showed early repeat surgery to be a factor with an independent prognostic value (OR: 4.7; 95% CI 2.2-10, p<0.0001). Delayed function and donor age older than 60 years were the other independent influential factors. CONCLUSION Surgical complications have an influence on graft survival. The need for early repeat surgery, delayed function, and donor age older than 60 years are independent predictors of graft survival.

Complicaciones quirúrgicas en el trasplante renal y su influencia en la supervivencia del injerto / Surgical complications in kidney transplantation and their influence on graft survival

Objetivo: Nuestro objetivo es analizar las complicaciones quirúrgicas en el trasplante renal y su influencia en la supervivencia del injerto. Material y métodos: Analizamos retrospectivamente 216 trasplantes renales realizados entre el 1 de enero de 2000 y el 31 de diciembre de 2008, analizando las complicaciones quirúrgicas y valorando su influencia sobre la supervivencia del injerto renal. Resultados: De los 216 trasplantes, 82 (38%) tuvieron algún tipo de complicación quirúrgica y 68 (31%) requirieron algún tipo de reintervención (23 en postoperatorio inmediato y 45 más allá de los 3 meses). Media de seguimiento de 48 meses (+/−33,4 desviación estándar) y mediana de seguimiento de 48 meses (rango de 0 a 166).No se han objetivado en receptor o donante factores que predispongan a la incidencia de complicaciones. La supervivencia del injerto es significativamente menor en los pacientes con complicaciones quirúrgicas (supervivencia a los 3 y a los 5 años del 86% [intervalo de confianza {IC} 95%: 83–89] y del 78%% [IC 95%: 73–82] vs. el 92% [IC 95%: 90–94] y el 88%% [IC 95%: 85–91]; p=0,004). La reintervención precoz, la trombosis venosa y la infección de herida son las complicaciones que tienen influencia independiente en la supervivencia. El estudio multivariado de la supervivencia del injerto de todo el grupo pone de manifiesto que la reintervención precoz es un factor de influencia independiente (odds ratio: 4,7; IC 95%: 2,2–10; p<0,0001). La función diferida y la edad del donante mayor de 60 años son los otros factores influyentes. Conclusiones: Las complicaciones quirúrgicas influyen en la supervivencia del injerto. La necesidad de cirugía precoz es una variable con valor pronóstico independiente sobre supervivencia del injerto junto con la función diferida y la edad del donante (AU)

Objectives: To analyze surgical complications in kidney transplantation and their influence on graft survival. Materials and methods: A retrospective analysis was made of the early and late surgical complications occurring in 216 consecutive kidney transplants performed at our institution and their influence on graft survival. Results: At least one surgical complication occurred in 82 (38%) of the 216 transplantations, and 68 (31%) required some type of repeat surgery, 23 in the early postoperative period and 45 more than 3 months after surgery. Mean follow–up was 48 months (SD +/−33.4), and median follow–up 48 months (range, 0–166 months).No recipient or donor factors predisposing to surgical complications were found. Graft survival was significantly shorter in patients with surgical complications [3- and 5-year survival rates of 86% (95% CI 83-89 %) and 78% (95% CI 73-82%) as compared to 92% (95% CI 90-94%) and 88% (95% CI 85-91%), p:0.004]. Early repeat surgery, venous thrombosis, and wound infection were among the complications having an independent influence on graft survival. A multivariate analysis of graft survival in the whole group showed early repeat surgery to be a factor with an independent prognostic value (OR: 4.7; 95% CI 2.2–10, p<0.0001). Delayed function and donor age older than 60 years were the other independent influential factors. Conclusion: Surgical complications have an influence on graft survival. The need for early repeat surgery, delayed function, and donor age older than 60 years are independent predictors of graft survival (AU)

Adrenalectomía laparoscópica por metástasis metácrona. Experiencia en 12 casos / Laparoscopic adrenalectomy for metachronous metastasis. Experience in 12 cases

