Adhesion molecules alpha, beta and gamma-catenin as prognostic factors of tumour progression in upper urinary tract urothelial tumours: the role of AKT-P/GSK-3beta/beta-catenin pathway.

OBJECTIVES To evaluate alpha, beta and gamma-catenin expression in upper urinary tract urothelial tumours (UUTC) and determine their value as prognostic factors; to investigate the correlation between the catenin complex and the AKT pathway. PATIENTS AND METHODS We retrospectively analysed 114 consecutive patients treated at our institution from 1990 to 2004; the mean follow-up was 54 months. Tumour samples were available from 70 patients, and included in tissue microarrays for immunohistochemical analysis. The antibodies used were anti-alpha, -beta and gamma-catenin, and antiphospho-AKT. The prognostic value of the expression of these molecules was analysed using tumour progression and cancer-specific survival as end-points. RESULTS Of the 114 patients, 27% developed tumour progression; the cancer-specific and overall survival were 77% and 60.6%, respectively. Abnormal alpha, beta and gamma-catenin expression was found in 44 (63%), 22 (31%) and 28 (41%) patients, respectively; the abnormal catenin expression patterns correlated with each other. Positive cytoplasm phospho-AKT expression was found in 27 (39%) patients. Three of them were found to have cytoplasmic beta-catenin accumulation and none of them nuclear expression. beta-catenin expression was the only one that was an independent marker of tumour progression, with a hazard ratio (95% confidence interval) of 3.1(1.2-8.6), together with grade (7.1, 1.2-55.8) and stage (4.6, 2.1-10). In the cancer-specific survival analysis, again beta-catenin was an independent prognostic factor (3.4, 1-11.5) together with stage (4.6, 2.2-9.8). CONCLUSIONS The loss of the normal membrane beta-catenin expression constitutes an independent factor of tumour progression and cancer-specific survival. Our data suggest that the AKT/GSK3beta/beta-catenin signalling pathway is not activated in the UUTC carcinogenesis.

[Experience with third, fourth and fifth kidney transplants and their complications.] / Experiencia en terceros, cuartos y quintos trasplantes renales y sus complicaciones.

OBJECTIVES: Kidney transplant may be a good choice to treat chronic renal failure even in patients with two or more previous renal grafts. However, there might be several surgical complications and other difficulties we have to deal with. The aim of this report is to analyze the third, fourth and fifth transplants performed in our center focusing on the surgical complications and graft and patient survivals. METHODS: We performed a retrospective analysis of the 73 third, fourth and fifth kidney transplants performed in our center between February 1975 and December 2015. Statistical analysis has been performed with IBM SPSS 23.0 software. RESULTS: 62 patients received a third graft, 10 received a fourth one and one patient received a fifth graft. The median age of the recipients was 48 years, while for donors it was 50. Median cold ischemia time was 21 hours. Transplantectomy was not necessary in 49.31% of the cases. In 59.7% of the cases the graft vessels were anastomosed to the external iliac vessels. There were 21 cases of relevant postoperative complications (27.4% of the total grafts). Vascular thrombosis appeared in 5.5%. After 49 months of follow-up, the 1-, 3-, and 5-year graft survival were 64.3%, 56.16% and 50.69%, respectively. CONCLUSIONS: A new renal transplant in patients with two or more previous grafts is feasible, being necessary to individualize the cases. In spite of being more complex operations than previous transplants with a higher complication rate, we can obtain both acceptable graft and patient survival outcomes with an appropriate approach.

Carcinosarcoma of the prostate: two cases with distinctive morphologic and immunohistochemical findings.

Carcinosarcomas (CS) of the prostate are very uncommon neoplasms defined by the admixture of malignant epithelial and mesenchymal components. We describe here two new examples of CS in two patients aged 66 and 77 years, the first without previous history of prostate adenocarcinoma and the second with a 5-year history of acinar type prostate adenocarcinoma. The diagnosis of CS was made on the cystoprostatectomy specimen in the first case and transurethral resection in the second case. Both biphasic tumours exhibited papillary areas of ductal differentiation and conventional adenocarcinoma in the epithelial component, as well as malignant fibrous histiocytoma and angiosarcomatous areas in the first case and solid, poorly differentiated epithelial areas with neuroendocrine features in the second case. Immunohistochemistry revealed over-expression of c-erb B2 in the papillary epithelial component of both cases, whereas the solid undifferentiated epithelial areas in the second patient expressed c-kit, CD10 and synaptophysin, thus conforming a very undifferentiated cell population. The angiosarcomatous component of the first case expressed CD31 and CD10. The clinical course of the cases was divergent; the first patient is free of disease after radical surgery and adjuvant therapy and the other died 5 months after the diagnosis of CS, having already developed liver metastases.

Complexed prostate-specific antigen for the detection of prostate cancer.

