Resección de metástasis pancreáticas: análisis de resultados quirúrgicos y oncológicos. Estudio de cohorte retrospectiva / Pancreatic resections for metastases in the pancreas: analysis of surgical and oncologic outcomes. A retrospective cohort study

RESUMEN Antecedentes: las metástasis pancreáticas, si bien son poco frecuentes, representan una entidad clínica cuyo diagnóstico probablemente se incrementará en el futuro por el aumento de los programas de seguimiento oncológico. Objetivo: describir los resultados quirúrgicos y oncológicos de una serie de pacientes operados por metástasis pancreáticas. Materiales y métodos: se realizó un estudio de cohorte retrospectivo, descriptivo, multicéntrico, de los pacientes sometidos a resecciones pancreáticas por metástasis entre enero de 2016 y diciembre de 2022, en tres efectores de salud por el mismo grupo quirúrgico. Resultados: fueron operados 19 pacientes, con una media de edad de 59 años (45-79), 11 de sexo femenino, en buen estado general y sin otra evidencia de enfermedad oncológica. El origen de los tumores primarios fue 14 en riñón (7 diagnosticados durante el seguimiento), uno carcinoma mamario, uno melanoma, uno testicular, uno colorrectal y uno de cuello de útero. Las técnicas quirúrgicas empleada fueron: 7 esplenopancreatectomías (5 videolaparoscópicas y 2 convencionales), 4 enucleaciones (3 convencionales y 1 videolaparoscópica), 3 duodenopancreatectomías cefálicas convencionales, 2 duodenopancreatectomías totales convencionales, 2 pancreatectomías centrales convencionales, y una pancreatectomía corporocaudal con preservación del bazo. No se registró mortalidad operatoria (dentro de los 90 días posoperatorios), y presentaron una supervivencia global y libre de enfermedad de 58 y 53 meses, respectivamente. Conclusión: la resección de metástasis pancreáticas, en casos seleccionados, con un abordaje multidisciplinario, y en centros de alto volumen de patología hepatobiliopancreática, es segura y permite buenos resultados oncológicos y de supervivencia global.

ABSTRACT Background: Pancreatic metastases are rare but are likely to be diagnosed more frequently in the future due to the increase in oncology surveillance programs. Objective: The aim of this study was to describe the surgical and oncologic outcomes of a series of patients undergoing surgery for pancreatic metastases. Materials and methods: We conducted a retrospective, descriptive, and multicenter cohort study on patients who underwent pancreatic resections for metastases in the pancreas by the same surgical group between January 2016 and December 2022 in three healthcare providers. Results: A total of 19 patients were operated on, mean age was 59 years (45-79), and 11 were women with good performance status and no other evidence of oncologic disease. Clear cell renal cell carcinoma was the primary tumor in 14 cases (7 diagnosed during surveillance), and the remaining primary tumors were one case of breast ductal carcinoma, one testicular cancer, one colorectal cancer, one melanoma and one cervical cancer. The surgical techniques used were pancreatectomies and splenectomies in 7 patients (5 via laparoscopy and 2 conventional procedures), 4 enucleations (3 conventional procedures and 1 laparoscopic surgery), 3 conventional cephalic pancreaticoduodenectomies, 2 conventional central pancreatectomies and one spleen-preserving distal pancreatectomy. No deaths were reported within 90 days of surgery, and overall survival and disease-free survival were 58 and 53 months, respectively. Conclusion: Resection of pancreatic metastases is safe and provides good oncologic outcomes and overall survival when performed with a multidisciplinary approach in centers with a high volume of hepatobiliary and pancreatic surgeries and in selected cases.

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.

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.

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.

