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Background: Our study aims to address two pivotal questions: "What are the recent advancements in understanding the etiology of urological tumors through Mendelian Randomization?" and "How can Mendelian Randomization be more effectively applied in clinical settings to enhance patient health outcomes in the future?", Methods: In our systematic review conducted in April 2023, we utilized databases like PubMed and Web of Science to explore the influence of Mendelian Randomization in urological oncological diseases. We focused on studies published from January 2018, employing keywords related to urological tumors and Mendelian Randomization, supplemented with MeSH terms and manual reference checks. Our inclusion criteria targeted original research studies, while we excluded reports and non-relevant articles. Data extraction followed a PICO-based approach, and bias risk was independently evaluated, with discrepancies resolved through discussion. This systematic approach adhered to PRISMA guidelines for accuracy and thoroughness in reporting., Results: From the initial 457 publications, we narrowed down to 43 full-text articles after screening and quality assessments. A deeper understanding of Mendelian Randomization can help us explore risk factors with a clear causal relationship to urological tumors. This insight may pave the way for future research in early diagnosis, treatment, and management of associated diseases., Conclusion: Our review underscores the value of MR in urogenital tumor research, highlighting its efficacy in establishing causality and its potential to clarify disease mechanisms. Despite challenges like large sample sizes and variant identification, MR offers new perspectives for understanding and managing these tumors, suggesting a trend towards more inclusive and diverse research approaches.

Background: Although several risk factors of kidney cancer have already been well-addressed, many remain underappreciated, such as chronic exposure to air pollution. This systematic review and meta-analysis aims to assess the association between air pollutant exposure and the risk of kidney cancer., Methods: With an exhaustive search equation including keywords related to air pollution and kidney cancer on EMBASE, PubMed, Web of science, Cochrane Library and CINAHL database, we identified all relevant articles published before March 23rd, 2023 (Prospero registration number: CRD42020187956). Using random-effects meta-analysis, we present pooled hazard ratios (with their respective 95% confidence interval) associated with a 10 µg/m 3 increase in each pollutant level. Heterogeneity was quantified by the I 2 statistic. Risks of methodological and publication bias were also both assessed using appropriate tools., Results: Of the 1919 records identified, our review included 19 articles (13 cohort, 5 registry-based and 1 case-control studies), of which 9 were suitable for the meta-analysis. We found a significantly increased risk of kidney cancer incidence for a 10 μg/m 3 elevation of both particulate matter of less than 10 µm (PM 10 ) (HR = 1.29 [1.10; 1.51], I 2  = 0%, p = 0.002) and nitrogen dioxide (NO 2 ) (HR = 1.10 [1.03; 1.18], I 2  = 20%, p = 0.004). Secondary analyses also suggest an increased risk of kidney cancer-related morbidity-mortality associated with PM 10 exposure., Conclusions: Overall, our findings suggest a potential association between exposure to increased levels of PM 10 and NO 2 and the risk of kidney cancer. These results should nonetheless be interpreted with caution due to the limited number of included studies and their significant risk of methodological bias., (© 2024. The Author(s).)

Acquired cystic kidney disease (ACKD) can occur in patients with chronic kidney disease and kidney failure, and its incidence increases with the duration of dialysis. In adults, ACKD is less common in the pre-dialysis group (~ 7%), but its incidence can be as high as 80% for those who are on dialysis for more than ten years. There is, however, very little information about the prevalence of ACKD in children. We report a case of malignant transformation of ACKD following a kidney transplant, highlighting the importance of surveillance of the native kidneys in paediatric patients who have been in long-term kidney replacement therapy., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7-9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01-1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52-0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21-4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with cancer. However, these therapies are associated with adverse events including de novo immune-related adverse events or flare of pre-exiting autoimmune disorders. Up to 80% of patients with cancer and pre-existing psoriasis (PsO) or psoriatic arthritis (PsA) experience PsO/PsA flare after initiating ICIs. Targeting the interleukin (IL)-17/IL-23 axis is a mainstream of the PsO/PsA treatment. However, whether this treatment can effectively control PsO/PsA with ICI exposure while preserving anti-tumour efficacy remains unknown., Case Reports: We report three patients with PsA and cancer, who received ICIs for their cancer treatment. All patients were male. Two patients had clear cell renal cell carcinoma, and one had melanoma. Two patients received anti-PD-1 antibody monotherapy, while one patient received combined anti-CTLA-4 and PD-1 antibody therapy. One patient had been receiving anti-IL-17A antibody (secukinumab), while the other two patients started anti-IL-17A antibody (ixekizumab) and anti-IL-23 antibody (guselkumab) after their PsA flared up during ICI treatment. Of note, with the anti-IL-17A or anti-IL-23 antibody treatment, their PsA remained in remission, and they well tolerated the ICI therapy. Importantly, all three patients showed persistent tumour responses to ICI therapy, including two complete remissions and one stable disease, respectively., Conclusions: These three cases suggest that targeting the IL-17/23 axis may be an effective and safe approach for patients with cancer and pre-existing PsA being considered for ICI therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5-8% of all kidney cancer cases and is associated with syndromes such as von Hippel-Lindau syndrome, Birt-Hogg-Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available.

Introduction: Kidney transplantation is the optimal treatment modality for patients with end-stage chronic kidney disease. The long-term mortality of kidney recipients is 48-82% lower than that of patients on the waiting list. However, the risk of developing malignancies in these patients is twice as high as in the healthy population. Specifically, the incidence of renal cell carcinoma (RCC) in transplant recipients is 10-30 times higher than in non-transplanted patients. The reason for the increased risk is poorly understood, but is most likely related to continuous immunosuppressive therapy. The problem of kidney graft neoplasia has not been adequately addressed in the medical literature., Objective: To determine the incidence of renal cell carcinoma in transplanted kidneys, enhance the efficacy of its treatment, and study the etiology of RCC development., Materials and Methods: A retrospective analysis of RCC incidence in kidney grafts was conducted in 3,270 patients who underwent kidney transplantation between 2013 and 2023. We evaluated the effectiveness of surgical interventions for these complications. Patients with histologically confirmed RCC of the transplanted kidney underwent genetic study to determine the etiology of the neoplasm., Results: The incidence of RCC in transplanted kidneys was found to be 0.95% (n = 31), 28 patients underwent laparoscopic resection of the renal transplant tumor, 2 patients were treated with radiofrequency ablation of the tumor. Transplantectomy was performed in 1 patient., Conclusion: Laparoscopic resection is an effective and safe method for the treatment of RCC in kidney transplants. Transplanted kidney cancer originates from the donor tissue. The clear cell variant of transplanted kidney cancer is a genetically determined disease., (© 2024. The Author(s).)