Objetivos: evaluar los resultados perioperatorios y oncológicos de la adrenalectomía laparoscópica por metástasis aislada. Material y métodos: estudio retrospectivo y descriptivo de 12 adrenalectomías laparoscópicas por metástasis de un total de 40 realizadas entre mayo de 1998 y abril de 2009. El tumor primario fue en siete casos de pulmón, en tres renal y en dos de colon. Los datos demográficos de la serie incluyeron edad, tiempo operatorio, sangrado, complicaciones, tamaño tumoral y estancia hospitalaria expresados como mediana. El análisis de supervivencia se hizo con el método de Kaplan-Meier. Resultados: el tiempo operatorio fue de 150 minutos (rango 90 a 206). El sangrado intraoperatorio fue de 60 cc (rango 15 a 150). Hubo complicaciones intraoperatorias en el 3% de los casos. El tamaño tumoral fue de 4,5 cm (rango 1,3 a 8,5). No se observaron márgenes positivos en las piezas de resección. La estancia hospitalaria fue de tres días (rango 3 a 5). La supervivencia actuarial fue del 55,6% a los 23 meses (rango 2 a 38), con una media y mediana de seguimiento de 20,9 y 23 meses, respectivamente. Conclusiones: la adrenalectomía laparoscópica por metástasis en pacientes seleccionados e suna técnica segura con resultados oncológicos superponibles a los de la cirugía abierta (AU)

Objective: To assess the peroperative and oncological results of laparoscopic adrenalectomy for an isolated metastasis. Material and methods: A retrospective, descriptive study was conducted of 12 laparoscopic adrenalectomies performed for metastases out of a total of 40 adrenalectomies performed from May 1998 to April 2009. The primary tumor was pulmonary in 7 patients, renal in 3, and colonic in 2. Demographic data collected included median age, operating time, blood loss, complications, tumor size, and length of hospital stay. The Kaplan-Meier method was used to analyze survival. Results: Operating time was 150 min (range, 90-206). Peroperative bleeding was 60 ml (range, 15-150). Peroperative complications occurred in 3% of patients. Tumor size was 4.5cm (range, 1.3-8.5). No positive margins were seen in the resected specimens. Hospital stay was 3 days (range 3-5). Actuarial survival was 55.6% at 23 months (range, 2-38) with mean and median follow-up times of 20.9 and 23 months. Conclusions: In selected patients, laparoscopic adrenalectomy for metastasis is a safe procedure with oncological results superimposable to those of open surgery (AU)

[Pelvic lymph node dissection (extended vs standard) and prostate cancer]. / Linfadenectomía (ampliada vs estándar) y cáncer de próstata.

The role and the potential benefit, if any, of pelvic lymphadenectomy in prostate cancer are still controversially discussed. It is generally accepted that PLND at time of radical prostatectomy is the only reliable diagnostic procedure to achieve as much individual histological staging information as possible to trigger postoperative adjuvant management. However, the extent of pelvic lymph node dissection (limited vs. extended) and the most suitable candidates for this procedure are still a matter of intense debate. The aim of this review is to critically evaluate the current status on lymph node dissection in prostate cancer.

[Gleason score 8-10 prostatic adenocarcinoma: prognostic influence in the biochemical progression free survival]. / Adenocarcinoma de próstata gleason clínico 8-10: influencia pronóstica en la supervivencia libre de progresión bioquímica.