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 de carcinoma renal de células claras en la vesícula biliar / Gallbladder metastasis of clear cell renal carcinoma

Resumen El carcinoma renal de células claras (CRCC) es una neoplasia maligna poco común que representa el 3% de todos los tumores malignos en adultos. Este tumor presenta una alta tendencia a desarrollar metástasis sincrónicas o metacrónicas en diferentes sitios anató micos. Aunque la metástasis en la vesícula biliar por CRCC es extremadamente rara, se han reportado casos esporádicos en la literatura médica. Presentamos el caso de una mujer de 78 años con antecedentes de carcinoma indiferenciado de cavum, carcinoma basocelular y CRCC en riñón derecho. Se sometió a nefrectomía radical. El análisis histopatológico confirmó el diagnóstico de CRCC sin invasión vascular ni ureteral. Dos años después, du rante el seguimiento, se detectó una lesión nodular en la vesícula biliar mediante tomografía computarizada. A pesar de la ausencia de síntomas, se decidió la resección quirúrgica. Se realizó colecistectomía laparoscópica sin complicaciones. El examen histopatológico confirmó la presencia de metástasis de CRCC en la vesícula biliar. La paciente evolucionó favorablemente encontrándose en seguimiento sin recurrencia. La metástasis vesicular por CRCC es extremadamente rara, pero los cirujanos deben considerarla en pacientes con antecedentes de CRCC. El diagnóstico diferencial prequirúrgico entre el carcinoma primario de vesícula biliar y la metástasis de CRCC puede ser desafiante y, a menudo, se confirma mediante el examen histopatológi co. La resección quirúrgica completa parece ser la mejor opción de tratamiento para lograr una supervivencia libre de enfermedad.

Abstract Clear cell renal cell carcinoma (ccRCC) is an uncom mon malignant neoplasm that accounts for 3% of all malignant tumors in adults. This tumor exhibits a high tendency to develop synchronous or metachronous me tastases in different anatomical sites. Although gallblad der metastasis from ccRCC is extremely rare, sporadic cases have been reported in the medical literature. We present the case of a 78-year-old woman with a history of undifferentiated nasopharyngeal carcinoma, basal cell carcinoma, and ccRCC in the right kidney. She un derwent radical nephrectomy. Histopathological analysis confirmed the diagnosis of ccRCC without vascular or ureteral invasion. Two years later, during follow-up, a nodular lesion was detected in the gallbladder through computed tomography. Despite the absence of symp toms, surgical resection was decided. Laparoscopic cho lecystectomy was performed without complications. Histopathological examination confirmed the presence of ccRCC metastasis in the gallbladder. The patient had a favorable outcome and is currently under follow-up without recurrence. Gallbladder metastasis from ccRCC is extremely rare, but surgeons should consider this possibility in patients with a history of ccRCC. Preoperative differential diagno sis between primary gallbladder carcinoma and ccRCC metastasis can be challenging and is often confirmed through histopathological examination. Complete sur gical resection is the best treatment option to achieve disease-free survival.

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.

La inmunoterapia en el manejo del cáncer renal metastásico: En tratamiento con inhibidores de checkpoint PD-L1 y/o anti-CTLA-4. A propósito de un caso / Case report about immunotherapy in management of metastatic renal cancer: Treatment with checkpoint PD-L1 and/or anti-CTLA-4 inhibitors

RESUMEN El carcinoma de células renales (CCR) aproximadamente el 15 por ciento se presentan como localmente avanzado o metastásico, donde la cirugía no es curativa. El pronóstico de los pacientes con CCR avanzado o metastásico puede variar desde unos meses hasta algunos años, según las características clínicas, patológicas, radiológicas de la enfermedad. El advenimiento del uso de anti monoclonales basado en la inmunoterapia como inhibidores de puntos de control en la terapia sistémica inicial para el CCR avanzado de células claras. Presentaremos un caso clínico donde la inmunoterapia juega un rol mediante el uso de anti monoclonales para el abordaje de un paciente varón con enfermedad renal metastásica que presenta respuesta clínica después del tratamiento quirúrgico e inmunoterapia por 2 años sin evidencia de enfermedad oncológica hasta la actualidad.

ABSTRACT Approximately 15 percent of renal cell carcinoma (RCC) present as locally advanced or metastatic, where surgery is not curative. The prognosis of patients with advanced or metastatic RCC can vary from a few months to a few years, depending on the clinical, pathological, and radiological characteristics of the disease. The advent of the use of anti-monoclonal-based immunotherapy as checkpoint inhibitors in initial systemic therapy for advanced clear cell RCC. We will present a clinical case where immunotherapy plays a role through the use of anti-monoclonal drugs to treat a male patient with metastatic kidney disease who presents a clinical response after surgical treatment and immunotherapy for 2 years without evidence of oncological disease to date.

