Voided Urine Samples Research Articles

CCL18 in a Multiplex Urine-Based Assay for the Detection of Bladder Cancer

The early detection of bladder cancer (BCa) is pivotal for successful patient treatment and management. Through genomic and proteomic studies, we have identified a number of bladder cancer-associated biomarkers that have potential clinical utility. In a case-control study, we examined voided urines from 127 subjects: 64 tumor-bearing subjects and 63 controls. The urine concentrations of the following proteins were assessed by enzyme-linked immunosorbent assay (ELISA); C-C motif chemokine 18 (CCL18), Plasminogen Activator Inhibitor 1 (PAI-1) and CD44. Data were compared to a commercial ELISA-based BCa detection assay (BTA-Trak©) and voided urinary cytology. We used analysis of the area under the curve of receiver operating characteristic curves to compare the ability of CCL18, PAI-1, CD44, and BTA to detect BCa in voided urine samples. Urinary concentrations of CCL18, PAI-1, and BTA were significantly elevated in subjects with BCa. CCL18 was the most accurate biomarker (AUC; 0.919; 95% confidence interval [CI], 0.8704-0.9674). Multivariate regression analysis highlighted CCL18 (OR; 18.31; 95% CI, 4.95-67.70, p<0.0001) and BTA (OR; 6.43; 95% CI, 1.86-22.21, p = 0.0033) as independent predictors of BCa in voided urine samples. The combination of CCL18, PAI-1 and CD44 improved the area under the curve to0.938. Preliminary results indicate that CCL18 was a highly accurate biomarker for BCa detection in this cohort. Monitoring CCL18 in voided urine samples has the potential to improve non-invasive tests for BCa diagnosis. Furthermore using the combination of CCL18, PAI-1 and CD44 may make the model more robust to errors to detect BCa over the individual biomarkers or BTA.

A pilot study of urinary microRNA as a biomarker for urothelial cancer

MicroRNAs (miRNAs) are part of a class of small ribonucleic acid (RNAs). They are important regulatory molecules, involved in several cell processes, such as developmental timing, stem cell division and apoptosis. Dysregulated miRNAs have been identified in several human malignancies, including bladder cancer tissue samples, and may confer a "tumour signature" that can be exploited for diagnostic purposes. We report on a prospective pilot study investigating the diagnostic capability of miRNAs in the urine of patients with urothelial cancer. Voided urine samples were collected from patients with urothelial carcinoma just prior to bladder tumour resection, as well as age-matched healthy control patients. Pathology demonstrated both low- and high-grade cancer. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed on the RNA extracts using primers for 4 miRNAs shown previously to be dysregulated in solid urothelial carcinomas with RNU6B as the endogenous control. Standard urine cytology was performed on all samples in a blinded fashion. Two miRNAs of interest were dysregulated in the urine from cancer patients with miR-125b showing an average 10.42-fold decrease (p < 0.01) and miR-126 showing an average 2.70-fold increase (p = 0.30) in the cancer samples compared to the normal controls. The sensitivity and specificity of the cytology on the same urine samples were 50% and 80%, respectively. Using these 2 miRNAs only, a decision-tree prediction model was generated for a validation cohort of patients yielding a specificity of 100% and a sensitivity of 80%. This preliminary study of candidate urinary miRNA in patients with low- and high-grade urothelial cancer demonstrated a significantly improved diagnostic accuracy over cytology. These results provide rationale for further studies on discovery and validation of candidate miRNAs in voided urine and may potentially lead to the development of a non-invasive and sensitive test for bladder cancer diagnosis and prognosis.

