Carcinoma intraductal de próstata concomitante y respuesta al tratamiento hormonal en el carcinoma de próstata metastásico / Concomitant intraductal carcinoma of the prostate and response to hormonal therapy in metastatic prostate carcinoma

Introducción y objetivo: La mayoría de los cánceres de próstata (CP) se clasifican como adenocarcinoma acinar. El carcinoma intraductal de la próstata (CIDP) es una entidad histológica distinta que se cree que representa la propagación retrógrada del adenocarcinoma acinar invasivo en los conductos prostáticos y acinos.Hemos analizado el impacto del CIDP en pacientes con cáncer de próstata resistente a la castración metastásico (CPRCm) y sin tratamiento hormonal previo (hormone-naïve).Pacientes y métodosEvaluamos retrospectivamente a 118 pacientes con CPRCm con diagnóstico inicial de cáncer de prostata metastásico (CPM) desde mayo del 2010 hasta septiembre del 2018. El grupo uno incluyó 81 personas con CPM con adenocarcinoma acinar y el grupo dos estuvo compuesto por 37 pacientes con CPM con CIDP.ResultadosLa edad media de presentación fue de 76 años (IQR 73,4 a 78,7) en el grupo uno y de 74 años (68,5 a 80,6) en el grupo dos. El valor medio del PSA en el momento del diagnóstico fue de 619 ng/mL (IQR 85 a 1.113) y 868 ng/mL (IQR 186 a 1.922), respectivamente. El tiempo hasta la resistencia a la castración fue de 24,7 meses (IQR 16,7 a 32,7) en el grupo uno y 10,2 meses (IQR 4,2 a 16,2) en el grupo dos (p = 0,007). El tiempo hasta la progresión en los pacientes con cáncer de próstata resistente a la castración (CPRC) fue: 10,6 meses (IQR 5,6 a 15,6) y 6,2 meses (3,2 a 9,2), respectivamente (p = 0,05). La supervivencia global fue de 57,9 meses en el grupo uno (IC 95% 56,4 a 59,5) y de 38 meses (IC 95% 19,9 a 48,06) en el grupo dos (p = 0,001). En el análisis multivariante, el subtipo de adenocarcinoma fue estadísticamente significativo p 0,014, IC 95% (Hazard Ratio [HR] 0,058, 0,006 a 0,56).ConclusionesEl CIDP parece ser un subtipo de CP que se asocia con una respuesta más corta al tratamiento hormonal cuando se compara con el adenocarcinoma acinar en pacientes con cáncer metastásico. (AU)

Introduction and objective: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini.We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.Patients and methodsWe retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.ResultsMean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (p = 0.007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (p = 0.05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (p = 0.001). In the multivariate analysis, adenocarcinoma subtype was statistically significant p 0.014, CI 95% (HR 0.058, 0.006-0.56).ConclusionsIDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. In daily clinical practice it might be interesting to take into account that patients with IDC-P may present shorter responses to first and second line hormonal treatments. (AU)

Concomitant intraductal carcinoma of the prostate and response to hormonal therapy in metastatic prostate carcinoma.

INTRODUCTION AND OBJECTIVE: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini. We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients. PATIENTS AND METHODS: We retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P. RESULTS: Mean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (P = .007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (P = .05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (P = .001). In the multivariate analysis, adenocarcinoma subtype was statistically significant P .014, CI 95% (HR 0.058, 0.006-0.56) CONCLUSIONS: IDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. Once IDC-P is identified, clinicians could extrapolate the relative poor response to hormonal therapy. Consequently, follow-up of these patients in this scenario should be more strict.

