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European urology 05/2013; · 7.67 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate the impact of tumor histology on clinicopathologic outcomes for patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). METHODS: We identified 807 patients with RCC and VTT who underwent nephrectomy at our institution between 1970 and 2008. All pathologic specimens were re-reviewed by a single urologic pathologist. Patients with non-clear cell RCC (non-ccRCC, n = 56) were matched 1:2 to patients with clear cell RCC (ccRCC) VTT based on symptoms at presentation, regional lymph node involvement, distant metastases, tumor thrombus level, nuclear grade, and sarcomatoid differentiation. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The 56 patients with non-ccRCC VTT included 26 papillary, 11 chromophobe, 5 collecting duct tumors, and 14 RCCs not otherwise specified. Compared to unmatched patients with ccRCC VTT (n = 751), patients with non-ccRCC VTT presented with larger tumor size (P = .02), higher nuclear grade (P = .04), and more frequent sarcomatoid differentiation (P <.001) and lymph node invasion (P <.001). However, when patients with non-ccRCC were matched to patients with ccRCC, no significant differences were noted with regard to 5-year metastases-free survival (41% vs 34%, P = .24) or cancer-specific survival (25% vs 27%, P = .97). CONCLUSION: Non-ccRCC VTT is associated with a high rate of adverse pathologic features. Nevertheless, when matched to patients with ccRCC, patients with non-ccRCC VTT did not have increased rate of recurrence or adverse survival. Aggressive surgical resection represents the mainstay of treatment in these cases, whereas continued efforts to optimize a multimodal management approach to such patients remain necessary.
Urology 05/2013; · 2.43 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate carbonic anhydrase IX (CAIX) expression as an independent prognostic marker for clear cell renal cell carcinoma (ccRCC). With recent smaller studies showing conflicting results, we aimed to update our initial analysis in 2007 with an additional 5-year follow-up. PATIENTS AND METHODS: We provided long-term follow-up of the same cohort used in our 2007 study (730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999). Associations of CAIX expression with RCC death and distant metastases were evaluated using Cox proportional hazards regression models. RESULTS: CAIX was expressed in 708 (97.0%) of the specimens; 163 tumours (22.3%) had low (≤85%) expression and 567 (77.7%) high (>85%) expression. There were 483 deaths and 265 RCC-specific deaths. The median follow-up for the 247 patients still under observation was 13.8 years. Univariately, low CAIX expression was associated with an increased risk of RCC death vs high expression (hazard ratio 1.62; P < 0.001). Low CAIX expression was not statistically significantly associated with RCC death or distant metastases after adjusting for nuclear grade or coagulative tumour necrosis. CONCLUSION: After additional long-term follow-up of our large cohort, our results continue to suggest that CAIX is not an independent prognostic marker for ccRCC.
BJU International 04/2013; · 2.84 Impact Factor
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ABSTRACT: OBJECTIVES: To evaluate risk factors associated with iatrogenic splenectomy during nephrectomy and to assess outcomes among patients undergoing nephrectomy for renal tumors. METHODS: Of 4323 patients who underwent nephrectomy at Mayo Clinic between 1992 and 2008, 33 (0.8%) had an iatrogenic/unplanned splenectomy. In a case-control study design, controls without splenectomy were matched 1:3 based on age, sex, surgical date, side of the renal tumor, surgical approach and surgeon. Perioperative features and survival were evaluated using conditional logistic and Cox regression. RESULTS: Among the 33 iatrogenic splenectomy patients, the majority (94%) underwent radical, open and left-sided nephrectomy. Primary tumor classification ≥T3 was the only clinicopathological risk factor significantly associated with splenectomy (odds ratio 3.4; P = 0.02). Compared with controls, patients with an iatrogenic splenectomy were more likely to have longer operative time (205 vs 171 min; P = 0.02), higher estimated blood loss (1.3 vs 0.3 L; P = 0.001), longer length of stay (median 7 vs 5 days; P = 0.03) and a higher likelihood for postoperative complications (odds ratio 5.3; P = 0.002). With a median of 9.8 years of follow up, splenectomy patients tended to have greater all-cause mortality (hazard ratio 1.6; P = 0.07), although this difference approached statistical significance. CONCLUSIONS: Iatrogenic splenectomy is a rare complication during nephrectomy and is associated with locally advanced tumors (≥pT3). It also carries prognostic significance for adverse perioperative outcomes and possibly diminished survival, although this warrants further study.
