Voided Urine Specimens Research Articles

MP01-09 CAN A GENE METHYLATION ASSAY IMPROVE THE PERFORMANCE OF CYTOLOGY?

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2016MP01-09 CAN A GENE METHYLATION ASSAY IMPROVE THE PERFORMANCE OF CYTOLOGY? Thomas Longo, Ajay Gopalakrishna, Joseph Fantony, Richmond Owusu, Raymond Lance, Wen-Chi Foo, Brant Inman, and Michael Abern Thomas LongoThomas Longo More articles by this author , Ajay GopalakrishnaAjay Gopalakrishna More articles by this author , Joseph FantonyJoseph Fantony More articles by this author , Richmond OwusuRichmond Owusu More articles by this author , Raymond LanceRaymond Lance More articles by this author , Wen-Chi FooWen-Chi Foo More articles by this author , Brant InmanBrant Inman More articles by this author , and Michael AbernMichael Abern More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1839AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Detection and surveillance of bladder cancer is a physical, financial, and psychological stress on the patient. Cytology is well established, but has suboptimal performance. Medicine has moved beyond single tests to panels of biomarkers. We have looked at two novel markers, TWIST1 and NID2, using gene methylation. Using data from our clinical trial, we have tried to improve urine cytology by combining it with our panel. METHODS After IRB approval, we conducted a multi-institutional prospective trial of subjects undergoing initial hematuria evaluation or surveillance for bladder cancer (9/2008-12/2010). Subjects underwent standard cystoscopy to determine the presence or absence of a bladder tumor. A voided urine specimen was also collected for the DNA methylation assay and for voided urine cytology. Specimens were blinded and processed at a central lab. Genomic DNA was isolated and analysis done with real-time methylation-specific PCR using specific primers and probes for NID2, TWIST1, and β-actin. Gene copy numbers of methylated NID2 and TWIST1 were later dichotomized as a methylated (TWIST1 ≥ 37 or NID2 ≥ 21) or not methylated. An assay was considered adequate if each sample had at least 10 copies of the β-actin gene isolated from the urine. Receiver operating characteristic curves were constructed and areas under the curve were calculated for cytology, the methylation assay, and the combination of cytology with the methylation assay. RESULTS Originally 222 subjects were tested with the assay, but 13 were inadequate samples, and 37 were missing a cystoscopy or cytology. Overall, 37% of subjects were undergoing a hematuria workup and 63% were on surveillance for NMIBC. Approximately 75% were male with the majority of prior cancers were Ta low-grade. The sensitivity and specificity for the methylation assay were 57% and 72% respectively. Interestingly, the methylation assay performed better in subjects with hematuria than in subjects undergoing NMIBC surveillance (sensitivity 74% versus 48%, specificity 81% versus 63%). The separate AUC for the methylation assay was calculated as 0.669. With the addition of the assay, the AUC for cytology increased from 0.704 to 0.773 (p < 0.01). CONCLUSIONS DNA methylation has shown promise as a tool for screening and surveillance. Our multi-institutional study has validated the methodology of this novel test. It suggests that it is applicable as an adjunct to cytology and offers a clinically meaningful improvement. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e4 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Thomas Longo More articles by this author Ajay Gopalakrishna More articles by this author Joseph Fantony More articles by this author Richmond Owusu More articles by this author Raymond Lance More articles by this author Wen-Chi Foo More articles by this author Brant Inman More articles by this author Michael Abern More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The first report: An analysis of bacterial flora of the first voided urine specimens of patients with male urethritis using the 16S ribosomal RNA gene-based clone library method

ObjectivesTo analyse the bacterial flora of urine from patients with male urethritis using the clone library method. MethodsUrine specimens from patients with urethritis were used. The bacterial flora was analysed according to the 16S ribosomal RNA gene-based clone library method. In addition, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum or Ureaplasma parvum were detected by the conventional PCR methods (TMA or real-time PCR) and data from the clone library and conventional PCR methods were compared. ResultsAmong 58 urine specimens, 38 were successfully analysed using the clone library method. From the specimens, 2427 clones were evaluated and 95 bacterial phylotypes were detected. N. gonorrhoeae was detected from 6 specimens and as the predominant bacterial species in 5 specimens. M. genitalium was detected from 5 specimens and as the predominant bacterial species in 3 specimens. C. trachomatis was detected from 15 specimens using the TMA method, but was detected from only 1 specimen using the clone library method. U. parvum was detected from only 2 specimens using the clone library method. In addition, Haemophilus influenzae and Neisseria meningitidis were also detected in 8 and 1 specimens, respectively. Gardnerella vaginalis, which is a potential pathogen for bacterial vaginitis in women, was detected in 10 specimens. ConclusionsThe clone library method can detect the occupancy rate of each bacteria species among the bacterial flora and may be a new method for bacterial analyses in male urethritis.

