bromochloroacetic-acid and Hematuria

Finding and development of new bladder cancer markers is still a very dynamic field. Because of the mass of all these markers it is impossible to report all of them. This paper reviews the role of bladder cancer markers in diagnosis and highlights the most important biomarkers studied and reported recently. A medline based literature search was performed to examine the field of bladder cancer markers. Major topics focus on selected bladder cancer markers from nearly all categories of the wide field of bladder cancer markers: Hematuria, FISH, FGFR3, SURVIVIN, u-PAR, TP53 mutation, HER-2/neu, TPA, NMP22, CK-19, CK-20, CYFRA 21-1. The use and clinical importance as diagnostic help are discussed. In this review a highlight to some of the most important markers was made. Further determination of recurrence and progression marker will contribute to establish better treatments for the individual patient. Molecular staging of urological tumors will allow selecting cases that will require systemic treatment. It is necessary and important to integrate under the same objectives basic and clinical research.

Topics: Antifreeze Proteins, Type I; Antigens, Neoplasm; Biomarkers, Tumor; Cysteine Proteinase Inhibitors; Hematuria; Humans; Inhibitor of Apoptosis Proteins; Keratin-19; Keratin-20; Keratins; Microtubule-Associated Proteins; Nuclear Proteins; Predictive Value of Tests; Receptor, ErbB-2; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Urokinase Plasminogen Activator; Sensitivity and Specificity; Survivin; Tissue Polypeptide Antigen; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms

Bladder cancer biomarker development has advanced significantly over the last decade, but has not yet been able to make a significant impact in the diagnosis and management of the disease. Many available markers are suitable, but do not meet the expectations of physicians and patients. Patients do not want to compromise accuracy in diagnosing bladder cancer for less-invasive tests. The review highlights the latest developments in bladder cancer biomarkers, including markers developed over the last year, and comments on the high standards placed on these markers which have delayed their widespread implementation into the urologic field.. New markers described in the last year include soluble Fas, urothelial carcinoma-associated 1 and human chorionic gonadotropin beta type II genes. The latter two markers represent the contribution of genomic technology to this field. Also described are updates to known markers, including long-term follow-up of hematuria screening, recent studies in DNA methylation for bladder cancer diagnosis and patient perspectives on bladder tumor markers.. Biomarkers for bladder cancer have been intensively scrutinized over the last decade, but despite new findings and good performance characteristics, they are currently not accepted in clinical practice.

Topics: Antigens, Neoplasm; beta-N-Acetylhexosaminidases; Biomarkers, Tumor; Carcinoembryonic Antigen; Complement Factor H; DNA Methylation; DNA Mutational Analysis; DNA, Neoplasm; Enzyme-Linked Immunosorbent Assay; Fas Ligand Protein; Gene Expression Regulation, Neoplastic; Genomics; Hematuria; Histone Acetyltransferases; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; In Situ Hybridization, Fluorescence; Inhibitor of Apoptosis Proteins; Keratins; Microsatellite Repeats; Microtubule-Associated Proteins; Molecular Diagnostic Techniques; Neoplasm Proteins; Nuclear Proteins; Patient Selection; Predictive Value of Tests; Prognosis; Proteomics; Reagent Kits, Diagnostic; Survivin; Telomerase; Transcription Factors; Urinary Bladder Neoplasms

We report a late recurrence of a cholesteatoma of the left kidney after 15 years. Both the initial case and the recurrence were treated by endourologic and percutaneous approaches.

Topics: Cholesteatoma; Female; Flank Pain; Hematuria; Humans; Keratins; Kidney Calculi; Kidney Diseases; Kidney Pelvis; Magnetic Resonance Imaging; Middle Aged; Nephrostomy, Percutaneous; Recurrence; Time Factors; Tomography, X-Ray Computed; Ultrasonography

We describe five patients who recently presented with gross hematuria secondary to inflammatory pseudotumors of the bladder along with a review of the literature. At presentation, four of the five patients were clinically misdiagnosed as malignancies of which two were further believed to be leiomyosarcomas on initial histological examination because of their spindle-cell appearance. Conservative excision either by transurethral resection or partial cystectomy was curative in all cases. The main importance of these rare, benign lesions is to differentiate them from malignant tumors for which they may be mistaken, thus avoiding radical surgery and its attendant complications.

Topics: Adolescent; Adult; Cystectomy; Desmin; Diagnosis, Differential; Diagnostic Errors; Female; Granuloma, Plasma Cell; Hematuria; Humans; Keratins; Leiomyosarcoma; Male; Middle Aged; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Vimentin

Hemangioblastoma is a benign tumor that can occur sporadically, or in association with von Hippel-Lindau disease in approximately one-quarter of the cases. Only exceptionally does it occur outside the central nervous system. This report describes 2 cases of sporadic renal hemangioblastoma, with 1 patient presenting with hematuria and polycythemia, and the other low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. Many of the tumor cells showed pleomorphic nuclei, but the mitotic figures were rare. The cytoplasm was eosinophilic, and occasionally finely vacuolated indicating the presence of lipid. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for α-inhibin, S100, and neuron-specific enolase. This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid angiomyolipoma, adrenal cortical carcinoma, and paraganglioma, deserves wider recognition for its occurrence as a primary renal tumor.

