Parasite-bacteria interrelationship.

Parasites and bacteria have co-evolved with humankind, and they interact all the time in a myriad of ways. For example, some bacterial infections result from parasite-dwelling bacteria as in the case of Salmonella infection during schistosomiasis. Other bacteria synergize with parasites in the evolution of human disease as in the case of the interplay between Wolbachia endosymbiont bacteria and filarial nematodes as well as the interaction between Gram-negative bacteria and Schistosoma haematobium in the pathogenesis of urinary bladder cancer. Moreover, secondary bacterial infections may complicate several parasitic diseases such as visceral leishmaniasis and malaria, due to immunosuppression of the host during parasitic infections. Also, bacteria may colonize the parasitic lesions; for example, hydatid cysts and skin lesions of ectoparasites. Remarkably, some parasitic helminths and arthropods exhibit antibacterial activity usually by the release of specific antimicrobial products. Lastly, some parasite-bacteria interactions are induced as when using probiotic bacteria to modulate the outcome of a variety of parasitic infections. In sum, parasite-bacteria interactions involve intricate processes that never cease to intrigue the researchers. However, understanding and exploiting these interactions could have prophylactic and curative potential for infections by both types of pathogens.

The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer.

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasis-induced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these metabolites emphasizing their potential effects on the dysregulation of the tumor suppressor gene p53 expression during urogenital schistosomiasis. Enhanced understanding of these potential carcinogens may not only shed light on urogenital schistosomiasis-induced neoplasia of the bladder, but would also facilitate development of interventions and biomarkers for this and other infection-associated cancers at large.

Parasite-Associated Cancers (Blood Flukes/Liver Flukes).

Parasitic infection remains as a persistent public health problem and can be carcinogenic. Three helminth parasites, namely, Clonorchis sinensis (liver fluke) and Opisthorchis viverrini as well as Schistosoma haematobium (blood fluke), are classified as Group 1 carcinogens by the World Health Organization's International Agency for Research on Cancer (IARC Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis), World Health Organization, International Agency for Research on Cancer, 2011). Infection by these parasites is frequently asymptomatic and is thus rarely diagnosed at early exposure. Persistent infection can cause severe cancer complications. Until now, the cellular and molecular mechanisms linking fluke infections to cancer formation have yet to be defined, although many studies have focused on these mechanisms in recent years, and numerous findings were made in various aspects of parasite-associated cancers. Herein, we only introduce the fluke-induced cholangiocarcinoma (CCA) and bladder carcinoma and mainly focus on key findings in the last 5 years.

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice.

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.

Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics.

Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer.

The biochemical value of urinary metalloproteinases 3 and 9 in diagnosis and prognosis of bladder cancer in Egypt.

BACKGROUND: Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. Few studies are available that describe this association with bladder cancer either related or unrelated to schistosoma infection.Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and prognostic biomarkers in different stages of schistosomal and non schistosomal bladder cancer was the aim of the present study.Urine samples were collected from 70 patients with schistosomal and non schistosomal bladder cancer at early and advanced stages and also from 12 healthy volunteers as controls. Urinary levels of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity of both markers were determined. RESULTS: Urinary levels of both MMP-3 and MMP-9 were significantly elevated in all bladder cancer patients compared with controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer ( 0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml) compared to control (0.016 ng/ml) and remained elevated in advanced stages (0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9 showed a significant elevation in advanced stages only of both schistosomal and non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control (0.409 ng/ml) and this elevation of both markers was much higher in non schistosomal bladder cancer. Both Metalloproteinases were specific for the diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was evident in the early stage (84.85% for MMP3, 27.28% for MMP9). CONCLUSIONS: MMP3 may be the recommended urinary metalloproteinases as early diagnostic biomarker in the early stages of both types of bladder cancer although both MMP9 and MMP3 can be used in the diagnosis of advanced stages. Further studies are required on large number of urine samples to confirm these results.

Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma.

BACKGROUND: High-grade urothelial carcinoma either non-Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem. AIM: Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker. MATERIAL AND METHODS: Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers' expression in S-UBC. RESULTS: The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1. CONCLUSION: Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.

Haematobium eggs detection in human bladder cancer and sporocysts in snail vectors: Seven cases report and a review of the Burkina Faso literature.

