Immunological response to renal cryoablation in an in vivo orthotopic renal cell carcinoma murine model.

PURPOSE: The immunological consequences of cryoablation for renal cell carcinoma are largely unknown. Cryoablation is an attractive therapeutic option for tumors due to its minimally invasive nature. Cryoablation is also potentially immunogenic. We describe the development of an animal model to deliver in vivo renal cryotherapy to orthotopically implanted renal cell carcinoma and the results of multiple immunological interrogations after cryoablation. MATERIALS AND METHODS: Four to 6-week-old female Balb/c mice (Jackson Laboratories, Bar Harbor, Maine) underwent renal subcapsular implantation of the syngeneic murine renal cell carcinoma Renca. Two weeks later contact cryoablation was done in tumor bearing kidneys. Another group of animals underwent cryoablation of normal kidneys. Animals were sacrificed 2 weeks after tumor injection or 1 and 2 weeks after cryoablation, respectively. Kidneys, spleens and draining lymph nodes were harvested. Evaluation consisted of immunohistochemistry, immunofluorescence and gene expression profiling using reverse-transcriptase polymerase chain reaction. RESULTS: Subcapsular tumor implantation was successful in all cases and confirmed histologically. No significant lymphocytic infiltrate was seen in tumor only animals but those treated with cryoablation (tumor and nontumor bearing) had a significant inflammatory response primarily in sublethal tissue injury and perivascular areas. After cryoablation most infiltrating cells were neutrophils, macrophages and T cells. Polymerase chain reaction showed increased interferon-gamma production in kidneys after cryoablation. CONCLUSIONS: This study shows the potential feasibility of this animal model for studying cryo-immunology. We confirm the absence of any significant immune cell infiltration in tumor bearing kidneys and report a significant inflammatory infiltrate after cryoablation, consisting primarily of neutrophils, macrophages, and CD4+ and CD8+ T cells with an increase in the T helper type 1/2 ratio. This orthotopic murine model can form the basis of future studies of additional immunological aspects of renal cryoablation.

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.

Renal function assessment in the era of chronic kidney disease: renewed emphasis on renal function centered patient care.

PURPOSE: Chronic kidney disease is more common than previously appreciated and it is now established as a major independent contributor to mortality. Serum creatinine is known to be an inaccurate reflection of the presence or development of chronic kidney disease. Since urologists frequently treat patients with coexistent chronic kidney disease, we reviewed the merits and limitations of the current methods to estimate renal function, and recent data indicating the importance of optimizing renal function during treatment. MATERIALS AND METHODS: A comprehensive literature review was performed to evaluate the laboratory, computational and imaging techniques for renal function estimation. RESULTS: Approximately 30% of elderly patients with normal serum creatinine (1.4 mg/dl or less) have chronic kidney disease based on an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m(2). The National Kidney Foundation currently recommends using a creatinine based estimate of glomerular filtration rate (eg Modification of Diet in Renal Disease formula) and has advocated a standardized classification for chronic kidney disease. Chronic kidney disease has been independently related to morbid cardiac events and all cause mortality in a dose dependent fashion, even after controlling for a variety of potentially confounding factors such as hypertension and diabetes. Many urological interventions can precipitate or exacerbate chronic kidney disease, most notably radical nephrectomy which is greatly overused. CONCLUSIONS: Practicing urologists should be cognizant of current methodologies to diagnose chronic kidney disease and its profound implications. Estimation of renal function is better using a serum creatinine based formula than individual serum creatinine values. Treatment goals should not be limited to avoidance of dialysis, but should also include greater efforts to optimize renal function in all patients and early referral for nephrological consultation.

Minimally invasive nephron sparing management for renal tumors in solitary kidneys.