International Journal of Urology 02/2013; · 1.75 Impact Factor
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Thomas D Atwell,
Grant D Schmit,
Stephen A Boorjian,
Jay Mandrekar,
A Nicholas Kurup,
Adam J Weisbrod,
George K Chow,
Bradley C Leibovich,
Matthew R Callstrom,
David E Patterson, Christine M Lohse,
R Houston Thompson
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ABSTRACT: The purpose of this article is to compare the efficacy and complication rates of percutaneous radiofrequency ablation (RFA) and cryoablation in the treatment of renal masses measuring 3.0 cm and smaller.
A retrospective review was performed of 385 patients with 445 tumors measuring 3.0 cm or smaller treated with thermal ablation from 2000 through 2010. Two hundred fifty-six tumors in 222 patients were treated with RFA (mean [± SD] tumor size, 1.9 ± 0.5 cm), and 189 tumors in 163 patients were treated with cryoablation (mean tumor size, 2.3 ± 0.5 cm). Major complications and efficacy as measured by technical success and local tumor recurrence rates were recorded.
There were five (1.1%) technical failures, including one (0.4%) among tumors treated with RFA and four (2.1%) among tumors treated with cryoablation (p = 0.17). Of the 218 tumors treated with RFA and with follow-up beyond 3 months, seven (3.2%) developed local tumor recurrence, at a mean of 2.8 years after treatment (range, 1.2-4.1 years). Of the 145 tumors treated with cryoablation and with follow-up beyond 3 months, four (2.8%) developed local tumor recurrence at a mean of 0.9 years after treatment (range, 0.3-1.6 years). For biopsy-proven renal cell carcinoma, estimated local recurrence-free survival rates at 1, 3, and 5 years after RFA were 100%, 98.1%, and 98.1%, respectively, compared with 97.3%, 90.6%, and 90.6%, respectively, after cryoablation (p = 0.09). Major complications occurred after 4.3% (10/232) of RFAs and 4.5% (8/176) of cryoablation procedures (p = 0.91).
RFA and cryoablation are both effective in the treatment of renal masses measuring 3 cm or smaller. Major complications with either procedure are infrequent.
American Journal of Roentgenology 02/2013; 200(2):461-6. · 2.78 Impact Factor
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ABSTRACT: Grading of renal cell carcinoma (RCC) has prognostic significance, and there is recent consensus by the International Society of Urological Pathology (ISUP) that for clear cell and papillary RCC, grading should primarily be based on nucleolar prominence. Microscopic tumor necrosis also predicts outcome independent of tumor grading. This study was undertaken to assess whether the incorporation of microscopic tumor necrosis into the ISUP grading system provides survival information superior to ISUP grading alone. Data on 3017 patients treated surgically for clear cell RCC, 556 for papillary RCC, and 180 for chromophobe RCC were retrieved from the Mayo Clinic Registry. Median follow-up periods were 8.9, 9.7, and 8.5 years, respectively. Four proposed grades were defined: grade 1: ISUP grade 1+ISUP grade 2 without necrosis; grade 2: ISUP grade 2 with necrosis+ISUP grade 3 without necrosis; grade 3: ISUP grade 3 with necrosis+ISUP grade 4 without necrosis; grade 4: ISUP grade 4 with necrosis or sarcomatoid/rhabdoid tumors. There was a significant difference in survival between each of the grades for clear cell RCC, and the concordance index was superior to that of ISUP grading. The proposed grading system also outperformed the ISUP grading system when cases were stratified according to the TNM stage. Similar results were not obtained for papillary RCC or chromophobe RCC. We conclude that grading for clear cell RCC should be based on nucleolar prominence and necrosis, that ISUP grading should be used for papillary RCC, and that chromophobe RCC should not be graded.
