Biomedical subjects

Christine M Lohse

Publications and source records attributed to Christine M Lohse.

At least 19 recordsLinked to original sources

PubMed2007

Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma.

PURPOSE: The accuracy of the pT3a primary tumor classification for renal cell carcinoma has been questioned recently. We investigated the association of perinephric and renal sinus fat invasion with death from renal cell carcinoma independent of tumor size. MATERIALS AND METHODS: We identified 2,165 patients treated with open radical nephrectomy or nephron sparing surgery for clinically localized, sporadic pT1a, pT1b, pT2 or pT3a renal cell carcinoma between 1970 and 2002. Patients with pT3a disease were then subdivided into 3 groups according to tumor size to match the size definitions for the pT1a, pT1b and pT2 tumor classifications. RESULTS: There were 834 patients with pT1a RCC, 674 with pT1b, 494 with pT2 and 163 with pT3a RCC. At last followup 317 patients died of RCC at a median of 3.8 years following surgery. The median followup among the 1,087 patients still alive at last followup was 7.8 years (range 0 to 34). The risk ratios (95% CI) for the association between fat invasion and death from RCC among patients with tumors 4 cm or smaller, 4 to 7 cm and more than 7 cm were 6.15 (1.84-20.50, p = 0.003), 4.12 (2.50-6.78, p <0.001) and 2.13 (1.53-2.97, p <0.001), respectively. These associations remained statistically significant in a multivariate analysis that included nuclear grade and histological coagulative tumor necrosis. CONCLUSIONS: Peripheral perinephric and renal sinus fat invasion was associated with death from RCC independent of tumor size. Our data contradict reports suggesting that pT3a tumors should be reclassified according to tumor size only.

Aged↗

PubMed2007

The impact of ischemia time during open nephron sparing surgery on solitary kidneys: a multi-institutional study.

PURPOSE: The safe duration of ischemia during nephron sparing surgery remains controversial. We performed a multi-institutional study to evaluate the renal effects of vascular clamping in patients with solitary kidneys. MATERIALS AND METHODS: Using the Cleveland Clinic and Mayo Clinic databases, we identified 537 patients with solitary kidneys who underwent open nephron sparing surgery. Renal complications were compared among patients who did not require vascular clamping (85), and those who had warm ischemia (174) and cold ischemia (278). RESULTS: Median patient age (63, 65, 64 years) and preoperative creatinine (1.4, 1.3, 1.4 mg/dl) were similar among patients with no ischemia, warm ischemia and cold ischemia, respectively. Median tumor size was smaller in patients with no ischemia (2.5 cm), compared to patients with warm (3.5 cm) and cold (4.0 cm) ischemia (p <0.001). Warm and cold ischemia was associated with a significantly increased risk of urine leak (p = 0.006), acute (p <0.001) and chronic (p = 0.027) renal failure, and temporary dialysis (p = 0.028) compared to patients with no ischemia. Warm ischemia longer than 20 minutes and cold ischemia longer than 35 minutes were associated with a higher incidence of acute renal failure (p = 0.002 and p = 0.003, respectively). Additionally, warm ischemia more than 20 minutes was associated with an increased risk of chronic renal insufficiency (41% vs 19%, p = 0.008), increase in creatinine greater than 0.5 (42% vs 15%, p <0.001) and permanent dialysis (10% vs 4%, p = 0.145). CONCLUSIONS: Vascular clamping during open nephron sparing surgery is associated with a higher incidence of renal complications. Attempts to limit warm ischemia to 20 minutes and cold ischemia to 35 minutes should be used when vascular clamping is necessary.

Adult↗

PubMed2007

Dynamic outcome prediction in patients with clear cell renal cell carcinoma treated with radical nephrectomy: the D-SSIGN score.