Reflex ImmunoCyt Testing for the Diagnosis of Bladder Cancer in Patients with Atypical Urine Cytology

BackgroundImmunoCyt/uCyt (Scimedx, Denville, NJ, USA) is a well-established urinary marker assay with high sensitivity for the diagnosis of urothelial carcinoma (UC) and can function as a second-level test to arbitrate atypical reads of urine cytology. ObjectiveTo determine the utility of uCyt as a reflex test for atypical cytology in patients undergoing a hematuria evaluation or surveillance with a history of UC. Design, setting, and participantsThe uCyt assay was performed as a second-level reflex test on all voided urine cytology tests read as atypical between January 2007 and June 2010 in an academic medical center. Records were retrospectively reviewed. Three hundred twenty-four patients underwent a total of 506 uCyt assays. InterventionReflex uCyt assay on atypical urine cytology. Outcome measurements and statistical analysisThe uCyt test characteristics include sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results and limitationsReflex uCyt was performed on 506 atypical voided urine samples that were followed by cystoscopy within 90 d. Reflex uCyt with a history of UC showed a sensitivity of 73%, a specificity of 49%, and an NPV of 80%. In those with a history of low-grade UC, reflex uCyt had a sensitivity of 75%, a specificity of 50%, and an NPV of 82%, while in those with a history of high-grade UC, it had a sensitivity of 74%, a specificity of 44%, and an NPV of 79%. Without prior history of UC, reflex uCyt had a sensitivity of 85%, a specificity of 59%, and an NPV of 94%. This study's limitations include its retrospective design and interobserver variability inherent to cystoscopy, which was used as the reference test. ConclusionsWhen used as a reflex test on atypical urine cytology, negative uCyt may predict a negative cystoscopy in select patients and modulate the urgency and further work-up in those with no prior history or low-grade disease.

1609 POTENTIAL USE FOR UROTHELIAL MUCOSA ENGINEERED WITH AUTOLOGOUS URINE DERIVED STEM CELLS SEEDED ON A POROUS COLLAGEN MATRIX IN HYPOSPADIAS REPAIR

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Lower Urinary Tract & Genitalia II1 Apr 20121609 POTENTIAL USE FOR UROTHELIAL MUCOSA ENGINEERED WITH AUTOLOGOUS URINE DERIVED STEM CELLS SEEDED ON A POROUS COLLAGEN MATRIX IN HYPOSPADIAS REPAIR Rongpei Wu, Guihua Liu, Shaofeng Wu, Anthony Atala, and Yuanyuan Zhang Rongpei WuRongpei Wu Winston Salem, NC More articles by this author , Guihua LiuGuihua Liu Winston Salem, NC More articles by this author , Shaofeng WuShaofeng Wu Winston Salem, NC More articles by this author , Anthony AtalaAnthony Atala Winston Salem, NC More articles by this author , and Yuanyuan ZhangYuanyuan Zhang Winston Salem, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1404AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Surgical repair of hypospadias often requires autogenous tissue, such as foreskin, bladder or oral mucosa to extend urethral segments. However, the procedure required to obtain these tissues is an invasive approach and it may lead to donor site morbidity. Additionally, adequate tissue for this substitution is not always available, and if the urethral defect is too long, this type of repair is not possible. Tissue-engineered tubular urethral tissues are an alternative option and allow for replacement of deficient urethral tissues with functionally equivalent ones. The goal of this study was to generate a 3-dimensional porous small intestinal submucosa (SIS) scaffold and recellularize this scaffold with urothelial cells (UC) and smooth muscle cells (SMC) derived from the differentiation of urine-derived stem cells (USC) in order to form engineered urethral tissue that could be used in hypospadias repair. METHODS Fresh SIS derived from pigs was decellularized with 5% peracetic acid (PAA). Cells were obtained from voided urine samples from healthy individuals. USC were isolated, characterized and induced to differentiate into UC and SMC. Differentiated UC and SMC derived from USC were seeded onto the SIS scaffolds in a layered co-culture fashion and cultured under dynamic conditions for one week. The seeded cells formed multiple uniform layers on the SIS and penetrated deeper into the porous matrix during dynamic culture. Urothelial and muscle cells derived from USC expressed UC markers (Uroplakin-III, AE1/AE3) or SMC markers (α-SM actin, desmin, and myosin), respectively, after implantation into athymic mice. RESULTS DNA content analysis showed that most nuclear material was removed from the SIS scaffold. Treatment with 5% PAA led to development of a highly porous surface with retention of less cellular material, and the decellularized SIS maintained the majority of the tensile strength of normal tissue. In 3-D dynamic culture, the seeded cells (UC and SMC) formed multiple, even layers on the surface of matrix. Cells also penetrated deeper into the lamina propria of the matrix compared to untreated matrix. Immunocytochemical staining indicated that the grafted USC expressed urothelial- and smooth muscle-specific markers both, in vitro and in vivo. CONCLUSIONS This study demonstrates that the decellularized SIS possesses appropriate 3-D porosity to prompt the induced USC to form multilayer of urothelium and SMC-matrix infiltration, which provides potential applications in urethral reconstruction in hypospdias repair. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e651 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rongpei Wu Winston Salem, NC More articles by this author Guihua Liu Winston Salem, NC More articles by this author Shaofeng Wu Winston Salem, NC More articles by this author Anthony Atala Winston Salem, NC More articles by this author Yuanyuan Zhang Winston Salem, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2210 DETECTION OF THE SECRETED PROSTATE CANCER BIOMARKER AGR2 IN VOIDED URINE

