Matthew N. Simmons

Kidney tumor location measurement using the C index method.

PURPOSE Tumor location assessment is essential to plan nephron sparing kidney surgery. We describe a method to quantify the proximity of kidney tumors to the renal central sinus for reporting and surgical management. MATERIALS AND METHODS Centrality index scoring was done using standard 2-dimensional cross-sectional computerized tomography images in 133 consecutive patients undergoing transperitoneal laparoscopic partial nephrectomy between September 2003 and November 2005. The Pythagorean theorem was used to calculate the distance from tumor center to kidney center. The distance was divided by tumor radius to obtain the centrality index. We assessed the correlation of the centrality index with laparoscopic partial nephrectomy operative parameters and the urological complication rate. Centrality index accuracy and interobserver variability were assessed. RESULTS A centrality index of 0 equates to a tumor that is concentric with the center of the kidney. A centrality index of 1 equates to a tumor with its periphery touching the kidney center. As the centrality index increases, the tumor periphery becomes more distant from the kidney center. Multivariate regression analysis revealed an association of the centrality index with warm ischemia time (p = 0.004), which is a surrogate for technical complexity. Interobserver correlation of centrality index values was greater than 93% with an estimated learning curve of 14 cases required for measurement variability to decrease below 10% of the mean centrality index of 10 consecutive cases. CONCLUSIONS Centrality index scoring provides a clinically useful measure of tumor centrality. This system may allow improved clinical and radiological assessment of kidney tumors, and improved reporting of quantitative tumor site.

“Trifecta” in Partial Nephrectomy

PURPOSE We introduce the concept of trifecta outcomes during robotic/laparoscopic partial nephrectomy, in which the 3 key outcomes of negative cancer margin, minimal renal functional decrease and no urological complications are simultaneously realized. We report serial trifecta outcomes in patients treated with robotic/laparoscopic partial nephrectomy for tumor in a 12-year period. MATERIALS AND METHODS A total of 534 patients had complete data available and were retrospectively divided into 4 chronologic eras, including the discovery era--139 from September 1999 to December 2003, conventional hilar clamping era--213 from January 2004 to December 2006, early unclamping era--104 from January 2007 to November 2008 and anatomical zero ischemia era--78 from March 2010 to October 2011. Renal functional decrease was defined as a greater than 10% reduction in the actual vs volume predicted postoperative estimated glomerular filtration rate. RESULTS Across the 4 eras tumors trended toward larger size (2.9, 2.8, 3.1 and 3.3 cm, p = 0.08) and yet the estimated percent of kidney preserved was similar (89%, 90%, 90% and 88%, respectively, p = 0.3). Recent eras had increasingly complex tumors that were more often 4 cm or greater (p = 0.03), centrally located (p <0.009) or hilar (p <0.0001). Nevertheless, with significant technical refinement warm ischemia time decreased serially (36, 32, 15 and 0 minutes, respectively, p <0.0001). Renal functional outcomes were superior in recent eras with fewer patients experiencing a decrease (p <0.0001). Uniquely, actual estimated glomerular filtration rate outcomes exceeded volume predicted estimated glomerular filtration rate outcomes only in the zero ischemia cohort in regard to other eras (-9.5%, -11%, -0.9% and 4.2%, respectively, p <0.001). Positive cancer margins were uniformly low at less than 1%. Urological complications trended lower in recent eras (p = 0.01). Trifecta outcomes occurred more commonly in recent eras (45%, 44%, 62% and 68%, respectively, p = 0.0002). CONCLUSIONS Trifecta should be a routine goal during partial nephrectomy. Despite increasing tumor complexity, trifecta outcomes of robotic/laparoscopic partial nephrectomy improved significantly in the last decade.

Functional Recovery After Partial Nephrectomy: Effects of Volume Loss and Ischemic Injury

PURPOSE We used what is to our knowledge a new method to estimate volume loss after partial nephrectomy to assess the relative contributions of ischemic injury and volume loss on functional outcomes. MATERIALS AND METHODS We analyzed the records of 301 consecutive patients who underwent conventional partial nephrectomy between 2007 and 2010 with available data to meet inclusion criteria. Percent functional volume preservation was measured at a median of 1.4 years after surgery. Modification of diet in renal disease-2 estimated glomerular filtration rate was measured preoperatively and perioperatively, and a median of 1.2 years postoperatively. Statistical analysis was done to study associations. RESULTS Hypothermia or warm ischemia 25 minutes or less was applied in 75% of cases. Median percent functional volume preservation was 91% (range 38%-107%). Percent glomerular filtration rate preservation at nadir and late time points was 77% and 90% of preoperative glomerular filtration rate, respectively. On multivariate analysis percent functional volume preservation and warm ischemia time were associated with nadir glomerular filtration rate while only percent functional volume preservation was associated with late glomerular filtration rate (each p <0.001). Late percent glomerular filtration rate preservation and percent functional volume preservation were directly associated (p <0.001). Recovery of function to 90% or greater of percent functional volume preservation predicted levels was observed in 86% of patients. In patients with de novo postoperative stage 3 or greater chronic kidney disease, percent functional volume preservation and Charlson score were associated with late percent glomerular filtration rate preservation. Warm ischemia time was not associated with late functional glomerular filtration rate decreases in patients considered high risk for ischemic injury. CONCLUSIONS In this cohort volume loss and not ischemia time was the primary determinant of ultimate renal function after partial nephrectomy. Technical modifications aimed at minimizing volume loss during partial nephrectomy while still achieving negative margins may result in improved functional outcomes.

