Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and a Profile of Dysregulated microRNAs.

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.

Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is the third most common urologic malignancy. First symptoms are usually unspecific and belated causing the stages to be high when diagnosed. As compensation, incidental detection of RCC by abdominal imaging techniques for other medical purposes is a reality that favours a decrease in the stage of new diagnosed tumours. Therefore, identifying novel predictive biomarkers for diagnosis, progression and prognosis of RCC is fundamental. RECENT FINDINGS: To date, several studies have demonstrated that microRNAs (miRNAs) play a role in the particular scenario of urologic tumors, and alterations at miRNA level are involved in the initiation, progression and metastases formation of renal cancer. In the present review, we have summarized the up­to­date preliminary clinical works on the role of urinary miRNA profiling in RCC, including an evaluation of its value as a potential biomarker for diagnosis, prognosis and follow up of RCC patients.

[Sentinel lymph node selective biopsy in prostate cancer.] / Ganglio centinela en cáncer de próstata.

OBJECTIVE: To validate the sentinel lymph node selective biopsy (SLNSB) in the staging of Prostate Cancer with Briganti Index > 5 by comparison with extended lymphadenectomy (ePLND) in a prospective longitudinal study. METHODS: SLNSB has been performed in 84 patients, the first 70 by injection of nanocoloids marked with Tc99m and preoperative SPECT-CT, and in the last 14 with mixed radiotracer (99mTc + ICG). After laparoscop ic removal of sentinel nodes all patients underwent an ePLND. RESULTS: SPECT-CT showed radiotracer deposits outside the territory of the ePLND in 76% of patients and laparoscopic gamma probe in 57%. The median number of sentinel nodes removed was 5.2 with a total average number of lymph nodes removed of 22. In all cases with metastatic nodes (28% in the series) there was at least one positive sentinel node but metastatic sentinel nodes outside of the territory of the ePLND were found in 6/24 patients (25%). The sensitivity, specificity, PPV and NPV of 99mTc were 100%, 96.07%, 90.47% and 100%, respectively. In 5 out of 14 patients with mixed radiotracer, lymph node involvement was detected. In all of them there was at least one sentinel node affected with 99mTc, and only 3 showed fluorescence with 100% sensitivity and 100% NPV for 99mTc and 60% sensitivity and 77.77% NPV for ICG. CONCLUSION: The SLNSB with 99mTc has a high sensitivity and a VPN of 100%, increasing the identification of lymphatic metastases outside the territory of the ePLND. Fluorescence can facilitate the visualization of the sentinel nodes when they have been previously located by the SPECT-CT, although the sensitivity and the NPV of the ICG are lower than that of the 99mTc.

OBJETIVO: Validar la biopsia selectiva de ganglio centinela (BSGC) en la estadificación del Cáncer de Próstata con Indice de Briganti > 5 mediante comparación con la linfadenectomía extendida (LFDe) en un estudio prospectivo longitudinal.MÉTODOS: Se ha realizado BSGC a 84 pacientes, los 70 primeros mediante inyección de nanocoloides marcados con Tc99m y SPECT-TC preoperatoria, y en los 14 últimos con radiotrazador mixto (Tc99m + ICG). A todos los pacientes tras la extracción laparoscópica de los ganglios centinelas se les realizó una LFDe. RESULTADOS: La SPECT-TC mostró depósitos del radiotrazador fuera del territorio de la LFDe en el 76% de los pacientes y la gammasonda laparoscópica en el 57%.La media de ganglios centinelas extraídos fue 5,2 con una media total de ganglios linfáticos extraídos de 22. En todos los casos con ganglios metastáticos (28% de la serie) hubo, al menos, un ganglio centinela positivo, encontrando ganglios centinela metastásicos fuera del territorio de la LFDe en 6/24 pacientes (25%). La sensibilidad, especificidad, VPP y VPN del Tc99m fue del 100%, 96,07%, 90,47% y 100%, respectivamente. En 5 de los 14 pacientes con radiotrazador mixto se detectó afectación ganglionar. En todos ellos hubo como mínimo un ganglio centinela afecto con Tc99m y sólo 3 mostraron fluorescencia, con sensibilidad del 100% y VPN del 100% para el Tc99m y sensibilidad del 60% y VPN del 77,77% para el ICG.CONCLUSIÓN: La BSGC con Tc99m tiene una alta sensibilidad y un VPN del 100%, aumentando la identificación de metástasis linfáticas fuera del territorio de la LFDe. La fluorescencia puede facilitar la visualización de los centinelas cuando se tiene una localización previa de los mismos con el SPECT-TAC, aunque la sensibilidad y el VPN del ICG es inferior al del Tc99m.