Adequacy in voided urine cytology specimens: The role of volume and a repeat void upon predictive values for high-grade urothelial carcinoma.

Adequacy assessment is one of the most controversial and overlooked components in the daily practice of cytopathology, because it is generally determined from limited samples. Because voided urine varies widely in terms of its volume and cellularity, there is little consensus about the proper role for these variables in assessing specimen adequacy. In this study, the authors explored the role of volume in voided urine specimens to determine whether it plays a role in determining adequacy for the detection of high-grade urothelial carcinoma. Voided urine specimens received at the authors' laboratory over the 9.5 years since the introduction of the Johns Hopkins Template for Reporting Urinary Cytopathology were analyzed for correlations between volume, specimen adequacy, and the diagnosis of high-grade malignancy. The same data set also was queried to determine whether a patient who provided a voided low-volume specimen could yield a higher volume specimen and thereby increase adequacy. In total, 15,731 voided urine specimens with a cumulative volume of 891 liters originating from 8594 individual patients were analyzed. Specimen adequacy increased linearly for each increment of volume submitted to the laboratory up to 30 mL, after which the correlation was nonlinear. Low-volume specimens below this cutoff also had lower fractions of specimens that were diagnosed as malignant or suspicious. Volume is an important component in the evaluation of adequacy for voided urine cytology specimens.

P05.12 Analysis of bacterial flora of the urine specimens from male patients with urethritis by the clone library method based on the 16s rrna gene

Introduction Chlamydia trachomatis , Mycoplasma genitalium or Trichomonas vaginalis are the pathogens for non-gonococcal urethritis, but pathogenicity of other microorganisms for the male urethral has not be confirmed. In this study, the bacterial flora of urine specimens from male patients with urethritis was analysed by the clone library method based on the 16S rRNA gene. Methods The first voided urine specimens of male patients with urethritis were collected. The detection of Neisseria gonorrheae, C.trachomatis were examined by transcriptional mediated amplification (TMA) method and M. genitalium , Ureaplasma urealyticum , Ureaplasma parvum and Mycoplasma hominis were examined by real-time PCR method. The urine specimens were strained by Ethidium bromide and the number of bacterial cells were counted. DNA was extracted from the urine and amplification of the 16S rRNA gene via PCR (universal primers) and determination of the nucleotide sequences of 96 colonies were performed. The homology search was performed with a basic local aligment search tool (BLAST) using in-house software system and phylotypes of bacteria in each specimens were analysed. Results Urine specimens were collected from 58 patients and the divided to 4 group; gonogoccal urethritis (n:9), chlamydial urethritis (n:12), non-chlamydial non gonococcal urethritis detecting with Ureaplasmas or Mycoplasmas (UM+NCNGU, n;15) and non-chlamydial non gonococcal urethritis detecting without Ureaplasmas or Mycoplasmas (UM-NCNGU, n:22). Cell numbers were higher in UM+NCNGU than in UM-NCNGU. Among specimens, 2427 clones in 38 bacterial flora could be analysed and 91 bacterial phylotypes were detected together with N.gonorrhoeae, C.trachomatis, Mycoplasmas or Ureaplasmas positive specimens among chlamydial urethritis or UM+NCNGU groups. Gardnerella vaginalis was detected with Mycoplasma/Ureaplasma in Chlamydial urethritis ot UM+NCNGU. Conclusion The clone library method by using 16S rRNA gene is the new technology for analysis the bacterial flora of urine with urethritis. The relationship between G. vaginalis and Ureaplasma/Mycoplasma was found by this analysis. Disclosure of interest statement This study was supported by Japan Society for Promotion Science (JSPS) KAKENHI Grant Number 25293337.

