OBJECTIVE
To evaluate the effect of vascular endothelial growth factor (VEGF, one of the most important angiogenetic factors) in renal cell carcinoma (RCC) by analysing many RCCs for the expression ...of immunohistochemical (IHC) VEGF‐staining related to clinicopathological findings and survival.
PATIENTS AND METHODS
VEGF immunostaining was examined with the tissue microarray (TMA) method on tumour samples from 229 patients and validated in 71 by ordinary tissue sections (TS). IHC VEGF expression was quantified by estimating the volume density and staining intensity on a three‐grade scale.
RESULTS
In most RCCs there was VEGF staining in the cell cytoplasm and membrane. In cell membranes the VEGF expression declined with storage time. IHC VEGF expression analysed by TMA and TS gave corresponding results. There was no difference in VEGF expression among conventional, papillary and chromophobe RCCs. There were significant correlations between VEGF expression and tumour size and stage. In univariate analysis VEGF expression correlated with survival, especially in conventional RCCs; this prognostic information was lost in multivariate analysis. The VEGF staining intensity correlated only with VEGF expression but not with any clinicopathological factors.
CONCLUSIONS
VEGF protein was present in most RCC cells. There was no difference in VEGF expression among the different RCC types. The correlation between VEGF expression and tumour stage and with prognosis indicates the significance of VEGF within tumour growth and progression in RCC.
Objective
To define guidelines for the follow‐up management of nonmetastatic renal cell carcinoma (RCC), by assessing tumour recurrences and the clinical course in patients who had undergone radical ...nephrectomy.
Patients and methods
The records of 187 patients with pT1–3, N0–X, M0 RCC who underwent radical nephrectomy between 1982 and 1997 were reviewed prospectively. Clinicopathological variables were compared with the time of first recurrence, site of metastasis and reason for diagnosis.
Results
Metastases were diagnosed in 98 sites in 56 of the 187 patients (30%). The risk for developing metastases increased with stage; 80% of the patients had their metastases diagnosed within 3 years (median 14.5 months) after nephrectomy. The time to first diagnosis was longer for patients with pT1 tumours and for those with skeletal metastases. The cause‐specific 5‐year survival rate for pT1 tumours was 95%, for pT2 87% and for pT3 tumours 37%. All patients with diploid pT1–2 RCC survived, having a survival advantage over those with aneuploid pT1–2 tumours (P=0.018). Also, pT1–2 tumours of < 5 cm were associated with better survival rates. Among 74 patients with pT3 tumours, 45 got metastases; DNA ploidy in these tumours did not influence survival. Of 30 patients with lung metastases, 28 were diagnosed during follow‐up, while 25 of 26 other metastatic sites were diagnosed because of symptoms.
Conclusions
The risk for tumour progression depends mainly on stage; these results indicate no need for follow‐up in patients with diploid pT1–2 tumours or with aneuploid pT1 tumours of < 5 cm. For patients with aneuploid pT1–2 tumours of > 5 cm and pT3 tumours, follow‐up is indicated.
Renal cell carcinoma is often characterised by extensive vascularity and angiogenic factors may be of importance for disease progression. Using a sandwich enzyme immunoassay, basic fibroblast growth ...factor (bFGF) was analysed in the sera from 206 patients with renal cell carcinoma before the initiation of therapy. The median bFGF level was 3.0 pg/ml (range <1.0–70.9 pg/ml). The serum levels were significantly correlated to tumour stage and nuclear grade. Patients with tumour thrombus to the renal or the inferior caval vein had significantly higher serum bFGF levels compared with those with non-invading tumours (P=0.007). Patients with serum bFGF levels above 3.0 pg/ml had a worse prognosis, compared with those with lower levels (P=0.001). Furthermore, patients with tumours with vein invasion had a worse prognosis compared with those without invasion. After multivariate analysis, only tumour stage and grade remained as independent prognostic factors.
Patients with malignancies often present with signs of inflammatory reactions such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Since interleukin-6 (IL-6) is a ...possible regulator of these reactions and has been proposed as a predictor of prognosis, the aim of the study was to analyse its clinical significance in patients with renal cell carcinoma. Serum samples were collected from 196 patients before any treatment. IL-6 was analysed by an enzymelinked immunoassay and compared with tumour grade, stage, acute-phase reactants and survival. Patients with renal cell carcinoma had significantly higher IL-6 levels (mean 28.1 ± 63.4 ng/l; median 8.3 ng/l) compared with controls (mean 1.7 ± 2.6 ng/l; median 0.5 ng/l;
P < 0.001). Serum IL-6 levels in patients with distant metastases were significantly higher than for patients with tumours confined to the kidney (
P = 0.02). This difference was more pronounced when serum IL-6 levels in patients with poorly differentiated tumours were compared with well-differentiated tumours (
P < 0.001). A significant correlation between the acute-phase reactants CRP, ESR and IL-6 levels was found. Survival time was significantly shorter (
P = 0.001) for patients with IL-6 levels above the median serum level compared with patients with lower levels. Similar significant prognostic results were obtained in the group of patients with metastatic disease, but not in group of patients with stage I–III. Serum levels of IL-6 correlated to tumour stage, grade and acute-phase reactants. Increased levels were related to the presence of metastases and adverse survival. Serum IL-6 proved univariate prognostic information but this prognostic significance was lost using a multivariate analysis.