OBJECTIVE: Hereby, we analyze the characteristics of the clinical Gleason 8-10 group of patients with in our series diagnosed of Prostate Cancer and treated by means of radical prostatectomy, and we try to ascertain which are the influence factors within this group upon progression and progression free survival. MATERIAL AND METHODS: From the global series of 781 patients with T1-T2 prostate cancer treated by means of radical prostatectomy between 1990 and 2004, we study 108 with a Gleason score on the biopsy of 8-10. Median PSA was 12 ng/ml and 50% were T2. Variables related to biochemical progression and progression free survival have been studied, comparing the group of Gleason 8-10 with the rest and analyzing, within the Gleason 8-10 group which are the related variables with progression and progression free survival, trying to find a predictive model. Contingency tables and logistic regression have been employed. For the survival analysis, Kaplan Meyer curves, log-rank and Cox models. RESULTS: Actual State: 62.7% (490/781) are alive and free of biochemical progression, 24.8% (194/781) are alive with biochemical progression, 2.9% (23/781) are dead by cancer and 1.9% (15/781) are dead by other cause and 7.6% (59/781) are lost. Biochemical progression study of the whole series (781 patients) Clinical Gleason score 8-10 is a influence factor on the univariate study (OR2,61 IC 95%: 1.7-4). In the progression free survival study (PFS) of the whole series (781 patients) the PFS in Clinical Gleason 8-10 at 3 and 5 years is 56 +/- 5% y 35 +/- 7%, significantly worse than the rest of the group (p < 0.0001). In the multivariate study of the influence factors on the PFS includes Clinical Gleason Score 8-10 as an independent prognostic factor (OR: 2.6 IC 95%: 1.6-4.12) p = 0.003, together with the clinical stage (OR: 1.,81 IC 95%: 1.18-2.78) p < 0.006, the PSA (OR: 1.03 IC 95%: 1.025-1.046) p < 0.0001 and the side of tumor on the biopsy (OR: 1.5 IC 95%: 1.01-2.24) p = 0.045. In the clinical Gleason score 8-10 group the influent factors on the PFS are. PSA (OR: 1.02 IC 95%: 1.003-1.04) and pathological stage (OR: 3.84 IC 95%: 1.77-8.27). Patients with a pT2 have a significantly better survival than those pT3 at 3 and 5 years (80 +/- 6%; 54 +/- 13% y 40 +/- 7%; 27 +/- 7%) (p < 0.0001). The best cut point for the PSA is 11 ng/ml. Patients with a PSA < 11 ng/ml have a 3 and 5 years survival better than those with >11 ng/ml PSA (74 +/- 7%, 30 +/- 22% y 40 +/- 7%, 26 +/- 7%) (p < 0.0001). CONCLUSIONS: Clinical Gleason Score 8-10 is a negative independent prognostic factor on the progression free survival, but its prognosis is better if they present a PSA prior surgery lower than 11 ng/ml and the pathological stage is a pT2.

Linfadenectomía (ampliada vs estándar) y cáncer de próstata / Pelvic lymph node dissection (extended vs standard) and prostate cancer

El papel y el beneficio potencial de la linfadenectomía en el cáncer de próstata sigue siendo motivo de controversia. Generalmente se acepta que la linfadenectomía en el momento de realizarse la prostatectomía radical es el único procedimiento diagnóstico que nos acerca a un estadiaje anatomopatológico más preciso permitiéndonos un mejor manejo postoperatorio. Sin embargo la extensión de la disección linfática (limitada vs extensa) y los candidatos más adecuados para estos procedimientos sigue siendo motivo de intenso debate. El propósito de este artículo de revisión es una evaluación crítica del papel actual de la disección linfática en el cáncer de próstata (AU)

The role and the potential benefit, if any, of pelvic lymphadenectomy in prostate cancer are still controversially discussed. It is generally accepted that PLND at time of radical prostatectomy is the only reliable diagnostic procedure to achieve as much individual histological staging information as possible to trigger postoperative adjuvant management. However, the extent of pelvic lymph node dissection (limited vs. extended) and the most suitable candidates for this procedure are still a matter of intense debate. The aim of this review is to critically evaluate the current status on lymph node dissection in prostate cancer (AU)

Adenocarcinoma de próstata gleason clínico 8-10: influencia pronóstica en la supervivencia libre de progresión bioquímica / Gleason score 8-10 prostatic adenocarcinoma: prognostic influence in the biochemical progression free survival