English

The objective of the study was to know if a spot protein/ creatinine ratio would provide an accurate quantification of proteinuria and whether it can replace the use of the 24 hours urine protein in preeclamptic women. 60 women with preeclampsia were recruited for the study. A stable renal function was ascertained by doing serum creatinine and blood urea nitrogen. The patients were instructed to collect the 24 hours urine starting from the second urine sample in the morning till the first urine sample the next day morning. A single voided urine specimen was obtained thereafter for determination of the protein/ creatinine ratio. The urine protein and creatinine were measured using a standard methods. In the present study it was observed that with proteinuria <300 mg a negative correlation exists between 24 hour urine protein and spot p/c ratio. This observation can be explained by the fact, that, the number of patients in this range of proteinuria was less and also in the exclusion criteria those patients with dipstick <1+ (like traces and negative) is excluded from the study

Benign-appearing urothelial tissue fragments in noninstrumented voided urine specimens are associated with low rates of urothelial neoplasia.

The presence of urothelial tissue fragments (UTF) in voided urine (VU) is often considered an abnormal finding that may be associated with the presence of urothelial papillary neoplasms. In the current study, the authors reviewed VU specimens containing benign-appearing UTF (BUTF) to determine the associated rate of urothelial neoplasia at the study institution. A retrospective search of the electronic pathology database system over a 5-year period (2009-2013) revealed 1131 VU specimens containing UTF. Of these, 459 cases (40.6%) did not have a recent history of instrumentation. Fifteen cases were excluded because the slides were not available for review. In the remaining 444 cases, 274 cases (61.7%) had BUTF. A total of 170 cases (38.3%) had UTF with atypical cytologic features and were therefore excluded. Of the 274 cases, 29 (10.6%) had follow-up surgical pathology specimens available. The overall rate of urothelial neoplasia on follow-up was 3.6% for low-grade urothelial neoplasia (10 cases) and 0.7% for high-grade urothelial carcinoma (2 cases). Forty-five cases (16.4%) were determined to have urinary tract stones on follow-up. The presence of BUTF in VU specimens requires careful examination of the medical history because their presence may be explained by recent instrumentation. If recent instrumentation is not identified, the etiology of BUTF is not usually determined; in the current study, BUTF were found to be associated with urinary tract stones in 16.4% of cases. They also present a low risk of low-grade urothelial neoplasia (3.6%) and high-grade urothelial carcinoma (0.7%) when compared with the overall benign category at the study institution (2.3% [P =.15] and 0.7%, respectively).

Atypical urothelial tissue fragments in noninstrumented voided urine specimens are associated with low but significantly higher rates of urothelial neoplasia than benign-appearing urothelial tissue fragments.

The interpretation of urothelial tissue fragments (UTF) in voided urine (VU) specimens is controversial. If UTF contain cytomorphologically atypical cells, the diagnosis often becomes more challenging. The authors previously analyzed the outcome of patients with benign-appearing UTF in 274 noninstrumented VU specimens. In this retrospective study, noninstrumented VU specimens containing UTF with atypical cytomorphological features (AUTF) were evaluated and compared with the previous results. The Johns Hopkins Hospital electronic pathology database was searched for VU cases containing UTF over a 5-year period. A total of 170 noninstrumented VU specimens containing AUTF were identified. Twenty-four specimens had subsequent or coincidental surgical pathology specimens with the following overall rates of neoplasia: high-grade urothelial carcinoma: 8.8% (15 specimens), low-grade urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with urolithiasis on follow-up. Twenty-five cases had follow-up cytology specimens, all of which were negative for malignancy. Of 72 cases without histopathologic, radiologic, or cytopathologic follow-up, 62 (86.1%) had a mean clinical follow-up of 22.5 months and 10 cases did not have clinical follow-up. The presence of AUTF in noninstrumented VU is associated with low rates of urothelial neoplasia but a statistically higher risk of urothelial neoplasia than the presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high-grade urothelial carcinoma is significantly higher in noninstrumented VU specimens containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition, urolithiasis is associated with AUTF in a substantial percentage of noninstrumented VU specimens.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma for differential diagnosis from benign papillary urothelial lesions: logistic regression analysis in SurePath(™) liquid-based voided urine cytology.

The diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology specimens is challenging because of its subtle, minimally atypical findings. Furthermore, as SurePath(™) liquid-based cytology (LBC) is becoming a widely used method in urine cytology, the inevitable cytomorphological alterations resulting from this technique call for new morphological diagnostic criteria in LGPUC. Logistic regression analysis was carried out on SurePath slides from surgically proven voided urine specimens. The study was designed to include a test set (n=141) and a validation set (n=61), and evaluated significant discriminative parameters between LGPUC and benign papillary urothelial neoplasm (BPUN). Of the seven cytological findings that were found to have statistical significance in univariate analysis, five were found to be independent variables: loss of polarity of papillaroid clusters, irregular contours, absence of columnar cells, hobnail features and hyperchromasia. These independent variables had an area under the curve (AUC) of 0.781. The distinctive cytological criteria identified above may prove to be helpful in cases in which other conventional criteria for LGPUC are insufficient for diagnosis.

Manual urine microscopy versus automated urine analyzer microscopy in patients with acute kidney injury.

To examine whether a significant difference exists between the reported ranges of granular and muddy brown casts in urine specimens using manual microscopy compared with an automated urine analyzer in a cohort of patients with acute kidney injury (AKI). Freshly voided urine specimens from 25 consecutive patients who were under evaluation by the Department of Nephrology for AKI were simultaneously examined using the iQ200 automated microscopy system and manual microscopy performed by a trained observer. We coded the results according to the number of pathological casts identified and performed a 3 × 2 Freeman-Halton extension of the Fisher exact probability test. Overall, the number of casts identified via manual microscopy differed significantly (P <.001) from the number identified via the automated microscopy system. This study provides evidence of the importance of performing a manual microscopic examination of urine sediment in patients with AKI. Further studies are needed to assess whether manual microscopy provides prognostic implications regarding renal recovery, hemodialysis dependency, and mortality.

Urothelial Fragments in Non-instrumented Voided Urine Specimens are Associated with Low Rates of Urothelial Neoplasia

AUC suspicious for HGUC (suspicious). Materials and Methods: All urine cytologies with surgical follow-up diagnosed as AUC and suspicious were retrieved over a three-year period. All cases were independently re-reviewed by two pathologists blinded to the final diagnosis. Cytologic features evaluated included cellularity (>10 cells, 10-25 cells, 3x), nuclear irregularity, nuclear pleomorphism and hyperchromasia. Cases were considered predictive for malignancy if HGUC was found within one year of the cytology.Multivariate analysis using backwards stepwise regression was performed (JMP Pro 10 software). Results: There were 282 urine cases with surgical follow-up (223 AUC and 59 suspicious). HGUC was found in 105 of the AUC cases (48%) and 41 of the suspicious cases (70%). The most significant cytologic features that correlated with HGUC were nuclear irregularity, increased nuclear: cytoplasmic ratio and hyperchromasia (see Table). The remaining cytologic features showed no statistically significant correlation. Conclusions: Our study shows that themost important urine cytologic features to predict HGUC are the combination of increased nuclear: cytoplasmic ratio, nuclear irregularity, and hyperchromasia. These findings confirm the recently published Johns Hopkins HGUC criteria for urine cytology. Other cytologic features such as nuclear pleomorphism, chromatin pattern, and cellularity were less significant. The HGUC rate on followup of AUC was high because only cases with surgical followup were included in the study.

Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents.

BackgroundUp to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes.MethodsIn this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency.ResultsRecent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms.ConclusionsNonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.

Photodynamic diagnosis of shed prostate cancer cells in voided urine treated with 5-aminolevulinic acid.

BackgroundPast attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. To improve the sensitivities, we evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples.MethodsOne hundred thirty-eight patients with an abnormal digital rectal exam (DRE) and/or abnormal prostate-specific antigen (PSA) levels were recruited between April 2009 and December 2010. Voided urine specimens were collected before prostate biopsy. Urine specimens were treated with 5-ALA and imaged by fluorescence microscopy and reported as protoporphyrin IX (PPIX) positive (presence of cells demonstrating simultaneous PPIX fluorescence) or PPIX negative (lack of cells demonstrating fluorescence).ResultsOf the 138 patients, PCa was detected on needle biopsy in 81 patients (58.7%); of these 81 patients with PCa, 60 were PPIX-positive (sensitivity: 74.1%). Although 57 patients did not harbor PCa by conventional diagnostic procedures, 17 of these at-risk patients were found to be PPIX-positive (specificity: 70.2%). PPIX–PDD was more sensitive compared with DRE and transrectal ultrasound and more specific compared with PSA and PSA density. The incidence of PPIX–PDD positivity did not increase with increasing total PSA levels, tumor stage or Gleason score.ConclusionsTo our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner. However, further studies are warranted to determine the role of PPIX–PPD for PCa detection.

