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.

Renal cell carcinoma, clear cell type with secondary polycythemia in a young Filipino male: A case report

Introduction@#Clear Cell Renal Cell Carcinoma, a renal cortical tumor characterized by malignant epithelial cells with clear cytoplasm and compact alveolar or acinar growth pattern interspersed with intricate arborizing vasculature.1 This is rare in people less than 45 years old. Though it has varied clinical manifestations, its classical triad: abdominal mass, hematuria, and groin pain only present in four to 17% of cases.2 We therefore present a case of renal cell carcinoma occurring in an unusual age group who presented with vague gastrointestinal symptoms and polycythemia which accounts only less than 5% of cases.3@*Case Presentation@#This is a case of a 28-year-old Filipino male who presented with epigastric pain with abdominal fullness and anorexia who later complained of frequent vomiting after solid and liquid intake. CBC revealed polycythemia. Gastroscopy with biopsy showed esophagitis Los Angeles classification Grade A and duodenal mass obstructing 95% of the lumen. Computed tomographic scan of whole abdomen revealed large renal mass, right of 15.9x9.35x11.34cm extending superiorly at the antropyloric region causing gastric luminal narrowing down to first and second segments of duodenum with a 4.2cm enlarged lymph node in aortocaval area. Magnetic resonance imaging revealed a huge complex right renal mass of 12x12x10cm in size extending beyond Gerota’s fascia with 8x5.2x6.2cm lymph node compressing the vena cava. Right radical nephrectomy was done for both supportive management to relieve the obstruction and for histologic diagnosis which revealed clear cell renal cell carcinoma. JAK2 gene mutation test was done to determine the cause of polycythemia and phlebotomy was performed to address the problem.@*Conclusion@#This case presents with vague gastrointestinal symptoms which is atypical of renal cell carcinoma, hence highlights the importance of properly investigating its cause. Furthermore, a multidisciplinary approach involving different subspecialties plays a significant role in the diagnosis and management in this patient.

Clinicopathological features of intravascular large B-cell lymphoma and collision tumors of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.

Progress in targeted inhibition of aerobic glycolysis combined with immunotherapy for renal cell carcinoma / 细胞与分子免疫学杂志

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

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.

Metastatic clear-cell renal carcinoma: an exceptional cause of ileocolonic intussusception in adults

Introduction: Intussusceptions in adults are rare, representing 1% to 5% of intestinal obstructions in this age group. This condition can be caused by benign and malignant lesions acting as lead points, the latter being the most frequent. Furthermore, the diagnosis is challenging due to the non-specific symptoms with variable duration. Case Presentation: A 43-year-old man, with a history of localized clear-cell renal carcinoma (ccRCC) treated 9 years earlier with a right radical nephrectomy, presented with bowel obstruction symptoms. An abdominal computed tomography scan showed an ileocolonic intussusception. Hence, the patient required a right hemicolectomy with ileotransverse anastomosis. The histopathological analysis showed a metastatic ccRC to the terminal ileum causing the intussusception. Discussion: Adult intussusceptions are rare. However, they should be considered in the differential diagnosis of patients with abdominal pain and symptoms of bowel obstruction. Metastases of renal cancer to the small bowel are uncommon and even more so in the form of intussusception. Definitive treatment must be tailored to the patient's condition and underlying cause. (AU)

Estudo comparativo entre os resultados per e pós-operatórios da nefrectomia parcial laparoscópica e da laparoscópica assistida por robô / Comparative study between the pre- and postoperative results of laparoscopic partial nephrectomy and robot-assisted laparoscopic nephrectomy