Valor del óxido nítrico nasal en el diagnóstico de la discinesia ciliar primaria / Value of nasal nitric oxide in the diagnosis of primary ciliary dyskinesia

Objetivo: Comunicar los valores de óxido nítrico nasal (ONn) en niños con discinesia ciliar primaria (DCP) comparados con los niveles de ONn en niños sanos y en niños afectos de asma, fibrosis quística (FQ) y bronquiectasias pos infecciosas. Pacientes y métodos: Se realizó la determinación de ONn en 9 niños con DCP, 36 niños asmáticos, 31 niños con FQ, 8 niños con bronquiectasias post infecciosas y 37 niños sanos. Se compararon los valores de ONn en las diferentes patologías y se determinó la sensibilidad y la especificidad de la prueba para el diagnóstico de DCP. Resultados: Todos los niños con DCP excepto uno (ONn 348 ppb) mostraron un valor de ONn inferior a 112 ppb, siendo la media de 88 ppb (IC95% 9,6–166). En los niños sanos, la media del ONn fue de 898 ppb (IC95% 801–995), en los asmáticos 1023 ppb (IC95% 911–1137), en los niños con FQ 438 ppb (IC95% 367–508) y en los pacientes con bronquiectasias pos infecciosas de 361 ppb (IC95% 252–470). El valor medio de ONn fue significativamente inferior (p<0,05) en los niños afectos de DCP respecto a todos los demás grupos. Un punto de corte de NOn ≤112 ppb mostró una sensibilidad del 88,9% y una especificidad del 99,1% para el diagnóstico de DCP [área bajo la curva ROC 0,98 (IC95% 0,94–0,99); p<0,0001; razón de probabilidad 95,1]. Conclusiones: Un valor de ONn ≤ 112 ppb en niños es altamente sugestivo de DCP aunque un valor superior no descarta por completo la enfermedad (AU)

Objective: The aim of this study is to report nasal nitric oxide (nNO) values in children with primary ciliary dyskinesia (PCD) and to compare them with nNO values in healthy children, asthmatic children, children with cystic fibrosis and children with post infectious bronchiectasis. Patients and methods: We determined nNO values in 9 children with PCD, 36 asthmatic children, 31 children with cystic fibrosis, 8 children with post infectious bronchiectasis and 37 healthy children. We compared nNO values between these different conditions and calculated sensitivity and specificity of nNO to diagnose PCD. Results: All children with PCD - except one (nNO 348 ppb) – had nNO values below 112 ppb, mean 88 ppb (95%CI 9.6–166). The nNO mean was 898 ppb (95%CI 801-995) in healthy children, 1023 ppb (95%CI 911–1137) in asthmatic children, 438 ppb (95%CI 367–508) in cystic fibrosis children and 361 ppb (95%CI 252–470) in children with post infectious bronchiectasis. The mean concentration of nNO was lower (P<0.05) in PCD patients, compared to the other groups. The measurement of nasal NO in our study population showed, at a cut-off level of ≤112 ppb, a sensitivity of 88.9% and a specificity of 99.1% in the diagnosis of PCD [ROC 0.98 (95%CI 0.94–0.99); P<0.0001; probability ratio 95.1]. Conclusions: The measurement of nasal NO appears to be a useful tool for screening children for PCD, in which a cut-off level of ≤112 ppb suggests the disease, although nNO above 112 ppb does not exclude PCD (AU)

[Value of nasal nitric oxide in the diagnosis of primary ciliary dyskinesia]. / Valor del óxido nítrico nasal en el diagnóstico de la discinesia ciliar primaria.

OBJECTIVE: The aim of this study is to report nasal nitric oxide (nNO) values in children with primary ciliary dyskinesia (PCD) and to compare them with nNO values in healthy children, asthmatic children, children with cystic fibrosis and children with post infectious bronchiectasis. PATIENTS AND METHODS: We determined nNO values in 9 children with PCD, 36 asthmatic children, 31 children with cystic fibrosis, 8 children with post infectious bronchiectasis and 37 healthy children. We compared nNO values between these different conditions and calculated sensitivity and specificity of nNO to diagnose PCD. RESULTS: All children with PCD - except one (nNO 348 ppb) - had nNO values below 112 ppb, mean 88 ppb (95%CI 9.6-166). The nNO mean was 898 ppb (95%CI 801-995) in healthy children, 1023 ppb (95%CI 911-1137) in asthmatic children, 438 ppb (95%CI 367-508) in cystic fibrosis children and 361 ppb (95%CI 252-470) in children with post infectious bronchiectasis. The mean concentration of nNO was lower (P<0.05) in PCD patients, compared to the other groups. The measurement of nasal NO in our study population showed, at a cut-off level of < or =112 ppb, a sensitivity of 88.9% and a specificity of 99.1% in the diagnosis of PCD [ROC 0.98 (95%CI 0.94-0.99); P<0.0001; probability ratio 95.1]. CONCLUSIONS: The measurement of nasal NO appears to be a useful tool for screening children for PCD, in which a cut-off level of < or =112 ppb suggests the disease, although nNO above 112 ppb does not exclude PCD.

