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Sample records for bladder urothelial carcinoma

  1. Isolated cardiac metastasis from plasmacytoid urothelial carcinoma of the bladder

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    Peck Joshua R

    2012-06-01

    Full Text Available Abstract A 57-year-old male with a history of hypertension presented with shortness of breath, intermittent substernal chest pain, subjective fevers, and a 30-pound weight loss. He was found to have a bladder mass four months prior to presentation, for which he underwent cystoscopy and surgical removal. Pathology demonstrated high-grade superficial plasmacytoid urothelial carcinoma extending into the submucosa but not the muscularis propria. Given the superficial nature of his bladder cancer, a cystectomy was deferred. He was subsequently lost to follow-up care. On arrival, physical exam was notable for tachycardia, tachypnea, and distant heart sounds. An ECG showed an incomplete right bundle branch block and sinus tachycardia. Computed tomography pulmonary angiography revealed a three-cm pericardial effusion. Transthoracic echocardiography confirmed this finding and revealed a mass in the right ventricle (RV extending into the outflow tract and infiltrating the free wall. The RV was dilated with an estimated RV systolic pressure of 37 mmHg. Pericardiocentesis yielded nearly one liter of serosanguinous fluid with non-diagnostic cytology. Partial median sternotomy with biopsy showed pathologic findings consistent with metastatic urothelial carcinoma, plasmacytoid variant. A PET scan showed increased uptake exclusively in the heart. The oncology team discussed options with the patient including chemotherapy and palliative care. The patient decided to withhold further therapy and went home with hospice care. He died two months later. Discussion Bladder cancer is the fourth most common cancer in men in the United States. Most patients (69% with metastatic bladder cancer have multiple organs involved; conversely, our patient had a PET scan indicating his disease was localized to the heart. Plasmacytoid urothelial carcinoma is a rare subtype of bladder cancer, and is estimated to make up less than three percent of all invasive bladder carcinomas. At

  2. Malignant glandular lesions and glandular differentiation in invasive/noninvasive urothelial carcinoma of the urinary bladder.

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    Behzatoğlu, Kemal

    2011-12-01

    Although the lumen of the urinary bladder is covered with only urothelial epithelium, malign glandular lesions (eg, nonurachal adenocarcinoma) and benign lesions (eg, cystitis cystica and cystitis glandularis) can also rarely occur in this site due to its characteristic embryologic development. Glandular differentiation is uncommon in urothelial carcinomas and is even less common in noninvasive urothelial cancers. In addition, in situ urothelial carcinomas are more likely to progress in the presence of glandular differentiation toward high-grade urothelial carcinomas and/or aggressive urothelial carcinomas. Pure nonurachal adenocarcinomas and mixed carcinomas (urothelial carcinoma and adenocarcinoma) are very rare, and their pathogenesis is not clear. Most of the nonurachal adenocarcinomas are thought to arise on the grounds of cystitis glandularus with intestinal metaplasia. Here, I present 2 cases with noninvasive urothelial carcinoma with substantial glandular differentiation showing progression to signet ring cell carcinoma and invasive urothelial carcinoma, one case with mixed carcinoma (urothelial carcinoma and adenocarcinoma) and another case with pure adenocarcinoma developing from cystitis glandularis with intestinal metaplasia, and discuss malign glandular lesions in the bladder and invasive/noninvasive urothelial carcinomas with glandular differentiation.

  3. Urothelial carcinoma arising within bladder diverticulum—Report of a case and review of the literature

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    Hung-En Chen

    2016-09-01

    Full Text Available Bladder diverticulum is an outpouching of bladder mucosa through the musculature of the bladder wall. The incidence of bladder diverticulum in Taiwan is about 1.7% in children and 23.4% in adults. Intradiverticular carcinoma of urinary bladder is uncommon. It ranges from 0.8% to 14.3%. Here we report a case of urothelial carcinoma within a bladder diverticulum. A 60-year-old male patient had history of BPH under medical treatment and right ureteral stone treated with extracorporeal shock wave lithotripsy (ESWL. He presented with painless gross hematuria about 3 months after ESWL. Intravenous pyelography showed a filling defect within the bladder diverticulum. Histopathological diagnosis of low grade urothelial carcinoma arising from the bladder diverticulum was made following cystoscopic biopsy. Laparoscopic partial cystectomy was performed with subsequent intravesical chemotherapy. Tumor recurrence was found not from the previous diverticulum but from another area during regular cystoscopy at the 6-month postoperative follow up. He underwent transurethral resection of bladder tumor. Pathology revealed a noninvasive, high grade urothelial carcinoma. There was no further bladder tumor recurrence during the 1-year follow-up period. Bladder-sparing surgery with close cystoscopy follow up for intradiverticular urothelial carcinoma can be applied as an alternative treatment modality.

  4. Multicystic urothelial carcinoma of the bladder with gland-like lumina and with signet-ring cells. A case report

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    Hes Ondrej

    2008-09-01

    Full Text Available Abstract We present the case of 80-year-old male with superficial papillary urothelial carcinoma of the urinary bladder with striking multicystic architecture with a combination of features of urothelial carcinoma with gland-like lumina, with signet-ring cell differentiation and microcystic pattern. However, the tumor shared the morphologic features of several variants of urothelial carcinoma, the most important differential diagnosis covered so-called florid Brunneriosis, cystitis cystica, and primary adenocarcinomas of the urinary bladder.

  5. Recurrence of Urothelial Bladder Carcinoma in the Colon Presenting as Hematochezia

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    Krzyzak, Michael; Barakat, Iskandar; Deeb, Liliane

    2016-01-01

    Patients with superficial bladder cancers remain clinically indolent after treatment with even a modicum of urologic intervention. However, with more invasive disease, the majority of patients experience recurrence. The conventional route of metastasis and recurrence in primary urothelial cell carcinoma is through lymphatic system, with regional lymph nodes, lungs, liver, brain, and bone being the most common sites. Isolated intraluminal colonic recurrence in the absence of local invasion is extremely rare. We report a unique case of urothelial cell carcinoma presenting with an isolated colonic mass, which unexpectedly, on immunohistostaining, proved to be primarily of urothelial rather than colonic origin.

  6. The role of circulating tumor cells in urothelial cell carcinoma of the bladder

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    N. Beije (Nick); S. Sleijfer (Stefan); J.L. Boormans (Joost)

    2015-01-01

    textabstractPatients with muscle-invasive urothelial cell carcinoma of the bladder have a 50 % chance to develop distant metastases despite curative local treatment. Reliable markers that predict the risk of developing metastases or that could be used to determine whether or not perioperative system

  7. Clinical significance of the reduction of UT-B expression in urothelial carcinoma of the bladder.

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    Li, Chun; Xue, Haogang; Lei, Yanming; Zhu, Jianqiang; Yang, Baoxue; Gai, Xiaodong

    2014-12-01

    Urea transporter B (UT-B) is a membrane protein and plays an important role in regulating urea concentration in bladder urothelial cells. It has been reported that UT-B gene mutations were related to bladder carcinogenesis, and UT-B deletion could induce DNA damage and apoptosis in bladder urothelium. However, the functions and clinical significance of UT-B in human bladder cancer remain unknown. The most common type of bladder cancer is urothelial carcinoma (UC). We hypothesized that UT-B expression was related to bladder UC progress. In this study, UT-B was detected using immunohistochemistry in 52 paraffin-embedded specimens of bladder UC and 10 normal urothelium specimens. The results showed that UT-B protein expression in UC tumor cells was significantly lower as compared with normal urothelial cells (P = 0.021). UT-B protein expression was significantly reduced with increasing histological grade (P = 0.010). UT-B protein expression in muscle-invasive stage was significantly lower than in non-muscle-invasive stage (P = 0.014). Taken together, our data suggest that the reduction or loss of UT-B expression may be related to the incidence, progression and invasiveness of bladder UC. UT-B may be a novel diagnostic or prognostic biomarker, as well as a potential therapeutic target in UC of the bladder.

  8. Immunohistochemical determination of ETS-1 oncoprotein expression in urothelial carcinomas of the urinary bladder.

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    Sari, Aysegul; Calli, Aylin; Gorgel, Sacit Nuri; Altinboga, Aysegul Aksoy; Kara, Cengiz; Dincel, Cetin; Cakalagaoglu, Fulya

    2012-03-01

    ETS-1 protooncogene is an important transcription factor that plays a role in the regulation of physiological processes, such as cell proliferation and differentiation. ETS-1 is thought to be related to the growth of carcinoma cells by its regulation of the transcription of matrix metalloproteinases and urokinase-type plasminogen activator. In this study, we aimed to investigate the expression pattern of ETS-1 oncoprotein in urothelial carcinomas of the urinary bladder and determine its relationship with histopathologic parameters, including tumor grade and stage. One hundred six specimens of urothelial carcinoma and a total of 14 normal urothelium were analyzed immunohistochemically with anti-ETS-1 monoclonal antibody. The normal urothelium showed positive ETS-1 immunostaining. ETS-1 expression remained high in low-grade and noninvasive tumors, whereas it frequently decreased in high-grade or invasive carcinomas. Interestingly, ETS-1 was highly expressed in the basal cell layer of the noninvasive urothelial carcinomas. ETS-1 expression showed a strong negative correlation with the tumor grade (PETS-1 expression than the muscle-invasive tumors (pT2; PETS-1 expression is significantly associated with high grade and advanced stage in urothelial carcinomas of the urinary bladder, and that the downregulation of ETS-1 expression may be a marker of the aggressiveness of such malignancies.

  9. Translating biology into clinic: new insights on prognostic and predictive biomarkers for urothelial bladder carcinoma

    OpenAIRE

    2013-01-01

    Tese de doutoramento em Ciências da Saúde Urothelial bladder carcinoma (UBC) represents a significant health problem, as a consequence of its heterogeneous natural history and clinical behavior. Most morbidity and mortality associated with UBC is caused by the muscle-invasive (MI) form of the disease, which represents about 20-30% of all newly diagnosed cases. Moreover, an important proportion of high risk non-muscle invasive (NMI) tumours relapse after transurethral resection and progress...

  10. Significance of a minor high-grade component in a low-grade noninvasive papillary urothelial carcinoma of bladder.

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    Reis, Leonardo O; Taheri, Diana; Chaux, Alcides; Guner, Gunes; Mendoza Rodriguez, Maria A; Bivalacqua, Trinity J; Schoenberg, Mark P; Epstein, Jonathan I; Netto, George J

    2016-01-01

    To assess the clinicopathological features and prognostic significance of the presence of 5% or less high-grade component in otherwise low-grade noninvasive bladder urothelial carcinoma, referred to as mixed-grade (MG) urothelial carcinoma, we reviewed all archival cases with such diagnosis between 2005 and 2014. Clinicopathological and outcome parameters were compared to those in our previously reported low- and high-grade noninvasive bladder urothelial carcinoma cohorts (LGUC and HGUC, respectively). The study included 31 MG urothelial carcinomas. Mean patient age was 67.6 years, and mean follow-up was 39.7 months. Intravesical treatment was administered in 15 patients (48.4%). Recurrence occurred in 14 cases (45.2%): 10 as LGUC and 4 as HGUC; there was no stage progression. Mean time to progression was 9 months (5-17 months), and there was no death of disease. MG urothelial carcinoma stage progression and dead of disease rates were comparable to that of LGUC. MG urothelial carcinoma stage progression was significantly lower than that of HGUC, P = .002, using Pearson χ(2) test. MG urothelial carcinoma patients with no intravesical treatment had higher incidence rate of grade progression (25%) compared to LGUC patients (7.9%); however, the difference was not statistically significant. MG urothelial carcinoma had a prognosis closer to "pure" LGUC than "pure" HGUC. Untreated MG urothelial carcinoma may have a higher rate of grade progression than LGUC, although more data are needed before this issue can be definitively addressed. Until such data are available, it is reasonable to keep MG urothelial carcinoma as a distinct grade category with potential management implications.

  11. Bladder extramedullary plasmacytoma and synchronous bladder urothelial transitional cell carcinoma: A case report and review of the literature

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    Karan Wadhwa

    2011-02-01

    Full Text Available Karan Wadhwa, Raj Singh, Lemke Z SolomonDepartment of Urology, Queen Alexandra Hospital, Portsmouth, UKAbstract: A 69-year-old man presented with sudden onset of macroscopic hematuria. While an ultrasound of the bladder revealed a posterior bladder mass, subsequent flexible cystoscopy demonstrated only an area of irregular urothelium. Initial general anesthetic cytoscopy and biopsy revealed conventional G2/3 T1 TCC. Histology of a further formal resection of this irregular area revealed carcinoma-in-situ and population of atypical cells with enlarged nuclei, prominent nucleoli, and varying quantities of cytoplasm showing plasma cell features. The immunohistochemistry was consistent with a plasmacytoma. There must be a high index of suspicion when ultrasound demonstrates a mass not detected by flexible cystoscopy, and biopsies/resection are advised to exclude extramedullary plasmacytoma (EMP as the cause. EMP of the urinary bladder is a rare entity with only 21 cases reported in the literature. In this report we describe a further case of EMP of the bladder associated with synchronous transitional cell carcinoma (TCC of the urothelium. We also highlight the important histopathological findings and review the current literature to report the outcomes of existing approaches to management of this rare form of bladder cancer. We believe this to be the first case reported in which a patient presented concurrently with bladder EMP and urothelial TCC. EMPs are highly radiosensitive tumors and in the case of head/neck disease, survival at 10 years is in the order of 65% following radical radiotherapy. Given the paucity of reported cases of primary bladder EMP, the optimal treatment regime remains unclear. In keeping with other anatomical sites current treatment is based to the assumed benefit of radical radiotherapy and prognosis appears to be better in those with no evidence of systemic disease.Keywords: bladder cancer, extramedullary plasmacytoma

  12. An Epidemiological Study of Cases of Urothelial Carcinoma of Urinary Bladder in a Tertiary Care Centre

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    Keya Basu

    2013-01-01

    Full Text Available Background: Urinary bladder cancer is the fourth most common malignancy in Western world. It is a heterogeneous disease with variable natural history. There is paucity of data in our country. Aims and Objectives: The present study aims to assess the risk factors contributing to urothelial carcinoma of bladder in the southern region of West Bengal and histopathological grading (WHO/ISUP. Materials and Methods: It was a retrospective study by multivariate analysis of case record proforma(CRP, agreed upon by a team of experts from the departments of Urosurgery and Pathology,CNMC&H, Kolkata from December, 2007 to November, 2009. Total 88 subjects who had at-tended in the department of urosurgery and al-ready been diagnosed either by cystoscopic bi-opsy or Transurethral Resection of Bladder Tumour (TURBT, were enrolled. Results: There was male preponderance (86.4 % male vs 13.6% female; the age range being 30-81 years(median 65. Hindus (81.8 % were affected more compared to Muslims (18.2 %. Blood group analysis showed highest incidence in B group (41% followed by O (32%. Tobacco smoking (75% cases revealed a strong relationship with bladder cancer and that was quantity and duration dependant. Less water intake(53.4% and poor socioeconomic status (82%were significant contributory factors. Analysis of occupational factors gave no epidemiological clue. Histopathological Examination (HPErevealed low grade urothelial carcinoma (51cases, high grade (24 cases and papilloma with low malignant potential (13 subjects. Conclusion: Proper epidemiological survey plays a pivotal role in bladder cancer to validate it in the disease control programme.

  13. Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

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    Nascimento e Pontes, Merielen Garcia; da Silveira, Sara Martorelli; Trindade Filho, José Carlos de Souza;

    2013-01-01

    in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors...... cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods "free-of-neoplasia." Our data are informative for further studies to better understand...

  14. Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection.

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    Blochin, Elen B; Park, Kay J; Tickoo, Satish K; Reuter, Victor E; Al-Ahmadie, Hikmat

    2012-11-01

    Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of self-catheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common well-differentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation.

  15. Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature

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    Hossein Tezval

    2012-10-01

    Full Text Available Clear cell variants of transitional cell carcinomas (TCC of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

  16. Transdifferentiation of Small Cell Carcinoma of the Urinary Bladder from Urothelial Carcinoma after Transurethral Resection of a Bladder Tumor, Intravesical Bacillus Calmette-Guerin Instillation, and Chemotherapy: A Case Report

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    Kento Morozumi

    2016-11-01

    Full Text Available A 73-year-old male underwent transurethral resection of a bladder tumor in August 2010 and April 2011. Pathological examination revealed urothelial carcinoma. After the surgery, chemotherapy and intravesical Bacillus Calmette-Guerin instillation were performed. In September 2014, he once again underwent transurethral resection of the bladder tumor for recurrence, and was again diagnosed with urothelial carcinoma, pT2, by pathological examination. After neoadjuvant chemotherapy, radical cystectomy for tumor recurrence was performed. Pathological examination at this time revealed small cell carcinoma, pT3N0. It is rare for urothelial carcinoma to change to small cell carcinoma, and the mechanism and cause of this change are still unknown. In this case report, we discuss what causes small cell carcinoma of the urinary bladder and review the literature regarding its origin.

  17. Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder.

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    Junqueira-Neto, Susana; Vieira, Filipa Q; Montezuma, Diana; Costa, Natália R; Antunes, Luís; Baptista, Tiago; Oliveira, Ana Isabel; Graça, Inês; Rodrigues, Ângelo; Magalhães, José S; Oliveira, Jorge; Henrique, Rui; Jerónimo, Carmen

    2015-07-01

    Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets.

  18. Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

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    Ning X

    2017-03-01

    Full Text Available Xin Ning, Yaoliang Deng Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China Background: Genomic profiling can be used to identify the predictive effect of genomic subsets for determining prognosis in bladder urothelial carcinoma (BUC after radical cystectomy. This study aimed to investigate potential gene and pathway markers associated with prognosis in BUC.Methods: A microarray dataset of BUC was obtained from The Cancer Genome Atlas database. Differentially expressed genes (DEGs were identified by DESeq of the R platform. Kaplan–Meier analysis was applied for prognostic markers. Key pathways and genes were identified using bioinformatics tools, such as gene set enrichment analysis, gene ontology, the Kyoto Encyclopedia of Genes and Genomes, gene multiple association network integration algorithm (GeneMANIA, Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection.Results: A comparative gene set enrichment analysis of tumor and adjacent normal tissues suggested BUC tumorigenesis resulted mainly from enrichment of cell cycle and DNA damage and repair-related biological processes and pathways, including TP53 and mitotic recombination. Two hundred and fifty-six genes were identified as potential prognosis-related DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the potential prognosis-related DEGs were enriched in angiogenesis, including the cyclic adenosine monophosphate biosynthetic process, cyclic guanosine monophosphate-protein kinase G, mitogen-activated protein kinase, Rap1, and phosphoinositide-3-kinase-AKT signaling pathway. Nine hub genes, TAGLN, ACTA2, MYH11, CALD1, MYLK, GEM, PRELP, TPM2, and OGN, were identified from the intersection of protein–protein interaction and GeneMANIA networks. Module analysis of protein–protein interaction and GeneMANIA networks mainly showed

  19. A case of a sporadic malignant peripheral nerve sheath tumor of the urinary bladder with concomitant in situ urothelial carcinoma treated by transuretheral resection

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    Aysegul Sari

    2011-01-01

    Full Text Available Malignant peripheral nerve sheath tumor (MPNST of the urinary bladder is a very rare clinical entity. The association of such a tumor with urothelial carcinoma is even more unusual. Differential diagnosis between coexisting two distinct primary tumors and carcinosarcoma of the urinary bladder is very important as both the treatment and prognosis vary widely. Herein, we report a case of an MPNST with a concomitant in situ urothelial carcinoma in a 53-year-old man. To our knowledge, this is the first documented case of MPNST of the bladder that is treated by transuretheral resection which is in contrast with the previous reports that used cystectomy.

  20. [A CASE OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER WITH SQUAMOUS DIFFERENTIATION RESPONDING TO PACLITAXEL AND CARBOPLATIN NEOADJUVANT CHEMOTHERAPY].

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    Banno, Eri; Nishino, Aki; Nagai, Yasuharu; Yasuda, Muneo; Tahara, Hideo; Kino, Shigeo; Kanno, Norihumi

    2015-07-01

    A 42-year-old man was referred to our hospital for macrohematuria. Computer tomography and magnetic resonance imaging revealed right hydronephrosis and a retroperitoneal mass, located next to right side of the bladder. Cystoscopy showed a protruded lesion covered with normal mucosa at the right lateral wall. The patient underwent transurethral resection of the bladder tumor and biopsies of the bladder wall. Histological examination showed squamous cell carcinoma. Neoadjuvant chemotherapy using paclitaxel and carboplatin (TC) was performed. A total cystectomy, right nephroureterectomy and construction of the ileal conduit were performed after one course of systemic chemotherapy. Histological examination showed urothelial carcinoma with squamous cell differentiation. Unexpectedly, a small amount of CIS was detected only in the vicinity of the TUR scar. The patient received 2 cycles of TC chemotherapy as adjuvant chemotherapy. Unfortunately, 11 months later, local recurrence and liver metastasis were detected. He died 17 months after the surgery.

  1. Intravesical therapy for urothelial carcinoma of the urinary bladder: a critical review

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    Daher C. Chade

    2009-12-01

    Full Text Available The management of non-muscle-invasive urothelial carcinoma of the bladder (UCB is a challenge for physicians and patients alike. This is largely due to the heterogeneous natural history of this disease, in which tumors range from indolent to rapidly progressive and eventually fatal. Moreover, the high rate of recurrence and progression cause significant morbidity, expense, and detriment to quality of life. The advent of effective and safe intravesical therapies has improved the management of non-muscle-invasive UCB. Nevertheless, despite over 30 years of research and clinical experience, the mechanism, risks, benefits, and optimal regimens and treatment algorithms remain unclear. Although immunotherapy with bacillus Calmette-Guerin (BCG has been the mainstay of intravesical treatment and represents a significant advance in the interaction of immunology and oncology, its clinical effectiveness is accompanied by a wide range of adverse events. Here, we review the literature on intravesical immunotherapy and chemotherapy with the aim of evaluating the clinical utility of the different treatments and providing recommendations. Many studies over the years have compared efficacy and toxicities of different agents and regimens, and certain conclusions are now well supported by high-level evidence. Future perspectives and promising advances in drug development are discussed and areas of improvement are identified in order to promote better cancer control and decrease the rate and severity of side-effects.

  2. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

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    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  3. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

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    Young H. Lee

    2014-11-01

    Full Text Available There is mounting evidence of oncogenic hepatocyte growth factor (HGF/Met signaling in urothelial carcinoma (UC of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  4. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder.

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    Lee, Young H; Apolo, Andrea B; Agarwal, Piyush K; Bottaro, Donald P

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  5. Unusual manifestations of secondary urothelial carcinoma

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    Chaohui Lisa Zhao

    2016-03-01

    Full Text Available High-grade papillary urothelial carcinoma regularly invades the bladder wall, adjacent prostate, seminal vesicles, ureters, vagina, rectum, retroperitoneum, and regional lymph nodes. In advanced stages, it may disseminate to the liver, lungs, and bone marrow. On rare occasions, unusual metastatic foci like skin have been reported. The incidence of urothelial carcinoma has increased with associated rise in variants of urothelial carcinoma and unusual metastatic foci. It is imperative that urologists and pathologists are aware of the unusual variants and unusual metastatic locations to expedite the diagnostic process. Hereby we report an unusual case of secondary involvement of spinal nerve by conventional urothelial carcinoma. Also a second case of rhabdoid variant of urothelial carcinoma showing synchronous involvement of bladder and subcutaneous tissue of upper extremity is presented.

  6. ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder.

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    Faraj, Sheila F; Chaux, Alcides; Gonzalez-Roibon, Nilda; Munari, Enrico; Ellis, Carla; Driscoll, Tina; Schoenberg, Mark P; Bivalacqua, Trinity J; Shih, Ie-Ming; Netto, George J

    2014-11-01

    AT-rich interactive domain 1A (ARID1A) is tumor suppressor gene that interacts with BRG1 adenosine triphosphatase to form a SWI/SNF chromatin remodeling protein complex. Inactivation of ARID1A has been described in several neoplasms, including epithelial ovarian and endometrial carcinomas, and has been correlated with prognosis. In the current study, ARID1A expression in urothelial carcinoma (UC) of the bladder and its association with clinicopathological parameters and outcome are addressed. Five tissue microarrays were constructed from 136 cystectomy specimens performed for UC at our institution. Nuclear ARID1A staining was evaluated using immunohistochemistry. An H-score was calculated as the sum of the products of intensity (0-3) multiplied by extent of expression (0%-100%). Average H-score per case was used for statistical analysis. ARID1A expression was categorized in low and high using Youden index to define the cut point. ARID1A expression significantly increased from normal to noninvasive UC to invasive UC. For both tumor progression and cancer death, Youden index yielded an H-score of 288 as the optimal cut point for ARID1A expression. Low ARID1A expression showed a tendency for lower risk of tumor progression and cancer mortality. Adding ARID1A expression to pathologic features offers a better model for predicting outcome than pathologic features alone. Low ARID1A expression was more frequently seen in earlier stage disease. There was a tendency for low ARID1A expression to predict better outcome. More importantly, the findings indicate that adding ARID1A expression to pathologic features increases the goodness of fit of the predictive model.

  7. Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder.

    Science.gov (United States)

    Gonzalez-Roibon, Nilda D; Chaux, Alcides; Al-Hussain, Turki; Osunkoya, Adeboye O; Bezerra, Stephania Martins; Hicks, Jessica; Epstein, Jonathan I; Netto, George J

    2013-04-01

    Plasmacytoid urothelial carcinoma is a rare but aggressive variant of bladder cancer with no clear therapeutic guidelines. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been linked to oncogenesis in conventional bladder cancer. Several antineoplastic agents targeting mTOR pathway are currently available. This study assesses mTOR pathway status as well as c-myc and p27 expression. We retrieved 19 archival cases of plasmacytoid urothelial carcinoma from two institutions. Whole tissue sections were evaluated for immunoexpression of phosphatase and tensin homolog (PTEN), phosphorylated mTOR, phosphorylated protein kinase B (AKT), phosphorylated S6, c-myc, and p27. We evaluated intensity (0 to 3+) and extent (0%-100%) of expression for all markers. An H score was calculated as the sum of products of intensity and extent for each marker and used during analysis. In addition, PTEN loss was defined as absence of expression in >10% of tumor cells. We encountered PTEN loss in 28%. Higher H score for nuclear phosphorylated AKT and a lower H score for phosphorylated S6 was encountered in muscle invasive tumors compared to non-muscle invasive tumors (P = .007 and P = .009, respectively). Although a trend for negative prognostic impact on overall survival for higher phosphorylated mTOR expression was noted (P = .051), markers expression levels failed to predict survival in our cohort. We found dysregulation of mTOR pathway members in urinary bladder plasmacytoid urothelial carcinoma, suggesting that the use of mTOR pathway inhibitors might be beneficial for patients with this aggressive tumor.

  8. The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder.

    Science.gov (United States)

    Rosevear, Henry M; Lightfoot, Andrew J; O'Donnell, Michael A; Griffith, Thomas S

    2009-12-01

    Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

  9. uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Pappot, Helle; Iversen, Benedikte Richter;

    2015-01-01

    The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling...... or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated...... investigations have generated new and valuable biological information about the cell types being involved in tumour invasion and progression through the plasminogen activation system....

