Our objective was to compare cancer-specific survival and to examine associations with outcome among the histologic subtypes of renal cell carcinoma (RCC). We studied 2385 patients whose first surgery between 1970 and 2000 was a radical nephrectomy for sporadic, unilateral RCC. All RCC tumors were classified following the 1997 Union Internationale Contre le Cancer and American Joint Committee on Cancer guidelines. There were 1985 (83.2%) patients with clear cell, 270 (11.3%) with papillary, 102 (4.3%) with chromophobe, 6 (0.3%) with collecting duct, 5 (0.3%) with purely sarcomatoid RCC and no underlying histologic subtype, and 17 (0.7%) with RCC, not otherwise specified. Cancer-specific survival rates at 5 years for patients with clear cell, papillary, and chromophobe RCC were 68.9%, 87.4%, and 86.7%, respectively. Patients with clear cell RCC had a poorer prognosis compared with patients with papillary and chromophobe RCC (p <0.001). This difference in outcome was observed even after stratifying by 1997 tumor stage and nuclear grade. There was no significant difference in cancer-specific survival between patients with papillary and chromophobe RCC (p = 0.918). The 1997 TNM stage, tumor size, presence of a sarcomatoid component, and nuclear grade were significantly associated with death from clear cell, papillary, and chromophobe RCC. Histologic tumor necrosis was significantly associated with death from clear cell and chromophobe RCC, but not with death from papillary RCC. Our results demonstrate that there are significant differences in outcome and associations with outcome for the different histologic subtypes of RCC, highlighting the need for accurate subtyping.

As tumor size increased there was a significant increase in the odds of having a malignant compared to a benign tumor, clear cell compared to papillary RCC and high grade compared to low grade malignancy.

In patients with clear cell renal cell carcinoma 1997 TNM stage, tumor size, nuclear grade and histological tumor necrosis were significantly associated with cancer specific survival. We present a scoring system based on these features that can be used to predict outcome.

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor. (Cancer Res 2006; 66(7): 3381-5)

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and͞or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and͞or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94 -10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre-and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.costimulation ͉ immunotherapy ͉ T lymphocyte ͉ tumor biomarker

OBJECTIVETo report the surgical management, complications and outcomes over three decades by tumour thrombus level for patients with renal cell carcinoma (RCC) and renal venous extension, as surgery is the most effective treatment. PATIENTS AND METHODSWe assessed 540 patients who underwent surgical resection for RCC with renal venous extension between 1970 and 2000. Early and late surgical complications, including operative mortality, were compared with tumour thrombus level using the chi-square, Fisher's exact and Wilcoxon rank-sum tests. Cancer-specific survival was estimated using the Kaplan-Meier method and compared across tumour thrombus levels using log-rank tests. RESULTSThere were 349 (64.6%) patients with level 0 thrombus and 191 (35.4%) with inferior vena cava thrombus, including 66 (12.2%) with level I, 77 (14.3%) with level II, 28 (5.2%) with level III, and 20 (3.7%) with level IV thrombus. Patients with a higher thrombus level had more early surgical complications (respectively for level 0 to IV, 8.6%, 15.2%, 14.1%, 17.9% and 30.0%, P < 0.001). However, there was no statistically significant difference in the incidence of late complications by thrombus level ( P = 0.445). The incidence of any early surgical complication decreased from 13.4% for patients treated in 1970-1989 to 8.1% for those treated in 1990-2000 ( P = 0.064); the respective operative mortality decreased from 3.8% to 2.0% ( P = 0.260), and in patients with inferior vena cava thrombus, from 8.1% to 3.8% ( P = 0.227). The respective duration of hospitalization decreased from a median of 8 to 7 days ( P < 0.001) but the incidence of late complications increased significantly over time ( P < 0.001.) Among patients with clear cell RCC, the respective estimated 5-year cancer-specific survival rates ( SE , number still at risk) for patients with level 0 to IV thrombus were 49.1 (3.0)% (125), 31.7 (6.4)% (14), 26.3 (6.1)% (11), 39.4 (10.7)% (7) and 37.0 (12.9)% (5), ( P = 0.028). There was a statistically significant difference in outcome for patients with level 0 vs those with level > 0 thrombus ( P = 0.002), but there was no significant difference in outcome by thrombus level among patients with inferior vena cava tumour thrombus ( P = 0.868).The Mayo clinic experience with renal carcinoma and venous tumour thrombus is presented in this section. The authors show that the surgical management of these patients continues to develop, and that complications and mortality are decreasing. They also show that cancer-specific survival is better with renal vein involvement only, as compared with vena caval involvement.

