Preoperative serum total cholesterol is a predictor of prognosis in patients with renal cell carcinoma: a meta-analysis of observational studies

ABSTRACT Purpose Several studies have demonstrated the strong correlation between the levels of preoperative serum total cholesterol (TC) and the survival of patients with surgically treated renal cell carcinoma (RCC). However, this association remains controversial. We performed a meta-analysis of published reports to evaluate the prognostic significance of the preoperative serum TC levels for patients with surgically treated RCC. Material and Methods The databases from MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library were systematically searched to identify the eligible studies published before August 2019. Multivariate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance by using random-effects models. Results Nine cohort studies comprising 15.609 patients were identified. Low preoperative serum TC levels were associated with poor cancer-specific survival (CSS; HR=0.98, 95% CI: 0.97-0.99; P=0.005; I2=74.2%) and progression-free survival (PFS; HR=0.69, 95% CI: 0.49-0.98; P=0.036; I2=80%) in patients with surgically treated RCC. However, no significant association was observed between low preoperative serum TC levels and shorter overall survival (HR=0.93, 95% CI: 0.87-1.00; P=0.057; I2=86.2%). Sensitivity analyses validated the reliability and rationality of the results. Conclusions Preoperative serum TC level is an independent poor prognostic factor for patients with surgically treated RCC, with lower levels associated with worse CSS and PFS. Hence, this parameter may provide additional guidance in the selection of therapeutic strategies to improve prognosis, considering that cholesterol is a broadly applied routine marker in clinical practice.

A higher circulating concentration of 25-hydroxyvitamin-D decreases the risk of renal cell carcinoma: a case-control study

ABSTRACT Objective: To investigate the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25 (OH) D], and renal cell carcinoma (RCC) risk in a case-control study, because the association between the two is unclear in China. Materials and Methods: A total of 135 incident RCC cases were matched with 135 controls by age and sex. The blood samples were collected on the first day of hospitalization before surgery to measure plasma 25 (OH) D. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) with adjustment for several confounders (e.g. age, gender, smoking and season of blood draw). Furthermore, the association of RCC with 25 (OH) D in units of 10 ng / mL as a continuous variable were also examined. Results: The average plasma 25 (OH) D concentrations in RCC were significantly lower compared with those of the controls (21.5 ± 7.4 ng / mL vs. 24.1 ± 6.6 ng / mL, respectively; P = 0.003). In the adjusted model, inverse associations were observed between circulating 25 (OH) D levels and RCC risk for 25 (OH) D insufficiency (20-30 ng / mL) with OR of 0.50 (95% CI: 0.29-0.88; P = 0.015) and a normal 25 (OH) D level (≥ 30 ng / mL) with OR of 0.30 (95% CI: 0.13-0.72; P = 0.007), compared with 25 (OH) D deficiency (< 20 ng / mL). Furthermore, results with 25 (OH) D as a linear variable indicated that each 10 ng / mL increment of plasma 25 (OH) D corresponded to a 12% decrease in RCC risk. Conclusions: This case-control study on a Chinese Han population supports the protective effect of a higher circulating concentration of 25 (OH) against RCC, whether the confounding factors are adjusted or not.

The diagnostic value of FNDC5/irisin in renal cell cancer

ABSTRACT Purposes: The aim of this study was to determine the diagnostic significance of fibronectin type III domain containing protein 5 (FNDC5)/Irisin levels in the sera of patients with renal cell cancer. Materials and Methods: In the study, 48 individuals were evaluated. The patient group included 23 subjects diagnosed with renal tumor, and the control group of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected and serum FNDC5/Irisin and carcinoembryonic antigen (CEA) levels were determined using enzyme-linked immunosorbent assay (ELISA). Results: FNDC5/irisin and CEA levels in renal cancer patients were significantly higher compared with the control group (p=0.0001, p=0.009, respectively). Also, FNDC5 levels was more sensitive and specific than CEA levels. The best cut-off points for FNDC5/irisin were >105pg/mL and CEA were >2.67ng/mL for renal cancer. Conclusions: FNDC5/Irisin may be used as a diagnostic biomarker for renal cancer.

Can preoperative neutrophil lymphocyte ratio predict malignancy in patients undergoing partial nephrectomy because of renal mass?

