Brian R. Lane

Every Minute Counts When the Renal Hilum Is Clamped During Partial Nephrectomy

BACKGROUND The safe duration of warm ischemia during partial nephrectomy remains controversial. OBJECTIVE Our aim was to evaluate the short- and long-term renal effects of warm ischemia in patients with a solitary kidney. DESIGN, SETTING, AND PARTICIPANTS Using the Cleveland Clinic and Mayo Clinic databases, we identified 362 patients with a solitary kidney who underwent open (n=319) or laparoscopic (n=43) partial nephrectomy using warm ischemia with hilar clamping. MEASUREMENTS Associations of warm ischemia time with renal function were evaluated using logistic or Cox regression models first as a continuous variable and then in 5-min increments. RESULTS AND LIMITATIONS Median tumor size was 3.4 cm (range: 0.7-18.0 cm), and median ischemia time was 21 min (range: 4-55 min). Postoperative acute renal failure (ARF) occurred in 70 patients (19%) including 58 (16%) who had a glomerular filtration rate (GFR) <15 ml/min per 1.73 m(2) within 30 d of surgery. Among the 226 patients with a preoperative GFR >or=30 ml/min per 1.73 m(2) and followed >or=30 d, 38 (17%) developed new-onset stage IV chronic kidney disease during follow-up. As a continuous variable, longer warm ischemia time was associated with ARF (odds ratio: 1.05 for each 1-min increase; p<0.001) and a GFR<15 (odds ratio: 1.06; p<0.001) in the postoperative period, and it was associated with new-onset stage IV chronic kidney disease (hazard ratio: 1.06; p<0.001) during follow-up. Similar results were obtained adjusting for preoperative GFR, tumor size, and type of partial nephrectomy in a multivariable analysis. Evaluating warm ischemia in 5-min increments, a cut point of 25 min provided the best distinction between patients with and without all three of the previously mentioned end points. Limitations include the retrospective nature of the study. CONCLUSIONS Longer warm ischemia time is associated with short- and long-term renal consequences. These results suggest that every minute counts when the renal hilum is clamped.

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.

Factors Predicting Renal Functional Outcome After Partial Nephrectomy

PURPOSE Compared to radical nephrectomy, partial nephrectomy better preserves renal parenchyma and function. Although several clinical factors may impact renal function after partial nephrectomy including preoperative function, age, gender and comorbidities, the contributions of tumor and surgical factors have not been well studied. We evaluate independent factors predicting functional outcomes after partial nephrectomy. MATERIALS AND METHODS Preoperative and all postoperative serum creatinine values for 1,169 patients undergoing partial nephrectomy were used to estimate glomerular filtration rate. Postoperative nadir glomerular filtration rate and ultimate glomerular filtration rate were analyzed using multiple pertinent covariates. RESULTS Median preoperative, postoperative nadir and ultimate glomerular filtration rates were 77, 57 and 71 ml per minute per 1.73 m(2), respectively. Increasing age, gender, lower preoperative glomerular filtration rate, solitary kidney, tumor size, ischemia time and longer time to nadir glomerular filtration rate significantly predicted postoperative nadir glomerular filtration rate and ultimate glomerular filtration rate. Acute loss of renal function predicted lower ultimate glomerular filtration rate. In the entire cohort, in patients with normal preoperative renal function, and in those with baseline stage 3 and those with stage 4 chronic kidney disease the incidence of postoperative acute kidney injury after partial nephrectomy was 3.6%, 0.8%, 6.2% and 34%, and the incidence of chronic end stage renal disease after partial nephrectomy was 2.5%, 0.1%, 3.7% and 36%, respectively. CONCLUSIONS Lower preoperative glomerular filtration rate, solitary kidney, older age, gender, tumor size and longer ischemic interval all predicted lower glomerular filtration rate after partial nephrectomy. Therefore, duration of renal ischemia is the strongest modifiable surgical risk factor for decreased renal function after partial nephrectomy, and efforts to limit ischemic time and injury should be pursued in open and laparoscopic partial nephrectomy.