PURPOSE: To date all prediction models for patients with renal cell carcinoma have estimated outcome in static fashion starting from the date of surgery only. We created a dynamic outcome prediction model for continual surveillance that accounts for the disease-free interval following surgery. MATERIALS AND METHODS: We identified 1,560 patients treated with radical nephrectomy for pM0 clear cell renal cell carcinoma between 1970 and 1999. The previously published stage, size, grade and necrosis score was used to stratify patients according to the risk of death from renal cell carcinoma. Cancer specific survival rates were calculated using the Kaplan-Meier method at surgery and at various disease-free intervals following surgery. RESULTS: At last followup 461 of the 1,560 patients had died of renal cell carcinoma at a median of 3.1 years following surgery. Median followup in patients still alive was 11.2 years. Patient outcome improved as the disease-free interval following surgery increased. For example, patients with a stage, size, grade and necrosis score of 5 had an estimated 5-year cancer specific survival rate of 69.6% at surgery. However, those who survived without disease for 1, 2 and 3 years following surgery had adjusted estimated 5-year cancer specific survival rates of 81.9%, 91.9% and 93.2%, respectively. Patients with a stage, size, grade and necrosis score of 7 had a 5-year cancer specific survival rate of 44.9% at surgery, which increased to 63.3%, 71.0% and 72.8% after 1 to 3 years of disease-free followup, respectively. CONCLUSIONS: Within each stage, size, grade and necrosis score cancer specific survival rates increase as the disease-free interval following surgery increases. We present a dynamic outcome prediction model that allows clinicians to continually adjust surveillance as the disease-free interval increases.

Adult↗

PubMed2006

Lower expression levels of the transforming growth factor beta receptor type II protein are associated with a less aggressive tumor phenotype and improved survival among patients with clear cell renal cell carcinoma.

Loss of expression of the transforming growth factor beta type II receptor (TbetaRII) has been implicated as an important event in renal carcinogenesis; however, its role as a potential prognostic factor remains poorly understood. Using archived tumor samples and long-term follow-up on a cohort of 280 clear cell renal cell carcinoma (ccRCC) patients treated with surgery from 1980 to 1998, we evaluated the association of TbetaRII expression and cancer-specific survival in both a univariate and multivariate setting. Low tumor expression of TbetaRII is associated with a less aggressive tumor phenotype at time of surgery. Moreover, those patients with lower levels of TbetaRII expression experience better cancer-specific survival than patients with higher levels of TbetaRII expression (log rank P = .034). Based on a Cox proportional hazard model adjusting for age, patients with tumors showing low (hazard ratio, 0.49; 95% confidence interval, 0.27-0.88) and moderate (hazard ratio, 0.7; 95% confidence interval, 0.40-1.23) TbetaRII expression are at decreased risk of RCC death compared with patients with tumors having high levels of TbetaRII expression. Adjustment for well-known pathologic predictors of RCC outcome attenuates the association of TbetaRII expression and ccRCC survival. Of interest, the association with TbetaRII expression appears more pronounced among those patients with tumors showing less aggressive phenotypes. Data from this investigation are the first to suggest that loss of TbetaRII expression is associated with improved ccRCC patient survival, especially among those patients with less aggressive disease profiles at time of surgery.

Adult↗

PubMed2006

Mononuclear cell infiltration in clear-cell renal cell carcinoma independently predicts patient survival.

BACKGROUND: The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. METHODS: A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. RESULTS: At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P < .001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028). CONCLUSIONS: Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC.

Carcinoma, Renal Cell↗

PubMed2006

High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma.

BACKGROUND: In a previous study of gene array data, the authors identified survivin as a candidate marker of aggressiveness in clear cell renal cell carcinoma (ccRCC). What remained in question was whether survivin expression at the protein level is an independent predictor of disease progression and cancer-specific survival. METHODS: Between 1990 and 1994, 312 patients underwent nephrectomy for ccRCC at Mayo Clinic Rochester and had paraffin tissue available. The authors performed immunohistochemistry with antisurvivin antibody, quantitated the expression by using an image-analysis system, and analyzed the association of survivin expression with disease progression and cancer-specific survival. RESULTS: Within the cohort, 97 patients (31.1%) had high levels of survivin expression. Patients who had high survivin expression levels were at significantly increased risk of death from RCC compared with patients who had low expression levels (risk ratio [RR], 5.3; 95% confidence interval [95% CI], 3.5-7.9). The 5-year cancer-specific survival rate was 43.0% for patients with high survivin expression and 87.2% for patients with low survivin expression. In multivariate analysis, survivin expression remained associated with death from RCC even after adjusting for the Eastern Cooperative Oncology Group performance status; 2002 Tumor, Lymph Node, Metastases (TNM) stage groupings and nuclear grade (RR, 2.4; 95%CI, 1.5-3.8); and the Mayo Clinic composite TNM stage groupings, tumor size, nuclear grade, and tumor necrosis (SSIGN) score (RR, 1.8; 95%CI, 1.1-2.9). Among 273 patients who had localized ccRCC, survivin expression was associated significantly with cancer progression (RR, 3.9; 95%CI, 2.4-6.2). CONCLUSIONS: Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies.

