Benjamin T. Larson

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.

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.

Partial nephrectomy is associated with improved overall survival compared to radical nephrectomy in patients with unanticipated benign renal tumours.

BACKGROUND Partial nephrectomy (PN) has been associated with improved overall survival (OS) in select cohorts with localised renal masses when compared to radical nephrectomy (RN). The driving forces behind these differences have been difficult to elucidate given the heterogeneity of previously compared cohorts. OBJECTIVE Compare OS in a subset of patients with unanticipated benign renal masses to minimise the confounding effect of cancer. DESIGN, SETTING, AND PARTICIPANTS We retrospectively evaluated 2608 consecutive clinical T1 enhancing renal masses that were treated with extirpative surgery at our institution between 1999 and 2006. Of these, 499 tumours (19%) were found to be benign on final pathology. Preoperative data and renal functional data were used to generate a propensity model that was then plugged into a multivariate model of survival. Median follow-up for the entire cohort was 50 mo (interquartile range [IQR]: 32-73). INTERVENTION All patients underwent PN or RN. MEASUREMENTS We measured OS and cardiac-specific survival. RESULTS AND LIMITATIONS Five-year OS estimates for the PN (n=388) and RN (n=111) cohorts were 95% (95% confidence interval [CI], 93-98) versus 83% (95% CI, 74-90), respectively (P<0.0001). On multivariate analysis, controlling for both comorbidity and age, RN was associated with a 2.5-fold increased risk of death compared to PN (hazard ratio [HR]: 2.5; 95% CI, 1.3-5.1). Postoperative estimated glomerular filtration rate (eGFR) was also an independent predictor of OS and cardiac-specific survival (HR: 0.97; 95% CI, 0.95-0.99 and HR: 0.96; 95% CI, 0.93-0.99, respectively). The retrospective nature of this analysis limits the strength of the conclusions. CONCLUSIONS PN was associated with better OS when compared to RN in patients with unanticipated benign tumours. This observed survival advantage appears partly to be the result of better preservation of eGFR, but other kidney functions or unmeasured factors may also play a role. These data indicate that PN should be aggressively pursued in any patient where PN is technically feasible.

Inadequacy of Biopsy for Diagnosis of Upper Tract Urothelial Carcinoma: Implications for Conservative Management

OBJECTIVE To report changes in grade and stage between initial diagnostic and repeat biopsies or resection for urothelial carcinoma (UTUC) and investigate the consequences for endoscopic management. Ureteroscopic management of upper tract UTUC is an alternative to nephroureterectomy, which is less invasive and preserves renal function. However, concerns about potential understaging, inaccurate grading, incomplete resection, lack of effective tertiary chemoprevention, and need for ureteroscopic surveillance limits it appeal. METHODS Clinicopathological records of patients with UTUC treated at our institution were reviewed. Fifty-six patients with a histologic diagnosis of UTUC and 2 or more consecutive biopsies or biopsy followed by surgical resection were included, resulting in 65 biopsy specimens. RESULTS The median interval between diagnostic biopsy and subsequent biopsy or resection was 6 weeks (range, 1 week to 60 months). Change in grade from the diagnostic biopsy occurred in 24 of 65 biopsies (37%), including 9 in which diagnosis changed from low to high grade. Change in the stage from the diagnostic biopsy occurred in 25 of 65 biopsies (38%). Overall, 24 (43%) patients were reclassified from low-grade, noninvasive disease to high-grade and/or invasive disease. CONCLUSION A change in grade and/or stage from the diagnostic biopsy occurred in more than one third of patients with UTUC managed conservatively. Because of the short median time interval between biopsies, this finding likely represents variability in tumor sampling on biopsy. Because of the concerns of undergrading and understaging, appropriate patient selection and vigilant endoscopic surveillance are mandatory for UTUC managed endoscopically.

Elective Partial Nephrectomy in Patients With Clinical T1b Renal Tumors Is Associated With Improved Overall Survival

OBJECTIVES Elective partial nephrectomy (PN) in patients with cT1b renal tumors is relatively unstudied. Most surgeons currently only perform radical nephrectomy (RN) in this population. Patients with localized kidney cancer may die from disease, but the risk of a non-cancerrelated death is significant and may be worsened by nephrectomy-induced chronic kidney disease (CKD). PN may offer the perfect combination of cancer control and preservation of renal function; therefore we compared overall and cancer-specific survival in patients treated for cT1b renal masses. METHODS From 1999 to 1906, 510 patients with renal tumors >4-7 cm, a glomerular filtration rate (GFR) >60, and a normal contralateral kidney underwent extirpative surgery (PN, n = 212 or RN, n = 298) at our institution. As the patients were not randomized, we generated a propensity model based on preoperative patient characteristics to control for selection bias. RESULTS Cancer-specific survival was similar between cohorts when compared by pathologic stage and grade. On multivariate analysis, RN was associated with postoperative CKD (odds ratio 3.4, 95% confidence interval [CI] 2.1-5.6). Survival analysis demonstrated that when controlling for the propensity score, PN was associated with better overall survival (hazard ratio 0.30, 95% CI = .13-.71). CONCLUSIONS Where technically feasible, PN offers cancer control equivalent to that of RN. Elective PN was associated with a significantly better overall survival in this cohort, even when controlling for age, tumor size, pathologic stage, and burden of comorbid diseases. The improvement in overall survival appears to be attributable in part to prevention of postoperative CKD.