Ganglio centinela en cáncer de próstata / Sentinel lymph node selective biopsy in prostate cancer

Objetivo: Validar la biopsia selectiva de ganglio centinela (BSGC) en la estadificación del Cáncer de Próstata con Indice de Briganti > 5 mediante comparación con la linfadenectomía extendida (LFDe) en un estudio prospectivo longitudinal. Métodos: Se ha realizado BSGC a 84 pacientes, los 70 primeros mediante inyección de nanocoloides marcados con Tc99m y SPECT-TC preoperatoria, y en los 14 últimos con radiotrazador mixto (Tc99m + ICG). A todos los pacientes tras la extracción laparoscópica de los ganglios centinelas se les realizó una LFDe. Resultados: La SPECT-TC mostró depósitos del radiotrazador fuera del territorio de la LFDe en el 76% de los pacientes y la gammasonda laparoscópica en el 57%.La media de ganglios centinelas extraídos fue 5,2 con una media total de ganglios linfáticos extraídos de 22. En todos los casos con ganglios metastáticos (28% de la serie) hubo, al menos, un ganglio centinela positivo, encontrando ganglios centinela metastásicos fuera del territorio de la LFDe en 6/24 pacientes (25%). La sensibilidad, especificidad, VPP y VPN del Tc99m fue del 100%, 96,07%, 90,47% y 100%, respectivamente. En 5 de los 14 pacientes con radiotrazador mixto se detectó afectación ganglionar. En todos ellos hubo como mínimo un ganglio centinela afecto con Tc99m y sólo 3 mostraron fluorescencia, con sensibilidad del 100% y VPN del 100% para el Tc99m y sensibilidad del 60% y VPN del 77,77% para el ICG. Conclusión: La BSGC con Tc99m tiene una alta sensibilidad y un VPN del 100%, aumentando la identificación de metástasis linfáticas fuera del territorio de la LFDe. La fluorescencia puede facilitar la visualización de los centinelas cuando se tiene una localización previa de los mismos con el SPECT-TAC, aunque la sensibilidad y el VPN del ICG es inferior al del Tc99m

Objective: To validate the sentinel lymph node selective biopsy (SLNSB) in the staging of Prostate Cancer with Briganti Index > 5 by comparison with extended lymphadenectomy (ePLND) in a prospective longitudinal study. Methods: SLNSB has been performed in 84 patients, the first 70 by injection of nanocoloids marked with Tc99m and preoperative SPECT-CT, and in the last 14 with mixed radiotracer (99mTc + ICG). After laparoscop ic removal of sentinel nodes all patients underwent an ePLND. Results: SPECT-CT showed radiotracer deposits outside the territory of the ePLND in 76% of patients and laparoscopic gamma probe in 57%. The median number of sentinel nodes removed was 5.2 with a total average number of lymph nodes removed of 22. In all cases with metastatic nodes (28% in the series) there was at least one positive sentinel node but metastatic sentinel nodes outside of the territory of the ePLND were found in 6/24 patients (25%). The sensitivity, specificity, PPV and NPV of 99mTc were 100%, 96.07%, 90.47% and 100%, respectively. In 5 out of 14 patients with mixed radiotracer, lymph node involvement was detected. In all of them there was at least one sentinel node affected with 99mTc, and only 3 showed fluorescence with 100% sensitivity and 100% NPV for 99mTc and 60% sensitivity and 77.77% NPV for ICG. Conclusion: The SLNSB with 99mTc has a high sensitivity and a VPN of 100%, increasing the identification of lymphatic metastases outside the territory of the ePLND. Fluorescence can facilitate the visualization of the sentinel nodes when they have been previously located by the SPECT-CT, although the sensitivity and the NPV of the ICG are lower than that of the 99mTc

Surgical Treatment of Completely Endophytic Renal Tumor: a Systematic Review.

PURPOSE OF REVIEW: An endophytic renal tumor represents a special surgical challenge in terms of location and safe removal. For this reason we wanted to review the existing literature on this subject. RECENT FINDINGS: In high-activity robotic centers, robot-assisted partial nephrectomy (RAPN) is a safe and efficacious surgical approach for completely endophytic renal tumors. As research innovation, the application of the radio-guided occult lesion localization technique (ROLL) facilitates the location and complete excision of the tumor during surgery. There are few studies that specifically report the experience with completely endophytic renal tumors. The endophytic tumor is usually smaller than exophytic. Frequently it represents a high complexity value in the different Score systems reported in the last decade. This surgery should be performed by experienced urologists regardless of the surgical approach they prefer (open, laparoscopic, or robotic). It is necessary to develop new techniques for intraoperative easy localization and intraoperative evaluation of surgical margins.