BACKGROUND: The description of a new method for the measurement of complexed prostate-specific antigen (cPSA) offers a new approach to the diagnosis of prostate cancer. PATIENTS AND METHODS: We measured PSA (Hybritech and Bayer), free PSA (Hybritech) and complexed PSA (Bayer) in 72 patients with prostate cancer and 128 with benign prostate hyperplasia. RESULTS AND CONCLUSION: We found an increase of sensitivity using 25 and 7 ng/mL as cut-offs for cPSA in relation to total PSA using as cut-offs 4 and 10 ng/mL (96 and 36% vs. 92 and 35.5%). Similar differences were found for specificity (78% and 31% for cPSA vs. 73% and 29% for total PSA). Therefore, we defined a gray zone for patients with cPSA between 2.5 and 7 ng/mL for which the measurement of the free/complexed PSA ratio saves an important number of negative biopsies maintaining a higher sensitivity.

[Usefulness of PSA and its fractions in the diagnosis of prostate cancer]. / Antígeno prostático específico y sus fracciones en el diagnóstico del cáncer de próstata.

BACKGROUND AND OBJECTIVE: The description of different forms of PSA has opened a new strategy in the diagnosis of prostate cancer. The measurement of the ratio between free PSA and PSA in the group of patients with a PSA level between 4 and 10 ng/ml decreases the number of negative biopsies. The aim of our study was to compare the diagnostic efficacy of PSA and PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between Pca and benign prostate hyperplasia (BPH). PATIENTS AND METHOD: We measured the serum levels of PSA, free PSA and cPSA in 56 patients with Pca and 94 patients with BPH. RESULTS: ROC curves were used for the comparison of tests. The biggest area under the curve (AUC) was observed for the ratios fPSA/cPSA and fPSA/PSA (0.718 and 0.712, respectively). When we compared the AUC between PSA and cPSA, then AUC for cPSA was higher than AUC for PSA (0.602 and 0.567, respectively). We observed similar results in the group of patients with PSA levels between 4 and 10 ng/ml. CONCLUSIONS: The diagnostic accuracy of cPSA is higher than that of PSA. Moreover, in the differential diagnosis between prostate cancer and BPH, the use of PSA ratios (fPSA/cPSA or fPSA/PSA) increases the diagnostic accuracy obtained with the measurement of PSA or cPSA.

HER-2/AKT expression in upper urinary tract urothelial carcinoma: prognostic implications.

AIM: To assess HER-2 and p-AKT expression in upper urinary tract urothelial carcinoma (UTUC) in order to determine their value as prognostic factors of tumour progression and cancer-specific survival. PATIENTS AND METHODS: One hundred consecutive UTUC patients were retrospectively included, between 1990-2004, in 4 tissue microarrays for immunostaining. Median follow-up: 33.03 months. RESULTS: Positive HER-2 expression was found in 10 cases and cytoplasmic p-AKT expression in 84 cases; the expression intensity was strong: 30 cases, moderate: 28 and weak: 26. Nuclear p-AKT expression was found in 6 patients: 1 with strong, and 5 with moderate intensity. Nuclear p-AKT expression was an independent factor for tumour progression (HR=4.145, p=0.013), together with grade (HR=4.557, p=0.009) and stage (HR=2.085, p=0.003). In cancer-specific survival analysis, nuclear p-AKT expression (HR=4.268, p=0.017), together with grade (HR=5.214, p=0.035) and stage (HR=2.666, p=0.002) were identified as independent prognostic factors. CONCLUSION: Nuclear p-AKT expression together with stage and grade constitute independent prognostic factors for tumour progression and cancer-specific survival.

Experiencia en terceros, cuartos y quintos trasplantes renales y sus complicaciones / Experience with third, fourth and fifth kidney transplants and their complications

Objetivos: El trasplante renal puede ser una buena opción terapéutica en la insuficiencia renal terminal, incluso en los pacientes con dos o más injertos previos. Sin embargo, pueden existir una serie de dificultades y complicaciones quirúrgicas a las cuales el equipo de trasplante debe enfrentarse. El objetivo de este artículo es revisar los terceros, cuartos y quintos trasplantes realizados en el Hospital Universitario Marqués de Valdecilla (HUMV) analizando las dificultades quirúrgicas, sus complicaciones y la supervivencia de injertos y pacientes. Método: Revisión retrospectiva desde Febrero de 1975 hasta Diciembre de 2015 que incluye 73 trasplantes (3º,4º y 5º) realizados en el HUMV. El estudio estadístico ha sido realizado con el programa informático IBM SPSS versión 23.0. Resultados: 62 pacientes han recibido un tercer trasplante, 10 de ellos posteriormente han recibido un cuarto y 1 única paciente ha recibido un quinto. La mediana de edad de los receptores fue 48 años y la de los donantes 50. La mediana de isquemia fría fue de 21 horas. No fue necesaria la trasplantectomía de los injertos previos en un 49,31 % de los casos. En un 59,7% de los casos se pudieron anastomosar los vasos del injerto a los vasos iliacos externos del receptor. Se registraron un 27,4% de complicaciones postquirúrgicas relevantes, con un 5,5% de trombosis en los vasos de los injertos. Tras una mediana de seguimiento global de 49 meses la supervivencia del injerto a 1, 3 y 5 años fue del 64,3%, 56,16% y 50,69% respectivamente. Conclusión: A pesar de ser necesario individualizar los casos, un nuevo trasplante en pacientes con dos o más injertos renales previos, sigue siendo una opción terapéutica a considerar. Aunque pueden ser cirugías complejas y de alto riesgo de complicaciones, con un manejo óptimo y cirujanos expertos se pueden obtener cifras de supervivencia de injerto aceptables (AU)

Objectives: Kidney transplant may be a good choice to treat chronic renal failure even in patients with two or more previous renal grafts. However, there might be several surgical complications and other difficulties we have to deal with. The aim of this report is to analyze the third, fourth and fifth transplants performed in our center focusing on the surgical complications and graft and patient survivals. Methods: We performed a retrospective analysis of the 73 third, fourth and fifth kidney transplants performed in our center between February 1975 and December 2015. Statistical analysis has been performed with IBM SPSS 23.0 software. Results: 62 patients received a third graft, 10 received a fourth one and one patient received a fifth graft. The median age of the recipients was 48 years, while for donors it was 50. Median cold ischemia time was 21 hours. Transplantectomy was not necessary in 49.31% of the cases. In 59.7% of the cases the graft vessels were anastomosed to the external iliac vessels. There were 21 cases of relevant postoperative complications (27.4% of the total grafts). Vascular thrombosis appea-red in 5.5%. After 49 months of follow-up, the 1-, 3-, and 5-year graft survival were 64.3%, 56.16% and 50.69%, respectively. Conclusions: A new renal transplant in patients with two or more previous grafts is feasible, being necessary to individualize the cases. In spite of being more complex operations than previous transplants with a higher complication rate, we can obtain both acceptable graft and patient survival outcomes with an appropriate approach (AU)

Comparison of several combinations of free, complexed, and total PSA in the diagnosis of prostate cancer in patients with urologic symptoms.

OBJECTIVES: To compare the diagnostic efficacy of prostate-specific antigen (PSA) and the PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between prostate cancer and benign prostatic hyperplasia. METHODS: We measured the serum levels of total PSA (tPSA; Hybritech and Bayer), fPSA (Hybritech), and cPSA (Bayer) in 72 patients with prostate cancer and 128 patients with benign prostatic hyperplasia. RESULTS: Receiver operating characteristic curves were used for comparison of these tests. The greatest area under the curve was observed for the fPSA/cPSA ratio and the fPSA/tPSA ratio (0.757 and 0.754, respectively). The substitution of the fPSA/tPSA ratio with the fPSA/cPSA ratio in the diagnostic scheme of prostate cancer improved the diagnostic accuracy, with similar sensitivity and an increment in specificity (41% versus 45%). CONCLUSIONS: The fPSA/cPSA ratio ensures a reduction in negative biopsies in the PSA gray zone. We suggest substituting the fPSA/tPSA ratio with the fPSA/cPSA ratio for patients with a PSA level between 4 and 10 ng/mL.

Antígeno prostático específico y sus fracciones en el diagnóstico del cáncer de próstata / Usefulness of PSA and its fractions in the diagnosis of prostate cancer

FUNDAMENTO Y OBJETIVO: La descripción de distintas formas circulantes de antígeno prostático específico (PSA) ha abierto una nueva estrategia en el diagnóstico del cáncer de próstata. La determinación del índice entre PSA libre y PSA total en el grupo de pacientes con valores de éste último entre 4 y 10 ng/ml ha disminuido el número de biopsias negativas. El objetivo de nuestro estudio ha sido comparar la eficacia diagnóstica del PSA y sus fracciones (PSA libre y PSA ligado a las proteínas inhibidoras de las proteasas o PSAc) en el diagnóstico diferencial entre cáncer de próstata e hiperplasia benigna de próstata. PACIENTES Y MÉTODO: Hemos dosificado la concentración de PSA total, PSA libre y PSAc en 56 pacientes con cáncer de próstata y 94 pacientes con hiperplasia benigna de próstata. RESULTADOS: Se han empleado curvas ROC para realizar la comparación de estos tests. Las mayores áreas bajo la curva se obtuvieron para los índices entre PSA libre y PSAc y entre PSA libre y PSA total (0,718 y 0,712, respectivamente). El área bajo la curva del PSAc fue mayor que la del PSA total (0,602 y 0,567, respectivamente). Los resultados hallados en el subgrupo de pacientes con valores de PSA total entre 4 y 10 ng/ml fueron semejantes a los del grupo total. CONCLUSIONES: La eficacia diagnóstica del PSAc es mayor que la del PSA total. En el diagnóstico diferencial entre cáncer de próstata e hiperplasia benigna de próstata el uso de los índices de PSA aumenta la eficacia diagnóstica obtenida con la dosificación de PSA total o PSAc (AU)