[Immunohistochemical expression of p53, p21, p16, and cyclin D1 in superficial bladder cancer. A tissue microarray study]. / Expresión inmunohistoquímica de p53, p21, p16 y ciclina D1 en el cáncer de vejiga superficial. Estudio en un soporte de tissue microarray.

INTRODUCTION AND OBJECTIVES: To retrospectively assess the relationship between immunohistochemical expression of p53, p21, p16, and cyclin D1, with recurrence, progression and survival in superficial bladder cancer. METHODS: 163 patients undergoing transurethral resection for superficial bladder cancer between February 1995 and March 2004. Tumor samples were included in a tissue microarray support that was serially sectioned for immunohistochemical staining. Grade and stage associations for each marker were evaluated by the Chi-square test. Assessment of the relationship with recurrence, progression, and survival Kaplan-Meier curves and log-rank test were used. RESULTS: There were no statistically significant differences in marker expression depending on tumor grade and stage, with the exception of Cyclin D1, that was significantly different depending on tumor stage (p=0.030). p21 expression was related to tumor recurrence (p=0.035), progression (p=0.008) and survival (p=0.034). p16 expression was also related to recurrence (p=0.048) and survival (p=0.047), but not to tumor progression (p=0.116). p53 and Cyclin D1 were not statistically associated with tumor recurrence, progression or survival. CONCLUSIONS: In our experience, only p16 and p21 may be useful in the management of superficial bladder tumors, as they are predictors of recurrence and survival in Ta and T1 patients.

Expresión inmunohistoquímica de p53, p21, p16 y Ciclina D1 en el cáncer de vejiga superficial. Estudio en un soporte de tissue microarray / Immunohistochemical expression of P53, P21, P16, and cyclin D1 in superficial Bladder cancer. A tissue microarray study

Introducción y objetivos: Evaluar, de forma retrospectiva, la relación entre la expresión inmunohistoquímica de p53, p21, p16 y ciclina D1, con la recurrencia, progresión tumoral y supervivencia en los carcinomas vesicales superficiales. Métodos: 163 pacientes sometidos a resección transuretral de tumor vesical superficial entre febrero de 1995 y marzo de 2004. Las muestras tumorales evaluadas estaban contenidas en un soporte de tissue microarray, al que se le realizaron varias secciones consecutivas para tinción inmunohistoquímica. La asociación del grado y estadio tumoral con los marcadores se valoró según el test de Chi-cuadrado y para valorar la relación con la recurrencia, progresión y supervivencia se utilizaron las curvas de Kaplan-Meier y se compararon con el log-rank test. Resultados: No se observaron diferencias estadísticamente significativas en la expresión de los marcadores según el grado y estadio tumoral a excepción de la Ciclina D1, que sí mostraba diferencias significativas según el estadio tumoral (p=0,030). La expresión de p21 se relacionó con la recurrencia tumoral (p=0,035), progresión (p=0,008) y supervivencia (p=0,034). La expresión de p16 también se relacionó con la recurrencia (p=0,048) y supervivencia (p=0,047), pero no con la progresión tumoral (p=0,116). La expresión de p53 y ciclina D1 no mostraron asociación estadísticamente significativa con la recurrencia y progresión tumoral ni con la supervivencia. Conclusiones: En nuestra experiencia, sólo los marcadores p16 y p21 pueden ser útiles en el manejo de los tumores vesicales superficiales por ser predictores de recurrencia y supervivencia en pacientes con estadios Ta y T1

