Multiple and hereditary renal tumors: a review for radiologists.

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2-4% of "sporadic" multifocality and 5-8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended. Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition. The concept of "non-hereditary" familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

Safety and efficacy of nivolumab therapy in patients with metastatic renal cell carcinoma and impaired kidney function.

INTRODUCTION: Patients with renal insufficiency, usually defined as those with creatinine clearance < 40 mL/min, were excluded from pivotal clinical trials, especially in studies involving nivolumab therapy in patients with renal cell carcinoma (RCC). The aim of the study is to evaluate the efficacy and safety of nivolumab in patients with metastatic RCC (mRCC) stratified according to creatinine clearance. MATERIAL AND METHODS: Data from mRCC patients treated with nivolumab were retrospectively analyzed. Patients were classified into two categories according to their estimated glomerular filtration rate (eGFR); the first category (C1) included patients with eGFR < 40 mL/min/1.73 m2 and the second category (C2) included those with eGFR ≥ 40 mL/min/1.73 m2. RESULTS: Of the 95 patients enrolled, 1. group included 26 patients (27.4%) and 2. group included 69 patients (72.6%). None of the pts in category 1 were on hemodialysis. Overall incidence of adverse events was not statistically different between the two groups (P = .469). The overall response rate ORR was 50% in the first group and 42.0% in the second group (P = .486). Median overall survival (OS) was longer with 23.3 months in the 2. group versus 11 months in the 1. group (P = .415). CONCLUSION: Renal insufficiency is a common problem in patients with advanced renal cancer since they often undergo nephrectomy and their renal function may also worsen while receiving tyrosine kinase inhibitor therapy. We found that there is no significant difference in the safety and efficacy of nivolumab treatment between two groups. Nivolumab appears to be a safe and effective agent in patients with renal impairment.

Tumores renales múltiples y hereditarios. Revisión por y para radiólogos / Multiple and hereditary renal tumors: A review for radiologists

El 80% de los carcinomas renales (CR) se diagnostican incidentalmente por imagen. Se aceptan un 2-4% de multifocalidad «esporádica» y un 5-8% de síndromes hereditarios, probablemente con infraestimación. Multifocalidad, edad joven, historia familiar, datos sindrómicos y ciertas histologías hacen sospechar un síndrome hereditario. Debe estudiarse individualmente cada tumor y multidisciplinarmente al paciente, con estrategias terapéuticas conservadoras de nefronas y un abordaje diagnóstico radioprotector. Se revisan los datos relevantes para el radiólogo en los síndromes de von Hippel-Lindau, translocación de cromosoma-3, mutación de proteína-1 asociada a BRCA, CR asociado a déficit en succinato-deshidrogenasa, PTEN, CR papilar hereditario, cáncer papilar tiroideo-CR papilar, leiomiomatosis hereditaria y CR, Birt-Hogg-Dubé, complejo esclerosis tuberosa, Lynch, translocación Xp11.2/fusión TFE3, rasgo de células falciformes, mutación DICER1, hiperparatoridismo y tumor mandibular hereditario, así como los principales síndromes de predisposición al tumor de Wilms.(AU)

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2-4% of “sporadic” multifocality and 5-8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended. Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition. The concept of “non-hereditary” familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.(AU)

The preoperative predictive factors for pathological T3a upstaging and positive surgical margin of clinical T1 renal cell carcinoma.

OBJECTIVES: The objective of this study is predict positive surgical margin (PSM) and pathological T3a (pT3a) upstaging in patients with clinical T1 (cT1) renal cell carcinoma (RCC). MATERIALS AND METHODS: 159 patients who underwent radical nephrectomy (RN) or partial nephrectomy (PN) for RCC. Patients' demographic, laboratory, radiological and pathological data that could predict PSM and pT3a upstaging pre-operatively were evaluated. The categorical and continuous variables were compared between the patient groups with or without PSM and/or pT3a upstaging using Pearson's chi-square test, and independent samples t-test or the Mann-Whitney U test, respectively. RESULTS: PT3a upstaging was detected in 32 (20.1%) patients, and PSM was detected in 28 (17.6%) patients. PT3a upstaging was detected in 27 and 5 patients who underwent open surgery and laparoscopic surgery, respectively (P < .001). In addition, pT3a upstaging was detected in 6 and 26 patients who underwent RN and PN, respectively (P < .001). Peritumoral fatty tissue thickness was 11.97 and 15.38 in the pT1 and pT3a patient groups, respectively (P = .022). In patients with pT3a upstaging, tumor size was larger, and renal nephrometry score and systemic immune-inflammation index (SII) were higher (P < .001, P < .001, and P = .022, respectively). It was determined that De Ritis ratio (DRR) and albumin-to-alkaline phosphatase (ALP) ratio (AAPR) parameters had significant prognostic values in predicting PSM (P = .024, and P = .001, respectively). ROC analysis indicated that tumor size predicted pT3a upstaging with 100% sensitivity and 98.6% specificity when its cut-off value was taken as 6.85 mm (AUC: 1.000, P < .001). In addition, logistic regression analysis revealed AAPR and DRR as significant predictors of PSM (P < .001, and P = .009, repsectively). CONCLUSION: The findings of this study indicated that the surgical technique of choice and the type of operation, tumor size, RNS value, peritumoral fatty tissue thickness, HU values of peritumoral and tumor side fatty tissues, and DRR and SII values can predict pT3a upstaging of patients with cT1 RCC, and that AAPR and DRR values can predict PSM.