You have accessJournal of UrologyProstate Cancer: Detection and Screening V1 Apr 20122210 DETECTION OF THE SECRETED PROSTATE CANCER BIOMARKER AGR2 IN VOIDED URINE Sue-Ing Quek, Melissa Ho, Michelle Loprieno, William Ellis, Lawrence True, Elizabeth Wayner, and Alvin Liu Sue-Ing QuekSue-Ing Quek Seattle, WA More articles by this author , Melissa HoMelissa Ho Seattle, WA More articles by this author , Michelle LoprienoMichelle Loprieno Seattle, WA More articles by this author , William EllisWilliam Ellis Seattle, WA More articles by this author , Lawrence TrueLawrence True Seattle, WA More articles by this author , Elizabeth WaynerElizabeth Wayner Seattle, WA More articles by this author , and Alvin LiuAlvin Liu Seattle, WA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2385AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer is currently screened by an imperfect test of measuring the blood level of prostate-specific antigen (PSA/KLK3). This test has a false positive rate of nearly 75% with the result that many men would have to undergo an unnecessary biopsy. PSA is not a good cancer biomarker because it is not cancer-specific. Better markers are needed. Comparative transcriptomics between sorted CD26+ cancer cells and CD26+ luminal cells identified AGR2 (anterior gradient 2) as one of the highest up-regulated genes encoding secreted proteins in cancer. Overexpression in primary tumors was verified by tissue microarray analysis: AGR2 expression was absent in non-cancer (n=111) and BPH (n=288) vs. elevated in cancer (n=659) and PIN (n=68). AGR2 encodes a 19-kDa secreted protein that might be found in voided urine. METHODS Mouse monoclonal antibodies (mAbs) were generated against recombinant AGR2. One antibody pair, P1G4 (IgG1) to capture and P3A5 (IgG2a) to detect, showed good performance characteristics in a sandwich ELISA. This assay could measure AGR2 at sub ng/ml quantities. RESULTS AGR2 was detected in tissue digestion media of tumor specimens (and not that of non-cancer specimens) and culture media of AGR2-secreting prostate cancer cell lines. Specificity of the newly obtained mAbs was validated by immunoprecipitation, frozen tissue immunohistochemistry, and Western blot analysis. An AGR2 ELISA was developed with P1G4 and P3A5. Voided urine samples were collected from pre-operative cancer patients, and urinary protein was desalted and concentrated by spin filtration. The amount of AGR2 detected was scored as pg/100 μg urinary protein, and then converted to pg/ml urine. This ELISA was able to detect AGR2 in urine, ranging from 3.6 to 181 pg/ml, in an initial cohort of samples. Higher values appeared to correlate with tumor size. AGR2 was not detected in the urine of healthy control and a bladder cancer patient as bladder cancer cells do not overexpress AGR2. CONCLUSIONS For prostate cancer, an AGR2 urine test could be used for diagnosis and screening. The data showed that developing such a test for clinical application is viable because AGR2 is specific to cancer cells, and is secreted into urine. Since urine is a waste product, large volumes can be collected repeatedly and concentrated for testing. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e891 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sue-Ing Quek Seattle, WA More articles by this author Melissa Ho Seattle, WA More articles by this author Michelle Loprieno Seattle, WA More articles by this author William Ellis Seattle, WA More articles by this author Lawrence True Seattle, WA More articles by this author Elizabeth Wayner Seattle, WA More articles by this author Alvin Liu Seattle, WA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