10-Year Oncologic Outcomes After Laparoscopic and Open Partial Nephrectomy

PURPOSE Open partial nephrectomy has proven long-term oncologic efficacy. Laparoscopic partial nephrectomy outcomes at 5 to 7 years of followup appear comparable to those of the open approach. We present the 10-year outcomes of patients who underwent laparoscopic or open partial nephrectomy for a single clinical stage cT1 7 cm or less renal cortical tumor. MATERIALS AND METHODS Of 1,541 patients treated with partial nephrectomy for a single cT1 tumor between 1999 and 2007 with a minimum 5-year followup, an actual followup of 10 years or greater was available in 45 and 254 after laparoscopic and open partial nephrectomy, respectively. RESULTS Median followup after laparoscopic and open surgery was 6.6 and 7.8 years, respectively. At 10 years the overall survival rate was 77.2%. The metastasis-free survival rate was 95.2% and 90.0% after partial nephrectomy for clinical T1a and T1b renal cell carcinoma, respectively (p <0.0001). Baseline differences between patients treated with laparoscopic and open partial nephrectomy accounted for most observed differences between the cohorts. The median glomerular filtration rate decrease was 16.9% after the laparoscopic approach and 14.1% after the open approach (p = 0.5). On multivariable analysis predictors of all cause mortality included advancing age (HR 1.52/10 years, p <0.0001), comorbidity (HR 1.33/1 U, p <0.0001), absolute indication (HR 2.25, p = 0.003) and predicted recurrence-free survival (HR 1.58/10% increased risk, p = 0.004) but not laparoscopic vs open operative approach (p = 0.13). Similarly, predictors of metastasis included absolute indication (HR 4.35, p <0.0001) and predicted recurrence-free survival (HR 2.67, p <0.0001) but not operative approach (p = 0.42). CONCLUSIONS The 10-year outcomes of laparoscopic nephrectomy and open partial nephrectomy are excellent in carefully selected patients with limited risk of recurrence for cT1 renal cortical tumors. Overall survival at 10 years is mediated by patient factors such as age, comorbidity and operative indication, and by cancer factors such as predicted recurrence-free survival but not by the choice of operative technique, which depends on surgeon preference and experience.

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 Function After Partial Nephrectomy: Effect of Warm Ischemia Relative to Quantity and Quality of Preserved Kidney

OBJECTIVE To evaluate the effects of warm ischemia time (WIT) and quantity and quality of kidney preserved on renal functional recovery after partial nephrectomy (PN). The effect of WIT relative to these other parameters has recently been challenged. METHODS We identified 362 consecutive patients with a solitary kidney who had undergone PN using warm ischemia. Multivariate models with multiple imputations were used to evaluate the associations with acute renal failure and new-onset stage IV chronic kidney disease (CKD). RESULTS The median WIT was 21 minutes (range 4-55), the median percentage of kidney preserved was 80% (range 25%-98%), and the median preoperative glomerular filtration rate (GFR) was 61 mL/min/1.73 m2 (range 11-133). Postoperative acute renal failure occurred in 70 patients (19%). Of the 226 patients with a preoperative GFR>30 mL/min/1.73 m2, 38 (17%) developed new-onset stage IV CKD during follow-up. On multivariate analysis, the WIT (P=.021), percentage of kidney preserved (P=.009), and preoperative GFR (P<.001) were significantly associated with acute renal failure, and only the percentage of kidney preserved (P<.001) and preoperative GFR (P<.001) were significantly associated with new-onset stage IV CKD during follow-up. Using our previously published cutpoint of 25 minutes, a WIT of >25 minutes remained significantly associated with new-onset stage IV CKD in a multivariate analysis adjusting for the quantity and quality factors (hazard ratio 2.27, P=.049). CONCLUSION Our results have validated that the quality and quantity of kidney are the most important determinants of renal function after PN. In addition, we have also demonstrated that the WIT remains an important modifiable feature associated with short- and long-term renal function. The precision of surgery, maximizing the amount of preserved, vascularized parenchyma, should be a focus of study for optimizing the PN procedure.