PURPOSE: We present a large series of minimally invasive nephron sparing surgery outcomes in solitary kidneys with a focus on treatment selection criteria, and oncological and functional outcomes. MATERIALS AND METHODS: Of 1,019 patients who underwent minimally invasive nephron sparing surgery since September 1997 at our institution 36, 36 and 29 underwent laparoscopic partial nephrectomy, cryoablation and radio frequency ablation, respectively, for tumors in a solitary kidney. Data, including patient and tumor characteristics, surgery details, complications, and postoperative renal function and intermediate term oncological outcomes in each patient, were obtained by telephone contact or from charts. The 3 groups were compared for perioperative, functional and oncological outcomes. RESULTS: On multivariate analysis tumor size, aspect and remnant kidney status were independent predictors of treatment selection. Cancer specific and overall survival at 2 years was 100% and 91.2% for laparoscopic partial nephrectomy, 88.5% and 88.5% for cryoablation, and 83.9% and 83.9% for radio frequency ablation, respectively. Disease-free survival was significantly better for laparoscopic partial nephrectomy than for cryoablation and radio frequency ablation (100% vs 69.6% and 33.2%, respectively, p <0.0001). The mean estimated glomerular filtration rate change for laparoscopic partial nephrectomy, cryoablation and radio frequency ablation of 17, 3 and 7 ml per minute per 1.73 m(2) reflected a 26%, 6% and 13% decrease from baseline, respectively, which was statistically significant (p = 0.0016). CONCLUSIONS: Laparoscopic partial nephrectomy and probe ablative procedures can be safely and efficiently done for renal tumor in patients with a solitary kidney. Intermediate term oncological outcomes are superior for laparoscopic partial nephrectomy despite somewhat poorer renal function outcomes than those of cryoablation and radio frequency ablation.

Differential expression in clear cell renal cell carcinoma identified by gene expression profiling.

PURPOSE: Gene expression profiling has been shown to provide prognostic information on patients with solitary sporadic renal cell carcinoma. To our knowledge there is no reliable way to differentiate synchronous renal metastasis from bilateral primary tumors in patients with bilateral renal cell carcinoma. We present data using a custom kidney cancer cDNA array that can predict the outcome in patients with unilateral and bilateral renal cell carcinoma. MATERIALS AND METHODS: Fresh frozen tissue from 38 clear cell renal cell carcinomas was analyzed using a cancer cDNA array containing 3,966 genes relevant to cancer or kidney development. Median followup was 5.3 years. Cancer recurred in 12 patients (43%) and 11 (39%) had died by the last followup. RESULTS: Using a training data set of 8 tumors a 44 gene expression profile distinguishing aggressive and indolent clear cell renal cell carcinoma was identified. Of 29 single clear cell renal cell carcinomas 16 and 13 were predicted to be indolent and aggressive, respectively, by the gene expression profile. Recurrence-free survival at 5 years was 68% and 42% in these 2 groups, respectively (p = 0.032). Clear cell renal cell carcinoma classified as indolent or aggressive according to SSIGN (stage, size, grade and necrosis) score showed a 5-year recurrence-free survival rate of 78% and 42%, respectively (p = 0.021). On Cox proportional hazards analysis the gene expression profile was not an independent predictor of recurrence-free survival after accounting for SSIGN score. Gene expression profile classification correlated with cancer specific survival at 5 years in 4 of 4 patients with metachronous clear cell renal cell carcinoma but in only 2 of 4 with bilateral synchronous clear cell renal cell carcinoma. CONCLUSIONS: Gene expression profiling using a kidney cancer relevant cDNA array can differentiate between aggressive and indolent clear cell renal cell carcinomas. Gene expression profile results may be most useful for unilateral clear cell renal cell carcinoma when results are discordant with predictions of tumor behavior based on standard clinicopathological features. In addition, gene expression profiling can provide prognostic information that may help characterize tumors of unknown clinical stage, such as bilateral metachronous clear cell renal cell carcinoma.

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.

Surgical resection of renal cell carcinoma after targeted therapy.

