Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Impact of preoperative body composition in patients with renal cell carcinoma submitted to surgical treatment / Impacto da composição corporal pré-operatória em pacientes com carcinoma de células renais submetidos a tratamento cirúrgico

Abstract Objective: To evaluate the impact of preoperative body composition in patients with renal cell carcinoma (RCC) undergoing surgical treatment. Materials and Methods: This was a retrospective study of 52 patients with RCC undergoing total or partial nephrectomy. Body composition assessment was performed using the body mass index, together with computed tomography analysis at the level of the third lumbar vertebra to measure the area of visceral adipose tissue, as well as the area and density of skeletal muscle mass. Results: Malnutrition, obesity and inadequate skeletal muscle gauge (SMG) were associated with higher hospital length of stay (p = 0.028, p = 0.02 and p = 0.012, respectively). Although the rates of postoperative symptoms and readmissions were low, survival was better among the patients with an adequate SMG than among those with an inadequate SMG (p = 0.003). Conclusion: Among patients with RCC undergoing surgical treatment, preoperative body composition does not seem to be associated with the rates of perioperative complications, although an inadequate SMG seems to be associated with worse overall survival.

Resumo Objetivo Avaliar o impacto da composição corporal pré-operatória em pacientes portadores de carcinoma de células renais (CCR) submetidos a tratamento cirúrgico. Materiais e Métodos: Foi realizado estudo retrospectivo de 52 pacientes portadores de CCR submetidos a tratamento cirúrgico. A avaliação da composição corporal foi realizada por meio do índice de massa corporal e análise da L3 obtida pela tomografia computadorizada para mensurar a área do tecido adiposo visceral, área e densidade da massa muscular esquelética. Resultados: Os pacientes desnutridos, obesos e que apresentaram produto muscular esquelético (PME) inadequado permaneceram mais tempo internados (p = 0,028, p = 0,02 e p = 0,012, respectivamente). As taxas de sintomas e reinternações no pósoperatório foram baixas em toda a amostra, no entanto, observou-se que pacientes com PME inadequado apresentaram uma pior sobrevida em relação aos pacientes com PME adequado (p = 0,003). Conclusão: A análise da composição corporal pré-operatória não mostrou associação com as taxas de complicações periope-ratórias em pacientes portadores de CCR submetidos a nefrectomia total ou parcial, no entanto, a inadequação do PME está associada a uma pior sobrevida.

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.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Metastatic and aggressive renal cell carcinoma mimicking a unilateral choroidal tuberculoma / Carcinoma de células renais metastático grave mimetizando tuberculoma de coroide unilateral

ABSTRACT Ocular metastases from systemic tumors are uncommon. The choroid is the most frequent target, with a preference for elderly individuals. Lung cancer is the predominant primary tumor that metastasizes to the eyes in males, although other ocular conditions such as uveitis and retinal lesions can mimic secondary tumor implants in ocular tissues. On fundoscopy, choroidal metastasis resembles other infectious processes, especially choroidal tuberculoma. Therefore, patients presenting with choroidal masses should undergo detailed clinical examinations, especially if the mass is the first manifestation of a systemic and severe disease. In this report, we describe a young man with a metastatic choroidal tumor secondary to papillary renal cell carcinoma mimicking a unilateral choroidal tuberculoma.

RESUMO A disseminação metastática ocular de tumores sistêmicos é incomum, ocorrendo principalmente na coroide e em pacientes idosos. O câncer de pulmão é considerado o principal tumor metastático ocular em homens, contudo, outras doenças oculares, como as uveítes e lesões retinianas, podem mimetizar os implantes secundários tumorais nos tecidos oculares. O aspecto fundoscópico das neoplasias da coroide pode apresentar similaridade com outros processos infecciosos, especialmente o tuberculoma de coroide. Dessa forma, a investigação clínica detalhada é de grande importância no diagnóstico de pacientes com massas coroideanas, especialmente quando configuram a primeira manifestação de uma doença sistêmica e grave. Relatamos um caso raro de metástase coroideana como primeira manifestação clínica do carcinoma de células renais em um homem jovem, mimetizando um tuberculoma de coroide.

Impact of preoperative body composition in patients with renal cell carcinoma submitted to surgical treatment.

