Conrad M. Tobert

Growth kinetics and active surveillance for small renal masses.

Purpose of reviewManagement options for small renal masses (SRMs) include excision, ablation, and active surveillance. Increasing interest in active surveillance, particularly for tumors of limited oncologic potential, in patients with other significant health concerns continues to rise, but precise protocols are still lacking. Recent findingsA review of 18 retrospective series of patients undergoing active surveillance for 957 SRMs indicates that the majority grew during observation (mean 0.32 cm/year), but only 1.4% metastasized during 32 months of follow-up (median). One published prospective series of 209 SRMs reported average growth of 0.13 cm/year and only 1% metastasized. Maximal tumor diameter (or volume) at presentation is a predictor of growth rate, high-grade disease, and likelihood of metastasis. SRMs less than 3 cm are very unlikely to metastasize and deferring treatment has not been associated with increased failure to cure. SummaryActive surveillance is a reasonable initial strategy in most patients with SRMs, particularly those with limited life-expectancy and increased perioperative risk. Intervention should be considered for growth to greater than 3–4 cm or by greater than 0.4–0.5 cm/year while on active surveillance.

Differential Use of Partial Nephrectomy for Intermediate and High Complexity Tumors May Explain Variability in Reported Utilization Rates

PURPOSE Partial nephrectomy has become a reference standard for tumors amenable to a kidney sparing approach but reported utilization rates vary widely. The R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and hilar tumor touching main renal artery or vein) nephrometry score was developed to standardize the reporting of tumor complexity with applicability in academic and community based settings. We hypothesized that tumor and surgeon factors account for variable use of partial nephrectomy. MATERIALS AND METHODS Clinical and R.E.N.A.L. nephrometry score data were analyzed on 1,433 cases performed between 2004 and 2011 by a total of 19 surgeons with varying partial nephrectomy utilization rates (0% to 100%) who practiced at a total of 2 academic centers and 1 community based health system. RESULTS Partial nephrectomy use increased during the study period from 36% before 2007 to 73% for 2010 to 2012 (p <0.0001). Increasing proportions of intermediate and high R.E.N.A.L. nephrometry score tumors were treated with partial nephrectomy during this time (35% to 86% and 11% to 36%, respectively, p <0.0001). Partial nephrectomy use was stable for low complexity tumors at 91% overall. Individual surgeons performed partial nephrectomy for 0% to 100% of intermediate complexity and 0% to 45% of high complexity tumors. On multivariable analysis surgery year, tumor size, each R.E.N.A.L. nephrometry score component, surgeon and annual surgeon volume predicted partial vs radical nephrectomy (each p <0.05). On multivariable analysis several surgeon factors, including surgeon volume, setting, fellowship training, and proportional use of minimally invasive and robotic partial nephrectomy, were associated with higher partial nephrectomy use (each p <0.002). CONCLUSIONS Surgeon and tumor factors contribute significantly to the choice of partial nephrectomy. The significant variation in partial nephrectomy use by individual surgeons appears to be caused by differential treatment for intermediate and high complexity tumors. This may be due to surgical volume, training, setting and the use of minimally invasive techniques.

Surgeon Assessment of Renal Preservation with Partial Nephrectomy Provides Information Comparable to Measurement of Volume Preservation with 3-Dimensional Image Analysis