Surgical Renal Ischemia: A Contemporary Overview

PURPOSE Partial nephrectomy is being increasingly performed to treat renal cell carcinoma. Because warm ischemia is induced during many open and laparoscopic partial nephrectomy surgeries, its impact on postoperative kidney function has received renewed attention. We assessed the current state of knowledge pertaining to warm ischemic kidney injury and renal functional outcomes. MATERIALS AND METHODS A review of the literature from 1947 to 2007 pertaining to warm ischemic kidney injury was performed. Data from relevant animal and clinical studies were assessed and compared. RESULTS Animal studies have described the relationship between the duration of warm ischemia and the magnitude of subsequent renal dysfunction. However, direct translation of these data to clinical practice is limited by significant anatomical and physiological differences among species. Current clinical data support a safe warm ischemia time limit of 30 minutes in patients with normal preoperative kidney function. To date no scientifically rigorous clinical study has established a warm ischemia dose-response curve. Additionally, no algorithm exists to predict the risk of acute kidney injury and chronic kidney disease in patients undergoing transient warm ischemia. CONCLUSIONS Clinical use of glomerular filtration rate measurement, kidney injury biomarkers and the application of glomerular filtration rate based renal functional diagnostic criteria may allow improved diagnosis, management and reporting of renal functional outcomes. Prospective, controlled clinical studies are much needed to accurately characterize the relationship between warm ischemia and renal dysfunction.

Effect of Parenchymal Volume Preservation on Kidney Function After Partial Nephrectomy

PURPOSE The percent of functional volume preservation is a primary determinant of functional outcome after partial nephrectomy. We assessed what is to our knowledge a novel method to estimate the percent of functional volume preservation to assess its effect on functional outcomes. MATERIALS AND METHODS We studied the glomerular filtration rate outcome based on the modification of diet in renal disease 2 in 39 patients with normal preoperative serum creatinine who underwent open or laparoscopic partial nephrectomy from January 2007 to December 2009. A cylindrical volume ratio method was used to estimate the percent of functional volume preservation on computerized tomography images obtained before and after partial nephrectomy. A model to predict the postoperative estimated glomerular filtration rate was based on multiplying the preoperative glomerular filtration rate by the percent of functional volume preservation, followed by adjustment for the functional contribution of the contralateral kidney. Correlation and multiple regression analysis was done to test the model. RESULTS The median preoperative, nadir and late estimated glomerular filtration rate in the cohort was 104 (range 53 to 234), 75 (range 21 to 189) and 90 ml per minute/1.73 m2 (range 45 to 228), respectively. The nadir and late estimated glomerular filtration rate was measured at a median of 2 (range 0 to 8) and 358 days (range 13 to 827), respectively. The median percent of functional volume preservation was 88% (range 50% to 100%) for the operated kidney and 94% (range 75% to 105%) when adjusted for total bilateral kidney volume. We noted a 96% correlation between the predicted and the observed late estimated glomerular filtration rate. On multivariate analysis the preoperative glomerular filtration rate (p<0.001) and ischemia time (p=0.02) correlated with the nadir glomerular filtration rate, and the preoperative glomerular filtration rate (p<0.001) and the percent of functional volume preservation (p=0.04) correlated with the late glomerular filtration rate. CONCLUSIONS These data support the notion that preoperative nephron endowment and the percent of functional volume preservation are the primary determinants of the long-term functional outcome after partial nephrectomy in patients with normal preoperative kidney function who have ischemia time within acceptable limits.