  10. Synchronous papillary urothelial carcinoma of urinary bladder and adenocarcinoma of stomach in a middle-aged man: An extremely rare association with therapeutic dilemma

    Directory of Open Access Journals (Sweden)

    Dodul Mondal

    2013-01-01

    Full Text Available Synchronous occurrence of urinary bladder carcinoma and gastric carcinoma is very rare. A middle-aged Asian man presented with complaints of hematuria which was diagnosed due to muscle invasive papillary urothelial carcinoma of urinary bladder. Metastatic work-up revealed simultaneous presence of locally advanced gastric adenocarcinoma. He was treated with TURBT for the bladder cancer and was planned for radical gastric resection followed by radiation to urinary bladder and stomach with concurrent chemotherapy. However, due to very advanced nature of the gastric tumor patient was treated only with palliative gastric resection followed by palliative radiation to both urinary bladder and stomach due to his poor performance status. Lack of published English literature and evidence related to such clinical entity made this an extremely rare clinical entity and treatment decision difficult.

  11. ROS generation via NOX4 and its utility in the cytological diagnosis of urothelial carcinoma of the urinary bladder

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    Fujimoto Kiyohide

    2011-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS production via NADPH oxidase (NOX contributes to various types of cancer progression. In the present research, we examined the pathobiological role of NADPH oxidase (NOX4-mediated generation of reactive oxygen species (ROS in urothelial carcinoma (UC of the urinary bladder, and demonstrated the utility of ROS labeling in urine cytology. Methods NOX4 gene was silenced in vivo and in vitro by NOX4 siRNA transfection with or without atlocollagen. Cell cycle and measurement of ROS were analyzed by flowcytometry. Orthotopic implantation animal model was used in vivo experiment. NOX4 expression in urothelial carcinoma cells was observed by immunohistochemical analysis using surgical specimens of human bladder cancer. Urine cytology was performed after treatment with ROS detection reagents in addition to Papanicolaou staining. Results NOX4 was overexpressed in several UC cell lines and the NOX inhibitor, diphenylene iodonium reduced intracellular ROS and induced p16-dependent cell cycle arrest at the G1 phase. Moreover, silencing of NOX4 by siRNA significantly reduced cancer cell growth in vivo as assessed in an orthotopic mouse model. Immunohistochemistry demonstrated high expression of NOX4 in low grade/non-invasive and high grade/invasive UC including precancerous lesions such as dysplasia but not in normal urothelium. Then, we assessed the usefulness of cytological analysis of ROS producing cells in urine (ROS-C. Urine samples obtained from UC cases and normal controls were treated with fluorescent reagents labeling the hydrogen peroxide/superoxide anion and cytological atypia of ROS positive cells were analyzed. As a result, the sensitivity for detection of low grade, non-invasive UC was greatly increased (35% in conventional cytology (C-C vs. 75% in ROS-C, and the specificity was 95%. Through ROS-C, we observed robust improvement in the accuracy of follow-up urine cytology for cases with previously

  12. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

    Science.gov (United States)

    Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo

    2015-01-01

    Background To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0–3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies. PMID:26046361

  13. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.

    Directory of Open Access Journals (Sweden)

    Francesco Massari

    Full Text Available To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential.In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3; c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive.beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively; 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02 and c-Myc 28 low vs 8 high (p-value 0.007. Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006.c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

  14. Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder urothelial carcinoma in T24 cells.

    Science.gov (United States)

    Xu, Song-Tao; Ding, Xiang; Ni, Qing-Feng; Jin, Shao-Ju

    2015-01-01

    The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.

  15. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-01-01

    Full Text Available Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3 bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after

  16. Alpha-T-catenin (CTNNA3) displays tumour specific monoallelic expression in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Meehan, Maria; Melvin, Audrey; Gallagher, Emma; Smith, James; McGoldrick, Alo; Moss, Catherine; Goossens, Steven; Harrison, Michèle; Kay, Elaine; Fitzpatrick, John; Dervan, Peter; Mc Cann, Amanda

    2007-06-01

    CTNNA3 (alpha-T-catenin) is imprinted with preferential monoallelic expression of the maternal allele in placental tissue. The allelic expression pattern of CTNNA3 in adult human cancer is unknown and warrants investigation as CTNNA3 stabilizes cellular adherence, a feature which if compromised could enable cells to acquire an increased capability to detach and invade. We document the frequency of monoallelic versus biallelic expression of CTNNA3 in urothelial carcinoma of the bladder (UCB) samples and compare the observed patterns with that found in the paired normal sample. DNA PCR reactions encompassing a transcribable SNP polymorphism within exon 12 of CTNNA3 were sequence analyzed to identify heterozygous cases. A total of 96 samples were analyzed and included 22 paired normal and tumor UCB cases, 38 formalin fixed paraffin embedded (FFPE) UCB samples consisting of 18 noninvasive pTa tumors and 20 lamina propria invasive pT1 tumors and 14 cell lines of various lineages. RT-PCR analysis of 35 heterozygous samples followed by sequence analysis allowed monoallelic versus biallelic patterns to be assigned. We have provided the first demonstration that CTNNA3 displays differing allelic expression patterns in UCB. Specifically, 35% (7/20) of informative UCB, showed monoallelic expression, a feature confined to the tumor, with normal urothelial samples displaying biallelic expression. Real time RT-PCR analyses, demonstrated a significantly lower (P = 0.00039) level of CTNNA3 in the tumor samples compared with the paired normals, all of which displayed biallelic expression. In conclusion, monoallelic and biallelic CTNNA3 expression patterns are demonstrable in tumor bladder tissue, whereas normal cases show only biallelic expression.

  17. Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinoma.

    Science.gov (United States)

    Moussa, Mona; Omran, Zeinab; Nosseir, Mona; Lotfy, Abeya; Swellam, Tarek

    2009-01-01

    Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX-2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections and urine cytology samples was performed for all cases using COX-2 (H-62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2 expression was sequentially up-regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (pUrine cytology samples were positive for COX-2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX-2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX-2 expression and hence proved to be valuable in

  18. Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer

    Science.gov (United States)

    2016-08-31

    Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage III Bladder Urothelial Carcinoma; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Urethral Cancer; Urethral Urothelial Carcinoma

  19. Telomere instability in papillary bladder urothelial carcinomas: Comparison with grading and risk of recurrence

    Directory of Open Access Journals (Sweden)

    Giuseppe Mucciardi

    2014-01-01

    Conclusions: Our study demonstrates that TL, TA and TBPs are altered in tumors and non-cancerous mucosa in patients with papillary urothelial NMIBC. Further studies are warranted to identify their suitability as a potential biomarker.

  20. Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

    Directory of Open Access Journals (Sweden)

    Sha N

    2015-11-01

    Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

  1. Plasmacytoid Urothelial Carcinoma of the Urinary Bladder Metastatic to the Duodenum: A Case Report—Diagnostic Relevance of GATA3 Immunohistochemistry

    Science.gov (United States)

    2017-01-01

    Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread. PMID:28255490

  2. Plasmacytoid Urothelial Carcinoma of the Urinary Bladder Metastatic to the Duodenum: A Case Report—Diagnostic Relevance of GATA3 Immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Hermann Brustmann

    2017-01-01

    Full Text Available Plasmacytoid urothelial carcinoma (PUC of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread.

  3. CD44 and MMP-2 expression in urothelial carcinoma

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    Gülgün ERDOĞAN

    2008-09-01

    Full Text Available Aim: CD44, one of the adhesion molecules, is thought to play an important role in cell-cell and cell-matrix interactions. Matrix metalloproteinases are degradative enzymes that remodel extracellular components. In this study the relation of MMP-2 and CD44 expressions with the histologic classification and the pathologic stage of urothelial carcinoma was revealed using immunohistochemistry.Material and Methods: Thirty-nine patients with urothelial carcinoma of the bladder were studied. The histological classification was performed according to WHO criteria. Patients were grouped as infiltrating urothelial carcinoma, low grade non-invasive papillary urothelial carcinoma, and high grade non-invasive papillary urothelial carcinoma. The pathological staging was done according to the TNM classification. Immunohistochemical staining using CD44 and MMP-2 antibodies was performed on tissue blocks.Results: CD44 immunoreactivity was detected in 77% (30/39 of the tumours which was significantly higher in non-invasive papillary urothelial carcinomas, low grade non-invasive papillary urothelial carcinomas, high grade infiltrating urothelial carcinomas (p≥0.05. MMP-2 expression was observed in 69% (27 of 39 of the tumours. There were no significant differences in MMP-2 expression between various histologic subtypes and noninvasive and infiltrative tumours.Conclusion: In conclusion, higher expression of CD44 is inversely correlated with infiltrative potential of urothelial carcinoma. These results should be supported by further studies.

  4. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

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    Susan K. Keay

    2014-01-01

    Full Text Available Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC, feline interstitial cystitis (FIC, and nonneurogenic idiopathic overactive bladder (OAB. These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.

  5. Upregulation of TRAG3 gene in urothelial carcinoma of the bladder

    OpenAIRE

    Karam, Jose A.; Huang, Sandra; Fan, Jinhai; Stanfield, Jennifer; Schultz, Roger A; Pong, Rey-Chen; Sun, Xiankai; Mason, Ralph P.; Xie, Xian-Jin; Niu, Gang; Chen, Xiaoyuan; Frenkel, Eugene P.; Sagalowsky, Arthur I.; Hsieh, Jer-Tsong

    2010-01-01

    Conventional chemotherapy is commonly used for advanced stages of bladder cancer with modest success and high morbidity. Identifying markers of resistance will allow clinicians to tailor treatment to a specific patient population. T24-tumorigenic cell line was grown orthotopically in nude mice and monitored using bioluminescence imaging and microcomputed tomography until they developed metastases. Stable sublines were then developed from primary bladder (T24-P), lung (T24-L) and bone (T24-B) ...

  6. Plasma and urine DNA levels are related to microscopic hematuria in patients with bladder urothelial carcinoma.

    Science.gov (United States)

    de Almeida, Eduardo Ferreira Pedroso; Abdalla, Tomás Elias; Arrym, Tiago Pedromonico; de Oliveira Delgado, Pamela; Wroclawski, Marcelo Langer; da Costa Aguiar Alves, Beatriz; de S Gehrke, Flávia; Azzalis, Ligia Ajaime; Alves, Sarah; Tobias-Machado, Marcos; de Lima Pompeo, Antonio Carlos; Fonseca, Fernando Luiz Affonso

    2016-11-01

    a) Objective: An increase in cell-free DNA was observed in the plasma of many cancer patients. This major biomarker can be used to differentiate patients with malignant neoplasms from those with benign neoplasms or healthy patients. Depending on the characteristic of the tumor, there are qualitative variations in the circulating cell-free DNA. Today, studies on the concentration of fragments of circulating cell-free DNA and their respective sizes in patients with bladder cancer are not plentiful in the literature. A 100% effective plasma tumor marker, which would help in the diagnosis and follow-up of bladder cancer, is yet to be developed; therefore, cell-free DNA levels in the plasma may represent a valuable biomarker for the diagnosis, prognosis and follow-up of patients with this type of tumor. b) Design and methods: In this study we analyze the kinetics of plasma and urine DNA concentrations in patients with bladder cancer, relating them to the other clinical laboratory variables. c) Results: Patients with hematuria showed a positive correlation with urine DNA. d) Conclusion: An increase in plasma and urine DNA was unprecedentedly reported over time, a fact that may come in handy in the prognosis of patients. Furthermore, microscopic haematuria is correlated with plasma and urinary DNA levels.

  7. Artificial intelligence for predicting recurrence-free probability of non-invasive high-grade urothelial bladder cell carcinoma.

    Science.gov (United States)

    Cai, Tommaso; Conti, Gloria; Nesi, Gabriella; Lorenzini, Matteo; Mondaini, Nicola; Bartoletti, Riccardo

    2007-10-01

    The objective of our study was to define a neural network for predicting recurrence and progression-free probability in patients affected by recurrent pTaG3 urothelial bladder cancer to use in everyday clinical practice. Among all patients who had undergone transurethral resection for bladder tumors, 143 were finally selected and enrolled. Four follow-ups for recurrence, progression or survival were performed at 6, 9, 12 and 108 months. The data were analyzed by using the commercially available software program NeuralWorks Predict. These data were compared with univariate and multivariate analysis results. The use of Artificial Neural Networks (ANN) in recurrent pTaG3 patients showed a sensitivity of 81.67% and specificity of 95.87% in predicting recurrence-free status after transurethral resection of bladder tumor at 12 months follow-up. Statistical and ANN analyses allowed selection of the number of lesions (multiple, HR=3.31, p=0.008) and the previous recurrence rate (>or=2/year, HR=3.14, p=0.003) as the most influential variables affecting the output decision in predicting the natural history of recurrent pTaG3 urothelial bladder cancer. ANN applications also included selection of the previous adjuvant therapy. We demonstrated the feasibility and reliability of ANN applications in everyday clinical practice, reporting a good recurrence predicting performance. The study identified a single subgroup of pTaG3 patients with multiple lesions, >or=2/year recurrence rate and without any response to previous Bacille Calmette-Guérin adjuvant therapy, that seem to be at high risk of recurrence.

  8. Upregulation of TRAG3 gene in urothelial carcinoma of the bladder

    Science.gov (United States)

    Karam, Jose A.; Huang, Sandra; Fan, Jinhai; Stanfield, Jennifer; Schultz, Roger A.; Pong, Rey-Chen; Sun, Xiankai; Mason, Ralph P.; Xie, Xian-Jin; Niu, Gang; Chen, Xiaoyuan; Frenkel, Eugene P.; Sagalowsky, Arthur I.; Hsieh, Jer-Tsong

    2010-01-01

    Conventional chemotherapy is commonly used for advanced stages of bladder cancer with modest success and high morbidity. Identifying markers of resistance will allow clinicians to tailor treatment to a specific patient population. T24-tumorigenic cell line was grown orthotopically in nude mice and monitored using bioluminescence imaging and microcomputed tomography until they developed metastases. Stable sublines were then developed from primary bladder (T24-P), lung (T24-L) and bone (T24-B) tissues. Chromosomal analysis and DNA microarray were used to characterize these sublines. qRT-PCR and immunohistochemistry (IHC) were used for validation. Epigenetic modifiers were used to study gene regulation. The cell viability was quantified with MTT assay. Chromosomal analysis revealed multiple alterations in metastatic cell lines compared to T24-P. DNA microarray analysis showed that Taxol-Resistance-Associated-Gene-3 (TRAG3) gene was the most upregulated gene. From qRT-PCR and IHC, TRAG3 was significantly higher in T24-L and T24-B than T24-P. TRAG3 gene expression is likely controlled by DNA methylation, but not histone acetylation. Interestingly, T24-B and T24-L cells were more resistant than T24-P to treatment with anti-microtubule agents such as docetaxel, paclitaxel and vinblastine. TRAG3 mRNA expression was higher in 20% of patients with ≤pT2 (n=10) and 60% of patients with ≥pT3 (n=20) compared to normal adjacent tissue (p=0.05). In addition, the median TRAG3 expression was 6.7-fold higher in ≥pT3 tumors compared to ≤pT2 tumors. Knowing the status of TRAG3 expression could help clinicians tailor treatment to a particular patient population that could benefit from treatment, while allocating patients with resistant tumors to new experimental therapies. PMID:20734393

  9. Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Matteo Santoni

    2012-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.

  10. MORPHOMETRY, DENSITOMETRY AND PATTERN-ANALYSIS OF PLASTIC-EMBEDDED HISTOLOGIC MATERIAL FROM UROTHELIAL CELL-CARCINOMA OF THE BLADDER

    NARCIS (Netherlands)

    VANDERPOEL, HG; BOON, ME; KOK, LP; VANDERMEULEN, EA; VANCAUBERGH, RD; DEBRUIJN, WC; DEBRUYNE, FMJ

    1991-01-01

    An image analysis method of grading histologic sections of bladder carcinoma was tested. The method was new in four respects. First, fixation of the biopsies a coagulant fixative was used. Second, 2-mu-m plastic sections were used to ensure the reproductibility of nuclear imaging. Third, a new stere

  11. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  12. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Skoneczna, Iwona; Kerst, J Martijn

    2015-01-01

    BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcin...... patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING: Lilly, Canadian Cancer Society Research.......BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial......, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint...

  13. 膀胱尿路上皮癌及正常膀胱组织microRNA21、205表达研究%Expression of miR-21 and miR-205 in urothelial cell carcinoma of bladder and normal bladder mucosa

    Institute of Scientific and Technical Information of China (English)

    马杰; 姜宁; 王国增; 郑景存; 贺伟; 刁海彦

    2012-01-01

    目的 探讨microRNAs (miRNAs)在膀胱尿路上皮癌与正常膀胱组织中的表达差异性及意义.方法 采用基于2-△△cT的实时定量PCR(Real-time PCR)方法 检测50例膀胱尿路上皮癌与21例正常膀胱组织中miR-21及miR-205的表达情况.结果 与正常组织相比,癌组织miR-21表达上调(P<0.01),miR-205表达下调(P<o.o1).癌组织中miR-21与miR-205表达量的比值约3.6倍于正常组织中表达量的比值.结论 miR-21高表达、miR-205低表达可能参与膀胱尿路上皮癌的发生、发展.%Objective To detect the expression of miR-21 and miR-205 in urothelial cell carcinoma of bladder and normal bladder mucosa and explore the relationship between microRNAs (miRNAs) and urothelial cell carcinoma of bladder. Methods 2△△CT Real-time PCR method was used for quantitative analysis of the expression of miR-21 and miR-205 in 50 urothelial cell carcinoma of bladder and 21 normal bladder tissues. Results Compared with normal bladder mucosa, the urothelial cell carcinoma of bladder tissues showed significant miR-21 over-expression (P<0. 01) and miR-205 down-regulation (P <0. 01). Cancer tissue showed miR-21: miR-205 ratio at least 3.6-fold higher than the quantitative ratio obtained from normal bladder tissue. Conclusion The over expression of miR-21 and lower expression of miR-205 may participate in recurrence urothelial cell carcinoma of bladder.

  14. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

    Science.gov (United States)

    Dhawan, Deepika; Paoloni, Melissa; Shukradas, Shweta; Choudhury, Dipanwita Roy; Craig, Bruce A; Ramos-Vara, José A; Hahn, Noah; Bonney, Patty L; Khanna, Chand; Knapp, Deborah W

    2015-01-01

    More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC) this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  15. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Deepika Dhawan

    Full Text Available More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  16. Management of the urethra in urothelial bladder cancer

    OpenAIRE

    Kanaroglou, Androniki; Shayegan, Bobby

    2009-01-01

    The standard of care in the management of invasive urothelial cancer of the bladder is radical cystectomy and pelvic lymphadenectomy. Although uncommon, recurrence of disease in the retained urethra following cystectomy carries a poor prognosis. The need for assessment of risk of recurrence is greater now than ever with wider adoption of orthotopic bladder substitution. This review will address the contemporary management of the urethra following cystectomy for urothelial cancer.

  17. Ureterocele urothelial carcinoma: managing a rare presentation.

    Science.gov (United States)

    Astigueta, Juan Carlos; Abad-Licham, Milagros; Silva, Eloy; Alvarez, Víctor; Piccone, Francis; Cruz, Enrique; Redorta, Joan Palou

    2016-01-01

    It is very uncommon for urothelial carcinoma to develop in an ureterocele. It is generally discovered in an imaging study or in connection with haematuria. We found very few reports in the literature. Here, we report on the case of a 71-year-old male who initially presented with haematuria and low back pain and who then underwent transurethral resection for an intraureterocele tumour. Pathology confirmed urothelial carcinoma.

  18. Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder

    Institute of Scientific and Technical Information of China (English)

    FENG Lang; MA Lin-lin; ZHANG Yu-hai; TIAN Ye; QU Chen-xue; WANG Yang

    2012-01-01

    Background Superficial urothelial carcinoma (SUC) of the bladder is a common urinary tract tumor in China.There is a high recurrence rate of this tumor even after surgery and intravesical instillation.Previous reports have described a suppression of the immune system in cancer patients.Dendritic cells (DCs) play a pivotal role in the induction of an effective antitumor immune response.The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy (IC) on peripheral blood DCs in subsets of patients with bladder SUC.@@Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study.All the patients had undergone transurethral resection (TUR) of their cancer and adjunctive IC after tumor removal.The patients were divided into a non-recurrence group (n=40) and a recurrence group (n=26) based on the presence or absence of tumor recurrence.Blood samples were taken preoperatively (PreOP),on postoperative days (POD) 1 and 7,and at postoperative month (POM) 3.Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets.@@Results The preoperative percentages of myeloid dendritic cells (mDCs) and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls (P <0.05).The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7,remaining higher than the preoperative values in POM 3 (P <0.05).The percentages of mDCs,and CD80 and CD86 in the non-recurrence group on PreOP,POD 7,and POM 3 were higher than those in recurrence group.@@Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function.Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.

  19. High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21: a study using formalin-fixed, paraffin-embedded archival tissues.

    Science.gov (United States)

    Chaux, Alcides; Cohen, Julie S; Schultz, Luciana; Albadine, Roula; Jadallah, Sana; Murphy, Kathleen M; Sharma, Rajni; Schoenberg, Mark P; Netto, George J

    2012-10-01

    Epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase family reported to be overexpressed in a variety of solid malignancies. Mutations in exons 19 to 21 of the tyrosine kinase domain have been detected in a subset of these tumors and its presence associated with a better response to EGFR inhibitors. Several clinical trials are currently underway to evaluate the performance of such drugs in patients with bladder cancer, but data on EGFR mutation status are limited. The current study assesses EGFR immunohistochemical expression and the presence of mutations in exons 19 and 21 by polymerase chain reaction in 19 bladder urothelial carcinomas from formalin-fixed, paraffin-embedded tissues. Representative paraffin sections were microdissected for DNA extraction using a pinpoint isolation system. Parallel sections were immunostained using a monoclonal anti-EGFR antibody. No mutations in exons 19 and 21 of EGFR were identified in any of the cases. Immunohistochemical EGFR positivity was observed in 14 of 19 cases. In summary, we found EGFR protein expression in 74% of urothelial carcinomas, but we failed to detect EGFR mutations at exons 19 to 21, suggesting that EGFR overexpression is not related to the presence of mutations in the tyrosine kinase domain of the gene. Mutation analysis of EGFR exons 19 and 21 is feasible in microdissected paraffin sections from archival tissues. Immunohistochemical expression of EGFR may not be useful to predict therapeutic response to EGFR inhibitors in patients with urothelial carcinomas. To explain EGFR immunohistochemical overexpression, other mechanisms besides mutations in the EGFR kinase domain should be investigated in future studies.

  20. Upper Tract Urothelial Carcinomas in Patients with Chronic Kidney Disease: Relationship with Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    Li-Jen Wang

    2014-01-01

    Full Text Available Chronic kidney disease and upper tract urothelial carcinomas display a bidirectional relationship. Review of the literature indicates that early diagnosis and correct localization of upper tract urothelial carcinomas in dialysis patients and kidney transplant recipients are important but problematic. Urine cytology and cystoscopy have limited sensitivity for the diagnosis of upper tract urothelial carcinomas in dialysis patients. Enhanced computed tomography and magnetic resonance imaging could prove useful for the detection and staging of upper tract urothelial carcinomas in dialysis patients. Renal ultrasound can detect hydronephrosis caused by upper tract urothelial carcinomas in kidney transplant recipients but cannot visualize the carcinomas themselves. High detection rates for upper tract urothelial carcinomas in kidney transplant recipients have recently been demonstrated using computed tomography urography, which appears to be a promising tool. To detect carcinomas in dialysis patients and kidney transplant recipients as early as possible, regular screening in asymptomatic patients and diagnostic work-up in symptomatic patients should be performed using a combination of urological and imaging methods. Careful assessment of subsequent recurrence within the contralateral upper urinary tract and the urinary bladder is necessary for dialysis patients and kidney transplant recipients with upper tract urothelial carcinomas.

  1. Upper tract urothelial carcinomas in patients with chronic kidney disease: relationship with diagnostic challenge.

    Science.gov (United States)

    Wang, Li-Jen; Lee, Shen-Yang; Teh, Bin Tean; Chuang, Cheng-Keng; Nortier, Joëlle

    2014-01-01

    Chronic kidney disease and upper tract urothelial carcinomas display a bidirectional relationship. Review of the literature indicates that early diagnosis and correct localization of upper tract urothelial carcinomas in dialysis patients and kidney transplant recipients are important but problematic. Urine cytology and cystoscopy have limited sensitivity for the diagnosis of upper tract urothelial carcinomas in dialysis patients. Enhanced computed tomography and magnetic resonance imaging could prove useful for the detection and staging of upper tract urothelial carcinomas in dialysis patients. Renal ultrasound can detect hydronephrosis caused by upper tract urothelial carcinomas in kidney transplant recipients but cannot visualize the carcinomas themselves. High detection rates for upper tract urothelial carcinomas in kidney transplant recipients have recently been demonstrated using computed tomography urography, which appears to be a promising tool. To detect carcinomas in dialysis patients and kidney transplant recipients as early as possible, regular screening in asymptomatic patients and diagnostic work-up in symptomatic patients should be performed using a combination of urological and imaging methods. Careful assessment of subsequent recurrence within the contralateral upper urinary tract and the urinary bladder is necessary for dialysis patients and kidney transplant recipients with upper tract urothelial carcinomas.

  2. The orthotopic Fischer/AY-27 rat bladder urothelial cell carcinoma model to test the efficacy of different apaziquone formulations.

    NARCIS (Netherlands)

    Arentsen, H.C.; Hendricksen, K.; Hulsbergen- van de Kaa, C.A.; Reddy, G.; Oosterwijk, E.; Alfred Witjes, J.

    2012-01-01

    OBJECTIVES: Apaziquone used intravesically showed significant activity in phase I and II marker lesion studies in non-muscle-invasive bladder cancer. The objective of this study was to assess antitumor activity and safety of 3 different formulations of intravesical apaziquone in an orthotopic rat bl

  3. Expression of cathepsin D in urothelial carcinoma of the urinary bladder: an immunohistochemical study including correlations with extracellular matrix components, CD44, p53, Rb, c-erbB-2 and the proliferation indices.

    Science.gov (United States)

    Ioachim, Elli; Charchanti, Antonia; Stavropoulos, Nikolaos; Athanassiou, Evangelia; Bafa, Maria; Agnantis, Niki J

    2002-01-01

    The immunohistochemical Cathepsin D (CD) expression of tumor and stromal cells was investigated in a series of 77 urothelial carcinomas of the urinary bladder with the intention to evaluate its prognostic significance and its contribution to the metastatic potential of bladder cancer. CD expression (clone D13A) was correlated with the expression of extracellular matrix components (collagen type IV, laminin, fibronectin), CD44, p53, pRb, proliferation indices (PCNA and MIB1) as well as with other conventional clininopathological features. CD expression (> 10% of positive tumor cells) was observed in 77.9% of the carcinomas. Stromal CD expression was detected in all cases. Linear collagen type IV and laminin deposit at the tumor-stroma border (in > 25% of the BM) was found in 26% and 57.6% of the cases, respectively. The CD of cancer cells (CCCD) was inversely-correlated with the CD of the stromal cells (p = 0.039), tumor grade (p = 0.0028), tumor stage (p = 0.0046), p53 protein (p = 0.05) and positively-correlated with CD44 (p = 0.002) and pRb (p = 0.05). The stromal cells CD (SCCD) showed a statistically significant positive correlation with tumor grade (p < 0.0001) and stage (p = 0.0001), and the proliferation indices PCNA and MIB1 (p = 0.0001 and p = 0.0002, respectively). These data suggest that both CD of tumor and stromal cells could play important roles in the expansion of urothelial carcinoma of the urinary bladder.

