Organ-Specific Monitoring of Solitary Kidney after Living Donation by Using Markers of Glomerular Filtration Rate and Urinary Proteins.

BACKGROUND: Effective follow-up after living kidney donation is important for maintaining the renal function of the donor. We investigated whether the estimated glomerular filtration rate (eGFR) and urinary protein and enzyme levels can provide important information regarding the state of the remaining kidney after donor nephrectomy. METHODS: Seventy-five living donations were included (prospective/retrospective) in the study. The following parameters were measured up to 1 year after donor nephrectomy: serum creatinine and cystatin C as markers of the GFR; the high-molecular-weight urinary proteins as markers of glomerular injury; and the low-molecular-weight urinary proteins and urinary enzymes as markers of tubular function. RESULTS: One year after kidney donation, the creatinine and cystatin C values were 1.38-fold increased than their initial values, while the eGFR was 32% lower. At that time, 38% of donors had a moderate or high risk of CKD progression. The biochemical urinary glomerular and tubular kidney markers examined showed different behaviors. After a transient increase, the glomerular proteins normalized. Conversely, the detection of low-molecular-weight urinary proteins and enzymes reflected mild tubular damage at the end of the study period. CONCLUSIONS: Our findings suggest that for the evaluation of mild tubular damage, low-molecular-weight marker proteins should be included in the urine diagnostic of a personalized living kidney donor follow-up.

In vivo isolation of circulating tumor cells in patients with different stages of prostate cancer.

Circulating tumor cells (CTCs) provide accurate information on the clinical stage of cancer progression. The present study examined the clinical validity and feasibility of a new medical device for the in vivo isolation of CTCs from the blood of patients with prostate cancer (PCa). The GILUPI CellCollector® (DC01) was applied in 188 cases. The CTC/prostate-specific antigen (PSA) profile of each patient was checked for therapeutic monitoring of patients with PCa. The CellCollector, which is a unique in vivo approach for the isolation of CTCs, was compared with the CellSearch® system, which is the current standard. Overall survival (OS) and diagnostic performance were evaluated. By in vivo isolation, 78.9% (56/71) of patients with metastatic disease (PCa-m) and 46.3% (24/53) of patients with localized disease (PCa-l) had ≥1 captured CTC. Kaplan-Meier analysis revealed that patients with PCa-m that had ≥5 CTCs had a significantly different OS compared with those with <5 CTCs (27.5 months vs. 37 months; HR 2.6; 95% CI 0.78-8.3). Patients with a higher number of CTCs at all time-points had the shortest median OS of 25 months (HR 1.9; 95% CI 0.4-11.6). The effectiveness of CTC isolation technologies demonstrated that in 65.7% of the applications, patients with cancer were positive for CTCs using the CellCollector. By contrast, the CellSearch system detected CTCs in 44.4% of applications. In vivo isolation of CTCs demonstrated the clinical viability of the CellCollector, related to the current standard for the isolation of CTCs from patients with PCa. The advantage of the in vivo device is that it overcomes the blood volume limitations of other CTC assays. Furthermore, the present study revealed that the CellCollector was well tolerated, and no adverse events (AEs) or serious AEs were reported.

Expression of GP88 (progranulin) in serum of prostate cancer patients is associated with Gleason scores and overall survival.

BACKGROUND: GP88/Progranulin is a well-recognized cell growth promoter in different cancers, and elevated serum GP88 levels have been described as negative prognostic factor in breast cancer. However, serum levels in prostate cancer (PCa) patients have not yet been studied. MATERIAL AND METHODS: We analyzed serum GP88 levels by enzyme immunosorbent assay and correlated them with clinicopathological parameters in PCa patients. PCa patients were separated into two groups based on the serum GP88 median level (low ≤44.56 ng/mL or high >44.56 ng/mL) and according to their median age (younger ≤66 years or elder patients >66 years). RESULTS: Low serum GP88 levels were more often detected in younger patients and high levels in elder patients (P=0.018; Fisher's exact test). PCa patients were separated into three groups, Gleason score (GS) ≤6; GS=7; and GS≥8. In receiver operating characteristic analyses, we could distinguish GS≤6 from GS=7 [area under the curve (AUC): 0.646; P=0.018] and GS≤6 from GS≥8 (AUC: 0.629; P=0.048) but not GS=7 from GS≥8. For survival analysis, GP88 levels were separated into two groups by an optimized cutoff value of 36.92 ng/mL. Using this GP88 stratification, all PCa patients and younger patients with a low serum GP88 level had a significantly better overall survival compared with patients with higher serum GP88 levels (log-rank test P=0.010 and P=0.024). CONCLUSION: Serum GP88 levels are significantly different depending on age and GS, and they are associated with the prognosis of PCa patients.

Serum levels of miR-320 family members are associated with clinical parameters and diagnosis in prostate cancer patients.

We studied the association of the serum levels of the microRNA family members miR-320a/-b/-c with clinico-pathological data to assess their applicability as diagnostic biomarker in prostate cancer (PCa) patients. The levels of miR-320a/-b/-c in 3 groups were evaluated by qRT-PCR (145 patients with PCa, 31 patients with benign prostatic hyperplasia (BPH) and 19 healthy controls). The levels of the three family members of miR-320 were directly correlated within each group (P < 0.001), but they differed significantly among the three groups (P < 0.001). The serum levels of the miR-320 family members were significantly increased in older patients compared to younger patients (≤ 66 years vs. > 66 years, P ≤ 0.001). In addition, the levels of all three miR-320 family members were significantly different in patients with low tumor stage compared with those with high tumor stage (miR-320a: P = 0.034; miR-320b: P = 0.006; miR-320c: P = 0.007) and in patients with low serum PSA compared with those with high serum PSA (≤ 4 ng vs. > 4 ng; miR-320a: P = 0.003; miR-320b: P = 0.003; miR-320c: P = 0.006). The levels of these miRNAs were inversely correlated with serum PSA levels. Detection in the serum samples of PCa patients with or without PSA relapse revealed higher levels of miR-320a/-b/-c in the group without PSA relapse before/after radical prostatectomy than in that with PCa relapse. In summary, the differences among the PCa/BPH/healthy control groups with respect to miR-320a/-b/-c levels in conjunction with higher levels in patients without a PSA relapse than in those with a relapse suggest the diagnostic potential of these miRNA-320 family members in PCa patients.

Differences in the frequencies of HLA-class I and II alleles between German patients with renal cell carcinoma and healthy controls.

The human leukocyte antigen (HLA) system is a major part of the human immune system and has an impact on tumor initiation, tumor progression, and immunosurveillance. Renal cell carcinoma tumors are considered to be immunogenic. Therefore, we studied the allele frequencies of four gene loci (HLA-A, -B, -C, and HLA-DR) in a cohort of German renal cell carcinoma (RCC) patients and in healthy controls. HLA-A-C were determined using serological methods, whereas HLA-C12, C14, C16, C18, and HLA-DR were characterized through the use of standard molecular biological methods. The occurrence of the HLA-C*12 allele was significantly increased in German RCC patients compared with healthy controls (P < 0.005; Fisher's exact test), whereas the occurrence of the HLA-DRB1*04 allele was significantly reduced in RCC patients compared with healthy controls (P < 0.05; Fisher's exact test). However, the presence of allele HLA-C*12 was not significantly associated with 10 year overall survival. We suggest that the frequency of HLA alleles can affect development of RCC and could add knowledge as predictive marker for future immunotherapies.

Five-year experience with the adjustable transobturator male system for the treatment of male stress urinary incontinence: a single-center evaluation.

BACKGROUND: We report on our 5-year experience with the adjustable transobturator male system (ATOMS®, A.M.I., Feldkirch, Austria). METHODS: Between 10-2009 and 10-2014, 54 patients received an ATOMS. The mean follow-up of this retrospective observational trial was 27.5 ± 18.4 (2.3-59) months. Within each follow-up, the following were evaluated: micturition protocol, 24-h pad count, uroflowmetry and residual volume. Statistical analysis was performed with SigmaPlot® 11.0, p < 0.05 considered as significant. RESULTS: Stress urinary incontinence (SUI) I°, II° and III° was seen in 1 (1.9 %), 16 (29.6 %) and 37 patients (68.5 %), respectively. In summary, 48.1 % of the patients became "dry" (0-"safty pad"/day), while 29.6 % achieved at least an "improvement" of about more than 50 % (1-2 pads/day), which corresponds to an overall success rate of 77.7 %. The mean number of pads/day decreased from 7.7 to 1.6. Regarding the initial degree of SUI, patients with mild or moderate incontinence had a significantly better outcome (p = 0.002, 95 % CI 0.9066 to 2.760). Postoperative complications were scaled according to the Clavien classification, in which we have seen 4 grade I-, 1 grade IIIa- and 9 grade IIIb-complications (overall 25.9 %). The evaluation of quality of life by ICIQ-SF showed a significant improvement (p = 0.0001, 95 % CI -14.56 to -11.75). CONCLUSION: The treatment of male SUI using the ATOMS incontinence system achieved the best results in patients with mild and moderate incontinence. For severe incontinent patients, the system represents an efficient alternative.