Objetivo: Analizar las características del grupo de pacientes con Adenocarcinoma de próstata Gleason clínico 8-10 en nuestra serie tratados mediante prostatectomía radical, e intentar averiguar que factores dentro del grupo influyen en la progresión y supervivencia libre de progresión. Material y Métodos: De una serie de 781 pacientes con Cáncer de Próstata T1-T2, tratados con Prostatectomía Radical entre 1990-2004, estudiamos108 con Gleason clínico 8-10. Mediana de PSA de 12 ng/ml, el 50% era T2.Se han estudiado las variables relacionadas con la progresión bioquímica y la supervivencia libre de progresión bioquímica, comparando el grupo Gleason 8-10 con el resto y analizando dentro del grupo Gleason 8-10 las variables relacionadas con la progresión y Supervivencia libre de progresión, buscando un modelo predictivo. Se han utilizado tablas de contingencia y regresión logística. Para el análisis de la supervivencia, Kaplan-Meyer, log-rank y modelos de Cox. Resultados: En el estudio de progresión bioquímica de la totalidad de la serie (781 pacientes). El Gleason clínico 8-10 es un factor influyente en el estudio univariado (OR: 2,61 IC 95%: 1,7-4).En el estudio de supervivencia libre de progresión (SLP) de la totalidad de la serie (781 pacientes) la SLP de los Gleason clínico 8-10 a 3 y 5 años es de 56 ± 5% y 35±7%, significativamente peor que la del resto del grupo (p<0,0001). El estudio Multivariado de los factores influyentes en la SLP incluye el Gleason 8-10 como factor de influencia independiente (OR:2,6 IC 95%: 1,6-4,12) p=0,003, junto al estadio clínico (OR:1,81 IC95%:1,18-2,78) p<0,006, el PSA (OR: 1,03 IC 95%:1,025-1,046) p<0,0001y el lado de afectación de la biopsia (OR:1,5 IC 95%:1,01-2,24) p=0,045.Dentro del Grupo Gleason Clínico 8-10 los factores influyentes en la SLP son: el PSA (OR:1,02 IC 95%:1,003-1,04), y el estadio patológico(OR:3,84 IC 95%: 1,77-8,27). Los pacientes pT2 tienen una supervivencia significativamente mejor que los pT3 a 3 y 5 años (80±6%; 54±13% y40±7%; 27±7%) (p<0,0001). El mejor punto de corte para PSA es 11 ng/ml. Los pacientes con PSA<11ng/ml tienen una supervivencia a 3 y 5 años significativamente mejor que los >11 ng/ml (74±7%, 30±22% y 40±7%,26±7%)(p<0,0001).Conclusión: El gleason clínico 8-10 es un factor negativo de influencia independiente en la supervivencia libre de progresión, pero su pronóstico es mejor si presentan un PSA previo <11ng/ml y si el estadio patológico es pT2 (AU)

Objective: Hereby, we analyze the characteristics of the clinical Gleason 8-10 group of patients with in our series diagnosed of Prostate Cancer and treated by means of radical prostatectomy, and we try to ascertain which are the influence factors within this group up on progression and progression free survival. Material and Methods: From the global series of 781 patients with T1-T2 prostate cancer treated by means of radical prostatectomy between 1990and 2004, we study 108 with a Gleason score on the biopsy of 8-10. Median PSA was 12 ng/ml and 50% were T2.Variables related to biochemical progression and progression free survival have been studied, comparing the group of Gleason 8-10 with the rest and analyzing, within the Gleason 8-10 group which are the related variables with progression and progression free survival, trying to find a predictive model. Contingency tables and logistic regression have been employed. For the survival analysis, Kaplan Meyer curves, log-rank and Cox models. Results: Actual State: 62,7% (490/781) are alive and free of biochemical progression, 24,8% (194/781) are alive with biochemical progression, 2,9%(23/781) are dead by cancer and 1,9% (15/781) are dead by other cause and 7,6% (59/781) are lost. Biochemical progression study of the whole series (781 patients) Clinical Gleason score 8-10 is a influence factor on the univariate study (OR: 2,61 IC95%: 1,7-4).In the progression free survival study (PFS) of the whole series (781 patients) the PFS in Clinical Gleason 8-10 at 3 and 5 years is 56 ± 5% y 35±7%,significantly worse than the rest of the group (p<0,0001). In the multivariate study of the influence factors on the PFS includes Clinical Gleason Score 8-10 as an independent prognostic factor (OR:2,6 IC 95%: 1,6-4,12) p=0,003, together with the clinical stage (OR:1,81 IC95%:1,18-2,78) p<0,006, the PSA(OR: 1,03 IC 95%:1,025-1,046) p<0,0001 and the side of tumor on the biopsy (OR:1,5 IC 95%:1,01-2,24) p=0,045.In the clinical Gleason score 8-10 group the influent factors on the PFS are. PSA (OR:1,02 IC 95%:1,003-1,04) and pathological stage (OR:3,84 IC95%: 1,77-8,27). Patients with a pT2 have a significantly better survival than those pT3 at 3 and 5 years (80±6%; 54±13% y 40±7%; 27±7%) (p<0,0001).The best cut point for the PSA is 11ng/ml. Patients with a PSA<11ng/ml have a 3 and 5 years survival better than those with >11ng/ml PSA (74±7%,30±22% y 40±7%, 26±7%)(p<0,0001).Conclusions: Clinical Gleason Score 8-10 is a negative independent prognostic factor on the progression free survival, but its prognosis is better if they present a PSA prior surgery lower than 11 ng/ml and the pathological stage is a pT2 (AU)