  4. Clinical utility of fluorescence in situ hybridization in bladder urothelial carcinoma%荧光原位杂交技术在膀胱尿路上皮癌中的临床应用研究

    Institute of Scientific and Technical Information of China (English)

    王勇; 李杰; 李鹏超; 魏俊峰; 唐敏; 李永飞; 黄婷; 吴云松; 王增军

    2012-01-01

    目的:本研究旨在利用荧光原位杂交技术(FISH)辅助诊断膀胱尿路上皮癌,以探讨其作为一种替代尿脱落细胞学的无创性检查在膀胱尿路上皮癌诊断中的应用价值.方法:收集30例健康志愿者的新鲜尿液,应用3、7、17号染色体及9号染色体p16位点探针标记,进行FISH检测,建立正常人群阈值;再收集95例因血尿或影像学检查拟诊为膀胱肿瘤的患者晨尿标本,分别作常规尿脱落细胞学检查和FISH检测,其中79例膀胱镜下活检或术后标本病理确诊为膀胱尿路上皮癌.FISH检测统计目标染色体畸变情况,并进一步分析与病理分级的关系.结果:FISH检测设定的正常阈值为3号染色体:3%;7号染色体:4%;17号染色体:3%;9号染色体p16位点:10%.FISH检测技术的敏感性为74.68%(59/79),高于尿脱落细胞学检查的35.44% (28/79),差异具有统计学意义(P>0.001),而FISH检测的特异性为93.75% (15/16),尿脱落细胞学检查特异性为87.50%(14/16),两者差异无统计学意义(P>0.05).不同病理分级下FISH检测的敏感性呈现为高级别高阳性率:低度恶性倾向的尿路上皮肿瘤为58.33%(7/12),尿路上皮癌Ⅰ级为54.17% (13/24),尿路上皮癌Ⅰ~Ⅱ级为86.36%(19/22),尿路上皮癌Ⅱ级和Ⅱ~Ⅲ级为94.44% (17/18),尿路上皮癌Ⅲ级为100% (3/3).敏感性随着病理分级的提高而呈现增高趋势.结论:FISH检测技术具备无创、高敏感性的特点,优于传统的尿脱落细胞学检查.不同分级的膀胱尿路上皮肿瘤其FISH检测的敏感性不同,表现为高级别高敏感性.FISH检测上述位点在低级别膀胱尿路上皮肿瘤中敏感性较高,大大提高了低级别尿路上皮肿瘤的检出率,有望成为一种常规的膀胱肿瘤复查指标.%Objective: Our study aims to use fluorescence in situ hybridization(FISH)for predicting the bladder urothelial carcinoma , m order to discuss its clinical utility m

  5. Urothelial Tumours of the Urinary Bladder: A Histopathological Study of Cystoscopic Biopsies

    Directory of Open Access Journals (Sweden)

    Sujan Vaidya

    2013-09-01

    Full Text Available ABSTRACT Introduction: Bladder tumours constitute one of the most common urological conditions. Urothelial (transitional cell carcinoma accounts for 90% of all primary tumours of the bladder. These tumours are an important cause of morbidity and mortality. The objective of this study was to present the histopathological patterns of urothelial tumours and to determine the grade and stage of these tumours. Methods: This is a 3 year retrospective study of urothelial tumours carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS, Lalitpur, Nepal. Data of all cystoscopic biopsies collected during this period were analyzed. Results: Urothelial (transitional cell tumours accounted for 97.59% (81 cases of all bladder tumours. Transitional cell carcinoma (TCC was the most common tumour which was present in 67 cases (80.72%. Of these, 32 (47.76% were low grade TCC while 35 (52.24% were high grade TCC. Maximum number of tumours (70.37% were superficial (pTa and pT1 while (29.63% were muscle invasive (pT2. Sixteen percent of low grade and 76.92% of high grade tumours showed muscle invasion. Detrusor muscle was absent in 23.88% cases (16/67. Conclusion: Transitional cell carcinoma was the most common bladder cancer. Most of these tumours were high grade. A large percentage of high grade carcinomas presented with muscle invasion. Pathological grade and muscle invasion are the most valuable prognostic predictors of survival. The importance of including smooth muscle in the biopsy specimens needs to be emphasized Key words: cancer, high grade, low grade, transitional, tumour, urinary bladder.

  6. MANAGEMENT OF CARCINOMA BLADDER: A REVIEW LITERATURE

    Directory of Open Access Journals (Sweden)

    Gurinderjit Singh

    2014-12-01

    Full Text Available Carcinoma of the bladder is a disease of the elderly. Bladder cancer is three times more common in males than in females and more common in whites than in blacks. Patients with bladder cancer have a 1% to 4% incidence of synchronous or metachronous upper t ract urothelial tumors. There are many risk factors for urothelial cancer, classified into (1 Genetic (2 chemical exposure, and (3 chronic irritation. Genetic abnormalities associated with CIS include alterations in the retinoblastoma gene (Rb, p53, an d PTEN. Chemical exposure has the most epidemiologic evidence to support it as an inciting agent (Aromatic amines, aniline dyes, and nitrites and nitrates. Chronic irritants include catheters, recurrent urinary track infections, Schistosoma haematobium, a nd irradiation. There are many studies that suggest high water consumption, vitamin intake, and various diets that are beneficial in preventing bladder cancer. However, none of these have shown any clear benefit with respect to prevention.

  7. GLPp16/CSP17探针在膀胱尿路上皮癌诊断中的应用%Application of GLPp 16/CSP 17 probe in the Diagnosis of Bladder Urothelial Carcinoma

    Institute of Scientific and Technical Information of China (English)

    张宇; 曾庆山; 张宁; 熊廷川; 汪清

    2012-01-01

    目的:探讨荧光原位杂交技术辅助诊断膀胱尿路上皮癌的可行性.方法:标记为17号染色体着丝粒及9号染色体p16位点9p21区带探针,采用荧光原位杂交技术(Fluorescence in Situ Hybridization FISH)对80例膀胱肿瘤患者尿液间期细胞核进行荧光原位杂交,以20例健康志愿者作为正常对照组,建立阈值.以术后病理结果作为诊断“金标准”,对80例膀胱肿瘤患者同时行尿脱落细胞学检查,与FISH进行比较.结果:17号染色体和9p21的畸变率分别为57.5%和63.8%.17号染色体畸变率主要表现为多倍体,与膀胱癌的分级有显著相关性(P<0.01);9号染色体畸变率主要变现为染色体缺失,与膀胱癌分期分级均无相关性(P>0.05).尿脱落细胞学灵敏度为12.2%,FTSH技术灵敏度为86.5%;两者差异有统计学意义(P<0.01).结论:荧光原位杂交技术可以作为膀胱尿路上皮癌诊断的一项重要方法,并可能在预后判断中具有重要临床意义.%Objective: To evaluate the possibility of Fluorescence in Situ Hybridization (FISH) in detecting Urothelial carcinoma of the urinary bladder. Methods: The probes of chromosome 17centromeres and chromosome 9 9p21 region (p16) were labeled by random primer method. FISH was performed on interphase nuclei of 80 urine specimens of suspected bladder urothelial carcinoma,all the urine specimens were analyzed by urinary cytology at the same time. The pathological diagnosis was the "Golden standard", to analyse the sensitivity and specificity of FISH and urinary cytology to diagnose bladder urothelial cancinoma. 20 normal donors were analyzed to establish threshold value. Results: The rate of aberration was 57.5%for chromosome 17 and 63.8% for chromosome 9p21 in urothelial carcinoma of the urinary bladder. All the aberrations had no correlation to tumor stage (P>0.05), the aberration of chromosome 17 was correlated to pathologic grade significantly (P0.05). We found a

  8. URACHAL CARCINOMA IN BLADDER

    Institute of Scientific and Technical Information of China (English)

    薛丽燕; 吕宁; 何祖根; 林冬梅; 刘秀云

    2004-01-01

    Objective: To investigate the clinicopathologic features and diagnostic criteria of urachal carcinoma in the bladder.Methods: Seven cases of urachal carcinoma in the bladder were analyzed retrospectively. Results: All the tumors were found locating in the dome of bladder. Of them, 4 were mucinous adenocarcinoma, one was well differentiated papillary enteric adenocarcinoma, one was well differentiated squamous carcinoma, and one was neuroendocrine carcinoma. Cystomorphous urachal remnants were found in 4 cases. The main complaint was hematuria and all patients underwent partial excision of bladder and urachus. Conclusion: Mucinous adenocarcinoma is the main histo-pathological type, and cystomorphous urachal remnants are often accompanied with urachal carcinoma in the bladder. The key diagnostic criteria of urachal carcinoma in bladder are site and histopathology. And to examine the specimens carefully to find the urachal remnants is important.

  9. Segregation analysis of urothelial cell carcinoma.

    NARCIS (Netherlands)

    Aben, K.K.H.; Baglietto, L.; Baffoe-Bonnie, A.B.; Coebergh, J.W.W.; Bailey-Wilson, J.E.; Trink, B.; Verbeek, A.L.M.; Schoenberg, M.P.; Witjes, J.A.; Kiemeney, L.A.L.M.

    2006-01-01

    A family history of urothelial cell carcinoma (UCC) confers an almost two-fold increased risk of developing UCC. It is unknown whether (part of) this aggregation of UCC has a Mendelian background. We performed complex segregation analyses on 1193 families ascertained through a proband with UCC of th

  10. Familial aggregation of urothelial cell carcinoma.

    NARCIS (Netherlands)

    Aben, K.K.H.; Witjes, J.A.; Schoenberg, M.P.; Hulsbergen-van de Kaa, C.A.; Verbeek, A.L.M.; Kiemeney, L.A.L.M.

    2002-01-01

    Urothelial cell carcinoma (UCC) is not considered to be a familial disease. Familial clustering of UCC was described in several case reports, however, some with an extremely early age at onset suggesting a genetic component. Epidemiological studies yielded inconsistent evidence of familial UCC, poss

  11. Epidemiology and risk factors of urothelial bladder cancer

    NARCIS (Netherlands)

    Burger, M.; Catto, J.W.; Dalbagni, G.; Grossman, H.B.; Herr, H.; Karakiewicz, P.; Kassouf, W.; Kiemeney, L.A.L.M.; La Vecchia, C.; Shariat, S.; Lotan, Y.

    2013-01-01

    CONTEXT: Urothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease. OBJECTIVE: To describe the incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the r

  12. Urothelial neoplasm of the bladder in childhood and adolescence: a rare disease

    Directory of Open Access Journals (Sweden)

    Haci Polat

    2016-04-01

    Full Text Available ABSTRACT Purpose: Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents. Materials and Methods: We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT. Results: Nine of the 11 patients (82% were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0–16 months until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1–4cm was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP, four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up. Conclusions: Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up.

  13. Bovine Papillomavirus Type 2 Infection and Microscopic Patterns of Urothelial Tumors of the Urinary Bladder in Water Buffaloes

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    Paola Maiolino

    2013-01-01

    Full Text Available Microscopic patterns of thirty-four urothelial tumors of the urinary bladder of water buffaloes from the Marmara and Black Sea Regions of Turkey are here described. All the animals grazed on lands rich in bracken fern. Histological diagnosis was assessed using morphological parameters recently suggested for the urinary bladder tumors of cattle. Papillary carcinoma was the most common neoplastic lesion (22/34 observed in this study, and low-grade carcinoma was more common (seventeen cases than high-grade carcinoma (five cases. Papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP, and invasive carcinomas were less frequently seen. Carcinoma in situ (CIS was often detected associated with some papillary and invasive carcinomas. De novo (primary CIS was rare representing 3% of tumors of this series. A peculiar feature of the most urothelial tumors was the presence in the tumor stroma of immune cells anatomically organized in tertiary lymphoid organs (TLOs. Bovine papillomavirus type-2 (PV-2 E5 oncoprotein was detected by molecular and immunohistochemistry procedures. Early protein, E2, and late protein, L1, were also detected by immunohistochemical studies. Morphological and molecular findings show that BPV-2 infection contributes to the development of urothelial bladder carcinogenesis also in water buffaloes.

  14. Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

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    Julian Arista-Nasr

    2016-04-01

    Full Text Available ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12 and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

  15. FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma

    NARCIS (Netherlands)

    B.W. van Rhijn (Bas); Th.H. van der Kwast (Theo); A.N. Vis (André); W.J. Kirkels (Wim); E.R. Boeve; A.C. Jobsis; E.C. Zwarthoff (Ellen)

    2004-01-01

    textabstractFibroblast growth factor receptor 3 (FGFR3) and P53 mutations are frequently observed in bladder cancer. We here describe the distribution of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell carcinomas. FGFR3 mutations were observed in 59% and P53 o

  16. Diagnosis and management of urothelial carcinoma in situ of the lower urinary tract: a systematic review

    NARCIS (Netherlands)

    Casey, R.G.; Catto, J.W.; Cheng, L.; Cookson, M.S.; Herr, H.; Shariat, S.; Witjes, J.A.; Black, P.C.

    2015-01-01

    CONTEXT: Urothelial carcinoma in situ (CIS) has a high propensity for progression. It is usually reported within the heterogeneous context of non-muscle-invasive bladder cancer (NMIBC) but warrants special consideration. OBJECTIVE: To review the contemporary literature on the diagnosis and managemen

  17. DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: a large cohort study.

    Science.gov (United States)

    Tsai, Meng-Chen; Li, Wei-Ming; Huang, Chun-Nung; Ke, Hung-Lung; Li, Ching-Chia; Yeh, Hsin-Chih; Chan, Ti-Chun; Liang, Peir-In; Yeh, Bi-Wen; Wu, Wen-Jeng; Lim, Sher-Wei; Li, Chien-Feng

    2016-11-29

    The migration ability of urothelial carcinoma corresponding to dismal prognosis had not been fully investigated. The interaction of extracellular collagen with a unique transmembrane receptor tyrosine kinase, Discoidin domain receptor 2 (DDR2), was selected by data mining. We arranged real-time reverse transcription polymerase chain reaction assays to evaluate the transcript levels in 26 urinary tract urothelial carcinoma and 26 urinary bladder urothelial carcinoma specimens, showing significantly increase corresponding to advanced primary stage (p = 0.003 and p DDR2 expression in 340 urinary tract urothelial carcinoma and 295 urinary bladder urothelial carcinoma. Assessments of the correlation to clinicopathologic features, disease-specific survival, and metastasis-free survival were conducted. The transcript levels in advanced stage were higher than those in early stage and were correlated with poor prognosis. The higher expression was positively correlated to higher pT status (p DDR2 resulted in a depletion of cellular viability, migratory, and invasive ability, supporting the oncogenic function of DDR2.

  18. Does urothelial cancer of bladder behave differently in young patients?

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-hua; LI You-yuan; HU Zhi-quan; ZHU Hui; ZHUANG Qian-yuan; QI Yong; YE Zhang-qun

    2012-01-01

    Background Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial.To optimize the management of young patients with bladder cancer,we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.Methods From 1994 to 2008,a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed.The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared.A survival analysis was performed using the Kaplan-Meier method and log-rank test,and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.Results Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis.Tumors in young bladder cancer patients tended to be less multifocal at diagnosis.In addition,young patients had a lower recurrence rate and longer recurrence interval than older patients.The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients.The univariats and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.Conclusions Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients.These findings argue for more conservative management approaches for young patients with bladder cancer.

  19. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

    Directory of Open Access Journals (Sweden)

    Taiji Tsukamoto

    2011-07-01

    Full Text Available Intravesical instillation of bacillus Calmette Guérin (BCG for the treatment of urothelial carcinoma (UC of the bladder is based on the BCG-induced immune response, which eradicates and prevents bladder cancer. The results of recent studies have suggested that not only major histocompatibility complex (MHC-nonrestricted immune cells such as natural killer cells, macrophages, neutrophils, etc., but also MHC-restricted CD8+ T cells play an important role and are one of the main effectors in this therapy. Better understanding of the mechanism of BCG immunotherapy supports the idea that active immunotherapy through its augmented T cell response can have great potential for the treatment of advanced UC. In this review, progress in immunotherapy for UC is discussed based on data from basic, translational and clinical studies. We also review the escape mechanism of cancer cells from the immune system, and down-regulation of MHC class I molecules.

  20. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Hiroshi, E-mail: hkitamu@sapmed.ac.jp; Tsukamoto, Taiji [Department of Urology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543 (Japan)

    2011-07-29

    Intravesical instillation of bacillus Calmette Guérin (BCG) for the treatment of urothelial carcinoma (UC) of the bladder is based on the BCG-induced immune response, which eradicates and prevents bladder cancer. The results of recent studies have suggested that not only major histocompatibility complex (MHC)-nonrestricted immune cells such as natural killer cells, macrophages, neutrophils, etc., but also MHC-restricted CD8{sup +} T cells play an important role and are one of the main effectors in this therapy. Better understanding of the mechanism of BCG immunotherapy supports the idea that active immunotherapy through its augmented T cell response can have great potential for the treatment of advanced UC. In this review, progress in immunotherapy for UC is discussed based on data from basic, translational and clinical studies. We also review the escape mechanism of cancer cells from the immune system, and down-regulation of MHC class I molecules.

  1. [Urothelial carcinoma in a pyelocaliceal cyst].

    Science.gov (United States)

    Abate, Danilo; Vella, Marco; Alonge, Vincenza; Serretta, Vincenzo

    2014-01-01

    Renal complex cysts are lesions whose nature can be either benign or malignant. Depending on the presence of septa, solid components, enhancement or calcifications, they are distinguished according to the Bosniak classification based on CT findings, as well as MRI and ETG. We report a rare case of urothelial carcinoma, originating over a pyelocalyceal cyst in a 50-year-old man, and classified as Bosniak IIF by CT and MRI investigations.

  2. 荧光原位杂交技术在膀胱尿路上皮癌诊断中的应用价值%Utility of fluorescence in situ hybridization for the diagnosis of bladder urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    黄建文; 安瑞华; 李运伟; 穆家贵; 甘秀国; 于雷; 原劲杨

    2012-01-01

    目的 探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在膀胱尿路上皮癌诊断中的应用价值. 方法 收集81例膀胱尿路上皮癌患者的新鲜尿液标本,分别行FISH和尿细胞学检测,并行膀胱镜检查;病理诊断泌尿系良性疾病12例合并8例临床诊断泌尿系良性疾病患者的尿液标本作对照.统计学分析FISH和尿细胞学检测诊断的特征值. 结果 81例均经病理检查确诊膀胱尿路上皮癌.非肌层浸润性膀胱尿路上皮癌34例,肌层浸润性癌14例;低级别42例,高级别24例;由于送检组织不完整,无法准确分期、分级者分别为33例和15例.FISH、尿细胞学和膀胱镜检查诊断膀胱尿路上皮癌的敏感性分别为72.8% (59/81) 、27.2% (22/81)和97.5% (79/81),FISH诊断敏感性高于尿细胞学检测(P<0.05),但低于膀胱镜检查(P <0.05);FISH和尿细胞学检测诊断特异性分别为85.0%(17/20)、100.0% (20/20),二者比较差异无统计学意义(P>0.05).FISH和尿细胞学检测诊断符合率分别为75.2% (76/101)、41.6%(42/101),二者比较差异有统计学意义(P<0.05). 结论 FISH检测诊断膀胱尿路上皮癌敏感性高、特异性强、无创,临床应用价值高.%Objective To evaluate the clinical value of fluorescence in situ hybridization (FISH) method for diagnosis of bladder urothelial carcinoma.Methods Urine samples from 81 patients suspected of having bladder urothelial carcinoma were collected for immediate urine cytology and FISH analysis.All patients underwent cystoscopy for identification of bladder lesions.Urine samples from 8 patients with benign disease of urinary system werealso analyzed by means of FISH and cytology.The sensitivity and specificity of FISH were compared with cytology.Results 81 subjects of bladder urothelial carcinoma were verified with pathology,which included 34 non-muscle invasive carcinoma,14 cases with muscle invasive carcinoma,42 cases with high

  3. Targeting molecular aberrations in urothelial carcinoma: are we almost there?

    Science.gov (United States)

    Apolo, Andrea B; Kwiatkowski, David J

    2013-01-01

    Advances in tumor biology and cancer genetics have led to the development of effective targeted therapies in oncology over the past decade. However, targeted drug development for urothelial carcinoma has been slower than for some other malignancies. The path forward in drug development is through a better understanding of the aberrant pathways driving urothelial tumor development. Steady progress has been made in the characterization of genomic alterations in urothelial carcinoma. The Cancer Genome Atlas (TCGA) project is well underway in the analysis of a large set of urothelial cancer specimens using multiple approaches and technologies. In addition, there are already many well-established mutations and genetic alterations in urothelial carcinoma that likely contribute in an important way to tumor development. In addition, urothelial cancer genome-wide association studies have identified common variants associated with urothelial cancer risk and protein expression that can potentially be therapeutically targeted. Furthermore, the MET pathway has emerged as an exciting target in multiple tumors, including urothelial carcinoma. Our knowledge of how to clinically target many emerging molecular aberrations in urothelial cancer is still in the early stages of development. However, there is much promise in the ongoing research being conducted in urothelial cancer molecular pathogenesis.

  4. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  5. A case report of a urothelial carcinoma arising in the renal pelvis with exuberant chondrosarcomatous element associated with adrenal metastasis

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    Deepa Ramakrishnan

    2014-01-01

    Full Text Available Sarcomatoid carcinoma is a rare malignant tumor that has both malignant epithelial and mesenchymal components. We describe a sarcomatoid carcinoma arising in the left renal pelvis of a 49-year-old man. The dominant component of the tumor was chondrosarcomatous, but there were also focal carcinomatous areas. The carcinomatous tumor cells consisted of papillary urothelial carcinoma. Immunohistochemical assay showed that the sarcomatous tumor cells were positive for vimentin and S 100 and negative for cytokeratin. The papillary urothelial carcinoma was positive for cytokeratin and negative for vimentin. The patient underwent neoadjuvant chemotherapy and after downsizing the tumor, radical nephrectomy was performed with excision of the cuff of bladder.

  6. Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

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    Takashi Nagai

    2016-03-01

    Full Text Available Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.

  7. Review of Topical Treatment of Upper Tract Urothelial Carcinoma

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    Kenneth G. Nepple

    2009-01-01

    Full Text Available A select group of patients with upper tract urothelial carcinoma may be appropriate candidates for minimally invasive management. Organ-preserving endoscopic procedures may be appropriate for patients with an inability to tolerate major surgery, solitary kidney, bilateral disease, poor renal function, small tumor burden, low-grade disease, or carcinoma in situ. We review the published literature on the use of topical treatment for upper tract urothelial carcinoma and provide our approach to treatment in the office setting.

  8. Trastuzumab therapy in metastatic bladder carcinoma: The proof of concept

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    Moussaid Y

    2014-08-01

    Full Text Available About 10% of metastatic urothelial carcinoma overexpress oncogenic HER2/neu receptor. Recent preliminary data suggest that patients with this particular molecular subset could benefit from trastuzumab therapy, which specifically targets the receptor and thus inhibits downstream activation pathway. Here we report a case illustrating this clinical benefit, with complete response reported as third line therapy in a heavily pretreated patient with diffuse metastatic urothelial carcinoma of the bladder. It also highlights the usefulness of 18-Fluorodeoxyglucose Positron Emission Tomography (18-FDG PET as a biomarker for response to trastuzumab.

  9. IMMUNOHISTOCHEMICAL ANALYSIS OF UROTHELIAL BLADDER CANCERS

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    Katarina Bevizova

    2013-01-01

    Full Text Available Malignant cancers of urinary bladder are the second most common malignancy of the urinary tract and the fourth most common malignancy in general, especially in men. The aim of this study was a retrospective analysis of selected markers (p53, Ki-67 and E-cadherin of urinary bladder cancers from the Department of Urology in Bratislava, Slovak Republic between years 2007 and 2009. We analysed 244 patients (202 males, 42 females with diagnosed bladder cancer via cystoscopy and subsequent transurethral resection. Patients’ age varied from 36 to 98 years. Obtained samples were fixed by 10% buffered formalin for 24 to 48 h. Subsequently, they were dehydrated in ascending ethanol series and embedded in paraffin. The parafin sections of 5 µm were prepared by microtome and they were stained by haematoxylin and eosin. The antibodies against to p53, Ki-67 and E-cadherin were used in immunohistochemical analysis. Statistical evaluation was performed via SPSS using non-parametric Kruskal-Wallis test and p values<0.05 were considered statistically significant. No significant differences in the expression of selected markers were found between genders. Expression of p53 and Ki-67, in G1 and G2 of low grade tumours was lower in comparison to their expression in G3 tumors. Expression of E-cadherin was the opposite in this case. The expression of p53 and Ki-67 positively correlated with tumor’s depth of invasion, while the expression of E-cadherin significantly decreased. In case of T4 tumors, the expression of all markers exhibited consistently high values. When analysing tumor multiplicity, the expression of p53 and Ki-67 significantly decreased, while the expression of E-cadherin significantly increased. Based on the obtained results it can be concluded that the analysis of p53, Ki-67 and E-cadherin expression is essential for diagnostics and prognostics of bladder cancer and should be routinely used in daily practise together with

  10. Pericardial Metastasis Induced Tamponade from Urothelial Carcinoma: A Rare Entity

    OpenAIRE

    Rafay Khan; Waqas Jehangir; Sunil Tulpule; Mohamed Osman; Shilpi Singh; Shuvendu Sen

    2016-01-01

    Urothelial carcinoma in a few cases may result in cardiac metastasis. A rare presentation of this condition is its diagnosis as a result of cardiac tamponade. Tamponade is an unusual entity as a result of urothelial carcinoma and has only been reported in four cases. There have also been only a total of fifteen cases of cardiac metastasis from this form of malignancy. It is through this discussion that we emphasize the importance of early detection and monitoring of cardiac symptoms with the ...