Objective: To evaluate the impact of preoperative body composition in patients with renal cell carcinoma (RCC) undergoing surgical treatment. Materials and Methods: This was a retrospective study of 52 patients with RCC undergoing total or partial nephrectomy. Body composition assessment was performed using the body mass index, together with computed tomography analysis at the level of the third lumbar vertebra to measure the area of visceral adipose tissue, as well as the area and density of skeletal muscle mass. Results: Malnutrition, obesity and inadequate skeletal muscle gauge (SMG) were associated with higher hospital length of stay (p = 0.028, p = 0.02 and p = 0.012, respectively). Although the rates of postoperative symptoms and readmissions were low, survival was better among the patients with an adequate SMG than among those with an inadequate SMG (p = 0.003). Conclusion: Among patients with RCC undergoing surgical treatment, preoperative body composition does not seem to be associated with the rates of perioperative complications, although an inadequate SMG seems to be associated with worse overall survival.

Objetivo: Avaliar o impacto da composição corporal pré-operatória em pacientes portadores de carcinoma de células renais (CCR) submetidos a tratamento cirúrgico. Materiais e Métodos: Foi realizado estudo retrospectivo de 52 pacientes portadores de CCR submetidos a tratamento cirúrgico. A avaliação da composição corporal foi realizada por meio do índice de massa corporal e análise da L3 obtida pela tomografia computadorizada para mensurar a área do tecido adiposo visceral, área e densidade da massa muscular esquelética. Resultados: Os pacientes desnutridos, obesos e que apresentaram produto muscular esquelético (PME) inadequado permaneceram mais tempo internados (p = 0,028, p = 0,02 e p = 0,012, respectivamente). As taxas de sintomas e reinternações no pósoperatório foram baixas em toda a amostra, no entanto, observou-se que pacientes com PME inadequado apresentaram uma pior sobrevida em relação aos pacientes com PME adequado (p = 0,003). Conclusão: A análise da composição corporal pré-operatória não mostrou associação com as taxas de complicações periope-ratórias em pacientes portadores de CCR submetidos a nefrectomia total ou parcial, no entanto, a inadequação do PME está associada a uma pior sobrevida.

Expressão de enzimas modificadoras de MRNA no carcinoma renal de células claras e no carcinoma de mama / Expression of MRNA-modifying enzymes in clear cell renal cell carcinoma and breast cancer

Após a transcrição, as moléculas de RNA podem ser alteradas por uma infinidade de modificações químicas distintas que ocorrem de maneira dinâmica, constituindo o epitranscriptoma. A primeira modificação de mRNA identificada foi a N6-metiladenosina (m6A), afetando quase todas as etapas do metabolismo do RNA, desde o processamento no núcleo até a tradução e decaimento no citoplasma, alterando assim os níveis de expressão gênica. A m6A é controlada por três grupos de proteínas, writers, readers e erasers. Na literatura estudos relatam que as proteínas que regulam a m6A possam estar mutadas e / ou exibir expressão alterada através de uma variedade de tipos de tumores, mais notavelmente o carcinoma de mama e o CRCC. Neste projeto, tivemos como objetivo determinar os níveis de expressão das enzimas modificadoras de mRNA, e suas correlações com dados clínicos e anatomopatológicos para CRCC e carcinoma de mama, o que pode nos ajudar a ampliar o conhecimento sobre os mecanismos moleculares associados a estas doenças. Em nossa coorte dos pacientes com CRCC, detectamos que a baixa expressão da writer RBM15B, se associa com variáveis relacionadas a progressão tumoral e apresenta pior SR e aumento de risco do paciente recidivar. A baixa expressão da FTO e alta da METTL14, se associam aos estágios mais agressivos de CRCC, podendo serem possíveis marcadores de prognóstico. No carcinoma de mama, os pacientes com expressão baixa da METTL14, apresentaram associação com pior prognóstico para esta doença, especificamente no subtipo molecular TN e aumento de risco em (RR = 4,772; p= 0,01), para óbito global. Sendo assim, acreditamos que interferência no mecanismo de controle da m6A no mRNA desencadeada por alterações de expressão destas proteínas, podem estar ligadas a alterações biológicas levando ao processo de tumorigênese

