Linear Muscle Segmentation for Metastatic Renal Cell Carcinoma: Changes in Clinic-Friendly Estimation Predict Survival Following Cytoreductive Nephrectomy.

INTRODUCTION: Baseline sarcopenia and postoperative changes in muscle mass are independently associated with overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN). Here we examine the relationships between preoperative (baseline), postoperative changes in muscle quantity, and survival outcomes following CN as determined by linear segmentation, a clinic-friendly tool that rapidly estimates muscle mass. MATERIALS AND METHODS: Our nephrectomy database was reviewed for patients with metastatic disease who underwent CN for RCC. Linear segmentation of the bilateral psoas/paraspinal muscles was completed for baseline imaging within 60 days of surgery and imaging 30 to 365 days postoperatively. Kruskal-Wallis for numerical and Fisher's exact test for categorical variables were used to test for differences between groups according to percent change in linear muscle index (LMI, cm2/m2). Multivariable Cox proportional hazards models evaluated associations between LMI percent change and cancer-specific (CSM) and all-cause mortality (ACM). Kaplan Meier curves estimated cancer-specific (CSS) and overall survival (OS). RESULTS: From 2004-2020, 205 patients were included of whom 52 demonstrated stable LMI (25.4%; LMI change < 5% [0Δ]), 60 increase (29.3%; LMI +5% [+Δ]), and 92 decrease (44.9%; LMI -5% [-Δ]). Median time from baseline imaging to surgery was 18 days, and time from surgery to postoperative imaging was 133 days. Median CSS and OS were highest among patients with 0Δ LMI (CSS: 133.6 [0Δ] vs. 61.9 [+Δ] vs. 37.4 [-Δ] months; P = .0018 || OS: 67.2 [0Δ] vs. 54.8 [+Δ] vs. 29.5 [-Δ] months; P = .0007). Stable LMI was a protective factor for CSM (HR 0.48; P = .024) and ACM (HR 0.59; P = .040) on multivariable analysis. DISCUSSION: Change in muscle mass after CN, as measured by the linear muscle segmentation technique, is independently associated with OS and CSS in patients following CN. Of note, lack of change was associated with longer survival.

Creatinine to Cystatin-C Ratio in Renal Cell Carcinoma: A Clinically Pragmatic Prognostic Factor and Sarcopenia Biomarker.

INTRODUCTION: Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy. METHODS: We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression. RESULTS: A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia. CONCLUSIONS: Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy.

Barriers and facilitators to physical activity prehabilitation in patients with kidney cancer.

PURPOSE: Timely and effective physical activity (PA) prehabilitation is an evidence-based approach for improving a patient's health status preoperatively. Identifying barriers and facilitators to PA prehabilitation can help inform best practices for exercise prehabilitation program implementation. We explore the barriers and facilitators to PA prehabilitation in patients undergoing nephrectomy. METHODS: A qualitative exploratory study was conducted by interviewing 20 patients scheduled for nephrectomy. Interviewees were selected via convenience sampling strategy. The interviews were semi-structured and discussed experienced and perceived barriers/facilitators to PA prehabilitation. Interview transcripts were imported to Nvivo 12 for coding and semantic content analysis. A codebook was independently created and collectively validated. Themes of barriers and facilitators were identified and summarized in descriptive findings based on frequency of themes. RESULTS: Five relevant themes of barriers to PA prehabilitation emerged: 1) mental factors, 2) personal responsibilities, 3) physical capacity, 4) health conditions, and 5) lack of exercise facilities. Contrarily, facilitators potentially contributing to PA prehabilitation adherence in kidney cancer included 1) holistic health, 2) social and professional support, 3) acknowledgment of health benefits, 4) exercise type and guidance, and 5) Communication channels. CONCLUSION AND KEY FINDINGS: Kidney cancer patient's adherence to physical activity prehabilitation is influenced by multiple biopsychosocial barriers and facilitators. Hence, adherence to physical activity prehabilitation requires timely adaptation of health beliefs and behavior embedded in the reported barriers and facilitators. For this reason, prehabilitation strategies should strive to be patient-centered and include health behavioral change theories as underlying frameworks for sustaining patient engagement and self-efficacy.

Low Skeletal Muscle as a Risk Factor for Worse Survival in Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus.