The American journal of surgical pathology 01/2013; · 4.06 Impact Factor
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ABSTRACT: PURPOSE: We evaluated the association of microvascular invasion (MVI) and capillary-lymphatic invasion (CLI) with patient outcome following nephrectomy for renal cell carcinoma (RCC). MATERIAL AND METHODS: We identified 1,433 patients surgically treated for sporadic, unilateral RCC between 2001 and 2008. All specimens were reviewed by a single uropathologist for MVI and CLI. Associations with time to metastases and death from RCC were evaluated using Cox proportional hazards models, controlling for established clinicopathologic prognostic variables. RESULTS: MVI and CLI were identified in 11% (119/1,103) and 2% (17/1,103) with clear cell, 2% (5/219) and <1% (1/219) with papillary, and 1% (1/86) and 0 with chromophobe RCC, respectively. Median follow-up for patients still alive was 6.4 years (range 0-11). In clear cell RCC, MVI was univariately associated with an increased risk of metastases (HR 3.5,p<0.001) and cancer-specific death (HR 3.0,p<0.001). However, on multivariate analyses, these associations were no longer statistically significant (HR 1.2,p=0.4 and HR 1.3,p=0.1, respectively). CLI remained significantly associated with an increased risk of metastases and death both univariately (HR 15.9,p<0.001 and HR 11.6,p<0.001, respectively) and on multivariate analyses (HR 3.2,p<0.001 and HR 3.1,p<0.001, respectively). CONCLUSIONS: MVI is associated with an increased risk of metastases and cancer death for patients with clear cell RCC, although this does not remain significant after controlling for established prognostic variables. Meanwhile, CLI appears to be independently associated with metastases and cancer death even after controlling for known prognostic risk factors; however, given its rarity, this feature may prove to be of limited clinical significance.
The Journal of urology 01/2013; · 4.02 Impact Factor
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ABSTRACT: BACKGROUND: Although partial nephrectomy (PN) has been associated with improved renal function compared with radical nephrectomy (RN) for renal cell carcinoma, the impact on overall survival (OS) remains controversial. OBJECTIVE: To evaluate comparative OS and renal function in patients following PN and RN for a renal mass where malignancy was not a confounding factor. DESIGN, SETTING, AND PARTICIPANTS: Using the Mayo Clinic Nephrectomy Registry, we retrospectively identified 442 patients with unilateral sporadic benign renal masses treated surgically with PN or RN between 1980 and 2008. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome measures were OS and the incidence of new-onset stage IV chronic kidney disease (CKD), determined using the Kaplan-Meier method. Cox models were used to test the association of nephrectomy type with these outcomes. RESULTS AND LIMITATIONS: Overall, 206 and 236 patients with benign renal masses were surgically treated with RN and PN, respectively. Patients who underwent RN were older (median age: 67 vs 64 yr; p=0.02) and had larger tumors (median size: 5.0 vs 2.7cm; p<0.001). Median follow-up for patients still alive at last follow-up was 8.3 yr (range: 0.1-27.9 yr). Estimated OS (95% confidence interval [CI]) rates at 10 and 15 yr were 69% (62-76%) and 53% (45-62%) for RN compared with 80% (73-87%) and 74% (65-83%) following PN (p=0.032). After adjusting for covariates of interest, patients treated with RN were significantly more likely to die from any cause (hazard ratio [HR]: 1.75; 95% CI, 1.08-2.83; p=0.023) or develop stage IV CKD (HR: 4.23; 95% CI, 1.80-9.93; p<0.001) compared with patients who underwent PN. Limitations include the retrospective design, selection bias for surgical approach, and referral bias to a tertiary care facility. CONCLUSIONS: Our data suggest that PN may confer a clinical benefit for improved renal function and better OS compared with RN after excluding the confounding effect of malignancy.
European urology 12/2012; · 7.67 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the accuracy of the pathologic inclusion criteria from all contemporary adjuvant trials in predicting disease progression (DP) for renal cell carcinoma (RCC).
A retrospective review was conducted on 1363 patients treated surgically for M0 RCC at the Mayo Clinic (Rochester, MN), from 1990 to 2001. Clinicopathologic features were reviewed to determine eligibility for the following trials: ARISER, ASSURE, EVEREST, PROTECT, SORCE, and S-TRAC. DP was defined as local recurrence or distant metastasis after surgery. The ability of each trial's inclusion criteria to accurately predict DP was evaluated by the c (concordance) index.
From the Mayo Clinic cohort, we determined that 41%, 45%, 45%, 33%, 47%, and 23% of the patients would have been eligible for the ARISER, ASSURE, EVEREST, PROTECT, SORCE, and S-TRAC clinical trials, respectively. Overall, 23% of all patients experienced DP (n = 317). Among eligible patients, 53%, 44%, 44%, 57%, 43%, and 59% developed DP during follow-up and 10%, 6%, 6%, 13%, 6%, and 18% went onto DP while not being eligible for the ARISER, ASSURE, EVEREST, PROTECT, SORCE, and S-TRAC trials, respectively. The c index of each trial to accurately predict DP from the pathologic inclusion criteria of ARISER, ASSURE, EVEREST, PROTECT, SORCE, and S-TRAC were 0.751, 0.751, 0.751, 0.742, 0.745, and 0.691, respectively.