203 ENDOTHELIAL DIFFERENTIATION OF HUMAN URINE DERIVED STEM CELLS FOR UROLOGICAL TISSUE REGENERATION

voided urine sample may contain malignant cells. In this study, we investigated whether cells isolated from upper urinary tract (UTCs) possess stem cell characteristics and could be an alternative cell source for bladder cancer patients. METHODS: Urine samples were collected from the upper urinary tract of 4 male bladder cancer patients using a ureteral catheter. The samples were centrifuged and the pellets were plated for primary culture. Cells were analyzed for colony forming unit, proliferation rate, cytogenetics, stem cell characterization and tumorigenicity. The results were compared with those of VUC collected from 3 healthy men. RESULTS: We were able to isolate cells possessing stem cell characteristics from urine, which were obtained from upper urinary tract. The UTCs were able to form colonies, had a higher proliferation rate than VUC and had normal karyotype without any chromosomal aberrations. The UTCs possessed stem cell characteristics (expression of CD44 , CD73 , CD90 , CD105 , SSEA4 ) and expressed several markers for urothelial, smooth muscle and endothelial cell lineages. The UTCs did not form teratoma when implanted into the subcapsular space of mouse kidney. CONCLUSIONS: The UTCs possessed stem cell characteristics and can potentially be an alternative cell source for urological tissue regeneration in bladder cancer patients.

Vascular Endothelial Growth Factor, Carbonic Anhydrase 9, and Angiogenin as Urinary Biomarkers for Bladder Cancer Detection

To investigate whether elevated urinary levels of vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9), and angiogenin are associated with bladder cancer (BCa). This was a case-control study in which voided urine samples from 127 patients (63 control subjects and 64 patients with BCa) were analyzed. The urinary concentrations of VEGF, CA9, angiogenin, and bladder tumor antigen (BTA) were assessed using enzyme-linked immunosorbent assays. We used the area under the curve of receiver operating characteristic curves to determine the ability of VEGF, CA9, and angiogenin to detect BCa in voided urine samples. Data were also compared with the findings from a commercial enzyme-linked immunosorbent assay-based BCa detection assay (BTA-Trak). The sensitivity, specificity, and positive and negative predictive values were calculated. The urinary concentrations of VEGF, CA9, angiogenin, and BTA were significantly elevated in those with BCa. VEGF was the most accurate urinary biomarker (area under the curve 0.886, 95% confidence interval 0.8301-0.9418). Furthermore, multivariate regression analysis highlighted VEGF (odds ratio 5.90, 95% confidence interval 2.60-13.40, P < .0001) as an independent variable. The sensitivity and specificity for VEGF (83% sensitivity and 87% specificity) outperformed those for BTA (80% sensitivity and 84% specificity). VEGF could be a valuable addition to voided urine sample analysis for the detection of BCa. Larger, prospective studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive evaluation of patients with BCa.