ABSTRACT Purpose: To evaluate the importance of preoperative neutrophil lymphocyte ratio (NLR) predicting malignancy in patients who undergo partial nephrectomy due to renal mass. Materials and Methods: Seventy nine patients who underwent open partial nephrectomy for renal masses were included in this retrospective study. In preoperative routine blood tests, renal ultrasonography and contrast-enhanced computed tomography were performed for all patients. Preoperative neutrophil lymphocyte ratio were compared in patients with clear cell renal cell carcinoma (Group1, 65 patients) and benign lesions (Group 2, 14 patients). The predictive ability of NLR was analyzed by ROC curves and Youden Index method was used to identify the cut-off value for NLR. Results: The mean age of patients was 59.8±11.7 years in Group1 and 57.4±12.6 years in Group 2 (p=0.493). The mean tumor size was 3.8±1.2 cm in Group 1 and 3.3±1.0 cm in Group 2 (p=0.07). The median NLR was 2.48 (1.04) in Group 1 and 1.63 (0.96) in Group 2 (p<0.001). The area under a ROC curve was 0.799 (p<0.001). Conclusions: Preoperative neutrophil lymphocyte ratio may predict renal masses that can not be distinguished radiologically. Our results must be confirmed by large and properly designed prospective, randomized trials.

Serum tissue factor as a biomarker for renal clear cell carcinoma

ABSTRACT Purpose to determine the usefulness of serum TF as a potential marker for patients with clear cell RCC. Materials and Methods prospective study of 30 patients with clear cell RCC submitted to nephrectomy and 16 controls without clear cell RCC treated surgically for other conditions. TF is a endothelium marker that was correlated with worse prognosis in a variety of solid tumors including RCC. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®). Results Mean preoperative serum TF levels in clear cell RCC patients and in controls were 66.8 pg/dL and 28.4 pg/dL, respectively (p<0.001). Mean postoperative serum TF levels in clear cell RCC patients were 26.3 pg/dL. In all patients with clear cell RCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dL in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (p=0.037). Conclusions We have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with clear cell RCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of clear cell RCC. Further studies are needed to validate these findings.

SCUBE1: a promising biomarker in renal cell cancer

ABSTRACT Purpose To investigate the efficacy of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) as a novel biomarker of renal tumors. Materials and Methods 48 individuals were included in the study. The patient group (Group-1) consisted of 23 subjects diagnosed with renal tumor, and the control group (Group-2) of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected following overnight fasting. Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1), soluble urokinase plasminogen activator receptor (suPAR) and carbonic anhydrase IX (CA IX) levels were measured from plasma samples. Patients in groups 1 and 2 were compared in terms of these biochemical parameters. Results The 23-member renal tumor group was made up of 17 (73.91%) male and 6 (26.08%) female patients with a mean age of 58.5±15.7 years (range 25 to 80). The 24-member healthy control group was made up of 16 (64%) male and 9 (36%) female subjects with a mean age of 52.4±9.12 years (range 40 to 67). Analysis revealed significant elevation in SCUBE-1 levels in the renal tumor group (p=0.005). No significant differences were detected between the groups with regard to CA IX or suPAR measurements (p=0.062 vs. p=0.176). Conclusions SCUBE-1 appears to represent a promising biomarker in the diagnosis and follow-up of patients with renal tumor.

Clinical significance of preoperative neutrophil -to - lymphocyte ratio in renal cell carcinoma

ABSTRACT Introduction: We investigated the prognostic significance of the neutrophil-to-lymphocyte ratio on tumor stage and Fuhrman nuclear grade in renal cell carcinoma. Methods: The records of 432 patients with RCC who underwent radical or partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Patients were classified as group lower tumor stage(T1 + T2) and higher(T3 + T4). As like tumor stage, Fuhrman nuclear grade were classified lower (G1+G2) and higher(G3+G4) too. The best NLR cut off value was 3.01. Two sample t-test or Mann–Whitney U-test used for the continuous variables and a chi-square test or Fisher's exact test used for the categorical variables. Results: Among the 432 total patients analyzed in our study, there were 275 males (63.7%) and 157 females (36.3%). Mean laboratory values were CRP 2.73 ± 1.93 mg/dL (normal less than 0.3), neutrophil count 4,23 ± 1.46/μL, lymphocyte count 1,61 ± 0,61/μL and NLR 2.64 ± 1.24. According to our data, statistically pretreatment NLR significantly correlated with CRP (p<0.0001). And tumor patologic stage (p=0.08), tumor histologic grade (p<0.001) was significantly associated with NLR. Discussion: We compared the relationship of preoperative NLR and NC parameters with RCC tumor stage and grade. And NLR were found to have statistically significant higher T stage and grade at RCC. Further studies with more patients are needed to confirm our study.

Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma

Hypercalcemia is found frequently in patients with cancer. Besides the etiology related to the malignancy, other causes should be considered in the differential diagnostic, as primary hyperparathyroidism, granulomatous diseases and the use of thiazide diuretics. We present a case report of a severe hypercalcemia due to a rare association and review the relevant literature. A female patient, 57 years old, sent to the Endocrinology Service of Hospital das Clínicas da Universidade do Paraná (SEMPR) in order to investigate severe hypercalcemia with frequent need of hospitalization. The patient was in chemotherapy treatment for recurrence of clear cell renal cancer. During the investigation she presented high level of parathyroid hormone (PTH) and parathyroid scintigraphy suggestive of hyperplasia/ adenoma of parathyroid, histopathological diagnosis was confirmed after parathyroidectomy. After surgery the patient presented undetectable levels of PTH. However, she continued with progressive increase of serum calcium, with no signs of bone metastases or change in vitamin D metabolism. The investigation showed high levels of PTH-related protein (PTHrP), leading us to the diagnosis of hypercalcemia of malignancy. The patient presented severe hypercalcemia due to the rare association of primary hyperparathyroidism and humoral hypercalcemia of malignancy due to secretion of PTHrP by tumor cells. The presence of isolated primary hyperparathyroidism, as a cause of hypercalcemia in cancer patients, has been described in approximately 5-10% of the patients. However, the association of primary hyperparathyroidism and humoral hypercalcemia of malignancy (which means with concomitant elevation of PTH and PTHrP) is rare, only three cases have been described in the literature. Arch Endocrinol Metab. 2015;59(1):84-8.

Serum protein profiling to identify biomarkers for small renal cell carcinoma.

Diagnostic biomarkers for early detection of renal cell carcinoma (RCC) are in great need. In the present study, we compared the serum protein profiles of patients with small RCC to those of healthy individuals to identify the differentially expressed proteins with potential to serve as biomarkers. Serum samples were collected from 10 patients with small RCC and 10 healthy individuals. The serum protein expression profiles were analyzed by two-dimensional (2-D) gel electrophoresis. Twenty-seven proteins with differences in expression levels between RCC patients and healthy volunteers were identified. Of these, 19 were expressed at different levels and eight were expressed in serum from the RCC group, but not from the control group. Six differentially expressed proteins identified by using mass spectrometry included coagulation factor XIII B, complement C3 and its precursor, misato homolog 1 (isoform CRA_b), hemopexin, and alpha-1-B-glycoprotein. Some of these serum proteins are known regulators of tumor progression in human malignancies. In conclusion, we successfully applied 2-D gel electrophoresis and identified six serum proteins differentially expressed between patients with small RCC and healthy volunteers. These proteins may provide novel biomarkers for early detection and diagnosis of human RCC.

Analysis of Changes in the Total Lymphocyte and Eosinophil Count during Immunotherapy for Metastatic Renal Cell Carcinoma: Correlation with Response and Survival

The aims of this study were to analyze lymphocyte and eosinophil counts in consecutive peripheral blood samples taken during immunotherapy for metastatic renal cell carcinoma (mRCC) and to correlate the findings with objective response and survival. A total of 40 patients with mRCC who received immunotherapy with interleukin-2, interferon-alpha, and 5-fluorouracil were analyzed. Objective responses were observed in 14 patients, including 2 (5%) who showed a complete response (CR) and 12 (30%) who showed a partial response (PR). Eleven patients (27%) achieved stable disease (SD), and 15 patients (38%) had progressive disease (PD). Changes from baseline in the total lymphocyte counts were significantly higher in the responding patients (CR+PR+SD) than in the non-responding patients (PD) (p=0.017), but no difference was seen in the total eosinophil counts (p=0.275). Univariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (p=0.017), the presence of a primary renal tumor (p<0.001) and the peripheral lymphocyte counts at week 4 (p=0.034) as prognostic factors, but a low ECOG performance status (p=0.003) and the presence of a primary renal tumor (p=0.001) were identified as independent poor prognostic factors by multivariate analysis. This study provides further evidence that changes in blood lymphocyte counts may serve as an objective indicator of objective responses.

Serum ferritin in renal cell carcinoma: effect of tumor size, volume grade, and stage.

AIM: To study the levels of serum ferritin in patients of renal cell carcinoma (RCC). PATIENTS AND METHODS: Serum ferritin levels were measured preoperatively in 32 patients with radiological evidence of RCC using an enzyme immunoassay. The largest diameter of the primary tumor was measured in the pathological specimens in patients undergoing radical nephrectomy while in patients with non-operable tumor maximum tumor dimension was taken from CT scan. Pathological staging was done according TNM-1997. RESULTS: Mean serum ferritin value in patients of RCC was 283.23+/-77.38 ng/ml while in controls the mean value was 79.98+/-32.96 ng/ml (P CONCLUSIONS: Serum ferritin levels are elevated in patients with RCC although its actual source is unclear. Further studies are needed to establish the role of ferritin in RCC.

Heterotopic bone formation in renal cell carcinoma (a case report).

A case of renal cell carcinoma with heterotopic bone formation occurring in a female aged 55 years has been reported. There was no haematuria and the morphological picture showed only ossified stroma and no sarcomatoid appearance.