Urinary Protein Biomarker Panel for the Detection of Recurrent Bladder Cancer

Up to 70% of patients with non-muscle-invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the United States. The purpose of this study was to test the performance of a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. This retrospective, multicenter study included a total of 125 subjects with a history of bladder cancer. Voided urine specimens were collected before procedure from these subjects (53 with confirmed tumor recurrence and 72 with confirmed non-tumor recurrence) for analysis. A prediction rule generated from the performance characteristics of 10 single biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SERPINE1, and SDC1) was measured using ELISA. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity). The combination of all 10 biomarkers outperformed any single biomarker with a calculated AUROC for the diagnostic panel of 0.904 [95% confidence interval (CI), 0.853-0.956]. The multiplex assay achieved an overall sensitivity of 79% and specificity of 88% for recurrent bladder cancer and significantly outperformed the Urovysion cytogenetic assay (sensitivity 42%, specificity 94%) and voided urinary cytology (sensitivity 33%, specificity 90%). A diagnostic panel of 10 urinary biomarkers that accurately detects primary bladder cancer also performs well for the detection of recurrent bladder cancer. The identification of a reliable urine-based surveillance and detection assay would be of benefit to both patients and the healthcare system.

Early evidence kits in sexual assault: an observational study of spermatozoa detection in urine and other forensic specimens

To determine the detection frequency of spermatozoa in early evidence kit specimens and in subsequent full forensic specimens in alleged sexual assault. Observational cohort study of 100 consecutive alleged sexual assault cases, presenting in Western Australia between 19th July 2008 and 6th February 2012, with both early evidence kit and full forensic evidence specimen collections. Eighty-eight cases were included in the study. Smears from all forensic specimens were analyzed by light microscopy to determine the detection frequency and structural characteristics of spermatozoa. Patient demographic features, characteristics of the alleged assault and details and timing of forensic collections were also recorded. Spermatozoa were detected in early evidence kit specimens in 35% (31/88) and in full forensic specimens in 42% (37/88) of all cases (irrespective of type of alleged penetration). In alleged penile-vaginal penetration, spermatozoa were detected in early evidence kit specimens in 40% (21/53) of cases when both first void urine and vulval gauze wipe were collected. Spermatozoa were detected in full forensic specimens in 45% (31/69) of cases. Spermatozoa were detected in early evidence kit oral rinse specimens in 6% (1/18) of cases of alleged penile-oral penetration and in early evidence perianal gauze wipe specimens in 33% (2/6) cases of alleged penile-anal penetration. Spermatozoa were detected in the early evidence kit first void urine specimen in a single case, 11% (1/9), in which the nature of the alleged assault was unknown. Spermatozoa were detected in early evidence kit specimens and not in full forensic specimens in 3% (3/88) of cases. Early evidence kit specimens are effective in recovery of spermatozoa, and in particular urine and vulval gauze wipe are worthwhile early forensic specimens for the detection of spermatozoa. Collection of early evidence specimens led to detection of spermatozoa-positive cases, which were not detected by subsequent full forensic specimen collection.

MP72-17 SCREENING FOR ASYMPTOMATIC BACTERURIA AT ONE MONTH AFTER ADULT KIDNEY TRANSPLANTATION : CLINICAL FACTORS AND IMPLICATIONS