After transcription, RNA molecules can be altered by a multitude of different chemical modifications that occur dynamically, constituting the epitranscriptome. The first mRNA modification identified was N6-methyladenosine (m6A), affects almost all steps of RNA metabolism, from processing in the nucleus to translation and decay in the cytoplasm, thus altering gene expression levels. m6A is controlled by three groups of proteins, writers, readers and erasers. Studies in the literature report that proteins that regulate m6A may be mutated and/or exhibit altered expression across a variety of tumor types, most notably breast cancer and ccRCC. In this project, we aimed to determine the expression levels of mRNA-modifying enzymes, and their correlations with clinical and anatomopathological data for ccRCC and breast cancer, which can help to expand our knowledge about the molecular mechanisms associated with these diseases. In our cohort of patients with ccRCC, we detected that the low expression of writer RBM15B is associated with characteristics related to tumor progression showing worse Relapse-Free survival and increased recurrence risk. Low expression of FTO and high expression of METTL14 are associated with more aggressive stages of ccRCC and may be possible prognostic markers. In breast cancer, patients with low METTL14 expression were associated with a worse prognosis, specifically in the TN molecular subtype, with increased death risk (RR = 4.772; p= 0.01). Therefore, we believe that interference in the m6A control mechanism in the mRNA triggered by changes in the expression of these proteins may be linked to biological alterations leading to the process of tumorigenesis

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.

A novel nomogram can predict pathological T3a upstaged from clinical T1a in localized renal cell carcinoma.

HYPOTHESIS: Nomogram can be built to predict the pathological T3a upstaging from clinical T1a in patients with localized renal cell carcinoma before surgery. PURPOSE: Renal cell carcinoma (RCC) patients with clinical T1a (cT1a) disease who are upstaged to pathological T3a (pT3a) have reduced survivals after partial nephrectomy. We aimed to develop a nomogram-based model predicting pT3a upstaging in RCC patients with preoperative cT1a based on multiple preoperative blood indexes and oncological characteristics. MATERIALS AND METHODS: Between 2010 and 2019, 510 patients with cT1a RCC were individually matched according to pT3a upstaging and pathological T1a (pT1a) at a 1:4 ratio using clinicopathologic features. Least absolute shrinkage and selection operator regression analysis was used to identify the most important risk factor from 40 peripheral blood indicators, and a predictive model was established. Multivariate logistic regression analysis was performed with the screened blood parameters and clinical data to identify significant variables. Harrell's concordance index (C-index) was applied to evaluate the accuracy of the model for predicting pT3a upstaging in patients with cT1a RCC. RESULTS: Out of 40 blood indexes, the top ranked predictor was fibrinogen (FIB). Age, the ratio of the tumor maximum and minimum diameter (ROD), FIB, and tumor size were all independent risk factors for pT3a upstaging in multivariate analysis. A predictive ARFS model (Age, ROD, FIB, tumor Size) was established, and the C-index was 0.756 (95% CI, 0.681-0.831) and 0.712 (95% CI, 0.638-0.785) in the training and validation cohorts, respectively. CONCLUSIONS: Older age, higher ROD, increased FIB level, and larger tumor size were independent risk factors for upstaging. The ARFS model has a high prediction efficiency for pT3a upstaging in patients with cT1a RCC.

Impacto da composição corporal pré-operatória nas taxas de complicações peri-operatorias em pacientes portadores de carcinoma de células renais submetidos a tratamento cirúrgico / Impact of preoperative body composition on perioperative complication rates in patients with renal cell carcinoma undergoing surgical treatment

Introdução: A desnutrição e a baixa massa muscular pré-operatória em pacientes portadores de tumores renais parece estar fortemente associada aos resultados oncológicos após a cirurgia, incluindo tempo de internação prolongado, maior risco de complicações pós operatórias e pior sobrevida global e específica do câncer. Objetivos: Avaliar o impacto da composição corporal pré-operatória nas taxas de complicações peri-operatórias em pacientes portadores de carcinoma de células renais submetidos a tratamento cirúrgico. Materiais e métodos: O estudo realizado foi retrospectivo e 52 de pacientes atenderam aos critérios de inclusão. A avaliação da composição corporal foi realizada por meio do índice de massa corporal (IMC), fórmula de estimativa de gordura corporal e análise da L3 obtida pela tomografia computadorizada (TC). Os dados relacionados ao tumor foram obtidos através do exame anatomopatológico. A presença de sintomas, complicações pré e pósoperatório e classificação de seguimento oncológico foram avaliados conforme registros em evoluções médicas. Os métodos de avaliação nutricional foram comparados entre si e correlacionados com os demais dados coletados. Resultados: Os pacientes desnutridos, obesos e que apresentaram produto muscular esquelético (PME) inadequado permaneceram mais tempo internados (p=0,028, p=0,02 e p=0,012). As taxas de sintomas e reinternações no pós operatório foram baixas em toda a amostra, no entanto, observou-se que pacientes com PME inadequado apresentaram uma pior sobrevida em relação aqueles com PME adequado (p=0,003). Conclusão: A análise da composição corporal pré-operatória não apresentou associação com as taxas de complicações peri-operatórias em pacientes portadores de CCR submetidos a nefrectomia total ou parcial.