Introduction and objectives: To retrospectively assess the relationship between immunohistochemical expression of p53, p21, p16, and cyclin D1, with recurrence, progression and survival in superficial bladder cancer. Methods: 163 patients undergoing transurethral resection for superficial bladder cancer between February 1995 and March 2004. Tumor samples were included in a tissue microarray support that was serially sectioned for immunohistochemical staining. Grade and stage associations for each marker were evaluated by the Chi-square test. Assessment of the relationship with recurrence, progression, and survival Kaplan-Meier curves and log-rank test were used. Results: There were no statistically significant differences in marker expression depending on tumor grade and stage, with the exception of Cyclin D1, that was significantly different depending on tumor stage (p=0.030). p21 expression was related to tumor recurrence (p=0.035), progression (p=0.008) and survival (p=0.034). p16 expression was also related to recurrence (p=0.048) and survival (p=0.047), but not to tumor progression (p=0.116). p53 and Cyclin D1 were not statistically associated with tumor recurrence, progression or survival. Conclusions: In our experience, only p16 and p21 may be useful in the management of superficial bladder tumors, as they are predictors of recurrence and survival in Ta and T1 patients

[Development of tissue microarray technology (TMA) for immunohistochemical study of molecular expression profiling in prostate cancer (part 1)]. / Desarrollo de un microarray tisular (TMA) para el estudio inmunohistoquímico del patrón de expresión molecular en el cáncer de próstata (parte 1).

Tissue microarray technology (TMA) is nowadays considered as a powerful tool for the high-throughput analysis of molecular expression pattern of cancer. In this manuscript we show the experience of both groups in the design and building of a TMA for the study of protein expression pattern of prostatecancer as well as a summary of the technical points to analyze the results obtained with this technology. Today, different data generated by the immunostained tissues are studied to achieve a molecular profile in different clinical scenarios.

Desarrollo de un microarray tisular (TMA) para el estudio inmunohistoquímico del patrón de expresión molecular en el cáncer de próstata (Parte 1) / Development of tissue microarray technology (TMA) for immunohistochemical study of molecular expression profiling in prostate cancer (Part 1)

El microarray tisular (TMA) es considerado hoy en día una potente herramienta para el análisis masivo del perfil molecular del cáncer. En este trabajo describimos la experiencia de ambos centros en el diseño y creación de un TMA para el estudio de la expresión molecular del cáncer de próstata así como una revisión de los diferentes aspectos técnicos necesarios para el análisis de los resultados obtenidos con esta técnica. En la actualidad, se están estudiando los datos generados por las distintas técnicas inmunohistoquímicas para la obtención de un patrón molecular en diferentes estadios clínicos

Tissue microarray technology (TMA) is nowadays considered as a powerful tool for the high-throughput analysis of molecular expression pattern of cancer. In this manuscript we show the experience of both groups in the design and building of a TMA for the study of protein expression pattern of prostate cancer as well as a summary of the technical points to analyze the results obtained with this technology. Today, different data generated by the immunostained tissues are studied to achieve a molecular profile in different clinical scenarios

[Oculopharyngeal muscular dystrophy: study of patients from seven Spanish families with different GCG expansions in PABP2 gene]. / Distrofia muscular oculofaríngea: estudio de pacientes pertenecientes a siete familias españolas con diferentes expansiones GCG en el gen PABP2.

INTRODUCTION: Autosomal dominant oculopharyngeal muscular dystrophy (OPMD), with late onset due to ptosis and/or dysphagia, is caused by short (GCG)8-13 triplet-repeat expansions in the polyadenylation binding protein 2 (PABP2) gene, which is localized in chromosome 14q11. The severity of the dominant OPMD as well as the number of expansions that cause the disease are variable. (GCG)9 is mentioned as the most frequent and the genotype/phenotype has still not been well-determined. OBJECTIVE: To describe the type of expansions (GCG)n found in Spanish families with OPMD, establishing if there is variability of them and the possible geno-phenotypical correlations. METHODS: Clinicopathological and molecular studies have been performed in 15 consecutive patients, belonging to seven Spanish families with OPMD. The muscular biopsy study under electronmicroscopy shows intranuclear inclusions (INIs) in all the examined patients (one patient per family). The genetic findings confirm the cause of the disease in all the affected members and in one clinically asymptomatic member of one recently examined family: three families (six, one and one studied members, respectively) present the (GCG)9 expansion, two families (one studied member each one) present the (GCG)10 expansion and two families (one and four studied members respectively) present the (GCG)11 expansion. In these 15 patients with a short GCG expansion causing OPMD, clinical tests for OPMD and a follow-up study of their clinical course have been carefully assessed: in patients with the (GCG)9 expansion major abnormalities appeared in extrinsic ocular mobility and more precocious presentation of limb girld (lumbopelvic preferentially) weakness leading to a great disability before the seventh decade of life under the seventies in some patients and sometimes leading to death. In patients with (GCG)10 and (GCG)11 expansions, eye movements are always preserved and the limb girld muscles weakness did not appear before the seventh decade. No correlation seems to exist between age of onset of the ptosis or dysphagia and the different (GCG)n expansions and the surgical treatment of ptosis, performed in eight patients, showed good results independently of the (GCG)n mutation. CONCLUSIONS: Although further clinical and genetic studies are necessary to establish a strict genotype/phenotype correlation in OPMD, we concluded that the (GCG)9 expansion involve more severe phenotypes than those related to the (GCG)10 or (GCG)11 expansions. Therefore, genetic testing could benefit prognosis in asymptomatic individuals.