PURPOSE The strongest predictors of renal function after partial nephrectomy are the preoperative glomerular filtration rate and the amount of preserved parenchyma. Measuring volume preservation by 3-dimensional imaging is accurate but time-consuming. Percent functional volume preservation was designed to replace surgeon assessment of volume preservation with a less labor intensive, objective assessment. We compared volume preservation with 3-dimensional imaging, percent functional volume preservation and surgeon assessment of volume preservation as predictors of renal function after partial nephrectomy. MATERIALS AND METHODS We calculated volume preservation with 3-dimensional imaging, percent functional volume preservation and surgeon assessment of volume preservation in 41 patients with preoperative and postoperative cross-sectional imaging available. Surgeon assessment was validated internally in another 75 patients. Short-term and long-term renal function was assessed with univariate and multivariate linear regression models. RESULTS Median parenchymal preservation was 85% (range 37% to 105%) by 3-dimensional imaging, 91% (range 51% to 114%) by percent functional preservation and 88% (range 45% to 99%) by surgeon assessment. Each method strongly correlated with nadir glomerular filtration rate (r(2) = 0.75, 0.65 and 0.78) and latest glomerular filtration rate (r(2) = 0.65, 0.66 and 0.67, respectively, each p <0.0001). Univariate analysis revealed that age, preoperative glomerular filtration rate, renal nephrometry score and each assessment were significant predictors of renal function (p <0.05). On multivariate analysis parenchymal preservation was the strongest predictor (p <0.0001). Models using volume preservation with 3-dimensional imaging, percent functional volume preservation and surgeon assessment of volume preservation were statistically similar in the ability to predict the nadir and latest glomerular filtration rates. In an additional validation cohort surgeon assessment remained strongly correlated with nadir glomerular filtration rate (r(2) = 0.74) and latest glomerular filtration rate (r(2) = 0.73, each p <0.0001). CONCLUSIONS Surgeon assessment of volume preservation provides a reliable estimate of renal functional preservation with characteristics comparable to those of more time intensive alternatives. We propose that surgeon assessment of volume preservation should be routinely reported to facilitate analysis of partial nephrectomy outcomes.

Emerging Impact of Malnutrition on Surgical Patients: Literature Review and Potential Implications for Cystectomy in Bladder Cancer

Purpose: Malnutrition is emerging as a significant factor in patient outcomes. A contemporary review of malnutrition has not been performed for the urologist. We review the available literature and current standards of care for malnutrition screening, assessment and intervention, focusing on patients with bladder cancer treated with cystectomy. Materials and Methods: Our multidisciplinary team searched PubMed® for available literature on malnutrition, focusing on definition and significance, importance to urologists, screening, assessment, diagnosis, immunological and economic impacts, and interventions. Results: The prevalence of malnutrition in hospitalized patients is estimated to range from 15% to 60%, reaching upward of 71% in those with cancer. Malnutrition has been shown to increase inflammatory markers, further intensifying catabolism and weight loss. Bladder cancer is catabolic and patients undergoing cystectomy have increased resting energy expenditure postoperatively. Data are emerging on the impact of malnutrition in the cystectomy population. Recent studies have identified poor nutritional status based on low albumin or sarcopenia (loss of muscle) as having an adverse impact on length of hospitalization, complications and survival. The current standard of care malnutrition assessment tool, the 2012 consensus statement of the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition, has not been evaluated in the urological literature. Perioperative immunonutrition in patients undergoing colorectal surgery has been associated with significant decreases in postoperative complications, and recent pilot work has identified the potential for immunonutrition to positively impact the cystectomy population. Conclusions: Malnutrition has a significant impact on surgical patients, including those with bladder cancer. There are emerging data in the urological literature regarding how best to identify and improve the nutritional status of patients undergoing cystectomy. Additional research is needed to identify malnutrition in these patients and interventions to improve surgical outcomes.

Impact of Reduced Glomerular Filtration Rate and Proteinuria on Overall Survival of Patients with Renal Cancer.

PURPOSE Although it is commonly staged according to glomerular filtration rate, an international work group recommended classifying chronic kidney disease by cause, glomerular filtration rate and albuminuria. Data on nonsurgical patients with chronic kidney disease indicate proteinuria to be an independent predictor of renal function decrease and mortality. We evaluated whether preoperative proteinuria impacted survival in patients undergoing nephrectomy. MATERIALS AND METHODS An institutional registry was queried for information regarding preoperative creatinine/glomerular filtration rate and urinalysis in 900 patients, including 362 and 538 treated with partial and radical nephrectomy, respectively. Patients were grouped according to glomerular filtration rate level (G1 to G5), proteinuria level (A1 to A3) and chronic kidney disease risk classification (low to very high). Kaplan-Meier and Cox proportional hazards analyses of overall survival were performed. RESULTS The preoperative glomerular filtration rate was less than 60 ml/minute/1.73 m(2) in 30% of patients (median 73, IQR 56-91) and 20% of patients had baseline proteinuria. According to the KDIGO (Kidney Disease Improving Global Outcomes) classification 23% of patients were at moderately increased, 11% were at high and 8% were at very high risk for chronic kidney disease progression. Kaplan-Meier analysis revealed that the preoperative glomerular filtration rate, proteinuria and chronic kidney disease risk group were associated with poor overall survival. In Cox proportional hazard models accounting for age, gender, race, tumor size, clinical stage and surgery type the glomerular filtration rate, proteinuria and chronic kidney disease risk group were highly significant predictors of overall survival (p <0.0001). CONCLUSIONS Preoperative proteinuria is a significant predictor of overall survival in patients who undergo nephrectomy. Classification according to preoperative glomerular filtration rate and proteinuria more accurately predicts survival than using the glomerular filtration rate alone after accounting for cancer stage. This information supports routine evaluation of proteinuria in patients with kidney cancer.