Characterization of Urine-derived Cells From Upper Urinary Tract in Patients With Bladder Cancer

To investigate whether cells isolated from the upper urinary tract (UTCs) possess stem cell characteristics and could be an alternative cell source for patients with bladder cancer. Current tissue engineering approaches for urologic tissue regeneration require invasive tissue biopsies to obtain autologous cells, and these procedures are associated with potential complications, such as donor site morbidity. Recently, cells isolated from voided urine (VUCs) have been proposed as an alternative cell source for urologic tissue engineering. However, VUCs should not be used in patients with bladder cancer, because the voided urine sample could contain malignant cells. Urine samples were collected from the upper urinary tract of 4 male patients with bladder cancer using a ureteral catheter. The samples were centrifuged and the pellets plated for primary culture. The cells were analyzed for colony-forming unit, proliferation rate, cytogenetics, stem cell characterization, and tumorigenicity. The results were compared with those of VUCs collected from 3 healthy men. The UTCs were able to form colonies, had a greater proliferation rate than the VUCs, and had a normal karyotype without any chromosomal aberrations. The UTCs possessed stem cell characteristics (expression of CD44+, CD73+, CD90+, CD105+, SSEA4+) and expressed several markers for urothelial, smooth muscle, and endothelial cell lineages. The UTCs did not form teratoma when implanted into the subcapsular space of a mouse kidney. The UTCs possessed stem cell characteristics and can potentially be an alternative cell source for urologic tissue regeneration in patients with bladder cancer.

Integrating metabolomic signatures and psychosocial parameters in responsivity to an immersion treatment model for adolescent obesity

With childhood obesity tripling in the past two decades alone, developing effective treatment to promote long-term weight loss and maintenance is critical. Unfortunately, while many children respond favorably to behavioral treatments, failure to lose and maintain weight loss is common. There is a critical need to determine non-invasive markers that can serve to predict an individual’s likelihood of having a positive response to treatment, and to monitor the treatment progress for early identification of those who may be at risk for relapse (e.g., weight gain) in order to provide more early, targeted and ongoing intervention of these high risk individuals. An exploratory investigation was conducted to determine: (a) the relevance of using metabolomics in delivering non-invasive markers to predict an individual’s responsiveness to an immersion treatment program, and (b) to integrate psychosocial and metabolomic profiles that can further serve to predict an adolescent’s positive response to weight loss. Obese adolescents (12–18 years old, BMI >95th percentile) attending a 3 weeks immersion healthy lifestyle camp, Take Off 4-Health (TO4-H), were recruited to provide first morning void urine samples and to complete psychosocial and health-behavior inventories at baseline and at the end of the 3 weeks program. Subjects were categorized as responders (decline of ≥0.5 BMI units) or non-responders (decline of <0.5 BMI units) based on weight loss between baseline and the end of the 3 weeks program. Subjects were additionally classified as having either a healthy or impaired self-esteem (impaired ≥20 or healthy <20) and depression (impaired ≥15 or healthy <15) at baseline and the end of the 3 weeks camp-based on their responses to psychosocial inventories. NMR based metabolomics was used to generate signatures of low molecular components in urine. Using multivariate analysis of signals, findings demonstrated a unique pattern for treatment responders vs. non-responders. Moreover, inspection of loadings plots and variable importance plots enabled the identification of a subset of metabolites and psychosocial variables that may assist in our understanding and prediction of adolescent responsivity to treatment for weight loss. For the psychosocial variables, improvement in self-esteem and depression did not correlate with weight loss, multivariate analysis of urinary metabolomics data using healthy and impaired classifications for self-esteem and depression did enable the determination of subsets of metabolites that best associated with impaired self-esteem and depression. Integrating the metabolomic and psychosocial data provided a marker profile pointing to both biochemical (metabolite) and psychosocial indexes (self-esteem and depression) that are most relevant to determining an individual’s overall response to treatment. This study demonstrates the utility of metabolomics in providing non-invasive markers that upon validation in a larger sample may be an extremely important tool in the early detection and clinical management of adolescent obesity.