Tumor metastásico en tejido blando a nivel del sacro secundario a carcinoma de células claras de riñón. Reporte de caso / Metastatic tumor in soft tissue at the level of the sacrum secondary toclear cell carcinoma of the kidney. A case report

Introducción. El cáncer de riñón es la undécima neoplasia maligna más común en los Estados Unidos Mexicanos. El carcinoma de células claras de riñón (CCR) es considerado la estirpe más frecuente y representa el 2-3 % de todos los cánceres a nivel mundial. En el contexto de la enfermedad metastásica, por lo general se identifica un tumor renal primario y las metástasis se localizan en pulmón, hueso, hígado, cerebro y, raramente, en tejidos blandos. Los pacientes con metástasis a tejidos blandos no tienen síntomas en las etapas iniciales y generalmente se identifican sólo cuando las lesiones aumentan de tamaño o durante el estudio de la pieza de resección quirúrgica. Caso clínico. Se presenta el caso de una paciente en la séptima década de la vida, con una metástasis en tejidos blandos de la región sacra, de 10 años de evolución posterior a una nefrectomía secundario a CCR. Resultados. Hallazgos clínicos e imagenológicos de un tumor bien delimitado. Se realizó resección quirúrgica de la lesión, bajo anestesia regional, con extirpación completa. Conclusión. Se recomienda que los pacientes con un sitio metastásico resecable y solitario sean llevados a resección quirúrgica con márgenes libres, como fue el caso de nuestra paciente, por su fácil acceso y ser una lesión única. En el CCR, además de su tratamiento quirúrgico inicial, es indispensable una estrecha vigilancia con examen físico e imágenes transversales, para detectar la presencia de metástasis y con ello evitar tratamientos tardíos.

Introduction. Kidney cancer is the eleventh most common malignancy in the United States of Mexico. Carcinoma renal cell (CRC) is considered the most frequent type and represents 2-3% of all cancers worldwide. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are located in the lung, bone, liver, brain, and rarely in soft tissue. Patients with soft tissue metastases do not have symptoms in the initial stages and are generally found only when the lesions increase in size or during the study of the surgical resection piece. Clinical case. In this case, we report a female patient in the seventh decade of life with a soft tissue metastasis located in the sacral region, 10 years after a nephrectomy secondary to CRC. Results. Clinical and radiological findings of a well-defined tumor. Surgical resection of the lesion is performed under regional anesthesia with complete excision. Conclusions. It is recommended that patients with a resectable and solitary metastatic site be candidates for surgical resection with free margins, as was the case with our patient due to its easy access and single lesion. In CRC, in addition to its initial surgical treatment, close surveillance with physical examination and cross-sectional images is essential to monitor the presence of metastases and thus avoid late treatments.

Manejo de masas renales en receptores de trasplante renal. Revisión colaborativa de los grupos de trabajo de trasplante renal y cáncer renal de la sección de jóvenes urológos (YAU) de la Asociación Europea de Urología (EAU) / How to manage renal masses in kidney transplant recipients? A collaborative review by the EAU-YAU kidney transplantation and renal cancer working groups

Introducción: Los receptores de trasplante renal (TR) tienen al menos cuatro veces más riesgo de desarrollar neoplasias renales que la población general. Dado que estos pacientes suelen albergar tumores bilaterales o multifocales, el tratamiento de las masas renales sigue siendo un tema controvertido. Objetivo Explorar el tratamiento actual de las masas renales en riñones nativos de pacientes con TR. Adquisición de la evidencia Se realizó una búsqueda bibliográfica en la base de datos Medline/PubMed y se incluyeron 34 estudios en la presente revisión. Síntesis de la evidencia La vigilancia activa es una opción terapéutica factible en pacientes frágiles con masas renales menores de 3 cm. Dado que la cirugía conservadora de nefronas no está justificada en el caso de masas en el riñón nativo, la nefrectomía radical es el tratamiento estándar para los tumores renales en riñones nativos de receptores de TR, con técnicas laparoscópicas asociadas a tasas de complicaciones perioperatorias significativamente menores en comparación con el abordaje abierto. La realización de nefrectomía bilateral de riñón nativo y TR en el mismo acto puede ser una opción terapéutica en pacientes con masa renal y enfermedad poliquística renal, particularmente ante la ausencia de diuresis residual. Los pacientes con enfermedad localizada y nefrectomía radical satisfactoria no requieren ajuste del tratamiento inmunosupresor. En los casos con metástasis, los agentes mTOR pueden garantizar una respuesta antitumoral eficaz, manteniendo a la vez el tratamiento inmunosupresor adecuado para proteger el injerto. Conclusiones El cáncer renal en riñones nativos postrasplante es un acontecimiento frecuente. La nefrectomía radical es el tratamiento de elección en masas renales localizadas. Aún no se ha implementado una estrategia de cribado estandarizada y ampliamente aprobada para las neoplasias malignas en las unidades renales nativas. (AU)