Multicenter Validation of Surgeon Assessment of Renal Preservation in Comparison to Measurement With 3D Image Analysis.

OBJECTIVE To validate the findings of a prior single-surgeon series with a multi-institutional comparison of three-dimensional imaging of volume preservation (3DVP) and surgeon assessment of volume preservation (SAVP) as predictors of renal function after partial nephrectomy (PN). Baseline renal function and preservation of functioning renal parenchyma are the strongest predictors of function after PN for presumed renal cancer. Prior studies have confirmed that measurement of volume preservation with 3DVP is accurate, but limited data exist to compare this time-consuming approach with SAVP. MATERIALS AND METHODS 3DVP and SAVP were calculated for 157 patients operated on by 13 surgeons at 2 institutions having both pre- and postoperative cross-sectional imaging. Renal function was assessed by univariable and multivariable linear regression methods. RESULTS Median ipsilateral parenchymal preservation was 87% by 3DVP (interquartile range: 76%-95%) and 85% by SAVP (interquartile range: 75%-90%). Both correlated strongly with each other (P <.0001) and no statistical differences in the correlation were observed for different individual surgeons. Each method was strongly correlated with postoperative glomerular filtration rate (P <.0001). Multivariable models using 3DVP and SAVP were statistically similar in predicting postoperative glomerular filtration rate (R(2) = 0.86 for both). However, SAVP was not interchangeable with 3DVP within a 5% margin of error (95% confidence interval: -0.11, 0.13) according to Bland-Altman analysis. CONCLUSION SAVP has been validated in a multicenter cohort of PN patients demonstrating it to provide a reliable estimate of renal functional preservation that is reproducible in contemporary practice. We propose that SAVP reporting should be performed routinely to facilitate analysis of PN outcomes and 3DVP used for research purposes.

Malnutrition Diagnosis during Adult Inpatient Hospitalizations: Analysis of a Multi-Institutional Collaborative Database of Academic Medical Centers

BACKGROUND Malnutrition is a significant problem for hospitalized patients. However, the true prevalence of reported malnutrition diagnosis in real-world clinical practice is largely unknown. Using a large collaborative multi-institutional database, the rate of malnutrition diagnosis was assessed and used to assess institutional variables associated with higher rates of malnutrition diagnosis. OBJECTIVE The aim of this study was to define the prevalence of malnutrition diagnosis reported among inpatient hospitalizations. DESIGN The University Health System Consortium (Vizient) database was retrospectively reviewed for reported rates of malnutrition diagnosis. PARTICIPANTS/SETTING All adult inpatient hospitalization at 105 member institutions during fiscal years 2014 and 2015 were evaluated. MAIN OUTCOME MEASURES Malnutrition diagnosis based on the presence of an International Classification of Diseases-Ninth Revision diagnosis code. STATISTICAL ANALYSIS Hospital volume and publicly available hospital rankings and patient satisfaction scores were obtained. Multiple regression analysis was performed to assess the association between these variables and reported rates of malnutrition. RESULTS A total of 5,896,792 hospitalizations were identified from 105 institutions during the 2-year period. It was found that 292,754 patients (5.0%) had a malnutrition diagnosis during their hospital stay. By institution, median rate of malnutrition diagnosis during hospitalization was 4.0%, whereas the rate of severe malnutrition diagnosis was 0.9%. There was a statistically significant increase in malnutrition diagnosis from 4.0% to 4.9% between 2014 and 2015 (P<0.01). Institutional factors associated with increased diagnosis of malnutrition were higher hospital volume, hospital ranking, and patient satisfaction scores (P<0.01). CONCLUSIONS Missing a malnutrition diagnosis appears to be a universal issue because the rate of malnutrition diagnosis was consistently low across academic medical centers. Institutional variables were associated with the prevalence of malnutrition diagnosis, which suggests that institutional culture influences malnutrition diagnosis. Quality improvement efforts aimed at improved structure and process appear to be needed to improve the identification of malnutrition.

