Robot-assisted radical nephroureterectomy using the KangDuo Surgical Robot-01 System versus the da Vinci System: a multicenter prospective randomized controlled trial.

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Results of Radical Nephrectomy and Inferior Vena Cava Thrombectomy.

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.

Single Port Robotic Nephrectomy via lower anterior retroperitoneal approach: feasible, safe and effective option in surgically complex patients.

PURPOSE: Minimally invasive radical nephrectomy is often preferred for larger renal tumours not suitable for partial nephrectomy (1). When performed with a multiport robot, the procedure is routinely performed with a transperitoneal approach, with recent studies highlighting important factors for surgical outcomes, including predictive factors (2), segmental artery unclamping techniques (3), and comparisons of robotic techniques (4). This video shows that SP Robot-Assisted Radical Nephrectomy (RARN) via a lower anterior approach is valuable in challenging cases. MATERIALS AND METHODS: We performed SP-RARN on two complex patients using a retroperitoneal lower anterior approach. The first patient, a 54-year-old female with a BMI of 36.8 kg/m², had a ventral hernia and bowel obstruction history, with a 9 cm right middle kidney mass. The second patient, a 58-year-old male with a BMI of 31.19 kg/m², had ESRD and was on peritoneal dialysis for 8 years, with a 3.4x3.7 cm mass in the right superior pole, suspected to be RCC. The surgical technique is detailed in the video. RESULTS: Both procedures were successful, with operative times of 173 and 203 minutes and blood loss of 150 mL. No complications occurred. Patients were discharged after 31 and 38 hours, respectively. Histopathology confirmed RCC. At the 3-month follow-up, no complications or readmissions were reported. Second patient continued peritoneal dialysis without issues. CONCLUSION: Retroperitoneal SP-RARN via the lower anterior approach avoids the peritoneal cavity, making it suitable for certain patients. In these patients, more so than in others, this procedure is feasible, safe, and less morbid than the standard multiport approach.

Real-world implementation of North American and SIOP strategies for the treatment of Wilms tumor in Uruguay.

Wilms tumor has been selected as an index tumor by the WHO Global Initiative for Childhood Cancer with the aim to improve cure rates worldwide. Nevertheless, there is a scarcity of published data on outcomes beyond those of the major cooperative groups. Therefore, we conducted a retrospective analysis including all patients with Wilms tumor treated at our referral center in Uruguay between 1995 and 2020. Treatment consisted of North American (NA) strategies in 23 cases (1995-2004), followed by the SIOP strategy in 35 cases thereafter. Staging included: I-II = 28, III = 7, IV = 14, and V = 9. There were no major surgical or medical complications; however, a delay in the administration of local radiotherapy was observed (median of 21 days after surgery). There were no cases of toxicity- or surgery-related deaths or treatment abandonment. Five-year probability of overall survival was 0.72 and 0.92 for the NA and SIOP groups, respectively. We conclude that outcomes were better for the SIOP strategy with no unexpected toxicities and high treatment compliance in both strategies. Timely implementation of radiotherapy was challenging.

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.

The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer.

BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. RESULTS: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. CONCLUSIONS: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.

Development and validation of prognostic nomograms for adult with papillary renal cell carcinoma: A retrospective study.

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.

Tumor-associated macrophages impair NK cell IFN-γ production and contribute to tumor progression in clear cell renal cell carcinoma.

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.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

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.

Machine Learning Gene Signature to Metastatic ccRCC Based on ceRNA Network.

Clear-cell renal-cell carcinoma (ccRCC) is a silent-development pathology with a high rate of metastasis in patients. The activity of coding genes in metastatic progression is well known. New studies evaluate the association with non-coding genes, such as competitive endogenous RNA (ceRNA). This study aims to build a ceRNA network and a gene signature for ccRCC associated with metastatic development and analyze their biological functions. Using data from The Cancer Genome Atlas (TCGA), we constructed the ceRNA network with differentially expressed genes, assembled nine preliminary gene signatures from eight feature selection techniques, and evaluated the classification metrics to choose a final signature. After that, we performed a genomic analysis, a risk analysis, and a functional annotation analysis. We present an 11-gene signature: SNHG15, AF117829.1, hsa-miR-130a-3p, hsa-mir-381-3p, BTBD11, INSR, HECW2, RFLNB, PTTG1, HMMR, and RASD1. It was possible to assess the generalization of the signature using an external dataset from the International Cancer Genome Consortium (ICGC-RECA), which showed an Area Under the Curve of 81.5%. The genomic analysis identified the signature participants on chromosomes with highly mutated regions. The hsa-miR-130a-3p, AF117829.1, hsa-miR-381-3p, and PTTG1 were significantly related to the patient's survival and metastatic development. Additionally, functional annotation resulted in relevant pathways for tumor development and cell cycle control, such as RNA polymerase II transcription regulation and cell control. The gene signature analysis within the ceRNA network, with literature evidence, suggests that the lncRNAs act as "sponges" upon the microRNAs (miRNAs). Therefore, this gene signature presents coding and non-coding genes and could act as potential biomarkers for a better understanding of ccRCC.

Robotic salvage partial nephrectomy following surgical and ablative therapies.