Introduction: Kidney transplant (KT) recipients have a four-times higher risk of renal malignancies compared to general population. As these patients frequently harbor bilateral or multifocal tumors, the management of renal masses is still under debate. Objective To explore the current management of the native kidney masses in KT patients.Acquisition of evidenceWe performed a literature search on MEDLINE/PubMed database. A number of 34 studies were included in the present review. Synthesis of evidence In frail patients with renal masses below 3 cm, active surveillance is a feasible alternative. Nephron-sparing surgery is not justified for masses in the native kidney. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, with laparoscopic techniques leading to significantly less perioperative complication rates as compared to the open approach. Concurrent bilateral native nephrectomy at the time of transplantation can be considered in patients with renal mass and polycystic kidney disease, especially if no residual urinary output is present. Patients with localized disease and successful radical nephrectomy do not require immunosuppression adjustment. In metastatic cases, mTOR agents can ensure efficient antitumoral response, while maintaining proper immunosuppression in order to protect the graft. Conclusions Post-transplant renal cancer of the native kidneys is a frequent occurrence. Radical nephrectomy is most frequently performed for localized renal masses. A standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented. (AU)

MiR-15b-5p Promotes Growth and Metastasis of Renal Clear Cell Carcinoma / MiR-15b-5p Promueve el Crecimiento y la Metástasis del Carcinoma Renal de Células Claras

SUMMARY: We investigated the expression and clinical significance of miR-15b-5p in clear cell renal cell carcinoma (RCC) through bioinformatics analysis and experimental verification. The differentially expressed miRNAs were screened in the GEO database. Venn diagram showed that there were 5 up-regulated miRNAs (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p, and has-miR-193a-3p) and only 1 down-regulated miRNA (has-miR-532-3p) that were commonly expressed between GSE189331 and GSE16441 datasets. This was further confirmed in TCGA. Further analysis showed that the has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p, and has-miR-15b-5p were closely related to tumor invasion, distant metastasis and survival probability. The expression of miR-15b-5p in ccRCC tissues was significantly higher than that in adjacent normal kidney tissues (P0.05). Following inhibition of miR-15b-5p expression, RCC cells had attenuated proliferation, increased apoptosis, and attenuated migration and invasion. has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC. miR-15b-5p is highly expressed in cancer tissues of ccRCC patients. It may promote proliferation, inhibit apoptosis and enhance cell migration and invasion of RCC cells. The has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, and has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC.

Investigamos la expresión y la importancia clínica de miR-15b-5p en el carcinoma de células renales (CCR) de células claras mediante análisis bioinformático y verificación experimental. Los miARN expresados diferencialmente se examinaron en la base de datos GEO. El diagrama de Venn mostró que había 5 miARN regulados positivamente (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p y has-miR-193a-3p). ) y solo 1 miARN regulado negativamente (has-miR-532-3p) que se expresaron comúnmente entre los conjuntos de datos GSE189331 y GSE16441. Esto fue confirmado aún más en TCGA. Un análisis más detallado mostró que has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p y has-miR-15b-5p estaban estrechamente relacionados con la invasión tumoral, la metástasis a distancia y la probabilidad de supervivencia. La expresión de miR-15b-5p en tejidos ccRCC fue significativamente mayor que la de los tejidos renales normales adyacentes (P 0,05). Tras la inhibición de la expresión de miR-15b-5p, las células RCC tuvieron una proliferación atenuada, un aumento de la apoptosis y una migración e invasión atenuadas. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC. miR-15b-5p se expresa altamente en tejidos cancerosos de pacientes con ccRCC. Puede promover la proliferación, inhibir la apoptosis y mejorar la migración celular y la invasión de células RCC. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E y has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC.

Metástasis Pancreática Metacrónica de un Carcinoma de Células Renales. Reporte de un Caso / Metachronic Pancreatic Metastasis of a Renal Cell Carcinoma. Case Report

El carcinoma de células renales (CCR) a nivel mundial presenta una incidencia de 431.288 casos anuales, causando 179.368 muertes en 2020. Sin embargo, a pesar de su incidencia, el desarrollo de metástasis pancreática (MP) de un RCC es un hecho inusual. El objetivo de este manuscrito fue reportar el caso de una paciente con una MP metacrónica de un CCR. Se trata de una paciente de 56 años, sexo femenino, nefrectomizada derecha hace 132 meses por un CCR, en adyuvancia con inmunoterapia. En un control imagenológico de rutina, se le pesquisó una lesión de aspecto tumoral en el cuerpo y cola del páncreas. Se intervino quirúrgicamente, realizándose una pancreatectomía córporo-caudal con preservación esplénica. Evolucionó de forma satisfactoria, sin complicaciones, siendo dada de alta al 4º día de su cirugía. El informe del estudio de la pieza operatoria con estudio inmunohistoquímico concluyó que se trataba de una MP de CCR. La paciente se encuentra en buenas condiciones generales y reinició quimioterapia con anticuerpos monoclonales. El seguimiento frecuente y prolongado de pacientes con antecedentes de CCR, facilita un diagnóstico y tratamiento oportuno de MP facilitando el mejor pronóstico de los pacientes, con tasas más altas de supervivencia.

SUMMARY: Renal cell carcinoma (RCC) worldwide has an incidence of 431,288 cases per year, causing 179,368 deaths in 2020. However, despite its incidence, the development of pancreatic metastasis (MP) from RCC is unusual. The aim of this manuscript was to report the case of a patient with a PM of a RCC. This is a 56-year-old female patient, underwent right nephrectomy 132 months earlier for RCC. While she was in adjuvant immunotherapy, in a routine imaging control, it was found a tumor lesion in the body and the tail of the pancreas. So, she underwent surgery, performing a corpora-caudal pancreatectomy with splenic preservation. Postoperative evolution was correct, without complications, and she was discharged on the 4th day after surgery. The report of the study of the surgical piece with an immunohistochemical study included, conclusive of PM of RCC. Currently, the patient is in good general condition and restarted chemotherapy with monoclonal antibodies. Frequent and prolonged follow-up of patients with a history of RCC facilitates timely diag- nosis and treatment of PM, facilitating the best prognosis for patients, with higher survival rates.

