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Background: Preoperative thrombocytosis (PTC) is frequently observed in various solid malignancies and often associated with an unfavourable oncological outcome., Objectives: The aim of this study was to investigate the influence of PTC in patients undergoing radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder on the oncological prognosis and additionally on perioperative blood transfusions (PBT)., Method: A retrospective analysis of 866 patients undergoing RC in a tertiary care centre was performed. PTC was defined as a platelet count >400 G/L. A chi-square test and Mann-Whitney test were used to investigate the association of PTC with categorical clinicopathological variables. A logrank test and multivariable Cox regression analyses were used to assess the association of PTC with cancer-specific survival., Results: PTC was detected in 8% (n = 67) of the patients and was significantly associated with muscle invasion (p = 0.004), advanced tumour stages (p = 0.003) and nodal metastases (p < 0.001) and with a higher rate of PBT (p< 0.001). In the multivariate analysis, PTC was significantly related to poor oncological survival (hazard ratio 2.23, 95% CI 1.51-3.30, p < 0.001)., Conclusion: PTC is significantly associated with an impaired oncological outcome in patients undergoing RC for UC. PTC therefore represents an independent and easy to determine prognostic parameter for patients' oncological outcome. Intriguingly, PTC is significantly associated with an increased rate of PBT., (© 2019 S. Karger AG, Basel.)

Objectives: Patients' oncological outcome after radical cystectomy (RC) due to urothelial carcinoma of the urinary bladder (UCB) is always up for debate. There is accumulating evidence on the influence of routine blood parameters. We aimed to identify reasonable and easy-to-detect biomarkers, such as preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels, as predictors of overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RC for UCB., Materials and Methods: This is a large single-center study in which both preoperative CRP and Hb levels were available in 1,043 patients undergoing RC for UCB from 2004 to 2018 with a median follow-up time of 22 months (mean 38, max. 170). We used the Kaplan-Meier method, log-rank test, and Cox regression models for assessment of OS and CSS. Using our data, we validated an existing outcome prediction score (TNR-C)., Results: Median CRP level was 0.5 mg/dL (IQR 0.2-1.4), and median Hb level was 13.4 g/dL (IQR 11.9-14.7). We found that patients with CRP values above the median reached a significantly lower median survival than those with CRP values below the median (23 vs. 83 months, p < 0.001). The TNR-C score was successfully validated, and we discriminated between 3 risk groups (5-year CSS: 76, 40, and 16% for low, intermediate, and high risk, respectively). We observed a similar outcome for patients with a Hb level below the median: CSS was significantly poorer than with Hb levels above the median (median CSS 27 vs. 91 months, p < 0.001). Multivariant analysis showed CRP and Hb levels to be independent prognostic parameters for CSS and OS., Conclusions: We found elevated preoperative CRP levels and decreased Hb levels to be independent prognostic factors indicating an unfavorable outcome in patients undergoing RC for UCB and were able to validate the TNR-C score in a large patient cohort. We propose using these routine biomarkers for individual risk stratification and optimization of therapeutic strategies in patients undergoing RC for UCB., (© 2020 S. Karger AG, Basel.)

Background: The activation of Fas/Fas ligand (FasL) and DR4-DR5/tumor necrosis factor-related-apoptosis-inducing ligand (TRAIL) pathways in cancer cells triggers apoptosis. The objective of this study was to investigate the prognostic value of soluble FasL (sFasL) and soluble (sTRAIL) in the serum of patients with bladder cancer., Methods: The sFasL and sTRAIL levels in the sera of patients with bladder cancer or healthy donors were determined using the enzyme-linked immunosorbent assay. Micro-culture tetrazolium viability assay and Western blot were used to analyze cell cytotoxicity and death receptors protein expression respectively., Results: Whether no difference in sTRAIL levels was seen between patients and controls, the level of sFasL was higher in patients than that in healthy donors. According to, sFasL level was the highest in the serum of patients with superficial stage or low- and medium-grade cancer. Moreover, sFasL in patients with superficial noninvasive bladder tumors or low- and medium-grade cancers was higher than that in patients with invasive carcinomas and high-grade cancers. Patients with high levels of sFasL survive longer than those with low levels, probably related to the cytotoxic potential of FasL preserved in its soluble form., Conclusion: The data suggest that monitoring the level of sFasL and its cytotoxic activity could be a prognostic marker in the follow-up of patients with bladder cancer., (© 2018 S. Karger AG, Basel.)