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.

Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic review and meta-analysis with epidemiological studies, showing that a 5 μg/m 3 increase in PM 2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 μg/m 3 increase in NO 2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM 2.5 levels to 5.8 μg/m 3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM 2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden., (© 2024. The Author(s).)

The purpose of this study is to determine the predictive factors of tuberous sclerosis complex (TSC)-associated kidney disease and its progression in children. Retrospective review of children with TSC in a tertiary children's hospital was performed. Relevant data were extracted, and Cox proportional hazards regression was used to establish predictors of kidney lesions. Logistic regression was conducted to identify factors predicting chronic kidney disease (CKD) and high-risk angiomyolipomas (above 3 cm). Kidney imaging data were available in 145 children with TSC; of these, 79% (114/145) had abnormal findings. The only significant predictive factor for cyst development was being female (HR = 0.503, 95% CI 0.264-0.956). Being female (HR = 0.505, 95% CI 0.272-0.937) and underweight (HR = 0.092, 95% CI 0.011-0.800) both lowers the risk of having angiomyolipomas, but TSC2 mutations (HR = 2.568, 95% CI 1.101-5.989) and being obese (HR = 2.555, 95%CI 1.243-5.255) increases risks. Ten (12%) of 81 children with kidney function tested demonstrate CKD stages II-V, and only angiomyolipomas above 3 cm predict CKD. Additionally, 13/145 (9%) children had high-risk angiomyolipomas, whereby current age (adjusted odds ratio (aOR) 1.015, 95% CI 1.004-1.026) and being overweight/obese (aOR 7.129, 95% CI 1.940-26.202) were significantly associated with angiomyolipomas above 3 cm., Conclusions: While gender and genotype are known predictors, this study includes the novel finding of nutritional status as a predictor of TSC-associated kidney disease. This study sheds light on a possible complex interplay of hormonal influences, obesity, and kidney angiomyolipomas growth, and further investigations focusing on the impact of nutritional status on TSC-associated kidney disease are warranted., What Is Known: • Gender and genotype are well-studied predictive factors in TSC kidney disease., What Is New: • Nutritional status may influence the development and the progression of kidney lesions in children with TSC and should not be overlooked. • Management guidelines of TSC-associated kidney disease can address nutritional aspects., (© 2024. The Author(s).)

Kidney cancer (KC) is a disease with a rising worldwide incidence estimated at 400 000 new cases annually, and a worldwide mortality rate approaching 175 000 deaths per year. Current projections suggest incidence continuing to increase over the next decade, emphasizing the urgency of addressing this significant global health trend. Despite the overall increases in incidence and mortality, striking social disparities are evident. Low- and middle-income countries bear a disproportionate burden of the disease, with higher mortality rates and later-stage diagnoses, underscoring the critical role of socioeconomic factors in disease prevalence and outcomes. The major risk factors for KC, including smoking, obesity, hypertension and occupational exposure to harmful substances, must be taken into account. Importantly, these risk factors also often contribute to kidney injury, a condition that the review identifies as a significant, yet under-recognized, precursor to KC. Finally, the indispensable role of nephrologists is underscored in managing this complex disease landscape. Nephrologists are at the forefront of detecting and managing kidney injuries, and their role in mitigating the risk of KC is becoming increasingly apparent. Through this comprehensive analysis, we aim to facilitate a more nuanced understanding of KC's epidemiology and determinants providing valuable insights for researchers, clinicians and policymakers alike., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of US adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations., Methods: Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through 25 May 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately., Results: Six cohort studies with 8 617 563 persons were included. Overall, the methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR 3.36, 95% confidence interval (CI) 2.32-4.88; aHR 2.04, 95% CI 1.77-2.36) and urothelial cancer (IRR 3.96, 95% CI 2.44-6.40; aHR 1.35, 95% CI 1.22-1.50) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR 1.89, 95% CI 1.56-2.30; urothelial carcinoma aHR 1.35, 95% CI 1.20-1.52) as well as in stages 4/5 CKD (kidney cancer aHR 2.30, 95% CI 2.00-2.66; urothelial carcinoma aHR 1.24, 95% CI 1.04-1.49)., Conclusions: Even moderate CKD is associated with elevated risk of kidney cancer and urothelial carcinoma. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney cancer has become known as a metabolic disease. However, there is limited evidence linking metabolic syndrome (MetS) with kidney cancer risk. This study aimed to investigate the association between MetS and its components and the risk of kidney cancer., Methods: UK Biobank data was used in this study. MetS was defined as having three or more metabolic abnormalities, while pre-MetS was defined as the presence of one or two metabolic abnormalities. Hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk by MetS category were calculated using multivariable Cox proportional hazards models. Subgroup analyses were conducted for age, sex, BMI, smoking status and drinking status. The joint effects of MetS and genetic factors on kidney cancer risk were also analyzed., Results: This study included 355,678 participants without cancer at recruitment. During a median follow-up of 11 years, 1203 participants developed kidney cancer. Compared to the metabolically healthy group, participants with pre-MetS (HR= 1.36, 95% CI: 1.06-1.74) or MetS (HR= 1. 70, 95% CI: 1.30-2.23) had a significantly greater risk of kidney cancer. This risk increased with the increasing number of MetS components (P for trend < 0.001). The combination of hypertension, dyslipidemia and central obesity contributed to the highest risk of kidney cancer (HR= 3.03, 95% CI: 1.91-4.80). Compared with participants with non-MetS and low genetic risk, those with MetS and high genetic risk had the highest risk of kidney cancer (HR= 1. 74, 95% CI: 1.41-2.14)., Conclusions: Both pre-MetS and MetS status were positively associated with kidney cancer risk. The risk associated with kidney cancer varied by combinations of MetS components. These findings may offer novel perspectives on the aetiology of kidney cancer and assist in designing primary prevention strategies., (© 2024. The Author(s).)

Purpose: Immunotherapy has been shown to improve cancer survival, but there are no consensus guidelines to inform use in patients with both cancer and autoimmune disease (AD). We sought to examine immunotherapy utilization patterns between cancer patients with and without AD., Patients and Methods: This retrospective cohort study utilized data from a de-identified nationwide oncology database. Patients diagnosed with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma were included. Outcomes of interest included first-line immunotherapy, overall immunotherapy, and number of immunotherapy cycles. We used logistic and Poisson regression models to examine associations between AD and immunotherapy utilization patterns., Results: A total of 25,076 patients were included (796 with AD). Patients with AD were more likely to be female, White, receive care at academic centers, and have ECOG ≥ 3. Controlling for demographic and clinical variables, AD was associated with lower odds of receiving first-line (odds ratio [OR] = 0.68, 95% confidence interval [CI] 0.56-0.82) and overall (OR = 0.80, 95% CI 0.67-0.94) immunotherapy. Among patients who received at least one cycle of immunotherapy, there was no difference in mean number of cycles received between patients with and without AD (11.3 and 10.5 cycles respectively). The incident rate of immunotherapy cycles received for patients with AD was 1.03 times that of patients without AD (95% CI 1.01-1.06)., Discussion: Patients with AD were less likely to receive immunotherapy as first-line and overall therapy for treatment of their advanced cancer. However, among those who did receive at least one cycle of immunotherapy, patients with AD received a similar number of cycles compared to patients without AD. This not only indicates that AD is not an absolute contraindication for immunotherapy in clinical practice but may also demonstrate overall treatment tolerability and net benefit in patients with AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To compare metabolic dysfunction-associated profiles between patients with diabetes who developed different obesity-related site-specific cancers and those who remained free of cancer during follow-up., Design: Retrospective cohort study., Setting: Public general outpatient clinics in Hong Kong., Participants: Patients with diabetes without a history of malignancy (n=391 921)., Primary Outcome Measures: The outcomes of interest were diagnosis of site-specific cancers (colon and rectum, liver, pancreas, bladder, kidney and stomach) during follow-up. Cox proportional hazards regression was applied to assess the associations between metabolic dysfunction and other clinical factors with each site-specific cancer., Results: Each 0.1 increase in waist-to-hip ratio was associated with an 11%-35% elevated risk of colorectal, bladder and liver cancers. Each 1% increase in glycated haemoglobin was linked to a 4%-9% higher risk of liver and pancreatic cancers. While low-density lipoprotein cholesterol and triglycerides were inversely associated with the risk of liver and pancreatic cancers, high-density lipoprotein cholesterol was negatively associated with pancreatic, gastric and kidney cancers, but positively associated with liver cancer. Furthermore, liver cirrhosis was linked to a 56% increased risk of pancreatic cancer. No significant association between hypertension and cancer risk was found., Conclusions: Metabolic dysfunction-associated profiles contribute to different obesity-related cancer outcomes differentially among patients with diabetes. This study may provide evidence to help identify cancer prevention targets during routine diabetes care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Our aimed to conduct a meta-analysis of cohort studies on risk of genitourinary (GU) cancers in workers exposed to welding fumes (WF)., Methods: We performed a systematic review of studies published on Pubmed, Scopus and Embase following PRISMA criteria. Two researchers selected cohort studies on WF exposure. From 2582 articles, 7 non-overlapping studies were included. Quality of studies was scored according to CASP. We run a random effects meta-analysis to calculate the relative risk (RR) and 95% confidence intervals (CI) of GU cancer, overall and stratified by cancer, country, and quality score., Results: We included seven studies reporting results on GU cancers, including prostate, bladder and kidney cancer (PC, BC, and KC). The RR was 1.19 (95% CI = 1.07-1.32, 16 risk estimates) for GU cancer; 1.13 (95% CI = 0.90-1.42, 4 risk estimates) for PC; 1.26 (95% CI = 0.98-1.60, 7 risk estimates) for BC and 1.28 (95% CI = 1.12-1.47, 5 risk estimates) for KC. Heterogeneity was present in all meta-analyses (p < 0.001). The increased risk was more pronounced in North American than in European studies (respectively, OR = 1.35, 95% CI = 1.18-1.55; OR = 1.13, 95% CI = 1.01-1.27 p heterogeneity = 0.03). There was no heterogeneity according to quality score (p = 0.4). Data were insufficient to investigate associations by industry or welding type. Publication bias for each cancer was excluded., Conclusion: This meta-analysis suggests increased risk of KC and BC, but not of PC, in workers exposed to WF. Confounding by other occupational and non-occupational risk factors could not be excluded. Data were not adequate to address the risk of specific exposure circumstances., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hyperprogressive disease (HPD) can be described as an accelerated increase in the growth rate of tumors combined with rapid clinical deterioration observed in a subset of cancer patients undergoing immunotherapy, specifically with immune checkpoint inhibitors (ICIs). The reported incidence of HPD ranges from 5.9% to 43.1% in patients receiving ICIs. In this context, identifying reliable predictive risk factors for HPD is crucial as it may allow for earlier intervention and ultimately improve patient outcomes., Methods: This study retrospectively analyzed ten metastatic renal cell carcinoma (mRCC) patients. The identification of HPD was based on the diagnostic criteria proposed by Ferrara R et al. This study aimed to investigate whether there is an association between LN size and HPD using a cutoff value of 3 cm for LN size. Given the limited sample size, Fisher's exact test was used to test this association. We conducted a Kaplan-Meier (KM) analysis to estimate the median overall survival (OS) of patients with HPD and compared it to those without HPD., Results: Three patients (30%) developed HPD, while seven (70%) did not. Fisher's exact test revealed a statistically significant association between the HPD and LN size ≥ 3 cm (p=0.008). In the HPD group, the median OS was significantly shorter, with a median OS of 3 months, whereas in the non-HPD group, the median OS was not reached (P =0.001)., Conclusion: The present study found a significant association between LN size ≥ 3 cm in the pretreatment period and HPD development., (© 2024 Mohammad S. Alkader et al., published by Sciendo.)

Objectives: The purpose of this study is to examine the cost-effectiveness of nivolumab (NIVO) plus ipilimumab (IPI) combination therapy (NIVO + IPI) compared with the sunitinib (SUN) therapy for Japanese patients with advanced renal cell carcinoma from the perspective of a Japanese health insurance payer., Methods: A lifetime horizon was applied, and 2% per annum was set as the discount rate. The threshold was set as $ 75 000 per quality-adjusted life-year (QALY) gained. For the analytical method, we used a partitioned survival analysis model to estimate the incremental cost-effectiveness ratio (ICER), which is calculated by dividing incremental costs by incremental QALYs. Progression-free survival, progressive disease, and death were set as health states. Additionally, cost parameters and utility weights were set as key parameters. We set the intermediate/poor-risk population as the base case. Scenario analysis was conducted for the intention-to-treat population and the favorable risk population. Furthermore, one-way sensitivity analysis and probabilistic sensitivity analysis were conducted for each population., Results: In the base-case analysis, the QALYs of NIVO + IPI and SUN were 4.32 and 2.99, respectively. NIVO + IPI conferred 1.34 additional QALYs. Meanwhile, the total costs in the NIVO + IPI and SUN were $692 288 and $475 481, respectively. As a result, the ICER of NIVO + IPI compared with SUN was estimated to be $162 243 per QALY gained. The parameter that greatly affected the ICER was the utility weight of progression-free survival in NIVO + IPI., Conclusions: NIVO + IPI for advanced renal cell carcinoma seems to be not cost-effective compared with the SUN in the Japanese healthcare system., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

To propose the centrality angle (C-angle) as a novel simple nephrometry score for the evaluation of tumor complexity and prediction of perioperative outcomes in nephron-sparing surgery (NSS) for renal tumors. The analysis was based on 174 patients who underwent robot-assisted partial nephrectomy retrospectively. C-angle was defined as the angle occupied by the tumor from the center of the kidney in the coronal CT images. Other nephrometry scores were calculated and compared with C-angle. Associations between C-angle and perioperative outcomes were examined. Significant differences were found in C-angle between tumors greater and less than 4 cm, exophytic and endophytic tumors, and hilar and non-hilar tumors. C-angle was correlated with other nephrometry scores, including RENAL, PADUA, and C-index. Significant positive correlations with WIT, operation time, and EBL, and significant negative correlations with preserved eGFR. C-angle could predict perioperative complications. Patients with a C-angle > 45° had worse perioperative outcomes, including longer operative time, longer WIT, lower rate of preserved eGFR, and complications. C-angle can be used to evaluate the complexity of renal tumors and predict perioperative outcomes. C-angle can potentially be used for decision-making in the treatment of patients and to guide surgical planning of NSS., (© 2024. The Author(s).)

Purpose: The use of systemic immune checkpoint blockade before surgery is increasing in patients with metastatic renal cell carcinoma, however, the safety and feasibility of performing consolidative cytoreductive nephrectomy after the administration of systemic therapy are not well described., Patients and Methods: A retrospective review of patients undergoing nephrectomy was performed using our prospectively maintained institutional database. Patients who received preoperative systemic immunotherapy were identified, and the risk of postoperative complications were compared to those who underwent surgery without upfront systemic treatment. Perioperative characteristics and surgical complications within 90 days following surgery were recorded., Results: Overall, we identified 220 patients who underwent cytoreductive nephrectomy from April 2015 to December 2022, of which 46 patients (21%) received systemic therapy before undergoing surgery. Unadjusted rates of surgical complications included 20% (n = 35) in patients who did not receive upfront systemic therapy and 20% (n = 9) in those who received upfront systemic immunotherapy. In our propensity score analysis, there was no statistically significant association between receipt of upfront immunotherapy and 90-day surgical complications [odds ratio (OR): 1.82, 95% confidence interval (CI): 0.59-5.14; P = 0.3]. This model, however, demonstrated an association between receipt of upfront immunotherapy and an increased odds of requiring a blood transfusion [OR: 4.53, 95% CI: 1.83-11.7; P = 0.001]., Conclusion: In our cohort, there was no significant difference in surgical complications among patients who received systemic therapy before surgery compared to those who did not receive upfront systemic therapy. Cytoreductive nephrectomy is safe and with low rates of complications following the use of systemic therapy., Competing Interests: Declaration of Competing Interest Maria Carlo has no conflicts of interest to disclose. Jonathan Coleman has no conflicts of interest to disclose. Lennert Eismann has no conflicts of interest to disclose. Darren Feldman reports research funding from Telix, BioNTech, Astellas, and Decibel Therapeutics; is a consultant for Telix and BioNTech; and reports royalties from UpToDate. Alvin Goh is a consultant for Medtronic. A. Ari Hakimi is on the Merck Advisory board. Sari Khaleel (KhaleelS@mskcc.org) has no conflicts of interest to disclose. Ritesh Kotecha reports advisory board consultation for Eisai; receives institutional research funding from Pfizer, Novartis, Takeda, and Allogene Therapeutics; and is supported in part by the Academy of Kidney Cancer Investigators of the CDMRP/DOD (KC200127). Chung-Han Lee reports honoraria from Ideology Health, Intellisphere, Research to Practice, American Institute of Continuing Medical Education, and Medscape; has a consulting or advisory role for Aveo, Cardinal Health, Eisai, Bristol Myers Squibb, Merck, Pfizer/EMD Serono, and Exelixis; and reports research funding from Eisai, Bristol Myers Squibb, Calithera Biosciences, Exelixis, Merck, and AstraZeneca. Richard Matulewicz has no conflicts of interest to disclose. Robert Motzer reports grants from Bristol Myers Squibb and Pfizer; grants and personal fees from Eisai, Exelixis, Merck, and Genentech/Roche; and personal fees from EMD Serono Research. Irina Ostrovnaya has no conflicts of interest to disclose. Stephen Reese has no conflicts of interest to disclose. Katiana Vazquez-Rivera has no conflicts of interest to disclose. Paul Russo has no conflicts of interest to disclose. Juan Arroyave Villada has no conflicts of interest to disclose. Martin Voss reports receiving commercial research grants from Bristol Myers Squibb, Pfizer, and Genentech/Roche; honoraria from Novartis and Bristol Myers Squibb; and travel/accommodation from AstraZeneca, Eisai, Novartis, and Takeda; and serving as a consultant/advisory board member for Alexion Pharmaceuticals, Aveo, Bayer, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, Genentech, GlaxoSmithKline, Merck, Natera, Onquality Pharmaceuticals, Novartis, and Pfizer. Charlie White has no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell carcinoma (RCC) after liver, kidney, heart and lung transplantation, respectively, and suggest that transplant patients can be screened early for tumors to avoid risk., Methods: PubMed, Embase and the Cochrane Library from their inception until August 16,2023. Retrospective and cohort studies which focus on the statistical data of standardized incidence ratios (SIRs) of RCC after solid organ transplantation (SOT) more than one year have been included and extracted. The study was registered with PROSPERO, CRD4202022343633., Results: Sixteen original studies have been included for meta-analysis. Liver transplantation could increase the risk of RCC (SIR = 0.73, 95%CI: 0.53 to 0.93) with no heterogeneity(P = 0.594, I 2  = 0.0%). And kidney transplantation could increase the risk of RCC(8.54, 6.68 to 10.40; 0.000,90.0%). Besides, heart and lung transplantation also could increase the risk of RCC(SIR = 0.73, 95%CI: 0.53 to 0.93; SIR = 1.61, 95%CI:0.50 to 2.71). Moreover, significance could also be found in most subgroups, especially the European group and retrospective study group. What's more, after removing studies which have a greater impact on the overall outcome in RCC rate after kidney transplantation, heterogeneity did not solve and significant different was also observed in the European group (7.15, 5.49 to 8.81; 0.000, 78.6%)., Conclusion: Liver, kidney, heart and lung transplantation patients have an increased risk of processing RCC compared to the general population and most subgroups, especially in geographic location of European subgroup, which suggested that patients should be screened frequently after transplantation., (© 2023. The Author(s).)