The free beta-subunit of human chorionic gonadotropin beta is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human ...chorionic gonadotropin beta expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin beta in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin beta in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin beta, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin beta were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin beta levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l(-1), P=0.0029). In multivariate analysis human chorionic gonadotropin beta, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin beta is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin beta in serum may be used to identify patents with increased risk of progressive disease.
OBJECTIVE: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. Surgery is the primary treatment in recurrent or metastatic disease. Radiotherapy has been used as an adjuvant to ...control subclinical local disease but is otherwise considered ineffective. DESIGN: We report on a patient with parathyroid carcinoma with hypercalcaemia and pulmonary metastases, treated with pamidronate and radiotherapy and later with surgery. METHODS: The treatment was evaluated using serial analysis of serum parathyroid hormone (PTH) and calcium, clinical evaluation and chest radiographs. RESULTS: Intravenous pamidronate alone had limited effect on hypercalcaemia. Following irradiation of the pulmonary lesions (34 Gy in ten fractions), serum levels of calcium and PTH decreased and pamidronate could be discontinued. The patient's general condition improved parallel to a radiological response. At clinical relapse 18 months following radiotherapy, the pulmonary metastases were resected and serum PTH was normalised. CONCLUSIONS: The results indicate that parathyroid carcinoma can be radiosensitive. Thus radiotherapy may be an alternative to palliate symptoms of hypercalcaemia in patients not suited for surgery.
Abstract
Introduction:
Completion times on gait tasks have been associated with risk for falls. While there is some evidence that sleep apnea is associated with worse performance on gait tasks, the ...association of sleep duration and quality—independent of sleep apnea—with gait task performance is not well understood.
Methods:
A subset of Wisconsin Sleep Cohort Study subjects (n=631; 45% female; mean range age=6545–82 years) participated in a protocol to assess gait, including: 1) the Timed Up & Go (TUG) task; and 2) the Timed Up & Go while counting backward by 3s and stepping over obstacles (TUG-CB,O). Subjects underwent overnight polysomnography and completed questionnaires including information about usual sleep habits and sleepiness. The following outcomes were regressed on nighttime and nap sleep duration, sleep efficiency and wake after sleep onset (WASO): 1) seconds to complete the TUG; 2) seconds to complete the TUG-CB,O; and 3) the difference in completion time between the TUG-CB,O and the TUG (ΔTUG), a measure of the “cognitive cost” of the obstacle avoidance and counting backwards tasks on the TUG. Results were adjusted for apnea hypopnea index (AHI), age, gender, BMI, alcohol and caffeine consumption, smoking, cardiovascular disease, and diabetes.
Results:
Shorter sleep duration (≤6 h vs 7–8 h) was associated with longer TUG-CB,O completion time (p<0.1) and greater ΔTUG (p<0.05). Longer sleep duration was not significantly associated with gait task performance. Taking longer naps was associated with longer completion times on TUG (p<0.05) and TUG-CB,O (p<0.01) and a larger difference ΔTUG (p<0.05). Lower sleep efficiency (p<0.05) and greater WASO (p<0.1) were both associated with greater ΔTUG. AHI was associated with longer completion times on the TUG and TUG-CB,O (p<0.05) in each of the models.
Conclusion:
Sleep duration and quality are associated with performance on gait tasks. The difference between the “baseline” TUG completion time and the TUG-CB,O, which adds two simultaneous cognitively taxing tasks, was consistently associated with sleep duration and quality predictors, suggesting that sleep deficits may affect cognitive functioning in a way that contributes to physical functioning.
Support (If Any):
NIH grants: National Heart, Lung, and Blood Institute (R01HL62252); National Center for Research Resources (1UL1RR025011).
It has been shown that both serum vascular endothelial growth factor (VEGF) and also platelet counts are associated with survival in renal cell carcinoma (RCC). It is not known, however, whether VEGF ...in serum relates to the angiogenic activity of the tumour or is derived from circulating blood components. Therefore, the interrelation between serum VEGF, platelet and leukocyte counts compared with health history, clinicopathological findings and outcome was evaluated in patients with RCC. Blood samples were collected before nephrectomy in 161 patients. Serum VEGF₁₆₅ was assessed by a quantitative ELISA method. Platelet and leukocyte counts were analysed routinely and obtained from medical records. The variables were compared using univariate and multivariate analysis. There were significant correlations between VEGF levels, and platelet (P < 0.001) and leukocyte counts (P < 0.001). Serum VEGF levels, platelet counts, as well as leukocyte counts correlated significantly to stage and grade. Platelet counts were significantly lower in men with medication (P = 0.042), and decreased with age particularly in women (P = 0.001). Age or medication did not affect VEGF levels or leukocyte counts. Both VEGF and platelets gave significant prognostic information in univariate analysis. Using Cox multivariate analysis, VEGF was the last variable to be excluded. Only stage and grade remained as independent prognostic factors. Both VEGF levels and platelet counts gave prognostic information but VEGF was more reliable as predictor of survival in patients with RCC.
Conventional renal cell carcinoma (cRCC) accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. ...Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival.
Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis) was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001). In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001).
cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Results from case‐control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship ...between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow‐up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m2) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03–1.94); height (HR = 1.61; 95% CI: 1.18–2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00–1.79) and waist‐to‐hip ratio (HR = 1.42, 95% CI: 1.05–1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30–7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.
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