333 Comparison of cytokeratin 20 with visual cytology and DNA image analysis in voided urine samples as diagnostic tools for bladder carcinoma

333 Comparison of cytokeratin 20 with visual cytology and DNA image analysis in voided urine samples as diagnostic tools for bladder carcinoma

ROLE OF PROGRANULIN GENE EXPRESSION AS A MOLECULAR BIOMARKER FOR BLADDER CANCER

Bladder cancer is the second most common cancer of the urinary system. Early diagnosis of this tumor and estimation of risk of future progression has a significant impact on prognosis. Although there are several molecular markers for the diagnosis and prognosis for this tumor, their accuracy is not ideal. Progranulin is a growth factor that may play a critical role in bladder cancer. Previous reports have shown that progranulin is essential for cellular proliferation. In this study, we examined whether progranulin gene expression can be a novel molecular marker for bladder cancer and evaluated its potential suitability as a urinary biomarker for bladder cancer diagnosis. Expression of progranulin gene in tissue and urine sediment of normal and bladder cancer samples was performed by semi-quantitative reverse transcription-PCR. Also, progranulin level was estimated in 90 voided urine samples, including 65 bladder cancer patients and 25 healthy volunteers using the quantitative enzyme immunoassay technique. Significant over-expression of progranulin was observed in bladder cancer cases. This over-expression was correlated with the stage and grade of the cancer. The urinary progranulin level was significantly higher in bladder cancer patients compared to control subjects (means: 18.39±0.56 and 9.17±0.41 ng mL-1, respectively; p<0.001). Furthermore, the urinary progranulin level at cut off value = 11.275 has a sensitivity = 93.8% and a specificity = 84% for cancer bladder diagnosis. Urinary progranulin may be considered as a simple, non-invasive test with acceptable sensitivity and specificity for bladder cancer diagnosis and may greatly improve the current diagnosis based on cytology. However, this is a preliminary study that opens the window for further researches to fully validate its results in progranulin and cancer bladder research.

Evidence of Uncultivated Bacteria in the Adult Female Bladder

Clinical urine specimens are usually considered to be sterile when they do not yield uropathogens using standard clinical cultivation procedures. Our aim was to test if the adult female bladder might contain bacteria that are not identified by these routine procedures. An additional aim was to identify and recommend the appropriate urine collection method for the study of bacterial communities in the female bladder. Consenting participants who were free of known urinary tract infection provided urine samples by voided, transurethral, and/or suprapubic collection methods. The presence of bacteria in these samples was assessed by bacterial culture, light microscopy, and 16S rRNA gene sequencing. Bacteria that are not or cannot be routinely cultivated (hereinafter called uncultivated bacteria) were common in voided urine, urine collected by transurethral catheter (TUC), and urine collected by suprapubic aspirate (SPA), regardless of whether the subjects had urinary symptoms. Voided urine samples contained mixtures of urinary and genital tract bacteria. Communities identified in parallel urine samples collected by TUC and SPA were similar. Uncultivated bacteria are clearly present in the bladders of some women. It remains unclear if these bacteria are viable and/or if their presence is relevant to idiopathic urinary tract conditions.

&lt;i&gt;Chlamydia trachomatis&lt;/i&gt; infection in an infertile population: a cross sectional study

<strong>Introduction: </strong>Chlamydia trachomatis is sexually transmitted and causes infection of the genital tract that leads to many long term complications. Invasive procedures in infected infertile females increase the risk of ascending infection and long term consequences. Though infertile individuals are considered a high risk population prevalence data for our population is not available. Furthermore, the use of risk factor identification in diagnosis is not well established. This study was planned to determine the prevalence of Chlamydia infection and to describe the socio-economic clinical characteristics that are associated with the presence of infection among a patient population who sought treatment for infertility at a tertiary care facility. <strong>Method: </strong>A cross sectional study was carried out among patients who sought infertility treatment at the infertility clinic of Colombo North Teaching Hospital, Ragama. Two hundred married couples were included in the study. The socio-economic data and any symptoms suggestive of genital infections were collected and Chlamydia trachomatis infection was diagnosed with a rapid antigen test using a commercial test kit. Intracervical swabs of the female and first void urine samples of the male were used. Data analysis was done to describe the prevalence of Chlamydia infection in each partner as well as to identify the number of couples where either partner was affected. Associations with recognized risk factors were identified. <strong>Results: </strong>Presence of symptoms was low in the males while one third of female subjects had one or more symptoms. The Chlamydia test revealed 12(6%) female and 6(3%) male study participants to be positive for current disease. These study participants were from 15 couples giving a prevalence rate of either partner being positive in 7.5% of couples. Of the risk factors identified the duration of marriage or infertility, education level, household income, alcohol use and smoking by the male, and presence of symptoms did not demonstrate a significant association with the presence of the disease. Partners staying away from each other were significantly associated with a positive result. <strong>Conclusion: </strong>There is 7.5% disease prevalence among infertile couples seeking treatment. Risk assessment and clinical symptoms have a limited value in identification of affected couples. Couples living separately have a high risk of Chlamydia infection. The high disease prevalence warrants either screening or empirical treatment of all infertile female patients undergoing invasive procedures. DOI: <a href="http://dx.doi.org/10.4038/sljog.v32i4.3989">http://dx.doi.org/10.4038/sljog.v32i4.3989</a> <em>SLJOG </em>2010; 32(4): 85-88<strong><em></em></strong>