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.

Performance of the Chronic Kidney Disease-Epidemiology Study Equations for Estimating Glomerular Filtration Rate Before and After Nephrectomy

PURPOSE Accurate renal function determination before and after nephrectomy is essential for proper prevention and management of chronic kidney disease due to nephron loss and ischemic injury. We compared the estimated glomerular filtration rate using several serum creatinine based formulas against the measured rate based on (125)I-iothalamate clearance to determine which most accurately reflects the rate in this setting. MATERIALS AND METHODS Of 7,611 patients treated at our institution since 1975 the measured glomerular filtration rate was selectively determined before and after nephrectomy in 268 and 157, respectively. Performance of the Cockcroft-Gault, Modification of Diet in Renal Disease Study, re-expressed Modification of Diet in Renal Disease Study and Chronic Kidney Disease-Epidemiology Study equations, each of which estimates the glomerular filtration rate, were determined using serum creatinine, age, gender, weight and body surface area. The performance of serum creatinine, reciprocal serum creatinine and the 4 formulas was compared with the measured rate using Pearsons correlation, Lins concordance coefficient and residual plots. RESULTS Median serum creatinine was 1.4 mg/dl and the median measured glomerular filtration rate was 50 ml per minute per 1.73 m(2). The correlation between serum creatinine and the measured rate was poor (-0.66) compared with that of reciprocal serum creatinine (0.78) and the 4 equations (0.82 to 0.86). The Chronic Kidney Disease-Epidemiology Study equation performed with greatest precision and accuracy, and least bias of all equations. Stage 3 or greater chronic kidney disease ((125)I-iothalamate glomerular filtration rate 60 ml per minute per 1.73 m(2) or less) was present in 44% of patients with normal serum creatinine (1.4 mg/dl or less) postoperatively. Such missed diagnoses of chronic kidney disease decreased 42% using the Chronic Kidney Disease-Epidemiology Study equation. CONCLUSIONS Glomerular filtration rate estimation equations outperform serum creatinine and better identify patients with perinephrectomy compromised renal function. The newly developed, serum creatinine based, Chronic Kidney Disease-Epidemiology Study equation has sufficient accuracy to render direct glomerular filtration rate measurement unnecessary before and after nephrectomy for cause in most circumstances.

Management of the Adrenal Gland During Partial Nephrectomy

PURPOSE Nephron sparing surgery is an increasingly used alternative to Robsons 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.

Gadolinium-enhanced MRI in the evaluation of minimally invasive treatments of the prostate: Correlation with histopathologic findings

OBJECTIVES To explore the use of magnetic resonance imaging (MRI) with gadolinium enhancement as a noninvasive method to image the extent of ablation after minimally invasive treatment. Minimally invasive methods for ablating prostatic tissue have emerged as a viable option in the treatment of prostate disease. As these devices enter the mainstream of patient care, imaging methods that verify the exact location, extent, and pattern of the ablation are needed. METHODS Nineteen patients with prostate cancer were evaluated. All received some type of minimally invasive treatment, post-treatment gadolinium-enhanced MRI sequences, and radical retropubic prostatectomy for histopathologic evaluation. Visual comparisons of gadolinium defects and areas of coagulation necrosis as seen on histopathologic evaluation were made by us. Volumetric and two-dimensional area measurements of the ablation lesions were also compared for correlation between the MRI and histopathologic results. RESULTS Gadolinium-enhanced MRI could be matched to histopathologic findings by visual comparison in 17 of the 19 cases. Surgically distorted histopathologic specimens and a small periurethral lesion caused 2 patients to have MRI and histopathologic results that could not be matched. Complete volumetric measurements were available for 16 of the 19 patients and correlated strongly (r = 0.924). The two-dimensional area data for all patients also showed significant correlation (r = 0.886). CONCLUSIONS Correlation with histopathologic findings showed gadolinium-enhanced MRI to be useful for determining the location, pattern, and extent of necrosis caused within the prostate by minimally invasive techniques. Gadolinium-enhanced MRI gives the urologist a useful tool to evaluate the effectiveness of new minimally invasive therapies.