Optimum outcome achievement in partial nephrectomy for T1 renal masses: a contemporary analysis of open and robot-assisted cases.

OBJECTIVES: To compare optimum outcome achievement in open partial nephrectomy (OPN) with that in robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: Using our institutional partial nephrectomy (PN) database, we reviewed 605 cases performed for unifocal clinical T1 renal masses in non-solitary kidneys between 2011 and 2015. Tetrafecta, which was defined as negative surgical margins, freedom from peri-operative complications, ≥80% renal function preservation, and no chronic kidney disease upstaging, was chosen as the composite optimum outcome. Factors associated with tetrafecta achievement were assessed using multivariable logistic regression, with adjustment for age, gender, race, Charlson comorbidity score, body mass index, chronic kidney disease, tumour size, tumour complexity and approach. RESULTS: The overall tetrafecta achievement rate was 38%. Negative margins, freedom from complications, and optimum functional preservation were achieved in 97.1%, 73.6% and 54.2% of cases, respectively. For T1a masses, the tetrafecta achievement rate was similar between approaches (P = 0.97), but for T1b masses, the robot-assisted approach achieved significantly higher tetrafecta rates (43.0% vs 21.3%; P < 0.01). On multivariable analysis, the robot-assisted approach had 2.6-fold higher odds of tetrafecta achievement than the open approach, primarily because of lower peri-operative morbidity, specifically related to wound complications. Positive surgical margin rates and renal function preservation were similar in the two approaches. CONCLUSIONS: Optimum outcomes are readily achieved regardless of PN approach. The robot-assisted approach may facilitate optimum outcome achievement for 4-7-cm masses by minimizing wound complications.

Is all chronic kidney disease created equal?

PURPOSE OF REVIEW: Chronic kidney disease (CKD) has generally been characterized functionally as a glomerular filtration rate (GFR) less than 60 ml/min/1.73 m², without accounting for cause, signs of structural damage, or relative risk of sequelae. Recently released guidelines define CKD as abnormalities of kidney structure or function, present for more than 3 months. We review the recent literature about CKD and its implications for renal surgery. RECENT FINDINGS: Most estimates of GFR are based on serum creatinine, after adjusting for age, race, sex, and/or body mass. Recent research indicates that many individuals have GFR values less than 60 ml/min/1.73 m² without other manifestations of CKD. Nephron loss due to normal aging or renal surgery (CKD-S) may have lower likelihood of CKD progression, and may infer better survival, compared to individuals with the same degree of CKD due to medical causes. Patients with mild and moderate CKD due to surgical nephron loss may benefit from an alternative measurement method of renal function such as cystatin-C-derived or directly measured GFR. SUMMARY: CKD includes a diverse group of individuals with reduced GFR from a variety of causes. Classification of CKD according to GFR, albuminuria, and cause, may improve the management of patients with reduced GFR, as some causes (e.g., nephrectomy and aging) appear to be associated with a relatively low risk of progression.

Long-Term Functional and Oncologic Outcomes Following Robotic Partial and Radical Nephrectomy: A Report from a Single Institution with up to 15 Years of Follow-Up.

Objective: To evaluate the long-term functional and oncologic outcomes after robotic partial nephrectomy (RAPN) and radical nephrectomy (RARN). Materials and Methods: A retrospective review was performed on 1816 patients who underwent RAPN and RARN at our institution between January 2006 and January 2018. Patients with long-term follow-ups of at least 5 years were selected. Exclusion criteria included patients with a previous history of partial or radical nephrectomy, known genetic mutations, and whose procedures were performed for benign indications. Statistical analysis was performed with results as presented. Results: A total of 769 and 142 patients who underwent RAPN and RARN, respectively, met our inclusion criteria. The duration of follow-up was similar after the two procedures with a median of ∼100 months. The 5- and 10-year chronic kidney disease (CKD) upstaging-free survivals were 74.5% and 65.9% after RAPN and 53% and 46.4% after RARN, respectively. Older age was identified as a potential predictor for CKD progression after RARN, whereas older age, higher body mass index, baseline renal function, and ischemia time were shown to predict CKD progression after RAPN. Renal cell carcinoma-related mortality rates for RAPN and RARN were equally 1.1%. No statistically significant differences were identified in the local recurrence, metastatic, and disease-specific survival between the two procedures. Conclusion: Compared with RARN, RAPN conferred a better CKD progression-free survival. Several factors were identified as potential predictors for clinically significant CKD progression both in the early and late postoperative phase. Long-term oncologic outcomes between the two procedures remained similarly favorable.

Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease.

PURPOSE: Chronic kidney disease from medical causes is present in 25% to 30% of patients before surgery for renal cancer. Although chronic kidney disease due to medical causes is typically associated with a 2% to 5% annual renal functional decline and decreased overall survival, reduced glomerular filtration rate occurring only after surgery may not have the same negative consequences. MATERIALS AND METHODS: All patients undergoing surgery for suspected renal malignancy were identified in an institutional registry. Median clinical followup was 6.6 years. RESULTS: Of 4,180 patients 28% had a preoperative glomerular filtration rate of less than 60 ml/minute/1.73 m(2) (chronic kidney disease due to medical causes) and in 22% the glomerular filtration rate decreased to less than 60 ml/minute/1.73 m(2) only after surgery (surgically induced chronic kidney disease). Preoperative glomerular filtration rate was a strong predictor of overall survival on univariable and multivariable analysis. The risk of death after renal surgery was 1.8, 3.5 and 4.4-fold higher in patients with preoperative chronic kidney disease stages 3, 4 and 5, respectively, vs normal preoperative glomerular filtration rate. Average overall loss of renal function was 23%, including 13% within 90 days after surgery and 3.5% annually thereafter. Postoperative glomerular filtration rate only predicted survival for patients with preexisting chronic kidney disease due to medical causes. Neither surgically induced chronic kidney disease nor postoperative glomerular filtration rate was a significant predictor of survival in patients without preexisting chronic kidney disease due to medical causes. Annual renal functional decline was 4.7% and 0.7% for patients with chronic kidney disease due to medical causes and surgically induced chronic kidney disease, respectively, with a greater than 50% reduction in glomerular filtration rate in 7.3% and 2.2%, respectively (p <0.0001). Annual renal functional decline greater than 4.0% was associated with a 43% increase in mortality (p <0.0001). CONCLUSIONS: Surgically induced chronic kidney disease is associated with a relatively low risk of progressive renal functional decline and impact on survival does not appear to be substantial during intermediate term followup. In contrast, preoperative chronic kidney disease due to medical causes places patients at increased risk, indicating nephron sparing surgery for such patients.

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.

Five to 10-year followup of open partial nephrectomy in a solitary kidney.

PURPOSE: Followup is limited in patients with a solitary kidney who undergo partial nephrectomy. We evaluated overall, cancer specific and recurrence-free survival, and renal function in patients 5 years or greater after open partial nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the Cleveland Clinic kidney cancer database, including only patients with a solitary kidney treated with open partial nephrectomy 5 or more years ago (from 1980 to June 2006) who had 6 months or more of followup. Survival and recurrence analyses were calculated using a Cox proportional hazards model. Results are shown as Kaplan-Meier survival curves. Linear regression analysis was done to assess postoperative renal function. RESULTS: A total of 282 patients fit our study inclusion criteria (mean followup 175 months), of whom 233 underwent open partial nephrectomy 10 or more years ago. Actual overall survival was 78.5% and 59.5% at 5 and 10 years, respectively. The average estimated glomerular filtration rate at 5 years or greater and 10 years or greater since open partial nephrectomy was 35.1 and 34.5 ml/minute/1.73 m(2) in 89.7% and 89.6%, respectively, of patients with stage 3 or greater chronic kidney disease. Eight survivors were on intermittent hemodialysis 5 years or more postoperatively, including 5 at 10 years or more. There were 76 recurrences for a calculated 5 and 10-year recurrence-free survival rate of 72% (95% CI 66-879) and 63% (95% CI 57-71), respectively. CONCLUSIONS: Open partial nephrectomy in the solitary kidney provides reliable long-term oncological control at 5 and 10 years. Predicted and actual outcomes correspond well. Although most patients have chronic kidney disease postoperatively, it appears stable with minimal progression to dialysis.