Atypical Location of Oral Metastasis as the First Manifestation of Renal Carcinoma. Case Report / Localización Atípica de Metastasis Oral como Primera Manifestación de Carcinoma Renal. Reporte de Caso

Oral cavity metastatic tumors derived from primary tumors from other corporal regions are rare, representing barely 1 % of all malignant tumors. Differential diagnosis of these lesions is challenging due to the wide spectrum of lesions with similar clinical presentation and especially when the presence of a primary tumor goes undetected. We present the case of a 55-year-old male with a painless tumor in the anterior maxillary region, vestibular gingiva and palate, with a 2-month evolution. Anatomopathological diagnosis was malignant clear cell tumor, highly suggestive of clear cell renal carcinoma metastasis, and the oral lesion constituted the first sign of illness.

Los tumores metastásicos de cavidad oral derivados de tumores primarios de otras regiones corporales son raros, representando apenas el 1 % de todos los tumores malignos. El diagnóstico diferencial de estas lesiones es desafiante debido al amplio espectro de lesiones con presentación clínica similar y especialmente cuando la presencia de un tumor primario pasa desapercibida. Presentamos el caso de un varón de 55 años con una tumoración indolora en región maxilar anterior, encía vestibular y paladar, de 2 meses de evolución. El diagnóstico anatomopatológico fue de tumor maligno de células claras, altamente sugestivo de metástasis de carcinoma renal de células claras, y la lesión bucal constituyó el primer signo de enfermedad.

Expresión de PD-L1 en cáncer renal, características pronósticas y utilidad en la práctica clínica habitual / Expression of PD-L1 in renal cancer, prognostic features and clinical utility of its routine staining

Introducción La expresión de PD-L1 en el carcinoma de células renales (CCR) se asocia a tasas de sobrevida y características clínico-patológicas pronósticas peores. Sin embargo, estos parecen responder mejor ante nuevos agentes terapéuticos. Conocer el comportamiento del CCR según la presencia de PD-L1 puede tener implicancias en la consejería de los pacientes y el abordaje terapéutico. Objetivo Identificar la presencia de PD-L1 en las células tumorales renales y analizar su asociación con los factores pronósticos de los pacientes, la sobrevida global (SG) y la sobrevida cáncer-específica (SCE). Metodología Análisis retrospectivo a partir de muestras de tejido de CCR obtenidas entre 2018 y 2021. Estudio inmunohistoquímico con anticuerpo monoclonal de ratón anti PD-L1, clon 22C3. Se definió PD-L1 «positivo» como una puntuación de proporción tumoral ≥ 1%. Comparación de factores pronósticos según la presencia o ausencia de PD-L1, y análisis univariante para la SG y la SCE. Resultados Un 14% (n=11) de la muestra era PD-L1(+). La edad media era de 59 años. No hubo diferencias estadísticamente significativas entre el estatus de PD-L1 y el estadio TNM, el grado nuclear y el tipo histológico. Los pacientes PD-L1(+) tuvieron peor SG con un HR de 5,27 (IC: 1,1-23,7; p=0,03) y la SCE mostró una tendencia desfavorable para PD-L1(+) con un HR de 4,79 (IC: 0,79-28,95; p=0,08). Conclusión La prevalencia de PD-L1 en el CCR es considerable. En este estudio, PD-L1(+) se asoció con una SG y SCE desfavorables, lo que justifica incorporar su uso rutinario en el CCR (AU)

Introduction The expression of PD-L1 in renal cell carcinoma (RCC) is associated with worse survival and prognostic clinical-pathological features. However, they seem to respond better to new therapeutic agents. Knowing the behavior of RCC according to the presence of PD-L1 may have implications for medical counseling and therapeutic approaches. Objective To identify the presence of PD-L1 in renal tumor cells and analyze its association with patientś prognostic factors, overall survival (OS) and cancer-specific survival (CSS). Methodology Retrospective analysis of RCC tissue samples, obtained between 2018 and 2021. Immunohistochemistry analysis with mouse monoclonal Anti PD-L1, clone 22C3. Definition of PD-L1 “positive” as a Tumor Proportion Score ≥ 1%. Comparison of prognostic factors according to the presence or absence of PD-L1, and univariate analysis for OS and CSS. Results 14% (n=11) of the sample were PD-L1(+). Average age was 59 years. There were no statistically significant differences between PD-L1 status and TNM stages, nuclear grade and histology. PD-L1(+) had worse OS with a HR of 5.27 (CI: 1.1-23.7; p=0.03) and CSS showed a unfavorable tendency for PD-L1(+) with a HR of 4.79 (CI: 0.79-28.95; p=0.08). Conclusion The prevalence of PD-L1 in RCC is considerable. In this study PD-L1(+) was associated with unfavorable OS and CSS. It seems reasonable to incorporate its routine use in RCC (AU)

How to manage renal masses in kidney transplant recipients? A collaborative review by the EAU-YAU kidney transplantation and renal cancer working groups.