The Use of a New CellCollector to Isolate Circulating Tumor Cells from the Blood of Patients with Different Stages of Prostate Cancer and Clinical Outcomes - A Proof-of-Concept Study.

BACKGROUND AND METHODS: Circulating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs. RESULTS: The mean CTC counts were 4.6 CTCs [range, 0-8] in patients with localized PCa, 16.8 CTCs [range, 10-25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0-98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively. CONCLUSION: Our results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1-29.39). This proof of concept was required for the approval of the use of the CellCollector in a clinical study for the in vivo isolation of CTCs from the blood stream of PCa patients by the Federal Institute for Drugs and Medical devices (Germany, BfArM).

The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer.

This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.

Granulocyte-to-dendritic cell-ratio as marker for the immune monitoring in patients with renal cell carcinoma.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been shown to be a predictor of patients' outcome for several types of malignancies. FINDINGS: Using multicolor flow cytometry we searched for predictive markers to monitor blood immune cells in patients with renal cell carcinoma undergoing surgery of the primary tumor. Due to a high standard deviation, pre-surgery NLR values did not significantly differ between tumor patients and the control group. In contrast, the granulocyte-to-dendritic cell (DC) ratio revealed significant higher values in tumor patients. Whereas NLR values did not differ between patients with early stage tumors and locally advanced tumors, the granulocyte/DC ratio was significantly different in these groups. Additionally, comparison of both ratios before and after tumor resection in the two groups "open surgery" and "laparoscopy" could demonstrate the suitability of granulocyte/DC ratio as a marker for immune monitoring. CONCLUSIONS: Granulocyte/DC ratio may serve as a new putative biomarker for the immune monitoring of tumor patients.

The adipocyte-derived hormone leptin has proliferative actions on androgen-resistant prostate cancer cells linking obesity to advanced stages of prostate cancer.

Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK) signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 µM) was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin's proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

Serum amyloid A: a biomarker for renal cancer.

BACKGROUND/AIM: Serum amyloid A (SAA) has been identified as a potential biomarker for renal cell carcinoma. We examined its diagnostic value in patients of different tumor stages. PATIENTS AND METHODS: In our study, 48 patients with localized and 67 patients with advanced renal tumors were included. 24 patients served as a control group. Interleukine 6 (IL-6), C-reactive protein (CRP) and SAA levels were measured preoperatively and at day 5 after nephrectomy. RESULTS: The IL-6, CRP and SAA levels in patients with advanced tumors are significantly higher than those of patients with localized tumors. Advanced tumors were identified with a sensitivity of 78% (SAA), 69% (CRP) and 44% (IL-6). The specificity was 82%, 82% and 94% for SAA, CRP and IL-6, respectively. CONCLUSION: Our results indicate that advanced renal cancers are accompanied by increased levels of acute-phase proteins such as CRP and SAA. SAA is found to be more sensitive than CRP for the indication of advanced renal cancer.

Laparoendoscopic single-site and conventional laparoscopic radical nephrectomy result in equivalent surgical trauma: preliminary results of a single-centre retrospective controlled study.

BACKGROUND: Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the morbidity and scarring associated with surgical intervention, and it has been proposed to result in less induced surgical trauma than conventional laparoscopy. OBJECTIVE: Investigate the surgical trauma after LESS radical nephrectomy (LESS-RN) and laparoscopic radical nephrectomy (LRN). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective single-centre study including 66 patients: 31 patients underwent LESS-RN and 35 historical control patients who had undergone LRN. LRNs were performed between April 2008 and May 2009; LESS-RNs were performed between May 2009 and February 2011. INTERVENTION: LESS-RN and LRN were both performed via a transperitoneal access. Blood samples were collected pre- and intraoperatively at 6, 24, and 48h, and at 5 d postoperatively. MEASUREMENTS: Serum concentrations of acute-phase markers, C-reactive protein (CRP), serum amyloid A (SAA) antibody, and interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured at each time point by enzyme-linked immunosorbent assay. Clinical data were collected by reviewing the patient's records. RESULTS AND LIMITATIONS: There were no differences in serum CRP and SAA levels between the groups (CRP: p=0.12; SAA: p=0.09) at all time points. The changes in IL-6 levels in the LRN group were statistically significantly higher compared with the LESS-RN group at 6h after surgery (p=0.02), whereas the LESS-RN group showed statistically significantly higher IL-6 levels than the LRN group at 24h after surgery (p=0.02). Also, the serum levels of the anti-inflammatory cytokine IL-10 showed different kinetics in each group, being higher in the LESS-RN during the early postoperative phase (at 6h: p=0.01) and higher in the LRN group at 48h after surgery (p=0.01). The limitations of this study were its nonrandomized character and the small cohort of patients. CONCLUSIONS: LESS-RN is as effective as LRN without compromising surgical and postoperative outcomes, but it does not add any significant advantage in comparison with traditional LRN in terms of systemic stress response and surgical trauma.

Adipocytokine: a new family of inflammatory and immunologic markers of invasiveness in major urologic surgery.

BACKGROUND: Laparoscopic surgery has been proposed to reduce surgical trauma and diminish patients' stress response. OBJECTIVE: To investigate the role of the adipocytokine, in combination with changes in other known inflammatory markers, in patients undergoing radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A total of 580 patients were enrolled in this prospective study. Laparoscopic extraperitoneal radical prostatectomy (LRP) was performed in 286 patients, and open retropubic radical prostatectomy (RRP) in 294 patients. INTERVENTION: Blood samples were collected preoperatively and up to 5 d postoperatively. MEASUREMENTS: Serum concentrations of acute phase markers, interleukins (IL), and the adipocytokine leptin were measured at each time point by means of enzyme-linked immunosorbent assay. Clinical data were collected and analysed. RESULTS AND LIMITATIONS: Patients undergoing LRP had significantly lower IL-6 and adipocytokine levels at all measurement time points. However, biphasic kinetics of adipocytokine serum levels were observed during the postoperative course in all patients. LRP was associated with less adipocytokine and IL-6 release, indicating a smaller degree of surgical insult and the minimal invasive nature of this procedure. The limitation of this study was its nonrandomised design. CONCLUSIONS: Adipocytokines might serve as additional immunologic markers of invasiveness in major urologic surgery.

Management of localized prostate cancer by retropubic radical prostatectomy in patients after renal transplantation.

BACKGROUND: The study aimed to report our experience with retropubic radical prostatectomy (RRP) for treatment of localized prostate cancer in renal transplant recipients (RTR). METHODS: Data of 16 RTR who had an RRP between 2001 and 2007 were retrospectively analysed and compared to the data of 294 non-transplanted patients who were operated for RRP during the same period. Diagnostic work-up consisted of digital rectal examination, serum prostate specific antigene levels, as well as Transrectal Ultrasonography (TRUS)-guided prostate biopsy. Follow-up was obtained in all patients with a mean follow-up time of 2.1 years in RTR. RESULTS: Mean time distance to the renal transplantation at the time of RRP was 81.2 ± 19.1 months. RRP was successfully performed and tolerated in all RTR without pelvic lymph node dissection. No major complications occurred during or after the operation. There were two minor complications in transplant group (prolonged haematuria and urinary leakage). Mean operative time was 108.3 ± 3.9 min in transplant group, which was significantly longer as in non-transplanted group (89.1 ± 4.1, P < 0.05). Mean estimated intra-operative blood loss was significantly lower in transplant group (P < 0.05). In RTR, one case of positive surgical margins was present (R(1): 6.2 vs. 12.3% in non-transplanted group, P < 0.05). None of the RTR had impairment of graft function. At follow-up, no case of biochemical recurrence was observed in RTR. CONCLUSIONS: RRP is safe and feasible for management of localized prostate cancer in patients with kidney allograft being under immunosuppression. However, concern about impairment of graft function, infection and wound healing remains important.

Shift of the f/t-PSA quotient in relation to renal insufficiency: consequences for the early detection of prostate carcinoma in patients with terminal renal failure.