Comparative outcomes of laparoscopic and open adrenalectomy for adrenocortical carcinoma: single, high-volume center experience.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare and clinically aggressive cancer. Previous studies reported increased recurrence rates associated with laparoscopic adrenalectomy (LA). We evaluated a single-center experience of LA versus open adrenalectomy (OA) for the management of ACC. METHODS: Between 1993 and 2011, 44 consecutive patients with primary ACC were treated at our institution. Baseline patient characteristics and surgical and pathological outcomes were compared between OA and LA groups. Multivariable Cox proportional hazards analysis was used to estimate the association between OA versus LA with recurrence-free and overall survival. RESULTS: Eighteen and 26 patients underwent LA and OA, respectively. Patients who underwent OA had larger tumors and more advanced clinical stage compared with LA group. During a median follow-up of 22 months, 22 recurrences and 26 deaths were observed. The 2-year, recurrence-free and overall survivals for OA and LA were 60 vs. 39 % (P = 0.7) and 54 vs. 58 % (P = 0.6), respectively. After adjusting for clinical stage, OA was associated with lower risk of recurrence (hazard ratio (HR) 0.4; 95 % confidence interval (CI) 0.2-1.2; P = 0.099) and improved overall survival (HR 0.5; 95 % CI 0.2-1.2; P = 0.122) compared with LA, although differences were not statistically significant. CONCLUSIONS: A nonstatistically significant increase in recurrence and death was observed among patients undergoing LA versus OA after adjusting for clinical stage. The rarity of this disease limits the ability to assess for significant differences in a single-institution series. Patients with suspected ACC should be considered for OA.

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.

Nephrometry score is associated with volume loss and functional recovery after partial nephrectomy.

PURPOSE: Functional volume preservation after partial nephrectomy is a primary determinant of kidney function. We identified tumor features, including R.E.N.A.L. (radius for tumor size as maximal diameter, exophytic/endophytic tumor properties, nearness of deepest portion of tumor to collecting system or sinus, anterior/posterior descriptor and location relative to polar line) and centrality index nephrometry scores, associated with volume loss after partial nephrectomy. MATERIALS AND METHODS: A chart and imaging review was done for 237 patients who underwent partial nephrectomy from 2007 to 2010 and met study inclusion criteria. R.E.N.A.L. and centrality index nephrometry scores were measured in all patients. Percent functional volume preservation was estimated a median of 1.4 years after surgery using the cylindrical volume ratio method. Statistical analysis was done to study associations. RESULTS: Independent tumor features associated with percent functional volume preservation included tumor diameter (p < 0.001) and the distance from tumor periphery to kidney center (p = 0.02). R.E.N.A.L. and centrality index scores were associated with percent functional volume preservation (each p < 0.001). Nephrometry scores were also associated with nadir and late percent glomerular filtration rate preservation. Tumors classified as highly complex, with a centrality index score of 1.5 or less and a R.E.N.A.L. score of 10 or greater, were associated with an average 28% to 30% functional parenchymal volume loss of operated kidneys. A mean 8% difference in percent functional volume preservation was observed among low, intermediate and high tumor complexity categories for R.E.N.A.L. and centrality index scores. CONCLUSIONS: R.E.N.A.L. and centrality index nephrometry scores were associated with changes in the percent functional volume preservation and the perioperative functional decrease. Nephrometry scores performed better than diameter alone on statistical analysis. Nephrometry scores may be useful to estimate the likelihood of operative volume loss and by proxy the functional outcome.