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombosis often requires nephrectomy and tumor thrombectomy. As an extensive and potentially morbid operation, patient preoperative functional reserve and body composition is an important consideration. Sarcopenia is a risk factor for increased postoperative complications, systemic therapy toxicity, and death solid organ tumors, including RCC. The influence of sarcopenia in RCC patients with tumor thrombus is not well defined. This study evaluates the prognostic ability of sarcopenia regarding surgical outcomes and complications in patients undergoing surgery for RCC with tumor thrombus. METHODS: We retrospectively analyzed patients with nonmetastatic RCC and tumor thrombus undergoing radical nephrectomy and tumor thrombectomy. Skeletal muscle index (SMI; cm2/m2) was measured on preoperative CT/MRI. Sarcopenia was defined using body mass index- and sex-stratified thresholds optimally fit via a receiver-operating characteristic analysis for survival. Associations between preoperative sarcopenia and overall (OS), cancer-specific survival (CSS), and 90-day major complications were determined using multivariable analysis. RESULTS: 115 patients were analyzed, with median (IQR) age and body mass index of 69 (56-72) and 28.6 kg/m2 (23.6-32.9), respectively. 96 (83.4%) of the cohort had ccRCC. Sarcopenia was associated with shorter median OS (P = .0017) and CSS (P = .0019) in Kaplan-Meier analysis. In multivariable analysis, preoperative sarcopenia was prognostic of shorter OS (HR = 3.38, 95% confidence interval [CI] 1.61-7.09) and CSS (HR = 5.15, 95% CI 1.46-18.18). Notably, 1 unit increases in SMI were associated with improved OS (HR = 0.97, 95% CI 0.94-0.999) but not CSS (HR = 0.95, 95% CI 0.90-1.01). No significant relationship between preoperative sarcopenia and 90-day major surgical complications was observed in this cohort (HR = 2.04, 95% CI 0.65-6.42). CONCLUSION: Preoperative sarcopenia was associated with decreased OS and CSS in patients surgically managed for nonmetastatic RCC and VTT, however, was not predictive of 90-day major postoperative complications. Body composition analysis has prognostic utility for patients with nonmetastatic RCC and venous tumor thrombus undergoing surgery.

Neoadjuvant Nivolumab and Ipilimumab for Nonmetastatic Renal Cell Carcinoma with Tumor Thrombus.

Renal cell carcinoma with level IV tumor thrombus is a condition necessitating aggressive surgical management. Many solid organ malignancies often benefit from neoadjuvant treatments for tumor debulking and improvement of surgical outcomes. However, neoadjuvant treatments for renal cell carcinoma have been limited by its resistance to traditional chemotherapy and radiation. Emerging treatment modalities, such as immunotherapies, are exciting new options that may be therapeutically effective. The combination of nivolumab and ipilimumab has exhibited success in managing metastatic renal cell carcinoma. Limited data exist for its use in nonmetastatic renal cell carcinoma with tumor thrombus. This case illustrates the use of nivolumab and ipilimumab combination therapy in delaying tumor growth, producing observable tumor thrombus histologic and radiologic treatment changes, and, most importantly, facilitating a less invasive surgical approach of a level IV renal cell carcinoma tumor thrombus.

Race-free renal function estimation equations and potential impact on Black patients: Implications for cancer clinical trial enrollment.

BACKGROUND: Black patients face disparities in cancer outcomes. Additionally, Black patients are more likely to be undertreated and underrepresented in clinical trials. The recent recommendation to remove race from the estimated glomerular filtration rate (eGFR) results in lower eGFR values for Black patients. The ramifications of this decision, both intended and unintended, are still being elucidated in the medical community. Here, the authors analyze the removal of race from eGFR for Black patients with cancer, specifically with respect to clinical trial eligibility. METHODS: In a cohort of self-identified Black patients who underwent nephrectomy at a tertiary referral center from 2009 to 2021 (n = 459), eGFR was calculated with and without race in commonly used equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]). The distribution of patients and changes within chronic kidney disease stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated on the basis of the utilization of the race coefficient. RESULTS: The median eGFR from CKD-EPI was significantly higher with race (76 ml/min/1.73 m2 ) than without race (66 ml/min/1.73 m2 ; p < .0001). The median eGFR from MDRD was significantly higher with race (71.0 ml/min/1.73 m2 ) than without race (58 ml/min/1.73 m2 ; p < .0001). Observing results in the context of common clinical trial cutoff points, the authors found that 13%-22%, 6%-12%, and 2%-3% more Black patients would fall under common clinical trial cutoffs of 60, 45, and 30 ml/min, respectively, depending on the equation used. A subanalysis of stage III-IV patients only was similar. CONCLUSIONS: Race-free renal function equations may inadvertently result in increased exclusion of Black patients from clinical trials. This is especially concerning because of the underrepresentation and undertreatment that Black patients already experience. PLAIN LANGUAGE SUMMARY: Black patients experience worse oncologic outcomes and are underrepresented in clinical trials. Kidney function, as estimated by glomerular filtration rate equations, is a factor in who can and cannot be in a clinical trial. Race is a variable in some of these equations. For Black patients, removing race from these equations leads to the calculation of lower kidney function. Lower estimated kidney function may result in more black patients being excluded from clinical trials. The inclusion of all races in clinical trials is important for offering best care to everyone and for making results from clinical trials applicable to everyone.