Although the pathologic inclusion criteria of contemporary adjuvant trials have notable differences, all 6 adjuvant trials demonstrated high predictive accuracy of DP. Overall, 43% to 59% of patients included for the adjuvant trials would develop DP, whereas 6% to 18% of patients excluded from the trials would develop DP during follow-up. Cancer 2012. © 2012 American Cancer Society.
Cancer 09/2012; 118(18):4412-20. · 4.77 Impact Factor
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ABSTRACT: Chromosomal rearrangements involving the anaplastic lymphoma kinase gene (ALK) at 2p23 result in fusion with various partner genes leading to aberrant production of oncogenic protein products in multiple tumor types. Recently, the ALK protein inhibitor crizotinib was shown to be an effective therapy in patients with ALK-rearranged non-small cell lung cancer. The goal of this study was to determine the frequency of ALK alterations in adult renal cell carcinoma (RCC) and define associated clinicopathologic features and outcome. RCCs from a cohort of 534 consecutive surgically treated adult patients were analyzed for alterations of ALK by fluorescence in situ hybridization. ALK rearrangements were identified in 2 of 534 (<1%) RCCs. Both showed similar histologic features and the patients had a poor outcome. ALK copy number gain was identified in 54 (10%) RCCs. In clear cell type RCC (CCRCC), ALK copy number gain was significantly associated with tumor size (P=0.02) and nuclear grade (P<0.001), and with a worse 10-year cancer-specific survival vs similar patients lacking ALK copy number gain (P=0.03). ALK rearrangement is rare in adult RCC but may be associated with distinct histological features and poor outcome. Another potential mechanism to elevate ALK expression, increased ALK gene copy number, was observed in 10% of adult CCRCC, where it is associated with a higher tumor grade and poorer outcome. Additional studies are necessary to determine whether patients RCCs with ALK rearrangement and/or those with an increase in ALK copy number would benefit from ALK inhibitor treatment.Modern Pathology advance online publication, 29 June 2012; doi:10.1038/modpathol.2012.107.
Modern Pathology 06/2012; · 4.79 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) with chromosomal rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) at Xp11.2 is a distinct subtype that was initially described in children and has been reported to display an indolent course. Recent reports have identified RCC with TFE3 rearrangements in adults and have suggested a more aggressive course in this population. However, only a few studies have examined these tumors in a large series of consecutively treated adults. We screened 632 RCCs from patients consecutively treated by surgery at a single institution by fluorescence in situ hybridization to detect TFE3 rearrangements. We identified 6 RCCs with TFE3 rearrangement. Patient ages ranged from 25 to 78 years and included 4 women and 2 men. Tumors showed significant histologic variability. Comparison of the clinical and pathologic features between RCCs with TFE3 rearrangements and RCCs without TFE3 rearrangements showed no significant differences. Follow-up period for patients with TFE3-rearranged RCC ranged from 0.8 to 16.5 years, with 4 of 6 dying from the disease. Cancer-specific survival for patients with TFE3-rearranged RCC was significantly worse than for patients with TFE3-rearrangement-negative papillary-type RCC (P<0.001) but not different from that for TFE3-rearrangement-negative clear cell-type RCC. In conclusion, we present an assessment of TFE3 rearrangement status in a large series of adults consecutively treated by surgery for RCC. Our findings confirm that RCCs with TFE3 rearrangement account for only approximately 1% of adult RCCs. The results also suggest that adult RCC with TFE3 rearrangement may be a clinically aggressive tumor.
The American journal of surgical pathology 05/2012; 36(5):663-70. · 4.06 Impact Factor
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ABSTRACT: To determine whether renal cell carcinoma (RCC) thrombi that reach the vena cava from the left kidney are associated with a greater risk of RCC death than equivalent thrombi from the right kidney.
Two hundred and fifty-nine patients treated with radical nephrectomy (1970-2006) for unilateral, sporadic RCC with level 1-4 RCC tumor thrombus were identified. Clinicopathologic features between patients with right-sided (N = 183) and left-sided (N = 76) thrombus were compared utilizing Wilcoxon rank sum and Fisher's exact tests. Associations with RCC-specific death using hazard ratios (HR) and 95 % confidence intervals (CIs) from Cox proportional hazards models were evaluated.
Left-sided RCC patients with thrombus are less likely to be clear cell subtype (85 % vs. 93 %; p = 0.013) and more likely to have nodal involvement (28 % vs. 16 %; p = 0.018) compared to right side RCC patients with thrombus. Overall, there is little evidence that the risk of RCC death is higher for left versus right-sided RCC thrombus (HR = 1.11; 95 % CI 0.81-1.53; p = 0.52). However, among those patients with a thrombus that has reached the vena cava (level III/IV), we observe evidence after multivariate adjustment that the risk of RCC death is higher for left versus right side patients (HR = 2.02; 95 % CI 0.91-4.47; p = 0.08).
Left side RCC with tumor thrombus is not associated with worse prognosis than right-sided tumors (all tumor thrombi levels). Our data suggest that among RCC patients with advanced tumor thrombi (level III/IV), a left side thrombus may be associated with worse prognosis compared to a right side thrombus.
International Urology and Nephrology 04/2012; 44(4):1005-12. · 1.47 Impact Factor
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ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There is great variability in the utilization of partial nephrectomy, but the causes of these variations are not well understood. The present study underscores the already observed phenomenon of surgical volume influencing surgical planning and outcomes, but it gets at why this might be so. We observe that high-volume renal surgeons have different thresholds of 'technical feasibility'. OBJECTIVE: • To investigate why there continues to be wide variability in the application of partial nephrectomy (PN) for treating small renal masses despite guidelines in the US and Europe stating that a PN is a standard of care for a patient with a T1 renal mass. PATIENTS AND METHODS: • In June 2009, 764 surgeon-members of the American Urologic Association (AUA) participated in a survey evaluating the management of renal masses. • Renal mass complexity was graded by nephrometry score (NS). • Multivariable logistic regression models with generalized estimating equations were constructed to evaluate how tumour, surgeon and practice-setting characteristics influence the use of PN. RESULTS: • The survey response rate was 19%. Each urological surgeon responded to eight scenarios, providing 6112 evaluable cases. • Tumour NS ranged from 4 to 10, and each unit increase in NS was associated with 59% increased likelihood of a surgeon offering RN on multivariable analysis (odds ratio [OR]= 1.59; 95% CI: 1.52-1.64). • When holding patient and tumour characteristics constant, the following surgeon and practice-setting characteristics significantly increased the odds of offering a PN: increasing renal case volume (OR = 1.57; 95% CI: 1.27-1.95), academic practice (OR = 1.80; 95% CI: 1.42-2.29), increasing PN % volume (OR = 3.7; 95% CI: 2.46-5.55) and younger surgeon age (≤40 vs >50 years) (OR = 1.64; 95% CI: 1.35-1.96). CONCLUSIONS: • The characteristics of a surgeon and the setting in which he or she practices influence the utilization of PN, the adherence to professional guidelines, and the threshold of tumour complexity at which a surgeon stops offering PN.