INTRODUCTION: Kidney transplant (KT) recipients have a four-times higher risk of renal malignancies compared to general population. As these patients frequently harbor bilateral or multifocal tumors, the management of renal masses is still under debate. OBJECTIVE: To explore the current management of the native kidney masses in KT patients. ACQUISITION OF EVIDENCE: We performed a literature search on MEDLINE/PubMed database. A number of 34 studies were included in the present review. SYNTHESIS OF EVIDENCE: In frail patients with renal masses below 3 cm, active surveillance is a feasible alternative. Nephron-sparing surgery is not justified for masses in the native kidney. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, with laparoscopic techniques leading to significantly less perioperative complication rates as compared to the open approach. Concurrent bilateral native nephrectomy at the time of transplantation can be considered in patients with renal mass and polycystic kidney disease, especially if no residual urinary output is present. Patients with localized disease and successful radical nephrectomy do not require immunosuppression adjustment. In metastatic cases, mTOR agents can ensure efficient antitumoral response, while maintaining proper immunosuppression in order to protect the graft. CONCLUSIONS: Post-transplant renal cancer of the native kidneys is a frequent occurrence. Radical nephrectomy is most frequently performed for localized renal masses. A standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented.

Expression of PD-L1 in renal cancer, prognostic features and clinical utility of its routine staining.

INTRODUCTION: The expression of PD-L1 in renal cell carcinoma (RCC) is associated with worse survival and prognostic clinical-pathological features. However, they seem to respond better to new therapeutic agents. Knowing the behavior of RCC according to the presence of PD-L1 has implications for medical counseling and therapeutic approaches. OBJECTIVE: To identify the presence of PD-L1 in renal tumor cells and analyze its association with patients' prognostic factors, overall survival (OS) and cancer-specific survival (CSS). METHODOLOGY: Retrospective analysis of RCC tissue samples, obtained between 2018 and 2021. Immunohistochemistry analysis with mouse monoclonal Anti PD-L1, clone 22C3. Definition of PD-L1 "positive" as a Tumor Proportion Score ≥1%. Comparison of prognostic factors according to the presence or absence of PD-L1, and univariate analysis for OS and CSS. RESULTS: 14% (n = 11) of the sample were PD-L1(+). Average age was 59 years. There were no statistically significant differences between PD-L1 status and TNM stages, nuclear grade and histology. PD-L1(+) had worse OS with a HR of 5.27 (CI: 1.1-23.7; P = .03) and CSS showed a unfavorable tendency for PD-L1(+) with a HR of 4.79 (CI: 0.79-28.95; P = .08). CONCLUSION: The prevalence of PD-L1 in RCC is considerable. In this study PD-L1(+) was associated with unfavorable OS and CSS. It seems reasonable to incorporate its routine use in RCC.

Seguridad y tolerabilidad de cabozantinib en cáncer renal y hepatocarcinoma / Safety and tolerability of cabozantinib in renal cancer and hepatocarcinoma

ntroducción: Cabozantinib es un fármaco indicado en el tratamiento de cáncer renal y hepatocarcinoma con efi-cacia demostrada en ensayos clínicos. Sin embargo, cuando analizamos su perfil de seguridad, los propios ensayos pivotales muestran un elevado porcentaje de efectos adversos, siendo necesario en muchos casos reducir la dosis o interrumpir el tratamiento debido a la toxicidad. Por ello, nuestro estudio pretende analizar la tolerabilidad y seguridad de cabozantinib en nuestra población. Método: Estudio observacional, retrospectivo y unicéntrico. Se evaluaron diferentes variables relacionadas con la seguridad y tolerabilidad del fármaco. Para valorar la toxicidad se utilizaron los criterios del National Cancer Institu-te (CTCAE versión 5.0). La tolerancia se evaluó basándose en la presencia de efectos adversos durante el tratamiento con cabozantinib. Se realizó un análisis estadístico descriptivo e inferencial de los datos. Resultados: Se incluyeron un total de 17 pacientes (edad media: 63,5 años). Todos ellos presentaron efectos ad-versos. Las principales toxicidades presentadas de cualquier grado fueron astenia, diarrea, toxicidad cutánea, hipo-magnesemia, hipertransaminemia y síndrome palmo-plantar. Un 41,2% fueron de grado 3, siendo las principales reacciones adversas la hipertransaminemia y la hipomagnesemia. Un 23,5% necesitaron un ingreso hospitalario debido a la toxicidad del fármaco. Un 94,1% de pacientes precisaron reducción de dosis por toxicidad a 40 mg. Conclusiones: Cabozantinib presenta un perfil de seguridad poco favorable con un alto porcentaje de efectos ad-versos que obligan a la reducción de dosis o a la interrupción del tratamiento. (AU)

Introduction: Cabozantinib is a drug indicated for the treatment of renal cancer and hepatocarcinoma with pro-ven efficacy in clinical trials. However, when we analyze its safety profile, the pivotal trials themselves show a high percentage of adverse effects, making it necessary in many cases to reduce the dose or interrupt treatment due to toxicity. Therefore, our study aims to analyze the tolerability and safety of cabozantinib in our population. Method: Observational, retrospective and single-center study. Different variables related to the safety and tolera-bility of the drug were evaluated. To assess toxicity, the National Cancer Institute criteria (CTCAE version 5.0) were used. Tolerance was assessed based on the presence of adverse effects during treatment with cabozantinib. A des-criptive and inferential statistical analysis of the data was performed. Results: A total of 17 patients were included (mean age: 63.5 years old). All of them presented adverse effects. The main toxicities presented of any grade were asthenia, diarrhea, skin toxicity, hypomagnesemia, hypertransamine-mia, and palmoplantar syndrome. 41.2% were grade 3 toxicity, the main adverse reactions being hypertransamine-mia and hypomagnesemia. Hospital admission due to drug toxicity was required by 23.5%. Dose reduction to 40 mg due to toxicity was required by 94.1% of patients. Conclusions: Cabozantinib has an unfavorable safety profile with a high percentage of adverse effects that require dose reduction or treatment interruption. (AU)