Laparoscopic Radical Versus Partial Nephrectomy for Tumors >4 cm: Intermediate-term Oncologic and Functional Outcomes

OBJECTIVES To compare the oncologic and functional outcomes of laparoscopic radical nephrectomy (LRN) and laparoscopic partial nephrectomy (LPN) for clinical Stage T1b-T3 renal cell carcinoma >4 cm in size. METHODS This retrospective analysis compared patients undergoing LRN (n = 75) or LPN (n = 35) at a tertiary referral center from April 2001 to December 2005 for Stage T1b-T3N0M0 renal cell carcinoma. The endpoints included radiologically verified systemic and local recurrence, cancer-specific mortality, overall mortality, and chronic kidney disease as determined from the calculated glomerular filtration rate and Kidney Foundation Dialysis Outcomes Quality Initiative diagnostic criteria. RESULTS The LRN group had larger tumors (5.3 vs 4.9 cm; P = .03), more T3a tumors (33% vs 9%; P = .006), and more clear cell pathologic features (85% vs 66%; P = .03). No surgical margins in either group were positive. The median follow-up was 57 months (range 27-79) for the LRN group and 44 months (range 27-85) for the LPN group (P = .1). The overall mortality (11% vs 11%), cancer-specific mortality (3% vs 3%), and recurrence (3% vs 6%) rates (P = .4) were equivalent. The postoperative decrease in the estimated glomerular filtration rate was less in the LPN group than in the LRN group at 13 and 24 mL/min, respectively (P = .03). Postoperatively, 2-stage increases in the chronic kidney disease stage occurred in 12% vs 0% of patients in the LRN and LPN groups, respectively (P < .001). CONCLUSIONS Our intermediate-term data have indicated that in appropriate patients with Stage T1b-T3 tumors >4 cm, LPN provides equivalent oncologic efficacy and superior renal functional outcomes compared with LRN. Future studies are required to confirm these trends.

Perioperative Efficacy of Laparoscopic Partial Nephrectomy for Tumors Larger than 4 cm

BACKGROUND Laparoscopic partial nephrectomy (LPN) is typically reserved for kidney tumors < or = 4 cm in size. The use of LPN in patients with larger tumors (> 4 cm) has not been systematically evaluated. OBJECTIVE To examine technical feasibility and perioperative safety and efficacy of LPN for clinical stage pT1b-T2 tumors > 4 cm. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective review of data from an Institutional Review Board-approved, prospectively maintained database of 425 LPN procedures over a 6-yr period (September 1999 through December 2005). Patients were grouped according to tumor size: control group 1: < 2 cm (n=89; 21% of patients); control group 2: 2-4 cm (n=278; 65% of patients); and study group 3: > 4 cm (n=58; 14% of patients). INTERVENTION Retroperitoneal and transperitoneal LPN. MEASUREMENTS Serum creatinine levels, estimated glomerular filtration rates. RESULTS AND LIMITATIONS For groups 1, 2, and 3, mean tumor size was 1.5 cm, 2.9 cm, and 6 cm in diameter, respectively (p<0.001). Study group 3 patients more often had an American Society of Anesthesiologists score > or = 3 (p<0.05), central tumors (p<0.001), pelvicalyceal repair (p=0.004), and heminephrectomy (p<0.001). Total operative time, estimated blood loss, and duration of hospital stay were equivalent. Mean warm ischemia time was 30 min, 32 min, and 38 min in groups 1, 2, and 3, respectively (p=0.007). Tumor size > 4 cm did not increase significant risk for positive tumor margins, intraoperative complications, or postoperative genitourinary complications. In each group preoperative stage > or = 3 chronic kidney disease (CKD) was present in 31%, 35%, and 44% of patients in groups 1, 2, and 3, respectively (p=0.15); postoperatively, stage 3-5 CKD incidence increased to 52%, 52%, and 63% in groups 1, 2, and 3, respectively (p=0.20). Patients with tumor size > 4 cm and preoperative stage 3-5 CKD had an 8-fold increase in risk for CKD stage progression. Limitations of the study include retrospective analysis and a relatively low number of patients in group 3. CONCLUSIONS Given laparoscopic expertise and appropriate patient selection, LPN is feasible and efficacious for kidney tumors > 4 cm. Indications for LPN should be expanded to include patients with amenable tumors > 4 cm in order to maximally preserve kidney function in these patients.

C-Index is Associated With Functional Outcomes After Laparoscopic Partial Nephrectomy