Aged↗

PubMed2006

B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival.

B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.

Aged↗

PubMed2006

Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up.

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.

Antigens, CD↗

PubMed2006

The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma.

BACKGROUND: Prognostic nomograms are used increasingly in clinical trials and to guide surveillance for patients with renal cell carcinoma (RCC). An elevated erythrocyte sedimentation rate (ESR) reportedly has been associated with a poor prognosis among patients with RCC, but the ESR is not incorporated into existing nomograms. Hence, the current study was conducted to expand on prior observations pertaining to the ESR as a prognostic indicator in patients with RCC. METHODS: The authors identified 3008 patients who underwent nephrectomy for RCC between 1970 and 2002. Disease-specific survival was estimated using the Kaplan-Meier method, and its association with the ESR and other clinical and pathologic features was evaluated using Cox proportional hazards regression analysis. RESULTS: A preoperative ESR was available for 1075 patients (35.7%), 501 of whom (46.6%) exhibited an elevated ESR, including 437 of 881 patients (49.2%) with clear cell RCC, 41 of 134 patients (30.6%) with papillary RCC, and 20 of 48 patients (41.7%) with chromophobe RCC. An elevated ESR was associated with adverse clinical, laboratory, and pathologic profiles for all three histologic subtypes. The risk ratios (RRs) and 95% confidence intervals (95% CIs) for death because of clear cell RCC, papillary RCC, and chromophobe RCC for patients with an elevated ESR were 3.6 (95% CI, 1.1-1.9), 3.8 (95% CI, 1.4-10.6), and 10.3 (95% CI, 1.2-89.5), respectively. The association between an elevated ESR and death from clear cell RCC persisted even after multivariate analysis (RR of 1.5; 95% CI, 1.2-2.0). CONCLUSIONS: An elevated ESR in patients with RCC suggested the presence of aggressive disease and poorer outcomes after surgical treatment. For patients with clear cell RCC, the ESR provided useful information above and beyond traditional prognostic algorithms, and it may be valuable for preoperative prognostication.

Adult↗

PubMed2006

Second primary malignancies associated with renal cell carcinoma histological subtypes.

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.

Carcinoma, Renal Cell↗

PubMed2006

The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma.

PURPOSE: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. MATERIALS AND METHODS: We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. RESULTS: We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. CONCLUSIONS: Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

Aged↗

PubMed2006

Extranodal extension in regional lymph nodes is associated with outcome in patients with renal cell carcinoma.

PURPOSE: The 2002 American Joint Committee on Cancer pN classification for renal cell carcinoma is based on the number of positive regional lymph nodes. We examined the associations of pathological features of lymph node metastases with patient outcome to improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied the records of 2,076 patients treated with radical nephrectomy for unilateral, sporadic pM0 renal cell carcinoma between 1970 and 2000. There were 34 patients with metastasis in a single regional lymph node (pN1) and 35 with metastases in more than 1 lymph node (pN2). Pathological features of lymph node metastases, including the number and percent of positive lymph nodes, total number of lymph nodes removed, grade, necrosis, extranodal extension, and largest dimension and surface area of metastases were determined by 2 urological pathologists (HHD and JCC). RESULTS: There was no statistically significant association between the pN classification and death from renal cell carcinoma (pN2 vs pN1 RR 1.05, 95% CI 0.62 to 1.79, p = 0.846). However, patients with extranodal extension were twice as likely to die of renal cell carcinoma than patients in whom metastases did not extend outside of the lymph node capsule (RR 2.02, 95% CI 1.18 to 3.45, p = 0.010). The 5-year cancer specific survival rate was 18% and 35% in patients with and without extranodal extension, respectively. CONCLUSIONS: We believe that a pN classification based on the presence or absence of lymph node metastases with a notation regarding the presence or absence of extranodal extension represents a significant improvement in the prognostic accuracy of the current pN classification.

Carcinoma, Renal Cell↗

PubMed2006

Conventional assessment of needle biopsy specimens is more useful than digital image analysis of proliferation and DNA ploidy in prediction of positive surgical margins at radical prostatectomy.