Lesiones metastásicas a glándula tiroides. Una serie de casos / Metastatic lesions to the thyroid gland. Case series

Las lesiones metastásicas representan hasta un 3 % de los tumores malignos de la glándula tiroides. La mayoría de los casos se originan de tumores de células renales y de pulmón. El abordaje diagnóstico implica una alta sospecha clínica en pacientes con primarios conocidos, sin embargo, puede ser la manifestación inicial de una enfermedad maligna extensa no diagnosticada hasta en un 20 % a 40 % de los pacientes. La biopsia por aguja fina ha demostrado buen rendimiento para el diagnóstico de los nódulos metastásicos. El pronóstico y la opción del tratamiento quirúrgico dependen del control local del primario y del estado de la enfermedad sistémica asociada, por lo tanto, debe ser individualizado. Por lo general, hasta un 80 % de los pacientes con compromiso de la tiroides tienen enfermedad metastásica multiorgánica, y la intención del tratamiento quirúrgico es con fines paliativos para prevenir las complicaciones derivadas de la extensión local de la enfermedad a las estructuras del tracto aerodigestivo superior en el cuello. Se presenta a continuación, una serie de seis casos de pacientes con lesiones metastásicas a glándula tiroides con primarios en riñón, mama y de melanomas

Metastatic lesions represent up to 3% of malignant tumors of the thyroid gland. Most cases originate from lung and renal cell tumors. The diagnostic approach implies a high clinical suspicion in patients with known primaries, however, it can be the initial manifestation of an extensive undiagnosed malignant disease in up to 20% to 40% of patients. Fine-needle biopsy has shown good performance for the diagnosis of metastatic nodules. The prognosis and the option of surgical treatment depend on the local control of the primary condition and the state of the associated systemic disease, therefore it must be individualized. In general, up to 80% of patients with thyroid involvement have multi-organ metastatic disease and surgical treatment is intended to be palliative to prevent complications resulting from local extension of the disease to structures of the upper aerodigestive tract in the neck. A case series of six patients with metastatic lesions to the thyroid gland with primaries in the kidney, breast and melanomas is presented below

Neoplasia papilar de polaridad inversa: un nuevo subtipo de tumor renal de buen pronóstico / Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis

Introducción: La neoplasia papilar renal de polaridad inversa (NPRPI) ha sido recientemente reconocida como una entidad separada de la clasificación tradicional de los carcinomas papilares de células renales por sus peculiares características histopatológicas, inmunofenotípicas y moleculares, y un comportamiento indolente. Material y métodos: En este trabajo aportamos 6 nuevos casos y realizamos una revisión de la literatura publicada al respecto hasta el momento actual, recopilándose un total de 104 casos. Resultados: Nuestros casos de NPRPI corresponden a 5 hombres y una mujer, con edades comprendidas entre los 47 y los 91 años. En 5 casos la NPRPI resultó un hallazgo incidental en piezas de nefrectomía indicada por la presencia de otro tumor renal y en uno la NPRPI fue el motivo de la intervención quirúrgica. Nuestros casos presentan tamaños entre los 2 y los 13mm, y una histología papilar con revestimiento en monocapa de células eosinófilas con núcleos de bajo grado en localización apical. Inmunohistoquímicamente muestran una constante positividad para GATA3 y negatividad para vimentina. Se identificaron mutaciones en KRAS en el 50% de ellos. Tras un seguimiento comprendido entre uno y 60 meses, 5 de los pacientes seguían vivos sin recurrencia o metástasis y uno falleció a causa de un carcinoma urotelial. Conclusiones: Nuestros casos concuerdan con las características clínicas y patológicas descritas en los publicados hasta el momento. Aportamos la primera serie nacional y corroboramos la existencia de unos criterios diagnósticos definidos y constantes que permiten considerar la NPRPI como una entidad propia distintiva. (AU)

Introduction: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior . Material and methods: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. Results: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. Conclusions: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity. (AU)

Nefrectomía parcial laparoscópica off-clamp tras la embolización del tumor en sala híbrida frente a nefrectomía parcial convencional: un análisis de pares emparejados por puntuación de propensión / Off-clamp laparoscopic partial nephrectomy in a hybrid room after tumor embolization versus conventional partial nephrectomy: A propensity score matched pair analysis