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.

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.

Limited warm ischemia during elective partial nephrectomy has only a marginal impact on renal functional outcomes.

PURPOSE: Ischemic damage during partial nephrectomy increases with each minute of warm ischemia, leading some groups to advocate hypothermia in all cases or partial nephrectomy without vascular occlusion as a primary technique. The renal functional implications of these approaches have not been well studied in patients who undergo elective partial nephrectomy. MATERIALS AND METHODS: We evaluated early and late renal functional outcomes in 1,132 patients with 2 functioning kidneys and normal preoperative serum creatinine who underwent partial nephrectomy without regional ischemia (58), with less than 30-minute warm ischemia (809) or with cold ischemia (265). RESULTS: The preoperative, postoperative and latest glomerular filtration rates were not significantly different in the 3 groups. At latest followup the relative decrease in renal function was less in cases without regional ischemia than in those with less than 30-minute warm ischemia and those with cold ischemia (0.5% vs 13% and 11%, respectively, p <0.001). In part this reflected selection bias since tumor size and the amount of parenchyma removed were lowest in that group (p <0.001). On multivariate analysis the percent of parenchyma preserved and the baseline glomerular filtration rate were strongly associated with the postoperative and latest glomerular filtration rates (p <0.001) but the partial nephrectomy approach was not (p >0.05). Adverse short or long-term renal functional outcomes were marginally increased in patients with 20 to 30-minute warm ischemia. However, such events were uncommon and renal failure developed in only 4 of 1,132 patients (less than 0.4%). CONCLUSIONS: During elective partial nephrectomy a warm ischemia time of less than 20 minutes is not associated with clinically relevant functional loss compared to that of alternative techniques. However, longer warm ischemia time may correlate with ischemic injury and should be avoided.

Presacral and retroperitoneal lymph node involvement in urothelial bladder cancer: results of a prospective mapping study.

PURPOSE: We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer. MATERIALS AND METHODS: As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal. We evaluated pathological features, treatment outcomes and cancer specific survival in patients with or without lymph node positive disease in the presacral and retroperitoneal regions. RESULTS: A median of 37 lymph nodes (IQR 27-49) were removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had metastatic disease in the presacral or retroperitoneal region. Four patients (3%) had an isolated solitary positive lymph node in these 2 templates. Two-year overall survival in patients without vs with presacral/retroperitoneal lymph node positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77) and 29% (95% CI 7-51), respectively (p = 0.02). CONCLUSIONS: A substantial proportion of patients have lymph node positive disease in the presacral and retroperitoneal regions, including some with isolated and/or solitary lymph node involvement. While the limited positive lymph node burden in these templates suggests a potential therapeutic role for extending the anatomical boundaries of lymph node dissection, patient survival was poor. Extended lymph node dissection provides important staging information but to our knowledge the therapeutic benefit has yet to be definitively proved.

Comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys reveals predominant role of nonmodifiable factors in determining ultimate renal function.

PURPOSE: Factors that determine renal function after partial nephrectomy are not well-defined, including the impact of cold vs warm ischemia, and the relative importance of modifiable and nonmodifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing partial nephrectomy. MATERIALS AND METHODS: From 1980 to 2009, 660 partial nephrectomies were performed at 4 centers for tumor in a solitary functioning kidney under cold (300) or warm (360) ischemia. Data were collected in institutional review board approved registries and followup averaged 4.5 years. Preoperative and postoperative glomerular filtration rates were estimated via the Chronic Kidney Disease-Epidemiology Study equation. RESULTS: At 3 months after partial nephrectomy median glomerular filtration rate decreased by equivalent amounts with cold or warm ischemia (21% vs 22%, respectively, p = 0.7), although median cold ischemic times were much longer (45 vs 22 minutes respectively, p <0.001). On multivariable analyses increasing age, larger tumor size, lower preoperative glomerular filtration rate and longer ischemia time were associated with decreased postoperative glomerular filtration rate (p <0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative glomerular filtration rate proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance. CONCLUSIONS: This nonrandomized, comparative study suggests that within the relatively strict parameters of conventional practice, ie predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after partial nephrectomy. Long-term renal function after partial nephrectomy is determined primarily by the quantity and quality of renal parenchyma preserved, although type and duration of ischemia remain the most important modifiable factors, and warrant further study.

