Biomedical subjects

Eugene D Kwon

Publications and source records attributed to Eugene D Kwon.

30 records · Page 2Linked to original sources

PubMed2005

pT2 classification for renal cell carcinoma. Can its accuracy be improved?

PURPOSE: The 2002 tumor classification for renal cell carcinoma (RCC) classifies pT2 tumors as more than 7 cm in greatest dimension, limited to the kidney. In this study we determined whether a size cutoff point exists within pT2 tumors and whether such subclassification would further improve the accuracy of the current tumor classification. MATERIALS AND METHODS: We studied 544 patients with unilateral, sporadic pT2 RCC treated with radical nephrectomy or nephron sparing surgery between 1970 and 2000. The association of tumor size with death from RCC was examined using martingale residuals from a Cox proportional hazards regression model to determine the optimal size cutoff point. RESULTS: There were 204 deaths from RCC a median of 3.8 years following nephrectomy. Univariately tumor size was significantly associated with death from RCC (risk ratio 1.08, 95% CI 1.04 to 1.13, p <0.001). A scatterplot of tumor size vs expected risk of death per patient suggested that a cutoff point between 9 and 10 cm was appropriate. When adjusted for regional lymph node involvement and distant metastases, the 10 cm cutoff point performed better than the 9 cm point (risk ratio 1.42, 95% CI 1.07 to 1.90, p = 0.017 vs 1.22, 95% 0.86 to 1.72, p = 0.268). Therefore, we propose using a 10 cm cutoff point to subclassify patients into pT2a and pT2b. CONCLUSIONS: Our data suggest that the prognostic accuracy of the 2002 pT2 tumor classification can be further improved by subclassifying patients with tumors greater than 7 and less than 10 cm into a pT2a category, and those with tumors 10 cm or greater into a pT2b category.

Carcinoma, Renal Cell↗

PubMed2005

Cancer specific survival for patients with pT3 renal cell carcinoma-can the 2002 primary tumor classification be improved?

PURPOSE: The 2002 primary tumor classification for renal cell carcinoma (RCC) does not distinguish between patients with tumor thrombus involving the renal vein only and those with inferior vena cava tumor thrombus below the diaphragm. We evaluated the association of tumor thrombus level and fat invasion with outcome to determine if further subclassification would improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied 675 patients treated with radical nephrectomy or nephron sparing surgery for pT3a (206, 30.5%), pT3b (422, 62.5%), pT3c (19, 2.8%) or pT4 (28, 4.2%) RCC at the Mayo Clinic between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression. RESULTS: There were 531 deaths from RCC at a median of 1.5 years following nephrectomy. Patients with pT3b RCC and level I, II or III tumor thrombus were significantly more likely to die of RCC compared to patients with pT3b RCC and level 0 tumor thrombus (risk ratio 1.62, p <0.001). Patients with peripheral perinephric or renal sinus fat invasion were also more likely to die of RCC compared to patients without fat invasion (risk ratio 1.87, p <0.001). Therefore, patients with pT3 RCC were reclassified into 4 groups as thrombus level 0 without fat invasion, fat invasion only, thrombus level 0 with fat invasion or thrombus level I, II or III without fat invasion, and thrombus level I, II or III with fat invasion or thrombus level IV. This reclassification significantly improved prediction of death from RCC compared with the current classification (c indexes of 0.61 versus 0.55, respectively). CONCLUSIONS: Further subclassification of the primary tumor classification for patients with pT3 RCC improved prognostic accuracy.

Carcinoma, Renal Cell↗

PubMed2005

Should direct ipsilateral adrenal invasion from renal cell carcinoma be classified as pT3a?

PURPOSE: The 2002 American Joint Committee on Cancer primary tumor classification for renal cell carcinoma (RCC) defines a tumor as pT3a if it invades the perinephric or renal sinus fat or directly invades the ipsilateral adrenal gland. In the current study we evaluated the association of direct ipsilateral adrenal invasion with outcome to determine if reclassification of these tumors as pT4 would improve the accuracy of the current tumor classification. MATERIALS AND METHODS: We studied 424 patients who underwent nephrectomy and adrenalectomy for unilateral, sporadic, pT3 or pT4 RCC between 1970 and 2000 at the Mayo Clinic. Cancer specific survival was estimated using the Kaplan-Meier method. RESULTS: Cancer specific survival for the 22 patients with pT3a or pT3b tumors that directly invaded the ipsilateral adrenal gland was significantly worse compared with that of patients with pT3a (p <0.001) or pT3b (p = 0.011) disease that did not invade the adrenal gland. There was no significant difference in the 5-year cancer specific survival between the patients with pT3a or pT3b tumors that directly invaded the ipsilateral adrenal gland and patients with pT4 tumors (cancer specific survival rates of 20% and 14%, respectively, p = 0.490). CONCLUSIONS: Although rare, RCC with direct ipsilateral adrenal invasion behaves more aggressively than tumors involving perinephric or renal sinus fat. We believe that RCC tumors with direct adrenal invasion should be classified as pT4.