  11. miRNA-625*在膀胱尿路上皮癌中的表达%Expression of miRNA-625* in urothelial carcinoma of the bladder

    Institute of Scientific and Technical Information of China (English)

    徐锋; 韩从辉; 刘有黄; 高建平; 张征宇; 葛京平; 位志峰; 程文

    2014-01-01

    Objective To detect the miRNA-625*expression in urothelial carcinoma of the bladder ( BUC) .Methods BUC and normal bladder mucosa tissues were collected and the total RNA was extracted routinely .Measuring the absorption value of RNA at 260 nm,280 nm,and 230 nm by NanoDrop ND-1000 in order to calculate RNA Quantification and Quality Assurance .RNA Integrity and gDNA contamination Test by Denaturing Agarose Gel Electrophoresis .The miRNA-625*expression was detected by using real-time quantitative polymerase chain reaction .Results RNA Quantification and RNA Integrity were qualified for the follow-up experiment ,the miRNA-625* finding was confirmed by real-time RT-PCR and the expression was significantly up-regulated in BUC tissues than those in normal bladder mucosa (P<0.05).Conclusion The expression level of miRNA-625*is significantly up-regulated in BUC,and it may be used for prediction of prognosis and as for targeted treatment of BUC.%目的:探讨miRNA-625*在膀胱尿路上皮癌中的差异表达。方法常规提取新鲜膀胱尿路上皮癌与正常膀胱黏膜组织中总RNA;使用分光光度计测定RNA在260 nm、280 nm和230 nm的吸光值,以计算浓度并评估纯度;用琼脂糖凝胶电泳检测RNA纯度及完整性;以RT-PCR方法检测标本中miRNA-625*的表达情况。结果 RNA质量检测合格后, miRNA-625*经RT-PCR验证与miRNA芯片分析结果一致。与正常膀胱黏膜上皮组织相比,膀胱尿路上皮癌中miRNA-625*表达显著上调( P<0.05)。结论 miRNA-625*在膀胱尿路上皮癌中表达上调,可作为膀胱尿路上皮癌诊断和预后判断的分子标志物。

  12. Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Allen, N.E.; Appleby, P.N.; Key, T.J.; Bueno-De-Mesquita, H.B.; Ros, M.M.; Kiemeney, L.A.L.M.; Tjonneland, A.; Roswall, N.; Overvad, K.; Weikert, S.; Boeing, H.; Chang-Claude, J.; Teucher, B.; Panico, S.; Sacerdote, C.; Tumino, R.; Palli, D.; Sieri, S.; Peeters, P.; Quiros, J.R.; Jakszyn, P.; Molina-Montes, E.; Chirlaque, M.D.; Ardanaz, E.; Dorronsoro, M.; Khaw, K.T.; Wareham, N.; Ljungberg, B.; Hallmans, G.; Ehrnstrom, R.; Ericson, U.; Gram, I.T.; Parr, C.L.; Trichopoulou, A.; Karapetyan, T.; Dilis, V.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Fagherrazzi, G.; Romieu, I.; Gunter, M.J.; Riboli, E.

    2013-01-01

    Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations

  13. Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer

    DEFF Research Database (Denmark)

    Reddy, Opal L; Cates, Justin M; Gellert, Lan L;

    2015-01-01

    We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations...

  14. Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management.

    Science.gov (United States)

    Paner, Gladell P; Zehnder, Pascal; Amin, Anmol M; Husain, Aliya N; Desai, Mihir M

    2011-01-01

    Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. Use of the World Health Organization 2004/International Society of Urological Pathology 1998 grading nomenclature and recent molecular studies highlight certain unique features of bladder urothelial neoplasms in young patients, particularly in patients below 20 years of age. In this meta-analysis and review, the clinical, pathologic, and molecular features and risk factors of bladder urothelial neoplasms in patients 40 years or less are presented and analyzed according to decades of presentation. Similar to older patients, bladder urothelial neoplasms in patients 40 years or younger occur more common in male patients, present mainly with gross painless hematuria, and are more commonly located at bladder trigone/ureteral orifices, but in contrast have a greater chance for unifocality. Delay in diagnosis of bladder urothelial neoplasms seems not to be uncommon in younger patients probably because of its relative rarity and the predominance of benign causes of hematuria in this age group causing hesitancy for an aggressive work-up. Most tumors in patients younger than 40 years were low grade. The incidence of low-grade tumors was the lowest in the first 2 decades of life, with incremental increase of the percentage of high-grade tumors with increasing age decades. Classification according to the World Health Organization 2004/International Society of Urological Pathology grading system identified papillary urothelial neoplasms of low malignant potential to be relatively frequent among bladder tumors of young patients particularly in the teenage years. Similar to grade, there was

  15. Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Ros, M.; Bueno-de-Mesquita, H.B.; Kampman, E.; Büchner, F.L.; Aben, K.K.; Egevad, L.; Overvad, K.; Tjonneland, A.; Roswall, N.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Moiros, S.; Kaaks, R.; Teucher, B.; Weikert, S.; Ruesten, A.V.; Trichopoulou, A.; Naska, A.; Benetou, V.; Saieva, C.; Pala, V.; Ricceri, F.; Tumino, R.; Mattiello, A.; Peeters, P.H.M.; Gils, van C.H.; Gram, I.T.; Engeset, D.; Chirlaque, M.D.; Ardanazx, E.; Rodriguez, L.

    2012-01-01

    Background - Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiven

  16. 荧光原位杂交法和全自动图像细胞仪在膀胱尿路上皮癌诊断中的应用%The application of fluorescence in situ hybridization and automated image cytometry in the diagnosis of urothelial carcinoma of bladder

    Institute of Scientific and Technical Information of China (English)

    顾沈阳; 雍永松; 王业华; 杜拥军

    2010-01-01

    目的 探讨荧光原位杂交法(FISH)和全自动图像细胞仪(ICM)在膀胱尿路上皮癌诊断中的应用.方法 在2008年8月至2009年3月共选取60例患者,包括20例非尿路上皮癌和40例膀胱尿路上皮癌的患者,取患者的尿液作常规尿细胞学检查、FISH和ICM检测.结果 FISH的敏感性显著高于ICM的敏感性(82.5%比62.5%,P<0.05)和常规尿细胞学的敏感性(82.5%比25.0%,P<0.05),同时ICM敏感性也高于常规尿细胞学的敏感性(62.5%比25.0%,P<0.05);FISH、ICM和常规尿细胞学检查的特异性都为100%,三者在特异性方面差异无统计学意义(P>0.05).FISH、ICM和常规尿脱落细胞学检测的敏感性与病理分期无相关性(P>0.05),但与分级有相关性(P<0.05).结论 FISH和ICM在膀胱尿路上皮癌诊断中,其特异性和常规尿细胞学检查一致,但敏感性显著高于常规尿细胞学检查;同时FISH在膀胱尿路上皮癌诊断中的敏感性高于ICM,所以FISH技术更有望成为膀胱尿路上皮癌无创性的诊断和检测手段.%Objective To discuss the application of automated DNA image cytometry(ICM) and fluorescence in sitn hybridization (FISH) in the diagnosis of urothelial carcinoma of bladder. Methods From August 2008 to March 2009,60 volunteers with informed consent were divided into two groups,40 patients proven as urothehal carcinoma of bladder by pathology and 20 healthy individuals as control.Urine was collected and tested by cytology, ICM and FISH. Results Overall sensitivity of FISH was significantly higher in detection of malignancy than that of ICM(82. 5% vs 62. 5%, P <0.05) and that of urine cytology ( 82. 5% vs 25.0%, P < 0. 05 ), while ICM was more sensitive to diagnose urothelial carcinoma of bladder than urine cytology(62. 5% vs 25.0%, P < 0. 05 ). Specificities of urine cytology,ICM and FISH were 100% in diagnosis of urothelial carcinoma of bladder (P > 0. 05 ). Sensitivities of urine cytology, ICM and FISH have no

  17. Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.

    Directory of Open Access Journals (Sweden)

    David J DeGraff

    Full Text Available Approximately 50% of patients with muscle-invasive bladder cancer (MIBC develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001, and loss of FOXA1 is associated with high histologic grade (p<0.001. Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes

  18. Plasmacytoid urothelial carcinoma of the urinary bladder: a clinicopathologic study of 16 cases%膀胱浆细胞样尿路上皮癌16例临床病理特征和预后分析

    Institute of Scientific and Technical Information of China (English)

    张伟; 蒋艳霞; 刘燕; 于文娟; 赵辉; 李玉军

    2013-01-01

    目的 探讨膀胱浆细胞样尿路上皮癌(PUC)的临床病理特征和预后.方法 对16例膀胱PUC进行临床病理学和免疫组织化学MaxVision法染色观察,并进行随访和文献复习.结果 本组患者男15例,女1例;年龄40~85岁(平均64岁),60岁以上者11例.首发症状大多数表现为肉眼血尿(15例).组织学上,瘤细胞黏附性差,多弥漫排列,也可呈条索状、乳头状、巢团状或腺泡状,胞质丰富,嗜酸性,核偏位、深染,呈显著的浆细胞样,核分裂象易见.多数瘤组织侵及固有膜或肌层.12例伴有尿路上皮癌成分.免疫组织化学:16例患者组织中AE1/AE3、上皮细胞膜抗原(EMA)、CK7、CK18均为弥漫强阳性,CK20和uroplakinⅢ各9例阳性,p63和E-cadherin分别有11例和10例表达,癌胚抗原阳性12例,p53阳性13例,CD138阳性15例,Ki-67阳性指数5%~70%(平均30%).而波形蛋白、白细胞共同抗原(LCA)、κ、λ、S-100蛋白、HMB 45、MelanA、平滑肌肌动蛋白及结蛋白均阴性.13例获得随访,随访时间3个月至10年,3例分别于术后3、27个月和5年死亡;2例复发,其中1例带瘤存活25个月,1例术后无瘤生存43个月;余8例术后7个月至10年健在.结论 PUC是尿路上皮癌的一种罕见亚型.免疫组织化学CK7、CK20、p63和uroplakinⅢ阳性,波形蛋白和LCA阴性有助于其诊断.%Objective To study the clinicopathologic features and prognosis of plasmacytoid urothelial carcinoma (PUC) of the urinary bladder.Methods The clinical and pathologic findings of 16 cases of PUC were retrospectively reviewed.Immunohistochemical study (MaxVision method) was carried out.The follow-up data were analyzed.Results There were altogether 15 males and 1 female.The age of patients ranged from 40 years to 85 years (median =64 years).Most patients (15/16) presented with hematuria.The tumor cells were small to medium in size and contained eccentric nuclei and moderate to abundant eosinophilic cytoplasm

  19. Expression of metastasis-associated protein 1 and Ezrin in bladder urothelial carcinoma%转移相关蛋白1和埃兹蛋白在膀胱尿路上皮癌中的表达

    Institute of Scientific and Technical Information of China (English)

    潘兆君; 黄伟佳; 瞿虎; 邹自灏; 高兴成

    2010-01-01

    Objective To detect the expression of metastasis- associated protein 1 (MTA- 1) and Ezrin in bladder urothelial carcinoma (BUC) and normal bladder mucosa, and to investigate their correlation with clinical pathology and prognosis. Methods The expression of MTA- 1 and Ezrin proteins was detected in 65 specimens of surgically resected BUC tissue and 30 of normal bladder mucosa with immunohistochemistry. The correlation of MTA- 1 and Ezrin expressions in BUC with clinicopathological parameters, the correlation between MTA-1 and Ezrin protein expressions and their effects on prognosis were also analyzed. Results In 65 specimens of BUC tissue, the positive rates of MTA- 1 and Ezrin expression were 72.3% (n=47) and 89.2% (n=58) , respectively, in contrast to 0% for both MTA- 1 and Ezrin expressions in 30 specimens of normal bladder mucosa, which reached the level of statistical difference (all P<0.01). The expression of MTA- 1 in BUC tissue was closely related to the clinical stages, tumor pathological grading, metastasis and recurrence (all P<0.01 ) , while the expression of Ezrin was closely related to the clinical stages, metastasis and recurrence (all P<0.01 ), and the expression of MTA-1 was positively correlated with Ezrin expression (r=0.742, P<0.01 ). The disease free survival (DFS) in patients with combined expression was significantly lower than that in those with negative expression of MTA- 1 and Ezrin (P<0.01). Conclusion The high expression of MTA-1 and Ezrin is related to the occurrence,progression, as well as invasion and metastasis of BUC.%目的 检测转移相关蛋白1(MTA-1)、埃兹蛋白(Ezrin)在膀胱尿路上皮癌(BUC)组织及正常膀胱黏膜组织中的表达,探讨两者与患者临床病理及预后之间的关系.方法 采用免疫组化法检测65例手术切除的BUC组织和30例正常膀胱黏膜组织中MTA-1和Ezrin蛋白表达,分析MTA-1和Ezrin在BUC中的表达与患者临床病理参数的关系,分析MTA-1和Ezrin

  20. The Role of Structural Extracellular Matrix Proteins in Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Andrea Brunner

    2007-01-01

    Full Text Available The extracellular matrix (ECM plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fi bronectin (FN, tenascin (Tn-C and thrombospondin 1 (TSP1 in UC. In addition, the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis.

  1. Denovo urothelial carcinoma of the upper and lower urinary tract in kidney--transplant patients with end-stage analgesic nephropathy.

    Science.gov (United States)

    Thon, W F; Kliem, V; Truss, M C; Anton, P; Kuczyk, M; Stief, C G; Brunkhorst, R

    1995-01-01

    Patients with end-stage analgesic nephropathy bear a higher risk for urothelial cancer than do patients with other renal diseases. In a retrospective study in patients with analgesic nephropathy and kidney transplants we analyzed the prevalence and clinical course of de novo urothelial cancer. Diagnosis of analgesic nephropathy was based on the patients' history and clinical data. Only patients under cyclosporine treatment were included. Between 1968 and 1993, 2,371 kidney transplants were performed on 2,072 patients in the Department of Abdominal and Transplant Surgery. The prevalence of analgesic nephropathy was 3.1%. Of 65 patients with analgesic nephropathy and kidney transplants, 10 (15.4%) developed urothelial carcinoma; 10.8%, bladder cancer; and 9.1%, renal pelvic cancer. The mean age at diagnosis was 56.1 years. Urothelial cancer occurred on average at 33.6 months posttransplantation. On average, 6 of 10 patients with urothelial cancer died of the disease at 16.9 months after the diagnosis. All patients with urothelial bladder cancer had a muscle-infiltrating tumor of moderate or high grade. Since urothelial renal pelvic cancer occurred in 9.1% of our patients with analgesic nephropathy and urological screening is insufficient in patients on dialysis, we suggest that prophylactic nephroureterectomy be performed on one side before transplantation and on the contralateral side at 3-6 months after transplantation. An aggressive approach is indicated in patients with urothelial cancer of the bladder.

  2. A Rare Cause of Testicular Metastasis: Upper Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Alper Nesip Manav

    2014-01-01

    Full Text Available Metastatic testicular cancers are rare. Primary tumor sources are prostate, lung, and gastrointestinal tract for metastatic testicular cancers. Metastasis of urothelial carcinoma (UC to the testis is extremely rare. Two-thirds of upper tract urothelial carcinoma (UTUC is of invasive stage at diagnosis and metastatic sites are the pelvic lymph nodes, liver, lung, and bone. We report a rare case of metastatic UTUC to the testis which has not been reported before, except one case in the literature. Testicular metastasis of UC should be considered in patients with hematuria and testicular swelling.

  3. Detection of bladder transitional cell carcinoma: urinary hTERT assay versus urine cytology

    OpenAIRE

    2009-01-01

    "nBackground: Transitional Cell Carcinoma (TCC) of bladder is the second most common urogenital malignancy and because of its high rate of recurrence (two third of tumors recur) vigilant surveillance is necessary. There have been a lot of efforts to find a proper biomarker for detecting urothelial cancers because available methods are expensive and invasive (like cystoscopy) or have a low degree of sensitivity (like urine cytology). Urothelial malignancies, like other cancers tend to exp...

  4. CD147在膀胱尿路上皮癌组织中的表达及临床意义%Expression and clinical significance of extracellular matrix metalloproteinase inducer molecule CD1 4 7 in bladder urothelial carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    刘敏; 毛向明; 薛义军; 邹晓峰; 袁源湖; 肖日海; 张国玺; 伍耿青; 王晓宁

    2014-01-01

    Objective To investigate the expression of extracellular matrix metalloproteinase inducer CD147 in patients with bladder urothelial carcinoma and its relationship with clinicopathologic features and prognosis.Methods RT-PCR and Western blot were used to evaluate the mRNA and protein expression of CD147 in cancer tissues and corresponding paracanerous tissues from 20 patients with bladder urothelial carcinoma;tissue microarray containing specimens from 108 patients with bladder urothelial carcino-ma and 20 normal controls was constructed and immunohistochemistry was applied to examine the expression of CD147,and the correlations between CD147 and clinicopathological characteristics and prognosis were also analyzed.Results Expression level of CD147 mRNA and protein in cancer tissues from 20 bladder urothelial carcinoma patients was significantly higher than that of cor-responding adjacent tissues(P0.05).Kaplan-Meier survival curves analysis showed that the survival time of patients with bladder urothelial carcinoma whose ex-pression of CD147 were high was significant lower than that of patients with bladder urothelial carcinoma whose expression of CD147 were low(P<0.01).Univariate analysis showed that histological grade,tumor stage,lymph node metastasis,tumor size and CD147 expression were all positively correlated with a poor prognosis(P<0.05).Cox-multivariate analysis revealed that histologi-cal grade,tumor stage,lymph node metastasis,and CD147 expression level were independent predictors of an unfavorable prognosis (P<0.05).Conclusion High expression of CD147 in bladder urothelial carcinoma may be correlate with the its progress and its expression state is an independent prognosis factor.%目的:探讨细胞外基质金属蛋白酶诱导因子CD147在膀胱尿路上皮癌组织中的表达及其与临床病理特征和预后的关系。方法应用RT-PCR和Western blot法检测CD147 mRNA和蛋白在20例膀胱尿路上皮癌和对应的癌旁组织中的表达

  5. Delayed Ureterectomy after Incomplete Nephroureterectomy for Upper Tract Urothelial Carcinoma: Pathologic Findings and Outcomes

    Directory of Open Access Journals (Sweden)

    E. Jason Abel

    2013-12-01

    Full Text Available Objectives To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. Materials and Methods After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. Results From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years. Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66. At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%, all with initial grade 3 renal pelvis lesions, developed metastatic disease. Conclusions Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks.

  6. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma

    OpenAIRE

    Zardawi, Ibrahim; Chong, Peter

    2016-01-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  7. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma.

    Science.gov (United States)

    Zardawi, Ibrahim; Chong, Peter

    2016-07-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  8. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Ibrahim Zardawi

    2016-07-01

    Full Text Available Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  9. Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma.

    Science.gov (United States)

    Munari, Enrico; Fujita, Kazutoshi; Faraj, Sheila; Chaux, Alcides; Gonzalez-Roibon, Nilda; Hicks, Jessica; Meeker, Alan; Nonomura, Norio; Netto, George J

    2013-12-01

    Upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of all urothelial carcinomas. Despite many shared features, key clinical and molecular genetic differences between upper tract and bladder urothelial carcinomas are becoming apparent. We have previously demonstrated alterations of mammalian target of rapamycin (mTOR) pathway in bladder carcinoma with a potential impact on biological behavior. In the current study, we evaluated the expression status and prognostic significance of mTOR pathway members in UTUC. Archival formalin-fixed and paraffin-embedded tissues from 99 primary UTUCs were retrieved from one of the authors' institution. Tissue microarrays were constructed with triplicate tumor samples and paired nonneoplastic urothelium. Tissue microarrays were analyzed using immunohistochemistry for mTOR pathway members: PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, and related markers p27 and c-MYC; correlation with clinicopathologic parameters and outcome was performed. We found significantly lower expression of PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, p27, and c-MYC in UTUC compared with paired benign urothelium (P < .0005). We found a strong positive correlation between PTEN and phos-AKT. Moderate correlation was observed between phos-mTOR and phos-S6, PTEN and p27, phos-AKT and p27, phos-S6 and p27, phos-mTOR and c-MYC, phos-S6 and c-MYC, and p27 and c-MYC. None of the evaluated biomarkers were associated with increased hazard ratios for tumor recurrence or for cancer-specific mortality, when adjusting for relevant clinicopathologic variables. Dysregulation of the mTOR pathway was observed in UTUC compared with normal urothelium, implicating a potential pathogenic role in tumor development. In our cohort, expression of the evaluated biomarkers had no prognostic value.

  10. The Diagnosis of Automated Image Cytometry 、Fluorescence in Situ Hybridization and Flow Cytometer for Urothelial Carcinoma of Bladder%全自动图像细胞法、荧光原位杂交法、流式细胞仪对膀胱肿瘤的诊断和意义

    Institute of Scientific and Technical Information of China (English)

    顾沈阳; 俞俊杰; 刘亚东; 王业华; 杜拥军

    2014-01-01

    Objective To study the application of fluorescence in situ hybridization and Automated Image Cytometry in the diagnosis of urothelial carcinoma of bladder and the expression of VEGF and VEGFR .Methods 60 patients were divided in-to two groups ,40 patients were diagnosed as urothelial carcinoma of bladder by pathology and 20 healthy individuals as control group.2Urine was collected and tested by ICM ,2FISH,cytology.The tissue of bladder cancer from 45 patients who have been as diagnosed bladder cancer and the mucosa of normal bladder was tested by FCM .Results Overall sensitivity of FISH was signifi-cantly higher than that of ICM (P<0.05) and urine cytology (P<0.05),and ICM was more sensitive than urine cytology (P<0.05).Sensitivities of ICM,FISH and urine cytology had significant correlation with grade (P<0.05).Conclusion FISH have significantly higher sensitivity in diagnosis of urothelial carcinoma of bladder than ICM and urine cytology .VEGF and VEGFR may be a new method in evaluation of bladder cancer .%目的:探讨荧光原位杂交法(FISH )及全自动图像细胞法(ICM)对膀胱肿瘤的诊断价值。方法对20例非尿路上皮癌和40例膀胱肿瘤患者的尿液采用全自动图像细胞法及FISH、进行尿细胞学检查。另对确诊的45例膀胱肿瘤患者肿瘤组织及10例排除膀胱肿瘤患者的正常膀胱黏膜,行流式细胞VEGF及VEGFR检测。结果 FISH的敏感性显著高于ICM的敏感性(P<0.05)和常规尿细胞学的敏感性(P<0.05),同时ICM敏感性也显著高于常规尿细胞学的敏感性(P<0.05);ICM、FISH和常规尿脱落细胞学检测的敏感性与患者病理分期无相关性(P>0.05),但与肿瘤病理分级显著相关(P<0.05)。结论 FISH对膀胱尿路上皮癌诊断的敏感性高于ICM和尿细胞学检查。 VEGF、VEGFR定量分析可作为膀胱肿瘤的生物学行为评估方法之一。

  11. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma.

    Science.gov (United States)

    Li, Jun; Wang, Ping; Wang, Bin

    2016-05-01

    Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma.The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement.The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma.This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement.

  12. Significance of CCR7 expression in bladder urothelial carcinoma%趋化因子受体CCR7在膀胱尿路上皮癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    周密; 张大宏; 祁小龙; 刘锋; 齐琳; 祖雄兵

    2013-01-01

    Objective To explore the CCR7 expression status in bladder urothelial carcinoma (BUC) and the relationship between CCR7 expression and lymph node metastasis,and analyze the impact of CCR7 expression on prognosis.Methods The expression levels of CCR7 in 57 BUC tissues and 10 normal bladder tissues were estimated by immunohistochemistry technique,and the correlation between CCR7 with lymph node metastasis,tumor stage,grade,number,size,relapse or not,and patients' age/sex of BUC was analyzed.The influence factors of lymph node metastasis were tested,and so were the influence factors of prognosis.Results The positive rate of CCR7 expression among 57 patients was 82.5% (47/57) (high expression rate was 45.6%),which was higher than that in normal bladder tissue (20.0%,all were low expression,P < 0.05).The high expression rate of CCR7 in lymph node metastasis group was 68.2% (15/22),higher than that in none lymph node metastasis group (31.4%,11/35,P < 0.01).The expression level of CCR7 had no significant correlation with tumor stage,grade or other parameters.CCR7 expression,tumor stage and tumor grade were correlated with lymph node status (P < 0.05),but only the first was an independent one.High CCR7 expression had a significant link with low relapse free survival (P < 0.05).Conclusion The expression of CCR7 was highly expressed in BUC,which may be a positive independent influence factor of lymph node metastasis,and a predictor of poor prognosis.%目的 研究膀胱尿路上皮癌(BUC)组织中趋化因子受体CCR7蛋白的表达情况,探讨CCR7蛋白表达与临床病理特征的相关性以及对BUC患者预后的影响. 方法 采用免疫组化染色法检测2006年1月至2009年12月57例因膀胱肿瘤行开放式根治性膀胱切除术的BUC组织以及10例正常膀胱组织中CCR7蛋白表达情况.分析CCR7蛋白表达与肿瘤分期、分级、大小、数量、发病次数、患者年龄、性别以及淋巴结转移之间的关系,分

  13. Conditional Survival in de novo Metastatic Urothelial Carcinoma.

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    Sumanta Kumar Pal

    Full Text Available Second-line therapy is frequently utilized for metastatic urothelial carcinoma, but there are limited data to guide this approach. While an assessment of overall survival based on registry data may not capture the impact of second- and third-line therapies on clinical outcome, this may be reflected in relative conditional survival (RCS.Patients with stage IV urothelial carcinoma diagnosed from 1990-2010 were identified from the Surveillance, Epidemiology and End Results (SEER dataset. The association of clinicopathologic variables with disease specific survival (DSS was explored through univariate and multivariate analyses. DSS in subgroups divided by time period (1990-2000 v 2001-2010 was compared using the Kaplan-Meier method and log-rank test. One-year RCS at annual landmarks up to 5 years was compared in subgroups divided by time period.Of 261,987 patients diagnosed with urothelial carcinoma from 1990-2010, 3,110 patients met criteria for the current analysis. Characteristics of patients diagnosed between 1990 and 2000 (n = 810 and 2001 to 2010 (n = 2,300 were similar and there was no significant difference in DSS between the two groups. On multivariate analysis, older age (age ≥ 80 was associated with shorter DSS (HR 1.79, 95%CI 1.48-2.15, but no association was found between time period of diagnosis and outcome. One-year RCS improved substantially through successive annual landmarks up to 5 years, but no differences were seen in subgroups divided by time of diagnosis.No difference in RCS was observed amongst patients with stage IV urothelial carcinoma diagnosed from 1990-2000 and 2001-2010. A lack of difference in RCS (more so than cumulative DSS may reflect a lack of progress in salvage therapies for the disease.

  14. Metastatic Transitional Cell Carcinoma of the Bladder to the Testis: A Case Report

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    Gregory N. Kozak

    2012-01-01

    Full Text Available An 84-year-old gentleman presented with onset of gross hematuria in September 2010. Follow-up investigations revealed T1 superficially invasive, poorly differentiated, papillary urothelial carcinoma. He subsequently had GreenLight laser for BPH and bladder neck contracture on two occasions. He developed a right hydrocele 16 months after initial presentation and during his hydrocelectomy, a rock-hard right epididymis and testicle were discovered. Pathology revealed metastatic urothelial carcinoma replacing nearly the entire testis with lymphovascular invasion.