BJU International 04/2012; · 2.84 Impact Factor
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Lucy J Schmidt,
Kelly Duncan,
Neelu Yadav,
Kevin M Regan,
Alissa R Verone, Christine M Lohse,
Elena A Pop,
Kristopher Attwood,
Gregory Wilding,
James L Mohler,
Thomas J Sebo,
Donald J Tindall,
Hannelore V Heemers
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ABSTRACT: Recently, we have identified serum response factor (SRF) as a mediator of clinically relevant androgen receptor (AR) action in prostate cancer (PCa). Genes that rely on SRF for androgen responsiveness represent a small fraction of androgen-regulated genes, but distinguish benign from malignant prostate, correlate with aggressive disease, and are associated with biochemical recurrence. Thus, understanding the mechanism(s) by which SRF conveys androgen regulation to its target genes may provide novel opportunities to target clinically relevant androgen signaling. Here, we show that the small GTPase ras homolog family member A (RhoA) mediates androgen-responsiveness of more than half of SRF target genes. Interference with expression of RhoA, activity of the RhoA effector Rho-associated coiled-coil containing protein kinase 1 (ROCK), and actin polymerization necessary for nuclear translocation of the SRF cofactor megakaryocytic acute leukemia (MAL) prevented full androgen regulation of SRF target genes. Androgen treatment induced RhoA activation, increased the nuclear content of MAL, and led to MAL recruitment to the promoter of the SRF target gene FHL2. In clinical specimens RhoA expression was higher in PCa cells than benign prostate cells, and elevated RhoA expression levels were associated with aggressive disease features and decreased disease-free survival after radical prostatectomy. Overexpression of RhoA markedly increased the androgen-responsiveness of select SRF target genes, in a manner that depends on its GTPase activity. The use of isogenic cell lines and a xenograft model that mimics the transition from androgen-stimulated to castration-recurrent PCa indicated that RhoA levels are not altered during disease progression, suggesting that RhoA expression levels in the primary tumor determine disease aggressiveness. Androgen-responsiveness of SRF target genes in castration-recurrent PCa cells continued to rely on AR, RhoA, SRF, and MAL and the presence of intact SRF binding sites. Silencing of RhoA, use of Rho-associated coiled-coil containing protein kinase 1 inhibitors, or an inhibitor of SRF-MAL interaction attenuated (androgen-regulated) cell viability and blunted PCa cell migration. Taken together, these studies demonstrate that the RhoA signaling axis mediates clinically relevant AR action in PCa.
Molecular Endocrinology 03/2012; 26(5):716-35. · 4.54 Impact Factor
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ABSTRACT: It has been reported that Fuhrman grading is not appropriate for chromophobe renal cell carcinoma (RCC). The objective of this study was to determine whether nucleolar grading and the recently described chromophobe RCC grading system by Paner and colleagues provide prognostic information. Pathologic features of 185 patients with chromophobe RCC treated surgically between 1970 and 2006 were reviewed, including nucleolar grade, chromophobe RCC grade, the 2010 TNM groupings, sarcomatoid differentiation, and coagulative tumor necrosis. Cancer-specific (CS) survival was estimated using the Kaplan-Meier method, and associations with CS survival were evaluated using Cox proportional hazard regression models. Twenty-three patients died from RCC at a mean of 3.0 years after surgery (median 1.3; range 0 to 16) with estimated CS rates (95% confidence interval) of 89% (84 to 94), 86% (81 to 92), and 85% (78 to 91) at 5, 10, and 15 years after surgery. Univariate associations with CS survival included the 2010 TNM stage groupings, sarcomatoid differentiation, coagulative tumor necrosis, chromophobe RCC grade, and nucleolar grade (all P<0.001). These last 4 features remained significantly associated with CS survival after adjusting for the 2010 TNM stage groupings. When the analysis was restricted to the 155 patients with nonsarcomatoid TNM stage groupings I and II chromophobe RCC, only stage grouping (I vs. II) was significantly associated with CS survival (P=0.03). Although the chromophobe RCC grading system described by Paner and colleagues and nucleolar grade are associated with CS survival in chromophobe RCC, they add no additional prognostic information once TNM stage and sarcomatoid differentiation are assessed.
The American journal of surgical pathology 02/2012; 36(6):851-6. · 4.06 Impact Factor
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ABSTRACT: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three-dimensional tumour volume (cm(3) ) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC-specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC.
• To address whether information on three-dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone.
• We identified 955 patients treated with radical nephrectomy or nephron-sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non-cystic clear-cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients. • We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis. • Univariate and multivariable associations with RCC-specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs).
• Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30-15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83-7.85; P= 0.10). • Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients. • Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC-specific death were similar. • Multivariable adjustment did not alter our findings.
• Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC. • Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.
BJU International 02/2012; 110(7):956-60. · 2.84 Impact Factor
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ABSTRACT: 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.
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).
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).
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.
Urology 02/2012; 79(2):356-60. · 2.43 Impact Factor
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ABSTRACT: We determined the clinical and pathological features associated with death from papillary renal cell carcinoma in 395 surgically treated patients.
Papillary renal cell carcinoma tissue slides from each patient were reviewed for type (1 or 2), grade, TNM stage, coagulative tumor necrosis and sarcomatoid differentiation. Associations of clinical and pathological features with death from renal cell carcinoma were evaluated using Cox proportional hazards regression models and summarized by the HR and 95% CI. Cancer specific survival was estimated using the Kaplan-Meier method.