Introduction: Malnutrition and low preoperative muscle mass in patients with renal tumors seems to be strongly associated with oncological outcomes after surgery, including prolonged hospital stay, increased risk of postoperative complications, and worse overall and cancer-specific survival. Aim: Evaluate the impact of preoperative body composition on perioperative complication rates in patients with renal cell carcinoma undergoing surgical treatment. Materials and methods: It was a retrospective study and 52 patients were included. Body composition assessment was performed using the body mass index, body fat estimation formula and L3 analysis obtained by computed tomography. Tumor-related data were obtained through anatomopathological examination. The presence of symptoms, pre and postoperative complications and classification of oncological follow-up were evaluated according to medical records. The nutritional assessment methods were compared and correlated with the other data collected. Results: Malnoutrition, obesity and inadequate skeletal muscle product was associated with length of stay (p=0.028, p=0.02 and p=0.012). The rates of symptoms and postoperative readmissions were low in all group, however, it was observed that patients with inadequate PME had a worse survival in relation to those with adequate PME (p=0.003). Conclusion: The analysis of preoperative body composition showed no association with the rates of perioperative complications in patients with CRC undergoing total or partial nephrectomy

Surgical insights for the management of variant histology in renal cell carcinoma

ABSTRACT Purpose: To review the current literature regarding variant (non-clear) histology of renal cell carcinoma (RCC) and the clinical management of these renal tumors. Material and Methods: A PubMed database search was performed in May 2020 focusing on variant RCC, its diagnosis and associated syndromes, tumor characteristics, and options for management. Results: A broad range of pathological, clinical and diagnostic characteristics amongst non-ccRCC variants were found to have an impact on the overall management of these tumors. The imaging modalities, frequency of surveillance, and timing for intervention were found to be dependent on the type of genetic alterations, type of histology, and tumor growth rates. The timing and type of surgery as well as the systemic therapy are tailored to the specific tumor type and patient. Conclusion: The findings of this review suggest that clinical management should be considered and adjusted for patients with non-ccRCC histological variants based on tumor subtype and genetic alterations.

Metástasis duodenal por hipernefroma, reporte de un caso / Duodenal metastasis from hypernephroma: a case report

RESUMEN Introducción: el hipernefroma representa del 2 % al 3 % de todas las neoplasias malignas del adulto. Sus patrones de metástasis no han sido definidos con precisión. La metástasis duodenal es considerada rara cuando se presenta. Presentación del caso: paciente masculino, de 48 años de edad, con antecedentes de nefrectomía derecha por presentar hipernefroma que a los siete meses de la intervención se diseminó a pulmón y fosa renal. Al año de la nefrectomía es valorado por presentar anemia crónica, sangre oculta en heces fecales positiva y sintomatología gastrointestinal. Se realizó colon por enema opaco que reveló infiltración de la pared y durante la realización de gastroscopia se realizó toma de muestra de lesión tumoral en duodeno. El análisis anatomopatológico de la biopsia duodenal mostró una lesión tumoral de células grandes anaplásicas con citoplasma vacuolado, PAS positivas y PAS Diastasa negativas, compatible con metástasis de carcinoma de células renales. Conclusiones: la aparición tardía de metástasis y la regresión espontánea del hipernefroma exigen un seguimiento integral y prolongado del personal médico a su cargo, en quienes la sospecha de diseminación siempre debe preponderar durante el abordaje clínico, aun cuando la clínica no sugiera los sitios más comunes.