You have accessJournal of UrologyTransplantation & Vascular Surgery II1 Apr 2014MP72-17 SCREENING FOR ASYMPTOMATIC BACTERURIA AT ONE MONTH AFTER ADULT KIDNEY TRANSPLANTATION : CLINICAL FACTORS AND IMPLICATIONS Yen Seow Benjamin Goh, Zhao Long Deng, Pei Shan, Cassandra Cheong, Bee Choo Tai, Ting Hui, Angeline Goh, Vathsala Anatharaman, and Ho Yee Tiong Yen Seow Benjamin GohYen Seow Benjamin Goh More articles by this author , Zhao Long DengZhao Long Deng More articles by this author , Pei ShanPei Shan More articles by this author , Cassandra CheongCassandra Cheong More articles by this author , Bee Choo TaiBee Choo Tai More articles by this author , Ting HuiTing Hui More articles by this author , Angeline GohAngeline Goh More articles by this author , Vathsala AnatharamanVathsala Anatharaman More articles by this author , and Ho Yee TiongHo Yee Tiong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2256AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary tract infections (UTI) are a significant cause of morbidity after kidney transplantation. Screening for asymptomatic bacteruria (AB) has proven beneficial in certain adults like pregnant women; but it is poorly studied in the transplant population. We reviewed the clinical features and implications of AB one month after kidney transplantation. METHODS A review of 176 adult kidney transplant patients (87(51%) male, 86(50%) living, mean age 47) from 2005-2012 was performed. Protocol urine cultures were taken at 1 month after transplantation for all patients, regardless of symptoms. Five patients were excluded with missing results. Bacteruria was defined as 10⁵ CFUs of pathogenic organism per millilitre of voided urine specimen. All patients with positive cultures were treated with appropriate antibiotics. Patients were analysed according to culture positivity for associated factors and outcomes including hospitalizations, graft and patient survival. RESULTS Among the 171 urine cultures, 41(24%) were positive for AB. Klebsiella penumoniae, E. coli and Enterococcus faecalis were the most common organisms, accounting for 34.1%, 26.8% and 22.0% of the isolates. Multi-resistant organisms accounted for 43.9% of the infections. Bacteruria was associated with deceased donor transplants (P=0.001) and female recipients (P=0.014). It was not associated (P=NS) with recipient age, race, native kidney disease, donor demographics, and regimen of induction or maintenance immunosuppression, delayed graft function and duration of ureteric stent. Logistic regression confirms female sex (RR 2.6 95% CI 1.2-5.6, P<0.001) and deceased donor recipients (RR 7.7 95% CI 1.9-3.1, P=0.02) were independent predictors of AB at 30 days. Patients with AB were significantly more likely to be hospitalized subsequently for symptomatic UTI (RR 4.6 95% CI 2.1-9.9, P=0.001). However, there was no significant difference in 1-year patient (100% vs. 97%) and graft survival (95.1% vs. 95.4%) between the groups with positive and negative culture. CONCLUSIONS AB 30 days post transplant can be predicted in deceased donor and female recipients, reflecting functional and anatomical differences in voiding function. It is predictive of increased morbidity of subsequent hospitalization for symptomatic UTI and high risk groups may warrant targeted prophylaxis. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e829-e830 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yen Seow Benjamin Goh More articles by this author Zhao Long Deng More articles by this author Pei Shan More articles by this author Cassandra Cheong More articles by this author Bee Choo Tai More articles by this author Ting Hui More articles by this author Angeline Goh More articles by this author Vathsala Anatharaman More articles by this author Ho Yee Tiong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

DETECTION OF &lt;i&gt;MYCOPLASMA HOMINIS&lt;/i&gt; IN PATIENTS WITH URINARY TRACT INFECTIONS

Mycoplasma hominis is one of the well known genital mycoplasma agent that has been recognized as potentially pathogenic species and associated with various infectious diseases in adult men and woman. The organism could cause pelvic inflammatory disease, postpartum, postabortion fever and pyelonephritis. The Aim of this prospective study was to detemine the occurrence and prevalence of Mycoplasma hominis in patients with urinary tract infections, since they are usually not detected by routine microbiological examination of urine samples in laboratory department. For this purpose, Culture method was to be attempted as the current laboratory methods of choice for detection urogenital mycoplasmas infections. This study was designed as a case-control study in which a total of 100 patients with mean age of the of 42.78±22.49 (95% CI = 39-49.17) in case group as well as a mean age of 48.18±18.81 ((95% CI = 42.83-53.53) in the control group. The patients of both sexes were investigated for the presence of M. hominis and they were admitted to the urology department at asser central hospital in Abha (a city in southwest region of Saudi Arabia), during over a period of one year (February, 2013-March, 2014). A detailed history with specific urinary symptoms and signs was obtained as a result. These patients were divided into two groups: The first group (or case group) and the second group (or control group): The case group, included 50 symptomatic patients who had been admitted in hospital and they were examined for the presence of one or more of the following specific urinary symptoms and signs: Urinary frequency, dysuria, suprapubic/pelvic pain. Unlike the case group, the control group included 50 asymptomatic patients who were free of any specific urinary symptoms and they were matched by the first group for their age index. First voided urine specimens were tested using urine microscopy, culture for M hominis was performed and the isolates were identified serologically by growth inhibition test (disc method). In the case group, 8 cases out of 50 and in control group 1 out 50 were positive for M. hominis infection. The incidence of M. hominis was higher and statistically significant among case symptomatic patients group (8/50, 16%) than control asymptomatic patients group patients (1/50, 2%). On applying tests of significance to the observed data for isolation of Mycolplasma hominis among cases and controls, the values were found to statistically significant. Chi-square test with Yate’s correction [χ2 4.396; p value 0.036] and the Fisher’s exact test (2 tailed) [p value = 0.0309] indicated the relevance of the findings. The Relative Risk (RR) for the occurrence of Mycoplasma hominis infection was estimated to be 8 (95% C.I = 1.0386 -61.6235). The odds ratio was determined to be 0.1071 (95% CI = 0.129-0.892) and the risk ratio was 0.2063 (95% CI = 0.0322-1.3224). This is the first report study for the detection of M hominis in patients with urinary tract infections performed in Saudi Arabia. Infection caused by M hominis was associated with higher incidence rate in patients with symptomatic urinary tract diseases. Further work studies is needed for their rapid detection of these organism in urine samples using other diagnostic methods such as PCR. Further knowledge of the role and the effect of this pathogen in patients with urinary tract infections can be a prospective field of study.