Investigation of Forces Involved in Closure of the Renal Remnant After Simulated Partial Nephrectomy

OBJECTIVE To investigate the potential biomechanical causes of the complications of partial nephrectomy (PN) in a preclinical model of sliding-clip renorrhaphy. PN is a reference standard for amenable small renal masses. One disadvantage of PN, however, is the risk of postoperative bleeding and/or urinary leak. MATERIALS AND METHODS Simulated tumor excision and reconstruction using sliding-clip renorrhaphy were performed on fresh porcine kidneys. Suture tension (newtons, N) was measured in nonperfused and perfused states. RESULTS Mean suture tension initially applied during renorrhaphy was 2.8 ± 0.7 N. After simulated perfusion to 120 mm Hg, increased tension was necessary to control fluid extravasation (average, 3.2 ± 0.7 N). For intravascular pressures above 200 mm Hg, an average tension of 3.4 ± 0.7 N was necessary to prevent observable leakage. The increase in suture tension under normal and hypertensive states averaged 21 ± 28% and 29 ± 31%, respectively. In experiments examining maximum suture tension before suture tear through, failure of the anchored sutures varied with the width of incorporated renal capsule. Mean forces were 5.7 ± 3.2, 8.8 ± 5.7, and 14.0 ± 6.0 N with 0.5, 1.0, and 1.5 cm of capsule, respectively. Review of video footage indicated that acute angles appear to contribute to suture failure. CONCLUSION This study demonstrates that the tension required to cause suture failure is only slightly higher than the tension typically applied during PN and necessary to control bleeding and urine leaks. After reperfusion of the kidney, the tension can increase by ≥ 29% under hypertensive conditions. Incorporation of sufficient (≥ 0.5 cm) capsule and avoidance of acute angles of entry or exit during closure of the kidney are likely to reduce suture failure.

Change in Platelet Count as a Prognostic Indicator for Response to Primary Tyrosine Kinase Inhibitor Therapy in Metastatic Renal Cell Carcinoma

To evaluate change in platelet count as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC).

Chronic Kidney Disease Is More Common in Locally Advanced Renal Cell Carcinoma

OBJECTIVE To retrospectively evaluate clinical predictors of chronic kidney disease (CKD) in renal cell carcinoma (RCC) patients to identify associations between patient- and tumor-specific factors with poorer renal function. CKD and RCC are interrelated, with 26%-44% of RCC patients having concomitant CKD at diagnosis. PATIENTS AND METHODS Institutional registries from Spectrum Health and University of California, San Diego, were queried for preoperative glomerular filtration rate and proteinuria status before radical or partial nephrectomy. Preoperative clinical and tumor factors were recorded; proteinuria was classified as A1 (<30 mg), A2 (30-300 mg), and A3 (>300 mg). CKD was grouped by Kidney Disease Improving Global Outcomes classification (low, moderately increased, high, very high). RESULTS We evaluated 1569 patients undergoing surgery for renal cortical tumors. CKD status was low risk in 860 (55%), moderately increased in 381 (24%), high in 194 (12%), and very high in 134 (9%) patients. Increased radius, exophytic or endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior or posterior, location relative to polar lines score, tumor size, and clinical tumor stage were strongly associated with increased CKD risk at baseline. Clinical stage T3/T4 disease had more at-risk patients than stages T2 and T1 disease (39.5% vs 22% and 19%, P = .0001). Clinical tumor stage and gender were the only predictors of proteinuria, lower glomerular filtration rate, and higher CKD risk group in both univariate and multivariate analyses. CONCLUSION Forty-five percent of patients with RCC had moderate or higher CKD before treatment. A positive correlation between pretreatment CKD and locally advanced RCC (cT3/T4) was present. This likely relates to increased loss of functional parenchyma with increasing tumor size or stage, with important implications in patient management.