ABSTRACT Introduction: hypernephroma represents 2 % to 3 % of all adult malignant neoplasms. Its metastatic patterns have not been precisely defined. Duodenal metastasis is considered rare when it occurs. Case Report: a 48-year-old-male patient, having a history of right nephrectomy due to hypernephroma, at 7 months after the surgery a spread to the lung and renal fossa was found. One year after nephrectomy he was evaluated for chronic anemia, positive fecal occult blood and gastrointestinal symptoms. An opaque colon enema was performed which revealed infiltration of the wall and during gastroscopy a sample of tumor lesion in the duodenum was taken. The pathological analysis of the duodenal biopsy showed an anaplastic large cell tumor lesion with vacuolated cytoplasm, PAS positive and PAS Diastase negative, compatible with metastasis of renal cell carcinoma. Conclusions: the late appearance of metastases and spontaneous regression of hypernephroma require a comprehensive and prolonged follow-up by the medical staff in charge, in those where the suspicion of dissemination should always prevail during the clinical approach, even when the clinical picture does not suggest the most common sites.

Dietary and circulating vitamin D and risk of renal cell carcinoma: a meta-analysis of observational studies

ABSTRACT Objective: This meta-analysis is the first to evaluate the associations of circulating and dietary intake of vitamin D with risk of risk of renal cell carcinoma (RCC). Our findings showed that higher circulating vitamin D level and dietary vitamin D intake were associated with a reduced risk of RCC. The possible explanation might be attributed to the anti-inflammatory effect, inhibiting cell proliferation, inducing cell differentiation and apoptosis. Materials and Methods: We searched the MEDLINE, EMBASE, and Scopus databases from their inception points through December 2018 for observational studies. The pooled relative risks (RRs) with corresponding 95% CIs were calculated using random-effects or fixed-effects models. The Newcastle-Ottawa scale was employed to assess the quality of the included studies. Results: A total of 9 publications were included in this meta-analysis. An overall analysis of the highest versus lowest intake levels revealed that circulating vitamin D level was protectively associated with risk of RCC 0.76 (95% CI: 0.64-0.89, P=0.001), with no evidence of heterogeneity (I2=38.8%, P=0.162). In addition, dietary vitamin D intake was associated with a reduced risk of RCC (RR: 0.86; 95% CI: 75-0.99, P=0.030). Statistical heterogeneity was not identified (I2=28.8%, P=0.199). Subgroup analyses results showed the gender differences, and the associations were significant in results with women participants (RR: 0.70; 95% CI: 0.55-0.88) and case-control studies (RR: 0.80, 95% CI: 0.67-0.95). Conclusion: Higher circulating vitamin D level and higher dietary vitamin D intake both might be associated with a reduced risk of RCC. Further high-quality randomized controlled trials are required in the future to confirm our results.

Epistaxis: the cause found beyond the nose.

Renal cell carcinoma (RCC) is a malignant disease that is often diagnosed at a metastatic stage. The head and neck represent up to 3% of the metastatic RCC, and the paranasal sinus area is one of the least involved sites. Here, we introduce the case of a 74-year-old female patient who presented with a history of traumatic nasal bleed. A cranial computed tomography scan and magnetic resonance imaging showed a fronto-ethmoidal mass with pachymeningeal involvement. A nasal biopsy from the paranasal sinuses was taken. On histopathological examination, metastatic clear cell carcinoma was the main hypothesis, which later was confirmed to be RCC on immunohistochemistry. On further radiological examination, an exophytic mass was depicted in the kidney's upper and middle pole. The patient had no renal complaints and was asymptomatic. Fronto-ethmoidal sinus is a rare site for metastatic RCC, especially in cases where the patient is asymptomatic. Early detection by keeping RCC metastasis as the differential diagnosis in such cases can lead to early treatment and improve the overall survival of the patient.

Bellini duct carcinoma.

The modern era has brought an appreciation that renal cell carcinoma (RCC) includes diverse subtypes derived from the various parts of the nephron, each with its distinctive genetic basis and tumor biology. Carcinoma of the collecting ducts of Bellini (CDC) is a rare subtype of RCC, with a predictably poor prognosis. This rare subtype represents less than 1% of all kidney carcinomas. It derives from presumably numerous chromosomal losses. It is of chief importance to differentiate CDC from other types of renal cell cancer. Typically, it is characterized by a firm, centrally located tumor with infiltrative borders. Regarding the histopathologic characteristics, we can find complex, highly infiltrative cords with inflamed (desmoplastic) stroma, with high-grade nuclei and mitoses. Most reported cases of CDC had been high grade, advanced stage, and unresponsive to conventional therapies. This rare form of disease highlights the importance of multidisciplinary teams in the management of cancer patients.