PURPOSE: The development of targeted agents for renal cell carcinoma has renewed interest in consolidative surgery due to the robust clinical responses seen with these agents. The integration of targeted therapy and surgery requires careful consideration due to the potential for increased perioperative morbidity. MATERIALS AND METHODS: We retrospectively identified patients with renal cell carcinoma treated with sunitinib, sorafenib or bevacizumab plus interleukin-2 before tumor resection. RESULTS: Between June 2005 and August 2008, 19 patients were treated with targeted therapy and subsequently underwent resection. Surgical extirpation involved an open and a laparoscopic approach in 18 and 3 cases, respectively, for locally advanced (8), locally recurrent (6) and metastatic disease (3). Two patients with extensive bilateral renal cell carcinoma were also treated to downsize the tumors to enable partial nephrectomy. Perioperative complications were noted in 16% of patients. One patient had a significant intraoperative hemorrhage and disseminated intravascular coagulopathy from a concomitant liver resection. An anastomotic bowel leak and abscess were noted postoperatively in another patient who underwent en bloc resection of a retroperitoneal recurrence and adjacent colon. Two patients (11%) had minor wound complications, including a wound seroma and a ventral hernia. Pathological analysis of 20 specimens revealed clear cell, chromophobe and unclassified renal cell carcinoma in 80%, 5% and 10% of cases, respectively. One patient (5%) had a pathological complete response. CONCLUSIONS: Surgical resection of renal cell carcinoma after targeted therapy is feasible with low morbidity in most patients. However, significant complications can occur, raising concern for possible compromise of tissue and/or vascular integrity associated with surgery in this setting.

Response of the primary tumor to neoadjuvant sunitinib in patients with advanced renal cell carcinoma.

PURPOSE: We assessed the activity of neoadjuvant sunitinib on primary renal tumors in patients with advanced renal cell carcinoma as well as the feasibility and safety of subsequent surgical resection. METHODS: A total of 19 patients with advanced renal cell carcinoma deemed unsuitable for initial nephrectomy due to locally advanced disease or extensive metastatic burden were treated with 50 mg sunitinib daily for 4 weeks on followed by 2 weeks off. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors every 2 cycles and the rate of conversion to resectable status was estimated. RESULTS: Median patient age was 64 years and initial median radiographic renal tumor size was 10.5 cm. Clinical stage was N+ (10) and M+ (15). No patients experienced a complete response. Partial responses of the primary tumor were noted in 3 patients (16%), 7 (37%) had stable disease and 9 (47%) had disease progression in the primary tumor. Overall tumor response included 2 patients (11%) with partial response, 7 (37%) with stable disease and 10 (53%) with disease progression. At a median followup of 6 months (range 1 to 15) 4 patients (21%) had undergone nephrectomy and 5 died of disease progression. No unexpected surgical morbidity was encountered. Viable tumor was present in all 4 specimens. Sunitinib was associated with grade 3-4 toxicity in 7 patients (37%) and treatment was discontinued in 1 due to toxicity. CONCLUSIONS: Administration of sunitinib in patients with advanced renal cell carcinoma with the primary tumor in place is feasible and can lead to a reduction in tumor burden that can facilitate subsequent surgical resection.

Active surveillance of renal masses in elderly patients.

PURPOSE: We identify and report on a large number of patients treated with active surveillance for incidentally diagnosed renal masses at our institution. MATERIALS AND METHODS: We identified all patients 75 years or older evaluated in our department for a renal mass between January 2000 and December 2006. A total of 110 patients with enhancing renal masses were initially treated with active surveillance and this group made up the cohort for our study. Medical records were reviewed for clinical and radiological followup, and vital status was obtained from the Social Security Death Index. Clinical and radiographic followup was available for review on 104 and 89 patients, respectively. RESULTS: Patients had a median age of 81 years (range 76 to 95) with a median Charlson comorbidity index of 2 (range 0 to 7) at diagnosis. Patients had as many as 9 tumors being followed (median of 1) with a median tumor size of 2.5 cm (range 0.9 to 11.2). During a median followup of 24 months (range 1 to 90) mean tumor growth rate was 0.26 cm per year. Of the 89 patients with radiological followup 38 (43%) exhibited no tumor growth on active surveillance. Comparison of the clinical and radiographic features of patients with tumor growth and those with stable disease revealed no statistical differences. Four patients (3.6%) were treated as a result of disease progression 12 to 54 months after diagnosis. At the conclusion of the study 34 patients (31%) were deceased. To our knowledge the renal mass did not contribute to the cause of death in any patient. CONCLUSIONS: Active surveillance of incidental renal masses appears to be a viable option for older patients with multiple medical comorbidities and a limited life expectancy.

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.

Correlation between loss of renal function and loss of renal volume after partial nephrectomy for tumor in a solitary kidney.