  15. Expression of thymidylate synthase in bladder urothelial carcinoma and its prognostic value%胸苷酸合成酶在膀胱尿路上皮癌中的表达及预后价值

    Institute of Scientific and Technical Information of China (English)

    赵伟; 孙茸; 赵守国; 赵南

    2011-01-01

    目的 探讨胸苷酸合成酶(TS)在膀胱尿路上皮癌(BUC)的表达情况及临床意义,评价TS预后价值,为肿瘤预后判断及治疗方案的选择提供帮助.方法 采用免疫组织化学染色(SP法)的方法检测54例BUC组织及15例正常膀胱组织的TS表达,通过回顾性随访,了解患者术后情况.以TS表达水平、临床病理变量及两个预后变量[无复发生存率(RFS)和总生存率(OS)]作为研究对象,探讨它们之间的关系,绘制生存曲线,进行Cox回归分析.结果 54例肿瘤标本中TS高表达率为46.30%(25/54),其中G1级为29.41%(5/17),G2级为46.43%(13/28),G3级为77.78%(7/9);Ta期为21.43%(3/14),T1期为26.32%(5/19),T2期为86.67%(13/15),T3期为66.67%(2/3),T4期为66.67%(2/3);TS表达水平与肿瘤分级、分期呈正相关(Kruskal-Wallis H,P=0.03,P<0.001).TS高表达患者术后复发率、病死率分别为60.00%(15/25)和44.00%(11/25),经生存分析和Cox回归分析,肿瘤的TS表达水平是术后复发(RR为2.65,95%CI 0.80~8.81,P<0.05)、死亡(RR为1.42,95%CI0.36~5.58,P<0.05)的独立预后因素.结论 随着TS表达水平升高,BUC发生恶性进展和复发的概率增加,测定其表达水平有助于选择恰当的治疗和随访方案.%Objective To investigate the expression of thymidylate synthase (TS) in bladder urothelial carcinoma(BUC) and its clinical significance, and to evaluate its prognostic value, thus to help predict the prognosis and choose therapy protocal. Methods The expression of TS was assessed by immunohistochemistry in 54 BUC and 15 normal bladder specimens, and all these clinical data were retrospectively analyzed after surgery. Expression of TS,clinicopathologic findings and two prognostic variances (relapse-free survival (RFS) and overall survival (OS)) were determined. The prognostic value of TS was estimated by survival curve and Cox proportional hazards model. Results Immunohistochemistry showed that 25 of 54 BUC cases (46. 30%) had high TS

  16. Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell

    Science.gov (United States)

    Xin, Jia-jia; Li, Jing; Zhang, Zi-dan; Hu, Xing-bin; Li, Ming-kai

    2015-03-01

    In this study, five new biscoumarin derivatives (1-5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48 h treatment at different concentration (1, 5 and 10 μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular Osbnd H⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

  17. Identification of nine genomic regions of amplification in urothelial carcinoma, correlation with stage, and potential prognostic and therapeutic value.

    Directory of Open Access Journals (Sweden)

    Yvonne Chekaluk

    Full Text Available We performed a genome wide analysis of 164 urothelial carcinoma samples and 27 bladder cancer cell lines to identify copy number changes associated with disease characteristics, and examined the association of amplification events with stage and grade of disease. Multiplex inversion probe (MIP analysis, a recently developed genomic technique, was used to study 80 urothelial carcinomas to identify mutations and copy number changes. Selected amplification events were then analyzed in a validation cohort of 84 bladder cancers by multiplex ligation-dependent probe assay (MLPA. In the MIP analysis, 44 regions of significant copy number change were identified using GISTIC. Nine gene-containing regions of amplification were selected for validation in the second cohort by MLPA. Amplification events at these 9 genomic regions were found to correlate strongly with stage, being seen in only 2 of 23 (9% Ta grade 1 or 1-2 cancers, in contrast to 31 of 61 (51% Ta grade 3 and T2 grade 2 cancers, p<0.001. These observations suggest that analysis of genomic amplification of these 9 regions might help distinguish non-invasive from invasive urothelial carcinoma, although further study is required. Both MIP and MLPA methods perform well on formalin-fixed paraffin-embedded DNA, enhancing their potential clinical use. Furthermore several of the amplified genes identified here (ERBB2, MDM2, CCND1 are potential therapeutic targets.

  18. Prognostic significance of the 2004 WHO/ISUP classification for prediction of recurrence, progression, and cancer-specific mortality of non-muscle-invasive urothelial tumors of the urinary bladder: a clinicopathologic study of 1,515 cases.

    Science.gov (United States)

    Pan, Chin-Chen; Chang, Yen-Hwa; Chen, Kuang-Kuo; Yu, Hui-Jung; Sun, Chih-Hao; Ho, Donald M T

    2010-05-01

    To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.

  19. 组蛋白去甲基化酶 JMJD2B 在肾透明细胞癌和膀胱尿路上皮癌中的表达%Expressions of JMJD2B in renal clear cell carcinoma and bladder urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    徐子程; 蔡宏宙; 喻彬; 须霆; 邹青

    2016-01-01

    目的 探讨组蛋白去甲基化酶JMJD2B在肾透明细胞癌和膀胱尿路上皮癌的表达.方法 病理确诊肾透明细胞癌患者 30例 ,膀胱尿路上皮癌患者10例.采用免疫组化法检测JMJD2B在人肾透明细胞癌和膀胱尿路上皮癌及其癌旁组织的表达.结果 JMJD2B主要定位于肾透明细胞癌的细胞核中.其在高分化及中分化的肾透明细胞癌组织中呈现弱阳性表达 ,其阳性表达细胞数仅占10% ;但在低分化肾透明细胞癌组织中却表达较少.膀胱尿路上皮癌及其癌旁组织中均无明显JMJD2B表达.结论 JMJD2B在高分化及中分化的肾癌组织中呈现弱阳性表达 ,在膀胱尿路上皮癌中未见JMJD2B表达.其在肾癌发生、发展中的意义值得进一步研究.%Objective To investigate the expression of JMJD2B in bladder renal clear cell carcinoma(RCCC) and bladder urothelial carcinoma (BUC) .Methods The expressions of JMJD2B were detected by immunohistochemistry in RCCC (30 cases) ,BUC (10 cases) ,and cancers-adjacent tissues .Results The expression of JMJD2B mainly located in the nuclei of RCCC .JMJD2B was weakly expressed in RCCC with well- and moderately differentiated and the cell number positively expressed JMJD2B acounted for 10% only .JMJD2B expression was rarely seen in poorly differen-tiated RCCC .There were no obvious JMJD2B expressions in BUC and its adjacent tissues .Conclusion JMJD2B is weakly expressed in RCCC with well- and moderately differentiated .There is no obvious JMJD2B expression in BUC .The significance of JMJD2B expression in the occurrence and developmen of RCCC needs to be studied further .

  20. Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

    2007-06-21

    Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

  1. Reference miRNAs for miRNAome analysis of urothelial carcinomas.

    Directory of Open Access Journals (Sweden)

    Nadine Ratert

    Full Text Available BACKGROUND/OBJECTIVE: Reverse transcription quantitative real-time PCR (RT-qPCR is widely used in microRNA (miRNA expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. No study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference miRNAs for miRNA expression studies by RT-qPCR in urothelial carcinoma. METHODS: Candidate reference miRNAs were selected from 24 urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. PRINCIPAL FINDINGS: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-5p, miR-181a, miR-181b, miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. CONCLUSIONS: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-101, miR-125a-5p, miR-148b, and miR-151-5p or three (miR-148b, miR-181b, and miR-874

  2. Clinical usefulness of fluorescence in situ hybridization for diagnosis and surveillance of bladder urothelial carcinoma%荧光原位杂交技术诊断和监测膀胱尿路上皮癌复发的临床应用

    Institute of Scientific and Technical Information of China (English)

    张宇; 胡岚亭; 倪泽称; 张宁; 汪清

    2012-01-01

    目的 探讨荧光原位杂交技术( fluorescence in situ hybridization,FISH)诊断和监测膀胱尿路上皮癌复发的可行性,并与尿脱落细胞学进行对比.方法 应用荧光标记的3、7、17号染色体着丝粒探针和9号染色体p16位点9p21区带探针,对80例疑似膀胱肿瘤患者尿脱落细胞进行FISH检测,并同期行尿脱落细胞学检测,以病理结果作为诊断“金标准”,和FISH进行比较;以20例健康志愿者作为正常对照组,建立FISH阈值.结果 FISH和尿脱落细胞学诊断膀胱尿路上皮癌特异度分别为86.7%和100%,差异无统计学意义(P>0.05).FISH和尿脱落细胞学诊断膀胱尿路上皮癌总体灵敏度分别为80%和32.3%.FISH和尿脱落细胞学在灵敏度以及肿瘤分期、分级、初发和复发等方面差异均有统计学意义(P<0.05).结论 FISH可能成为一种新的早期诊断和监测膀胱癌术后复发的有效方法.%Objectives To evaluate the performance of the Fluorescence in Situ Hybridization (FISH) assay in comparison with that of urinary cytology for the detection of bladder urothelial carcinoma in routine clinical practice.Methods The probes of chromosome 3,7,17centromeres and chromosome 9 9p21 region ( p16 ) were labeled by random primer method.FISH was performed on interphase nuclei of 80 urine specimens of suspected bladder urothelial carcinoma,all the urine specimens were analyzed by urinary cytology at the same time.The pathological diagnosis was the" Golden standard",to analyse the sensitivity and specificity of FISH and urinary cytology to diagnose bladder urothelial carcinoma.20 normal donors were analyzed to establish threshold value.Results The overall specificity was 86.7% with FISH and 100% with cytology,although this difference was not statistically significant(p >0.05 ).We found a significant difference between the overall sensitivities of FISH and cytology( 80% vs.32.3%,respectively; p <0.05 ).The differences

  3. Proteomics research on muscle-invasive bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Yan

    2011-06-01

    Full Text Available Abstract Background Aimed to facilitate candidate biomarkers selection and improve network-based multi-target therapy, we perform comparative proteomics research on muscle-invasive bladder transitional cell carcinoma. Laser capture microdissection was used to harvest purified muscle-invasive bladder cancer cells and normal urothelial cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results A total of 885/890 proteins commonly appeared in 4 paired samples. 295/337 of the 488/493 proteins that specific expressed in tumor/normal cells own gene ontology (GO cellular component annotation. Compared with the entire list of the international protein index (IPI, there are 42/45 GO terms exhibited as enriched and 9/5 exhibited as depleted, respectively. Several pathways exhibit significantly changes between cancer and normal cells, mainly including spliceosome, endocytosis, oxidative phosphorylation, etc. Finally, descriptive statistics show that the PI Distribution of candidate biomarkers have certain regularity. Conclusions The present study identified the proteome expression profile of muscle-invasive bladder cancer cells and normal urothelial cells, providing information for subcellular pattern research of cancer and offer candidate proteins for biomarker panel and network-based multi-target therapy.

  4. Renal Embolization and Urothelial Sclerotherapy for Recurrent Obstructive Urosepsis and Intractable Haematuria from Upper Tract Urothelial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Nicholas, E-mail: nibrown@cantab.net [St Vincent’s Hospital, Department of Interventional Radiology (Australia); Olayos, Elizabeth; Elmer, Sandra; Wong, Lih-Ming [St Vincent’s Hospital, Department of Urology (Australia); Brooks, Duncan M; Jhamb, Ashu [St Vincent’s Hospital, Department of Interventional Radiology (Australia)

    2016-03-15

    Management of intractable haematuria and obstructive urosepsis from upper tract urothelial carcinoma can be problematic in patients not suitable for surgery, chemotherapy or radiotherapy. Interventional radiology techniques provide alternative approaches in this setting, such as complete kidney embolization to cease urine output, percutaneous nephrostomy, antegrade injection of sclerotherapy agents and sterilisation of the upper collecting system. Related approaches have been successfully employed to sclerose renal cysts, lymphoceles, chyluria and intractable lower tract haemorrhage. No reports of percutaneous, antegrade sclerotherapy in the upper urinary tract have previously been published. We present a case of recurrent haematuria and obstructive urosepsis caused by invasive upper tract urothelial carcinoma in a non-operative patient, which was treated with renal embolisation and percutaneous upper tract urothelial sclerotherapy.

  5. Renal Embolization and Urothelial Sclerotherapy for Recurrent Obstructive Urosepsis and Intractable Haematuria from Upper Tract Urothelial Carcinoma.

    Science.gov (United States)

    Brown, Nicholas; Olayos, Elizabeth; Elmer, Sandra; Wong, Lih-Ming; Brooks, Duncan M; Jhamb, Ashu

    2016-03-01

    Management of intractable haematuria and obstructive urosepsis from upper tract urothelial carcinoma can be problematic in patients not suitable for surgery, chemotherapy or radiotherapy. Interventional radiology techniques provide alternative approaches in this setting, such as complete kidney embolization to cease urine output, percutaneous nephrostomy, antegrade injection of sclerotherapy agents and sterilisation of the upper collecting system. Related approaches have been successfully employed to sclerose renal cysts, lymphoceles, chyluria and intractable lower tract haemorrhage. No reports of percutaneous, antegrade sclerotherapy in the upper urinary tract have previously been published. We present a case of recurrent haematuria and obstructive urosepsis caused by invasive upper tract urothelial carcinoma in a non-operative patient, which was treated with renal embolisation and percutaneous upper tract urothelial sclerotherapy.

  6. Primary Signet-Ring Carcinoma in the Bladder Presenting as a Hypervascular Luminal Polypoid Mass

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    Jeong, Min Sun; Choi, Seung A; Jung, Yoon Young; Cho, Young Kwon [Dept. of Radiology, Eulji Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of); Lee, Won Mi [Dept. of Pathology, Eulji Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of); Lee, Seung Wook [Dept. of Urology, Eulji Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of)

    2012-01-15

    Primary signet-ring carcinoma is a very aggressive and rare variant of a primary urinary bladder cancer, accounting for less than 1% of cases. We reported on a 76-year-old patient with primary signet-ring carcinoma who occurred metastatic lymphadenopathy with extranodal invasion causing intraluminal tumor thrombi in the adjacent vein, and pulmonary metastasis over the course of three months. We demonstrated the computed tomography findings of primary signet-ring carcinoma of the bladder and correlated the imaging findings with the pathologic features. We reviewed the distinguishing imaging findings of the primary signet-ring carcinoma compared with urothelial cell carcinoma, the most common subtype of the bladder cancer.

  7. Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.

    Science.gov (United States)

    Allen, Naomi E; Appleby, Paul N; Key, Timothy J; Bueno-de-Mesquita, H B; Ros, Martine M; Kiemeney, Lambertus A L M; Tjønneland, Anne; Roswall, Nina; Overvad, Kim; Weikert, Steffen; Boeing, Heiner; Chang-Claude, Jenny; Teucher, Birgit; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Palli, Domenico; Sieri, Sabina; Peeters, Petra; Quirós, Jose Ramón; Jakszyn, Paula; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Wareham, Nick; Ljungberg, Börje; Hallmans, Göran; Ehrnström, Roy; Ericson, Ulrika; Gram, Inger Torhild; Parr, Christine L; Trichopoulou, Antonia; Karapetyan, Tina; Dilis, Vardis; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fagherrazzi, Guy; Romieu, Isabelle; Gunter, Marc J; Riboli, Elio

    2013-02-01

    Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.

  8. Urothelial carcinoma of the upper urinary tract diagnosed via FGFR3 mutation detection in urine: a case report

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    Silverberg Daniel M

    2012-08-01

    Full Text Available Abstract Background Upper urinary tract cancer is typically diagnosed with urine cytology and imaging techniques. These assays can be limited by sensitivity, specificity, or technical issues making some diagnoses difficult. Case presentation A 73-year old man presented to the clinic with a right renal pelvis filling defect that was detected by a CT-scan performed for unrelated reasons. Urine cytology was negative. Cystoscopy, retrograde pyelogram, and partial ureteroscopy were unable to visualize the lesion resulting in an indeterminate diagnosis. A subsequent CT scan confirmed the renal lesion which appeared to have become larger and was consistent with urothelial carcinoma. A urine based genetic assay was used to test for the presence of urothelial carcinoma. This assay evaluates the presence of mutations in fibroblast growth factor receptor 3 (FGFR3. Mutations in FGFR3 are known to be associated with urothelial carcinoma and have a positive predictive value of 95% when detected in patients with no history of TCC. A mutation in exon 10 (Y375C of FGFR3 was identified. Nephroureterectomy was performed and the subsequent pathology confirmed urothelial carcinoma. In addition, PCR analysis on isolated tumor tissue indicated the tumor carried the same FGFR3 mutation as that of the DNA isolated from urine, consistent with the tumor being the origin of the mutant DNA. Conclusion This study indicates that the FGFR3 urine assay, which was originally developed to monitor bladder cancer, is also a useful tool for diagnosing upper urinary tract cancer in a real-life setting.

  9. Urine cytology of micropapillary carcinoma of the urinary bladder.

    Science.gov (United States)

    Sakuma, Takahiko; Furuta, Michiko; Mimura, Akihiro; Tanigawa, Naoto; Takamizu, Ryuichi; Kawano, Kiyoshi

    2011-11-01

    A case of micropapillary carcinoma (MPC) of urinary bladder is presented, in which the urine smear was studied in detail in an attempt to better characterize the cytologic findings of MPC. When the voided urine was examined in low power, cancer cells were scattered in the specimens as compact papillary/spheroidal clusters composed of pleomorphic cancer cells. Solitary carcinoma cells were occasionally observed. High power view of the smear revealed that the papillae/spheroids consisted of high-grade urothelial carcinoma cells. The cancer cells had pleomorphic nuclei with coarsely granular chromatin and thickened, irregular nuclear membrane, and thick cytoplasm. Histologically, the tumor in the resected bladder appeared as small nests with surrounding hallo both in the luminal surface and in the site of wall involvement. These tightly bound papillary/spheroidal clusters comprised of highly atypical cancer cells were the most specific cytologic finding in the urine of MPC, which were considered as a key diagnostic clue of MPC. The background of the urine smear showed numerous granulocytes and bacilli compatible with cystitis, which is a previously known complication of MPC. Differential diagnoses of MPC from those with pertinent cytologic findings such as conventional UC (including glandular differentiation), and primary/secondary adenocarcinoma of urinary bladder are discussed with a brief review of literature.

  10. Metastatic patterns of bladder carcinoma.

    Science.gov (United States)

    Tabbara, W S; Mehio, A R

    1984-01-01

    The authors reviewed 227 new bladder cancers from two main hospitals in Beirut Lebanon. They analyzed the morphologic features of these tumours, insisting particularly on the number, the size, the site, the grade, the stage, the mode of spread and the vascular permeation. The latter four factors appear to be directly related to the metastatic spread of these tumours. The metastatic patterns are summarized, regional lymph node metastases being the main problem because of therapeutic implications (radical surgery, radiotherapy and chemotherapy). The problems of generalized carcinoma, unusual lymph node metastases and solitary distant metastases are also considered.

  11. Challenges in the Diagnosis of Urothelial Carcinoma Variants: Can Emerging Molecular Data Complement Pathology Review?

    Science.gov (United States)

    Solomon, James P; Lowenthal, Brett M; Kader, A Karim; Parsons, J Kellogg; Flaig, Thomas W; Siefker-Radtke, Arlene O; Dyrskjøt, Lars; Hansel, Donna E

    2016-10-18

    Urothelial carcinoma can exhibit a wide variety of histopathologic phenotypes or variant morphologies, classifications of which have recently been revised in the 2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. Many of these variants not only present diagnostic challenges, but also have clinical implications that affect patient prognosis and treatment strategies. This review will discuss these variant morphologies and their relationship to current understanding of the underlying biology of urothelial carcinoma and molecular classification paradigms.

  12. Does subdivision of the "atypical" urine cytology increase predictive accuracy for urothelial carcinoma?

    Science.gov (United States)

    Bostwick, David G; Hossain, Deloar

    2014-12-01

    Urine cytology is routinely used for early diagnosis and monitoring of patients with hematuria or a history of urothelial carcinoma, but its clinical utility is greatly diminished by a high frequency of "atypical" specimens, reportedly around 20% in the literature. We compared our results with double-stained urine cytology specimens (papanicolaou and acid hematoxylin stains) with published results with only a single or double papanicolaou stain. The acid hematoxylin stain enhanced nuclear chromatin staining, eliminated significant background debris, and improved visibility of diagnostic cells in the presence of obscuring blood. Medical records of all urine cytologies received between 2005 and 2012 in our laboratories were reviewed. The study group consisted of all cases with bladder biopsy follow-up within one year of cytology. Of 43,131 urine cytologies diagnosed in our laboratories, biopsy follow-up results were available within one year in 10,473 cases, including 852 for symptoms and 1,461 for follow-up of bladder cancer. An additional 6,427 cases had cystoscopy results in which no biopsy was obtained. Cases were classified as negative (81.6%), atypical, favor reactive (2.9%), atypical, favor neoplastic (7.3%), suspicious (5.7%), and malignant (2.5%), with subsequent frequencies for urothelial cancer on biopsy of 13.3%, 31.1%, 37.6%, 53.6%, and 74.3%, respectively. No significant difference was found if atypical was subdivided into two categories: favor reactive and favor neoplastic. Subdivision of the atypical category did not improve diagnostic accuracy. Addition of the acid hematoxylin stain decreased the incidence of atypical urine cytologies from about 20% to 10.2%.

  13. Evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall obtained by transurethral intravesical echotomography

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    Milošević Radovan

    2007-01-01

    Full Text Available Background/Aim. Transitional cell carcinoma (TCC is the most frequent tumor of the bladder and represents 95−98% of blader neoplasams and 2−3% of all carcinomas in the body. In urogenital oncology more frequent is only prostatic cancer. Evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall represents the clinical base in treatment planning and prognosis. Clinical investigation and convential radiological procedures have a low level of accuracy in estimating the local growth of the tumor. The aims of our investigation were to determine the depth of infiltration of urothelial carcinoma in the vesical wall in the investigated group of patients by transurethral intravesical echotomography (TIE and computerised tomography (CT scan and to compare results obtained by both methods with pathohistological (PH results, and, based on the difference of the results determine which method was more accurate in the evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall. Methods. Thirty patients with TCC of the bladder both genders, aged 51−81 years were involved in our investigation. In all of these patients, radical cystectomy (RC was performed. This was neccessary to provide the defintive PH result. Transurethral intravesical echotomography was performed by ultrasound scanner type 1846 Bruel and Kjaer, sond type 1850, and the CT scan was perfomed by Pace plus, General Electric, U.S.A. The specimen for the definitive PH result obtained by RC includes all standards of the TNM classification. Results. Using CT scan, the most frequent was T1 stage (17 patients or 56.68%. Using TIE, the most frequent was T2 stage (22 patients or 73.33%. After RC the most frequent was T2 stage (21 patients or 70%. The Kolmogorov-Smirnov test, showed a high significant difference between the results obtained using CT and definitive PH results after RC. The same test showed no statistically significant difference between

  14. Breast metastasis from carcinoma of gall bladder

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    Ajaz Ahmad Malik

    2013-01-01

    Full Text Available Carcinoma of gall bladder has early lymphatic and haematogenous spread. Most common extra abdominal site of metastasis is the lung. Metastasis to breast from carcinoma of breast is very rare. Our case describes an interesting case of carcinoma of gall bladder metastising to breast. A 50-year-old female presented to our outpatient department with a small nodule on upper outer quadrant of left breast. Patient had a history of cholecystectomy done for symptomatic gall stones 2 years back. Histopathological examination of the gall bladder specimen showed adenocarcinoma of the gall bladder with invasion to lamina propria. No additional treatment was offered to the patient. The breast nodule was excised and sent for histopathological examination. Histopathological examination revealed metastising adenocarcinoma. Patient was subjected to palliative chemotherapy (Gamcitabine and carboplatin. However, patient died of hepatic encephalopathy after 5 months. Our case reports an unusual site of metastasis from carcinoma of gall bladder which is very rare.

  15. The genetic difference between Western and Chinese urothelial cell carcinomas: infrequent FGFR3 mutation in Han Chinese patients.

    Science.gov (United States)

    Yuan, Xiaotian; Liu, Cheng; Wang, Kun; Liu, Li; Liu, Tiantian; Ge, Nan; Kong, Feng; Yang, Liu; Björkholm, Magnus; Fan, Yidong; Zhao, Shengtian; Xu, Dawei

    2016-05-01

    Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC), renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies dependent on geographical areas and tumor locations, which indicates different oncogenic mechanisms and/or different genetic susceptibility/environment exposure. The activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most frequent genetic events in UCCs. These mutations have clinical utilities in UCC initial diagnostics, prognosis, recurrence monitoring and management. However, the vast majority of the results are obtained from studies of UCC patients in Western countries, and little has been known about these in Han Chinese patients. In the present study, we screened the FGFR3 gene and TERT promoter for mutations in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger Sequencing. TERT promoter mutations occurred at a high frequency in these UCC patients, comparable with that seen in Western patients, however, the FGFR3 mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy have limited clinical utility in these patients. Our results underscore the need for extensive characterization of cancer genomes from diverse patient populations, thereby contributing to precision medicine for cancer treatment and prevention.

  16. The genetic difference between Western and Chinese urothelial cell carcinomas: infrequent FGFR3 mutation in Han Chinese patients

    Science.gov (United States)

    Liu, Li; Liu, Tiantian; Ge, Nan; Kong, Feng; Yang, Liu; Björkholm, Magnus; Fan, Yidong; Zhao, Shengtian; Xu, Dawei

    2016-01-01

    Urothelial cell carcinoma (UCC) includes urothelial bladder carcinoma (UBC), renal pelvic carcinoma (RPC) and ureter carcinoma (UC), and its incidence varies dependent on geographical areas and tumor locations, which indicates different oncogenic mechanisms and/or different genetic susceptibility/environment exposure. The activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene and telomerase reverse transcriptase (TERT) promoter are the most frequent genetic events in UCCs. These mutations have clinical utilities in UCC initial diagnostics, prognosis, recurrence monitoring and management. However, the vast majority of the results are obtained from studies of UCC patients in Western countries, and little has been known about these in Han Chinese patients. In the present study, we screened the FGFR3 gene and TERT promoter for mutations in 116 UBC, 91 RPC and 115 UC tumors from Han Chinese patients by using Sanger Sequencing. TERT promoter mutations occurred at a high frequency in these UCC patients, comparable with that seen in Western patients, however, the FGFR3 mutation was surprisingly lower, only 9.4% for UBCs, 8.8% for RPCs and 2.6% for UCs, respectively. Taken together, the FGFR3 gene is an infrequent target in the pathogenesis of Han Chinese UCCs, and its mutation detection and targeted therapy have limited clinical utility in these patients. Our results underscore the need for extensive characterization of cancer genomes from diverse patient populations, thereby contributing to precision medicine for cancer treatment and prevention. PMID:27029078

  17. Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

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    Francesco Mistretta

    2014-01-01

    Full Text Available Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1, a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect.

  18. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  19. Nuclear morphometry in typing and grading urothelial neoplasms of urinary bladder

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    Mehmet KEFELİ

    2007-01-01

    Full Text Available In this study, by using image analyzer, the different diagnostic categories for urinary tumors described in WHO/ISUP 1998 classification were analyzed for the nuclear morphometric features and the data were statistically compared. Fifty six cases of urothelial neoplasia of urinary bladder diagnosed between 2002 and 2006 were selected from the archives of Ondokuz Mayis University, Department of Pathology. The cases were re-classified according to WHO/ISUP 1998 criteria. In each case morphometric assessment was performed for average 100-150 tumor cell nuclei and 10 largest tumor cell nuclei on the digitalized image. For each the selected cell, nuclear area (µm2, perimeter (µm, form factor, maximum and minimum diameters (µm were determined. We have found that morphometric analysis and WHO/ISUP 1998 classification show parallelism in the typing/grading of urothelial neoplasia of the urinary bladder. The standard use of nuclear morphometric features as an ancillary method for the classification of urinary neoplasms in difficult cases can be considered, however further studies that will include the prognostic data are needed.

  20. Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas.