Prognostic Value of Sarcopenia and Albumin in the Surgical Management of Localized Renal Cell Carcinoma.

INTRODUCTION: A universally accepted model for preoperative surgical risk stratification in localized RCC patients undergoing nephrectomy is currently lacking. Both the evaluation of body composition and nutritional status has demonstrated prognostic value for patients with cancer. This study aims to investigate the potential associations between sarcopenia and hypoalbuminemia and survival outcomes in patients with localized kidney cancer treated with partial or radical nephrectomy. MATERIALS AND METHODS: We retrospectively analyzed 473 patients with localized RCC managed with radical and partial nephrectomy. Skeletal muscle index (SMI) was measured from preoperative CT and MRI. Sarcopenic criteria were created using BMI- and sex-stratified thresholds. Relationships between sarcopenia and hypoalbuminemia (Albumin <3.5 g/dL) with overall (OS), recurrence-free (RFS), and cancer-specific survival (CSS) were determined using multivariable and Kaplan-Meier analysis. RESULTS: Of the 473 patients, 42.5% were sarcopenic and 24.5% had hypoalbuminemia. Sarcopenia was significantly associated with shorter OS (HR=1.51, 95% CI 1.07-2.13), however, was nonsignificant in the RFS (HR = 1.33, 95% CI 0.88-2.03) and CSS (HR=1.66, 95% CI 0.96-2.87) models. Hypoalbuminemia predicted shorter OS (HR=1.76, 95% CI 1.22-2.55), RFS (HR=1.86, 95% CI 1.19-2.89), and CSS (HR=1.82, 95% CI 1.03-3.22). Patients were then stratified into low, medium, and high-risk groups based on the severity of sarcopenia and hypoalbuminemia. Risk groups demonstrated an increasing association with shorter OS (all p<0.05). Reduced RFS was observed in the medium risk-hypoalbuminemia (HR=2.18, 95% CI 1.16-4.09) and high-risk groups (HR=2.42, 95% CI 1.34-4.39). Shorter CSS was observed in the medium risk-hypoalbuminemia (HR=2.31, 95% CI 1.00-5.30) and high-risk groups (HR=2.98, 95% CI 1.34-6.61). CONCLUSION: Localized RCC patients with combined preoperative sarcopenia and hypoalbuminemia displayed a two to a three-fold reduction in OS, RFS, and CSS after nephrectomy. These data have implications for guiding prognostication and treatment election in localized RCC patients undergoing extirpative surgery.

Clinic friendly estimation of muscle composition: Preoperative linear segmentation shows overall survival correlated with muscle mass in patients with nonmetastatic renal cell carcinoma.