PURPOSE: Partial nephrectomies in the salvage setting after ablative or surgical therapy remain challenging cases that are underreported in the literature (1-5). The aim of this video is to demonstrate techniques for robotic salvage partial nephrectomy to manage recurrent renal cell carcinoma (RCC) after failed prior partial nephrectomy and primary cryotherapy. MATERIALS AND METHODS: A 55-year-old man after previous robotic-assisted right partial nephrectomy presented with a 2.5 cm locally recurrent renal mass abutting the collecting system. A 59-year-old man with right renal cell carcinoma initially treated with cryoablation presented local recurrence. CT imaging demonstrated 2.6 cm right renal mass consistent with tumor recurrence at previous treatment site. RESULTS: Both procedures were completed in under 180 minutes. Clamp time was 22 minutes after the previous partial nephrectomy and 25 minutes after previous cryotherapy. There were no perioperative complications. Pathology in both cases demonstrated pT1a clear cell RCC with negative margins. Both patients have since no evidence of recurrent disease on follow-up imaging at 1 and 2 years, respectively. CONCLUSIONS: Salvage robotic partial nephrectomy should be considered as a feasible treatment option after failure of initial therapy-surgical or ablative. A salvage procedure is often more challenging than its standard therapy-naïve counterpart due to development of dense inflammation after previous interventions. Despite this, robotic partial nephrectomies in the salvage setting can be safely carried out with good surgical outcomes, particularly when utilizing intraoperative ultrasound to identify tumor margins and key anatomy.

Clinical safety and efficacy of microwave ablation for small renal masses.

PURPOSE: CT-guided MWA is a safe and effective tool that should be utilized in the treatment of small renal masses (SRMs). We aim to clarify the utility of CT-guided MWA by examining patient outcomes such as recurrence, treatment success, changes in renal function, and complications. METHODS: A retrospective review of consecutive patients with SRMs who underwent same day renal mass biopsy (RMB) and CT-guided MWA between 2015 and 2022 was performed. Treatment safety was assessed by 30-day complications according to the Clavien-Dindo system and change in eGFR >30 days post-procedure. Treatment efficacy was defined by local recurrence and incomplete treatment rates and calculated using the Kaplan-Meier method. RESULTS: A total of 108 renal masses were found in 104 patients. The overall complication rate was 7.4% (8/108), of which 4 were major complications (3.7%). For those with renal function available >30 days post ablation, the median eGFR was 47.2 (IQR: 36.0, 57), compared to 52.3 (IQR: 43.7, 61.5) pre-ablation, p<0.0001. 5-year local recurrence free survival was 86%. Among those with biopsy proven malignancy (n= 66), there were five local recurrences (7.54%) occurring at a median of 25.1 months (IQR 19.9, 36.2) and one case (1.5%) of incomplete treatment. CONCLUSIONS: As the medical field continues to evolve towards less invasive interventions, MWA offers a valuable tool in the management of renal masses. With low major complication and recurrence rates, our findings support the utility of CT-guided MWA as a tool for treatment of SRMs.

Enfermedad oncoproliferativa en el receptor de trasplante renal. Nuestra experiencia / Oncoproliferative diseases in kidney transplant recipients. Our experience

Introducción: El cáncer conlleva a una mortalidad de hasta 12 % en los pacientes trasplantados, y se considera la tercera causa de morbilidad y mortalidad en los receptores, al ser estos susceptibles a desarrollar enfermedades oncoproliferativas, a largo plazo. Objetivo: Describir la incidencia de neoplasias en receptores de trasplante renal. Métodos: Estudio descriptivo y longitudinal que incluyó 15 receptores de trasplante renal funcionante, con diagnóstico de neoplasias malignas en diferentes localizaciones en el período comprendido entre enero de 2017 y junio de 2023 en el servicio de Nefrología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro» de Santa Clara, Villa Clara. Resultados: Predominaron los hombres y el color de piel blanca: 53,3 % y 73,3% respectivamente, con tiempo postrasplante superior a tres años en 12 pacientes (80 %). El antecedente de exposición al citomegalovirus representó el 80 %; la infección bacteriana de la vía respiratoria y digestiva fue la más frecuente. Conclusiones: La neoplasia intraepitelial cervicouterina, la de colon con metástasis hepática y las cerebrales resultaron las más frecuentes, y fueron tratadas con cirugía, quimioterapias o ambas, según los criterios quirúrgicos en cada caso; no obstante, la mortalidad fue elevada. La estirpe neoplásica preponderante fue la neoplasia intraepitelial cervical en un 26,6 %. La mortalidad fue alta y la supervivencia fue menor en el sexo masculino, sin rebasar los dos años posteriores al diagnóstico.

Introduction: cancer entails a mortality of up to 12 % in transplanted patients and is considered the third leading cause of morbidity and mortality in recipients who are susceptible to develop oncoproliferative diseases in the long term. Objective: to describe the incidence of neoplasms in renal transplant recipients. Methods: we carried out a descriptive and longitudinal study including 15 functioning renal transplant recipients who were diagnosed with malignant neoplasms in different locations in the Nephrology service at "Arnaldo Milián Castro" Clinical and Surgical University Hospital in Santa Clara, Villa Clara between January 2017 and June 2023. Results: males and white skin color predominated: 53.3 % and 73.3% respectively, with post-transplant time greater than three years in 12 patients (80 %). The history of cytomegalovirus exposure represented 80 %; bacterial infection of the respiratory and digestive tracts was the most frequent. Conclusions: cervicouterine intraepithelial neoplasia, colon cancer with liver and brain metastases were the most frequent and treated with surgery chemotherapies or both according to the surgical criteria in each case; however, mortality was elevated. Cervical intraepithelial neoplasia predominated in a 26.6 %. Mortality was high and survival was lower in males, without exceeding two years after the diagnosis.

Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810.

PURPOSE: Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. PATIENTS AND METHODS: Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. RESULTS: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. CONCLUSION: Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.