Background: CD138/Syndecan-1 (Sdc-1) is expressed on the tumor and stromal cells of invasive bladder carcinoma. CD138/Sdc-1 shedding from the cell surface is associated with the invasive phenotype in lung and breast cancers., Patients and Methods: Soluble CD138/Sdc-1 was measured in the sera of 86 bladder cancer patients and 57 healthy individuals by a commercial ELISA assay., Results: Soluble Sdc-1 was increased in the sera of patients with bladder cancer (138.42 ± 81.85 vs. 86.48 ± 82.58 ng/ml, p = 0.0003). Patients aged over 70 years had higher levels of CD138/Sdc-1 in their sera (159.7 ± 15.77 vs. 124.5 ± 9.99 ng/ml, p = 0.025), and soluble Sdc-1 levels were higher in the sera of patients with moderately differentiated tumors compared to poorly differentiated ones (170.47 ± 85.06 vs. 101.79 ± 68.24 ng/ml, p = 0.01). The soluble Sdc-1 level was higher in muscle-invasive (154.45 ± 83.60 vs. 89.9 ± 55.02 ng/ml) but not lymphatic-invasive (106.25 ± 52.10 vs. 123.43 ± 63.76 ng/ml) tumors (p = 0.027 and 0.45, respectively). A non-significant trend of soluble Sdc-1 increase in the sera of male patients compared to female patients was observed (145.38 ± 85.47 vs. 110.20 ± 59.04 ng/ml, p = 0.054)., Conclusion: The elevated levels of soluble CD138/Sdc-1 in older bladder cancer patients and those with muscular invasion sheds some light on the mechanisms of the disease invasion., (© 2015 S. Karger AG, Basel.)

Objective: To investigate the impact of preoperative serum C-reactive protein (CRP) on clinicopathological features and prognosis in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU)., Patients and Methods: Data of 265 patients from three German centers who underwent RNU for UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a categorical and continuous variable for the prediction of recurrence-free survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS) using uni- and multivariate Cox regression analyses., Results: The optimal cutoff for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was significantly associated with pT3/4 and pN+ in a preoperative model including age, gender, tumor multifocality, tumor localization and the Eastern Cooperative Oncology Group Performance Status. In a multivariable Cox regression model adjusted for features significant in univariable analysis, categorized and continuous CRP levels were both independent predictors for RFS [hazard ratio (HR) 1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p = 0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036)., Conclusions: Elevated preoperative CRP is significantly associated with aggressive tumor biology and an independent predictor for poor survival after RNU. Preoperative serum CRP represents an easily obtainable and cost-effective marker in UTUC and may help in counseling patients with regard to operative management and/or adjuvant or neoadjuvant therapies., (2014 S. Karger AG, Basel.)

Purpose: To predict the invasiveness of urothelial bladder carcinoma using a logistic regression model on preoperative peripheral blood samples., Patients and Methods: Hospital data of patients operated for urothelial carcinoma were reviewed retrospectively. Preoperative blood samples were collected before the first cystoscopic examination. Any kind of infection or inflammation was an exclusion criterion. Patients were grouped as having a non-muscle-invasive or muscle-invasive urothelial carcinoma. The mean age was 69 years and was determined as the cut-off value. According to receiver operating characteristic curves, threshold points were determined for lymphocytes, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), thrombocytes and mean platelet volume. Demographic specialties, parameters obtained from blood samples, tumor size and multiplicity were evaluated and significant parameters were put into a logistic regression model., Results: The study group consisted of 80 non-muscle-invasive and 102 muscle-invasive patients. Age (≤69 vs. >69), female gender, NLR (2.57), mean platelet volume (7.9/fl) and platelet count (400,000/µl) were significant parameters and put in a model. Using odds ratios, the probability of tumor invasiveness was calculated by a formula., Conclusion: Age, female gender, NLR and platelet count were found to be the predictors of invasiveness of urothelial carcinoma., (Copyright © 2012 S. Karger AG, Basel.)

Introduction: Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, involvement of trace elements in the tumorigenesis of transitional cell carcinoma of the bladder has been poorly investigated. The aim of this study was to examine the relationship between zinc, copper and bladder cancer., Materials and Methods: Zinc and copper concentration and Cu/Zn ratio in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of the control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumor stage., Results: While the copper concentrations reached statistically higher values in the bladder cancer tissue, the zinc levels in the sera and bladder tissue of the patients with this carcinoma were substantially lower as compared to those of the control group. The serum Cu/Zn ratio was significantly higher in the bladder cancer group and this increase was greater in the patients with muscle-invasive neoplasm., Conclusions: The results obtained suggest a relationship between trace elements and the bladder cancer., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To investigate galectin-8 expression patterns in normal urothelium and bladder cancer specimens and to elucidate its prognostic value., Materials and Methods: 162 samples of non-muscle-invasive transitional cell carcinoma, 25 samples of muscle-invasive transitional cell carcinoma and 10 samples of normal urothelium were investigated by immunohistochemistry using tissue microarrays. Complete patient and tumor characteristics were compared with galectin-8 staining patterns. The likelihood of tumor recurrence and progression was analyzed based on a 3-year follow-up., Results: Loss of galectin-8 was associated with the likelihood of tumor recurrence in univariate (p < 0.05) and multivariate analyses (p < 0.01). No significance was observed for tumor progression. Patients whose specimens showed weak galectin-8 expression had a shorter recurrence-free interval (42 vs. 12 months; p < 0.01, log-rank test). All of the 10 normal urothelium samples showed high galectin-8 expression. Decreased staining was found to be associated with higher tumor stages and grades (p < 0.0001, one-way ANOVA). A significant difference was found comparing normal urothelium with any tumor stage (p < 0.01), pTa vs. pT1 tumors (p < 0.05) and non-muscle-invasive vs. muscle-invasive tumors (p < 0.0001)., Conclusions: Loss of galectin-8 might be an early step in the development of malignant lesions of the bladder and is a significant independent predictor of recurrence., (Copyright © 2011 S. Karger AG, Basel.)

Background: Vascular endothelial growth factor (VEGF) and its receptors are major regulators of cancer cell growth and metastases. We investigated the association between serum VEGF levels and clinicopathological parameters in bladder cancer patients. We also evaluated the effects of VEGF and its receptor inhibitor on proliferation and invasion in bladder cancer cell lines., Methods: Serum VEGF levels were measured in 52 patients with bladder cancer and 45 healthy controls. In highly invasive bladder cancer cell lines (T-24, UMUC-3 and J82), we assessed the effect of VEGF on proliferation and invasion of bladder cancer cell lines. The effect of VEGF receptor (VEGFR) tyrosine kinase inhibitor against bladder cancer cell lines was also measured., Results: Serum levels of VEGF were significantly higher in patients with muscular invasive bladder cancer than in patients with superficial bladder cancer (p < 0.005). VEGF increased tumor proliferation in a dose-dependent manner in all cell lines. VEGFR-2 tyrosine kinase inhibitor inhibited proliferation in all three cell lines, and inhibited invasion in T24., Conclusions: In bladder cancer, the serum VEGF level correlates significantly with muscular invasiveness. This study suggests that VEGF promotes tumor proliferation and invasion through VEGFR-2. VEGF-targeted therapy may be effective in treating invasive bladder cancers., (Copyright 2009 S. Karger AG, Basel.)

Introduction: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence., Patients and Methods: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry., Results and Conclusion: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR., (2008 S. Karger AG, Basel)

Introduction: Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS)., Material and Methods: Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months., Results: Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2-4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed., Conclusion: Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.