[Histopathologic validation of the tissue-microarray technology of urothelial cancer. Our experience]. / Validación histopatológica de la tecnología tissue-microarray de cáncer de urotelio. Nuestra experiencia.

INTRODUCTION: The array technology offers: a big advance to clinic and basic investigator, it provides a variety of technics (immunohistochemistry, FISH, proteomics) to understand the molecular mechanisms of cancer. It offers scale economy in reagents versus the conventional methods. Array most be ratified because the sample is so reduced. MATERIAL AND METHODS: 52 consecutive cases have been chosen from paraffin blocks of bladder and ureteral cancer which are 5-7 years old, a tissue array has been made; disks have been arranged in lines and columns, in an aleatory way, in order to guide it's reading. It has been evaluated by a pathologist with any relation to specimen selection. RESULTS: 87 sheets ha been obtained. Number 1 has been dyed with HE. Has been discrepancy in 27% of sample's stage. Has not been a discrepancy in histopathologic diagnostic. There is no sample's representation in 11 points (17%). DISCUSSION: Our results offer good results in sample's validation. The sample's antigenicity of tissue is conserved. Array sample's represent a 97%, similarly to all unit of conventional sections of the specimen.

Validación histopatológica de la tecnología tissue-microarray de cáncer de urotelio. Nuestra experiencia / Histopatological validation of tissue-microarray technology in uroletial cancer. Our experience

INTRODUCCIÓN: La tecnología array ofrece: gran ventaja a los investigadores clínicos y básicos, facilita aplicar gran cantidad de técnicas (inmunohistoquímica, FISH, proteómica) para comprender los mecanismos moleculares del cáncer, ofrece economía de escala en los reactivos versus los procedimientos convencionales. Dado que la representación de la muestra es muy reducida, es exigible previamente validar el array. MATERIAL Y MÉTODOS: A partir de bloques de parafina de carcinomas de urotelio almacenados, cuya antigüedad oscilaba entre 5-7 años, se han seleccionado 52 casos consecutivos; se ha construido un array de tejido; los discos se colocaron en filas y columnas de manera aletoria, dibujando un topograma para guía de lectura. Se validó por otro patólogo ajeno a la selección de las muestras. RESULTADOS: Se han obtenido 87 laminillas. La número 1 se ha teñido con HE. Ha habido discrepancia en el 27% de las muestras en el estadiaje. No ha existido discrepancia en el diagnóstico histológico. En 11 puntos (17%) no hay representación de la muestra. DISCUSIÓN: Nuestros resultados ofrecen unos buenos resultados en la validación de las muestras. La antigenicidad del tejido está conservada. Las muestras seleccionadas en el array representan alrededor del 97%, similar a todo el conjunto de las secciones convencionales de la muestra problema (AU)

INTRODUCTION: The array technology offers: a big advance to clinic and basic investigator, it provides a variety of technics (immunohystochemistry, FISH, proteomics) to undestand the molecular mechanisms of cancer. It offers scale economy in reagents versus the conventional methods. Array most be ratified because the sample is so reduced. MATERIAL AND METHODS: 52 consecutive cases have been cloosen from paraffin blocks of bladder and ureteral cancer which are 5-7 years old, a tissue array has been made; disks have been arranged in lines and columns, in an aleatory way, in order to guide it’s reading. It has been evaluated by a pathologist with any relation to specimen selection. RESULTS: 87 sheets ha been obtained. Number 1 has been dyed with HE. Has been discrepancy in 27% of sample’s stage. Has not been a discrepancy in hystopathologic diagnostic. There is no sample’s representation in 11 points (17%). DISCUSSION: Our results offer good results in sample’s validation. The sample’s antigenicity of tissue is conserved. Array sample’s represent a 97%, similary to all unit of conventional sections of the specimen (AU)

[The role of the electron microscope in the study of muscular diseases]. / Papel de la microscopía electrónica en el estudio de las enfermedades musculares.

AIMS: Our study examines the most significant aspects of electron microscopy in primary and secondary myopathies from the point of view of the day-to-day activity of a general ultrastructural diagnosis laboratory. DEVELOPMENT: We review cases of neuromuscular pathologies in which electron microscopy has contributed to greater accuracy in diagnosis or the understanding of the pathogenic process, and our own data were tested against the existing literature. CONCLUSIONS: As stated in several recent papers, our experience shows that electron microscopy is still a very important tool in the field of muscular diseases and can provide crucial diagnostic data, confirm the results obtained by other techniques or help settle the physiopathological foundations of many of these disorders.

[Comparative study of the effect of complete prolonged neoadjuvant hormonal blockade versus standard hormonal blockade]. / Estudio comparativo del efecto del bloqueo hormonal completo neoadyuvante prolongado frente al estándar.

INTRODUCTION: Radical prostatectomy is considered as a curative treatment option in clinically localised prostate cancer patients. Therapy failure is related to positive surgical margins and/or extracapsular extension. The use of neoadjuvant combined androgen blockade (CAB) withdrawal therapy, mainly in cT2 disease, has been shown to decrease positive margin rates. However, CAB therapy remains controversial since there is no proof that this approach confers any benefit in relation to biochemical and clinical disease-free survival. Increasing negatives surgical margins and lower tumour volume (TV) with prolonged CAB therapy has been recently reported. AIM: To analyse the effect of 6 months neoadjuvant CAB therapy in front of 3 months in clinically localised prostate cancer patients submitted to radical prostatectomy. PATIENTS AND METHODS: The pathological stage and TV in forty-two patients treated by 6 months in front of thirty-four patients treated by 3 months were studied. The relationship of clinical stage and initial PSA concentration were analysed. RESULTS: TV was significantly lower in 6 months treated patients (0.97 cc vs. 0.48 cc, p = 0.05). The lowest TV was observed in cT1 patients, but significant differences only were observed in cT2 (1.5 cc vs. 0.86 cc, p = 0.04). No relationship between TV and PSA was obtained. No differences in the incidence of organ-confined disease were seen depending of the CAB length (47% vs. 43%, p = NS). However, increasing incidence of specimen-confined disease was observed in 6 months treated patients (56% vs. 74%, p = 0.05). CONCLUSION: The duration of neoadjuvant CAB can affect both TV and surgical margin status. Lower TV and increasing incidence of specimen-confined disease with 6 months CAB treatment were observed. Patients with palpable disease may be more benefited by this treatment option.

Papel de la microscopía electrónica en el estudio de las enfermedades musculares / The role of the electron microscope in the study of muscular disease

Objetivo. Se estudian los aspectos más significativos de la microscopía electrónica de las miopatías primarias y secundarias, desde el punto de vista de la actividad cotidiana de un laboratorio general de diagnóstico ultraestructural. Desarrollo. Se revisan los casos de patología neuromuscular en los que la microscopía electrónica ha podido contribuir a una mejor precisión diagnóstica o comprensión patogénica y se contrastan nuestros datos con la bibliografía existente. Conclusiones. Tal como señalan diversos artículos aparecidos recientemente, nuestra experiencia pone de manifiesto que la microscopía electrónica es todavía una herramienta muy necesaria en el campo de las enfermedades musculares y puede aportar datos diagnósticos decisivos, confirmar los resultados de otras técnicas o contribuir a aclarar las bases fisiopatológicas de muchas de estas afecciones (AU)

Aims. Our study examines the most significant aspects of electron microscopy in primary and secondary myopathies from the point of view of the day-to-day activity of a general ultrastructural diagnosis laboratory. Development. We review cases of neuromuscular pathologies in which electron microscopy has contributed to greater accuracy in diagnosis or the understanding of the pathogenic process, and our own data were tested against the existing literature. Conclusions. As stated in several recent papers, our experience shows that electron microscopy is still a very important tool in the field of muscular diseases and can provide crucial diagnostic data, confirm the results obtained by other techniques or help settle the physiopathological foundations of many of these disorders (AU)

Estudio comparativo del efecto del bloqueo hormonal completo neoadyuvante prolongado frente al estándar / The effect of long-term neoadjuvant combined androgen blockade withdrawal therapy. Comparative study with standard therapy

INTRODUCCIÓN: La prostatectomía radical es considerado un tratamiento curativo del cáncer de próstata clínicamente localizado. El fallo quirúrgico potencial viene dado por la positividad de los márgenes y/o por la extensión extracapsular. Ha sido comunicada una reducción en la incidencia de márgenes quirúrgicos positivos, especialmente en estadios clínicos T2, con el empleo del bloqueo hormonal completo neoadyuvante1. Sin embargo, el bloqueo previo a la cirugía sigue siendo un tratamiento controvertido dado que no ha sido demostrado ningún beneficio en relación con el intervalo libre de progresión ni supervivencia. Recientemente, ha sido comunicada una mayor incidencia de márgenes libres y reducción del volumen tumoral en las piezas de prostatectomía sometidas a bloqueo más prolongado que el estándar de 3 meses. OBJETIVO: Analizar el efecto del bloqueo hormonal neoadyuvante durante 6 meses frente al estándar de 3 meses en pacientes con cáncer de próstata clínicamente localizado y sometidos a prostatectomía radical. PACIENTES Y MÉTODOS: Se estudia el volumen tumoral y el estadio patológico en 42 pacientes sometidos a 6 meses de bloqueo frente a 34 pacientes sometidos a bloqueo estándar de 3 meses. Se analiza la relación existente con el estadio clínico y con la concentración de PSA. RESULTADOS: El volumen tumoral fue significativamente menor en el grupo de pacientes tratado durante 6 meses (0,976 cc vs 0,48 cc, p = 0,05). En función del estadio clínico el menor volumen se observó en los pacientes T1 pero la diferencia fue sólo significativa en los T2 (1,5 cc vs 0,86 cc, p = 0,04). No se observó relación entre el volumen tumoral y la concentración de PSA. Al analizar el estadio patológico, no existieron diferencias en función del tiempo de bloqueo en la incidencia de tumor no confinado (47 por ciento vs 43 por ciento, p N.S.). Sin embargo, se observó un incremento en la incidencia de tumor confinado al espécimen en el grupo sometido a 6 meses de bloqueo (56 por ciento vs 73,7 por ciento, p = 0,05). CONCLUSIÓN: La duración del bloqueo neoadyuvante puede afectar tanto al volumen tumoral como al estado de los márgenes quirúrgicos. Se observa menor volumen tumoral e incremento en la incidencia de tumor confinado al espécimen con un tratamiento más prolongado que el considerado estándar. Los pacientes con tumores palpables parecen beneficiarse en mayor medida de esta modalidad de bloqueo (AU)

A longer duration of neo-adjuvant combined androgen blockade prior to radical prostatectomy may lead to lower tumour volume of localised prostate cancer.

OBJECTIVES: To analyse tumour volume (TV) in clinically localised prostate cancer patients treated with neo-adjuvant combined androgen blockade (CAB) therapy prior to radical prostatectomy. PATIENTS AND METHODS: Two hundred consecutive patients treated between 1996 and 2000 were retrospectively analysed. Fifty patients underwent radical prostatectomy alone and 45 were treated with CAB for 1-3 months, 83 for 4-6 months and 22 for more than 6 months before surgery. Logistic regression analysis was performed to identify the strongest independent prognosticator of organ-confined disease. RESULTS: No evidence of residual cancer was found in 11 specimens (5.6%). Regarding TV, 20 specimens showed less than 0.1cc, 33 between 0.1 and 0.49cc and 86 more than 0.5cc. Smaller TV was found in CAB-treated patients. Significant correlation was observed between treatment duration and TV. In logistic regression analysis, only CAB duration and TV were significantly correlated with organ-confined disease. CONCLUSIONS: Prominent regressive features and lower TV were found after neo-adjuvant CAB. It seems that more prolonged treatment may lead to greater tumoural regression. Only tumour burden and length of CAB therapy were independent variables significantly correlated with pathologically localised prostate cancer.