Correlation of Radiographic Imaging and Histopathology Following Cryoablation and Radio Frequency Ablation for Renal Tumors

PURPOSE Followup after radio frequency ablation and cryotherapy for small renal lesions lacks pathological analysis. The definition of successful tumor ablation has been the absence of contrast enhancement on posttreatment magnetic resonance imaging or computerized tomography. We hypothesized that adding post-ablation kidney biopsy would help confirm treatment success. MATERIALS AND METHODS From April 2002 to March 2006 a total of 109 renal lesions in 88 patients were ablated with percutaneous radio frequency ablation and from September 1997 to January 2006 a total of 192 lesions in 176 patients were treated with laparoscopic cryoablation. Patients were followed with radiographic imaging and post-ablation biopsy at 6 months. RESULTS Radiographic success at 6 months was 85% (62 cases) and 90% (125) for radio frequency ablation and cryoablation, respectively. At 6 months 134 lesions (45%) were biopsied and success in the radio frequency ablation cohort decreased to 64.8% (24 cases), while cryoablation success remained high at 93.8% (91). Six of 13 patients (46.2%) with a 6-month positive biopsy after radio frequency ablation demonstrated no enhancement on posttreatment magnetic resonance imaging or computerized tomography. In patients treated with cryoablation all positive biopsies revealed posttreatment enhancement on imaging just before biopsy. CONCLUSIONS We observed a poor correlation between radiographic imaging and pathological analysis. We recommend post-radio frequency ablation followup biopsy due to the significant risk of residual renal cell cancer without radiographic evidence, although to our knowledge the clinical significance of these viable cells remains to be determined. In contrast, radiographic images of renal lesions treated with cryotherapy appeared to correlate adequately with corresponding histopathological findings in our series.

Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients

Background:Failures of prophylaxis against Pneumocystis carinii pneumonia (PCP) in AIDS patients do occur, but no evidence for drug resistance has yet been presented. Objective:To determine whether mutations in the sulfa and sulfone drug target are associated with failure of prophylaxis using a sulfa-containing agent. Methods:Portions of the gene for P. carinii dihydropteroate synthase (DHPS), the sulfa and sulfone target, from 27 patients (20 of whom had AIDS) diagnosed with PCP between 1976 and 1997 were amplified using polymerase chain reaction and sequenced. Seven of the 27 patients (all of whom had AIDS) were receiving sulfa or sulfone drugs as prophylaxis for PCP. Results:Mutations were found at only two amino-acid positions and were significantly more common in patients who received sulfa/sulfone prophylaxis. Mutations were observed in five (71%) out of seven isolates from AIDS patients receiving sulfa/sulfone as prophylaxis compared with only two (15%) out of 13 specimens from AIDS patients who did not (P = 0.022). No mutations were seen in isolates from seven non-HIV-infected patients, none of whom were on prophylaxis. Mutations were only observed in specimens obtained in 1995–1997. Conclusions:Mutations in two amino-acid positions were significantly more common in AIDS patients with PCP who failed sulfa/sulfone prophylaxis. These amino acids appeared to be directly involved in both substrate and sulfa binding, based on homology to the Escherichia coli DHPS crystal structure. Thus, the results were consistent with the possibility that mutations in the P. carinii DHPS are responsible for some of the failures of sulfa/sulfone prophylaxis in AIDS patients.

Active treatment of localized renal tumors may not impact overall survival in patients aged 75 years or older

Although nephrectomy cures most localized renal cancers, this oncologic benefit may be outweighed by the renal functional costs of such an approach. In this study, the authors examined overall survival in 537 patients who had localized renal tumors ≤7 cm detected at age ≥75 years to investigate whether surgical intervention improved survival compared with active surveillance.

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.