Utility of urine cytology in evaluating hematuria with sonographically suspected bladder lesion in patients older than 50 years.

Purpose:Investigate the utility of urine cytology (UC) in patients older than 50 years with hematuria and sonographically suspected bladder lesion.Patients and Methods:Between April 2010 and June 2012, 152 patients above 50 years suffering from hematuria were included in this study. In all patients, ultrasound revealed a lesion suspected to be bladder cancer. Voided urine specimens were taken from all patients and transported to Pathology laboratory and processed within 1-3 h. All patients have undergone a cystoscopy examination and biopsy was taken from any suspicious lesion. The cytological diagnosis was reported as one of three categories, positive or negative or suspicious for malignancy.Results:One hundred thirty three (87.5%) patients in this study proved to have bladder carcinoma in histopathological examination. The sensitivity of UC was 53.4% and only five patients were suspicious. Percentage of positive cytology was highest among patients having gross hematuria (51.3%), posterior wall lesions (75%), papillonodular configuration (81.8%), invasive cancer (59.1%) and bilharzial affection (52.5%).Conclusion:Hematuria in patients older than 50 years with sonographically suspected bladder lesion mandates cystoscopy and biopsy. UC does not add more significant information in this group of patients.

Diagnosis of bladder cancer from the voided urine specimens using multi-target fluorescence in situ hybridization

The present study aimed to evaluate the diagnostic value of chromosomal analysis by fluorescence in situ hybridization (FISH) for bladder cancer in light of the histological diagnosis. Several valuable observations using FISH technologies in voided urine cells were also reported. The multi-target FISH-containing probes for the centromeres of chromosomes 3, 7 and 17 and the 9p21 locus were applied to cytospin specimens prepared from voided urine. Urine samples from 53 bladder cancer patients and 30 patients with benign alterations were used for this study. The histological observations of surgical resection specimens showed that the specificity and sensitivity for the technique were 100.0 and 88.0%, respectively. Statistical analyses showed that there was no significant correlation between FISH-positive rate and the tumor stage/grade (P<0.05). However, the proportion of tumor cells with genetic abnormalities positively correlated with the tumor stage (P<0.01). Furthermore, the number of abnormal cells in muscle-invasive pT2 was significantly higher than that in non-muscle-invasive pTa, pT1 (P<0.01). Of 50 patients with bladder cancer, polysomies of chromosomes 3, 7 and 17 were detected in 84.0, 48.0 and 78.0% of cases, respectively, and loss of the 9p21 gene was detected in 80.0% of cases. In addition, the detailed results from different urine specimens showed that FISH assay was required. FISH assay for chromosomes 3, 7 and 17 and 9p21 has a high specificity and sensitivity in the detection of bladder cancer and may reduce the necessity for cytoscopy treatment.

Should we treat asymptomatic bacteriuria after renal transplantation?