Schistosoma haematobium plays a central role in the development of bladder cancer in Burkina Faso. The objective of this study was to determine the presence of S. haematobium in the bladder cancer and in vector snails. For the first time, formalin-fixed tissues embedded in paraffin were analyzed by immunohistochemistry and PCR. Molecular detection has resulted in 7/7 positive bladder cancer. Finally, as the snail vectors were positive. We suggest the use of molecular methods in the snail vectors for the detection of cysts and in cancerous tissues in larger studies.

CD44s and CD44v6 in diagnosis and prognosis of human bladder cancer.

UNLABELLED: The cell adhesion molecules (CAMs) CD44 standard (CD44s) and its variant 6 (CD44v6) are involved in the progression and invasion of human malignancies. However, discrepancies in the prognostic value of CD44s and CD44v6 expression need to be addressed. AIMS: To investigate the expression of CD44s and CD44v6 in bladder carcinomas and relate the results to the established prognostic factors. MATERIALS AND METHODS: 50 bladder carcinoma specimens, 30 cases with transitional cell carcinoma (TCC: 6 bilharzial and 24 nonbilharzial) and 20 cases with squamous cell carcinoma (SCC: 8 bilharzial and 12 nonbilharzial), were included. Immunohistochemical analysis for CD44s and CD44v6 was carried out using avidin-biotin peroxidase method. RESULTS: The level of both CD44s and CD44v6 in TCC was significantly higher in invasive than in preinvasive tumors and normal urothelium (p < .05). A direct association between the percentage of expression of both markers and the grade of TCC (p < .05) was observed. An inverse correlation between CD44s and SCC was seen, where metaplastic urothelium showed higher expression than invasive carcinomas. No association was observed between the expressions of both CD44s and CD44v6 and bilharzial ova, sex and age of the patient, or size of the tumor. CONCLUSIONS: The authors report statistically significant correlation between CD44s and CD44v6 expression and increasing grade and stage of TCC. No such correlation with SCC and with bilharzial cystitis, sex and age of the patient, or size of the tumor was documented.

Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosoma haematobium infection.

To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-κB in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-κB activation, leading to tumor development.

Bilharzial vs non-bilharzial related bladder cancer: pathological characteristics and value of cyclooxygenase-2 expression.

OBJECTIVE: • To assess the expression pattern of cyclooxygenase-2 (COX-2) in bilharzial and non-bilharzial related bladder cancer (BBC and NBBC) and its association with clinical outcome after radical cystectomy (RC). We also determined the clinico-pathological differences between BBC and NBBC. PATIENTS AND METHODS: • Immunohistochemical (IHC) staining for COX-2 was performed on archival bladder specimens from 315 patients treated with RC between 1997 and 2003. • Patients were divided into 2 groups: Group 1 comprised 205 patients (65%) with BBC and group 2 comprised 110 patients (35%) with NBBC. • Clinico-pathological differences were compared and altered IHC expression of COX-2 was correlated with clinical outcome in both groups. RESULTS: • The study included 315 patients (239 males and 76 females) with median age 54 y (range 31-79) and median follow up of 63.2 months after RC. • There was significant difference in histological types, tumor stage, grade, and architecture and COX-2 alterations between both groups (P < 0.05). • BBC presented with lower grade, higher stage, and non-papillary non-urothelial carcinoma. COX-2 overexpression was associated with pathological T stage (P= 0.01), grade (P < 0.001) and lymphovascular invasion (LVI) (P= 0.041). • COX-2 expression was an independent predictor of disease recurrence (HR 1.9, CI 0.99-3.626 and P= 0.05) and cancer specific mortality (HR 2.8, CI 1.155-6.73 and P= 0.023) only in BBC but not in NBBC (HR 1.6, CI 0.598-4.364, P= 0.344 and HR 0.349, CI 0.076-1.595, P= 0.175, respectively). CONCLUSIONS: • BBC differs pathologically and biologically from NBBC. BBCs present more frequently as low-grade, high stage non-papillary and non-urothelial cancers. BBCs with COX-2 alterations are associated with worse outcome after RC. • Our findings support the need for further evaluation of COX-2 and inflammatory signaling pathways as well as COX-2-targeted prevention and therapies in BC.

Microscopic investigations in a diabetic rat urinary bladder infected with Trichosomoides crassicauda.