A incidência dos casos de neoplasia de rim tem aumentado consideravelmente e o emprego da cirurgia minimamente invasiva poupadora de néfrons é, atualmente, considerado o padrão ouro para tumores T1a e T1b. Essa cirurgia pode ser realizada de forma minimamente invasiva, por meio da técnica laparoscópica e laparoscópica assistida por robô. No entanto, faz-se necessário um estudo para avaliar os resultados dessas duas técnicas, tendo em vista uma crescente difusão da técnica robô assistida e um maior número de cirurgiões em treinamento. Soma-se a isso a importância de preservação renal e de segurança oncológica, possibilitada pela nefrectomia parcial, que ainda é subutilizada devido à maior dificuldade técnica de realizá-la pela via laparoscópica. OBJETIVO: comparar a cirurgia aparoscópica com a cirurgia laparoscópica assistida por robô na realização da nefrectomia parcial, no período per e pós-operatório, quanto aos resultados de cada uma delas. MÉTODO: trata-se de uma coorte retrospectiva de 209 pacientes com neoplasia de rim localizado, submetidos à nefrectomia parcial laparoscópica no Hospital Madre Teresa, no período de outubro de 2014 a junho de 2019, e à nefrectomia parcial assistida por robô, no Hospital Felício Rocho, entre os anos de 2018 a 2021. Os dados do estudo foram coletados e gerenciados, usando-se as ferramentas eletrônicas de captura de dados REDCap, além da pesquisa de prontuário. A análise dos dados foi realizada utilizandose o software SPSS versão 25. Em todos os testes estatísticos, foi considerado um nível de significância de 5%. RESULTADOS: em relação a fatores clínicos e cirúrgicos, observou-se que o tempo cirúrgico em horas, a permanência no hospital e a permanência no CTI foram maiores no grupo de nefrectomia parcial laparoscópica, quando comparados à nefrectomia parcial laparoscópica assistida por robô. Variáveis como complicações operatórias, hemotransfusão no per operatório, tipo de tumor, tamanho da lesão na peça cirúrgica e margens acometidas não mostraram diferença significativa entre os grupos (p>0,05). As complicações pós-operatórias foram mais frequentes no grupo de nefrectomia parcial laparoscópica (16,7%) quando comparadas ao grupo nefrectomia parcial laparoscópica assistida por robô (7,0%). O estadiamento pós-operatório também apresentou diferença significativa entre os grupos, sendo que os estádios iniciais (T0 e T1) foram proporcionalmente maiores no grupo de nefrectomia parcial laparoscópica, quando comparados ao grupo nefrectomia parcial laparoscópica assistida por robô. Já os estádios (T2 e T3) foram mais incidentes no grupo de nefrectomia parcial laparoscópica assistida por robô em relação ao outro grupo. CONCLUSÃO: com base nos resultados, pode-se afirmar que a técnica robô-assistida apresenta ganhos técnicos significativos e possibilita a ressecção de tumores tecnicamente mais difíceis, com menor taxa de complicações no pós-operatório. Apresenta tempo cirúrgico e tempo de internação hospitalar reduzidos em comparação com a cirurgia realizada por laparoscopia, além de alta precoce para aqueles que necessitam de unidade de terapia intensiva no pósoperatório.

Kidney cancer cases have increased considerably, and minimally invasive nephronsparing surgery is currently considered the gold standard for T1a and T1b tumors. This surgery can be performed minimally invasively, using the laparoscopic and robotassisted laparoscopic techniques. However, a study to evaluate the results of these two techniques is necessary, considering the increasing diffusion of the robot-assisted technique and the larger number of surgeons in training. Added to this is the importance of renal preservation and oncologic safety, made possible by partial nephrectomy, which is still underutilized due to the incredible technical difficulty of performing it laparoscopically. OBJECTIVE: To compare laparoscopic surgery with robot-assisted laparoscopic surgery in performing partial nephrectomy, in the per- and postoperative periods, regarding the results of each. METHODS: This is a retrospective cohort of 209 patients with localized kidney cancer who underwent laparoscopic partial nephrectomy at Hospital Madre Teresa from October 2014 to June 2019 and robot-assisted partial nephrectomy at Hospital Felício Rocho between the years 2018 and 2021. Study data were collected and managed using REDCap electronic data capture tools and chart search. Data analysis was performed using SPSS version 25 software. A 5% significance level was considered in all statistical tests. RESULTS: Regarding clinical and surgical factors, surgical time in hours, hospital stay, and intensive care unit stay were higher in the laparoscopic partial nephrectomy group when compared to the robot-assisted laparoscopic partial nephrectomy. Variables such as operative complications, intraoperative blood transfusion, tumor type, size of the lesion on the surgical specimen, and affected margins showed no significant difference between groups (p>0.05). The variable postoperative complications showed higher frequency in the laparoscopic partial nephrectomy group (16.7%) compared to the robot-assisted partial nephrectomy group (7.0%). Postoperative staging also showed significant differences between groups, with early stages (T0 and T1) proportionally higher in the laparoscopic partial nephrectomy group when compared to the robot-assisted laparoscopic partial nephrectomy group. Stages (T2 and T3) were higher in the laparoscopic robot-assisted partial nephrectomy group compared to the other group. CONCLUSION: Based on the results, it can be stated that the robot-assisted technique presents significant technical gains and allowed the resection of tumors that are technically more difficult and with a lower rate of complications in the postoperative period. It presented reduced surgical time and hospital stay compared to the surgery performed by laparoscopy. In patients who need to be referred to the intensive care unit postoperatively, the robot-assisted technique demonstrates a reduction in the length of stay in the intensive care unit.