Topics: Biomarkers, Tumor; Female; Hemangioblastoma; Hematuria; Humans; Immunohistochemistry; Inhibins; Keratins; Kidney Neoplasms; Low Back Pain; Male; Middle Aged; Nephrectomy; Phosphopyruvate Hydratase; Polycythemia; S100 Proteins

We report seven cases of renal medullary carcinoma collected from several institutions in Brazil. In spite of a relatively high incidence of sickle cell trait in Brazil, this is a rare tumor. All patients were males between the ages of 8 and 69 years (mean 22 years). From the collected information, the most frequent presenting symptoms were gross hematuria and flank or abdominal pain. The duration of symptoms ranged from 1 week to 5 months. Most of the tumors were poorly circumscribed arising centrally in the renal medulla. Size ranged from 4 to 12 cm (mean 7 cm) and hemorrhage and necrosis were common findings. All seven cases described showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. All cases disclosed the characteristic reticular pattern consisting of tumor cell aggregates forming spaces of varied size, reminiscent of yolk sac testicular tumors of reticular type. Other findings included microcystic, tubular, trabecular, solid and adenoid-cystic patterns, rhabdoid-like cells and stromal desmoplasia. A peculiar feature was suppurative necrosis typically resembling microabscesses within epithelial aggregates. The medullary carcinoma of the 69-year-old patient was associated with a conventional clear cell carcinoma. To our knowledge, this association has not been previously reported and the patient is the oldest in the literature. The survival after diagnosis or admission ranged from 4 days to 9 months. The 8-year-old African-Brazilian patient with a circumscribed mass is alive and free of recurrence 8 years after diagnosis. This case raises the question whether a periodic search for renal medullary carcinoma in young patients who have known abnormalities of the hemoglobin gene and hematuria could result in an early diagnosis and a better survival.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Brazil; Carcinoembryonic Antigen; Carcinoma, Medullary; Child; Flank Pain; Hematuria; Humans; Immunohistochemistry; Keratins; Kidney Medulla; Kidney Neoplasms; Male; Mucin-1; Neoplasm Metastasis; Risk Factors; Sickle Cell Trait; Time Factors; Treatment Outcome; Vimentin

The urinary concentration of soluble cytokeratin 19 fragments, measured by the CYFRA 21-1 assay, may be used for the noninvasive, early detection of bladder carcinoma.. This prospective study examined urine samples from 325 patients. The authors included 152 patients who presented with hematuria or irritative voiding symptoms (Group 1), 107 patients who were under surveillance after undergoing transurethral resection of bladder carcinoma (Group 2), 46 patients with urinary tract pathology other than bladder carcinoma (Group 3), and 20 healthy participants (Group 4). The urine concentration of CYFRA 21-1 was measured by an immunoradiometric assay. The patients in Groups 1 and 2 underwent cytoscopy and urine cytopathology. Biopsies were obtained if a tumor was seen on cytoscopy or if there was a suspicion of carcinoma in situ (CIS).. The optimal cut-off concentration for the detection of primary bladder tumors, 4.9 microg/L, resulted in a sensitivity of 79.3% and a specificity of 88.6%. The optimal threshold for the detection of recurrent bladder tumors (excluding patients who had been treated with intravesical bacillus Calmette-Guerin [BCG]), 4.04 microg/L, resulted in a sensitivity of 76.2% and a specificity of 84.2%. There was no significant advantage for centrifugation of the urine samples or for determination of the creatinine concentration in the urine samples. The CYFRA 21-1 assay of urine samples provided a three-fold greater sensitivity compared with the sensitivity of cytology for detecting Grade 1 transitional cell tumors. CYFRA 21-1 detected 91.9% of Grade 3 tumors, 100% of CIS, and 92.8% of invasive bladder tumors (T2 or higher classification). The CYFRA 21-1 assay detected all tumors that had positive cytology with the exception of only one tumor. Conversely, the assay identified 71% of primary tumors and 65% of recurrent tumors that were missed by cytopathology. Urinary stones, infection, and previous intravesical BCG immunotherapy caused many false positive results.. The urinary CYFRA 21-1 assay is a useful test for the noninvasive detection of bladder carcinoma and for surveillance of patients who were not treated previously with BCG. It may be used in combination with urine cytology and bladder ultrasound. Multi-institutional trials are required to compare the accuracy as well as the cost of this combination of tests with cystoscopy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Female; Hematuria; Humans; Immunoassay; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; ROC Curve; Sensitivity and Specificity; Urinary Bladder Neoplasms