Rats are widely used laboratory animals and have several parasites. One of these are helminths, known not only to cause serious effects on the experimental results in healthy subjects, but also in subjects with heavy infections. One of the relatively pathologic helminth is Trichosomoides crassicauda, which lives in the nodules of the urinary bladder. It is known that diabetics are more prone to infections with several microorganisms. Observations in a diabetic rat bladder showed T. crassicauda eggs inside the transitional epithelium, and structural changes in the bladder epithelium were evident. Urinary-bladder tissues taken from streptozotocin-injected diabetic subjects and citrate buffer-injected control subjects were fixed, embedded in araldite and investigated under a light microscope. Distinct changes in the histological structure of a diabetic urinary bladder transitional epithelium were observed after T. crassicauda infection. Many papillomas were formed and the epithelial tissues were completely degenerated. In addition, electron microscopic examinations also revealed degeneration of the subepithelial tissues.

Protocols for Preparation and Mass Spectrometry Analysis of Clinical Urine Samples to Identify Candidate Biomarkers of Schistosoma-Associated Bladder Cancer.

Advances in mass spectrometry instrumentation have revolutionized analytical capability in clinical proteomics. In parallel, various sample preparation methods have been developed to try to address the inherent complexity and dynamic range of clinical samples, typically involving a combination of depletion of abundant proteins followed by extensive prefractionation. However, the depth of coverage routinely achieved in discovery proteomics experiments on peripheral fluids such as serum, still leaves something to be desired, especially if no depletion or prefractionation is done in order to increase the throughput of clinical samples. Remarkably, despite being an easily accessible, typically sterile and diagnostically rich clinical sample, urine is often overlooked and as such has received less development effort. As an ultrafiltrate of blood, urine contains proteins and protein fragments originating from all parts of the body which may have diagnostic or prognostic potential if accurately and reproducibly quantified. Here, we describe an efficient and simple method for the concentration of urine samples by methanol-chloroform precipitation and subsequent in-solution tryptic digestion prior to discovery or targeted mass spectrometry analysis. We exemplify this method by reference to the discovery of novel candidate urinary biomarkers of schistosomiasis. Importantly, the methods described here have been used to identify >1900 protein groups in human urine by label-free discovery proteomics, without requiring any prior depletion or prefractionation, making this approach amenable to high throughput clinical biomarker studies in many diseases.

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer.

BACKGROUND: Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between nm23-H1, Rb, EGFR and p53 in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC). METHODS: nm23-H1, Rb, EGFR and p53 expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate. RESULTS: Overexpression of EGFR and p53 proteins was detected in 66.1% and 35.6%; respectively. Loss of nm23-H1and Rb proteins was detected in 42.4% and 57.6%; respectively. Increased EGFR and loss of nm23-H1 RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between p53 and EGFR overexpression (p < 0.0001), nm23 loss (protein and RNA), lymph node status (p < 0.0001); between the incidence of local recurrence and EGFR RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression (p < 0.0001) and mutation (p = 0.04). Advanced disease stage correlated significantly with increased EGFR (protein and RNA) (p = 0.003 & 0.01), reduced nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p = 0.004). OS rates correlated significantly, in univariate analysis, with p53 overexpression (p = 0.011), increased EGFR (protein and RNA, p = 0.034&0.031), nm23-H1 RNA loss (p = 0.021) and aberrations of > or = 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of > or = 2 affected markers were independent prognostic factors. CONCLUSION: nm23-H1, EGFR and p53 could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (> or = 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.

Schistosoma haematobium causing pulmonary schistosomiasis in a returning traveller.

Schistosomiasis is infrequently seen in the UK, but remains an important cause of haematuria in endemic areas. It may also be complicated by systemic illness, and can affect multiple organs, including the bladder, liver and lungs. We discuss a case of haematuria associated with lower abdominal discomfort and dry cough/wheeze in a returning traveller diagnosed as pulmonary and urinary schistosomiasis, caused by Schistosomahaematobium This case was particularly notable for the radiological findings seen on CT scan of the chest (figure 2A,B), as well as the characteristic sago nodules discovered within the bladder. It is also unusual to see pulmonary schistosomiasis associated with S. haematobium, an organism more typically characterised by bladder involvement. It is important to consider schistosomiasis and its complications, while rare in the western world, it remains an important differential diagnosis in at-risk groups with considerable morbidity if untreated.

Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis.