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    Guangping Tai

    Full Text Available The mammalian ureter contains a water-tight epithelium surrounded by smooth muscle. Key molecules have been defined which regulate ureteric bud initiation and drive the differentiation of ureteric mesenchyme into peristaltic smooth muscle. Less is known about mechanisms underlying the developmental patterning of the multilayered epithelium characterising the mature ureter. In skin, which also contains a multilayered epithelium, cytokeratin 15 (CK15, an acidic intermediate filament protein, marks cells whose progeny contribute to epidermal regeneration following wounding. Moreover, CK15+ precursor cells in skin can give rise to basal cell carcinomas. In the current study, using transcriptome microarrays of embryonic wild type mouse ureters, Krt15, coding for CK15, was detected. Quantitative polymerase chain reaction analyses confirmed the initial finding and demonstrated that Krt15 levels increased during the fetal period when the ureteric epithelium becomes multilayered. CK15 protein was undetectable in the ureteric bud, the rudiment from which the ureter grows. Nevertheless, later in fetal development, CK15 was immunodetected in a subset of basal urothelial cells in the ureteric stalk. Superficial epithelial cells, including those positive for the differentiation marker uroplakin III, were CK15-. Transformation-related protein 63 (P63 has been implicated in epithelial differentiation in murine fetal urinary bladders. In wild type fetal ureters, CK15+ cells were positive for P63, and p63 homozygous null mutant ureters lacked CK15+ cells. In these mutant ureters, sections of the urothelium were monolayered versus the uniform multilayering found in wild type littermates. Human urothelial cell carcinomas account for considerable morbidity and mortality. CK15 was upregulated in a subset of invasive ureteric and urinary bladder cancers. Thus, in ureter development, the absence of CK15 is associated with a structurally simplified urothelium whereas

  1. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    OpenAIRE

    Fleischmann, Achim; Thalmann, George; Perren, Aurel; Seiler,Roland

    2014-01-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumor...

  2. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.

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    Minna M Boström

    Full Text Available Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker, MAC387 (polarized towards type 1 macrophages, and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.

  3. Maintenance of bladder urothelia integrity and successful urothelialization of various tissue-engineered mesenchymes in vitro.

    Science.gov (United States)

    Bouhout, Sara; Tremblay, Julie; Bolduc, Stephane

    2015-10-01

    Tissue-engineering offers the opportunity to produce hybrid tissues in vitro. The induction of bladder urothelial cells (BUCs) differentiation in vitro has been assessed by several research groups to build bladder models for fundamental studies and clinical applications. However, BUC induction of advanced differentiation in culture remains a challenging task. To reach this goal, optimal culture conditions are required, notably the use of specific additives as well as proper mesenchymal support. The best positive control for BUCs functional state monitoring is native urothelium collected from healthy bladder samples. In order to establish the best culture conditions to maintain and promote BUC differentiated state, native urothelia were cultured on various mesenchymes. Native bladder mesenchymes were used as controls for the maintenance of native urothelia. Histological and ultrastructural analyses showed the necessity to have a cellularized mesenchyme for rapid formation of a pseudostratified urothelium, allowing apical membrane rearrangement of the superficial cells in culture. Taken together, the results strongly suggest that it is possible to conserve the integrity of urothelia in vitro and, thus, potentially use them for eventual clinical applications and pharmacological investigations.

  4. Combined thermo-chemotherapy for recurrent bladder cancer after bacillus Calmette-Guerin.

    NARCIS (Netherlands)

    Nativ, O.; Witjes, J.A.; Hendricksen, K.; Cohen, M.; Kedar, D.; Sidi, A.; Colombo, R.; Leibovitch, I.

    2009-01-01

    PURPOSE: Despite an initial adequate response many patients with nonmuscle invasive urothelial cell carcinoma of the bladder eventually have recurrence after intravesical bacillus Calmette-Guerin treatments. We evaluated the efficacy of combined bladder wall hyperthermia and intravesical mitomycin C

  5. Lipid Cell and Micropapillary Variants of Urothelial Carcinoma of the Ureter

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    Yu Miyama

    2015-11-01

    Full Text Available We report on a case of urothelial carcinoma (UC with lipid cell and micropapillary variants in the ureter. A 64-year-old man presented with gross hematuria. Urinary cytology revealed the presence of atypical urothelial cells. Computed tomography and drip infusion/retrograde pyelography identified a mass-occupying lesion in the left mid-ureter, as well as left hydronephrosis. A clinical diagnosis of left ureteral cancer was given and the patient underwent left nephroureterectomy. Microscopically, the major component of the tumor was a conventional high-grade UC. In the invasive region, however, lipid cell and micropapillary variants of UC were also observed. Upon immunohistochemical analysis, all of the components were diffusely positive for cytokeratin 7 and p53. Intense membranous expression of human epidermal growth factor receptor 2 (HER2 was also observed in both the lipid cell and micropapillary variants of UC, whereas weak and incomplete staining was observed in most regions of the conventional UC. The pathological stage was pT3 N2. Multiple times, the patient experienced recurrence of the UC in the urinary bladder and urethra. Although the patient underwent total cystectomy and urethrectomy, 52 months following the initial surgery, signs of local recurrence developed, as well as multiple lymph node and bone metastases. The patient died 75 months following the initial surgery. To the best of our knowledge, this is the first reported case of a lipid cell variant of ureteral UC. The overexpression of HER2 may be associated with both the lipid cell and micropapillary variants of UC.

  6. Urinary Bladder Cancer in Yemen

    Science.gov (United States)

    Al-Samawi, Abdullah Saleh; Aulaqi, Saleh Mansoor

    2013-01-01

    Objectives The aims of this study are to highlight the clinicopathological features of urinary bladder cancer in Yemen, and to describe the histological grading of urothelial neoplasms according to the World Health Organization and International Society of Urologic pathology (WHO/ISUP 1998) classification. Methods This is a descriptive record-based study of 316 cases of bladder cancer diagnosed by two pathologists at the Department of pathology, Sana'a University from 1st January 2005 to 30th April 2009. The diagnoses were made on hematoxylin and eosin stained sections and categorized according to WHO/ISUP 1998 classification. Results Out of 316 urinary bladder cancers, 248 (78%) were urothelial neoplasms, 53 (17%) were squamous cell carcinoma, 7 (2%) were adenocarcinoma, and 3 (1%) were rhabdomyosarcoma. The remaining cases were metastatic carcinomas (n=3), small cell carcinoma (n=1), and non-Hodgkin's lymphoma (n=1). The urothelial neoplasms observed were carcinoma in situ 4 (2%), papilloma 7 (3%), papillary urothelial neoplasm of low malignant potential 26 (11%), papillary urothelial carcinoma of low grade 107 (43%), papillary urothelial carcinoma of high grade 18 (7%), and non-papillary urothelial carcinoma of high grade 85 (34%), with 60 years mean age for males and 58 years for females; along with a male to female ratio of 4:1. The peak incidence was observed in the 61-70 years age group. Conclusion This study documents a high frequency of urothelial neoplasms, mostly papillary urothelial carcinoma of low grade and non-papillary urothelial carcinoma of high grade with male preponderance and peak incidence in 6th decade of age. PMID:24044060

  7. Urinary Bladder Cancer in Yemen

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    Abdullah Saleh Al-Samawi

    2013-09-01

    Full Text Available Objectives: The aims of this study are to highlight the clinicopathological features of urinary bladder cancer in Yemen, and to describe the histological grading of urothelial neoplasms according to the World Health Organization and International Society of Urologic pathology (WHO/ISUP 1998 classification.Methods: This is a descriptive record-based study of 316 cases of bladder cancer diagnosed by two pathologists at the Department of pathology, Sana'a University from 1st January 2005 to 30th April 2009. The diagnoses were made on hematoxylin and eosin stained sections and categorized according to WHO/ISUP 1998 classification.Results: Out of 316 urinary bladder cancers, 248 (78% were urothelial neoplasms, 53 (17% were squamous cell carcinoma, 7 (2% were adenocarcinoma, and 3 (1% were rhabdomyosarcoma. The remaining cases were metastatic carcinomas (n=3, small cell carcinoma (n=1, and non-Hodgkin's lymphoma (n=1. The urothelial neoplasms observed were carcinoma in situ 4 (2%, papilloma 7 (3%, papillary urothelial neoplasm of low malignant potential 26 (11%, papillary urothelial carcinoma of low grade 107 (43%, papillary urothelial carcinoma of high grade 18 (7%, and non-papillary urothelial carcinoma of high grade 85 (34%, with 60 years mean age for males and 58 years for females; along with a male to female ratio of 4:1. The peak incidence was observed in the 61-70 years age group.Conclusion: This study documents a high frequency of urothelial neoplasms, mostly papillary urothelial carcinoma of low grade and non-papillary urothelial carcinoma of high grade with male preponderance and peak incidence in 6th decade of age.

  8. Longitudinal change in renal function after nephroureterectomy in patients with upper tract urothelial carcinoma

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    Chih-Yuan Chou

    2015-06-01

    Conclusion: In this study, it was found that the average renal function of the patients with upper tract urothelial carcinoma is not as good as the general population. More than half of the normal renal function patients have new onset chronic kidney disease after surgery. For preventing further deterioration of renal function, the implication of partial nephrectomy or segmental ureterectomy for selected patients with localized urothelial carcinoma should be re-examined. Besides, neoadjuvant chemotherapy should be considered for those who are not good candidates for local treatment.

  9. Small cell carcinoma of the urinary bladder--a new case report.

    Science.gov (United States)

    Petrescu, Amelia; Berdan, Gabriela; Hulea, Ionela; Gaitanidis, Raluca; Ambert, V; Jinga, V; Damian, D; Codreanu, O; Andrei, F; Niculescu, L

    2007-01-01

    Primary pure small cell carcinoma of the urinary bladder is an extremely rare and highly aggressive tumor with an average five-year survival rate of less than 10% as cited by multiple case reports. It accounts for about 0.5-1% of all bladder tumors. We present the case of a 44-years-old man, smoker (10 cigarettes/day) hospitalized in the Department of Urology, from the "Prof. dr. Th. Burghele" Hospital, Bucharest, for one month intermittent hematuria. Ultrasonography showed a sessile tumoral mass, sized 37/30mm. Transurethral resection of the tumor mass was performed and tissue fragments were sent to the pathologic lab to establish the histologic type, the degree of differentiation and invasion. Fragments of the tumor were fixed in 10% formaldehyde, paraffin embedded and processed as standard technique; the sections were stained with HE, VG and immunohistochemically with: CROMO, EMA, NSE, CD56, NK1, p53 and betaHCG. The microscopic examination reveled a tumor proliferation composed of two distinct components: extensive small cells areas and foci of typical low grade (G2) papillary urothelial carcinoma. The small cell are uniformly, round, with increased nucleo-cytoplasmic ratio, eosinophyl cytoplasm, hyperchromatic nuclei, finely granular chromatin and inconspicuous nucleoli. Immunohistochemical stains showed diffuse positive staining of the small cell component for CROMO, EMA, NSE, CD56, NK1 and urothelial carcinoma component stained focally for betaHCG. The rate of cell proliferation was increased (p53 - 80% positive reaction). Conclusions. A diagnosis of small cell carcinoma coexisting with low-grade urothelial carcinoma was established. Because of aggressive behavior and distinct treatment, the pathologist should watch out for the presence of small cell carcinoma component.

  10. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    Science.gov (United States)

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome.

  11. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

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    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

  12. Sarcopenia as a prognostic biomarker of advanced urothelial carcinoma.

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    Hiroshi Fukushima

    Full Text Available OBJECTIVES: Sarcopenia, a novel concept reflecting the degenerative loss of skeletal muscle mass, is an objective indicator of cancer cachexia. We investigated its role as a prognostic biomarker in advanced urothelial carcinoma (UC patients. METHODS: This retrospective study consisted of 88 UC patients with cT4 and/or metastases to lymph nodes/distant organs. Skeletal muscle index (SMI, an indicator of whole-body muscle mass, was measured from computed tomography (CT images at the diagnosis. Sarcopenia was defined as SMIs of <43 cm(2/m(2 for males with body mass index (BMI <25 cm(2/m(2, <53 cm(2/m(2 for males with BMI ≥ 25 cm(2/m(2, and <41 cm(2/m(2 for females. Predictors of overall survival (OS were examined using Cox proportional hazard models. RESULTS: Sixty-seven patients (76% died during the median follow-up of 13 months. The median OS rate was 13 months. Multivariate analysis revealed that SMI was a significant and independent predictor of shorter OS (hazard ratio (HR 0.90, P <0.001. In the present cohort, 53 (60% were diagnosed with sarcopenia. The median OS rates were 11 and 31 months for sarcopenic and non-sarcopenic patients, respectively (P <0.001. On multivariate analysis, sarcopenia was a significant and independent predictor of shorter OS (HR 3.36, P <0.001, along with higher C-reactive protein (CRP (P = 0.001, upper urinary tract cancer (P = 0.007, higher lactate dehydrogenase (LDH (P = 0.047, and higher alkaline phosphatase (ALP (P = 0.048. CONCLUSION: Sarcopenia, which is readily evaluated on routine CT scans, is a useful prognostic biomarker of advanced UC. Non-sarcopenic patients can expect long-term survival. Evaluating sarcopenia can be helpful for decision-making processes in the management of advanced UC patients.

  13. Hypercalcemia in Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review

    Science.gov (United States)

    McHugh, Jonathan B.; Miller, David C.; Esfandiari, Nazanene H.

    2013-01-01

    Objective. We here report a patient with upper urinary tract urothelial carcinoma with hypercalcemia likely due to elevated 1,25-dihydroxyvitamin D. Methods. We present a clinical case and a summary of literature search. Results. A 57-year-old man, recently diagnosed with a left renal mass, for which a core biopsy showed renal cell carcinoma, was admitted for hypercalcemia of 11.0 mg/mL He also had five small right lung nodules with a negative bone scan. Both intact parathyroid hormone and parathyroid hormone-related peptide were appropriately low, and 1,25-dihydroxyvitamin D was elevated at 118 pg/dL. The patient's calcium was normalized after hydration, and he underwent radical nephrectomy. On the postoperative day 6, a repeat 1,25-dihydroxyvitamin D was 24 pg/mL with a calcium of 8.1 mg/dL. Pathology showed a 6 cm high-grade urothelial carcinoma with divergent differentiation. We identified a total of 27 previously reported cases with hypercalcemia and upper tract urothelial carcinoma in English. No cases have a documented elevated 1,25-dihydroxyvitamin D level. Conclusion. This clinical course suggests that hypercalcemia in this case is from the patient's tumor, which was likely producing 1,25-dihydroxyvitamin D. Considering the therapeutic implications, hypercalcemia in patients with upper urinary tract urothelial carcinoma should be evaluated with 1,25-dihydroxyvitamin D. PMID:23476827

  14. Hypercalcemia in Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review

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    Keiko Asao

    2013-01-01

    Full Text Available Objective. We here report a patient with upper urinary tract urothelial carcinoma with hypercalcemia likely due to elevated 1,25-dihydroxyvitamin D. Methods. We present a clinical case and a summary of literature search. Results. A 57-year-old man, recently diagnosed with a left renal mass, for which a core biopsy showed renal cell carcinoma, was admitted for hypercalcemia of 11.0 mg/mL He also had five small right lung nodules with a negative bone scan. Both intact parathyroid hormone and parathyroid hormone-related peptide were appropriately low, and 1,25-dihydroxyvitamin D was elevated at 118 pg/dL. The patient’s calcium was normalized after hydration, and he underwent radical nephrectomy. On the postoperative day 6, a repeat 1,25-dihydroxyvitamin D was 24 pg/mL with a calcium of 8.1 mg/dL. Pathology showed a 6 cm high-grade urothelial carcinoma with divergent differentiation. We identified a total of 27 previously reported cases with hypercalcemia and upper tract urothelial carcinoma in English. No cases have a documented elevated 1,25-dihydroxyvitamin D level. Conclusion. This clinical course suggests that hypercalcemia in this case is from the patient’s tumor, which was likely producing 1,25-dihydroxyvitamin D. Considering the therapeutic implications, hypercalcemia in patients with upper urinary tract urothelial carcinoma should be evaluated with 1,25-dihydroxyvitamin D.

  15. External Beam Radiotherapy for Focal Lymphoepithelioma-Like Carcinoma in the Urinary Bladder: A Case Report and Literature Review

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    Nobuhiro Kushida

    2015-01-01

    Full Text Available Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx characterized by prominent lymphoid infiltration. Carcinomas that resemble lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have been reported in other organs. A tumor in the bladder is categorized by the percentage of the total area occupied by the lymphoepithelioma-like carcinoma pattern, with the prognosis dependent on the percentage. We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing a component of urothelial carcinoma G3>G2. His general condition was such that he could not tolerate radical cystectomy or systemic chemotherapy. External beam radiotherapy (total 60 Gy was given to the bladder, including the lymph node metastatic lesion. No cancer recurrence was detected by regular follow-up computed tomography and cystoscopy. He eventually died of other causes 48 months later. Although treatment for focal lymphoepithelioma-like carcinoma generally requires multifocal therapies, in the present case, the bladder became tumor free. We also summarize previously reported lymphoepithelioma-like carcinoma cases treated with radiotherapy.

  16. CA 19-9 as a serum marker in urothelial carcinoma

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    Mahander Pall

    2012-01-01

    Conclusions: Serum CA19-9 is a marker of aggressiveness of urothelial carcinoma and is almost invariably raised in patients with metastatic disease. Thus, it may be used as a prognostic marker but not as a screening tool due to its low sensitivity.

  17. Holmium laser fulguration of superficial urothelial carcinoma of the pendulous urethra

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    Michael A Liss

    2012-01-01

    Full Text Available Urothelial carcinoma may occur anywhere in the urinary tract including the pendulous urethra. To prevent urethral stricture after resection and monopolor fulguration we describe the use of the holmium laser to fulgurate recurrent pTa UC from the urethra. The surgical approach was staged and provided excellent long term results for management of superficial UC.

  18. Clinical outcome of primary small cell carcinoma of the urinary bladder

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    Hou CP

    2013-08-01

    Full Text Available Chen-Pang Hou,1,2 Yu-Hsiang Lin,1,2 Chien-Lun Chen,1,2 Phei-Lang Chang,1,2 Ke-Hung Tsui1,2 1Department of Urology, Chang Gung Memorial Hospital-Linko, Taiwan, Republic of China; 2College of Medicine, Chang Gung University, Taiwan, Republic of China Purpose: Primary small cell carcinoma of the urinary bladder is a rare malignant disease. It accounts for less than 1% of all urinary bladder carcinomas. The purpose of this study is to review the clinical features, the treatment modalities, and the overall survival of these patients. We also compare the clinical outcomes between patients of bladder small cell carcinoma (SCC and bladder urothelial carcinoma (UC. Materials and methods: We reviewed the charts of patients with bladder tumors from January 1995 to December 2012 in the Chang Gung Memorial Hospital. A total of 2421 malignant bladder tumor patients were reviewed and there were 18 patients who were diagnosed with primary bladder SCC. The patients' characteristics, including age, gender, smoking history, presented symptoms, tumor size, locations, clinical stages, treatment modalities, pathology appearance, recurrence conditions, and survival conditions were all recorded. We also compared the clinical outcomes and the overall survival rates between patients with bladder SCC and those with UC. Results: Bladder SCC accounted for about 0.74% of all bladder malignancies in our institution. The mean age at diagnosis was 70.67 years, and the male-to-female ratio was 2.6:1. Thirteen patients had a history of cigarette smoking. All patients presented with symptoms of gross hematuria, and three of them had bladder tamponade requiring blood clot evacuation by cystoscopy. Only one patient had T1 disease, ten patients had stage III disease, and seven patients had lymph node or distant metastasis (stage IV disease. The mean tumor size was 4.29 cm in diameter. For the majority (61.11% of patients, SCC coexisted with UC components. The average survival time

  19. Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy.

    Science.gov (United States)

    Matsumoto, Kazumasa; Mochizuki, Kohei; Hirayama, Takahiro; Ikeda, Masaomi; Nishi, Morihiro; Tabata, Ken-ichi; Okazaki, Miyoko; Fujita, Tetsuo; Taoka, Yoshinori; Iwamura, Masatsugu

    2015-01-01

    This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine 1,000 mg/m2 on days 1, 8 and 15 and nedaplatin 70 mg/m2 on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.

  20. HLA class I expression in bladder carcinomas.

    Science.gov (United States)

    Cabrera, T; Pedrajas, G; Cozar, J M; Garrido, A; Vicente, J; Tallada, M; Garrido, F

    2003-10-01

    HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.

  1. HERV-K and LINE-1 DNA methylation and reexpression in urothelial carcinoma

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    Ulrike eKreimer

    2013-09-01

    Full Text Available Changes in DNA methylation frequently accompany cancer development. One prominent change is an apparently genome-wide decrease in methylcytosine that is often ascribed to DNA hypomethylation at retroelements comprising nearly half the genome. DNA hypomethylation may allow reactivation of retroelements, enabling retrotransposition and causing gene expression disturbances favoring tumor development. However, neither the extent of hypomethylation nor of retroelement reactivation are precisely known. We therefore assessed DNA methylation and expression of three major classes of retroelements (LINE-1, HERV-K and AluY in human urinary bladder cancer tissues and cell lines by pyrosequencing and quantitative reverse transcription–polymerase chain reaction, respectively. We found substantial global LINE-1 DNA hypomethylation in bladder cancer going along with a shift towards full-length LINE-1 expression. Thus, pronounced differences in LINE-1 expression were observed, which may be promoted, among others, by LINE-1 hypomethylation. Significant DNA hypomethylation was found at the HERV-K_22q11.23 proviral long terminal repeat (LTR in bladder cancer tissues but without reactivation of its expression. DNA methylation of HERVK17, essentially absent from normal urothelial cells, was elevated in cell lines from invasive bladder cancers. Accordingly, the faint expression of HERVK17 in normal urothelial cells disappeared in such cancer cell lines. Of 16 additional HERV-Ks, expression of 7 could be detected in the bladder, albeit generally at low levels. Unlike in prostate cancers, none of these showed significant expression changes in bladder cancer. In contrast, expression of the AluYb8 but not of the AluYa5 family was significantly increased in bladder cancer tissues. Collectively, our findings demonstrate a remarkable specificity of changes in expression and DNA methylation of retroelements in bladder cancer with a significantly different pattern from that

  2. Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

    LENUS (Irish Health Repository)

    Gallagher, D J

    2013-09-01

    Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity.

  3. Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness

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    Afonso, Julieta; Santos, Lúcio L.; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-01-01

    abstract Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells’ compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. PMID:26636903

  4. New miRNA Profiles Accurately Distinguish Renal Cell Carcinomas and Upper Tract Urothelial Carcinomas from the Normal Kidney

    OpenAIRE

    Apostolos Zaravinos; George I Lambrou; Nikos Mourmouras; Patroklos Katafygiotis; Gregory Papagregoriou; Krinio Giannikou; Dimitris Delakas; Constantinos Deltas

    2014-01-01

    BACKGROUND: Upper tract urothelial carcinomas (UT-UC) can invade the pelvicalyceal system making differential diagnosis of the various histologically distinct renal cell carcinoma (RCC) subtypes and UT-UC, difficult. Correct diagnosis is critical for determining appropriate surgery and post-surgical treatments. We aimed to identify microRNA (miRNA) signatures that can accurately distinguish the most prevalent RCC subtypes and UT-UC form the normal kidney. METHODS AND FINDINGS: miRNA profiling...

  5. The expression sequence tag is an effective method for screening DNA segments that predict urinary bladder transitional cell carcinoma prognosis

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    Yang PS

    2014-09-01

    Full Text Available Pei-Shan Yang,1,* Yu-Chao Hsu,1,2,* Yu-Hsiang Lin,1,2 Cheng-Pang Hou,1,2 Chien-Lun Chen,1,2 Phei-Lang Chang,1–3 Horng-Heng Juang,3,4 Ke-Hung Tsui1–3 1Department of Urology, Chang Gung Memorial Hospital at Linkou, Taiwan, Republic of China; 2School of Medicine, Chang Gung University, Taiwan, Republic of China; 3Bioinformation Center, Chang Gung Memorial Hospital, Taiwan, Republic of China; 4Department of Anatomy, School of Medicine, Chang Gung University, Taiwan, Republic of China; Kwei-Shan, Tao-Yuan, Taiwan, Republic of China *These authors contributed equally to this workPurpose: We validated the use of expression sequence tags (ESTs as an effective method of screening for DNA segments that could predict urothelial cell carcinoma and for identifying ESTs with such predictive value.Patients and methods: From 2004 to 2009, eleven patients were enrolled in this study: six with high-grade bladder carcinoma and five with low-grade bladder carcinoma. ESTs were used to screen for differential gene expression in a high-grade cell line (MGH-U1 and in a premalignant cell line (MGH-U4. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction were used to validate the degree of EST expression and the prognostic value of ESTs.Results: Apoferritin H subunit (FTH1 protein exhibited increased expression in high-grade bladder carcinoma compared with that seen in low-grade carcinoma. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction both supported the higher expression of FTH1 in high-grade urothelial carcinoma.Conclusion: ESTs are useful for detecting the FTH1 protein, which predicts the prognosis of patients with bladder carcinoma.Keywords: expression sequence tag, transitional cell carcinoma, FTH1

  6. Carcinoma Gall Bladder: Past, Present, and Future

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    Ghosh Y

    2014-12-01

    Full Text Available Carcinoma gall bladder is a very aggressive disease with poor outcomes. Despite achievements in the field of advanced imaging techniques, there is a very high mortality rate of the disease Cancer is the second most common disease in India responsible for maximum mortality with about 0.3 million deaths per year. The magnitude of cancer problem in the Indian Sub-continent (sheer numbers is increasing due to poor to moderate living standards and inadequate medical facilities. Women are more commonly affected than men. The peak incidence occurs in people in their 60s, but the disease age range is from 29 to 90 years of age and there is great geographic and ethnic variation. Carcinoma gall bladder, a disease of old age, is now found in the younger age group and presents with greater ferocity.

  7. A Case with Significant Proteinuria Caused by Secreted Protein from Urothelial Carcinoma

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    Masanori Sakakima

    2011-01-01

    Full Text Available 58-year-old female was admitted to our hospital complaining isolated proteinuria of 1.7 g/day. Abdominal echography showed right-sided unilateral hydronephrosis, and computed tomography pointed out a tumor of the right renal pelvis, suggesting cancer of renal pelvis. The right nephroureterectomy was carried out. Pathological diagnosis was urothelial carcinoma. Renal tissue revealed no apparent glomerulopathy with tubular atrophy, interstitial fibrosis, and mildly-to-moderately interstitial mononuclear cell infiltration. Immunofluorescence study showed no deposition of immunoreactanct, and electron microscopy showed almost normal glomerulus without electron dense deposit. Proteinuria disappeared within 6 days after the operation. Moderate amount of proteinuria in our patient was probably caused by secreted protein from urothelial carcinoma. This condition is rare but should be taken into account in patients with even moderate amount of proteinuria.

  8. The occult urothelial cancer.

    Science.gov (United States)

    Ragonese, Mauro; Racioppi, Marco; D'Agostino, Daniele; Di Gianfrancesco, Luca; Lenci, Niccolò; Bientinesi, Riccardo; Palermo, Giuseppe; Sacco, Emilio; Pinto, Francesco; Bassi, Pier Francesco

    2016-05-24

    Transitional cell carcinoma (TCC) is the tumor that most frequently affects the urinary tract. The most common location is in the bladder; the diagnosis, as the follow-up, is based on urine cytology, endoscopic, and radiological examinations. Urinary cytology is an important non invasive tool used in the diagnosis and follow-up of patients with TCC. A positive urine cytology result is highly predictive of the presence of TCC, even in the presence of normal cystoscopy, because malignant cells may appear in the urine long time before any cystoscopically visible lesion becomes apparent. The presence of a positive urinary cytology, in the absence of clinical or endoscopic evidence of a TCC, can identify an occult urothelial cancer, located in any site of the urinary tract (upper urinary tract, bladder, prostatic urethra). Most of the urothelial tumors of the renal pelvis and ureters are diagnosed by radiological examinations, but we can observe a high rate of false negatives. In order to improve the diagnostic role of urinary cytology and other conventional examinations, numerous molecular markers have been identified; however, the real clinical application remains unclear. Photodynamic diagnosis and narrow band imaging (NBI) cystoscopy increase the diagnostic accuracy of endoscopic examinations in the presence of lesions not easily detectable. The aim of this review is to analyze the current diagnostic standards in the presence of occult urothelial cancer.

  9. Tissue engineering of urethra using human vascular endothelial growth factor gene-modified bladder urothelial cells.

    Science.gov (United States)

    Guan, Yong; Ou, Lailiang; Hu, Gang; Wang, Hongjun; Xu, Yong; Chen, Jiatong; Zhang, Jun; Yu, Yaoting; Kong, Deling

    2008-02-01

    Acquired or congenital abnormalities may lead to urethral damage or loss, often requiring surgical reconstruction. Urethrocutaneous fistula and strictures are common complications, due to inadequate blood supply. Thus, adequate blood supply is a key factor for successful urethral tissue reconstruction. In this study, urethral grafts were prepared by seeding rabbit bladder urothelial cells (UCs) modified with human vascular endothelial growth factor (VEGF(165)) gene in the decellularized artery matrix. A retroviral pMSCV-VEGF(165)-GFP vector was cloned by insertion of VEGF open reading frame into the vector pMSCV-GFP (murine stem cell virus [MSCV]; green fluorescent protein [GFP]). Retrovirus was generated using package cell line 293T. Rabbit UCs were expanded ex vivo and modified with either MSCV-VEGF(165)-GFP or control MSCV-GFP retrovirus. Transduction efficiency was analyzed by fluorescence-activated cell sorting. The expression of VEGF(165) was examined by immunofluorescence, reverse transcript-polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay (ELISA). Decellularized rabbit artery matrix was seeded with genetically modified UCs and was subsequently cultured for 1 week prior to subcutaneous implantation into nude mice. Four weeks after implantation, the implants were harvested and analyzed by fluorescence microscopy, and by histologic and immunohistochemical staining. Ex vivo transduction efficiency of UCs was greater than 50% when concentrated retrovirus was used. The modified cells expressed both VEGF and GFP protein. Furthermore, the VEGF-modified UCs secreted VEGF in a time-dependent manner. Scanning electron microscopy and histochemical analysis of cross sections of the cultured urethral grafts showed that the seeded cells were attached and proliferated on the luminal surface of the decellularized artery matrix. In the subcutaneously implanted vessels, VEGF-modified cells significantly enhanced neovascularization and the

  10. Detection of bladder transitional cell carcinoma: urinary hTERT assay versus urine cytology

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    Yahyazadeh SR

    2009-04-01

    Full Text Available "nBackground: Transitional Cell Carcinoma (TCC of bladder is the second most common urogenital malignancy and because of its high rate of recurrence (two third of tumors recur vigilant surveillance is necessary. There have been a lot of efforts to find a proper biomarker for detecting urothelial cancers because available methods are expensive and invasive (like cystoscopy or have a low degree of sensitivity (like urine cytology. Urothelial malignancies, like other cancers tend to express a large amount of telomerase. The aim of this study was to evaluate the possible application of voided urine human telomerase reverse transcriptase (hTERT mRNA assay in detecting low-grade bladder carcinoma in comparison with urine cytology. "nMethods: Voided urine samples were collected from 49 patients who were supposed to go under operation. Samples were examined by both Quantitative Real-time RT-PCR (for measuring hTERT mRNA level and cytology; the results were then compared to the final pathologic studies. "nResults: Regardless of clinical stage and or pathological grade of tumor, sensitivity of telomerase test and urine cytology was 74% and 16% respectively. There was a strong correlation between results of urine cytology and stage and/or grade of tumor; however, sensitivity of telomerase test was acceptable regardless of stage and or grade of tumor. There was a statistically significant difference between sensitivity of urine cytology and telomerase test (p<0.001. "nConclusion: Detection of hTERT-mRNA can potentially be used as a non-invasive method for diagnosis and follow up of bladder carcinoma instead of urine cytology.

  11. Urothelial injury to the rabbit bladder from various alkaline and acidic solutions used to dissolve kidney stones.

    Science.gov (United States)

    Reckler, J; Rodman, J S; Jacobs, D; Rotterdam, H; Marion, D; Vaughan, E D

    1986-07-01

    Different irrigating solutions are used clinically to dissolve uric acid, cystine and struvite stones. These studies were undertaken to assess the toxicity to the rabbit bladder epithelium of several commonly used formulations. Test solutions were infused antegrade through a left ureterotomy overnight. Bladders were removed and routine histological sections made. A pH 7.6 solution of NaHCO3 appeared harmless. The same solution with two per cent acetylcysteine produced slight injury. All pH 4 solutions caused significant damage to the urothelium. Hemiacidrin, which contains magnesium, produced less damage than did other pH 4 solutions without that cation. Our data tend to support Suby's conclusions that addition of magnesium reduces urothelial injury even though the presence of magnesium will slow dissolution of struvite.

  12. HpD Photobiology And Photodynamic Therapy Of Bladder Carcinoma

    Science.gov (United States)

    Lin, Chi-Wei

    1988-02-01

    Bladder carcinoma is considered one of the most favorable targets for the application of photodynamic therapy (PDT) due to the accessibility of the bladder for light delivery. Examination of the bladder and surgical procedures are routinely performed by the insertion of an optical instrument called cystoscope through the urethra. Thus, the treatment of bladder cancer by PDT can be conducted through the cystoscope with minimal invasion. However, to achieve optimal results from this treatment, one must consider both the structure of the bladder and the nature of the carcinoma.

  13. Loss of Sh3gl2/Endophilin A1 Is a Common Event in Urothelial Carcinoma that Promotes Malignant Behavior

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    Shyama Majumdar

    2013-07-01

    Full Text Available Urothelial carcinoma (UC causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1 as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1 enhanced proliferation and colony formation in vitro, 2 inhibited EGF-induced EGFR internalization and increased EGFR activation, 3 stimulated phosphorylation of Src family kinases and STAT3, and 4 promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression.

  14. Penile-preserving surgery for primary urothelial carcinoma of male urethra

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    Haoping Tai

    2015-06-01

    Full Text Available Primary urethral carcinoma is a rare cancer, comprising <1% of all malignancies. The location of this lesion presents a certain dilemma of treatment between efficacy and quality of life. We report an 84-year-old male patient, with a history of chronic hepatitis C, hypertension, and transient ischemic accident, who presented with dysuria and acute urinary retention. The intravenous urography showed mild prostatic enlargement, but no stone or filling defect was noted in the upper urinary tract. On urethrocystoscopy, multiple papillary tumors were found at the pendulous urethra, and the pathology of biopsy confirmed urothelial carcinoma. The patient was admitted, and electroresection with fulguration of urethral tumors was performed owing to the patient's old age and poor performance status. Intraurethral and intravesical chemotherapy with mitomycin C was regularly given at the outpatient clinic. Recurrent urothelial carcinomas were noted twice in the first 2 years of follow up, and repeated transurethral resections were done. Unfortunately, liver cirrhosis with hepatocellular carcinoma was diagnosed last June, for which he received transcatheter arterial chemoembolization. No recurrence of urethral cancer has been found on semiannual cystoscopy in the past 3 years. Penile-preserving surgery is a reasonable surgical option for elderly primary urethral carcinoma patients with acceptable oncological outcome and good quality of life.

  15. Elevating the Horizon: Emerging Molecular and Genomic Targets in the Treatment of Advanced Urothelial Carcinoma.

    Science.gov (United States)

    Kurtoglu, Metin; Davarpanah, Nicole N; Qin, Rui; Powles, Thomas; Rosenberg, Jonathan E; Apolo, Andrea B

    2015-10-01

    Despite recent advances in the identification of genomic alterations that lead to urothelial oncogenesis in vitro, patients with advanced urothelial carcinomas continue to have poor clinical outcomes. In the present review, we focus on targeted therapies that have yielded the most promising results alone or combined with traditional chemotherapy, including the antiangiogenesis agent bevacizumab, the human epidermal growth factor receptor 2 antibody trastuzumab, and the tyrosine kinase inhibitor cabozantinib. We also describe ongoing and developing clinical trials that use innovative approaches, including dose-dense scheduling of singular chemotherapy combinations, prospective screening of tumor tissues for mutational targets and biomarkers to predict chemosensitivity before the determination of the therapeutic regimen, and novel agents that target proteins in the immune checkpoint regulation pathway (programmed cell death protein 1 [PD-1] and anti-PD-ligand 1) that have shown significant potential in preclinical models and early clinical trials. New agents and targeted therapies, alone or combined with traditional chemotherapy, will only be validated through accrual to developing clinical trials that aim to translate these therapies into individualized treatments and improved survival rates in urothelial carcinoma.

  16. Prognostic role of KiSS-1 and possibility of therapeutic modality of metastin, the final peptide of the KiSS-1 gene, in urothelial carcinoma.

    Science.gov (United States)

    Takeda, Toshikazu; Kikuchi, Eiji; Mikami, Shuji; Suzuki, Eriko; Matsumoto, Kazuhiro; Miyajima, Akira; Okada, Yasunori; Oya, Mototsugu

    2012-04-01

    The KiSS-1 gene has been reported to be a metastasis suppressor gene in human melanoma. The gene product was isolated from human placenta as the ligand of GPR54, a G protein-coupled receptor, and the C-terminally amidated peptide of 54 amino acids is called metastin. The binding of metastin to GPR54 has been shown to inhibit tumor metastasis in some tumor cells; however, its function remains unclear in urothelial carcinoma. We first evaluated KiSS-1 expression and GPR54 expression in 151 patients with upper urinary tract urothelial carcinoma to determine their prognostic significance. Next, we examined the role of metastin in the invasiveness and lung metastasis of MBT-2 variant (MBT-2V), which is a highly metastatic murine bladder cancer cell. Multivariate analysis revealed that KiSS-1 expression was an independent predictor of metastasis and overall survival. However, GPR54 expression was not selected. Hematogeneous metastasis had a significantly lower level of KiSS-1 expression compared with lymph node metastasis. Metastin treatment significantly reduced the invasiveness of MBT-2V cells and inhibited the DNA-binding activity of NF-κB by blocking its nuclear translocation, leading to a reduction in the expression and activity of matrix metalloproteinase-9. Metastin treatment dramatically prevented the occurrence of lung metastatic nodules (6.3 ± 2.3, n = 15) compared with controls (30.4 ± 5.1, n = 15; P metastin may be an effective inhibitor of metastasis in urothelial carcinoma through its blockade of NF-κB function.

  17. Oncologic Outcomes after Anterior Exenteration for Muscle Invasive Bladder Cancer in Women

    DEFF Research Database (Denmark)

    Gregg, Justin R; Emeruwa, Curran; Wong, Johnson;

    2016-01-01

    PURPOSE: We investigated oncologic and urinary outcomes after anterior exenteration for urothelial cell carcinoma in females, identifying tumor characteristics associated with female pelvic organ involvement. We hypothesized that a lack of trigonal or bladder floor tumor, intraoperative palpable ...

  18. Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical University—Shuang Ho Hospital, Taipei, Taiwan (China); Huang, Yung-Kai [School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University and Hospital, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Lai, Li-An [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2013-10-01

    Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C, IL-8 − 251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C and IL-8 − 251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α − 308 A/A and IL-8 − 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α − 308 A/A or IL-8 − 251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 − 251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 − 251 T/T genotype for each SD increase in DMA%. - Highlights: • Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC. • Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC. • Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC.

  19. ILEOCYSTOPLASTY IN INVASIVE URINARY BLADDER CARCINOMA

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2009-01-01

    Full Text Available Objective: to assess the results of surgical treatment of patients with the intestinal urinary bladder, to characterize its early and late postoperative complications, and to develop their correction tactics.  Subjects and methods. The results of treatment in 198 patients who had undergone ileocystoplasty were analyzed.  Results. The developed diagnostic approach and the determined examination periods could reduce the number of late postoperative complications of ileocystoplasty: acute and chronic pyelonephritis from 19.4 to 7.6%, urolithiasis from 17.2 to 1.9%, bladder dysfunction from 25.8 to 7.6%, and metabolic acidosis from 4.3 to 1.9%, and prevent the development of ureterovesical anastomosis stricture.  Conclusion. Radical cystectomy with the ileoplasty using an isolated segment of the ileum in patients with invasive urinary bladder carcinoma has been the operation of choice no longer; it has become an essential surgical adjunct. This method permits overall 5-year survival to be achieved in 69.7% of patients.  

  20. Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine.

    Science.gov (United States)

    Lance, R S; Aldous, W K; Blaser, J; Thrasher, J B

    1998-03-04

    Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in

  1. Granulocyte-Colony Stimulating Factor Producing Infiltrating Urothelial Carcinoma of the Left Renal Pelvis: A Case Report

    Directory of Open Access Journals (Sweden)

    Takamasa Horiuchi

    2017-01-01

    Full Text Available We report a case of granulocyte-colony stimulating factor (G-CSF producing infiltrating urothelial carcinoma of the left renal pelvis. The patient was referred to our hospital for fever and anorexia. Blood tests showed elevated level of leukocytosis without any infectious diseases. The serum concentration of G-CSF was remarkably elevated. Abdominal computed tomography (CT revealed a huge mass in the left renal pelvis and para-aortic lymph node enlargement. He was underwent left nephroureterectomy and para-aortic lymphadenectomy. The histological examination revealed infiltrating urothelial carcinoma with positive staining for G-CSF antibody. The postoperative course was smooth and the leukocyte count became normalized within a week postoperatively. However, multiple lung metastasis and leukocytosis were revealed about 2 months after the operation. G-CSF producing infiltrating urothelial carcinoma of the renal pelvis is reported to have a significantly poor prognosis, so it is very important to monitor closely after the operation.

  2. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakiba, Camille [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Cornelis, François [Department of Radiology, Pellegrin Hospital, Bordeaux (France); Descat, Edouard [Department of Radiology, Saint-Augustin Clinic, Bordeaux (France); Gross-Goupil, Marine [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Sargos, Paul [Department of Radiotherapy, Bergonié Cancer Institute, Bordeaux (France); Roubaud, Guilhem [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Houédé, Nadine, E-mail: nadine.houede@chu-nimes.fr [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Department of Medical Oncology, Nimes University Hosptital, Nîmes (France)

    2015-06-15

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI{sub 35s}) and venous phases (rSI{sub 80s}) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI{sub 80s} was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

  3. Massive Upper Gastrointestinal Bleeding Secondary to Duodenal Metastasis of Transitional Cell Carcinoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Carlos H.F. Chan

    2011-04-01

    Full Text Available Acute upper gastrointestinal (UGI bleeding is a common problem in our clinical practice and is often due to peptic ulcer diseases. Occasionally, malignancy may be implicated in these situations. Here we report a rare case of UGI bleeding secondary to metastatic transitional cell carcinoma (TCC of the urinary bladder. A 62-year-old man with a history of stage IIIb TCC of the urinary bladder presented with hematemesis. Endoscopy showed a large tumor in the second stage of the duodenum that occupied 40% of the duodenal circumference, over 7 cm in length. Biopsies revealed a poorly differentiated malignant neoplasm consistent with metastasis from urothelial carcinoma that was identical to the previous surgical specimen of the urinary bladder. He was treated with supportive therapy and intravenous proton pump inhibitor and was discharged home 2 weeks later. Two weeks after discharge, the patient returned to the hospital with a painful swelling of the floor of his mouth. Biopsy again showed the same cancer type. He had unremitting bleeding from his mouth requiring multiple transfusions and a course of palliative radiation therapy. He progressively deteriorated in his cardiopulmonary and neurological functions and expired with cardiopulmonary arrest one month later.

  4. Management of transitional cell carcinoma of the urinary bladder in dogs: a review.

    Science.gov (United States)

    Fulkerson, Christopher M; Knapp, Deborah W

    2015-08-01

    Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma, is the most common form of urinary bladder cancer in dogs, affecting tens of thousands of dogs worldwide each year. Canine TCC is usually a high grade invasive cancer. Problems associated with TCC include urinary tract obstruction, distant metastases in >50% of affected dogs, and clinical signs that are troubling both to the dogs and to their owners. Risk factors for TCC include exposure to older types of flea control products and lawn chemicals, obesity, female sex, and a very strong breed-associated risk. This knowledge is allowing pet owners to take steps to reduce the risk of TCC in their dog. The diagnosis of TCC is made by histopathology of tissue biopsies obtained by cystoscopy, surgery, or catheter. Percutaneous aspirates and biopsies should be avoided due to the risk of tumor seeding. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it. Approximately 75% of dogs respond favorably to TCC treatment and can enjoy several months to a year or more of good quality life. Many promising new therapies for TCC are emerging and with the close similarity between TCC in dogs and high grade invasive bladder cancer in humans, new treatment strategies found to be successful in canine studies are expected to help dogs and to be subsequently translated to humans.

  5. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.

    Science.gov (United States)

    Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A; Tang, Moon-shong

    2014-06-15

    Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.

  6. Identifying distinct classes of bladder carcinoma using microarrays

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Andersen, Thomas Thykjær; Kruhøffer, Mogens;

    2003-01-01

    Bladder cancer is a common malignant disease characterized by frequent recurrences. The stage of disease at diagnosis and the presence of surrounding carcinoma in situ are important in determining the disease course of an affected individual. Despite considerable effort, no accepted...... immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. Here we report the identification of clinically relevant subclasses of bladder carcinoma using expression microarray analysis of 40 well characterized bladder tumors. Hierarchical cluster analysis...... of 68 tumors. The classifier provided new predictive information on disease progression in Ta tumors compared with conventional staging (P expression patterns in 31 tumors by applying a supervised learning...

  7. Lynch syndrome and exposure to aristolochic acid in upper-tract urothelial carcinoma: its clinical impact?

    Science.gov (United States)

    Colin, Pierre; Seisen, Thomas; Mathieu, Romain; Shariat, Sharohkh F.

    2016-01-01

    The purpose of the current review was to describe the clinical risk for Lynch syndrome (LS) after exposure to aristolochic acid (AA) in cases of upper urinary-tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed using the Medline database (National Library of Medicine, PubMed) using the following keywords: epidemiology, risk factor, AA, Balkan nephropathy (BNe), LS, hereditary cancer, hereditary non-polyposis colorectal cancer (HNPCC), mismatch repair genes, urothelial carcinomas, upper urinary tract, renal pelvis, ureter, Amsterdam criteria, genetic counselling, mismatch repair genes, genetic instability, microsatellite, and Bethesda guidelines. LS is a specific risk for UTUC, which is the third most frequent cancer (in its tumor spectrum) after colon and uterine lesions. Mutation of the MSH2 gene is the most commonly described cause of UTUC in LS. Diagnosis is based on clinical suspicion and is guided by Bethesda and Amsterdam criteria. It is secondarily confirmed by immunohistochemical analyses of the tumor and a search for gene mutations. The presence of LS in patients with UTUC is a favorable prognosis factor for survival during follow-ups. AA is a specific environmental risk factor for UTUC and tubulo-interstitial nephropathy. It has been involved in the development of nephropathies in link with the Balkan disease and intake of Chinese herbal medicine. More broadly, the use of traditional plant medicines from the genus Aristolochia has created worldwide public-health concerns. UTUCs share common risk factors with other urothelial carcinomas such as tobacco or occupational exposure. However, these tumors have also specific risk factors such as AA exposure and LS that clinicians should be aware of because of their clinical implication in further management and follow-up.

  8. Study of the reproducibility of the 2004 World Health Organization classification of urothelial neoplasms

    Directory of Open Access Journals (Sweden)

    Pallavi Sharma

    2015-01-01

    Full Text Available The aim of the study was to evaluate urinary bladder biopsies showing papillary urothelial neoplastic lesions based on the 2004 WHO/ISUP classification of Urothelial Neoplasms of the Urinary Bladder, to assess the reproducibility of the bladder carcinoma grade. Fifty consecutive transurethral tumor resection biopsies were evaluated by four pathologists independently. The final diagnoses of each pathologist were subjected to statistical analysis to assess the degree of interobserver variability and reproducibility of this classification. Significant interobserver variation was found in the reporting of urothelial neoplasms. In 22 instances there was difference in opinion between PUNLMP and low-grade carcinoma, and in 59 instances between low and high grade carcinoma. The 4 observers never unanimously agreed on the diagnosis of PUNLMP.

  9. 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic cytotoxicity with arsenic trioxide in human urothelial carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kuan-Lin Kuo

    Full Text Available 2-Methoxyestradiol (2-ME, an endogenous derivative of 17β-estradiol, has been reported to elicit antiproliferative responses in various tumors. In this study, we investigated the effects of 2-ME on cell viability, proliferation, cell cycle, and apoptosis in human urothelial carcinoma (UC cell lines. We used two high-grade human bladder UC cell lines (NTUB1 and T24. After treatment with 2-ME, the cell viability and apoptosis were measured by MTT assay and flow cytometry (fluorescence-activated cell sorting, with annexin V-FITC staining and propidium iodide (PI labeling. DNA fragmentation was analyzed by agarose gel electrophoresis. Flow cytometry with PI labeling was used for the cell cycle analyses. The protein levels of caspase activations, poly (ADP-ribose polymerase (PARP cleavage, phospho-histone H2A.X, phospho-Bad, and cell cycle regulatory molecules were measured by Western blot. The effects of the drug combinations were analyzed using the computer software, CalcuSyn. We demonstrated that 2-ME effectively induces dose-dependent cytotoxicity and apoptosis in human UC cells after 24 h exposure. DNA fragmentation, PARP cleavage, and caspase-3, 7, 8, 9 activations can be observed with 2-ME-induced apoptosis. The decreased phospho-Bad (Ser136 and Ser155 and mitotic arrest of the cell cycle in the process of apoptosis after 2-ME treatment was remarkable. In response to mitotic arrest, the mitotic forms of cdc25C, phospho-cdc2, cyclin B1, and phospho-histone H3 (Ser10 were activated. In combination with arsenic trioxide (As2O3, 2-ME elicited synergistic cytotoxicity (combination index <1 in UC cells. We concluded that 2-ME significantly induces apoptosis through decreased phospho-Bad and arrests bladder UC cells at the mitotic phase. The synergistic antitumor effect with As2O3 provides a novel implication in clinical treatment of UC.

  10. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    Science.gov (United States)

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (Ptumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  11. Expression of OCT4A: The First Step to the Next Stage of Urothelial Bladder Cancer Progression

    Directory of Open Access Journals (Sweden)

    Wojciech Jóźwicki

    2014-09-01

    Full Text Available OCT4 (octamer-binding transcription factor is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p—tumor extent confined to mucosa (T1 tumors and the highest in pTis (non-papillary tumor extent confined to urothelium and pT2 (tumor extent including muscularis propria tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

  12. Calpain3 is expressed in a proteolitically active form in papillomavirus-associated urothelial tumors of the urinary bladder in cattle.

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    Sante Roperto

    Full Text Available BACKGROUND: Calpain 3 (Capn3, also named p94, is a skeletal muscle tissue-specific protein known to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A. Recent experimental studies have hypothesized a pro-apoptotic role of Capn3 in some melanoma cell lines. So far the link between calpain3 and tumors comes from in vitro studies. The objective of this study was to describe Capn3 activation in naturally occurring urothelial tumors of the urinary bladder in cattle. METHODS AND FINDINGS: Here we describe, for the first time in veterinary and comparative oncology, the activation of Capn3 in twelve urothelial tumor cells of the urinary bladder of cattle. Capn3 protein was initially identified with nanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC-MS/MS in a co-immunoprecipitation experiment on E2F3, known to be a transcription factor playing a crucial role in bladder carcinogenesis in humans. Capn3 expression was then confirmed by reverse transcription polymerase chain reaction (RT-PCR. Finally, the Ca(2+-dependent proteolytic activity of Capn3 was assayed following ion exchange chromatography. Morphologically, Capn3 expression was documented by immunohistochemical methods. In fact numerous tumor cells showed an intracytoplasmic immunoreactivity, which was more rarely evident also at nuclear level. In urothelial tumors, bovine papillomavirus type 2 (BPV-2 DNA was amplified by PCR and the expression of E5 protein, the major oncogenic protein of BVP-2, was detected by western blotting, immunohistochemistry, and immunofluorescence. E2F3 overexpression and pRb protein downregulation were shown by western blotting. CONCLUSION: The role of capn3 protein in urothelial cancer of the urinary bladder remains to be elucidated: further studies would be required to determine the precise function of this protease in tumor development and progression. However, we suggest that activated Capn3 may be involved in molecular

  13. Radionuclide targeting with particular emphasis on urinary bladder carcinoma

    CERN Document Server

    Sjöström, A

    2001-01-01

    primary bladder carcinoma tumours was investigated. Both receptors were expressed in the majority of metastases and primary tumours. Targeting the EGF receptor and/or HER-2 in urinary bladder carcinoma is an exciting new concept The incidence of urinary bladder carcinoma is increasing and many patients die every year of this disease despite assumed radical therapy. Thus, there is a need for improved methods of diagnosis and therapy. Radionuclide targeting is based on achieving specific delivery of radioactive nuclides to tumour cells with minimal damage to surrounding normal tissues. Two possible target structures are the epidermal growth factor (EGF) receptor and the related receptor HER-2. Cellular binding and retention of sup 1 sup 2 sup 5 I-EGF-dextran conjugates was investigated in two bladder carcinoma cell lines. The conjugate bound specifically to the EGF receptor with delayed maximum binding, limited intracellular degradation and prolonged cellular retention compared to sup 1 sup 2 sup 5 I-EGF. EGF w...

  14. Geographic Variation of Chronic Kidney Disease Prevalence: Correlation with the Incidence of Renal Cell Carcinoma or Urothelial Carcinoma?

    Directory of Open Access Journals (Sweden)

    Yit-Sheung Yap

    2015-01-01

    Full Text Available Background. The aim of this study is to evaluate whether geographic variations in the prevalence of late-stage chronic kidney disease (CKD exist and are associated with incidence rates of renal cell carcinoma (RCC, upper tract urothelial carcinoma (UTUC, or lower tract urothelial carcinoma (LTUC. Methods. Prevalence rates of late-stage CKD for 366 townships (n>30 in Taiwan were calculated for 1,518,241 and 1,645,151 subjects aged 40 years or older in years 2010 and 2009, respectively. Late-stage CKD prevalence in year 2010 was used as a training set and its age-adjusted standardized morbidity rates (ASMR were divided into three groups as defined <1.76%, 1.76% ≤ ASMR < 2.64%, and ≥2.64%, respectively. Year 2009, defined as the validation set, was used to validate the results. Results. The ASMR of late-stage CKD in years 2010 and 2009 were 1.76%, and 2.09%, respectively. Geographic variations were observed, with notably higher rates of disease in areas of the central, southwestern mountainside, and southeastern seaboard. There were no significant differences among different combined risk groups of RCC, UTUC, and LTUC incidence. Conclusion. The substantial geographic variations in the prevalence of late-stage CKD exist, but are not correlated with RCC, UTUC, or LTUC incidence.