Topics: Adult; Biomarkers, Tumor; Carcinoma, Medullary; Chorionic Gonadotropin, beta Subunit, Human; Fatal Outcome; Female; Hematuria; Humans; Keratins; Kidney Neoplasms; Mucin-1; S100 Proteins; Sickle Cell Trait

Exfoliated human urinary tract epithelial cells and renal tubular cells from urinary sediments of healthy adults, of urological patients and of internal patients were isolated and cultured. Cells started proliferating within 1 week after seeding a sediment. Proliferating cells formed colonies of different morphologies, designated as type-1 or type-2 cell colonies. Type-1 cell colonies showed irregular contours and spindle-like cells within the colonies. Subcultivation of type-1 cells for up to six passages was possible. Type-2 cell colonies showed smooth-edged contours and subcultivation was not possible. The epithelial character of type-1 cells was demonstrated by positive immunohistochemical staining for cytokeratin-7. In contrast to carbonic anhydrase-positive stained Madin Darby canine kidney cells (MDCK), which were used as positive controls for renal tubular cells, type-1 cells were carbonic anhydrase-negative on staining with the cobalt phosphate method. This indicates that type-1 cells were not of renal tubular origin. Type-2 cells were positively stained for carbonic anhydrase, indicating that type-2 cells were renal tubular cells. Type-2 cell colonies could be assigned to two subgroups with different cell forms. Colonies of cobblestone-like cells more often occurred than type-2 cell colonies with spindle-like cells, which are described in this study for the first time. Colonies with cobblestone-like cells formed domes (hemicysts), whereas spindle-like type-2 cell colonies did not. Cultures of urinary sediments from healthy adults, elderly multimorbid patients treated with furosemide, and urological patients with urolithiasis treated with sulfamethoxazole/trimethoprim and/or with a percutaneous nephrostomy catheter were compared. In 52% of all cultured sediments from healthy adults, in 30% of those from multimorbid patients, and in 75-80% of those from urological patients cells proliferated to colonies. The ratios of type-1 to type-2 cell colonies were 3.3:1 (healthy adults), 1.4:1 (urological patients with urolithiasis), and 1.8:1 (urological patients with urolithiasis, urine was directly collected from the renal pelvis with a percutaneous nephrostomy catheter). Successful cultures of the urinary sediments from these three groups revealed means of 3 or 4 colonies, 14 colonies, and 21 colonies, respectively. Differences in the number of colonies in relation to sex were observed only for the group of urological patients. It was shown that type-1 c

Topics: Adolescent; Adult; Aged; Animals; Carbonic Anhydrases; Cells, Cultured; Culture Techniques; Dogs; Epithelial Cells; Female; Hematuria; Humans; Keratin-7; Keratins; Kidney Tubules; Male; Middle Aged; Nephrostomy, Percutaneous; Urinary Calculi; Urinary Tract; Urine

Of the 20 known cytokeratins, CK-19 is expressed in normal urothelium, whereas the recently identified CK-20 is expressed in urothelial carcinoma cells but not in normal urothelial cells. The aim of this study was to examine whether CK-20 expression could serve as a noninvasive test in which malignant urothelial cells in urine are detected and monitored.. In the current study, the authors used reverse transcriptase-polymerase chain reaction (RT-PCR) methods to determine the expression of CK-20 in cells separated from the urine of patients with bladder carcinoma. Cells were obtained from the urine of 87 patients divided into the following 2 groups: 1) 14 healthy volunteers without any known history of transitional cell carcinoma (TCC), and 2) 73 patients with hematuria suspected for TCC of the bladder. For control purposes, CK-20 expression was examined in cells of 1) bladder carcinoma tumors of 5 patients, 2) blood of either patients with bladder carcinoma (n = 5) or healthy controls (n = 5), and 3) three different cell lines. RNA of the various cell pellets was extracted and RT-PCR was performed with CK-20 and CK-19 primers (CK-19 was used as a marker for normal epithelial cells).. CK-20 amplification band (370 bp) was obtained with mRNA extracted from TCC cells of either bladder tumor or HT-29 line (a CK-20 colon carcinoma line). Sensitivity of the method was found to be 91%, whereas specificity was 67%. Among the 7 false-positive cases, 3 showed atypia, 3 hyperplasia, and 1 metaplasia, and 2 underwent previously successful TCC tumor removals, suggesting that the CK-20 test also responded to premalignant lesions. No false-positive cases were found in the healthy control group. No other preparation, including blood of the patients of with TCC, showed the CK-20 amplification band.. These results indicate that CK-20 is a potential biomarker for noninvasive detection of bladder carcinoma by assaying uroepithelial cells from the voided urine specimen with RT-PCR.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Transitional Cell; False Positive Reactions; Female; Gene Expression Regulation, Neoplastic; Hematuria; HT29 Cells; Humans; Hyperplasia; Keratins; Male; Metaplasia; Middle Aged; Polymerase Chain Reaction; Precancerous Conditions; RNA, Messenger; Sensitivity and Specificity; Transcription, Genetic; Tumor Cells, Cultured; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium