[Role of immunocytology in the evaluation of patients with painless gross hematuria]. / Rolle der Immunzytologie in der Abklärung von Patienten mit schmerzloser Makrohämaturie.

OBJECTIVE: Gross hematuria is a highly worrisome episode in a patient's history mainly due to the fact that the prevalence of bladder cancer is significant in this group of patients. In this prospective study the role of immunocytology in the evaluation of patients with gross hematuria was investigated. MATERIALS AND METHODS: Ucyt is an immunocytological assay based on microscopic detection of tumor-associated antigens on urothelial cells. The study included 103 consecutive patients with a first episode of painless gross hematuria without prior transitional cell carcinoma. Urine samples were obtained from all patients and examined cytologically and immunocytologically. RESULTS: Clinical assessment by physical examination, laboratory tests, endoscopy, and imaging modalities yielded urothelial cancer in 22 cases (21%). Further diagnoses were BPH (30%), inflammation (10%), urolithiasis (7%), and"further conditions" (16%). In 17 patients the reasons for hematuria were not determined. For cystoscopy, immunocytology, and conventional urine cytology a sensitivity of 89 (excluding UUT), 86, and 45% was observed. Specificity was 94, 82, and 89%, respectively. Two and three bladder tumors were not detected by cystoscopy and immunocytology, respectively. CONCLUSIONS: The combination of cystoscopy and immunocytology yielded 100% sensitivity, while combining cystoscopy and cytology only marginally improved the sensitivity of cystoscopy alone. Since sensitivity appears to be of key relevance in the assessment of patients with gross hematuria, the authors suggest the addition of a sensitive noninvasive test to the diagnostic armamentarium in this situation.

Immunocytology in the assessment of patients with asymptomatic hematuria.

Painless hematuria has remained a diagnostic challenge in daily urological practice. Key problem in the assessment of these patients is the discrimination between malignant and non-malignant conditions. In this prospective study the role of immunocytology in the evaluation of patients with hematuria was investigated. Ucyt is a commercially available immunocytological assay based upon microscopical detection of tumor-associated antigens on the membrane of urothelial cells by immunofluorescence. Between October 2000 and July 2007, 301 consecutive patients with a first episode of painless hematuria without prior transitional cell carcinoma were included. Urine samples were obtained from all patients and examined cytologically and immunocytologically. Clinical assessment by physical examination, laboratory tests, endoscopy and imaging in 228 cases with microhematuria and 66 cases with gross hematuria yielded bladder cancer in 10 (4.6%) and 17 (27%) patients, respectively. Clinical workup demonstrated that composition of both groups was entirely different. Sensitivity of cystoscopy and immunocytology was similar in both groups. Furthermore, a negative finding in cystoscopy and immunocytology virtually excluded the presence of urothelial cancer. However, while predictive values of immunocytology were clearly superior to cytology in gross hematuria, cytology performed better in the microhematuria cohort. Combination of cystoscopy and immunocytology yield 100% sensitivity in the assessment of patients with painless hematuria. Based upon performance characteristics the authors recommend to replace urine cytology by a more sensitive marker like immunocytology in gross hematuria. In patients with microhematuria immunocytology could be used to select for patients at risk for urothelial cancer and thus spare negative patients from further examinations.

[Analyses of the role of immunocytology in the differential diagnosis of patients with asymptomatic microhematuria]. / Untersuchungen zur Rolle der Immunzytologie in der Abklärung von Patienten mit asymptomatischer Mikrohämaturie.

INTRODUCTION: Discriminating between malignant and nonmalignant conditions remains a challenge in the evaluation of patients with asymptomatic microhematuria. In this prospective study the role of immunocytology in the assessment microhematuria was studied. MATERIAL AND METHODS: uCyt is a commercially available immunocytological assay based on microscopical detection of tumor-associated antigens in urothelial cells by immunofluorescence. Between September 2000 and December 2006, 222 consecutive patients with newly diagnosed painless microhematuria without prior transitional cell carcinoma were included. All urine samples were examined cytologically and immunocytologically. A total of 211 samples (95%) were assessable. RESULTS: Clinical examination by physical examination, cystoscopy, laboratory tests, and imaging yielded bladder cancer in ten cases (4%). Further diagnoses were BPH (27%), cystitis (including IC) (12%), urolithiasis (9%), urethral or ureteral strictures (6%), papilloma (2%), and"further conditions" (16%). In 52 patients (23%) reasons for hematuria were not identified. Immunocytology was positive in 8 of 10 bladder tumors (80%) and negative in 178 patients with non-tumor-related hematuria (89%). CONCLUSIONS: The high sensitivity and good specificity of immunocytology is comparable with that reported in the literature despite a very low disease prevalence in this population. If assessment of these patients would have only been based on immunocytology, 180 costly and invasive diagnostic procedures would have been saved, with only 29 individuals (14%) undergoing these examinations unnecessarily. The authors conclude that these findings justify further investigation of this issue.

Damage in vitro to various organs and tissues by rubescenslysin from the edible mushroom Amanita rubescens.

Rubescenslysin, a haemolytic protein from Amanita rubescens, disrupted the cytoplasmic membrane of human leucocytes which were more sensitive than erythrocytes. In the isolated hearts of rats and guinea pigs it caused systolic contracture, which was preceded by potassium outflow and sometimes by a transient positive inotropic effect. On the electrically stimulated guinea-pig left atrium it showed at first a positive, followed by a negative inotropic effect; on the spontaneously beating right atrium it produced transient positive followed by negative inotropic and chronotropic effects. Atria were less sensitive than intact hearts. In the isolated rat phrenic nerve-diaphragm preparation it produced a contracture, which was associated with reduction of indirect and direct contractility. In the isolated guinea-pig ileum it produced a slow contraction followed by tachyphylaxis. As excitability declined due to rubescenslysin, so did excitability by acetylcholine and potassium. Atropine and pheniramine had only feeble antagonistic effects, but papaverine was more powerful. In isolated rat hepatocytes, rubescenslysin caused a rapid outflow of potassium and coarse cell protrusions while later the cells became stainable with trypan blue. In the isolated perfused rat liver it produced a rapid outflow of potassium and of cytoplasmic and mitochondrial enzymes, and a somewhat slower outflow of lysosomal beta-glucuronidase, accompanied by a rise in the lactate/pyruvate ratio and a decrease in bile production. In the isolated perfused rat kidney it caused an outflow of cytoplasmic and mitochondrial enzymes, together with massive proteinuria and serious restriction of sodium and potassium reabsorption and of urine output. In all the tissues investigated the effects of rubescenslysin began within a few min, were dose-dependent and practically irreversible. There were only minor differences in sensitivity between various organs and species. The observations indicate that the toxin is relatively nonspecific in its attack on components of cell membranes.