Purpose: Sarcopenia is associated with decreased survival and increased complications in patients with renal cell carcinoma. Readily identifying patients with low muscle composition that may experience worse outcomes or would benefit from preoperative intervention is of clinical interest. Traditional body composition analysis methods are resource intensive; therefore, linear segmentation with routine imaging has been proposed as a clinically practical alternative. This study assesses linear segmentation's prognostic utility in nonmetastatic renal cell carcinoma. Materials and Methods: A single institution retrospective analysis of patients that underwent nephrectomy for nonmetastatic renal cell carcinoma from 2005-2021 was conducted. Linear segmentation of the bilateral psoas/paraspinal muscles was completed on preoperative imaging. Total muscle area and total muscle index associations with overall survival were determined by multivariable analysis. Results: 532 (388 clear cell) patients were analyzed, with median (IQR) total muscle index of 28.6cm2/m2 (25.8-32.5) for women and 33.3cm2/m2 (29.1-36.9) for men. Low total muscle index was associated with decreased survival (HR=1.96, 95% CI 1.32-2.90, p<0.001). Graded increases in total muscle index were associated with better survival (HR=0.95, 95% CI 0.92-0.99, p=0.006). Conclusions: Linear segmentation, a clinically feasible technique to assess muscle composition, has prognostic utility in patients with localized renal cell carcinoma, allowing for incorporation of muscle composition analysis into clinical decision-making. Muscle mass determined by linear segmentation was associated with overall survival in patients with nonmetastatic renal cell carcinoma.

Association of grit and overall survival in patients undergoing nephrectomy for renal cell carcinoma.

Background: Quantifying grit with the Short Grit Scale (Grit-S) has shown ability to predict success in various academic and professional domains. Grit has yet to be analyzed in patients with cancer. Methods: This study is a longitudinal analysis of prospectively distributed Grit-S surveys to patients undergoing radical or partial nephrectomy. Patients who completed a preoperative Grit-S survey with confirmed renal cell carcinoma (RCC) were included in the analysis. The relationship between preoperative grit scores and overall survival (OS) was determined using Cox proportional-hazard models and Kaplan-Meier analysis. Results: A total of 323 patients with RCC that completed the Grit-S survey prior to nephrectomy were included in the study. Median Grit score was 3.9. Most patients were male (67.5%), White (69.3%), and greater than 60 years old (57.0%) with a median age of 62 at the time of surgery. Patients scoring above or below the median grit score had similar baseline characteristics. As a binary variable, lower preoperative grit was significantly associated with shorter OS [hazard ratio (HR) =2.02, 95% confidence interval (CI): 1.12-3.63, P=0.019] on multivariable analysis. Unit changes in grit were not significantly associated with OS (HR =0.77, 95% CI: 0.53-1.14, P=0.193). Conclusions: Lower grit scores may predict decreased OS in RCC patients undergoing nephrectomy. The Grit-S survey may have utility in preoperative evaluation. Further research assessing grit in other malignancies and how to psychologically optimize patients prior to surgery are needed.

Data regarding covariates significantly associated with sarcopenia and varying albumin statuses in patients with renal cell carcinoma.

Poor functional, nutritional, and muscle status is a significant negative predictor for surgical and survival outcomes in patients with cancer, including renal cell carcinoma. This dataset displays results from preoperative muscle composition analysis and albumin levels in a large cohort (n = 473) of patients undergoing surgery for renal cell carcinoma. Data was obtained from retrospective review of prospectively maintained databases and retrospective image analysis. The optimal cut-point for skeletal muscle index (sarcopenia) was determined by a receiver operatic characteristic analysis to optimally stratify cohort, adjusting for BMI and sex. A threshold value of 3.5 g/dL was used to categorize normal versus low serum albumin. Patients were stratified into low risk (non-sarcopenic and normal albumin), medium risk (non-sarcopenic and low albumin, or sarcopenic and normal albumin), and high risk (sarcopenic and low albumin) groups. This data could potentially be used in future studies to determine other relationships between nutrition and musculature in renal cell carcinoma patients.

Resection of retroperitoneal tumors with inferior vena cava involvement without caval reconstruction.

BACKGROUND AND OBJECTIVES: Retroperitoneal tumors with involvement of the inferior vena cava (IVC) often require resection of the IVC to achieve complete tumor removal. This study evaluates the safety and efficacy of IVC ligation without caval reconstruction. METHODS: A retrospective chart review of patients who underwent IVC ligation (IVC-Ligation) and IVC resection with reconstruction (IVC-Reconstruction) at our institution between May 2004 and April 2021 was performed. Outcomes from the two surgical techniques were compared via univariate analysis using the Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Forty-nine IVC-Ligation and six IVC-Reconstruction surgeries were identified. There were no differences in baseline demographics, tumor characteristics, complication rates, postoperative morbidity, or overall 5-year survival between groups. IVC-Reconstruction patients were more likely to require intensive care unit admission (83% vs. 33%; p = 0.0257) and the IVC-Ligation cohort had a tendency to present with nondebilitating postoperative lymphedema (35% vs. 0%; p = 0.1615), which resolved for most patients. CONCLUSIONS: IVC-Ligation is a viable surgical option for select patients presenting with retroperitoneal tumors with IVC involvement and provides acceptable short- and medium-term outcomes.