PURPOSE: We assessed the correlation between reduced renal function and parenchymal volume following partial nephrectomy. MATERIALS AND METHODS: In 21 of 42 patients with tumors in a solitary kidney who were enrolled in a study measuring function before and after surgery underwent computerized tomography, and measurement of the glomerular filtration rate and estimated glomerular filtration rate (the latter at baseline and 2 to 6 months) before and after surgery. A segmentation algorithm was used to measure renal parenchymal volume. The percent of renal parenchymal volume loss was correlated with the percent loss in glomerular filtration rate using the Pearson correlation coefficient. RESULTS: Mean +/- SD net preoperative volume was 284 +/- 67 cc (range 179 to 413) and mean net postoperative volume was 240 +/- 61 cc (range 119 to 346) with an absolute functional volume loss of between 5 and 160 cc. The average percent of parenchymal volume loss was 15% (range -2% to 47%). The mean loss of the measured glomerular filtration rate 3 days postoperatively was 33.9% (range -70.7% to 74.4%) and the estimated glomerular filtration rate 2 to 6 months postoperatively was 19.7 % (-6.0% to 45.5%). There was a low degree of correlation between the percent volume loss and the percent measured glomerular filtration rate loss at 3 days (r = 0.28, p = 0.22). However, there was a moderate degree of correlation between the percent volume loss and the percent estimated glomerular filtration rate loss at 2 to 6 months (r = 0.48, p = 0.03). CONCLUSIONS: In patients with partial nephrectomy the renal parenchymal volume loss correlates best with the renal function loss several months after surgery. Estimates of volume loss may be useful for predicting postoperative renal function when planning partial nephrectomy in patients with a solitary kidney.

Renal mass biopsy--a renaissance?

PURPOSE: Advances in our understanding of the natural history and limited aggressive potential of many small renal masses, expanding treatment options and the integration of molecular factors into prognostic and therapeutic algorithms have stimulated renewed interest in percutaneous renal mass biopsy. MATERIALS AND METHODS: A comprehensive literature review was performed using MEDLINE/PubMed to evaluate the indications, techniques, complications and efficacy of renal mass biopsy. RESULTS: Reported techniques of renal mass biopsy vary widely with different modes of radiographic guidance, needle size, number of cores and pathological analyses. Percutaneous renal mass biopsy with 2 or 3 cores using 18 gauge needles may improve diagnostic accuracy without increasing morbidity. Serious complications of percutaneous biopsy are rare and the minor complication rate in recent series has been less than 5%. The reported rate of technical failure of renal mass biopsy due to insufficient material was about 9% before 2001 and 5% in more recent studies. The likelihood of indeterminate or inaccurate pathological findings has decreased from 10% to 4% when comparing clinical studies before and since 2001. Currently a total success rate of greater than 90% is attainable using renal mass biopsy with standard histopathological analysis. Recent studies demonstrated that combining immunohistochemical and molecular analyses may further improve renal mass biopsy accuracy. CONCLUSIONS: Research on expanded analysis of percutaneous renal mass biopsy specimens should remain a top priority. Enhanced renal mass biopsy should not change treatment in most patients with small renal masses, who should be treated with surgical excision. However, future clinical algorithms will likely incorporate enhanced biopsy in situations in which decision making is more challenging.

Clinical correlates of renal angiomyolipoma subtypes in 209 patients: classic, fat poor, tuberous sclerosis associated and epithelioid.

PURPOSE: Angiomyolipomas classically present radiographically as fat containing lesions but some fail to demonstrate fat content. Histologically confirmed angiomyolipomas uniformly follow a benign course but rare epithelioid variants of angiomyolipoma can recur and metastasize. We investigated the clinical, radiographic and histological characteristics of each angiomyolipoma subtype. MATERIALS AND METHODS: Pertinent data were recorded for 209 patients surgically treated for angiomyolipoma in 219 kidneys from 1981 to 2007. Classic and fat poor angiomyolipomas were classified radiographically based on the presence or absence of fat and classified histologically based on the presence of triphasic, monophasic or epithelioid histology. RESULTS: Median radiographic size was 3.2, 4.9 and 10 cm in patients with a single angiomyolipoma (59% of patients), multiple angiomyolipomas and tuberous sclerosis (probable or definite), respectively. In these 3 groups 65%, 47% and 33% of lesions were not suspected radiographically (fat poor angiomyolipoma). Fat poor angiomyolipomas were more commonly single, smaller and in older patients. Triphasic histology was evident in 76% of angiomyolipomas with 16% demonstrating a predominance of 1 component and 8% containing epithelioid features. Despite potentially aggressive findings in 18% (eg presence within the perinephric fat, lymph node involvement) no angiomyolipoma recurred during a mean followup of 3.4 years (range 0 to 24). A total of 28 (13%) patients with angiomyolipoma had concomitant renal cell carcinoma. CONCLUSIONS: A surprisingly high number of resected angiomyolipomas was not suspected radiographically indicating the importance of precise radiographic characterization to minimize nephrectomy for fat poor angiomyolipoma, which should remain a research priority. In this sizeable single institution series no triphasic, monophasic or epithelioid angiomyolipoma recurred despite potentially aggressive findings in a substantial proportion of cases.