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.

Autoimmune encephalitis related to nivolumab followed by tumor regression / Encefalitis autoinmune relacionada con nivolumab se guida de regresión tumoral

Abstract Immune checkpoints inhibitors have shown a re markable improvement in overall survival of stage IV renal cell carcinoma patients. Nevertheless, there is a wide range of immune-related adverse events (IRAE) that arise from these revolutionary treatments. Autoim mune encephalitis is a rare but severe central nervous system IRAE in these cancer patients. The severities of these IRAEs preclude patients from continuing im munotherapy treatment. Few cases of autoimmune encephalitis with immunotherapy have been described in the literature and optimal clinical management of these events as well as patient's immune-mediated response after treatment suspension is still unclear. Here, we report a case of a 67 years-old woman with stage IV renal cell carcinoma under treatment with nivolumab who developed autoimmune encephalitis. After high doses of corticosteroids patient's condition improved significantly with full recovery after 5 days of treatment. Even though nivolumab was not reinstalled, a persistent response of her oncologic disease was evi denced. We expect that this case can contribute to the existing literature of both subjects, the management of autoimmune encephalitis as grade IV immune related adverse event and the responses of immune checkpoint inhibitors after IRAE.

Resumen Los inhibidores de puntos de control inmunológico han mostrado una importante mejoría en la supervi vencia global de los pacientes con carcinoma de riñón estadio IV. Sin embargo, existe una amplia variedad de efectos adversos inmunomediados que surgen a partir de estos tratamientos revolucionarios. La encefalitis au toinmune es un infrecuente pero grave efecto adverso inmunomediado del sistema nervioso central en estos pacientes. La gravedad de este cuadro impide que los pa cientes continúen con el tratamiento de inmunoterapia. Se han descrito pocos casos de encefalitis autoinmune con inmunoterapia en la literatura y aún no está claro el manejo clínico óptimo de estos eventos, ni cómo continua la respuesta inmunomediada después de la suspensión del tratamiento. Presentamos el caso de una mujer de 67 años con carcinoma de células renales estadio IV que desarrolló encefalitis autoinmune durante el tratamiento con nivolumab. La paciente mejoró significativamente luego del inicio del tratamiento con altas dosis de cor ticoides, con una recuperación completa después de 5 días del mismo. Si bien el nivolumab no se reinició, se evidenció una respuesta persistente de su enfermedad oncológica. Esperamos que este caso pueda contribuir a la literatura existente de ambos temas, el manejo de la encefalitis autoinmune como efecto adverso inmunome diado grado IV y las respuestas que se obtienen con la inmunoterapia luego de estos efectos adversos.

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)

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.

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.

Curcumin Inhibits Proliferation of Renal Cell Carcinoma in vitro and in vivo by Regulating miR-148/ADAMTS18 through Suppressing Autophagy / 中国结合医学杂志

OBJECTIVE@#To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism.@*METHODS@#In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment.@*RESULTS@#Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate.@*CONCLUSION@#Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.