Objetivo: La nefrectomía parcial laparoscópica off-clamp tras la embolización arterial superselectiva (NPLh) en un quirófano híbrido es un abordaje mínimamente invasivo prometedor. En este estudio comparamos los resultados quirúrgicos perioperatorios de esta técnica innovadora con los de la técnica estándar de nefrectomía parcial laparoscópica convencional (NPLc).Pacientes y métodos: En total se incluyeron 86 y 127 pacientes tratados con NPLh y NPLc, respectivamente. Las dos técnicas se compararon en términos de complicaciones quirúrgicas, pérdida de sangre estimada (PSE), tiempo quirúrgico, duración de la estancia hospitalaria (DEH), márgenes quirúrgicos y tasa de consecución de la Trifecta (definida como duración de isquemia caliente <25min, márgenes quirúrgicos negativos y ausencia de complicaciones). Se utilizó una puntuación de propensión basada en la edad, el sexo, el índice de masa corporal (IMC), la tasa de filtración glomerular estimada (TFGe) preoperatoria y el tamaño tumoral para un emparejamiento 1:1 de los pacientes de cada grupo. Tras el emparejamiento, se obtuvieron dos grupos de 67 pacientes con características similares.Resultados: La tasa de conversión a cirugía abierta, las complicaciones y la PSE fueron similares entre ambos grupos. Por el contrario, el tiempo quirúrgico, la DEH y las tasas de Trifecta favorecieron la NPLh. El análisis multivariante demostró que la NPLh tenía un 70% más de probabilidades de lograr la Trifecta que la NPLc en todos los grupos de edad y para cualquier tamaño tumoral en toda la población del estudio.Conclusión: En comparación con el abordaje convencional, la nefrectomía parcial laparoscópica sin clampado después de la embolización arterial superselectiva en una sala híbrida mostró resultados quirúrgicos satisfactorios inmediatos y alcanzó una mayor tasa de consecución de la Trifecta. Se necesitan resultados funcionales y oncológicos a medio y a largo plazo para establecer esta

Objective: Off-clamp laparoscopic partial nephrectomy in a hybrid operating room after superselective arterial embolization (hLPN) is a promising minimally invasive approach. In this study, we compared the perioperative surgical outcomes of this innovative technique with the conventional standard of care laparoscopic partial nephrectomy (cLPN) technique.Patients and methods: Overall, 86 and 127 patients treated with hLPN and cLPN, respectively, were included. These two techniques were compared in terms of surgical complications, estimated blood loss (EBL), operative time, length of stay (LOS), surgical margins, and Trifecta achievement rate (defined as warm ischemia duration <25min, negative surgical margins and absence of complications). A propensity score based on age, gender, BMI, preoperative eGFR and tumor size was used for a 1:1 matching of patients of each group. After matching, two groups of 67 patients with similar characteristics were obtained.Results: Conversion rate to open surgery, complications and EBL were similar in both groups. Conversely, operative time, LOS and Trifecta rates favored hLPN. The multivariate analysis showed that hLPN had a 70% higher chance of Trifecta achievement than cLPN in all age groups and for all tumor size across the study population.Conclusion: Compared to a conventional approach, off-clamp laparoscopic partial nephrectomy in a hybrid room after superselective arterial embolization showed satisfying immediate surgical outcomes and reached a higher rate of Trifecta achievement. Mid and long-term functional and oncological results are needed to establish this minimally invasive surgical alternative (AU)

Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis.

INTRODUCTION: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior. MATERIAL AND METHODS: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. RESULTS: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13 mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. CONCLUSIONS: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity.

Síndrome de Birt-Hogg-Dubé: afectación pulmonar en 2 casos / Birt-Hogg-Dubé Syndrome: Lung Involvement in 2 Cases

El síndrome de Birt-Hogg-Dubé es una rara enfermedad autosómica dominante causada por la mutación patogénica del gen de la foliculina, que se expresa principal mente en tres órganos que incluyen el pulmón, la piel y el riñón, y produce quistes pulmonares, tumores renales y cutáneos. Desde el punto de vista respiratorio es poco sintomática, pero los quistes presentan alto riesgo de neumotórax, por lo que es imprescindible realizar una adecuada semiología radiológica de los quistes para un diagnóstico oportuno. Los tumores más importantes son los renales porque incluyen varios tipos de carcinomas renales; debido a esto requieren seguimiento estricto y, en muchos, casos cirugía. Presentamos dos casos de pacientes con este síndrome; uno confirmado por la mutación genética y el otro, por la confirmación histológica de fibrofoliculoma, ambos criterios mayores para el diagnóstico de esta enfermedad. Es fundamental el diagnóstico temprano de esta entidad de acuerdo con lo expuesto anteriormente, por lo que hacemos esta revisión con una amplia discusión sobre la afectación pulmonar, la semiología radiológica de los quistes y los criterios diagnósticos.

The Birt-Hogg-Dubé syndrome is a rare autosomal dominant disease caused by the pathogenic mutation of the folliculin gene, which is mainly expressed in three organs that include the lung, the skin and the kidney, and produces lung cysts, and renal and skin tumors. From the respiratory point of view, it doesn't have many symptoms, but cysts have high risk of pneumothorax, so it is indispensable to carry out the correct radiological semiology of the cysts for a timely diagnosis. The most important tumors are the renal, because they include several types of renal carcinomas; that is why they require strict follow-up and, in many cases, surgery. We present two cases of patients with this syndrome: one confirmed by the genetic mutation, and the other one by the histological confirmation of fibrofolliculoma, both major criteria for the diagnosis of this disease. The early diagnosis of this entity is of fundamental importance, according to what has been previously presented, so we conduct this review with a broad discus sion about lung involvement, the radiological semiology of the cysts, and diagnostic criteria.

