Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.

Multidisciplinary cancer disease classification using adaptive FL in healthcare industry 5.0.

Emerging Industry 5.0 designs promote artificial intelligence services and data-driven applications across multiple places with varying ownership that need special data protection and privacy considerations to prevent the disclosure of private information to outsiders. Due to this, federated learning offers a method for improving machine-learning models without accessing the train data at a single manufacturing facility. We provide a self-adaptive framework for federated machine learning of healthcare intelligent systems in this research. Our method takes into account the participating parties at various levels of healthcare ecosystem abstraction. Each hospital trains its local model internally in a self-adaptive style and transmits it to the centralized server for universal model optimization and communication cycle reduction. To represent a multi-task optimization issue, we split the dataset into as many subsets as devices. Each device selects the most advantageous subset for every local iteration of the model. On a training dataset, our initial study demonstrates the algorithm's ability to converge various hospital and device counts. By merging a federated machine-learning approach with advanced deep machine-learning models, we can simply and accurately predict multidisciplinary cancer diseases in the human body. Furthermore, in the smart healthcare industry 5.0, the results of federated machine learning approaches are used to validate multidisciplinary cancer disease prediction. The proposed adaptive federated machine learning methodology achieved 90.0%, while the conventional federated learning approach achieved 87.30%, both of which were higher than the previous state-of-the-art methodologies for cancer disease prediction in the smart healthcare industry 5.0.

Renal Function Preservation in Purely Off-Clamp Sutureless Robotic Partial Nephrectomy: Initial Experience and Technique.

The aim of our study is to evaluate the effectiveness and safety of a sutureless off-clamp robot-assisted partial nephrectomy (sl-oc RAPN), particularly its impact on renal function. A multicenter study was conducted from April 2021 to June 2022. Patients diagnosed with a renal mass of >2 cm and a PADUA score of ≤6 consecutively underwent an sl-oc RAPN procedure. Tumor features, patients characteristics, and intraoperative outcomes were assessed. An evaluation of renal function was performed preoperatively, and again at 1 and 3 months after surgery by measuring the creatinine and blood urea nitrogen levels. The renal function of the two separate kidneys was assessed by a sequential renal scintigraphy performed before and at least 30 days after surgery. A total of 21 patients underwent an sl-oc RAPN. The median age was 64 years (IQR 52/70), the median tumor diameter was 40 mm (IQR 29/45), and the median PADUA score was 4 (3.5/5). The intraoperative outcomes included operative time (OT), 90 (IQR 74/100) min; estimated blood loss (EBL), 150 (IQR 50/300) mL; and perioperative complications, CD > 3 1(5%); only two patients presented positive surgical margins in their final histology (2/21, 10%). Compared to the preoperative value, a decrease in renal function was highlighted with a statistically significant median decrease of 10 mL/min (p < 0.01). The renal scintigraphy showed an overall decrease in renal function compared to the preoperative value, with a range in the operated kidney that varied from 0 to 15 mL/s and from 0% to 40%, with a median value of 4 mL/s and 12%. sl-oc RAPN is a safe procedure, with a minimal impact on kidney function alteration. This technique has proven effective in preserving renal function and maintaining optimal oncological outcomes with limited complications.

Recurrences after nephron-sparing treatments of renal cell carcinoma: a competing risk analysis.

PURPOSE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. CONCLUSION: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.

PURPOSE: Immune checkpoint inhibitors have revolutionized the treatment of renal cell carcinoma (RCC), but many patients do not respond to therapy and the majority develop resistant disease over time. Thus, there is increasing need for alternative immunomodulating agents. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may play a role in resistance to approved immune checkpoint inhibitors and is being investigated as a potential therapeutic target. The purpose of this study was to quantify TIGIT positivity in tumor-infiltrating T cells in RCC. METHODS: We employed tissue microarrays containing specimens from primary RCC tumors, adjacent normal renal tissue, and RCC metastases to quantify TIGIT within tumor-infiltrating CD3+ T cells using quantitative immunofluorescent analysis. We also compared these results to TIGIT+ CD3+ levels in four other tumor types (melanoma, non-small cell lung, cervical, and head and neck cancers). RESULTS: We did not observe significant differences in TIGIT positivity between primary RCC tumors and patient-matched metastatic samples. We found that the degree of TIGIT positivity in RCC is comparable to that in lung cancer but lower than that in melanoma, cervical, and head and neck cancers. Correlation analysis comparing TIGIT positivity to previously published, patient-matched spatial proteomic data by our group revealed a negative association between TIGIT and the checkpoint proteins PD-1 and LAG3. CONCLUSION: Our findings support careful evaluation of TIGIT expression on T cells in primary or metastatic RCC specimens for patients who may be treated with TIGIT-targeting antibodies, as increased TIGIT positivity might be associated with a greater likelihood of response to therapy.

The Landscape of Stereotactic Ablative Radiotherapy (SABR) for Renal Cell Cancer (RCC).

Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.

Emerging Role of Hippo-YAP (Yes-Associated Protein)/TAZ (Transcriptional Coactivator with PDZ-Binding Motif) Pathway Dysregulation in Renal Cell Carcinoma Progression.

Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney tumor subtype, has a poor prognosis and a high mortality rate. Core Hippo signaling inactivation (e.g., LATS kinases) leads to the nuclear translocation of YAP/TAZ where they bind to co-transcriptional factors such as TEAD promoting transcription of genes which initiates various fibrotic and neoplastic diseases. Loss of expression of LATS1/2 kinase and activation of YAP/TAZ correlates with poor survival in RCC patients. Renal-specific ablation of LATS1 in mice leads to the spontaneous development of several subtypes of RCC in a YAP/TAZ-dependent manner. Genetic and pharmacological inactivation of YAP/TAZ reverses the oncogenic potential in LATS1-deficient mice, highlighting the therapeutic benefit of network targeting in RCC. Here, we explore the unique upstream controls and downstream consequences of the Hippo-YAP/TAZ pathway deregulation in renal cancer. This review critically evaluates the current literature on the role of the Hippo pathway in RCC progression and highlights the recent scientific evidence designating YAP/TAZ as novel therapeutic targets against kidney cancer.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Introduction: Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Methods: Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Results: Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Discussion: Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Primary extrarenal papillary type II renal cell carcinoma presenting as a pelvic mass: a case report and review of the literature.

We report a case of a 57 years old woman with a solitary mass located in the pelvis diagnosed as an extrarenal papillary renal cell carcinoma, in the absence of a primary renal cancer. The diagnosis was based on cytomorphological features and further confirmed by immunochemistry findings following surgical excision. The hypothesis of a tumor developing in a supernumerary or ectopic kidney was excluded, since no normal renal tissue could be identified in the specimen and in the preoperative computed tomography and MRI images.

Long-term consequences of positive surgical margin after partial nephrectomy for renal cell carcinoma: multi-institutional analysis.

INTRODUCTION: The aim of the study was to determine the impact of positive surgical margins (PSM) after PN on very long-term recurrence in a contemporary cohort. METHODS: Patients who underwent PN for a localized renal tumour were included. Patients were stratified according to the presence of PSM. Data on patients' characteristics, the tumour, the peri- and postoperative events were collected. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method and compared by the log-rank test. Sensitivity analyses using weighted propensity score analysis was performed to account for potential selection biases arising from the nonrandom allocation of patients to different groups. RESULTS: A total of 1115 patients were included in the study. The incidence of PSM was 5.4% (n = 61). The median follow-up time was 51 months for the PSM group and 61 months for the NSM group (p = 0.31). Recurrence rates were significantly higher in the PSM group (13%, n = 8) compared to the NSM group (7%, n = 73) (p = 0.05). This resulted in a significant reduction in DFS in the PSM group (p = 0.004), particularly pronounced in patients with clear cell renal cell carcinoma. Additionally, OS was significantly lower in the PSM group (p < 0.01). Propensity score analysis confirmed a decrease in DFS for the PSM group (p = 0.05), while there was no significant difference in OS between the two groups (p = 0.49). CONCLUSION: In this retrospective multicenter study, PSM impact on oncological outcomes, increasing recurrence, but no difference in OS was observed post-adjustment for biases.

Long-term Renal Function Outcomes After Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma Including Patients with a Solitary Kidney: A Report from the International Radiosurgery Oncology Consortium of the Kidney.

BACKGROUND AND OBJECTIVE: Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney. METHODS: Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR). KEY FINDINGS AND LIMITATIONS: In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr. CONCLUSIONS AND CLINICAL IMPLICATIONS: With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline. PATIENT SUMMARY: With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.

Socioeconomic and Demographic Disparities in Immunotherapy Utilization for Advanced Kidney and Bladder Cancer.

OBJECTIVES: Immunotherapy (IO) drugs have been increasingly utilized in locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) and urothelial carcinoma of the bladder (UC). Multiple trials have demonstrated clear survival benefit, however, there are often barriers to access for these advanced therapies which has been demonstrated in other non-urologic malignancies. The goal of this study was to assess socioeconomic and demographic factors associated with the receipt of IO for advanced ccRCC and UC. MATERIALS AND METHODS: We queried the National Cancer Database (NCDB) for patients with stage IV ccRCC and UC. The study period was 2015 to 2020 for ccRCC (FDA approval date of IO) and 2017 to 2020 for UC (FDA approval date of broadened indication for IO, initial limited approval in 2016). The primary outcome of interest was receipt of IO therapy using multivariable logistic regression, adjusting for relevant socioeconomic and demographic variables. RESULTS: We identified 15,926 patients with stage IV ccRCC and 10,380 patients with stage IV UC of which 5,419 (34.0%) and 2,231 (21.5%) received IO therapy, respectively. IO utilization increased with each successive year. In both malignancies, treatment at a non-academic facility, education level, income, and insurance were independently associated with IO utilization. For ccRCC, black (OR = 0.77, 95% CI, 0.64-0.93, P = 0.009) and Hispanic race (OR = 0.73, 95% CI, 0.61-0.86, P = 0.006) were each associated with decreased IO utilization but there were no independent associations between race and receipt of IO in patients with UC. CONCLUSIONS: In the era of FDA-approved IO therapy for advanced ccRCC and UC, this national cohort analysis suggests that IO utilization is increasing over time, but significant disparities exist based on income, education, and insurance status in both malignancies. Additionally, patients treated at non-academic facilities were less likely to receive IO therapy for these specific genitourinary malignancies. In ccRCC, additional disparities were seen black and Hispanic races which each were associated with lower odds of IO receipt. Identifying strategies to mitigate these differences and provide equitable access to IO therapy is of imperative need.

Upfront versus deferred cytoreductive nephrectomy following targeted or immunotherapy: a population-based propensity score-matched analysis of perioperative complications.

PURPOSE: To evaluate the incidence of postoperative complications after cytoreductive nephrectomy (CN) following first-line treatment for metastatic renal cell carcinoma (mRCC), and to compare it with postoperative complications of upfront CN. METHODS: For this population-based retrospective study, the PearlDiver Mariner database (PearlDiver Technologies, Colorado Springs, CO), a database of insurance billing records was analyzed. Using relevant ICD-9/10 and CPT codes, patients diagnosed with mRCC between 2011 and 2021, who received first-line systemic molecular therapy (SMT), either tyrosine kinase inhibitors (TKI) or immune-checkpoint inhibitors (ICI), were identified. The selected population was stratified into two cohorts according to the timing of CN (deferred: after SMT vs. upfront: before SMT). Propensity-score matching (PSM) was performed as per baseline patients' characteristics to control for potential confounders between the two cohorts. The primary outcome was to compare 30-day postoperative complications rate between patients undergoing upfront vs. deferred CN. RESULTS: After PSM, 162 patients who received upfront CN were compared with 162 patients who underwent deferred CN. The overall rate of 30-day postoperative complications was statistically significantly higher in patients undergoing deferred CN (33.9%), compared to patients treated with upfront CN (21%, p < 0.01). In addition, the rate of both medical (26.5% vs. 14.2%, p < 0.01) and surgical (14.8 vs. 7.4%, p = 0.03) complication rate was statistically significantly higher in deferred vs. upfront CN. Multivariable logistic regression analysis revealed that none of the treatment regimens significantly predicted the occurrence of postoperative complications. CONCLUSION: Patients undergoing deferred CN experience a higher rates of overall, medical, and surgical 30-day postoperative complications compared to those receiving upfront surgery. Findings from this study should be interpreted within the limitations of this type of analysis.

Psychosocial distress after radical prostatectomy, radical cystectomy, or (partial) nephrectomy - a comprehensive analysis of 4,290 German cancer patients during the COVID-19 pandemic.

AIM: To evaluate and identify predictors of psychosocial distress (PD) in patients after surgical treatment for prostate cancer (PC), bladder cancer (BC), or kidney cancer (KC) during the COVID-19 pandemic in a large, multi-institutional cohort. MATERIAL AND METHODS: Patients undergoing inpatient rehabilitation (IR) after radical prostatectomy (RP), radical cystectomy (RC), or (partial) nephrectomy in one IR center in 2021 were included. PD was evaluated by the Questionnaire on Stress in Cancer Patients (QSC-R23) at the beginning (T1) and the end (T2) of IR. Regression analyses were performed to identify disease-specific predictors for high PD. RESULTS: A total of 4,290 patients (3,413 after RP, 563 after RC, 314 after (partial) nephrectomy) were included in this study. Median PD decreased significantly during IR across all tumor entities (each p < 0.001). The number of PC and BC patients suffering from high PD decreased significantly (each p < 0.001), but not in KC patients (p = 0.310). Younger age independently predicts high PD in all three malignancies, while additionally positive surgical margins (p = 0.016), ileal conduit (IC; p < 0.001), and nephrectomy (p = 0.032) independently predict high PD in PC, BC, and KC patients, respectively. During the Covid-19 pandemic the demand for individual psycho-oncologic counseling increased significantly in PC (p = 0.03) and KC (p = 0.001) patients. CONCLUSION: Younger age independently predicts high PD in the three main urological malignancies. Positive surgical margins in PCa, IC in BCa, and nephrectomy in KC are disease-specific independent predictors for high PD in the early period after surgical treatment. IMPLICATIONS FOR CANCER SURVIVORS: Disease-specific predictors for high PD may help clinicians identify patients at risk and may guide timely referrals to psycho-oncologic counseling in the early period after uro-oncologic surgery.

Factors influencing health-related quality of life in patients with bladder or kidney cancer: a prospective cohort study of the impact of nutritional status and frailty phenotype.

PURPOSE: This study aimed to investigate the impact of nutritional status and frailty phenotype and the predictors of temporal changes on health-related quality of life (HRQoL) of patients with bladder or kidney cancer. METHODS: Frailty phenotype, Patient-Generated Subjective Global Assessment, and Quality-of-life questionnaire Core-30 were applied twice to patients diagnosed with bladder or kidney cancer. Patients also completed a sociodemographic questionnaire, and clinical data were collected from records. RESULTS: Sixty-two individuals completed the study, mostly male, with a mean age of 62.5 (± 11.4) years. The median time of follow-up was 14.5 months. Role functioning, emotional functioning, and fatigue improved over time (p < 0.05). The factors that negatively affected the long-term quality of life summary score were being female, malnourished, pre-frail and frail, cancer treatment, performance status, and lower income. Using the multivariate model, being malnourished (ß = - 7.25; 95% CI, - 10.78 to - 3.71; p < 0.001), frail (ß = - 7.25; 95% CI, - 13.39 to - 1.11; p = 0.021), and each one-point increase in performance status (ß = - 6.9; 95% CI, - 9.54 to - 4.26; p < 0.001), were the ones that most negatively impacted the HRQoL between the two assessments. CONCLUSION: This study confirmed that frailty, nutritional status, and performance status are the main predictors of HRQoL of patients with bladder or kidney cancer over time. IMPLICATIONS FOR CANCER SURVIVORS: These findings may be the first step towards highlighting the importance of preventing malnutrition and frailty, in favor of a better long-term QoL for cancer patients.

Surgical outcomes of novel retroperitoneal low anterior vs posterior and transperitoneal access in single-port partial nephrectomy.

PURPOSE: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. METHODS: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. RESULTS: Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. CONCLUSION: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.

l-2-Hydroxyglutarate contributes to tumor radioresistance through regulating the hypoxia-inducible factor-1α signaling pathway.

l-2-Hydroxyglutarate (l-2-HG) has been regarded as a tumor metabolite, and it plays a crucial role in adaptation of tumor cells to hypoxic conditions. However, the role of l-2-HG in tumor radioresistance and the underlying mechanism have not yet been revealed. Here, we found that l-2-HG exhibited to have radioresistance effect on U87 human glioblastoma cells, which could reduce DNA damage and apoptosis caused by irradiation, promote cell proliferation and migration, and impair G2/M phase arrest. Mechanistically, l-2-HG upregulated the protein level of hypoxia-inducible factor-1α (HIF-1α) and the expression levels of HIF-1α downstream target genes. The knockdown of l-2-hydroxyglutarate dehydrogenase (L2HGDH) gene promoted the tumor growth and proliferation of U87 cells in nude mice by increasing HIF-1α expression level in vivo. In addition, the low expression level of L2HGDH gene was correlated with the short survival of patients with glioma or kidney cancer. In conclusion, our study revealed the role and mechanism of l-2-HG in tumor radioresistance and may provide a new perspective for overcoming tumor radioresistance and broaden our comprehension of the role of metabolites in tumor microenvironment.

Expression of hsa-miRNA-15b, -99b, -181a and Their Relationship to Angiogenesis in Renal Cell Carcinoma.

BACKGROUND: MicroRNAs (miRNAs) play a regulatory role in various human cancers. The roles of hsa-miR-15a-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p have not been fully explored in the angiogenesis of renal cell carcinoma (RCC). AIMS: The present study aimed to evaluate the expression of these miRNAs in tumorous and adjacent healthy tissues of RCC. METHODS: Paired tumorous and adjacent normal kidney tissues from 20 patients were studied. The expression levels of hsa-miR-15b-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p were quantified by TaqMan miRNA Assays. Putative targets were analyzed by qRT-PCR. RESULTS: Significant downregulation of all three miRNAs investigated was observed in tumorous samples compared to adjacent normal kidney tissues. Spearman analysis showed a negative correlation between the expression levels of miRNAs and the pathological grades of the patients. Increased expression of vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α), a tissue inhibitor of metalloproteinases-1 (TIMP-1), was observed in tumorous samples compared to adjacent normal tissues. Depletion of tissue inhibitors of metalloproteinase-2 (TIMP-2) and metalloproteinase-2 (MMP-2) was detected compared to normal adjacent tissues. The examined miRNAs might function as contributing factors to renal carcinogenesis. However, more prospective studies are warranted to evaluate the potential role of miRNAs in RCC angiogenesis.