Renal functional outcomes after partial nephrectomy with extended ischemic intervals are better than after radical nephrectomy.

PURPOSE: Partial nephrectomy is now a standard of care for clinical stage T1 renal cancers amenable to a nephron sparing approach. Based on tumor size and location, some partial nephrectomies can be more challenging and necessitate longer ischemic intervals, and radical nephrectomy is considered an alternative standard of care for these tumors. We evaluate whether partial nephrectomy with extended ischemia provides improved renal functional outcomes compared with radical nephrectomy. MATERIALS AND METHODS: Renal functional outcomes were analyzed in 2,402 consecutive patients with serum creatinine 1.4 mg/dl or less and 2 functioning kidneys treated for cT1 renal cancer at Cleveland Clinic with partial (1,833, 76%) or radical nephrectomy (569, 24%). Patients treated with partial nephrectomy were grouped according to duration of ischemia using the categories of limited (less than 30 minutes), unknown or extended (greater than 30 minutes). RESULTS: Patients in all 4 groups had similar preoperative creatinine (median 0.9 mg/dl) and estimated glomerular filtration rate (median 82 to 84 ml/minute/1.73 m(2)). Patients undergoing radical nephrectomy on average were older, and had more comorbidities and larger tumors (p <0.001). Regardless of type of surgery, this cohort as a whole was at low risk (less than 1%) for renal failure (estimated glomerular filtration rate less than 15 ml/minute/1.73 m(2)). However, patients in the radical nephrectomy cohort were far more likely (p <0.001) to have an estimated glomerular filtration rate less than 45 ml/minute/1.73 m(2) (35%) than any of the partial nephrectomy groups (limited 11%, unknown 15%, extended ischemia 19%). CONCLUSIONS: Even when performed with extended ischemia, partial nephrectomy is associated with renal functional outcomes superior to those of radical nephrectomy for clinical stage T1 renal cancers. Partial nephrectomy should be considered even for tumors in which anticipated ischemia may exceed 30 minutes.

Nephrectomy induced chronic renal insufficiency is associated with increased risk of cardiovascular death and death from any cause in patients with localized cT1b renal masses.

PURPOSE: Radical nephrectomy has traditionally been preferred to partial nephrectomy in patients with localized renal cell cancer because of its simplicity and established cancer control. Recent data suggest that these patients have significant competing risks of death, some of which may be increased by chronic renal insufficiency. Therefore, we compared overall survival, cancer specific survival and cardiac specific survival in patients undergoing partial or radical nephrectomy for cT1b tumors. MATERIALS AND METHODS: From 1999 to 2006, 1,004 patients with renal masses between 4 and 7 cm underwent extirpative surgery, partial nephrectomy (524) or radical nephrectomy (480). We generated a propensity model based on preoperative patient characteristics, and then modeled survival with the additional variables of pathological stage and new baseline renal function. RESULTS: On multivariate analysis cancer specific survival was equivalent for patients treated with partial nephrectomy or radical nephrectomy. Those patients undergoing radical nephrectomy lost significantly more renal function than those undergoing partial nephrectomy. The average excess loss of renal function observed with radical nephrectomy was associated with a 25% (95% CI 3-73) increased risk of cardiac death and 17% (95% CI 12-27) increased risk of death from any cause on multivariate analysis. CONCLUSIONS: Partial nephrectomy offers cancer specific survival equivalent to that of radical nephrectomy and is technically feasible in at least 50% of patients with cT1b tumors. Preservation of renal function was significantly better in patients treated with partial nephrectomy. Postoperative renal insufficiency was a significant independent predictor of overall and cardiovascular specific survival, and efforts should be made to limit the renal function loss associated with surgery for localized renal masses.