PURPOSE The C-index is a morphometric descriptor of renal masses that incorporates tumor size and site. We examined associations of the C-index with kidney function after laparoscopic partial nephrectomy. MATERIALS AND METHODS We retrospectively reviewed the records of 131 patients who underwent laparoscopic partial nephrectomy for a single kidney tumor. We calculated the C-index from preoperative contrast enhanced computerized tomography images. Estimated glomerular filtration rate was calculated using the modification of diet in renal disease 2 equation. Nadir estimated glomerular filtration rate was calculated using peak serum creatinine within 7 days of surgery. RESULTS The median C-index was 2.7 (range 0.7 to 9.6). The median preoperative and nadir estimated glomerular filtration rate was 78 (range 23 to 148) and 54 ml/minute/1.73 m2 (range 15 to 127, p<0.001). The mean±SD total glomerular filtration rate decrease was 28%±16%. On univariate analysis we noted a positive correlation between log C-index and the nadir estimated glomerular filtration rate (r=0.29, p=0.002), and a negative correlation between log C-index and the percent decrease in the estimated glomerular filtration rate (r=-0.4, p<0.001). On multivariate analysis the estimated glomerular filtration rate percent decrease was significantly associated with log C-index (p=0.005) and warm ischemia time (p<0.001) but not with tumor diameter or the preoperative estimated glomerular filtration rate. Of patients with a C-index of 2.5 or less 70% showed a 30% or greater decrease in the estimated glomerular filtration rate vs 32% of those with a C-index of greater than 2.5 (RR 2.2, p<0.001). CONCLUSIONS The C-index is associated with the postoperative nadir estimated glomerular filtration rate and the percent decrease in the estimated glomerular filtration rate after laparoscopic partial nephrectomy. A C-index of less than 2.5 correlated with a 2.2-fold increased risk of a 30% or greater estimated glomerular filtration rate decrease after laparoscopic partial nephrectomy.

Association Between Warm Ischemia Time and Renal Parenchymal Atrophy After Partial Nephrectomy

PURPOSE Renal parenchymal volume decrease after partial nephrectomy is associated with late functional outcomes. We examined the relative effects of resection related and atrophy related volume change on late kidney function. MATERIALS AND METHODS Data were analyzed from a cohort of 187 patients who underwent open, laparoscopic or robotic partial nephrectomy between 2009 and 2011. Total change in kidney size after surgery was expressed as percent functional volume preservation measured using the cylindrical volume ratio method. Renal atrophy was expressed as parenchymal thickness preservation, and was assessed by measuring parenchymal thickness before and after partial nephrectomy in regions of the operated kidney distant from the site of resection. Standard statistical analyses were conducted to assess relationships among variables. RESULTS Mean (± SD) percent functional volume preservation was 92% (± 8%), which correlated with a late percent glomerular filtration rate preservation of 91% (± 12%). Mean parenchymal thickness preservation for the cohort was 99% (± 4%). Minimal atrophy was observed in patients with warm ischemia time less than 40 minutes (parenchymal thickness preservation range 98% to 100%). Atrophy was more pronounced in patients with warm ischemia time greater than 40 minutes (parenchymal thickness preservation 96%). Multivariate regression analysis showed correlation of percent functional volume preservation with atrophy; correlation of warm ischemia time, diameter-axial-polar nephrometry score and atrophy with percent functional volume preservation; and correlation of Charlson score and diameter-axial-polar nephrometry score with percent decrease in glomerular filtration rate. CONCLUSIONS In most patients with warm ischemia time less than 40 minutes the incidence of parenchymal atrophy was minimal, suggesting that the kidney volume decrease after partial nephrectomy was predominantly resection related. Kidney volume decrease after partial nephrectomy in patients with warm ischemia time greater than 40 minutes appeared to be due to a combination of resection related and atrophy related changes.

Diameter-Axial-Polar Nephrometry: Integration and Optimization of R.E.N.A.L. and Centrality Index Scoring Systems

PURPOSE The R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) and centrality index nephrometry scores enable systematic, objective assessment of anatomical tumor features. We systematically compared these systems using item analysis test theory to optimize scoring methodology. MATERIALS AND METHODS Analysis was based on 299 patients who underwent partial nephrectomy from 2007 to 2011 and met study inclusion criteria. Percent functional volume preservation, and R.E.N.A.L. and centrality index scores were measured. Late percent glomerular filtration rate preservation was calculated as the ratio of the late to the preoperative rate. Interobserver variability analysis was done to assess measurement error. All data were statistically analyzed. RESULTS A novel scoring method termed DAP (diameter-axial-polar) nephrometry was devised using a data based approach. Mean R.E.N.A.L., centrality index and DAP scores for the cohort were 7.3, 2.5 and 6 with 84%, 90% and 95% interobserver agreement, respectively. The DAP sum score and all individual DAP scoring components were associated with the clinical outcome, including percent functional volume preservation, warm ischemia time and operative blood loss. DAP scoring criteria allowed for the normalization of score distributions and increased discriminatory power. DAP scores showed strong linear associations with percent functional volume preservation (r(2) = 0.97) and late percent glomerular filtration rate preservation (r(2) = 0.81). Each 1 unit change in DAP score equated to an average 4% change in kidney volume. CONCLUSIONS DAP nephrometry integrates the optimized attributes of the R.E.N.A.L. and centrality index scoring systems. DAP scoring was associated with simplified methodology, decreased measurement error, improved performance characteristics, improved interpretability and a clear association with volume loss and late function after partial nephrectomy.