Metástasis parotídea de carcinoma de células claras renal con presencia simultánea de pseudoaneurisma arterial. Caso clínico y revisión de la literatura / Parotid metastasis of clear cell renal carcinoma with simultaneous presence of arterial pseudoaneurysm. Case report and review of literature

Las metástasis en glándula parótida son muy poco frecuentes. Presentamos el caso de una mujer de 73 años cuyos antecedentes oncológicos principales a destacar son carcinoma ductal infiltrante de mama tratado con mastectomía y linfadenectomía axilar y, posteriormente, carcinoma de células renales de célula clara bilaterales metacrónicos tratados con nefrectomía radical. Desde entonces la mujer se encuentra en diálisis. Presenta tumoración en parótida de 4 cm, que radiológicamente es catalogada como pseudoaneurisma arterial intraparotídeo. Tras la extirpación de la parótida, seis años después de la última nefrectomía, en el estudio anatomopatológico se observa, junto a vasos dilatados, lesión neoplásica compatible morfológica e inmunohistoquímicamente con metástasis de carcinoma de células renales de célula clara. Se ha realizado una profunda revisión de la literatura encontrando menos de 60 casos descritos de metástasis parotídea de carcinoma de células renales de célula clara. Analizándolos observamos metástasis en otros lugares en el 61 % de los mismos, principalmente pulmonares, óseas y en glándulas adrenales, existiendo mayor porcentaje de segundas metástasis (70 %) cuando hay sincronía entre carcinoma renal y metástasis parotídea. En conclusión, presentamos un caso inusual de metástasis tardía de carcinoma renal de célula clara en parótida, y el primero, según nuestro conocimiento, que se diagnostica como hallazgo incidental en la extirpación de un aneurisma intraparotídeo. (AU)

Parotid gland metastases are very rare. We present the case of a 73-year-old woman whose main oncological history to highlight is infiltrating ductal carcinoma of the breast treated with mastectomy and axillary lymphadenectomy and after that. metachronous bilateral clear cell renal cell carcinoma treated with radical nephrectomy. Since then, the woman has been on dialysis. It presents a 4 cm parotid tumor, which is radiologically classified as an intraparotid arterial pseudoaneurysm. After extirpation of the parotid gland, six years after the last nephrectomy, in the pathological study, together with dilated vessels, a neoplastic lesion compatible morphologically and immunohistochemically with metastasis of clear cell renal cell carcinoma is observed. A thorough review of the literature has been carried out, finding less than 60 reported cases of parotid metastasis from clear cell renal cell carcinoma. Analyzing them, we observed metastases in other places in 61 % of them, mainly lung, bone and adrenal glands, with a higher percentage of second metastases (70 %) when there was a synchrony between renal carcinoma and parotid metastasis. In conclusion, we have presented an unusual case of late metastasis of clear cell renal carcinoma in the parotid, and the first –to our knowledge–, which is diagnosed as an incidental finding in the removal of an intraparotid aneurysm. (AU)

La radiómica mejora la utilidad del ADC en la diferenciación entre el oncocitoma renal y el carcinoma cromófobo de células renales: resultados preliminares / Radiomics improves the utility of ADC for differentiation between renal oncocytoma and chromophobe renal cell carcinoma: preliminary findings

Objective Differentiation between renal oncocytoma (RON) and chromophobe renal cell carcinoma (chRCC) remains challenging. We aimed to assess the accurate apparent diffusion coefficient (ADC) radiomics features in differentiating these tumors.Materials and methods This single-center retrospective study included 14 patients with histopathologically proven RON (n=6) and chRCC (n=8) who underwent magnetic resonance imaging. Features were extracted from ADC maps. Features with an intraclass correlation coefficient >0.90, an intergroup p<0.01 and interrater differences with normal distribution underwent agreement and receiver operating characteristic curve analyses.Results Overall, 6 features qualified for further analysis and Bland-Altman plots revealed acceptable agreement for all. Only 1 first order feature and 5 high order texture features successfully predicted RON with more than 90% sensitivities and specificities more than 80%.Conclusion Squared mean ADC and certain gray level run length matrix features extracted by radiomics of ADC mapping provide quite high diagnostic precision in terms of distinguishing between RON and chRCC (AU)

Objetivo La diferenciación entre el oncocitoma renal (OR) y el carcinoma de células renales cromófobo (CCRcr) sigue siendo un desafío. Nuestro objetivo es evaluar la precisión de las características radiómicas del coeficiente de difusión aparente (ADC) para diferenciar estos tumores.Materiales y métodos Este estudio retrospectivo unicéntrico incluyó a 14 pacientes con OR (n = 6) y CCRcr (n = 8) confirmado por informe histológico que recibieron una resonancia magnética. Las características se extrajeron de los mapas de ADC. Las características con un coeficiente de correlación intraclase > 0,90, un p < 0,01 intergrupo y diferencias interevaluadores con distribución normal se sometieron a análisis de concordancia y de curva característica de funcionamiento del receptor.Resultados En total, se obtuvieron seis características para el análisis posterior y los gráficos de Bland-Altman revelaron una concordancia aceptable para todas ellas. Sólo una característica de primer orden y cinco características de textura de orden superior predijeron con éxito el OR con una sensibilidad superior al 90% y una especificidad superior al 80%.Conclusión La media cuadrada del ADC y ciertas características de la matriz de longitud de secuencia de nivel de gris extraídas por la radiómica del mapa de ADC proporcionan una precisión diagnóstica bastante alta en cuanto a la distinción entre OR y CCRcr (AU)