To cast light on mechanisms underlying development of urothelial carcinomas (UCs) of the urinary bladder associated with Schistosomiasis, we immunohistochemically analyzed the relationship between oxidative stress markers, DNA single strand breaks (ssDNA) which could also measure the levels of base damage and apoptosis in DNA, and expression of DNA repair genes with levels of nitric oxide synthases in bladder carcinomas of Egyptian patients with or without Schistosoma hematobium infection. Marked elevation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels was found in squamous cell carcinomas and UCs associated with Schistosomiasis when compared with non-Schistosomal carcinomas. This was accompanied by strong over expression of the DNA-repair genes, 8-oxoguanine-DNA-glycosylase and apurinic/apyrimidinic endonuclease, as well as increased formation levels of ssDNA. Expression levels of inducible nitric oxide synthase (iNOS) which is known to be indirectly related to oxidative stress was higher in Schistosomal than in the non-Schistosomal carcinomas. However, expression of endothelial nitric oxide synthase was slightly stronger in non-Schistosomal than in the Schistosomal carcinomas. In conclusion, these findings suggest a strong correlation between Schistosoma haematobium infection and increased levels of oxidative stress accompanied by a continuous DNA damage and repair in UCs, all directly correlating with elevated iNOS.

Heat shock protein expression independently predicts survival outcome in schistosomiasis-associated urinary bladder cancer.

BACKGROUND: Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. These molecules have been studied in several malignancies, among which bladder carcinoma. This is the first study attempting to clarify the significance of HSP27 and HSP70 in schistosomiasis-associated bladder carcinoma and their relation to prognosis. METHODS: HSP27 and HSP70 were localized immunohistochemically in tissue sections from 75 chistosomiasis-associated bladder carcinomas. Their expression was correlated with clinical and pathological features and their impact on 5-year disease-free survival was studied with univariate and multivariate analysis. RESULTS: In all, 45 and 51 patients were positive for HSP27 and HSP70 expression, respectively. A significant correlation was found between expression of both HSPs and tumor grade, stage, DNA ploidy and recurrence. In univariate analysis, a statistically significant association of HSP27 and HSP70 expression with 5-year disease-free survival was found. In a multivariate Cox proportional hazards model, both HSP27 and HSP70 maintained a statistically significant impact on survival. CONCLUSIONS: The current results indicate that expression of HSP27 and HSP70 may have prognostic relevance in patients with schistosomiasis-associated bladder cancer. HSPs may be useful markers for patients with this type of bladder carcinoma and may be used for predicting disease progression.

Performance of urinary survivin as a non-invasive molecular marker of bladdercarcinoma in a schistosomiasis endemic area.

OBJECTIVE: To compare the sensitivity, specificity, positive predictive value, negative predictive value of urinary survivin and that of urine cytology in the diagnosis of bladder carcinoma in a schistosoma endemic area. DESIGN AND SETTING: This is a 12-month prospective study of patients with features of bladder carcinoma as study group and patients with other urologic conditions and healthy volunteers as control group. PARTICIPANTS: Patients with features of bladder carcinoma formed the study group, while patients with other urological conditions and healthy volunteers formed the control group. RESULTS: There were 52 patients in study group and 36 patients in control group. The mean ages of patients in the study and control groups were 47.17 ± 17.00 and 44.19 ± 18.89 years respectively. There were 48 males and 4 females in the study group, giving a male: female ratio of 12:1. Thirty-one (60 %) of the patients were farmers and 44 patients (85%) had history suggestive of schistosomiasis at childhood. The sensitivity of urine cytology and survivin in the study were 29.1% and 100.0% respectively. The specificity of urine cytology and survivin were 100.0% and 100.0% respectively (p= 0.05). The marker was associated with false positive (FP) results in patients with prostate cancer. CONCLUSION: Urinary survivin is highly sensitive, specific and predictive of bladder carcinoma in our environment. The marker is associated with false positive results in patients with prostate cancer. FUNDING: By authors.

The atypical urothelial cancer patient: management of bladder cancers of non-transitional cell histology and cancers of the ureters and renal pelvis.

Non-transitional cell neoplasms of the bladder and upper tract transitional cell carcinomas (ureter and renal pelvis) represent only a small fraction of urothelial carcinomas. Clinicians faced with the rare case are always confronted with management dilemmas complicated by the scarcity of published experience to guide decisions. The current review brings together the best of the limited published data in an attempt to provide some reasonable context to help in the management of these difficult neoplasms.