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The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.
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PURPOSE OF REVIEW: Renal Cell Carcinoma (RCC) with invasion into the inferior vena cava (IVC) is a rare and mortal condition. Patients with RCC have an average life expectancy of no more than six months, thus requiring an aggressive surgical approach. We analyze the outcomes of patients that underwent surgery at a single medical institution. RECENT FINDINGS: The analysis of recent series of successful treatment with radical nephrectomy and IVC thrombectomy shows a 5 year survival from 45 to 69%. We found in the analyzed series that the success of the treatment in these patients depends on the resection of the renal tumor and venous thrombectomy. We found that at our medical institution nephrectomy and IVC thrombectomy with primary repair have no intraoperative mortality and no pulmonary embolism. Nephrectomy and thrombectomy of IVC is a reliable approach for patients with advance RCC.
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Carcinoma de Células Renais , Neoplasias Renais , Nefrectomia , Trombectomia , Veia Cava Inferior , Humanos , Neoplasias Renais/cirurgia , Veia Cava Inferior/cirurgia , Nefrectomia/métodos , Trombectomia/métodos , Carcinoma de Células Renais/cirurgia , Resultado do Tratamento , Invasividade NeoplásicaRESUMO
The upper urinary tract is the most common human organ system affected by congenital anomalies. A Horseshoe kidney is a fusion anomaly, it can be described as a fusion across the midline of 2 distinct functioning kidneys. The incidence of renal tumors in a Horseshoe kidney is higher than in the normal population. We present a 60-year-old male patient with a history of Horseshoe kidney and a diagnosis of clear cell renal cell carcinoma who underwent a combined therapeutic approach, guided by interventional radiology. This approach involved selective transarterial embolization and microwave ablation. Three months after surgery and with abdominal MRI follow-up, there is evidence of a non-viable tumor, indicating a favorable response to the intervention.
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PURPOSE: This study aims to develop radiomics models and a nomogram based on machine learning techniques, preoperative dual-energy computed tomography (DECT) images, clinical and pathological characteristics, to explore the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC). METHODS: We retrospectively recruited of 87 patients diagnosed with ccRCC through pathological confirmation from Center I (training set, n = 69; validation set, n = 18), and collected their DECT images and clinical information. Feature selection was conducted using variance threshold, SelectKBest, and the least absolute shrinkage and selection operator (LASSO). Radiomics models were then established using 14 classifiers to predict TME cells. Subsequently, we selected the most predictive radiomics features to calculate the radiomics score (Radscore). A combined model was constructed through multivariate logistic regression analysis combining the Radscore and relevant clinical characteristics, and presented in the form of a nomogram. Additionally, 17 patients were recruited from Center II as an external validation cohort for the nomogram. The performance of the models was assessed using methods such as the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The validation set AUC values for the radiomics models assessing CD8+, CD163+, and αSMA+ cells were 0.875, 0.889, and 0.864, respectively. Additionally, the external validation cohort AUC value for the nomogram reaches 0.849 and shows good calibration. CONCLUSION: Radiomics models could allow for non-invasive assessment of TME cells from DECT images in ccRCC patients, promising to enhance our understanding and management of the tumor.
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OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.
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Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Humanos , Masculino , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Prognóstico , Adulto , Idoso , Reprodutibilidade dos Testes , Estadiamento de Neoplasias , Programa de SEERRESUMO
INTRODUCTION: Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS: In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS: Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION: RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.
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PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , América Latina , Consenso , SunitinibeRESUMO
Tumor-associated macrophages (TAM) are abundant in several tumor types and usually correlate with poor prognosis. Previously, we demonstrated that anti-inflammatory macrophages (M2) inhibit NK cell effector functions. Here, we explored the impact of TAM on NK cells in the context of clear-cell renal cell carcinoma (ccRCC). Bioinformatics analysis revealed that an exhausted NK cell signature strongly correlated with an M2 signature. Analysis of TAM from human ccRCC samples confirmed that they exhibited an M2-skewed phenotype and inhibited IFN-γ production by NK cells. Moreover, human M0 macrophages cultured with conditioned media from ccRCC cell lines generated macrophages with an M2-skewed phenotype (TAM-like), which alike TAM, displayed suppressive activity on NK cells. Moreover, TAM depletion in the mouse Renca ccRCC model resulted in delayed tumor growth and reduced volume, accompanied by an increased frequency of IFN-γ-producing tumor-infiltrating NK cells that displayed heightened expression of T-bet and NKG2D and reduced expression of the exhaustion-associated co-inhibitory molecules PD-1 and TIM-3. Therefore, in ccRCC, the tumor microenvironment polarizes TAM toward an immunosuppressive profile that promotes tumor-infiltrating NK cell dysfunction, contributing to tumor progression. In addition, immunotherapy strategies targeting TAM may result in NK cell reinvigoration, thereby counteracting tumor progression.
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Carcinoma de Células Renais , Interferon gama , Neoplasias Renais , Células Matadoras Naturais , Macrófagos Associados a Tumor , Células Matadoras Naturais/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Interferon gama/metabolismo , Interferon gama/imunologia , Humanos , Animais , Camundongos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Progressão da Doença , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Receptor de Morte Celular Programada 1/metabolismoRESUMO
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.
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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.