[Extracorporeal circulation and hypothermy surgery in tumors with vena cava extension: 20 years experience at the University Clinic of Navarra]. / Cirugía con circulación extracorpórea e hipotermia en tumores con extensión a vena cava: 20 años de experiencia de la clínica Universitaria de Navarra.

OBJECTIVE: We present our 20 years experience treating patients with vena cava extension in whom an extracorporeal circulation, hypothermia, cardio circulatory arrest (ECC-H-CCA) in order to perform, together with a tumoral resection, a thrombus resection. MATERIAL AND METHODS: From 1985 to 2005 a total of 28 retroperitoneal tumor were treated: 25 renal cancers, a Wilms tumor, a paratesticular rabdomiosarcoma, and a pheocromocitoma. All of them had an extension by means of thrombus above the suprahepatics veins. All of them were treated by means of ECC-H-CCA for thrombus extraction. A descriptive study of the serie is performed as well as a Kaplan Meyer survival study. RESULTS: Surgical complications were present within 10 patients (35%), with a surgical mortality of two patients (7%): one intra-operatively because a massive embolism of the lungs and the other because of a lung embolism on the 4th post-operative day. Global actuarial survival was 29.1+/-10% at three years and 17.5+/-8% at five years. Analyzing only who do not have metastatic lesions, nor lymph nodes at diagnosis their three year survival was 50.9+/-16.3% and 32.2+/-16% at five years. Mean while those who have any metastatic lesion at diagnosis their three and five years survival was 20.8+/-12% and 10.4+/-9% respectively. CONCLUSIONS: The employ of surgical techniques with ECC-H-CCA with in oncological pathology associated with vena cava thrombus is justified and its employment does not worsen the survival; it is indicated because its results, allowing a complete tumoral resection in a safe and reproducible fashion.

Cirugía con circulación extracorpórea e hipotermia en tumores con extensión a vena cava: 20 años de experiencia de la Clínica Universitaria de Navarra / Extracorporeal circulation and hypothermy surgery in tumors with vena cava extension: 20 years experience at the Univeristy Clinic of Navarra

Objetivo: Presentamos 20 años de experiencia en pacientes con tumores con extensión a vena cava en los que se realizaron circulación extracorpórea, hipotermia, parada cardiaca y exanguino transfusión (CEC-H-PC-E) para que junto con la resección tumoral se resecara el trombo tumoral en su totalidad. Material y Métodos: Entre los años 1985 y 2005 se trataron 28 tumores retroperitoneales: 25 tumores renales, un tumor de Wilms, un rabdomiosarcoma paratesticular y un feocromocitoma. Todos ellos presentaban extensión en forma de trombo en la vena cava por encima de las venas suprahepáticas. A todos se les realizó CEC-H-PC-E para la extracción del trombo tumoral. Se realiza una descripción de la serie así como un análisis de la supervivencia de Kaplan-Meier. Resultados: Se presentaron complicaciones quirúrgicas en 10 pacientes (35%), con una mortalidad quirúrgica de dos pacientes (7%): intraoperatoria por embolismo pulmonar masivo en un paciente y al 4º día postquirúrgico por embolismo pulmonar. La supervivencia actuarial global fue de 29,1±10% a tres años y 17,5±8% a cinco años. Analizando por separado aquellos que tienen que no presentan lesiones metastásica ni ganglionares en el diagnóstico su supervivencia fue a tres años del 50,9±16,3% y del 38,2±16% a cinco años. Mientras aquellos que presentan algún tipo de lesión a distancia presentaron una supervivencia a tres y cinco años de 20,8±12% y 10,4±9% respectivamente. Conclusiones: La utilización de técnicas quirúrgicas con CEC-H-PC-E en patologías tumorales que se asocian a trombo en vena cava, esta justificada y su utilización no empeora la supervivencia; está indicada por sus resultados, permitiendo una resección tumoral de una manera segura y reproductible (AU)