Adrenal Gland Neoplasms↗

PubMed2005

Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses.

PURPOSE: We compared histological subtype, pathological features and outcome of patients with solid renal masses who were 18 to 40 years old vs patients who were 60 to 70 years old. MATERIALS AND METHODS: We conducted a retrospective review of the Mayo Clinic Nephrectomy Registry from 1970 to 2000, and identified 124 patients 18 to 40 years old and 1,067 patients 60 to 70 years old available for analysis. RESULTS: There was no significant difference in the incidence of benign solid renal masses between patients 18 to 40 years old and those 60 to 70 years old (13.7% vs 10.2%). Among patients with renal cell carcinoma (RCC), younger patients were more likely to have chromophobe RCC (13.1% vs 3.6%) and less likely to have clear cell RCC (70.1% vs 81.5%) than older patients. Among patients with clear cell RCC, younger patients were more likely to have stage pT2b or lower tumors (82.7% vs 69.9%) and a higher incidence of cystic clear cell RCC (10.7% vs 2.2%) than older patients. Younger patients had an improved cancer specific survival compared with older patients but this difference was not statistically significant (risk ratio 0.71, p =0.127). CONCLUSIONS: We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.

Adenocarcinoma, Clear Cell↗

PubMed2005

Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma?

PURPOSE: Perinephric and renal sinus fat invasion are classified as pT3a renal cell carcinoma (RCC) according to the 2002 American Joint Committee on Cancer. We investigated the prognostic significance of each of these pathological features using a cohort of pT3a patients. MATERIALS AND METHODS: Between 1970 and 2002, 205 patients without direct adrenal invasion underwent nephrectomy for pT3a clear cell RCC. The associations of fat invasion with death from RCC were evaluated using Cox proportional hazards regression models. RESULTS: Of the 162 patients with perinephric fat invasion and 43 patients with renal sinus fat invasion 95 (59%) and 31 (72%), respectively, died of RCC. Patients with renal sinus fat invasion were 63% more likely to die of RCC compared with those with perinephric fat invasion (RR 1.63, 95% CI 1.09-2.46, p=0.018). In addition, the risk of death persisted in multivariate analysis after adjusting for regional lymph nodes and distant metastases (RR 1.91, 95% CI 1.26-2.89, p=0.002) and after adjusting for the Mayo Clinic SSIGN (stage, size, grade and necrosis) score (RR 1.90, 95% CI 1.25-2.88, p=0.003). CONCLUSIONS: Our results indicate that clear cell tumors invading the renal sinus fat are more aggressive than tumors with perinephric fat involvement. We believe both of these features should be individually assessed during routine pathological examination. External validation is needed before suggesting a change to the TNM staging system.

Adipose Tissue↗

PubMed2005

A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials.

PURPOSE: We developed a clinically useful scoring algorithm to predict cancer specific survival for patients with clear cell metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: We studied 727 patients treated with radical nephrectomy for clear cell RCC from 1970 to 2000 who had distant metastases at nephrectomy (285) or in whom metastases subsequently developed (442). A scoring algorithm to predict cancer specific survival was developed using the regression coefficients from a Cox proportional hazards model. RESULTS: There were 606 deaths from clear cell RCC at a median of 1.0 years (range 0 to 14) following metastatic RCC. Constitutional symptoms at nephrectomy (+2), metastases to the bone (+2) or liver (+4), metastases in multiple simultaneous sites (+2), metastases at nephrectomy (+1) or within 2 years of nephrectomy (+3), complete resection of all metastatic sites (-5), tumor thrombus level I to IV (+3), and the primary pathological features of nuclear grade 4 (+3) and histological tumor necrosis (+2) were significantly associated with death from RCC. All patients started with a score of 0 and points were added or subtracted as indicated in parentheses. Cancer specific survival rates at 1 year were 85.1%, 72.1%, 58.8%, 39.0%, and 25.1%, respectively, for patients with scores of -5 to -1, scores of 0 to 2, scores of 3 to 6, scores of 7 or 8, and scores of 9 or more. CONCLUSIONS: This scoring algorithm can be used to predict cancer specific survival for patients with metastatic clear cell RCC.

Adenocarcinoma, Clear Cell↗

PubMed2004

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.

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 and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or 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.

Antigens, CD↗

PubMed2004

Augmentation of T cell levels and responses induced by androgen deprivation.