OBJECTIVES: The preoperative prediction of the likelihood of positive surgical margins (+SMs) at radical retropubic prostatectomy (RRP) may be useful for counseling and determining the surgical approach. The aim of this study was to assess the additional value of digital image analysis (DIA) of ploidy and proliferation on needle biopsies, in addition to the known preoperative predictors of +SMs at RRP. METHODS: We identified 454 patients treated by RRP at our institution from 1995 to 1998 for prostate cancer verified by transrectal ultrasound-guided biopsy, with a specimen adequate for DIA. Patients receiving preoperative hormonal therapy were excluded. The clinical features, transrectal ultrasound-guided biopsy findings, and DIA evaluation of MIB-I immunostaining and DNA ploidy were assessed in a multivariate logistic regression model to predict for +SMs at RRP. RESULTS: The mean +/- SD age at treatment was 64.5 +/- 6.5 years, the percentage of positive cores was 40.4% +/- 24.3%, the median prostate-specific antigen level was 6.3 ng/mL (range 0.6 to 112.0), median biopsy Gleason score was 6 (range 4 to 9), and median percentage of diploid nuclei was 67% (range 0% to 100%). Of the 454 patients, 185 (40.7%) had +SMs; this finding was time dependent (1995 to 1996, 45% and 1997 to 1998, 31%; P = 0.004). Univariately, preoperative prostate-specific antigen, biopsy Gleason score, extent of cancer on biopsy, MIB-1 expression, percentage of diploid or nondiploid nuclei, and year of surgery were predictive for +SMs. On multivariate analysis, the preoperative prostate-specific antigen level, biopsy Gleason score, percentage of positive cores, and year of surgery remained significant. CONCLUSIONS: The results of our study have shown that the likelihood of +SMs at RRP is best predicted on the basis of conventional prognostic factors. The DIA features of needle biopsies did not provide additional predictive power.

Adult↗

PubMed2006

Permanent prostate brachytherapy: pathologic implications as assessed on radical prostatectomy specimens of broadening selection criteria for monotherapy.

OBJECTIVES: To assess the impact of clinical selection criteria on pathologic features among patients treated by radical retropubic prostatectomy and to evaluate the implications of broadening eligibility for permanent prostate brachytherapy monotherapy. METHODS: A consecutive series of 423 patients with prostate cancer, who underwent diagnostic biopsy and subsequent radical retropubic prostatectomy, were selected for this study. Four subgroups were defined using the American Brachytherapy Society selection criteria, including prostate size limits (group 1), no prostate size limits (group 2A), a modified set of criteria (group 2B), and clinical Stage T1-T2 (group 3). The rates of extraprostatic extension, seminal vesicle invasion, and lymph node involvement were compared. RESULTS: Adverse pathologic features at radical retropubic prostatectomy were noted in 8 (9.3%) of 86 patients in group 1, 11 (5.6%) of 195 patients in group 2A, 35 (12.0%) of 292 patients in group 2B, and 90 (21.8%) of 413 patients in group 3. The rates of extraprostatic extension, seminal vesicle invasion, and lymph node involvement appeared comparable among groups 1 (5.8%, 3.5%, and 0.0%, respectively), 2A (3.6%, 2.1%, and 0.0%, respectively), and 2B (6.9%, 3.8%, and 1.4%, respectively), but were greater in group 3 (9.7%, 7.8%, and 4.4%, respectively). CONCLUSIONS: Judicious broadening of the clinical selection criteria may allow a greater number of patients to be eligible for permanent prostate brachytherapy monotherapy by including patients whose risk of having adverse pathologic features is comparable to that of patients currently deemed suitable for permanent prostate brachytherapy monotherapy. Prospective assessment of oncologic outcomes of such an approach is required.

Adult↗

PubMed2006

Greater body mass index is associated with better pathologic features and improved outcome among patients treated surgically for clear cell renal cell carcinoma.

OBJECTIVES: Obesity increases the risk of developing renal cell carcinoma (RCC); however, it remains unclear whether obesity is associated with RCC aggressiveness and survival. We used data from a large cohort of patients treated surgically for clear cell RCC to evaluate the association of obesity with the pathologic features of tumor aggressiveness and cancer-specific outcomes. METHODS: From 1988 to 2002, 970 patients underwent nephrectomy at Mayo Clinic Rochester for clear cell RCC and had body mass index (BMI) data available. To evaluate the association of BMI at surgery with the tumor pathologic features, we used the chi-square and Fisher's exact tests. We then analyzed the association of BMI with cancer-specific survival using Kaplan-Meier curves and Cox regression models. RESULTS: Overweight (BMI 25 to less than 30 kg/m2) and obese (BMI 30 kg/m2 or more) patients were more likely to present with less-aggressive tumors compared with normal-weight patients (BMI less than 25 kg/m2). The 5-year cancer-specific survival rate was 62.3%, 76.9%, and 81.7% for the normal, overweight, and obese patients, respectively. The overweight (hazard ratio 0.64, 95% confidence interval 0.49 to 0.84) and obese (hazard ratio 0.48, 95% confidence interval 0.36 to 0.66) patients were at a reduced risk of RCC death compared with patients with a BMI in the normal range. The inverse association of BMI with survival was attenuated after adjustment for well-known pathologic predictors of tumor aggressiveness. CONCLUSIONS: BMI offers little additional prognostic information beyond the accepted prognostic features; however, the association of an increased BMI with a less-aggressive disease profile at presentation warrants further exploration.

Adult↗

PubMed2006

Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma.

PURPOSE: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevectrade mark) may be effective treatment for these aggressive tumors. We determined the frequency of KIT expression and mutation in a large series of high grade RCCs. MATERIALS AND METHODS: We identified 194 patients who underwent nephrectomy for unilateral, sporadic nuclear grade 4 RCC between 1970 and 2002, including 123 with sarcomatoid differentiation. Sections from representative paraffin embedded tissue blocks were immunostained in an autostainer using ethylenediaminetetraacetic acid antigen retrieval, a polyclonal KIT antibody and the avidin-biotin peroxidase complex method. Mutational analysis was performed in all immunopositive and select negative cases by polymerase chain reaction amplification of KIT exons 9, 11, 13 and 17. RESULTS: Only 7 tumors (3.6%) showed KIT expression, including 5 of the 123 (4.1%) with sarcomatoid differentiation. Four of the 7 tumors showed focal staining only. No mutations were identified in the 7 positive cases or in 8 randomly selected negative samples. Death from RCC occurred in all 7 patients with KIT positive tumors at a median of 0.6 years (range 0.3 to 2.3) and in 139 of 187 with KIT negative tumors at a median of 0.8 years (range 0 to 10.2). CONCLUSIONS: KIT expression was identified in less than 5% of high grade RCCs with or without sarcomatoid differentiation but none of the tumors showed KIT mutations. These findings indicate that imatinib therapy is unlikely to be effective in patients with high grade RCC.

Carcinoma, Renal Cell↗

PubMed2006

Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup.

PURPOSE: SWL has revolutionized the management of nephrolithiasis and it is a preferred treatment for uncomplicated renal and proximal ureteral calculi. Since its introduction in 1982, conflicting reports of early adverse effects have been published. However, to our knowledge the long-term medical effects associated with SWL are unknown. We evaluated these adverse medical effects associated with SWL for renal and proximal ureteral stones. MATERIALS AND METHODS: Chart review identified 630 patients treated with SWL at our institution in 1985. Questionnaires were sent to 578 patients who were alive in 2004. The response rate was 58.9%. Respondents were matched by age, sex and year of presentation to a cohort of patients with nephrolithiasis who were treated nonsurgically. RESULTS: At 19 years of followup hypertension was more prevalent in the SWL group (OR 1.47, 95% CI 1.03, 2.10, p = 0.034). The development of hypertension was related to bilateral treatment (p = 0.033). In the SWL group diabetes mellitus developed in 16.8% of patients. Patients treated with SWL were more likely to have diabetes mellitus than controls (OR 3.23, 95% CI 1.73 to 6.02, p <0.001). Multivariate analysis controlling for change in body mass index showed a persistent risk of diabetes mellitus in the SWL group (OR 3.75, 95% CI 1.56 to 9.02, p = 0.003). Diabetes mellitus was related to the number of administered shocks and treatment intensity (p = 0.005 and 0.007). CONCLUSIONS: At 19 years of followup SWL for renal and proximal ureteral stones was associated with the development of hypertension and diabetes mellitus. The incidence of these conditions was significantly higher than in a cohort of conservatively treated patients with nephrolithiasis.

Adolescent↗

PubMed2005

Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma.

BACKGROUND: Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS: Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes. RESULTS: Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS: Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.

Antigens, CD↗