Objective: We present our 20 years experience treating patients with vena cava extension in whom an extracorporeal circulation, hypothermia, cardio circulatory arrest (ECC-H-CCA) in order to perform, together with a tumoral resection, a thrombus resection. Material and Methods: From 1985 to 2005 a total of 28 retroperitoneal tumor were treated: 25 renal cancers, a Wilms tumor,a paratesticular rabdomiosarcoma, and a pheocromocitoma. All of them had an extension by means of thrombus above the suprahepatics veins. All of them were treated by means of ECC-H-CCA for thrombus extraction. A descriptive study of the serieis performed as well as a Kaplan Meyer survival study. Results: Surgical complications were present within 10 patients (35%), with a surgical mortality of two patients (7%): one intraoperatively because a massive embolism of the lungs and the other because of a lung embolism on the 4th post-operative day. Global actuarial survival was 29.1±10% at three years and 17,5±8% at five years. Analyzing only who do not have metastaticlesions, nor lymph nodes at diagnosis their three year survival was 50,9±16,3% and 32,2±16% at five years. Mean while those who have any metastatic lesion at diagnosis their three and five years survival was 20,8±12% and 10,4±9% respectively. Conclusions: The employ of surgical techniques with ECC-H-CCA with in oncological pathology associated with vena cava thrombus is justified and its employment does not worsen the survival; it is indicated because its results, allowing a complete tumoral resection in a safe and reproducible fashion (AU)

Expresion del receptor de esteroides y xenobioticos (SXR) y del gen de multirresistencia drogas (MDR1) y de los polimorfismos de las enzimas GSTs, SULTs y CYP en tumores vesicales profundos, analisis de su expresion y correlación con otros factores pronósticos / Steroid and xenobiotic receptor (SXR), multidrug resistance gene (MDR1) and GSTs, SULTs and CYP polymorphism expression in invasive bladder cancer, analysis of their expression and correlation with other prognostic factors

Introducción: El receptor de esteroides y xenobióticos SXR se ha demostrado su activación por parte de numerosos medicamentos, incluidos potentes inductores del citocromo P450, como la rifampicina y el cotrimazol. La función del SXR es bien conocida, y consiste en regular de manera positiva la trascripción del citocromo P450 3A4 (CYP3A4) y el gen de multirresistencia a drogas (multidrug resistance gene) MDR1, se considera una llave clave en el mecanismo regulador del metabolismo de los xenobióticos encontrándose involucrado en todas las fases de detoxificación Múltiples enzimas involucradas en el metabolismo y la degradación de hidrocarburos policíclicos aromáticos (PAH) son polimórficas en humanos, incluyendo la glutation S-transferasa (GSTs), N-acetiltransferasa (NATs), sulfotransferas (SULTs)1A1 y el citocromo p450 (CYP)1B1. Objetivos: Los objetivos que nos hemos planteado son los siguientes: 1. Analizar la expresión del factor de trascripción SXR y del MDR1 en vejiga mediante RT-PCR en tiempo real, tanto en vejiga tumoral como vejiga normal. 2. Analizar la relación de los factores clínicos y patológicos con la expresión del SXR y del MDR1. 3. Analizar la expresión de los polimorfismos de CYP1B1, GSTM1 GSTT1 y SULT1A1, y su correlación con distintos factores clínico patológicos y moleculares. Material y Métodos: De manera prospectiva se calculó un tamaño muestral necesario para este estudio. Se incluyeron 67 pacientes de dos instituciones distintas (Hospital Universitario Miguel Servet (49 HUMS) y Clínica Universitaria de Navarra (18 CUN)), diagnosticados de cáncer vesical infiltrante y tratados mediante cistectomía radical, se le realizó la determinación de la expresión de SXR y MDR1 mediante PCR cuantitativa en tiempo real, así como de los polimorfismos CYP1B1, GSTM1 GSTT1 y SULT1A1 mediante RFLP (restricción de la longitud del fragmento del polimorfismo). Se correlaciona mediante tablas de contingencia la correlación con el resto de los factores pronósticos. Resultados: La media de seguimiento de los pacientes fue de 23,7 meses, con una mediana de 28,26 meses. De los 67 pacientes estudiados, 31 pacientes (46,3%) presentaron progresión de la enfermedad, bien en forma de recidiva local, metástasis a distancia o ambos, con un tiempo medio a recidiva de 12,4 meses, mediana de 10 meses, con un rango de 1,1 mes a 31,9 meses. 36 pacientes (53,7%) no presentaron evidencia de progresión de la enfermedad. El receptor de esteroides y xenobióticos SXR así como el gen de multirresistenia a drogas (Multidrug resistance gene (MDR1)), se expresan en vejiga normal (0,94ΔCt y 0,94ΔCt) y en vejiga tumoral de la pieza de cistectomía (1,09 ΔCt y 0,45 ΔCt). Hemos analizado su expresión de manera cuantitativa y de manera cualitativa. La expresión de SXR se correlaciona con la presencia de carcinoma in situ (p=0,024), infiltración vasculo-linfática (p=0,05) mientras que MDR1 se correlaciona con la presencia de infiltración vasculo linfática (p=0,05) A su vez ambos la presencia de ambos factores se correlaciona entre ellos (p=0,011) Los polimorfismos: CYP1B1, GSTM1, GSTT1 y SULT1A1, se expresan en vejiga pero su expresión no guarda correlación con ningún factor pronóstico Conclusiones: El SXR y el MDR1 se expresan tanto en vejiga normal y tumoral. Y que dicha expresión guarda una correlación con factores pronósticos con influencia en la supervivencia descritas en la literatura