The impact of minimally invasive techniques on open partial nephrectomy: a 10-year single institutional experience.

PURPOSE: With the advent of minimally invasive, nephron sparing surgical options we hypothesized that the indications, perioperative parameters and complication rates of open partial nephrectomy may have changed significantly during a 10-year period. MATERIALS AND METHODS: Open partial nephrectomy was compared during 2, 3-year periods. From 1994 to 1996 (before laparoscopic partial nephrectomy, cryoablation and radio frequency ablation) 208 cases were compared vs 347 open partial nephrectomies performed from 2004 to 2006 with regard to indications, perioperative parameters and complication rates. RESULTS: There were no significant differences between the groups with regard to age (59 vs 58 years), gender (65.5% vs 65.0% male) and tumor size (3.9 vs 3.6 cm). Tumors removed in the recent era were more often in a solitary kidney (40.0% vs 15.6%) and centrally located (55.6% vs 37.3%), and pathological evaluation more often revealed higher grade (Fuhrman 3 or 4) (43.1% vs 27.8%, each p <0.0001). Despite increased technical difficulty ischemia time in the more recent era was shorter (19.1 vs 40.6 minutes, p = 0.0000), and the urological and overall complication rates were statistically similar (7.5% vs 8.9%, p = 0.6071 and 19.1% vs 14.4%, p = 0.1723, respectively). CONCLUSIONS: At a tertiary referral center the introduction of minimally invasive, nephron sparing surgical techniques has drawn away less complicated, less aggressive tumors, reserving the bulk of more complicated central tumors for open partial nephrectomy without decreasing the total number of open cases. With experience these more difficult central tumors are being successfully treated with decreased warm ischemia time and complication rates that are comparable to those in historical series.

Outcomes of partial nephrectomy in patients on chronic oral anticoagulant therapy.

PURPOSE: We report our experience with patients requiring long-term anticoagulation therapy who underwent open or laparoscopic partial nephrectomy for renal tumors at our institution. We compared outcomes with those in a control group undergoing partial nephrectomy with no anticoagulation requirements. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,031 patients who underwent laparoscopic or open partial nephrectomy from 2000 to 2005. Since 2000, 31 open and 16 laparoscopic partial nephrectomies were performed in patients on chronic warfarin, clopidogrel or cilostazol. Anticoagulation was appropriately discontinued perioperatively. The 47 anticoagulated cases were compared with 47 nonanticoagulated controls that were carefully matched for surgical approach, partial nephrectomy defect size, tumor size and location, procedure year and warm ischemia time. Investigators were blinded to all clinical outcomes throughout the matching process. Bleeding and thrombotic outcomes were then analyzed. RESULTS: The 2 groups were well matched for resection bed size, tumor size, tumor location (central vs peripheral), solitary kidney, operative time and warm ischemia time (each p >or=0.3). Controls had significantly higher intraoperative blood loss (300 vs 200, p <0.05) and a greater postoperative decrease in hemoglobin (3.5 vs 2.4 mg/dl, p <0.001). However, transfusion rates were similar in the 2 groups (each 15%). Five patients on anticoagulation had thrombotic events postoperatively vs none in the control group. CONCLUSIONS: Patients on anticoagulation are at higher perioperative risk but with careful perioperative management of anticoagulation therapy partial nephrectomy can be performed in a safe and efficacious manner. To our knowledge this is the largest study of outcomes in this complex patient population.

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.

Surgical salvage of renal cell carcinoma recurrence after thermal ablative therapy.

