Serum biomarkers for diagnosis and characterization of prostate cancer. / Biomarcadores plasmáticos en el diagnóstico y caracterización del cáncer de próstata.

PSA is the most widely used diagnosticand prognostic biomarker in prostate cancer (PCa).However, its lack of specificity has generated the needto search for new complementary markers. In thisscenario, blood plasma constitutes one of the sourcesof search for new markers, which have been tried tobe combined with PSA and other clinical variables inorder to develop tests that increase their diagnosticspecificity.This narrative review of the literature provides anoverview of commercially available plasma biomarkers and tests for use in different clinical settingsfor PCa. The most studied markers to help select theappropriate patients for initial and / or repeat biopsyhave been: PHI, 4K, STHLM3. These markers havebeen oriented towards the diagnosis of the so-calledclinically signifi cant PCa, trying to validate and calibratetheir algorithms in different populations. Giventhe development and evolution in the diagnosis of PCa,there is still a lack of evidence of the impact of magneticresonance imaging (MRI) when used in combinationwith these new markers, as well as its possiblerole in the screening of the disease and not only in theearly diagnosis process. Furthermore, there are only asmall number of studies that have directly comparedthese tests with each other and with PSA, so there isnot enough evidence to know which test has the bestproperties in each clinical scenario. In order to clarifythe true diagnostic role of these new biomarkers, newprospective, comparative studies in different populationsare absolutely necessary to evaluate their clinicalutility in combination with MRI and fusion biopsy.

El PSA es el biomarcador diagnóstico ypronóstico más ampliamente utilizado en cáncer deprostata (CaP). Sin embargo, su falta de especificidadha generado la necesidad de buscar nuevos marcadorescomplementarios. En este escenario, el plasmasanguíneo constituye una de las fuentes de búsquedade nuevos marcadores, los cuales han tratado decombinarse con el PSA y otras variables clínicas conel objeto de desarrollar tests que aumentaran su especificidaddiagnóstica.En esta revisión narrativa de la literatura se proporcionauna descripción general de los biomarcadoresplasmáticos y tests disponibles comercialmentepara ser utilizados en diferentes contextos clínicosdel CaP. Los test más estudiados para ayudar a seleccionarlos pacientes adecuados para la biopsia inicialy / o repetida han sido: PHI, 4K, STHLM3. Estos testse han orientado hacia el diagnóstico del denominadoCaP clínicamente significativo, intentando validary calibrar sus algoritmos en diferentes poblaciones.Dado el desarrollo y evolución en el diagnóstico deCaP, aún existe una falta de evidencia del impacto de la resonancia magnética (RM) al ser empleada encombinación con estos nuevos marcadores, así comosu posible papel en el screening de la enfermedad yno solo en el proceso de diagnóstico precoz. Además,solo se dispone de una pequeña cantidad de estudiosque hayan comparado directamente estos test entreellos y con el PSA, de modo que no existe evidenciasuficiente para saber qué test tiene mejores propiedadesen cada escenario clínico. En el escenarioactual, para poder aclarar el verdadero papel diagnósticode estos nuevos biomarcadores, son absolutamentenecesarios nuevos estudios prospectivos,comparativos y en diferentes poblaciones, que evalúensu utilidad clínica en combinación con la RM yla biopsia fusión.

Biomarcadores plasmáticos en el diagnóstico y caracterización del cáncer de próstata / Serum biomarkers for diagnosis and characterization of prostate cáncer

El PSA es el biomarcador diagnóstico y pronóstico más ampliamente utilizado en cáncer deprostata (CaP). Sin embargo, su falta de especificidadha generado la necesidad de buscar nuevos marcadores complementarios. En este escenario, el plasmasanguíneo constituye una de las fuentes de búsqueda de nuevos marcadores, los cuales han tratado decombinarse con el PSA y otras variables clínicas conel objeto de desarrollar tests que aumentaran su especificidad diagnóstica.En esta revisión narrativa de la literatura se proporciona una descripción general de los biomarcadores plasmáticos y tests disponibles comercialmentepara ser utilizados en diferentes contextos clínicosdel CaP. Los test más estudiados para ayudar a seleccionar los pacientes adecuados para la biopsia inicialy / o repetida han sido: PHI, 4K, STHLM3. Estos testse han orientado hacia el diagnóstico del denominado CaP clínicamente significativo, intentando validary calibrar sus algoritmos en diferentes poblaciones.Dado el desarrollo y evolución en el diagnóstico deCaP, aún existe una falta de evidencia del impacto de la resonancia magnética (RM) al ser empleada encombinación con estos nuevos marcadores, así comosu posible papel en el screening de la enfermedad yno solo en el proceso de diagnóstico precoz. Además,solo se dispone de una pequeña cantidad de estudiosque hayan comparado directamente estos test entreellos y con el PSA, de modo que no existe evidenciasuficiente para saber qué test tiene mejores propiedades en cada escenario clínico. En el escenarioactual, para poder aclarar el verdadero papel diagnóstico de estos nuevos biomarcadores, son absolutamente necesarios nuevos estudios prospectivos,comparativos y en diferentes poblaciones, que evalúen su utilidad clínica en combinación con la RM yla biopsia fusión. (AU)

PSA is the most widely used diagnosticand prognostic biomarker in prostate cancer (PCa).However, its lack of specificity has generated the needto search for new complementary markers. In thisscenario, blood plasma constitutes one of the sourcesof search for new markers, which have been tried tobe combined with PSA and other clinical variables inorder to develop tests that increase their diagnosticspecificity.This narrative review of the literature provides anoverview of commercially available plasma biomarkers and tests for use in different clinical settingsfor PCa. The most studied markers to help select theappropriate patients for initial and / or repeat biopsyhave been: PHI, 4K, STHLM3. These markers havebeen oriented towards the diagnosis of the so-calledclinically signifi cant PCa, trying to validate and calibrate their algorithms in different populations. Giventhe development and evolution in the diagnosis of PCa,there is still a lack of evidence of the impact of magnetic resonance imaging (MRI) when used in combination with these new markers, as well as its possiblerole in the screening of the disease and not only in theearly diagnosis process. Furthermore, there are only asmall number of studies that have directly comparedthese tests with each other and with PSA, so there isnot enough evidence to know which test has the bestproperties in each clinical scenario. In order to clarifythe true diagnostic role of these new biomarkers, newprospective, comparative studies in different populations are absolutely necessary to evaluate their clinicalutility in combination with MRI and fusion biopsy. (AU)

Does Adding Standard Systematic Biopsy to Targeted Prostate Biopsy in PI-RADS 3 to 5 Lesions Enhance the Detection of Clinically Significant Prostate Cancer? Should All Patients with PI-RADS 3 Undergo Targeted Biopsy?

INTRODUCTION: Our aim was to assess the value of adding standard biopsy to targeted biopsy in cases of suspicious multiparametric magnetic resonance imaging (mp-MRI) and also to evaluate when a biopsy of a PI-RADS 3 lesion could be avoided. METHODS: A retrospective study of patients who underwent targeted biopsy plus standard systematic biopsy between 2016-2019 was performed. All the 1.5 T magnetic resonance images were evaluated according to PI-RADSv.2. An analysis focusing on the clinical scenario, lesion location, and PI-RADS score was performed. RESULTS: A total of 483 biopsies were evaluated. The mean age was 65 years, with a PSA density of 0.12 ng/mL/cc. One-hundred and two mp-MRIs were categorized as PI-RADS-3. Standard biopsy was most helpful in detecting clinically significant prostate cancer (csPCa) in patients in the active surveillance (AS) cohort (increasing the detection rate 12.2%), and in peripheral lesions (6.5%). Adding standard biopsy showed no increase in the detection rate for csPCa in patients with PI-RADS-5 lesions. Considering targeted biopsy in patients with PI-RADS 3 lesions, a higher detection rate was shown in biopsy-naïve patients versus AS and in patients with a previous negative biopsy (p = 0.002). Furthermore, in these patients, the highest rate of csPCa detection was in anterior lesions [42.9% (p = 0.067)]. CONCLUSIONS: Our results suggest that standard biopsy could be safely omitted in patients with anterior lesions and in those with PI-RADS-5 lesions. Targeted biopsy for PI-RADS-3 lesions would be less effective in peripheral lesions with a previous negative biopsy.

New Approach to Guide Target Prostate Biopsy: Technique and Initial Experience.

OBJECTIVE: To describe the technique of transrectal biopsy with a new device that fuses multiparametric magnetic resonance (mpMRI) and ultrasound images in real time to guide target biopsies and to evaluate our initial experience. METHODS: Patients with persistent suspicion of prostate cancer despite a previous negative biopsy and who had an mpMRI before the biopsy were selected. All patients underwent target biopsy plus standard systematic biopsy. Significant prostate cancer (sig PCa) was defined according to the Epstein criteria for standard biopsy and Gleason grade of ≥7 and a positive core length of ≥5 mm for target biopsy. RESULTS: The first 40 patients were evaluated. The median age was 65 years old. In a sagittal isotropic sequence, the fusion process was started. The fusion can be improved by using different tools such as concordant points and Global Positioning System corrections tools. In the target biopsy, a median of 4 cores was taken, whereas in the standard biopsy, 12 cores were taken. Twenty-two patients were diagnosed with prostate cancer; of these patients, 17 were diagnosed with sig PCa. The fusion target biopsy diagnosed more sig PCa than the standard biopsy; however, it was not statistically significant (37.5% vs 25%, P=.08). The probability of being diagnosed with cancer increased in correlation with the Prostate Imaging Reporting and Data System score, without reaching statistical significance (k=0.45, P=.08). CONCLUSIONS: This new device is a useful tool to guide biopsy in patients with target lesions in an mpMRI to increase the detection of sig PCa. A larger cohort would be required to show significant differences.

Extracorporeal shock wave lithotripsy for distal ureteral calculi: improved efficacy using low frequency.

OBJECTIVES: To compare low versus high frequency for lithotripsy in the management of distal ureteral calculi. METHODS: A total of 154 patients with radio-opaque calculi (0.5-1 cm diameter) in the distal ureter were randomized to be given either lithotripsy at 80 or 60 pulses per min (high frequency or low frequency groups, respectively). The number of waves and sessions received, and time to total resolution were measured. A Dornier Compact Delta lithotripter was used. RESULTS: A total of 72 patients were assigned to the high frequency group and 78 to the low frequency group. Four patients were excluded from the study because of intolerance of the procedure. The size was slightly lower in low frequency group, whereby an analysis of covariance was carried out to eliminate the size factor, with the limit established as 0.7 cm. The low frequency group received 2980 ± 1211 waves, and the high frequency group received 5752 ± 3121 (P<0.001). The success rate was higher in the low frequency group (100%) than in the high frequency group (92.9%; P=0.02). If adjusted to the size of the calculus with a threshold of 0.7 cm, there was a difference, although it was not statistically significant. The time to elimination of the fragments was higher in the high frequency group (17.68 days) than in the low frequency group (7.15 days; P<0.001). The number of sessions necessary for resolution was higher in the high frequency group (1.56) than in the low frequency group (1.14; P<0.001). CONCLUSIONS: Lithotripsy at 60 pulses provides better outcomes than lithotripsy at 80 pulses for the treatment of distal ureteral calculi.

¿A qué nivel se produce la fragmentación del ADN en pacientes infértiles con varicocele? / Analysis of the site of DNA fragmentation in infertile men with varicocele