Enfermedad renal crónica y aparición de metástasis posterior a nefrectomía radical y parcial por carcinoma renal de células claras / Chronic kidney disease and clear renal cell carcinoma metastasis following radical or partial nephrectomy

RESUMEN Introducción: El uso de la nefrectomía parcial para el tratamiento del carcinoma de células renales en estadios tempranos se ha convertido en una de las intervenciones preferidas para estos pacientes en la Argentina. Sin embargo, sus resultados en el país a largo plazo aún se desconocen. En este estudio analizamos la progresión a enfermedad renal crónica y aparición de metástasis posterior a nefrectomía parcial y radical, en pacientes con carcinoma de células renales. Material y métodos: Se realizó un estudio de cohorte retrospectivo. Se incluyeron a todos los pacientes con carcinoma renal de células claras en estadio T1 que, entre 2006 y 2012, se sometieron a nefrectomía parcial en nuestro hospital. Se realizó un seguimiento hasta enero del 2018. Resultados: Se incluyeron 32 pacientes (19 con nefrectomía radical y 13 con nefrectomía parcial). Comparado con el grupo de nefrectomía parcial, los individuos sometidos a nefrectomía radical presentaron mayor progresión a enfermedad renal crónica (nefrectomía radical 63,2% vs nefrectomía parcial 15,4%; p=0,007). No existieron diferencias en el tiempo de seguimiento de ambos grupos (nefrectomía radical 69,3 ± 23,8 vs nefrectomía parcial 72,5 ± 26,9 meses; p=0,73). Los sujetos sometidos a nefrectomía radical tuvieron 11 veces mayor riesgo de progresión a enfermedad renal crónica que los de nefrectomía parcial (HR ajustado 11,12, IC95 1,24-99,9; p=0,031) ajustado por los demás factores de riesgo tradicionales. Ningún paciente con estadio T1a presentó metástasis durante todo el seguimiento, independientemente del tipo de cirugía. Conclusión: En nuestro estudio, la nefrectomía parcial preserva mejor la función renal a largo plazo que la nefrectomía radical y tiene un excelente perfil de seguridad oncológico en pacientes con carcinoma de células renales en estadio T1a. La nefrectomía radical fue un factor de riesgo independiente de progresión a enfermedad renal crónica.

ABSTRACT Introduction: Partial nephrectomy to treat early-stage renal cell carcinoma has become one of the surgeries of choice for patients in Argentina. However, long-term results in the country are unknown. In this study, we analyzed the progression to chronic kidney disease and the appearance of metastasis after partial or radical nephrectomy in renal cell carcinoma patients. Methods: A retrospective, cohort study was conducted. We included all patients suffering from T1 stage clear cell renal carcinoma who, between 2006 and 2012, underwent partial nephrectomy in our hospital. Follow-up continued until January 2018. Results: Thirty-two patients were included (19 had undergone radical nephrectomy and 13, partial nephrectomy). Subjects who had radical nephrectomy showed a more rapid progression to chronic kidney disease as compared to the subjects in the partial nephrectomy group (radical nephrectomy 63.2% vs. partial nephrectomy 15.4%; p=0.007). There were no differences in the follow-up period in both groups (radical nephrectomy 69.3% ± 23.8 months vs. partial nephrectomy 72.5 ± 26.9 months; p=0.73). Risk of progression to end-stage chronic kidney disease was 11 times higher for subjects who had undergone radical nephrectomy as compared to subjects who had had partial nephrectomy (adjusted HR 11.12; 95% CI: 1.24-99.9; p=0.031), adjusted by the rest of traditional risk factors. None of the T1a patients had metastasis during follow-up, regardless of the type of surgery. Conclusion: According to the findings of our study, partial nephrectomy preserves long-term renal function better than radical nephrectomy and has an excellent oncologic safety profile in T1a stage renal cell carcinoma patients. Radical nephrectomy was an independent risk factor of progression to chronic kidney disease.

A comparison of oncologic and functional outcomes in patients with pt3a renal cell carcinoma treated with partial and radical nephrectomy.