Androgen has been implicated as a negative regulator of host immune function and a factor contributing to the gender dimorphism of autoimmunity. Conversely, androgen deprivation has been suggested to potentiate male host immunity. Studies have shown that removal of androgen in postpubertal male mice produces an increase in size and cellularity of primary and peripheral lymphoid organs, and enhances a variety of immune responses. Yet, few details are known about the effect of androgen removal on T cell-mediated immunity. In this study, we demonstrate two pronounced and independent alterations in T cell immunity that occur in response to androgen deprivation, provided by castration, in postpubertal male mice. First, we show that levels of T cells in peripheral lymphoid tissues of mice are increased by androgen deprivation. Second, T cells from these mice transiently proliferate more vigorously to TCR- and CD28-mediated costimulation as well as to Ag-specific activation. In addition, androgen deprivation accelerates normalization of host T and B cell levels following chemotherapy-induced lymphocyte depletion. Such alterations induced by androgen deprivation may have implications for enhancing immune responses to immunotherapy and for accelerating the recovery of the immune system following chemotherapy.

Androgens↗

PubMed2004

Immunotherapy for urological malignancies.

PURPOSE: For decades urologists have successfully used immunotherapy in the battle against cancer. Interleukin-2 in renal cell carcinoma and bacillus Calmette-Guerin in bladder cancer are standard primary and/or adjunctive therapies for these diseases. Recent advances in our understanding of mechanisms governing immune system activation have fostered a myriad of novel immunotherapeutic approaches that show great promise in vivo but have had limited success in human trials to date. This review highlights current immunotherapy strategies that may prove to be successful treatments for urological cancers. MATERIALS AND METHODS: We performed a MEDLINE literature search for articles relating to immunotherapy in bladder, prostate and renal cell carcinoma in animals and humans. We included the most promising developments in this review. RESULTS: In addition to combining existing therapies to improve their efficacy, novel approaches that attempt to exploit the immune system ability to identify, target and eradicate malignancies are now being developed. These therapies include the use of antitumoral monoclonal and bi-specific antibodies, manipulation of T-lymphocyte costimulatory molecules and the administration of newly discovered cytokines as well as the development of antitumor vaccines. CONCLUSIONS: To date the full potential of immunotherapy for the treatment of urological malignancies has not been recognized. As our knowledge of the immune system expands, so too may our ability to manipulate it to affect tumor regression. This review describes the most recent and most promising developments in immunotherapy for urological malignancies.

Animals↗

PubMed2003

Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials.

BACKGROUND: The 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. METHODS: The 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. RESULTS: The 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). CONCLUSIONS: In 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.

Adenocarcinoma, Clear Cell↗

PubMed2003

Prostate cancer: advances in immunotherapy.

The absence of curative therapies for advanced or recurrent forms of prostate cancer has prompted a vigorous search for novel treatment strategies. Immunotherapy encompasses one particularly promising systemic approach to the treatment of prostate cancer. Immune-based strategies for treating prostate cancer have recently been facilitated by the identification of a number of prostate tissue/tumour antigens that can be targeted, either by antibody or T cells, to promote prostate tumour cell injury or death. These same prostate antigens can also be used for the construction of vaccines to induce prostate-specific T cell-mediated immunity. Greater insight into specific mechanisms that govern antigen-specific T cell activation has brought with it a number of innovative methods to induce and enhance T cell-mediated responses against prostate tumours. For instance, autologous dendritic cells loaded with prostate antigens have proved useful to induce prostate-specific T cell activation. Similarly, in vivo manipulations of T cell costimulatory pathway receptors can greatly facilitate tumour-specific T cell activation and potentiate T cell-mediated responses against a number of malignancies, including prostate cancer. For example, blocking T cell cytotoxic lymphocyte-associated antigen 4 (CTLA-4) receptor binding to its ligand prevents the down-regulation of T cell responses and can even potentiate T cell antitumoural immunity in mouse models of prostate cancer. Androgen ablation (AA) may induce prostate tumour/tissue-specific T cell mediated inflammation and, as such, a phase II trial is currently in progress to ascertain whether CTLA-4 blockade can enhance AA-induced treatment responses in patients with advanced prostate cancer. Nevertheless, further basic and clinical investigation is still required to establish immunotherapy as a true prostate cancer treatment option.

Androgens↗

PubMedDate not supplied

Anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy for the treatment of prostate cancer.

Costimulatory pathway ligands and receptors can deliver either positive or negative signals to help determine the ultimate fate of activated T lymphocytes. Cytotoxic T lymphocyte antigen-4 (CTLA-4) represents one of the most extensively studied receptors in the costimulatory pathway and has recently been shown to function as a potent inhibitor of T cell-mediated immunity. T-cell expression of CTLA-4 indirectly facilitates tumor progression by restraining host antitumoral immunity. In contrast, administration of a monoclonal antibody to block CTLA-4 function can alleviate restraints on T-cell activity to promote immune-mediated tumor regression. We review the preclinical and clinical experience with CTLA-4 blockade as a promising immunotherapeutic approach to treat patients with advanced prostate cancer.

Animals↗