PURPOSE: Thermal ablative therapies, including cryoablation and radio frequency ablation, have become viable options for the management of small renal tumors. However, initial data have suggested higher local recurrence rates for ablation compared to partial nephrectomy. We evaluated options for salvage of ipsilateral tumor recurrence after previous ablation. MATERIALS AND METHODS: Records of renal surgeries performed at our institution between September 1997 and December 2006 were reviewed to identify patients with ipsilateral tumor recurrence after radio frequency ablation or cryoablation, and clinical characteristics and treatment were defined. RESULTS: Recurrence rates at our hospital were 13 of 175 (7.4%) after cryoablation and 26 of 104 (25%) after radio frequency ablation, and 3 additional cases of post-cryoablation recurrence were referred from elsewhere. Overall repeat ablation was performed in 26 patients who experienced post-ablative recurrence. However, 12 patients (33%) were not candidates for repeat ablation due to large tumor size, disease progression or repeat ablative failure. In this group 1 patient received systemic therapy, 1 refused further treatment and 10 underwent attempted extirpation. Partial nephrectomy was only possible in 2 patients and both required an open approach. Remaining patients were treated with radical nephrectomy (7) or had the procedure aborted due to strong patient preference to avoid dialysis (1). Laparoscopic surgery was only possible in 4 cases. Extensive perinephric scarring was encountered in all salvage operations following cryoablation. CONCLUSIONS: Primary thermal ablation for small renal masses may preclude or complicate subsequent surgical salvage. Cryoablation in particular can lead to extensive perinephric fibrosis which can complicate attempts at salvage. Appropriate patient selection for thermal ablation remains of paramount importance.

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.

Intraoperative placing of drains decreases the incidence of lymphocele and deep vein thrombosis after renal transplantation.

OBJECTIVE: To investigate the effect of placing a prophylactic drain during renal transplantation on the incidence of lymphocele, wound complication and deep venous thrombosis (DVT) in renal transplant recipients induced with sirolimus vs calcineurin inhibitors (CNI), as sirolimus-based immunosuppression is a risk factor for the formation of fluid collections after transplantation. PATIENTS AND METHODS: We analysed 165 consecutive adult renal transplant patients at our institution between January 2004 and February 2005. Group 1 (84) did not receive an intraoperative drain and group 2 (81) did. Recipients were analysed within each group based on immunosuppression (sirolimus or CNI) and whether they had wound complication, fluid collection, lymphocele treatment, or DVT. RESULTS: In group 1 and 2, respectively, the wound complication rate was 22.6% vs 13.6% (P = 0.134), the fluid collection rate 45.2% vs 16.% (P < 0.001), the lymphocele treatment rate 19.0% vs 2.5% (P = 0.001) the DVT rate 14.3% vs 4.9% (P = 0.043) the fluid collection rate (for CNI) 26.5% vs 16.0% (P = 0.246), the lymphocele treatment rate (for CNI) 5.9% vs 0% (P = 0.084), the fluid collection rate (sirolimus) 58.0% vs 16.1% (P < 0.001) and lymphocele treatment rate (sirolimus) 28% vs 6.5% (P = 0.018). Multivariate analysis of risk factors for fluid collection showed significance for no drain (odds ratio 3.30, P = 0.002), associated wound complication (2.41, P = 0.041) and sirolimus (2.48, P = 0.015). CONCLUSIONS: Placing a drain during transplantation decreased the incidence of fluid collection, lymphocele treatment and DVT. The reduction of fluid collection and lymphocele were significant for patients treated with sirolimus. We recommend placing a drain in patients undergoing induction with sirolimus-based immunosuppression.

Choice of operation for clinically localized renal tumor.

The cornerstone of treatment for localized renal tumors is surgical excision, which until recently was accomplished primarily through radical nephrectomy. The last 2 decades have seen a rapid evolution in the surgical management of renal cell carcinoma, marked by the increased use of nephron-sparing surgery and the application of minimally invasive techniques. A plethora of surgical options now are available. This article discusses the optimal surgical approach to renal tumors in various clinical scenarios. In all these discussions we assume that a proactive approach to treatment is indicated and desired, recognizing that active surveillance is always an additional option to consider in certain subpopulations such as the elderly or infirm.