Introduction: Steroid and Xenobiotic Receptor (SXR) has demonstrated its activation by numerous drugs, including cytochrome P450 potent inducers like rifampicina or cotrimazol. The role of SXR is well known, and lies regulating in a positive manner cytochrome P450 3A4 (CYP3A4) transcription and the multidrug resistance gene (MDR1), it’s considered a key in the xenobiotic detoxification mechanism, being involved in all phases of the detoxification process. Enzymes involved in Policyclic Aromatic hidrocarbures (PAH) metabolism and degradation are polymorphic in humans, including glutation S-transferases (GSTs), N-acetiltransferases (NATs), sulfotransferases (SULTs)1A1 and cytochrome p450 (CYP)1B1. Objectives: The objectives we’ve planned are: 1. Analyze the expression of the transcription factor SXR and MDR1 in bladder by means of RT-PCR real time, both in normal bladder and in tumoral bladder. 2. Analyze the relation between clinical and pathological factors with the expression of SXR and MDR1. 3. Analyze the expression of the polymorphims CYP1B1, GSTM1 GSTT1 and SULT1A1 and their correlation with different clinic-pathological and molecular factors. Material and Methods: In a prospective way the size of the sample was estimated. In 67 patients from two institutions (Hospital Universitario Miguel Servet (49 HUMS) and Clinica Universitaria de Navarra (18 CUN)), diagnosed of invasive bladder cancer and treated by means of radical cystectomy, were determined the expression of both SXR and MDR1 by means of real time PCR, as well as the polymorphisms CYP1B1, GSTM1 GSTT1 y SULT1A1 by means of RFLP (Restriction fragment length polymorphism). Correlations with other prognostic factors by contingency tables were performed. Results: Average follow up was 23,7 months with a median of 28,26 months. Of the 67 patients studied, 31 patients (46,3) presented disease progression, in form of local recurrence or in distant metastasis or both. With a average time to progression of 12,4 months and a median of 10 months, with a range of 1,1 month to 31,9 month. 36 patients (53,7%) did not have any evidence of disease progression during follow up. The Steroid and Xenobiotic Receptor as well as the Multidrug Resistance Gene (MDR1) are expressed in both normal bladder (0,94ΔCt y 0,94ΔCt) and tumoral bladder in the cystectomy specimen(1,09 ΔCt y 0,45 ΔCt). We’ve analyzed their expression in a quantitative manner and in a qualitative manner. The expression of SXR correlates with the presence of ca. in situ (p=0,024), vasculo-lymphatic invasion (p=0,05) mean while MDR1 correlates with presence of vasculo-lymphatic invasion (p=0,05) Both factors are correlate between each others (p=0,011). Polymorphisms: CYP1B1, GSTM1, GSTT1 and SULT1A1, are expressed in these patients but their expression doesn’t correlates with any prognostic factor Conclusions: Both SXR and MDR1 are expressed in normal bladder as well as in tumoral bladder. And their expression correlates with different prognostic factors with influence in the survival described in the literature

[Steroid and xenobiotic receptor (SXR), multidrug resistance gene (MDR1) and GSTs, SULTs and CYP polymorphism expression in invasive bladder cancer, analysis of their expression and correlation with other prognostic factors]. / Expresion del receptor de esteroides y xenobioticos (SXR) y del gen de multirresistencia drogas (MDR1) y de los polimorfismos de las enzimas Gsts, SULTs y CYP en tumores vesicales profundos, analisis de su expresion y correlación con otros factores pronósticos.

INTRODUCTION: Steroid and Xenobiotic Receptor (SXR) has demonstrated its activation by numerous drugs, including cytochrome P450 potent inducers like rifampicina or cotrimazol. The role of SXR is well known, and lies regulating in a positive manner cytochrome P450 3A4 (CYP3A4) transcription and the multidrug resistance gene (MDR1), it's considered a key in the xenobiotic detoxification mechanism, being involved in all phases of the detoxification process. Enzymes involved in Policyclic Aromatic hidrocarbures (PAH) metabolism and degradation are polymorphic in humans, including glutation S-transferases (GSTs), N-acetiltransferases (NATs), sulfotransferases (SULTs)1A1 and cytochrome p450 (CYP)1B1. OBJECTIVES: The objectives we've planned are: 1. Analyze the expression of the transcription factor SXR and MDR1 in bladder by means of RT-PCR real time, both in normal bladder and in tumoral bladder. 2. Analyze the relation between clinical and pathological factors with the expression of SXR and MDR1. 3. Analyze the expression of the polymorphims CYP1B1, GSTM1 GSTT1 and SULT1A1 and their correlation with different clinic-pathological and molecular factors. MATERIAL AND METHODS: In a prospective way the size of the sample was estimated. In 67 patients from two institutions (Hospital Universitario Miguel Servet (49 HUMS) and Clinica Universitaria de Navarra (18 CUN)), diagnosed of invasive bladder cancer and treated by means of radical cystectomy, were determined the expression of both SXR and MDR1 by means of real time PCR, as well as the polymorphisms CYP1B1, GSTM1 GSTT1 y SULT1A1 by means of RFLP (Restriction fragment length polymorphism). Correlations with other prognostic factors by contingency tables were performed. RESULTS: Average follow up was 23.7 months with a median of 28.26 months. Of the 67 patients studied, 31 patients (46.3) presented disease progression, in form of local recurrence or in distant metastasis or both. With a average time to progression of 12.4 months and a median of 10 months, with a range of 1.1 month to 31.9 month. 36 patients (53.7%) did not have any evidence of disease progression during follow up. The Steroid and Xenobiotic Receptor as well as the Multidrug Resistance Gene (MDR1) are expressed in both normal bladder (0.94DeltaCt y 0.94DeltaCt) and tumoral bladder in the cystectomy specimen (1.09 DeltaCt y 0.45 DeltaCt). We've analyzed their expression in a quantitative manner and in a qualitative manner. The expression of SXR correlates with the presence of ca. in situ (p=0.024), vasculo-lymphatic invasion (p=0.05) mean while MDR1 correlates with presence of vasculo-lymphatic invasion (p=0.05) Both factors are correlate between each others (p=0.011). Polymorphisms: CYP1B1, GSTM1, GSTT1 and SULT1A1, are expressed in these patients but their expression doesn't correlates with any prognostic factor CONCLUSIONS: Both SXR and MDR1 are expressed in normal bladder as well as in tumoral bladder. And their expression correlates with different prognostic factors with influence in the survival described in the literature.