Avaliação do valor prognóstico da expressão imuno-histoquímica das proteínas renina, eritropoietina e catepsina D em pacientes portadores de carcinoma de células renais do tipo células claras / Analysis of the immunohistochemical expression and the prognostic value of renin, erythropoietin, and cathepsin D in patients with clear cell renal cell carcinoma

INTRODUÇÃO: Nas últimas décadas, houve uma migração do diagnóstico do carcinoma de células renais (CCR) para estádios mais precoces. Contudo, não houve uma concomitante redução das taxas de mortalidade. Características tumorais e relacionadas aos pacientes apresentam o maior impacto prognóstico, particularmente estádio clínico, tamanho tumoral, grau nuclear e subtipo histológico. No entanto, agrupá-las com outros parâmetros, inclusive biomoleculares, pode levar a uma análise mais acurada. OBJETIVO: Nosso objetivo foi avaliar a expressão imuno-histoquímica (IHQ) e o valor prognóstico da eritropoietina (EPO), da catepsina D (CTSD), além de entender se a expressão concomitante da renina (REN), com cada um desses dois marcadores, interfere nos desfechos oncológicos do CCR do tipo células claras (CCRcc) em pacientes não metastáticos. MATERIAL E MÉTODOS: Foram analisados dados de 729 pacientes com CCRcc submetidos a tratamento cirúrgico no A.C.Camargo Cancer Center entre 1985 e 2016. Todas as lâminas passaram por revisão anatomopatológica central por uropatologistas especializadas. Blocos de tissue microarray (TMA) foram construídos com amostras duplicadas de cada caso e as reações IHQ foram realizadas com clones de anticorpos previamente selecionados para REN, EPO e CTSD. As expressões de REN e EPO foram classificadas qualitativamente em "positiva" ou "negativa". A expressão da CTSD foi classificada em "expressão fraca ou ausente" ou "forte expressão". Foram analisadas associações com as variáveis clínicas e patológicas e as taxas de sobrevida global (SG), sobrevida câncer específica (SCE) e sobrevida livre de recorrência (SLR) em 10 anos. RESULTADOS: A REN mostrou-se positiva em 426 casos (70,6%) e negativa em 177 (29,4%). A expressão positiva de EPO ocorreu em 86,6% da amostra. Já a CTSD, apresentou expressão fraca ou ausente em 58,2% e expressão forte em 41,3% dos casos. A expressão de EPO não impactou os desfechos oncológicos, nem se associou com variáveis clínicas ou patológicas de destaque, mesmo quando analisada em conjunto com a expressão de REN. Esta última, quando ausente, associou-se com idade mais elevada, anemia pré-operatória, tamanho tumoral, infiltração de gordura perirrenal, hilo ou seio renal, invasão microvascular, necrose, alto grau nuclear de ISUP e estádio clínico III-IV. Por outro lado, a forte expressão de CTSD também se associou com várias dessas variáveis de pior prognóstico. A ausência de expressão IHQ de REN e a forte expressão de CTSD, tanto de modo isolado, como em conjunto, foram fatores preditores de pior SG e SCE em 10 anos. A ausência da primeira e, particularmente, a combinação dos dois fatores influenciaram negativamente também a SLR. CONCLUSÃO: Enquanto a EPO não demonstrou valor prognóstico neste estudo, a ausência de REN, a forte expressão de CTSD, além da combinação destes dois fatores, foram capazes de se associar com piores desfechos oncológicos no CCR não metastático

INTRODUCTION: In the last decades, it has been observed a stage migration in renal cell carcinoma (RCC). However, there was no concomitant reduction in mortality rates. The tumoral factors, such as the clinical stage, tumor size, nuclear grade, or histologic subtype, have been characterized as major predictors. Nonetheless, an improvement of this analysis can be achieved after combine them with other variables, including biomolecular factors. PURPOSE: To assess the immunohistochemical (IHC) expression and the prognostic value of erythropoietin (EPO) and cathepsin D (CTSD), besides evaluating if the concomitant expression of the previously studied protein renin (REN), with each one of the other markers, can influence the prognostic outcomes in non-metastatic patients. MATERIAL AND METHODS: A total of 729 patients with clear cell renal cell carcinoma (ccRCC) who underwent surgical treatment at A.C.Camargo Cancer Center between 1985 and 2016 were evaluated. All cases of the tumor bank were centrally reviewed by dedicated uropathologists. IHC expression patterns of the markers were assessed with a tissue microarray technique. REN and EPO were classified as "positive" or "negative expression". CTSD was grouped in "absent or weak expression" or "strong expression". Associations among clinical and pathological variables and the studied markers, besides of the 10-year overall survival (OS), cancer specific survival (CSS), and recurrence free survival (RFS) rates were described. RESULTS: The REN expression was positive in 426 (70.6%) cases, and the EPO positive expression was observed in 86.6%. It was evidenced an absent or weak expression of CTSD in 58.2%, and a strong expression in 41.3% of this cohort. EPO expression showed no impact on survival rates, even if concomitantly assessed with REN. The negative expression of REN associated with advanced age, preoperative anemia, larger tumors, perirenal fat, hilum or renal sinus infiltration, microvascular invasion, necrosis, high nuclear grade, and clinical stages III or IV. On the other hand, the strong expression of CTSD associated with poor prognostic variables. Both of these expression patterns of REN and CTSD were unfavorable predictors of 10-year OS and CSS. Particularly, the combination of negative REN and strong CTSD expression presented worse impact on these rates than the isolated analysis of each one, including a higher risk of recurrence. CONCLUSION: The loss of REN expression and the strong expression of CTSD were independent prognostic factors in non-metastatic ccRCC, particularly when the concomitant expression pattern of both markers is present. The immunohistochemical expression of EPO did not influence survival rates in this study.

Metástasis de cáncer de células claras renal en cuerdas vocales. Reporte de un caso / Metastasis of renal clear cell carcinoma in vocal cords. A Case report

Introducción: Las metástasis a distancia de tumores primarios a cuerdas vocales son poco frecuentes. Las metástasis a laringe con mayor frecuencia corresponden a melanomas y carcinomas, afectando principalmente a la región supraglótica. Las metástasis a cabeza y cuello de los carcinomas de células renales (CCR) tienen una incidencia de 14-16%. Se presenta el caso de un paciente con metástasis de carcinoma de células claras renal a cuerdas vocales, cuya importancia recae en que es un caso poco frecuente y no existen reportes similares en el país. Paciente masculino, 57 años, con disfonía de 3 meses de evolución. Nasofibroscopía evidencia lesión polipoídea en cuerda vocal y ventrículo izquierdo. Se realiza microcirugía laríngea, enviando muestra a biopsia diferida, resultando lesión metastásica de CCR células claras. Evaluado por nefrología, se pesquisa tumor renal izquierdo sugerente de CCR. Las metástasis de neoplasias remotas a laringe son infrecuentes. Se considera al CCR el tercero en frecuencia respecto a neoplasias infraclaviculares. Éstas se pueden presentar hasta 10 años después del tratamiento del primario. Se recomienda seguimiento a largo plazo y énfasis a nuevos síntomas en región de cabeza y cuello, teniendo en consideración antecedente de CCR en pacientes con disfonía y lesiones polipoídeas en cuerdas vocales.

Introduction: The metastasis of distant site primary tumors to the vocal cords is infrequent. The most frequent source of metastasis to the larynx is melanomas and carcinomas, mainly affecting the supraglottic region. The metastasis to the head and neck of renal cell carcinomas (RCC) has an incidence of 14-16%. To present a case of metastasis of clear renal cell carcinoma to the vocal cords, since it is very infrequent, and there are no similar reports in the country. A male patient, 57 years old, presenting dysphonia for a duration of 3 months. Nasofibroscopy showed a polypoid lesion in the left vocal cord and ventricle. Larynx microsurgery was performed, and a sample was sent for biopsy, which reported a metastatic lesion of RCC clear cells. When assessed by nephrology, a left renal tumor is found, suggesting RCC. The metastasis of distant site neoplasias are infrequent. RCC is considered the third in frequency concerning to infraclavicular neoplasias. These can present up to 10 years after the treatment of the primary. Long term follow-up is recommended, and an emphasis on new symptoms in the head and neck region, considering the history of RCC in patients with dysphonia and polypoid lesions in vocal cords.

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

IMP-1 inhibits renal cell carcinoma 786-O cell growth by targeting EphrinB2 signaling pathway

Abstract EphrinB2 plays a critical role in tumor growth. In this study, we studied the antitumor activity of imperatorin derivative IMP-1 in renal cell carcinoma (RCC) by regulating EphrinB2 pathway.. Results showed that IMP-1 inhibited the proliferation of 786-O cells in a dose- and time-dependent manner. More importantly, knockdown and transfection of EphrinB2 altered the inhibitory effect of IMP-1 on the activity of 786-O cells. IMP-1 arrested 786-O cell cycle at G0/G1 phase by decreasing the expression of cyclin D1 and cyclin E. Moreover, IMP-1 regulated Bcl-2 family proteins' expression, thus inducing apoptosis of 786-O cells. IMP-1 down-regulated the expression of EphrinB2, Syntenin1 and PICK1. Then, IMP-1 decreased the phosphorylation of Erk1/2 and AKT. In all, IMP-1 could regulate the EphrinB2 pathway in order to inhibit 786-O cell growth by arresting the cell cycle at G0/G1 phase and inducing cell apoptosis. Thus, IMP-1 may present as a potential strategy for RCC treatment.

Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation / 中华病理学杂志

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma / 中国医学科学杂志(英文版)

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma / 南方医科大学学报

OBJECTIVE@#To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM).@*METHODS@#We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient.@*RESULTS@#In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05).@*CONCLUSION@#ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.