Objetivo: Establecer a qué nivel se produce la fragmentación del ácido desoxirribonucleico (FADN), intratesticular o en la vía seminal, en varones infértiles con varicocele. Material y métodos: Análisis preliminar sobre 15 sujetos en estudio por infertilidad de un año de evolución con varicocele como causa más probable de su alteración. Realizamos FADN en semen previo a la varicocelectomía quirúrgica. Durante la intervención, se obtuvo una muestra testicular mediante biopsia (TESE), para la medición de FADN en espermatozoides intratesticulares, con el objetivo de establecer sus valores y si había diferencias respecto al semen. Resultados: Quince pacientes fueron intervenidos de varicocele izquierdo. En el seminograma, la alteración más frecuente fue la oligoastenozoospermia. Presentaron ADN fragmentado en semen 9 pacientes con una media de 47,8% (rango 38,8-59,2%), y en 6 fueron normales (media 27,4%; rango 12,7-35,3%). La FADN en testículo presentó valores más elevados que en el semen, estando alterados en 14 de los 15 pacientes (media 62,3%, rango 39,0-83,3%). Conclusiones: La FADN parece tener un papel importante en la fisiopatología actual del varicocele y aumenta en el semen de varones infértiles con esta alteración. Derivado de nuestros resultados, podríamos deducir que el mecanismo más importante de fragmentación se situaría a nivel intratesticular, en contra de lo que actualmente se postula. Confirmar esta hipótesis con mayor número de casos supondría un avance significativo en el conocimiento y aplicaciones clínicas en cuanto a esta patología (AU)

Objective: To establish the site at which intratesticular or seminal DNA fragmentation (DNAF) occurs in infertile men with varicocele. Material and Methods: A preliminary analysis was performed in a 1-year study of 15 patients in whom the suspected cause of infertility was varicocele. Analysis of DNAF was performed in semen prior to surgical varicocelectomy. To measure DNAF in intratesticular sperm, testicular samples were obtained by biopsy during the intervention. Results: Fifteen patients had left varicocele surgery. The most frequent abnormality observed in the semen was oligoasthenozoospermia. Nine patients had DNAF (average: 47.8%, range: 38.8-59.2%), and six were normal (average; 27.4%, range: 12.7-35.3%). DNAF levels were higher in testicular tissue samples than in semen (average: 62.3%, range: 39.0-83.3%). Only one of these patient samples did not reveal DNAF. Conclusions: DNAF seems to be related to the physiopathology of varicocele and is present at higher levels in the semen of infertile men with this alteration. In view of these results, we deduce that DNA fragmentation will primarily occur in the testes, which is contrary to current understanding. Testing this hypothesis in studies that include more patients would allow important advances to be made in the knowledge and treatment of this alteration (AU)

Hand metastasis from renal carcinoma.

Renal carcinoma may develop metachronous distant metastases without evidence of regional or local disease recurrence. These lesions may be misdiagnosed because of its benign-like appearance and lack of evidence of other disease spread.

[New epidemiologic patterns and risk factors in renal cancer]. / Nuevos patrones epidemiológicos y factores de riesgo en cáncer renal.

Incidence of renal carcinoma, one of the most fatal solid neoplasms, has steadily increased in Western society. Moreover, these tumors are being increasingly detected in their early stages. As with most cancers, the underlying causes of the disease remain unknown. However, understanding of pathogenesis of this tumor is rapidly advancing, and will allow for new treatments for advanced disease. Understanding of the influence of easily avoidable risk factors may allow for prevention of thousands of deaths caused by renal cancer.

[Paired kidneys in transplant]. / Riñones parejos en trasplante.

OBJECTIVES: Many factors affect the graft and patient survival on the renal transplant outcome. These factors depend so much of the recipient and donor. We accomplished a study trying to circumvent factors that depend on the donor. We checked the paired kidneys originating of a same donor cadaver. PATIENTS AND METHOD: We examined the risk factors in the evolution and follow-up in 278 couples of kidney transplant. We describe their differences, significance, the graft and patient survival, their functionality in 3 and 5 years and the risk factors implicated in their function. We study immunogenic and no immunogenic variables, trying to explain the inferior results in the grafts that are established secondly. We regroup the paired kidneys in those that they did not show paired initial function within the same couple. RESULTS: The results yield a discreet deterioration in the graft and patient survival for second group establish, superior creatinina concentration, without obtaining statistical significance. The Cox regression study establishes the early rejection (inferior to three months) and DR incompatibility values like risk factors. CONCLUSIONS: This model of paired kidneys would be able to get close to best-suited form for risk factors analysis in kidney transplant from cadaver donors, if more patients examine themselves in the same way. The paired kidneys originating from the same donor do not show the same function in spite of sharing the same conditions of the donor and perioperative management.

Nuevos patrones epidemiológicos y factores de riesgo en cáncer renal / New epidemiologic patterns and risk factors in renal cancer

El carcinoma renal constituye una de las neoplasias sólidas más letales. En la sociedad occidental se ha producido un constante aumento de la incidencia de este tumor, además de un incremento en la detección de tumores en estadíos precoces. Como ocurre en la mayoría de los cánceres, las causas de la enfermedad permanecen en gran medida desconocidas. Sin embargo, el conocimiento sobre la patogenia última de este tumor avanza rápidamente, permitiendo nuevos tratamientos para la enfermedad avanzada. El conocimiento de la influencia de factores de riesgo fácilmente evitables puede permitir evitar miles de muertes causadas por el cáncer renal (AU)

Incidence of renal carcinoma, one of the most fatal solid neoplasms, has steadily increased in Western society. Moreover, these tumors are being increasingly detected in their early stages. As with most cancers, the underlying causes of the disease remain unknown. However, understanding of pathogenesis of this tumor is rapidly advancing, and will allow for new treatments for advanced disease. Understanding of the influence of easily avoidable risk factors may allow for prevention of thousands of deaths caused by renal cancer (AU)

Riñones parejos en trasplante / Paired kidneys in transplant

Objetivos: Muchos factores afectan la supervivencia del injerto y paciente en el resultado de un trasplante renal. Estos factores dependen tanto del receptor como del donante. Realizamos un estudio intentando obviar factores que dependen del donante. Revisamos los riñones parejas provenientes de un mismo donante cadáver. Pacientes y métodos: Analizamos los factores de riesgo en la evolución y seguimiento de 556 trasplantes renales que corresponden a 278 parejas de riñones. Describimos sus diferencias, su significación, la supervivencia de injerto y paciente, su funcionalidad a 3 y 5 años y los factores de riesgo implicados en su función. Se estudian variables inmunológicas y no inmunológicas intentando explicar los resultados inferiores en los injertos que se implantan en segundo lugar. Se reagrupan los riñones parejos en aquellos que no mostraron función pareja inicial dentro de la misma pareja. Resultados: Los resultados arrojan un discreto empeoramiento en la supervivencia de injerto y paciente para el grupo de segundo implante, cifras superiores de creatinina, sin obtener significación estadística. El estudio por regresión de Cox solo establece como factores de riesgo el rechazo precoz (inferior a tres meses) y la tasa de incompatibilidad DR. Conclusiones: Este modelo de riñones parejos podría acercarnos de forma más adecuada al análisis de los factores de riesgo en trasplante de donante cadáver, si más pacientes se analizan de la misma forma. Los riñones parejas provenientes del mismo donante no muestran igual función a pesar de compartir las mismas condiciones del donante y del manejo peroperatorio (AU)

Objectives: Many factors affect the graft and patient survival on the renal transplant outcome. These factors depend so much of the recipient and donor. We accomplished a study trying to circumvent factors that depend on the donor. We checked the paired kidneys originating of a same donor cadaver. Patients and method: We examined the risk factors in the evolution and follow-up in 278 couples of kidney transplant. We describe their differences, significance, the graft and patient survival, their functionality in 3 and 5 years and the risk factors implicated in their function. We study immunogenic and no immunogenic variables, trying to explain the inferior results in the grafts that are established secondly. We regroup the paired kidneys in those that they did not show paired initial function within the same couple. Results: The results yield a discreet deterioration in the graft and patient survival for second group establish, superior creatinina concentration, without obtaining statistical significance. The Cox regression study establishes the early rejection (inferior to three months) and DR incompatibility values like risk factors. Conclusions: This model of paired kidneys would be able to get close to best-suited form for risk factors analysis in kidney transplant from cadaver donors, if more patients examine themselves in the same way. The paired kidneys originating from the same donor do not show the same function in spite of sharing the same conditions of the donor and perioperative management (AU)