Introduction: To investigate the prognostic importance of the changes in serum p53 antibody titrations during follow-up of patients who had anti-p53 antibody-positive invasive bladder tumors with transitional epithelial cells., Materials and Methods: The study group consisted of 23 clinically T3

Introduction: The potential value of serum levels of intercellular adhesion molecule-1 (ICAM-1) in the staging and pathological nature of bladder cancer was investigated in this study., Materials and Methods: A total of 90 patients (mean age 64.5 +/- 7.1) having transitional cell carcinoma of the bladder and 30 control patients (mean age 64.0 +/- 5.5) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery, at the same hour of the day., Results: The preoperative sICAM-1 levels were found to be 46.2 +/- 14.7 and 28.0 +/- 7.8 ng/ml in the tumor group and the control group respectively, which is significantly higher (p = 0.00). The ICAM-1 levels were not different in the invasive tumor group (36 patients) and the superficial tumor group (54 patients; 47.3 +/- 13.8 ng/ml in the invasive group and 45.5 +/- 15.3 ng/ml in the superficial tumor group; p = 0.520). The serum levels of sICAM-1 were significantly higher in grade III tumors than grade I and II tumors (62.0 +/- 8.7, 38.4 +/- 11.9 and 42.2 +/- 8.2 ng/ml respectively; p = 0.000). The mean serum sICAM-1 levels in tumors >3 cm and <3 cm were found to be 52.6 +/- 15.8 and 40.7 +/- 11.0 ng/ml respectively which is statistically significant (p = 0.000)., Conclusions: In this study, serum ICAM-1 levels were found to be related to tumor presence, grade and size. Larger series are needed for the thorough understanding of the role of ICAM-1 in bladder cancer., (Copyright 2003 S. Karger AG, Basel)

Introduction: Reactive oxygen species-induced damage to DNA plays a major role in carcinogenesis., Methods: In order to estimate the level of oxidative damage in bladder cancer, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined in DNA isolated from peripheral blood leukocytes of healthy adults and patients with superficial transitional cell carcinoma. Patients with transitional cell carcinoma of the bladder and control individuals were similar in age. In this study, the level of 8-OHdG in DNA in male subjects was measured by the high-performance liquid chromatography-electrochemical detector method., Results: The 8-OHdG levels in DNA from leukocytes of bladder cancer patients were significantly higher than those in controls., Conclusion: Reduction of oxidative stress is thought to be a very important measure for primary prevention of bladder cancer., (Copyright 2003 S. Karger AG, Basel)

Background: Mutations of p53 gene were demonstrated in many solid tumors with varying frequency. We analyzed the relationship between p53 protein expression in bladder cancer tissue, p53 autoantibodies in serum and the clinical course of 32 patients with and 10 patients without transitional cell carcinoma of the urinary bladder., Materials and Methods: In the 32 patients studied, bladder cancer was diagnosed as pTaG1-2 in 8 cases, pT1G2 in 6, pT1G3 in 7, pT2G2-3 in 7, pT3G2-3 in 3 and pT4 in 1 patient. Anti-p53 antibodies were detected by an enzyme-linked immunosorbent assay. Immunohistochemical staining was performed using a standardized alkaline phosphatase monoclonal anti-alkaline phosphatase method. To prove the statistical significance of tumor grading and staging, the Kruskal-Wallis test was applied (p < 0.01). The mean follow-up was 26 months., Results: We found 12.5% p53 autoantibody-positive sera without a statistically significant correlation with tumor grade (p = 0.0569) and category (p = 0.612). Three of 4 patients who had p53 autoantibody-positive sera died within 9 months. All of these sera-positive patients had p53 protein-positive tumor tissue. Control sera were all negative for p53 autoantibodies., Conclusion: This study shows a strong relationship between p53 protein overexpression and the occurrence of p53 autoantibody in bladder cancer. The expression of p53 autoantibodies seems to be an event in cases of bladder cancer with an unfavorable tumor-specific outcome. Because of the small number of cases and the short follow-up time, further quantitative studies will hopefully demonstrate whether this might be of prognostic importance., (Copyright 2000 S. Karger AG, Basel)

Two rare cases of urothelial tumor with high serum carcinoembryonic antigen (CEA) and TA-4 levels are presented. One is a case of lymph node metastasis due to bladder tumor: pathological diagnosis revealed mucoepidermoid carcinoma. The other is a case of left renal pelvic tumor: pathological diagnosis revealed transitional cell carcinoma with glandular and squamous differentiation. The serum CEA and TA-4 levels, high before surgery, decreased after surgery.

In 47 patients with transitional cell carcinoma (TCC) of the bladder, we investigated the relationship between tissue laminin distribution and serum laminin levels. The results were compared with those obtained from 6 patients with pathologically proven normal bladder mucosa as well as those obtained previously from 50 controls and 16 patients with benign bladder disorders. Interruption of the basement membrane (BM) laminin staining pattern was correlated with high serum laminin levels (r = 0.34; p < 0.01). The majority of patients with discontinuous BM laminin staining (82%) showed elevated serum laminin levels above the upper limit of normal range. In addition, the mean value of serum laminin P1 was significantly higher in patients with discontinuous BM than that in patients with intact BM (t = 3.18; p < 0.005). These data suggest that the high serum laminin levels in TCC patients are largely caused by the process of BM breakdown and loss.

We report a patient with gynecomastia and ectopic production of human chorionic gonadotropin (HCG) by a transitional cell carcinoma of the bladder. In the present case, serum HCG levels and gynecomastia paralleled the clinical course. On admission, the patient was suffering from invasive transitional cell carcinoma (grade 3) of the bladder with metastasis to the left inguinal lymph nodes, together with gynecomastia. The serum HCG level was also elevated. After anticancer chemotherapy, the apparent bladder lesion and gynecomastia disappeared, and the serum HCG level declined to within normal limits. About 2 months after discharge, when the patient suffered from recurrent invasive tumors of the bladder, gynecomastia reappeared and the serum HCG level again became elevated. beta-HCG was demonstrated in biopsy tissue using the immunoperoxidase technique. The presence of beta-HCG was always focally demonstrated and was shown to be localized in the cytoplasm of the tumor cells.

In a combined (cross-sectional and longitudinal) study, the serum concentration of laminin P1 was measured by radioimmunoassay in 16 patients with benign inflammatory bladder disorders and 47 patients with transitional cell carcinoma of the bladder. The results were compared with the serum laminin P1 values in 50 healthy control subjects. In the cross-sectional study, the mean value of serum laminin P1 was significantly higher in bladder cancer patients than either the controls (p < 0.0001) or patients with benign inflammatory bladder disorders (p < 0.001). Similarly, the mean values of all different stages of grades of the tumor were significantly higher than either the controls or patients with benign inflammatory disorders. Progressive increase in the mean values of serum laminin P1 could also be found with deterioration of the stage or grade of the tumor. However, the difference between the mean values of the different cancer stages or grades did not reach statistical significance. In the longitudinal study, no significant difference could be detected between the mean values of patients with superficial tumor recurrence and those with remission of the disease (p > 0.5). Nevertheless, in the invasive cancer group, the levels of serum laminin P1 were directly proportional with progression of the disease (Z = 2.94; p < 0.01).

In a prospective study we have included the specific red cell adherence (SRCA) test for the identification of blood group isoantigens in the investigation of patients with bladder tumor. The preliminary results, relating the SRCA test to grade and stage in 50 patients are presented. None of the SRCA-positive tumors were of high-grade malignancy (WHO III), and only SRCA-negative tumors had invasive properties at the time of investigation. 8 of 9 patients with carcinoma in situ were SRCA-negative.