Factors influencing the chronic post-surgical pain after laparoscopic surgery for elderly patients with urinary tract tumors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the incidence and potential influence factors that contribute to chronic post-surgical pain (CPSP) in elderly patients with urinary tract tumors who underwent laparoscopic procedures.@*METHODS@#A retrospective study was conducted to collect the clinical data of 182 elderly patients with urinary tract tumors who were ≥65 years and underwent laparoscopic surgery from October 2021 to March 2022 in Peking University Third Hospital. The patients'demographic information, medical history and the severity of postoperative pain were collected. Telephone follow-ups were made 6 months after surgery, and the patients' CPSP conditions were recorded. The diagnostic criteria of CPSP were referred to the definition made by the International Association for the Study of Pain (IASP): (1) Pain that developed or increased in intensity after surgical procedure and persisted for at least 3 months after surgery; (2) Pain that localized to the surgical field or projected to the innervation territory of a nerve situated around the surgical area; (3) Pain due to pre-existing pain conditions or infections and malignancy was excluded. The patients were divided into two groups based on CPSP diagnosis. Risk factors that predisposed the patients to CPSP were identified using univariate analysis. A multivariate Logistic regression model using back-forward method was designed, including both variables that significantly associated with CPSP in the univariate analysis (P < 0.1), and the variables that were considered to have significant clinical impact on the outcome.@*RESULTS@#Two hundred and sixteen patients with urinary tract tumors who had undergone laparoscopic surgery were included, of whom, 34 (15.7%) were excluded from the study. For the remaining 182 patients, the average age was (72.6±5.2) years, with 146 males and 36 females. The incidence of CPSP at the end of 6 months was 31.9% (58/182). Multiva-riate regression analysis revealed that age ≥75 years (OR=0.29, 95% CI: 0.12-0.73, P=0.008) was the protecting factors for postoperative chronic pain in the elderly patients with urinary tract tumors undergoing surgical treatment, while renal cancer (compared with other types of urinary tract tumors) (OR=3.68, 95% CI: 1.58-8.58, P=0.003), and the 24 h postoperative moderate to severe pain (OR=2.57, 95% CI: 1.14-5.83, P=0.024) were the independent risk factors affecting CPSP.@*CONCLUSION@#Age < 75 years, renal cancer and the 24 h postoperative moderate to severe pain are influence factors of the occurrence of CPSP after laparoscopic surgery in elderly patients with urinary tract tumors. Optimum postoperative multimodal analgesia strategies are suggested to prevent the occurrence of CPSP.

Risk factors for massive hemorrhage after radical nephrectomy and removal of venous tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus.@*METHODS@#From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant.@*RESULTS@#Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003).@*CONCLUSION@#Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.

Clinicopathologic features and prognosis of young renal tumors with tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To retrospectively analyze clinical data of patients under 40 years old who underwent surgical treatment for renal tumors with tumor thrombus from January 2016 to December 2022 at Peking University Third Hospital, and to evaluate the surgical effect and investigate the relationship between clinicopathological characteristics and prognosis.@*METHODS@#The clinical data of 17 young patients with renal tumor thrombus were retrospectively analyzed, and the clinicopathological features and prognosis were summarized. The patients were grouped according to the presence or absence of symptoms, 2017 American Joint Committee on Cancer (AJCC) clinical stage, and postoperative combined adjuvant therapy. Kaplan-Meier method was used to plot the survival curve, and Log-rank test was used to compare the differences in postoperative survival time and progression-free survival time between the different groups. The relationship between clinicopathological features and prognosis was analyzed.@*RESULTS@#All the 17 patients received venous tumor thrombectomy, including 16 patients (94.1%) who underwent radical nephrectomy and 1 patient (5.9%) who underwent partial nephrectomy. Twelve patients (70.6%) had symptoms and 5 (29.4%) had no symptoms before operation. A total of 17 renal tumors were observed, with 2 patients (11.8%) identified as benign and 15 patients (88.2%) classified as malignant. Among the malignant tumors, 1 patient (6.7%) was diagnosed as clear cell carcinoma, while the remaining 14 patients (93.3%) were categorized as non-clear cell carcinoma. In terms of tumor stage, 8 patients (53.3%) were classified as stage Ⅲ according to the AJCC classification, while 7 patients (46.7%) were categorized as stage Ⅳ. Additionally, 6 patients (40%) received multiple adjuvant therapy, while 9 patients (60%) did not undergo such treatment. The follow-up period ranged from 2 to 78 months, with a median follow-up of 41 months. During this time, 3 patients (20%) died. The median survival time after surgery was 39.0 (2.3, 77.8) months, and the progression-free survival time was 16.4 (2.3, 77.8) months. There was no significant difference in postoperative survival time and progression-free survival time among young patients with renal tumor with tumor thrombus, based on the presence of symptoms before surgery (P=0.307, P=0.302), clinical stage of AJCC (P=0.340, P=0.492), and postoperative adjuvant therapy (P=0.459, P=0.253) group.@*CONCLUSION@#The pathological types of young patients with renal tumor with tumor thrombus are more complex and varied due to symptoms, and the proportion of non-clear cell carcinoma in malignant tumor with tumor thrombus is higher. Symptomatic and non-clear cell carcinoma may be potentially associated with poor prognosis. Surgical operation combined with adjuvant therapy is a relatively safe and effective treatment for young patients with renal tumor and tumor thrombus.