Management of the adrenal gland during partial nephrectomy.

PURPOSE: Nephron sparing surgery is an increasingly used alternative to Robson's radical nephroadrenalectomy. The indications for adrenalectomy in patients undergoing partial nephrectomy are not clearly defined and some surgeons perform it routinely for large and/or upper pole renal tumors. We analyzed initial management and oncological outcomes of adrenal glands after open partial nephrectomy. MATERIALS AND METHODS: Institutional review board approval was obtained for this study. During partial nephrectomy the ipsilateral adrenal gland was resected if a suspicious adrenal nodule was noted on radiographic imaging, or if intraoperative findings indicated direct extension or metastasis. RESULTS: Concomitant adrenalectomy was performed in 48 of 2,065 partial nephrectomies (2.3%). Pathological analysis revealed direct invasion of the adrenal gland by renal cell carcinoma (1), renal cell carcinoma metastasis (2), other adrenal neoplasms (3) or benign tissue (42, 87%). During a median followup of 5.5 years only 15 patients underwent subsequent adrenalectomy (0.74%). Metachronous adrenalectomy was ipsilateral (10), contralateral (2) or bilateral (3), revealing metastatic renal cell carcinoma in 11 patients. Overall survival at 5 years in patients undergoing partial nephrectomy with or without adrenalectomy was 82% and 85%, respectively (p = 0.56). CONCLUSIONS: Adrenalectomy should not be routinely performed during partial nephrectomy, even for upper pole tumors. We propose concomitant adrenalectomy only if a suspicious adrenal lesion is identified radiographically or invasion of the adrenal gland is suspected intraoperatively. Using these criteria adrenalectomy was avoided in more than 97% of patients undergoing partial nephrectomy. Even using such strict criteria only 13% of these suspicious adrenal nodules contained cancer. The rarity of metachronous adrenal metastasis and the lack of an observable benefit to concomitant adrenalectomy support adrenal preservation during partial nephrectomy except as previously outlined.

Laparoscopic assisted ileal ureter: technique, outcomes and comparison to the open procedure.

PURPOSE: Ureteral replacement with interposition of a bowel segment has traditionally required a large incision with substantial associated morbidity and prolonged time to convalescence. During the last 7 years a technique for laparoscopic assisted ileal interposition has evolved that mimics our open approach. We present a comparative analysis of functional and perioperative outcomes between patients undergoing laparoscopic or open ileal ureter replacement at our institution. MATERIALS AND METHODS: A search of all procedures from 1980 to the present revealed 7 patients undergoing laparoscopic and 7 undergoing open ileal interposition. Functional and perioperative data from these patients are compared, and a detailed description of technique for the laparoscopic procedure is presented. RESULTS: Narcotic analgesic use in morphine equivalents (median 38.9 vs 322.2 mg, p = 0.035) and time to convalescence (median 4 vs 5.5 weeks, p = 0.03) were significantly less in the laparoscopic group. A trend toward shorter hospital stay (median 5 vs 8 days, p = 0.101) was also noted in patients in the laparoscopic group. There was no evidence of anastomotic stricture for patients in either group at last followup. CONCLUSIONS: Despite the small number of subjects involved a significant advantage was noted for postoperative recovery after laparoscopic compared to open ileal interposition. A detailed understanding of this complicated procedure can help prevent inherent pitfalls.

Transcriptomic and Protein Analysis of Small-cell Bladder Cancer (SCBC) Identifies Prognostic Biomarkers and DLL3 as a Relevant Therapeutic Target.

PURPOSE: Transcriptomic profiling can shed light on the biology of small-cell bladder cancer (SCBC), nominating biomarkers, and novel therapeutic targets. EXPERIMENTAL DESIGN: Sixty-three patients with SCBC had small-cell histology confirmed and quantified by a genitourinary pathologist. Gene expression profiling was performed for 39 primary tumor samples, 1 metastatic sample, and 6 adjacent normal urothelium samples (46 total) from the same cohort. Protein levels of differentially expressed therapeutic targets, DLL3 and PDL1, and also CD56 and ASCL1, were confirmed by IHC. A SCBC PDX model was utilized to assess in vivo efficacy of DLL3-targeting antibody-drug conjugate (ADC). RESULTS: Unsupervised hierarchical clustering of 46 samples produced 4 clusters that correlated with clinical phenotypes. Patients whose tumors had the most "normal-like" pattern of gene expression had longer overall survival (OS) compared with the other 3 clusters while patients with the most "metastasis-like" pattern had the shortest OS (P = 0.047). Expression of DLL3, PDL1, ASCL1, and CD56 was confirmed by IHC in 68%, 30%, 52%, and 81% of tissue samples, respectively. In a multivariate analysis, DLL3 protein expression on >10% and CD56 expression on >30% of tumor cells were both prognostic of shorter OS (P = 0.03 each). A DLL3-targeting ADC showed durable antitumor efficacy in a SCBC PDX model. CONCLUSIONS: Gene expression patterns in SCBC are associated with distinct clinical phenotypes ranging from more indolent to aggressive disease. Overexpression of DLL3 mRNA and protein is common in SCBC and correlates with shorter OS. A DLL3-targeted ADC demonstrated in vivo efficacy superior to chemotherapy in a PDX model of SCBC.

Comparison of laparoscopic and open partial nephrectomy for tumor in a solitary kidney.

PURPOSE: We compared the postoperative and renal functional outcomes of patients undergoing open or laparoscopic partial nephrectomy for tumor in a solitary functioning kidney. MATERIALS AND METHODS: Between 1999 and 2006, 169 open and 30 laparoscopic partial nephrectomies were performed for 7 cm or smaller tumors in a solitary functioning kidney. Data were collected in an institutional review board approved registry and median followup was 2.0 years. Preoperative and postoperative glomerular filtration rates were estimated with the abbreviated Modification of Diet in Renal Disease equation. RESULTS: By 3 months after open or laparoscopic partial nephrectomy, the glomerular filtration rate decreased by 21% or 28%, respectively (p = 0.24). Postoperative dialysis was required acutely after 1 open partial nephrectomy (0.6%) and 3 laparoscopic partial nephrectomies (10%, p = 0.01), and dialysis dependent end stage renal failure within 1 year occurred after 1 open partial nephrectomy (0.6%) and 2 laparoscopic partial nephrectomies (6.6%, p = 0.06). In multivariate analysis warm ischemia time was 9 minutes longer (p <0.0001) and the chance of postoperative complications was 2.54-fold higher (p <0.05) with laparoscopic partial nephrectomy. Longer warm ischemia time (more than 20 minutes) and preoperative glomerular filtration rate were associated with poorer postoperative glomerular filtration rate in multivariate analysis. Notwithstanding the association with warm ischemia time, the surgical approach itself was not an independent predictor of postoperative glomerular filtration rate (p = 0.77). CONCLUSIONS: While laparoscopic partial nephrectomy is technically feasible for tumor in a solitary kidney, warm ischemia time was longer and complication rates higher compared with open partial nephrectomy. In addition, although average loss of renal function at 3 months is equivalent (after accounting for warm ischemia time), a greater proportion of patients required dialysis temporarily or permanently after laparoscopic partial nephrectomy in this initial series. Therefore, open partial nephrectomy may be the preferred nephron sparing approach at this time for these patients at high risk for chronic kidney disease.