Blood group antigens and carcinoembryonic antigen (CEA) were sought in the tissues of 37 bladder tumor cases using enzyme antibody method. A correlation (p less than 0.01) was found between the extinction of ABO (H) and progressive malignant states of the tumor or invasion stage. Significant correlation (p less than 0.05) was observed between the presence of CEA and the invasion stage. The state of the T antigen, however, did not reflect the malignancy grade or invasion stage. The states of ABO (H) and CEA significantly reflected (p less than 0.05) the prognosis, as did the malignancy grade and invasion stage, while the state of the T antigen did not correlate with the prognosis. Although there was a correlation (p less than 0.01) between the extinction of ABO (H) blood group antigens and the presence of CEA, the state of T antigen did not significantly correlate with ABO (H) antigen or CEA. From what has been mentioned, the search for intratissue ABO (H) antigens and CEA is important and will provide a useful auxiliary means in diagnosing biopsy specimens.

We used the specific red cell adherence (SRCA) technique to detect the A, B, O cell surface antigen on 61 transitional cell carcinomas of the urinary bladder seen from 1979 to 1982 at the Urology Department of Kaohsiung Medical College Hospital. It was suggested in this study that the loss of surface antigen had good correlation with both the pathological grade and clinical stage of tumors. On the other hand, the patients deprived of the surface antigen were poorer in prognosis than those with positive surface antigens. Among the four groups of A, B, O and AB patients, patients with blood group O had higher mortality rates, and more susceptibility to loss of the surface antigen. This study also demonstrated that the activation of surface antigen will reduce as the age increased. Of 11 patients with recurrent stage A tumors in this study, 8 had positive surface antigen and 3 had negative surface antigen. In 8 cases of positive surface antigen, 1 (13%) subsequently developed an invasive tumor. In contrast, 2 (67%) among the 3 negative surface antigens developed invasive tumors and the statistics showed significant differences (p less than 0.05). Consequently, the SRCA technique may be valuable for predicting malignant potential in early stage cancer of the bladder.

The role of blood group ABO(H) surface isoantigen measurement in bladder cancer is discussed. The basis for this test is examined and an attempt is made to place the current status of this test in proper perspective.

6 patients with recurrent high grade superficial bladder cancer were treated with human recombinant alpha-2-Interferon (alpha 2-IFN). After initial transurethral electroresection of macroscopically visible tumor, human recombinant alpha 2-IFN was administered by daily intramuscular injections for a period of 6 weeks. The influence of IFN on the patients' immune reactivity was assessed by determination of the natural killer (NK) cell activity. Within the first week, in all the patients an increase of the NK cell activity was noted. This, however, was only a short-term effect. An increase of the IFN dosage did not lead to further NK cell stimulation. Determination of the IFN serum levels during IFN treatment revealed maximum levels of 260 IU/ml. They were measured 2 weeks after therapy begin. During treatment no further increase of IFN serum levels were found. The augmentation of the NK cell activity does not seem to depend on IFN serum levels. The amount of IFN found in patients' sera did not effect tumor cell growth in vitro.

Serum level of peptide hormones LH, FSH, TSH and prolactin have been measured in patients with urogenital tumor. In this randomized study we found a frequent elevation of TSH and prolactin, which did not correlate. Increased serum level of TSH was confirmed to be without any elevation of serum T3 and T4. In some of these patients ectopic production of peptides may account for this abnormality. Systemic change of peptides in elderly patients, however, must be taken into consideration as well.

Two cases of hypercalcemia associated with transitional cell carcinoma and negative bone scan are described. In both cases hypercalcemia appeared while there was evidence of tumor spread. Although hypercalcemia was controlled, both patients died shortly thereafter. Hypercalcemia rarely occurs in transitional cell carcinoma and its appearance may suggest spreading of the tumor and poor prognosis.

13,14-Dihydro-15-keto-prostaglandin F2 alpha (13,14-DHK-PGF2 alpha) represents a stable product of degradation after pulmonary flow and it is shown to be reliably measured by radioimmunoassay. In patients with urogenital tumors, serum levels of 13,14-DHK-PGF2 alpha are distinctly elevated when compared to a control group. The rate of synthesis of this compound in urogenital tumors, however, appears to be different.