[Nephrectomy of a giant hypernephroma (5,150 g)]. / Nefrectomía de un hipernefroma gigante (5.150 g).

We report a giant renal adenocarcinoma (5150 g weight) excised in a 52 years old male. He presented a severe clinical symptoms: serious haematuria, fever (40 degrees C), left flank pain, abdominal discomfort and weight loss (10 kg). The patient underwent left renal artery embolization because of severe anemia (blood transfusion: 4 uu) but haematuria didn't decrease; that's why radical surgery was advised. Until our knowledge this case is the largest removed kidney adenocarcinoma published in the world literature (Medline 1966-2001).

Nefrectomía de un hipernefroma gigante (5.150 G) / Nephrectomy of a giant renal adenocarcinoma (5.150 g)

Presentamos un adenocarcinoma renal gigante (5150 g) extirpado a un paciente varón de 52 años. Se presentó con una severa clínica: hematurias abundantes, fiebre (40º), lumbalgia izquierda, molestias abdominales y pérdida de peso (10 kg).El paciente fue sometido a embolización de arteria renal debido a anemia por hemorragia (se transfundieron 4uu) pero, al no ceder la hematuria, se indicó la cirugía radical. En la revisión bibliográfica (Medline 1966-2001) no hemos encontrado publicado ningún carcinoma renal extirpado de este peso, por lo que este caso podría tratarse del más voluminoso publicado hasta la fecha (AU)

[Association between heroin consumption in pregnancy and structural abnormalities of the respiratory cilia in newborn infants]. / Asociación entre el consumo de heroína durante la gestación y anomalías estructurales de los cilios respiratorios en el período neonatal.

OBJECTIVE: To describe structural abnormalities of the respiratory cilia in newborn infants whose mothers consumed heroin during pregnancy. PATIENTS AND METHODS: The medical records of 295 newborn infants whose mothers consumed heroin either throughout or at some time during pregnancy and who were cared for in Hospital del Mar in Barcelona (Spain) between January 1982 and December 1997 were reviewed. Seven infants with neonatal respiratory distress after the withdrawal syndrome period were selected. Diagnoses were established by electron microscopy of nasal mucosa samples. RESULTS: All seven newborns with prolonged neonatal respiratory distress had ultrastructural abnormalities of the ciliary axoneme similar to those of primary ciliary dyskinesia or immotile cilia syndrome. The incidence of this alteration in this series was higher than that in the general population. CONCLUSIONS: These data suggest a possible association between ultrastructural abnormalities of the ciliary axoneme and prolonged neonatal respiratory distress in the infants of heroin-consuming mothers.

Intercellular junctions, apical differentiation, and infiltrative features in colon cancer: an ultrastructural study. The Colon Cancer Team at IMAS.

Changes in the structure and number of cell junctions have been related to the infiltrative and metastatic potential of tumor cells. Apparently, the loss of cell adhesion should be coordinated with significant changes in the apical and basal cell domains. The authors have performed a sequential ultrastructural study of cells in the superficial, middle, and deep regions of well- and moderately differentiated colon adenocarcinomas. This was to investigate the differences in the organization of different membrane domains among tumor cells in the in situ areas, the advancing, infiltrative edge of the tumors, and the infiltrating zones between these two extreme zones. The results of the study suggest that the organization of these domains is not strictly coordinated, and that, for each infiltration level, both a settling and an infiltrating cell population can be found. These findings could explain the fact that apparently well-differentiated tumors are able to seed distant tissues with individual cells, rather than with well-differentiated glandular aggregates that would hardly be able to reach the vessel lumina without significantly modifying their organization.