Fluorescence in situ hybridization assay detects upper urinary tract transitional cell carcinoma in patients with asymptomatic hematuria and negative urine cytology

We evaluated the performance of a multiprobe FISH (fluorescence in situ hybridization) assay for noninvasive detection of upper urinary tract transitional cell carcinoma (UUT-TCC) in patients with asymptomatic hematuria and negative urine cytology. Voided urine samples from 285 patients with asymptomatic hematuria and negative urine cytology were prospectively analyzed by FISH technique. FISH assays were performed to detect chromosomal changes frequently associated with TCC, including aneuploidy of chromosomes 3, 7 and 17, and loss of the 9p21 locus. Eleven (3.9%) had a positive FISH result. Of the 11 patients, nine (81.8%) were found to have a TCC of the upper urinary tract, while no patients with negative FISH findings were found to have UUT-TCC. In this selected cohort, the sensitivity and specificity of FISH for the detection of UUT-TCC was 100% and 99.3%, respectively. Our preliminary data suggest that the clinical utility of FISH assay of chromosomes 3, 7, 9, and 17 as a noninvasive ancillary test for the diagnosis of UUT-TCC in a selected patient population with asymptomatic hematuria and negative urine cytology and by significant high sensitivity and specificity may be a reliable diagnostic approach for early detection of UUT-TCC patients. Further larger prospective and multicenter trials are needed to confirm our results.

Cytological findings in routine voided urine samples with hematuria from a tertiary care center in south India

Background:Regardless of the availability of newer and more sophisticated modalities of investigation, urinary tract cytology still remains the most commonly used non-invasive test for the diagnosis of bladder cancer.Aims:As hematuria is the commonest presenting symptom in patients with malignancy of urinary tract, we undertook this study to know the usefulness of urine cytology in evaluation of the hematuric patients for malignancy.Materials and Methods:A total of 21,557 fresh voided urine samples received at our tertiary care referral centre over a period of three years were included in the study. Of these, 1428 cases had hematuria, criteria of either gross or microscopic. Results:Among these hematuric cases included in the study, 32.5% (464 cases) were found to have positive finding of atypical cells. In these cases with atypia, 9.5% (136 cases) were proved to have malignancy both with the histopathological biopsy and cystoscopic findings. Other cases of atypia were found to be of reactive origin, either due to instrumentation or foreign body. A large number of hematuric cases, that is, 964 cases (67.5%) were negative for atypical cells.Conclusions:The limited ability of urine cytology to detect low grade bladder tumors, its subjectivity and lack of uniformity in reporting, all render urine cytology a less than perfect tool. With added collaboration between clinician and cytopathologist, urine cytology can be used an adjunct tool in evaluation of patients with hematuria.

A typical category in the voided urine samples

A typical category in the voided urine samples

A cross-sectional study of breast cancer biomarkers among shift working nurses

ObjectivesIn 2007, the International Agency for Research on Cancer classified long-term shift work as a probable carcinogen, with the strongest evidence for breast cancer. One proposed mechanism involves night-time light...

Urine Collection in the Emergency Department: What Really Happens in There?