BACKGROUNDThe objective of the current study was to develop an algorithm to predict progression to metastases after radical nephrectomy for patients with clinically localized renal cell carcinoma (RCC) to allow stratification of patients for potential adjuvant therapy trials.METHODSThe authors identified 1671 sporadic patients with clinically localized, unilateral clear cell RCC who underwent radical nephrectomy between 1970 and 2000. The clinical features examined included age, gender, smoking history, recent onset hypertension, performance status, and presenting symptoms. The pathologic features examined included surgical margins, tumor stage, regional lymph node status, tumor size, nuclear grade, histologic tumor necrosis, sarcomatoid component, cystic architecture, and multifocality. Metastases free survival was estimated using the Kaplan–Meier method. A multivariate Cox proportional hazards regression model was fit to determine associations between the clinical and pathologic features and distant metastases.RESULTSThe median follow‐up was 5.4 years (range, 0–31 years). Metastases occurred in 479 patients at a median of 1.3 years (range, 0–25 years) after nephrectomy. The estimated metastases free survival rates were 86.9% at 1 year, 77.8% at 3 years, 74.1% at 5 years, 70.8% at 7 years, and 67.1% at 10 years. Multivariate analysis showed that the following features were associated with progression to metastases: tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis (P < 0.001 for all).CONCLUSIONSIn patients with clear cell RCC, tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis showed statistically significant associations with progression to metastatic RCC. The authors present a scoring algorithm based on these features that can be used to predict disease progression after patients undergo radical nephrectomy for clinically localized clear cell RCC. Cancer 2003;97:1663–71. © 2003 American Cancer Society.DOI 10.1002/cncr.11234

Objective L‐dopa is the most widely used and most effective therapy for Parkinson disease (PD), but chronic treatment is associated with motor complications in the majority of patients. It has been hypothesized that providing more continuous delivery of L‐dopa to the brain would reduce the risk of motor complications, and that this might be accomplished by combining L‐dopa with entacapone, an inhibitor of catechol‐O‐methyltransferase, to extend its elimination half‐life. Methods We performed a prospective 134‐week double‐blind trial comparing the risk of developing dyskinesia in 747 PD patients randomized to initiate L‐dopa therapy with L‐dopa/carbidopa (LC) or L‐dopa/carbidopa/entacapone (LCE), administered 4× daily at 3.5‐hour intervals. The primary endpoint was time to onset of dyskinesia. Results In comparison to LC, patients receiving LCE had a shorter time to onset of dyskinesia (hazard ratio, 1.29; p = 0.04) and increased frequency at week 134 (42% vs 32%; p = 0.02). These effects were more pronounced in patients receiving dopamine agonists at baseline. Time to wearing off and motor scores were not significantly different, but trended in favor of LCE treatment. Patients in the LCE group received greater L‐dopa dose equivalents than LC‐treated patients (p < 0.001). Interpretation Initiating L‐dopa therapy with LCE failed to delay the time of onset or reduce the frequency of dyskinesia compared to LC. In fact, LCE was associated with a shorter time to onset and increased frequency of dyskinesia compared to LC. These results may reflect that the treatment protocol employed did not provide continuous L‐dopa availability and the higher L‐dopa dose equivalents in the LCE group. ANN NEUROL 2010;68:18–27