HYPOTHESIS: Partial Nephrectomy is oncological safe in patients with pT3a RCC. PURPOSE: To compare the oncological and functional outcomes of patients with pT3a RCC scheduled for PN and RN. MATERIALS AND METHODS: We retrospectively reviewed patients with pT3a N0 M0 RCC who underwent partial or radical nephrectomy from 2005 to 2016. Perioperative characteristics, including estimated glomerular filtration rate, tumor size, pathological histology, and RENAL nephrometry score, were compared between patients scheduled for partial or radical nephrectomy. We used multivariable Cox proportional hazards regression models to compare overall survival, cancer-specific survival, and recurrence-free survival between planned procedure type. RESULTS: Of the 589 patients, 369 (63%) and 220 (37%) were scheduled for radical and partial nephrectomy, respectively; 26 (12%) of the scheduled partial nephrectomy cases were intraoperatively converted to radical nephrectomy. After adjusting for tumor size and histology, there were no statistically significant differences in overall survival (hazard ratio 0.66; 95% CI, 0.38-1.13), cancer-specific survival (hazard ratio 0.53; 95% CI, 0.16-1.75), or recurrence-free survival (hazard ratio 0.66; 95% CI, 0.34-1.28) between patients scheduled for partial or radical nephrectomy. Fewer patients scheduled for partial nephrectomy had estimated glomerular filtration rate reductions 3 to 9 months after surgery than patients scheduled for radical nephrectomy. CONCLUSION: We found no evidence that patients scheduled to undergo partial nephrectomy had poorer oncologic outcomes than patients scheduled to undergo radical nephrectomy. In select patients with pT3a renal cell carcinoma in whom partial nephrectomy is deemed feasible by the surgeon, partial nephrectomy should not be discouraged.

Surgical Insights for the Management of Variant Histology in Renal Cell Carcinoma.

PURPOSE: To review the current literature regarding variant (non-clear) histology of renal cell carcinoma (RCC) and the clinical management of these renal tumors. MATERIAL AND METHODS: A PubMed database search was performed in May 2020 focusing on variant RCC, its diagnosis and associated syndromes, tumor characteristics, and options for management. RESULTS: A broad range of pathological, clinical and diagnostic characteristics amongst non-ccRCC variants were found to have an impact on the overall management of these tumors. The imaging modalities, frequency of surveillance, and timing for intervention were found to be dependent on the type of genetic alterations, type of histology, and tumor growth rates. The timing and type of surgery as well as the systemic therapy are tailored to the specific tumor type and patient. CONCLUSION: The findings of this review suggest that clinical management should be considered and adjusted for patients with non-ccRCC histological variants based on tumor subtype and genetic alterations.

Survival nomogram for patients with bone metastatic renal cell carcinoma: A population-based study

ABSTRACT Purpose: Increased attention has been focused on the survival of renal cell carcinoma (RCC) patients with bone metastasis. This study proposed to establish and evaluate a nomogram for predicting the overall survival (OS) and cancer-specific survival (CSS) of RCC patients with bone metastasis. Materials and Methods: RCC patients with bone metastasis between 2010 and 2015 were captured from the surveillance, epidemiology and end results (SEER) database. Univariate and multivariate cox regressions were performed to assess the effects of clinical variables on OS and CSS. The nomogram based on the Cox hazards regression model was developed. Concordance index (C-index) and calibration curve were performed to evaluate the accuracy of nomogram models, receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were conducted to assess the predict performance. Results: A total of 2.471 eligible patients were enrolled in this study. The patients were assigned to primary (n=1.672) and validation (n=799) cohorts randomly. The 1-, 2-, and 3-year OS and CSS nomogram models were constructed based on age at diagnosis, sex, marital status, pathological grade, T-stage, N-stage, brain/liver/lung metastasis, surgery, radiotherapy and chemotherapy. The c for OS and CSS prediction was 0.730 (95% confidence interval [CI]: 0.719-0.741) and 0.714 (95%CI:0.702-0.726). The calibration curves showed significant agreement between nomogram models and actual observations. ROC and DCA indicated nomograms had better predict performance. Conclusions: The nomograms for predicting prognosis provided an accurate prediction of OS and CSS in RCC patients with bone metastasis, and contributed clinicians to optimize individualized treatment plans.

Pembrolizumab plus axitinib and nivolumab plus ipilimumab as first-line treatments of advanced intermediate- or poor-risk renal-cell carcinoma: a number needed to treat analysis from the Brazilian private perspective.

BACKGROUND: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. METHODS: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. RESULTS: Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,773,865 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. CONCLUSION: At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.