Univariate analysis revealed that symptoms, tumor thrombus, tumor size, perinephric/renal sinus fat invasion, 2010 primary tumor classification, regional lymph node involvement, distant metastasis, 2010 TNM stage group, grade, tumor necrosis, sarcomatoid differentiation and papillary renal cell carcinoma type were associated with death from renal cell carcinoma. Grade was more strongly associated with death from renal cell carcinoma than papillary renal cell carcinoma type. Multivariate analysis indicated that symptoms, 2010 TNM stage group and grade jointly were significantly associated with death from renal cell carcinoma.
This large series of patients with papillary renal cell carcinoma reveals features associated with death from renal cell carcinoma and confirms that grade is more predictive of outcome than papillary renal cell carcinoma type.
The Journal of urology 11/2011; 187(1):54-9. · 4.02 Impact Factor
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ABSTRACT: Partial nephrectomy is the recommended management for small renal masses. Percutaneous ablation is safe and effective with comparable short-term cancer specific survival. Currently to our knowledge data are lacking on the impact of thermal ablation on renal function preservation. We examined the impact on renal function of partial nephrectomy vs percutaneous ablation in patients with a solitary kidney.
We performed a retrospective review to identify patients with a solitary kidney who underwent partial nephrectomy or percutaneous ablation at Mayo Clinic Rochester between 2003 and 2009. Preoperative characteristics and 3-month posttreatment renal function were compared using the Wilcoxon rank sum, chi-square and Fisher exact tests.
During the study period 50 patients underwent percutaneous ablation and 62 underwent partial nephrectomy. At partial nephrectomy no ischemia was used in 30 cases (48%), a median of 28 minutes of cold ischemia was used in 26 (42%) and a median of 18 minutes of warm ischemia was used in 6 (10%). Patients who underwent partial nephrectomy were younger (median age 62.5 vs 68.5 years, p = 0.01) and harbored larger tumors (median 3.5 vs 2.5 cm, p = 0.005) with higher nephrometry scores (median 9 vs 7, p = 0.03). At 3-month posttreatment followup no differences were noted between the 2 groups in glomerular filtration rate (p = 0.91), change in glomerular filtration rate (p = 0.77) or change in chronic kidney disease stage (p = 0.87). Similar results were observed when adjusting for age, tumor size and nephrometry score on multivariate analysis.
With judicious use of ischemia partial nephrectomy, even for more complex tumors, has short-term renal function outcomes similar to those of percutaneous ablation.
The Journal of urology 09/2011; 186(5):1786-90. · 4.02 Impact Factor
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ABSTRACT: To characterize the incidence and clinicopathologic factors associated with late recurrence after surgical resection for renal cell carcinoma (RCC) because the recurrence patterns >5 years after nephrectomy have been poorly described.
We identified 1454 patients treated with nephrectomy for localized RCC from 1970 to 2000 who had remained free of disease for 5 years. Subsequent tumor recurrence was classified as renal recurrence and distant metastasis. The incidence of recurrence >5 years from surgery was estimated using the Kaplan-Meier method. The associations of clinicopathologic variables with late recurrence were analyzed using Cox proportional hazard regression models.
With a median postoperative follow-up of 13.9 years (range 5.1-38.9), 63 patients (4.3%) experienced late renal recurrence at a median of 9.3 years (range 5.1-25.3), and 172 patients (11.8%) developed late distant metastases at a median of 9.6 years (range 5.1-26.6) after surgery. The estimated recurrence-free survival rate at 10 and 15 years was 97.3% and 95.2% for renal recurrence, and 93.1% and 85.9% for distant metastases, respectively. On multivariate analysis, increased tumor size (hazard ratio [HR] 1.12; P < .001) was associated with late renal tumor recurrence, and increased tumor size (HR 1.07; P = .018), clear cell or collecting duct histologic features (HR 3.76; P < .001), and tumor Stage pT1b (HR 2.8; P < .001), pT2a (HR 4.5; P < .001), pT2b (HR 3.4; P = .007), and pT3-pT4 (HR 5.1; P < .001) were associated with distant metastasis.
After an initial 5-year postoperative disease-free interval, approximately 5% and 15% of patients will develop renal recurrence and distant metastases, respectively, during the next decade. Therefore, long-term surveillance remains necessary after nephrectomy.
Urology 09/2011; 78(5):1101-6. · 2.43 Impact Factor