Infections remain a major cause of morbidity and mortality in the modern kidney transplantation era [1]. Symptomatic urinary tract infections (UTIs), which are defined as the association of a positive urine culture with the presence of symptoms or signs referable to UTI, are usually divided into lower tract (cystitis) and upper tract (pyelonephritis) infections. It is the most common infection in this population, both short-term as well as long-term post-transplantation [2]. As a consequence, UTI is the leading cause of antibiotic administration in kidney transplant recipients [3]. The highest incidence of symptomatic UTIs occurs during the first months after transplantation [4, 5]. In a registry study conducted by the Spanish Network for Research on Infection in Transplantation (RESITRA) in 2052 kidney transplant recipients with at least 1 year of follow-up, symptomatic UTIs occurred in 150 patients (7.3%) with an incidence rate of 0.45 episodes per 1000 transplantation days [4]. Escherichia coli and Enterococcus are known to account for more than half of bacterial UTIs post-kidney transplantation [2–5]. In a time of increasing resistance to antimicrobial agents and rising health-related costs, factors that trigger UTIs need to be understood, and if possible prevented. As in the general population, female gender is the strongest risk factor for UTI in kidney transplant recipients [4, 6, 7]. In comparison with men, the shorter urethra contributes to this phenomenon. Other risk factors such as advanced age, diabetes mellitus, primary end-stage renal disease, urinary tract abnormalities, cadaveric donor kidney, graft dysfunction and rejection, CMV infection and prolonged time on dialysis prior to transplantation have been pinpointed in some series [2, 6–10]. Identification of treatable risk factors is of interest as it may lead to a reduction in the frequency of symptomatic UTIs. Whether asymptomatic bacteriuria is a modifiable risk factor for symptomatic episodes and could impact the global prognosis of the transplanted patient (and should therefore be screened for and treated) remains controversial [11]. The Infectious Diseases Society of America (IDSA) defines asymptomatic bacteriuria as isolation of a specified quantitative count of bacteria (≥10 CFU/mL) in an appropriately collected urine sample obtained from a person without symptoms or signs referable to a UTI [12]. While a single urine specimen is sufficient to define asymptomatic bacteriuria in men, it is usually defined in women as two consecutively voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥10 CFU/mL. This definition stems from a study showing that, in non-transplanted women, when the first specimen contains at least 10 bacteria per millilitre of urine, there is an 80% probability that the patient has true bacteriuria [13]. That 20% of women have a negative second culture is thought to reflect transient bacteriuria rather than contamination [14]. Asymptomatic bacteriuria is a common event after renal transplantation. For instance, Fiorante et al. showed that 51% of the recipients develop asymptomatic bacteriuria—as defined by the IDSA guidelines—during the 3 years following transplantation [15]. Therefore, the question of its management remains a daily unsolved problem for transplant physicians. Antibiotic overuse could lead to the emergence of bacterial resistance and antimicrobial agents’ side effects. In addition, important costs are associated with the strategy of systematic screening and treatment of post-kidney transplantation asymptomatic bacteriuria, such as the costs of urinalyses, antibiotics and even hospitalization of asymptomatic patients. This is a matter of concern in a time of limited health-care resources. To date, no study has demonstrated a clear benefit in treating asymptomatic bacteriuria with antimicrobial agents in kidney transplant recipients [15–17]. Of the studies published addressing this question, only one was prospective. This small trial, conducted in 88 Iranian patients, did not show a statistically significant decreased rate of symptomatic UTIs when kidney transplant recipients with asymptomatic bacteriuria were treated with a 10-day course of antibiotics [17]. Nine of the 43 treated patients (21%) developed symptomatic UTI during the 9–12 months of follow-up, in comparison with 14 F U L L R E V IE W

Significance of atypical category in voided urine specimens prepared by liquid-based technology: Experience of a single institution

The goal of this study was to evaluate the clinical significance of atypical cytology in voided urine samples. We also studied any differences in outcome that may exist between the patients being surveyed versus high risk for urothelial carcinoma (UC). This was a retrospective study of all voided urine specimens with "atypical" cytology over a 10-year period. The patients were categorized into those with and without a prior diagnosis of UC as the "surveillance" and "de novo" (DG) groups. Follow-up was obtained. Clinical impact and outcomes of the 2 groups were compared. In this study, 5.7% of voided urine specimens were atypical. Mean age of patients in years, male/female ratio, and time to diagnosis in days was 59 versus 71, 23:15 versus 22:1, and 95 versus 43 in the DG and surveillance group, respectively. Rate of progression to UC was similar in both groups. High-grade UC was significantly higher in the DG. Approximately 20% of patients in the DG were subsequently diagnosed with UC. The common causes for the atypical diagnosis that did not progress to UC were stones and benign prostatic hyperplasia. In the absence of an etiology for the atypia, further investigations are warranted.