Case report: Important considerations for a renal mass on a solitary kidney in an adult with history of childhood wilms tumor.

Adult survivors of childhood Wilms tumor are at an increased risk of secondary malignant neoplasms. The presence of a solitary kidney further complicates clinical management in this population. Herein, we present the case of a 37 year old female with a history of childhood Wilms tumor presenting with a secondary renal neoplasm. We highlight important clinical considerations for renal function preservation and present a finding of predisposition to kidney stone formation due to urinary stasis from distorted ureter architecture secondary to tumor mass effect.

Low free testosterone is associated with increased mortality in frail surgical patients.

BACKGROUND: Preoperative frailty has been associated with adverse postoperative outcomes. Additionally, low testosterone has been associated with physical frailty and cognitive decline. However, the impact of simultaneous frailty and low testosterone on surgical outcomes is understudied. METHODS: Preoperative frailty status and testosterone levels were obtained in patients undergoing a diverse range of surgical procedures. Preoperative frailty was evaluated independently and in combination with testosterone through the creation of composite risk groups. Relationships between preoperative frailty and composite risk groups with overall survival were determined using Kaplan-Meier and logistic regression analyses. Bivariate analysis was used to determine the associations between frailty and testosterone status on postoperative complications, length of hospital stay, and readmission rates. RESULTS: Median age of the cohort was 63 years, and the median follow-up time was 105 weeks. Thirty-one patients (23%) were frail, and 36 (27%) had low free testosterone. Bivariate analysis demonstrated a statistically significant relationship between preoperative frailty and overall survival (P = .044). In multivariate analysis, coexisting frailty and low free testosterone were significantly associated with decreased overall survival (hazard ratio 4.93, 95% confidence interval, 1.68-14.46, P = .004). CONCLUSION: We observed preoperative frailty, both independently and in combination with low free testosterone levels, to be significantly associated with decreased overall survival across various surgical procedures. Personalizing the surgical risk assessment through the incorporation of preoperative frailty and testosterone status may serve to improve the prognostication of patients undergoing major surgery.

Ovotesticular Disorder Mimicking Acute Spermatic Cord Torsion.

Ovotesticular disorder is a rare form of sexual development in which a patient may have one ovary and one testis, or more commonly a gonad or gonads containing both ovarian and testicular tissue. Patients with this condition typically present in infancy with ambiguous genitalia. Delayed presentations of clinically symptomatic, older patients with normal external genitalia are extremely rare. We present a case of a 14-year-old male with normal external genitalia who presented with symptoms and signs consistent with spermatic cord torsion but found to have ovotesticular disorder on evaluation.

Left renal vein nutcracker syndrome and concurrent IVC duplication: Surgical treatment.

Multiple vascular anomalies may be encountered in patients with nutcracker syndrome; further compounding the surgical complexity in managing this condition. A 28-year-old male presented with persistent flank pain and hematuria. Imaging revealed narrowing of the left renal vein at the aortomesenteric junction, and a dilated vein consistent with the left gonadal vein. On surgical exploration, a duplicated IVC was found. The patient underwent a right caval-to-left caval bypass using a cryopreserved femoral vein homograft. The surgery was well tolerated and completely resolved the patient's symptoms.

Juxtaglomerular Cell Tumor: A Rare Presentation of a Surgically Curable Cause of Secondary Hypertension in the Pediatric Population.

Hypertension is often the primary presenting symptom of multiple renal pathologies. Overactivity of the Renin-Angiotensin-Aldosterone-System (RAAS) is a common cause and usually results from an induced physiologic response. However, conditions do exist that involve autonomous renin production. Juxtaglomerular cell tumors (JGCT), or reninomas, are renal lesions that cause refractory hypertension via this mechanism. Symptoms and lab abnormalities usually subside with surgical resection of these tumors. Here, we present a case of a 13-year old female with uncontrolled hypertension secondary to reninoma treated with partial nephrectomy, with focus on initial presentation, diagnostic evaluation, and surgical management of this uncommon tumor.