BACKGROUND: Whether the quotient of free to total PSA (f/t-PSA) can be used to increase the specificity in the early detection of prostate carcinoma is a matter of discussion in cases of renal failure. We therefore compared f/t-PSA values of patients with kidney failure and patients after successful kidney transplantation. PATIENTS AND METHODS: The serum levels of total PSA (t-PSA) and free PSA (f-PSA) were determined in 57 patients. For those where t-PSA was between 2 and 10 ng/ml the f/t-PSA quotient was calculated. Out of the 57 patients, 32 suffered from renal failure (15 cases with prostate carcinoma, 17 with benign prostate disorder), the other 25 had successfully undergone kidney transplantation with a working transplant (10 with prostate carcinoma, 15 with benign prostate disorder). RESULTS: There were no statistically significant differences between the t-PSA levels of the various groups of patients. The f/t-PSA quotients, however, were consistently higher for the patients with kidney failure than for those with a kidney transplant or with a normal kidney function. There were no differences in the f/t-PSA quotients between transplant recipients and men with normal kidney function. CONCLUSION: For the use of the f/t-PSA quotient as a tool to support the decision for or against a prostate biopsy, it should be borne in mind that the cut-off criteria determined for men with a normal kidney function cannot be applied to patients who suffer from kidney failure. The f/t-PSA quotient of patients with terminal renal failure is often shifted towards higher values. On the other hand, there is no statistically significant difference between the f/t-PSA quotients of kidney transplant recipients and patients with normal kidney function, therefore the same diagnostic criteria apply in this case.

Is the determination of the soluble interleukin-2 receptor after application of interleukin-2 receptor antibodies still appropriate for immunological monitoring after renal transplantation?

INTRODUCTION: The use of monoclonal antibodies against the alpha-chain of the membrane-bound interleukin-2 receptor (IL-2Ralpha) as immune suppressants causes characteristic changes in the levels of soluble interleukin-2 receptor (sIL-2R) in serum and urine. METHODS: 38 kidney transplant patients were included in this study. 28 of them received an induction therapy with the IL-2R antibody basiliximax (Simulect) in addition to standard immunosuppression, 10 patients constituted the control group. RESULTS: Time courses of sIL-2R levels of Simulect patients with and without complications after transplantation have been compared. It turned out that of a total of 18 cases with complications 15 cases could be identified by their elevated sIL-2R levels, which corresponds to a sensitivity of 83%. CONCLUSION: Acute rejection, CMV infection, extrarenal bacterial infection and pyelonephritis in the transplant all cause a significant increase of the sIL-2R level even after application of Simulect.

Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF).

BACKGROUND: Tissue hypoxia is a major stimulus for the up-regulation of vascular endothelial growth factor (VEGF). Anemia might theoretically impact on angiogenesis via impairment of tissue oxygenation. We have investigated this hypothesis in patients with solid cancers and benign diseases. PATIENTS AND METHODS: 49 patients with untreated locoregionally confined solid cancers of the head and neck, cervix, rectum and lung and 59 additional patients with non-malignant diseases (36 normemic patients without serious diseases and 23 patients with renal anemia) were enrolled and the impact of anemia on plasma VEGF levels were determined. VEGF was measured with a commercially available sandwich enzyme immunoassay technique. RESULTS: Plasma levels of VEGF were 16.2 +/- 12.7 pg/ml in 36 normemic patients without malignant disease, 49.2 +/- 34.5 pg/ml in 49 patients with cancers (p < 0.001), and 89.9 +/- 67.8 pg/ml in 23 patients with renal anemia (p = 0.001). VEGF levels in cancer patients were significantly correlated with hemoglobin (hb) levels and platelet counts (each p = 0.001), but not with type of tumor, stage, histology or age. Patients with cancers had higher plasma levels of VEGF than patients with non-malignant diseases in case of hb > or = 12 g/dl (33.1 +/- 17.5 vs 16.6 +/- 13.0 pg/ml, p < 0.001) and in case of hb between 11.0 and 11.9 g/dl (56.1 +/- 26.4 vs 18.5 +/- 14.5 pg/ml, p = 0.038). In case of a hb < 11 g/dl, plasma VEGF levels were significantly elevated in patients with and without cancers (67.0 +/- 47.5 vs 88.9 +/- 68.8 pg/ml, n.s.). In a multivariate model, a significant association between low hb levels and increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia, changes in hb under erythropoietin treatment were inversely correlated with changes in plasma VEGF levels with decreasing VEGF after increase in hb (p = 0.01). CONCLUSIONS: Anemic patients have elevated levels of VEGF. The data suggest that anemia might impact on the progression of angiogenesis in malignant and benign diseases.