Introduction:In women with suspected urinary tract infection (UTI), a non-contaminated voided specimen is considered important for valid urinalysis and culture results. We assess whether midstream parted-labia catch (MSPC) instructions were provided by nurses, understood, and performed correctly, according to the patient.Methods:We conducted a cross-sectional survey of English- and Spanish-speaking female patients submitting voided urine samples for urinalysis for suspected UTI. The survey was conducted in a public teaching hospital emergency department (ED) from June to December 2010, beginning 2 months after development and dissemination of a nursing MSPC instructions protocol. Research assistants administered the survey within 2 hours of urine collection. Nurses were unaware of the study purpose.Results:Of 129 patients approached, 74 (57%) consented and were included in the analysis. Median age was 35; 44% were Latino. Regarding instructions from nurses, patients reported the following: 45 (61%; 95% CI 50–72%) received any instructions; of whom 37 (82%; 95% CI 71–93%) understood them completely. Sixteen (36%; 95% CI 22–51%) were instructed to collect midstream; and 7 (16%; 95% CI 6–29%) to part the labia. Regardless of receiving or understanding instructions, 33 (45%; 95% CI 33–57%) reported actually collecting midstream, and 11 (15%, 95% CI 8–25%) parting the labia.Conclusion:In this ED, instructions for MSPC urine collection frequently were not given, despite a nursing protocol, and patients rarely performed the essential steps. An evidence-based approach to urine testing in the ED that considers urine collection technique, is needed.

Urinary Survivin mRNA Expression and Urinary Nuclear Matrix Protein 22 BladderChek® and Urine Cytology in the Detection of Transitional Cell Carcinoma of the Bladder

Objective: To compare the diagnostic performance of urine cytology (UC), survivin mRNA expression, and the NMP22 BladderChek® (NMP22BC) test for the detection, grading and staging of transitional cell carcinoma (TCC) of the bladder. Materials and Methods: Voided urine samples collected from 25 healthy controls and 80 patients diagnosed with TCC of the bladder were subjected to UC, the NMP22BC test and reverse-transcription real-time PCR for survivin mRNA expression. Results: Survivin mRNA expression showed the highest sensitivity (87.5%) followed by the NMP22BC test (61.3%) while UC exhibited the lowest sensitivity (40%). All three urine markers had a similar specificity of 96% (95% CI 80.5–99.3%). Survivin mRNA expression was the only urine marker that showed a significant difference in relation to tumour histological grade (χ² 8.5, p = 0.015). None of the three urine markers was significantly related to tumour pathological stages. Conclusion: The diagnostic sensitivity of urinary survivin mRNA expression was superior to that of UC and the NMP22BC test and correlates with tumour pathological grade but not stage.

Intravesical Bacillus Calmette-Guérin Outcomes in Patients With Bladder Cancer and Asymptomatic Bacteriuria

The outcome of intravesical bacillus Calmette-Guérin therapy was studied in patients with asymptomatic bacteriuria. A total of 243 patients with high risk, nonmuscle invasive bladder cancer received induction intravesical bacillus Calmette-Guérin therapy. Before starting bacillus Calmette-Guérin they submitted voided urine samples for culture and were treated with bacillus Calmette-Guérin regardless of culture results without antibiotics. Patients were followed every 3 months for tumor recurrence or progression up to 2 years. Of the 243 patients 61 (25%) had significant bacteriuria (greater than 10(4) or greater than 10(5) cfu/ml single organism). Febrile urinary tract infection developed in 1 patient (1.6%) and 2 overall (0.8%) after completing induction bacillus Calmette-Guérin therapy. No patients were admitted to the hospital for bacillus Calmette-Guérin or bacterial sepsis. The 2-year recurrence-free survival rate was 71% vs 73% in uninfected patients (p = 0.73). These data suggest that intravesical bacillus Calmette-Guérin is safe in patients who have asymptomatic bacteriuria and the 2-year disease-free intervals are similar to those of uninfected patients. Such strategy facilitates the timely administration of bacillus Calmette-Guérin therapy and avoids the overuse of antibiotics.