A meta-analysis published in 2018 indicated a significant association between the dietary inflammatory index (DII) and risk of urologic cancers (UC). The number of included studies was limited, and more research has been published on this topic since then. The current study aimed to find a more precise estimate of the association between dietary inflammatory potential and risk of UC by updating the previous meta-analysis. The PubMed and Embase databases were searched between January 2015 and April 2023 to identify eligible articles. Combined relative risk (RR) and 95% confidence intervals (CI) were calculated by random-effects model to assess the association between dietary inflammatory potential and risk of UC by comparison of the highest versus the lowest category of the DII/empirical dietary inflammatory pattern (EDIP) or by using the continuous DII/EDIP score. The analysis, including 23 studies with 557,576 subjects, showed different results for UC. There was a significant association for prostate cancer among case-control studies (RR = 1.75, 95% CI: 1.34-2.28), whereas among cohort studies a null association was found (RR = 1.02, 95% CI: 0.96-1.08). For bladder cancer, a nonsignificant association was observed in both case-control (RR = 1.59, 95% CI: 0.95-2.64) and cohort studies (RR = 1.03, 95% CI: 0.86-1.24). Pooled RR from 3 case-control studies displayed a statistically significant association between the DII and risk of kidney cancer (RR = 1.27, 95% CI: 1.03-1.56). Although DII was positively associated with all types of UC, no association was found for EDIP. The present meta-analysis confirmed that an inflammatory diet has a direct effect on the development of prostate cancer and kidney cancer. Large-scale studies are needed to demonstrate the association between dietary inflammatory potential and risk of UC and provide effective nutritional advice for UC prevention. PROTOCOL REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023391204)., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the efficacy of routine use of intraoperative ultrasonography (IOUS) in improving perioperative outcomes in patients undergoing IOUS-guided laparoscopic nephrectomy (IOUS-LN) and conventional laparoscopic nephrectomy (C-LN)., Patients and Methods: This was a parallel-arm, single-blinded, randomised controlled trial (CTRI/2021/12/038906). All patients undergoing LN, either for benign or malignant causes, were included. Patients undergoing partial/cytoreductive nephrectomy, with venous thrombus were excluded. In the study arm, IOUS-guided renal vascular assessment was performed after colon mobilisation and a standard LN was performed in the control arm. The primary outcome was intraoperative duration. The secondary outcomes were blood loss, need for open conversion, blood transfusion, perioperative complications, duration of Intensive Care Unit (ICU) stay and length of hospitalisation (LOH). The patients were followed for 3 months after surgery., Results: A total of 104 patients were included, with 52 in each arm. Demographic characteristics were comparable in both arms. A significant reduction in the operative duration (mean [sd] 181.69 [40.8] vs 199.7 [41.8] min, P = 0.02) was seen in the IOUS-LN group. The difference in blood loss showed no significant difference when compared between both groups (median [interquartile range] 84.55 [74-105.5] vs 99.95 [78.5-111] mL, P = 0.08). On subgroup analysis, the reduction in the operative duration was significant in patients who underwent laparoscopic simple nephrectomy (LSN; mean [sd] 194.4 [42.5] vs 221.2 [36.4] min, P = 0.01), whereas comparable operative durations were seen in patients undergoing laparoscopic radical nephrectomy (LRN; mean [sd] 168.96 [35.3] vs 178.3 [35.9] min, P = 0.34). Similar conversion rates were seen in both groups (P = 0.98) along with blood transfusions (P = 0.78). The LOH, ICU stay, and complications were similar in both groups. Significantly less blood loss (P = 0.03) was noted with IOUS in patients undergoing LSN. IOUS did not influence any outcomes in patients undergoing LRN., Conclusion: Intraoperative ultrasonography significantly reduced the operative duration in LN, but with no significant reduction in the volume of blood loss. Significant reduction in intraoperative duration and blood loss was seen in patients who underwent LSN on subgroup analysis., (© 2023 BJU International.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition; however, its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients., Methods: A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed., Results: Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1-5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1,147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7-7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9-56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7-95.1, I2 = 66.9%])., Conclusion: ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however, may become apparent as outcomes and life expectancy amongst APDKD patients improve., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated., (© 2023. Springer Nature Limited.)

Background: Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess body weight., Methods: Using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: (i) BMI at specific ages; (ii) adulthood BMI trajectories; (iii) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and (iv) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC., Results: A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared with individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight [HR, 1.49; 95% confidence interval (CI), 1.19-1.87], from normal BMI to obesity (HR, 2.22; 95% CI, 1.70-2.90), and from overweight to obesity (HR, 2.78; 95% CI, 1.81-4.27). Compared with individuals who were never overweight (WYO = 0), elevated HRs were observed among individuals who experienced low (HR, 1.31; 95% CI, 0.99-1.74), medium (HR, 1.57; 95% CI, 1.20-2.05), and high (HR, 2.10; 95% CI, 1.62-2.72) WYO tertile. Weight gain of ≥10 kg was associated with increased RCC incidence for each age span., Conclusions: Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk., Impact: It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk., (©2023 American Association for Cancer Research.)

Background : High dietary inflammatory index (DII®) scores, representing pro-inflammatory diets, have been associated with increased risks for numerous cancers. However, the evidence for renal cancer is limited. In the present study, we aimed to assess the association between DII and renal cancer risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. Methods : Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards model with adjustment for various potential confounders. Results : After a median 12.2 years of follow-up, this study recorded 443 renal cancer cases among 101 190 individuals. The DII score was positively associated with renal cancer risk in multivariable analyses. The HR in the highest DII tertile compared to the lowest tertile was 1.38 (95% CI 1.03-1.84). This was also true when DII was analyzed as a continuous variable. The HR of one-unit increment in DII for renal cancer risk was 1.07 (95% CI 1.01-1.12). Conclusion : In this large American cohort, pro-inflammatory diet, as estimated by higher DII scores, was significantly associated with a greater risk of renal cancer. Future large prospective studies are warranted to verify these preliminary findings.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with an estimated incidence of one in 5000 to 10,000 live births worldwide. Two million people of all races and genders are estimated to have TSC secondary to mutations in one of two tumor suppressor genes, TSC1 or TSC2. The respective TSC1 and 2 gene products - hamartin and tuberin - form cytoplasmic heterodimers that inhibit mTOR-mediated cell growth and division. When mTOR inhibition is lost, people with TSC develop characteristic and usually benign tumors in various organ systems. Kidney tumors and cysts are common, particularly in the setting of TSC2 gene mutations. In most TSC patients, the number of kidney cysts is limited, their morphology is simple, their size is small, and their clinical significance is negligible. In some, cyst morphology progresses from simple to complex with the risk of malignant transformation. In others, aggressive accumulation and growth of kidney cysts can cause hypertension, impaired kidney function, and progression to kidney failure. This educational review summarizes current knowledge and remaining open questions regarding cystic kidney disease in TSC, emphasizing detection, classification, surveillance, and treatment options., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

The most common form of kidney cancer is clear cell renal cell carcinoma (ccRCC). Biallelic VHL tumor suppressor gene inactivation is the usual initiating event in both hereditary (VHL Disease) and sporadic ccRCCs. The VHL protein, pVHL, earmarks the alpha subunits of the HIF transcription factor for destruction in an oxygen-dependent manner. Deregulation of HIF2 drives ccRCC pathogenesis. Drugs inhibiting the HIF2-responsive growth factor VEGF are now mainstays of ccRCC treatment. A first-in-class allosteric HIF2 inhibitor was recently approved for treating VHL Disease-associated neoplasms and appears active against sporadic ccRCC in early clinical trials., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers., Methods: This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers., Results: A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P < 0.01) differences between the MetS and non-MetS groups (0.70% vs. 0.48%, 0.27% vs. 0.15%, and 0.22% vs. 0.13%, respectively). Compared to the non-MetS group, the risk of developing urologic [HR (95% CI) = 1.29 (1.08-1.55)], kidney [HR (95% CI) = 1.74 (1.28-2.37)], and prostate [HR (95% CI) = 1.47 (1.04-2.07)] cancers was significantly higher in the MetS group. In the MetS group, elevated BP increased the risk of developing of urologic cancer [HRs (95% CI) = 1.35 (1.10-1.66)] and kidney cancer [HR (95% CI) = 1.74 (1.21-2.51)], while central obesity increased the risk of developing prostate cancer [HR (95% CI) = 1.68 (1.18-2.40)]., Conclusions: MetS increased the risk of developing urologic, kidney, and prostate cancers but had no association with the development of bladder cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: This study is to compare risks of developing renal cell carcinoma or urothelial cancer between hemodialysis (HD) and peritoneal dialysis (PD) patients., Methods: The age-, sex-, and index year-matched patients with newly diagnosed end-stage kidney disease (ESKD) undergoing dialysis [HD (N = 22,587) or PD (N = 11,547)] from 2000 to 2015 in Taiwan were identified. Patients were followed until the development of renal cell carcinoma or urothelial cancer, renal transplantation, death, or the end of follow-up (December 31, 2017). The hazard ratio (HR), and sub-hazards ratio (SHR), in which death was considered as a competing risk, of developing renal cell carcinoma or urothelial cancer were compared between the HD and PD patients., Results: The incidence rate of renal cell carcinoma was higher in the PD group than in age-, sex-, and index year-matched HD group (11.5 versus 5.52 per 10,000 person-years), with an adjusted HR of 2.15 (95% confidence interval (CI) = 1.59, 2.92), and an adjusted SHR of 1.97 (95% CI = 1.46, 2.67). The incidence rate of urothelial cancer was also higher in the PD group than in corresponding HD group (40.3 and 34.0 per 10,000 person-years), with an adjusted HR of 1.15 (95% CI = 1.00, 1.33) and an adjusted SHR of 1.08 (95% CI = 0.94, 1.25). These findings were further validated in propensity score-matched dialysis cohorts., Conclusions: ESKD patients undergoing PD are at a higher risk of developing renal cell carcinoma than those on HD, but risks of developing urothelial cancer are similar among the two groups., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Opinion Statement: PRCC is a unique histologic entity compared to other forms of renal cell carcinoma, harboring distinct molecular drivers. The WHO 2022 classification is further emphasizing the molecular biology by making molecular classifications of PRCC subclassifications and discontinuing the morphologic type 1 and type 2 classification system. We agree with this functional classification system and encourage all future clinical trials to only include patients with similar diagnosis instead of conducting basket trials (including all nccRCC together) which limits the scientific value of those conclusions. Based on recent disease-specific clinical trial (S1500, PAPMET), the current standard of care for patients with treatment naïve PRCC is cabozantinib. Prospective clinical trials clearly establish that immune checkpoint inhibitor therapy has meaningful activity in PRCC. The data to date include only single-arm clinical trials of combination immune therapy. Despite the positive and encouraging results, we need validation through randomized studies because of the overestimation of effect size seen in single-arm trials. These randomized trials are currently underway and enrolling. We strongly encourage all physicians to support these studies and enroll patients with PRCC to these trials in order to continue improving the standard of care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Obesity, defined by body mass index (BMI), is an established risk factor for specific renal cell carcinoma (RCC) subtypes such as clear cell RCC, the most common RCC histology. Many studies have identified an association between obesity and improved survival after diagnosis of RCC, a potential "obesity paradox." Clinically, there is uncertainty whether improved outcomes observed after diagnosis are driven by stage, type of treatment received, or artifacts of longitudinal changes in weight and body composition. The biological mechanisms underlying obesity's influence on RCC are not fully established, but multiomic and mechanistic studies suggest an impact on tumor metabolism, particularly fatty acid metabolism, angiogenesis, and peritumoral inflammation, which are known to be key biological hallmarks of clear cell RCC. Conversely, high-intensity exercise associated with increased muscle mass may be a risk factor for renal medullary carcinoma, a rare RCC subtype that predominantly occurs in individuals with sickle hemoglobinopathies. Herein, we highlight methodologic challenges associated with studying the influence of obesity on RCC and review the clinical evidence and potential underlying mechanisms associating RCC with BMI and body composition., Competing Interests: Declaration of Competing Interest NV has no conflicts of interest to disclose. AM reports ownership of equities in Oltre Medical Consulting, LLC (Toulouse, France). AWH reports advisory board consulting to Janssen and Intellisphere and travel support from Dava Oncology. JLM reports advisory board consulting for Bristol Myers Squibb, Roche, and Merck. PM reports honoraria for service on a scientific advisory board for Mirati Therapeutics, Bristol Myers Squibb, and Exelixis; consulting for Axiom Healthcare Strategies; non-branded educational programs supported by Exelixis and Pfizer; and research funding for clinical trials from Takeda, Bristol Myers Squibb, Mirati Therapeutics, Gateway for Cancer Research, and UT MD Anderson Cancer Center., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Opinion Statement: Current treatment options for patients with metastatic renal cell carcinoma (mRCC) are limited to immunotherapy with checkpoint inhibitors and targeted therapies that inhibit the vascular endothelial growth factor receptors (VEFG-R) and the mammalian target of rapamycin (mTOR). Despite significantly improved outcomes over the last few decades, most patients with mRCC will ultimately develop resistance to these therapies, thus highlighting the critical need for novel treatment options. As part of the VHL-HIF-VEGF axis that rests at the foundation of RCC pathogenesis, hypoxia-inducible factor 2α (HIF-2α) has been identified as a rationale target for mRCC treatment. Indeed, one such agent (belzutifan) is already approved for VHL-associated RCC and other VHL-associated neoplasms. Early trials of belzutifan indicate encouraging efficacy and good tolerability in sporadic mRCC as well. The potential inclusion of belzutifan and other HIF-2α inhibitors into the mRCC treatment armamentarium either as a single agent or as combination therapy would be a welcome addition for patients with mRCC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Studies have shown an inverse association between alcohol consumption and kidney cancer risk. We postulate that this inverse association may be further influenced by other risk factors., Methods: We used an Australian cohort, the 45 and Up Study, recruited between 2005 and 2009 to investigate the association between alcohol consumption, and other potential risk factors and kidney cancer incidence. The median follow-up was 5.4 years., Results: Of the 267,357 participants aged ≤45 years living in New South Wales, 497 were diagnosed with kidney cancer. There was a significant inverse association between alcohol consumption and risk of kidney cancer (P = .027), and a significant inverse dose-response relationship (P = .011). There was a significant interaction between alcohol consumption and socioeconomic status (P interaction = .001). Participants residing in higher socioeconomic areas (the two most advantaged quintiles) who consumed 8-10 drinks or greater than 10 drinks per week, respectively, had a lower risk of kidney cancer compared to the group who consumed 1-4 drinks per week (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, HR 0.51, 95% CI 0.31-0.83) with a dose-response trend of HR 0.62 (95% CI 0.42-0.93) per 7 drink increase in weekly alcohol consumption., Conclusions: There could be an inverse association between alcohol consumption and risk in those residents in higher socioeconomic areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To develop a 3D scoring system of tumor anatomy and intrarenal relationship for assessing surgical complexity and outcomes of robot-assisted partial nephrectomy (RAPN)., Methods: We prospectively enrolled patients with a renal tumor who had a 3D model and underwent RAPN between Mar 2019 and Mar 2022. The ADDD nephrometry consisted of the contact surface area between tumor and parenchyma (A), the depth of tumor invasion into the renal parenchyma (D 1 ), the distance from tumor to the main intrarenal artery (D 2 ), and to the collecting system (D 3 ). The primary outcomes included perioperative complication rate and trifecta outcome (WIT ≤ 25 min, negative surgical margins, and no major complications)., Results: We enrolled a total of 301 patients. The mean tumor size was 2.93 ± 1.44 cm. There were 104 (34.6%) patients, 119 (39.5%) patients, and 78 (25.9%) patients in the low-, intermediate-, and high-risk groups, respectively. Each point increase in the ADDD score increased the risk of complications [hazard ratio (HR) 1.501]. A lower grade indicated a lower risk of failed trifecta (HR low group 15.103, intermediate group 9.258) and renal function damage (HR low risk 8.320, intermediate risk 3.165) compared to the high-risk group. The AUC of ADDD score and grade were 0.738 and 0.645 for predicting major complications, 0.766 and 0.714 for predicting trifecta outcome, and 0.746 and 0.730 for predicting postoperative renal function reservation., Conclusion: The 3D-ADDD scoring system shows the tumor anatomy and its intraparenchymal relationships and has better efficacy in predicting surgical outcomes of RAPN., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To assess the necessity of prophylactic drain placement in retroperitoneal laparoscopic nephroureterectomy with open distal ureterectomy for upper tract urothelial cancer., Methods: Between July 2011 and March 2021, 200 patients with localized clinical Tis-T3 upper urinary tract urothelial carcinoma underwent laparoscopic nephroureterectomy with open distal ureterectomy. After removing the specimen, drainage tubes were placed on the renal beds and/or in the retrovesical spaces. Drain tubes were omitted for most patients after 2017. We compared the postoperative outcomes between the patients with drain placement (D+ group) and without drain placement (D- group) using propensity score matching., Results: A total of 164 patients (90 in the D+ group and 74 in the D- group) were enrolled, and matched pairs of 108 patients were analyzed. There was no significant difference in the incidence of complications according to Clavien-Dindo grade in the two groups after the propensity score matching. There was no significant difference in the incidence of postoperative lymphocele (n = 5 vs. 9, p = 0.395) and symptomatic lymphocele (n = 1 vs. 1, p = 1) between the two groups. The length of hospital stay was significantly shorter in the D- group (11 vs. 8 days, p < 0.0001)., Conclusions: We found that omitting the drainage tube after laparoscopic radical nephroureterectomy did not increase postoperative complications or lymphocele and shortened the post-hospital stay., (© 2023 The Japanese Urological Association.)

Background: The role of cigarette smoking as a prognostic factor for kidney cancer (KC) is unclear. In this population-based study, we analyze cancer-specific survival (CSS) outcomes among KC patients by smoking status at diagnosis in the diverse state of Florida., Methods: All primary KC cases from the Florida Cancer Registry diagnosed during 2005-2018 were analyzed. Cox proportional regression was conducted to assess the determinants of KC survival, including age, sex, race/ethnicity, socioeconomic status, histology type, cancer stage, and treatment received with a particular focus on smoking status (smokers at diagnosis referred to as current smokers, former smokers, and never smokers)., Results: Among all 36,150 KC patients, 18.3% were smokers at diagnosis (n = 6629), 32.9% were former smokers (n = 11,870), and 48.8% were never smokers (n = 17,651). Age-standardized five-year survival for current, former, and never smokers was 65.3 (95% CI: 64.1-66.5), 70.6 (95% CI: 69.7-71.5), and 75.3 (95% CI: 74.6-76.0) respectively. In multivariable analysis, current and former smokers had an estimated 30% and 14% higher risk of KC death compared to never smokers, respectively, after adjusting for potential confounders (HR: 1.30, 95% CI: 1.23-1.40; HR: 1.14, 95% CI: 1.10-1.20)., Conclusion: Smoking independently contributes to poorer survival, across all KC stages. Clinicians should encourage and facilitate participation in cigarette smoking cessation programs targeted at current smokers. Prospective studies are warranted to assess the role of different types of tobacco use and cessation programs on KC survival., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology., Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use., Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Mounting evidence suggests that the gut microbiota plays a crucial role in the development and treatment of various cancers. Recent research on the urinary microbiota challenges the long-standing belief that urine is sterile, as urinary microbiota has been implicated in the development of bladder and prostate cancers, similar to the role of gut microbiota in cancer development. Although the precise involvement of microbiota in the proliferation and differentiation of renal cell carcinoma (RCC) remains unclear, dysbiosis is considered one possible mechanism by which microbiota may contribute to RCC development and treatment. This review summarizes potential mechanisms by which gut microbiota may contribute to the development of RCC, and provides evidence for the involvement of urinary microbiota in RCC. We also explore the role of gut microbiota in RCC treatment and propose that the composition of gut microbiota could serve as a predictive marker for the potential efficacy of immune checkpoint inhibitors (ICIs) in RCC patients. Additionally, evidence suggests that modulating the abundance and distribution of microbiota can enhance the therapeutic effects of drugs, suggesting that microbiota may serve as a promising adjuvant therapy for RCC. Overall, we believe that further investigation into the gut and urinary microbiome of RCC patients could yield valuable insights and strategies for the prevention and personalized treatment of RCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Wan, Li, Chen and Yang.)

Background: Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation., Methods: We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis., Results: During a follow-up of 12 years (interquartile range 8-14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03-8.27], adjusting for smoking (OR 4.020, 95% CI 1.34-12.02) and other covariates. PTDM was not associated with other types of cancer., Conclusions: Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death-ligand 1 expression; time-to-surgery; and disease-free survival (DFS). Twenty patients were evaluable for safety and 17 for efficacy. The ORR was 11.8%, and 24-month DFS probability was 88·0% (95% CI 61.0 to 97.0). There were no grade 4/5 treatment-related adverse events. Sitravatinib PK did not change following the addition of nivolumab. Correlative blood and tissue analyses showed changes in the tumour microenvironment resulting in an immunologically active tumour by the time of surgery (median time-to-surgery: 50 days). The primary endpoint of this study was not met as short-term neoadjuvant sitravatinib and nivolumab did not substantially increase ORR., (© 2023. The Author(s).)

Kidney transplantation is now a well-established renal replacement therapy. However, renal transplant recipients are reported to have an increased incidence of cancer. Although the recommended waiting period after each cancerous event in a recipient is indicated in the literature, there is no absolute certainty that cancer will develop even after the recommended waiting period. In this study, we experienced a case of bladder cancer after the recommended waiting period in a patient who had bladder preservation after a right nephrectomy and left nephroureterectomy. A 61-year-old man lost his right kidney due to renal cancer in 2007 and his left kidney to urothelial carcinoma in November 2017. The patient wanted a kidney transplant and bladder preservation at the time of the left nephroureterectomy. The patient's wife offered to donate a kidney. After 2 years of hemodialysis, there was no recurrence or metastasis, and with the approval of the Ethics Committee, the patient received a kidney transplant in January 2020. Although the patient's renal function was good after the transplant, a bladder tumor was found 20 months later and was resected transurethrally. The pathology was nonmuscle invasive bladder cancer. This patient, who had lost both kidneys, was treated with bladder preservation therapy. After subsequent kidney transplantation, he developed bladder cancer. Explaining to the patient the possibility of recurrence after a certain period and the increased risk of cancer, in-depth consultation with the patient is necessary regarding bladder preservation. Regular checkups should be continued after transplantation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: 3D virtual models (3DVMs) are nowadays under scrutiny to improve partial nephrectomy (PN) outcomes. Five different Trifecta definitions have been proposed to optimize the framing of "success" in the PN field. Our aim is to analyze if the use of 3DVMs could impact the success rate of minimally invasive PN (mi-PN), according to the currently available definitions of Trifecta., Materials and Methods: At our Institution 250 cT1-2N0M0 renal masses patients treated with mi-PN were prospectively enrolled. Inclusion criteria were the availability of contrast-enhanced CT, baseline and postoperative serum creatinine, and eGFR. These patients were then compared with a control group of 710 patients who underwent mi-PN with the same renal function assessments, but without 3DVMs. Multivariable logistic regression (MLR) models were used to predict the trifecta achievement according to the different trifecta definitions., Results: Among the definitions, Trifecta rates ranged between 70.8% to 97.4% in the 3DVM group vs. 56.8% to 92.8% in the control group (all p values < 0.05). 3DVMs showed better postoperative outcomes in terms of ΔeGFR, ( - 16.6% vs.  - 2.7%, p = 0.03), postoperative complications (15%, vs 22.9%, p = 0.002) and major complications (Clavien Dindo > 3, 2.8% vs 5.6%, p = 0.03). At MLR 3DVMs assistance independently predicted higher rates of successful PN across all the available definitions of Trifecta (OR: 2.7 p < 0.001, OR:2.0 p = 0.0008, OR:2.8 p = 0.02, OR 2.0 p = 0.003)., Conclusions: The 3DVMs availability was found to be the constant predictive factor of successful PN, with a twofold higher probability of achieving Trifecta regardless of the different definitions available in Literature., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Lipidomics focuses on the in-depth analysis of lipids, which are crucial macromolecules involved in a wide range of metabolic pathways. The increased intracellular accumulation of different classes of lipids in renal cell carcinoma (RCC) and prostate cancer (PCa) cells may be caused by elevated absorption or by increased de novo lipogenesis as a consequence of lipid metabolism reprogramming. The involvement of cholesterol metabolism in cancer's aberrant pathways has also been demonstrated., Areas Covered: This review provides an update on the most important lipidomics studies and applications in RCC and PCa, with a particular focus on how knowledge of aberrant lipid pathways may be used to identify biomarkers and novel therapeutic targets. In addition, the application of this methodologies have led to novel cancer subtypes identification and patient's risk stratification. Tracking tumor progression using specific biofluid metabolite profiles offers a huge translational opportunity for urological malignancies., Expert Opinion: Lipidomics is a promising branch of 'omics' approach and should include in next decade new standardized analysis methods and randomized clinical trials in order to reach the aim to use this high-throughput technique in patient-tailored therapy perspective.

Renal cell carcinoma (RCC) is associated with high mortality rates worldwide and survival among RCC patients has not improved significantly in the past few years. A better understanding of the pathogenesis of RCC can enable the development of more effective therapeutic strategies against RCC. Hyaluronan (HA) is a glycosaminoglycan located in the extracellular matrix (ECM) that has several roles in biology, medicine, and physiological processes, such as tissue homeostasis and angiogenesis. Dysregulated HA and its receptors play important roles in fundamental cellular and molecular biology processes such as cell signaling, immune modulation, tumor progression and angiogenesis. There is emerging evidence that alterations in the production of HA regulate RCC development, thereby acting as important biomarkers as well as specific therapeutic targets. Therefore, targeting HA or combining it with other therapies are promising therapeutic strategies. In this Review, we summarize the available data on the role of abnormal regulation of HA and speculate on its potential as a therapeutic target against RCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin and Zong.)