  15. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A;

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC...

  16. Combined microsatellite and FGFR3 mutation analysis enables a highly sensitive detection of urothelial cell carcinoma in voided urine

    NARCIS (Netherlands)

    B.W. van Rhijn (Bas); I. Lurkin (Irene); D.K. Chopin; W.J. Kirkels (Wim); J.P. Thiery (Joachim); Th.H. van der Kwast (Theo); F. Radvanyi (Franois); E.C. Zwarthoff (Ellen)

    2003-01-01

    textabstractPURPOSE: Fibroblast growth factor receptor 3 (FGFR3) mutations were reported recently at a high frequency in low-grade urothelial cell carcinoma (UCC). We investigated the feasibility of combining microsatellite analysis (MA) and the FGFR3 status for the detection of UC

  17. Immunohistochemical profile of the penile urethra and differential expression of GATA3 in urothelial versus squamous cell carcinomas of the penile urethra.

    Science.gov (United States)

    Chaux, Alcides; Han, Jeong S; Lee, Stephen; Gonzalez-Roibon, Nilda; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J

    2013-12-01

    The penile urethra has a distinctive morphology not yet fully characterized by immunohistochemistry. In addition, both urothelial and squamous cell carcinomas have been reported in the penile urethra, and the distinction between these 2 tumors might be difficult. The purposes of this study are to assess the histology and immunohistochemical profile (CK20, CK7, p63, and GATA3) of the penile urethra and to assess the usefulness of Trans-acting T-cell-specific transcription factor (GATA3) and human papillomavirus detection in distinguishing urothelial versus squamous cell carcinomas. Normal penile urethra was evaluated in 11 total penectomies. The penile urethra was lined by 2 cell layers: a superficial single layer of CK7+, CK20-, and p63- columnar cells and a deep stratified layer of CK7-, CK20-, and p63+ cubical cells. Both layers were GATA3+, supporting urothelial differentiation. In addition, 2 tissue microarrays and 6 surgical specimens of primary tumors of the penile urethra (3 urothelial and 3 squamous cell carcinomas) were evaluated for GATA3 expression. In the tissue microarrays, 22 of 25 upper tract urothelial carcinomas and 0 of 38 penile squamous cell carcinomas were GATA3+. In the surgical specimens, GATA3 was positive in all urothelial carcinomas and negative in all squamous cell carcinomas. Human papillomavirus was detected in 2 of 3 squamous cell carcinomas and in 0 of 3 of the urothelial carcinomas. In conclusion, the penile urethra is covered by epithelial cells that are unique in morphology and immunohistochemical profile. In addition, our study suggests that GATA3 and human papillomavirus detection are useful markers for distinguishing urothelial carcinomas from squamous cell carcinomas of the penile urethra.

  18. Diagnostic Value of Liquid-Based Cytology in Urothelial Carcinoma Diagnosis: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    You Luo

    Full Text Available To evaluate the value of liquid-based cytology (LBC in the diagnosis of urothelial carcinoma.Diagnostic studies were searched for the diagnostic value of LBC in urothelial carcinoma in PubMed, Embase, Cochrane Library, Web of Science, CBM and CNKI. The latest retrieval date was September 2014. The data were extracted and the quality of the included studies was independently assessed by 2 reviewers. Stata 13 software was used to perform the statistical analysis. The research was conducted in compliance with the PRISMA statement.Nineteen studies, which included 8293 patients, were evaluated. The results of the meta-analysis showed that the pooled sensitivity and specificity of LBC were 0.58 (0.51-0.65 and 0.96 (0.93-0.98, respectively. The diagnostic odds ratio (DOR was 31 (18-56 and the area under the curve (AUC of summary receiver operating characteristic (SROC was 0.83 (0.80-0.86. The post-test probability was 80% when a positive diagnosis was made. Compared with high grade urothelial carcinoma (HGUC, the sensitivity of detecting low-grade urothelial carcinoma (LGUC was significantly lower, risk ratio of sensitivity was 0.54 (0.43-0.66, P<0.001. However, no significant sensitivity improvement was observed with LBC when compared with traditional cytospin cytology, risk ratio was 1.03 (0.94-1.14, P = 0.524.Despite LBC having a pooled 58% positive rate for urothelial carcinoma diagnosis in our meta-analysis, no significant improvement in sensitivity was observed based on the studies evaluated. Further research is needed to validate these findings.

  19. Enterovesical fistula caused by a bladder squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chun-Hsiang Ou Yang; Keng-Hao Liu; Tse-Ching Chen; Phei-Lang Chang; Ta-Sen Yeh

    2009-01-01

    Enterovesical fistulas are not uncommon in patients with inflammatory or malignant colonic disease, however,fistulas secondary to primary bladder carcinomas are extremely rare. We herein reported a patient presenting with intractable urinary tract infection due to enterovesical fistula formation caused by a squamous cell carcinoma of the urinary bladder. This patient underwent en bloc resection of the bladder dome and involved ileum, and recovered uneventfully without urinary complaint. To the best of our knowledge, this is the first case reported in the literature.

  20. Patterns of nucleolar organizer region in urinary bladder cancer in view of 2004 WHO classification of urothelial neoplasms

    Directory of Open Access Journals (Sweden)

    Priti Soin

    2012-01-01

    Full Text Available Context: The last decade has seen a tremendous upheaval since introduction of WHO-1998 classification (modified in 2004 of bladder carcinoma, which only recently seems to have settled down. We compare both old (WHO-1973 and new (2004 classifications with argyrophilic nucleolar organizer region (AgNOR score. Aims: To compare WHO/ISUP (World Health Organization/International Society of Urologic Pathologists consensus classification-2004 and WHO-1973 classification of bladder carcinoma and to establish correlation between AgNOR scores and various grades of carcinoma bladder. Materials and Methods: Sixty H and E (Hematoxylin and Eosin stained sections of transitional cell carcinoma bladder were graded according to WHO/ISUP (2004 and WHO (1973 classification systems and the results were compared. This was then followed by AgNOR staining of the paraffin-embedded sections and subsequent AgNOR scores were calculated and given as total score, extranucleolar score, intranucleolar score, and nucleolar score. These were correlated with the grade of the tumor. Statistical Analysis Used: ANOVA test. Results: It was observed that the two grading systems, WHO/ISUP (2004 and WHO (1973 correlated with each other. Also it was observed that the total AgNOR score and extranucleolar AgNOR score increased with the grade of the tumor and thus increasing scores carry significance in assessment of the grade of the tumor. However, intranucleolar and nucleolar scores showed variable degree of overlap in various grades of the bladder tumors. Conclusions: WHO/ISUP (2004 classification correlated well with the WHO (1973 classification. The total AgNOR score was found to be helpful in assessment of the grade of the tumor but the distribution of the AgNOR carried little significance.

  1. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.

    Directory of Open Access Journals (Sweden)

    Cristina Balbás-Martínez

    Full Text Available Urothelial bladder cancer (UBC is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2-20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors (P = 0.05. In a second series (n = 84, we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03 but it is not correlated with p53 overexpression (P = 0.30. We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.

  2. Risk stratification for kidney sparing procedure in upper tract urothelial carcinoma

    Science.gov (United States)

    Khene, Zine-Eddine; Mathieu, Romain; Kammerer-Jacquet, Solène-Florence; Seisen, Thomas; Roupret, Morgan; Shariat, Shahrokh F.; Peyronnet, Benoit

    2016-01-01

    Risk stratification for kidney sparing procedures (KSP) to treat upper tract urothelial carcinoma (UTUC) is a major issue. A non-systematic Medline/PubMed literature search was performed using the terms “upper tract urothelial carcinoma” with different combinations of keywords to review the current knowledge on this topic. Original articles, reviews and editorials in English language were selected based on their clinical relevance. Available techniques for KSP include segmental ureterectomy and endoscopic resection through a percutaneous or flexible ureteroscopic access. These approaches were traditionally restricted to patients with imperative indications. Current recommendations suggest that selected patients with normal contralateral kidney should also be candidates for such treatments. Modern imaging and endoscopy have improved to accurately stage and grade the tumor while various prognostic clinical factors and biomarkers have been proposed to identify tumor with aggressive features and worse outcomes. Several predictive models using different combinations of such baseline characteristics may help clinicians in clinical decision making. However, risk-adapted based approach that has been proposed in recent guidelines to identify patients who are more likely to benefit from KSP only relies on few clinical and pathological factors. Despite growing understanding of the disease, treatment of UTUC remains challenging. Further efforts and collaborative multicenter studies are mandatory to improve risk stratification to decide and promote optimal KSP in UTUC. These efforts should focus on the integration of promising biomarkers and predictive tools in clinical decision making.

  3. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  4. High-grade papillary urothelial carcinoma of the urinary tract: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center.

    Science.gov (United States)

    Chaux, Alcides; Karram, Sarah; Miller, Jeremy S; Fajardo, Daniel A; Lee, Thomas K; Miyamoto, Hiroshi; Netto, George J

    2012-01-01

    About one half of all bladder neoplasms are noninvasive, and in those, the histologic grade is a crucial prognosticator. Few single-center studies have assessed the recurrence, progression, and cancer-related mortality rates of noninvasive high-grade papillary urothelial carcinomas. With this aim, we evaluated the clinicopathologic and outcome features of 85 patients with high-grade papillary urothelial carcinoma. Median age was 68 years, and 80.5% were men. Tumor size ranged from 0.3 to 13.0 cm (median, 1.6 cm). Recurrence was found in 36.5% of the patients, whereas tumor progression, defined as invasion of lamina propria or beyond, was identified in 40% of all cases. When present, lesion reappearance involved mostly 1 to 2 episodes. Metastasis appeared in 20% of the patients, and 15% died of disseminated bladder cancer. All cancer-related deaths occurred in the group of patients with progression, whereas patients with recurrence showed similar outcomes to those with no recurrence. For patients with tumor progression, clinical stage was significantly associated with outcome (P = .002). As for prognosis, tumor size was strongly associated with progression (P < .01). In conclusion, recurrence, progression, and cancer-specific mortality rates were 36.5%, 40%, and 15%, respectively. All the patients who died of cancer had a history of tumor progression. Patients with recurrences showed similar outcomes to those with no recurrence. Tumor size was strongly associated with tumor progression and cancer-specific survival, whereas clinical stage was significantly associated with outcome in the progression group. In light of the high recurrence and progression rates of high-grade papillary urothelial carcinoma, strict clinical surveillance aimed to detect early recurrent lesions, especially in patients with larger tumors, is warranted.

  5. A Giant Pedunculated Urothelial Polyp Mimicking Bladder Mass in a Child: A Rare Case

    Directory of Open Access Journals (Sweden)

    Mehmet Kaba

    2014-01-01

    Full Text Available Ureteral fibroepithelial polyps are rarely seen benign tumors with mesodermal origin. These polyps can involve kidney, pelvis, ureter, bladder, and urethra. The most common symptoms are hematuria and flank pain. The choice of treatment is either endoscopic or surgical resection of polyp by sparing kidney. Here, we presented a pediatric case with giant, fibroepithelial polyp that mimics bladder tumor, originating from middle segment of the ureter.

  6. Rapamycin instead of mycophenolate mofetil or azathioprine in treatment of post-renal transplantation urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    HU Xiao-peng; MA Lin-lin; WANG Yong; YIN Hang; WANG Wei; YANG Xiao-yong; ZHANG Xiao-dong

    2009-01-01

    Background Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin (RPM) in combination with low-dose calcineurin inhibitor (CNI) in treating 15 renal allograft recipients which developed urothelial carcinoma were observed. Methods Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil (MMF) or azathioprine (Aza). The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4-6 ug/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored. Results Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved, with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments. Conclusion Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.

  7. Heat shock protein 70 expression in relation to apoptosis in primary bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Ling-feng; GUAN Kao-peng; YE Hai-yun; REN Liang; YAN Zheng; WANG Shen-wu; HOU Shu-kun

    2005-01-01

    @@ Bladder carcinoma is the most common tumor in the urinary system. In 1996, a sample investigation showed that bladder carcinoma, in which more than 90% was mainly primary bladder transitional cell carcinoma (BTCC), was one of the ten highest mortality malignant tumors in China. Bladder carcinoma represented 2% of all malignant tumors and has the fifth most common malignancy in men in Europe and North America.1

  8. N-Acetylation of p-aminobenzoic acid and p-phenylenediamine in primary porcine urinary bladder epithelial cells and in the human urothelial cell line 5637.

    Science.gov (United States)

    Föllmann, Wolfram; Blaszkewicz, Meinolf; Behm, Claudia; Degen, Gisela H; Golka, Klaus

    2012-01-01

    N-Acetyltransferases (NAT) are important enzymes in the metabolism of certain carcinogenic arylamines, as N-acetylation decreases or prevents their bioactivation via N-hydroxylation. To study such processes in the bladder, cell culture models may be used, but metabolic competence needs to be characterized. This study focused on the N-acetylation capacity of two urothelial cell systems, using p-aminobenzoic acid (PABA) and the hair dye precursor p-phenylenediamine (PPD), two well-known substrates of the enzyme NAT1. The constitutive NAT1 activity was investigated using primary cultures of porcine urinary bladder epithelial cells (PUBEC) and in the human urothelial cell line 5637 to assess their suitability for further in vitro studies on PABA and PPD-induced toxicity. N-Acetylation of PABA and PPD was determined by high-performance liquid chromatography (HPLC) analysis in cytosols of the two cell systems upon incubation with various substrate levels for up to 60 min. The primary PUBEC revealed higher N-acetylation rates (2.5-fold for PABA, 5-fold for PPD) compared to the 5637 cell line, based on both PABA conversion to its acetylated metabolite and formation of mono- and diacetylated PPD. The urothelial cell systems may thus be useful as a tool for further studies on the N-acetylation of aromatic amines via NAT1.

  9. Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines.

    Science.gov (United States)

    Tomlinson, Darren C; L'Hôte, Corine G; Kennedy, Wendy; Pitt, Eva; Knowles, Margaret A

    2005-11-15

    Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that play key roles in proliferation, differentiation, and tumorigenesis. FGFR3 was identified as the major family member expressed in both normal human urothelium and cultured normal human urothelial (NHU) cells and was expressed as the IIIb isoform. We also identified a splice variant, FGFR3 Delta8-10, lacking exons encoding the COOH-terminal half of immunoglobulin-like domain III and the transmembrane domain. Previous reports have assumed that this is a cancer-specific splice variant. We showed that FGFR3 Delta8-10 is a normal transcript in NHU cells and is translated, N-glycosylated, and secreted. Primary urothelium expressed high levels of FGFR3 transcripts. In culture, levels were reduced in actively proliferating cells but increased at confluence and as cells approached senescence. Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Delta8-10. In bladder tumor cell lines derived from aggressive carcinomas, there were significant alterations in the relative expression of isoforms including an overall decrease in the proportion of FGFR3 Delta8-10 and predominant expression of FGFR3 IIIc in some cases. In summary, alternative splicing of FGFR3 IIIb in NHU cells represents a normal mechanism to generate a transcript that regulates proliferation and in bladder cancer, the ratio of FGFR3 isoforms is significantly altered.

  10. Polyoma (BK) virus associated urothelial carcinoma originating within a renal allograft five years following resolution of polyoma virus nephropathy.

    Science.gov (United States)

    Salvatore, Steven P; Myers-Gurevitch, Patricia M; Chu, Stacy; Robinson, Brian D; Dadhania, Darshana; Seshan, Surya V

    2016-03-01

    A direct role for BK polyomavirus infection in malignant tumors of renal allografts and urinary tract is emerging. Case reports suggest a link between BK virus (BKV) reactivation and development of malignancy in renal allograft recipients. Herein we describe the first case of BKV positive invasive urothelial carcinoma within the renal allograft, presenting with chronic diarrhea and weight loss 5 years following resolution of BK viremia/nephropathy (BKVN). Unique to our case was the remote history of BK viremia/BKVN, rising titer of anti-HLA antibody and presence of renal limited urothelial carcinoma with microinvasion of malignant cells staining positive for SV40 large T antigen (T-Ag). These findings suggest that persistence of subclinical BKV infection within the renal allograft may play a role in the malignant transformation of epithelial cells. Patients with history of BKVN may be at risk for kidney and urinary tract malignancy despite resolution of BK viremia/BKVN.

  11. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Nicolas, E-mail: simplissimus@gmx.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de [Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Splittstoesser, Vera, E-mail: Veri.sp@web.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de [Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany); Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  12. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma

    OpenAIRE

    Li, Jun; Wang, Ping; Wang, Bin

    2016-01-01

    Abstract Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma. The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland wi...

  13. Enterovesical Fistula Secondary to Squamous Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Sellers, William; Fiorelli, Robert

    2015-11-01

    Enterovesical fistulas are a well-known complication of inflammatory and malignant bowel disease. Bladder carcinoma, however, is an extremely rare etiology. We describe a case of squamous cell carcinoma of the bladder with an enterovesical fistula. This rare phenomenon has never been previously reported in western literature. We review the diagnosis, work up and treatment of enterovesical fistulas. Unfortunately, the prognosis for these highly invasive tumors is very poor and the treatment is often palliative. The high morbidity and mortality makes management of these patients exceptionally challenging.

  14. Granulocyte-Colony Stimulating Factor Producing Infiltrating Urothelial Carcinoma of the Left Renal Pelvis: A Case Report

    OpenAIRE

    2016-01-01

    We report a case of granulocyte-colony stimulating factor (G-CSF) producing infiltrating urothelial carcinoma of the left renal pelvis. The patient was referred to our hospital for fever and anorexia. Blood tests showed elevated level of leukocytosis without any infectious diseases. The serum concentration of G-CSF was remarkably elevated. Abdominal computed tomography (CT) revealed a huge mass in the left renal pelvis and para-aortic lymph node enlargement. He was underwent left nephroureter...

  15. The differential expression of EphB2 and EphB4 receptor kinases in normal bladder and in transitional cell carcinoma of the bladder.

    Directory of Open Access Journals (Sweden)

    Xiuqing Li

    Full Text Available Effective treatment of transitional cell carcinoma (TCC of the bladder requires early diagnosis. Identifying novel molecular markers in TCC would guide the development of diagnostic and therapeutic targets. Ephrins mediate signals via tyrosine kinase activity that modulates diverse physiologic and developmental processes, and ephrins are increasingly implicated in carcinogenesis. The aim of our study was to examine the differential regulation of EphB4 and EphB2 in normal bladder and in TCC of the bladder in 40 patients undergoing radical cystectomy for curative intent. Immunostaining and Western blotting revealed that normal urothelium expresses EphB2 (20 of 24 cases, 83% of the time not EphB4 (0 of 24 cases, 0%. In sharp contrast, TCC specimens show loss of EphB2 expression (0 of 34 cases, 0% and gain of EphB4 expression (32 of 34, 94%. Furthermore, EphB4 signal strength statistically correlated with higher tumor stage, and trended toward the presence of carcinoma in situ (CIS. These results are confirmed by analysis of normal urothelial and tumor cell lines. EphB2 is not a survival factor in normal urothelium, while EphB4 is a survival factor in TCC. Treatment of bladder tumor xenograft with an EphB4 inhibitor sEphB4-HSA leads to 62% tumor regression and complete remission when combined with Bevacizumab. Furthermore, tissue analysis revealed that sEphB4-HSA led to increased apoptosis, decreased proliferation, and reduced vessel density, implicating direct tumor cell targeting as well as anti-angiogenesis effect. In summary loss of EphB2 and gain of EphB4 expression represents an inflection point in the development, growth and possibly progression of TCC. Therapeutic compounds targeting EphB4 have potential for diagnosing and treating TCC.

  16. Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

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    Shian-Shiang Wang

    Full Text Available BACKGROUND: Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC and the clinicopathological status. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05 than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638 had a 4.75-fold (95% CI = 1.204-18.746 increased risk of invasive cancer. CONCLUSION: The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

  17. Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer.

    NARCIS (Netherlands)

    Hendricksen, K.; Cornel, E.B.; Reijke, T.M. de; Arentsen, H.C.; Chawla, S.; Witjes, J.A.

    2012-01-01

    PURPOSE: We studied the safety and efficacy of multiple adjuvant apaziquone instillations in patients with high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Patients with high risk nonmuscle invasive urothelial carcinoma of the bladder underwent transurethral resection of all bladd

  18. Urothelial atypia and survival rate of 500 unselected patients with primary transitional-cell tumour of the urinary bladder

    DEFF Research Database (Denmark)

    Rosenkilde Olsen, P; Wolf, H; Schroeder, T

    1988-01-01

    were taken at the initial cystoscopy in 391 patients (78%) to identify urothelial atypia. The over-all cumulative 5 years survival-rate was 48%. Submucosal and muscle invasion had major influence on survival, whereas tumour grade was less important. Patients with urothelial atypia fared significantly...

  19. MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1

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    Olsson Hans

    2013-01-01

    Full Text Available Abstract Background Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors. Methods After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression. Results Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038. Conclusions MDM2 SNP309 promoter polymorphism and mutations in

  20. Bladder tumours in children: An interesting case report of TCC with a partial inverted growth pattern.

    Science.gov (United States)

    El Rahman, Davide Abed; Salvo, Giuseppe; Palumbo, Carlotta; Rocco, Bernardo; Rocco, Francesco

    2014-09-30

    Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic and prognostic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. We report on a 16 years old girl with transitional cell carcinoma of the bladder with a partial inverted growth pattern who presented with gross hematuria. Ultrasonography revealed a papillary lesion in the bladder; cystoscopic evaluation showed a 15 mm papillary lesion with a thick stalk located in the left bladder wall. Pathologic evaluation of the specimen was reported as "low grade transitional cell carcinoma of the bladder with a partial inverted growth pattern".

  1. Deficiency of pRb family proteins and p53 in invasive urothelial tumorigenesis.

    Science.gov (United States)

    He, Feng; Mo, Lan; Zheng, Xiao-Yong; Hu, Changkun; Lepor, Herbert; Lee, Eva Y-H P; Sun, Tung-Tien; Wu, Xue-Ru

    2009-12-15

    Defects in pRb tumor suppressor pathway occur in approximately 50% of the deadly muscle-invasive urothelial carcinomas in humans and urothelial carcinoma is the most prevalent epithelial cancer in long-term survivors of hereditary retinoblastomas caused by loss-of-function RB1 mutations. Here, we show that conditional inactivation of both RB1 alleles in mouse urothelium failed to accelerate urothelial proliferation. Instead, it profoundly activated the p53 pathway, leading to extensive apoptosis, and selectively induced pRb family member p107. Thus, pRb loss triggered multiple fail-safe mechanisms whereby urothelial cells evade tumorigenesis. Additional loss of p53 in pRb-deficient urothelial cells removed these p53-dependent tumor barriers, resulting in late-onset hyperplasia, umbrella cell nuclear atypia, and rare-occurring low-grade, superficial papillary bladder tumors, without eliciting invasive carcinomas. Importantly, mice deficient in both pRb and p53, but not those deficient in either protein alone, were highly susceptible to subthreshold carcinogen exposure and developed invasive urothelial carcinomas that strongly resembled the human counterparts. The invasive lesions had a marked reduction of p107 but not p130 of the pRb family. Our data provide compelling evidence, indicating that urothelium, one of the slowest cycling epithelia, is remarkably resistant to transformation by pRb or p53 deficiency; that concurrent loss of these two tumor suppressors is necessary but insufficient to initiate urothelial tumorigenesis along the invasive pathway; that p107 may play a critical role in suppressing invasive urothelial tumor formation; and that replacing/restoring the function of pRb, p107, or p53 could be explored as a potential therapeutic strategy to block urothelial tumor progression.

  2. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    Directory of Open Access Journals (Sweden)

    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  3. Parafibromin Staining Characteristics in Urothelial Carcinomas and Relationship with Prognostic Parameters

    Science.gov (United States)

    Karaarslan, Serap; Yaman, Banu; Ozturk, Hakan; Kumbaraci, Banu Sarsik

    2015-01-01

    Background: Parafibromin is a recently defined tumor suppressor gene. The aim of our study was to determine the relationships of parafibromin expression in urothelial carcinomas (UCs) with prognostic parameters and to evaluate the use of parafibromin as a potential marker of UC. Methods: Parafibromin expression was assessed in 49 UC specimens using immunohistochemistry. The correlations between parafibromin expression and clinical and pathologic parameters were investigated. Results: Of the patients, 42 (85.7%) were male, and the mean age was 69.6 ± 8.2 years (range, 54 to 88 years). Morphologically, the UCs were divided into two groups: papillary (n = 27) and non-papillary (n = 22). There were seven low-grade (14.3%) and 42 high-grade (85.7%) tumors. Parafibromin was negative in 13 tumors (26.5%), partially positive in 19 tumors (38.8%), and positive in 17 tumors (34.7%). Parafibromin expression was more negative in UCs from upper urinary locations (n=17) and with muscularis propria invasion (n=28), which was statistically significant (p = .009 and p = .007, respectively). There was no statistically significant relationship between parafibromin expression and gender, age, tumor grade, survival, or disease-free survival. Conclusions: We found that UC cases with parafibromin positivity had less of a tendency to show muscularis propria invasion and were more commonly located in the lower urinary system. These results need to be confirmed with studies based on larger case series. PMID:26395176

  4. Pro- and Antiapoptotic Markers in Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy

    Science.gov (United States)

    Jankovic-Velickovic, Ljubinka; Stojnev, Slavica; Ristic-Petrovic, Ana; Dolicanin, Zana; Hattori, Takanori; Mukaisho, Kenichi; Stojanovic, Mariola; Stefanovic, Vladisav

    2011-01-01

    The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper-tract urothelial carcinoma (UTUC) has been recently confirmed. The aim of this study was to determine apoptosis-related marker(s) specific for BEN-associated UTUC. Present investigation included 105 patients with UTUC, 44 from BEN region and 61 control tumors. Altered expression of Survivin was more often present in BEN UTUC with high grade and solid growth (P < 0.005; P < 0.05) than in control tumors. Significantly lower expression of proapoptotic marker Bax was found in BEN tumors with high grade, high stage, necrosis, and without metaplastic change (P < 0.05; 0.05; 0.05; 0.05) compared to control tumors with the same features. Group (BEN-related/control), stage, growth pattern, and caspase 3 activity were significantly associated with the expression of Bax (P = 0.002, 0.034, 0.047, 0.028, resp.,). This investigation identifies Bax as specific marker of BEN-associated UTUC. Decrease of pro-apoptotic protein Bax together with alteration of Survivin may be indicative for specific disturbances of intrinsic apoptotic pathway in UTUC arising in endemic areas. PMID:22125429

  5. Urothelial carcinoma with oncocytic features: an extremely rare case presenting a diagnostic challenge in urine cytology.

    Science.gov (United States)

    Tajima, Shogo

    2015-01-01

    Recognizing histological variants in urothelial carcinoma (UC) is important because some may be associated with different clinical outcomes and/or therapeutic approaches; being aware of unusual histological variants may also be crucial in preventing diagnostic misinterpretations. Histological variants based on cytoplasmic features, such as clear-cell, plasmacytoid, rhabdoid, and lipoid-rich variants, are described in invasive UC; however, these cytoplasmic features are not formally defined and not usually encountered in non-invasive UC. Oncocytic cytoplasm has not been well described in either invasive or non-invasive UC. Herein, we report an exceedingly rare case of UC with oncocytic features arising in the right renal pelvis, which presented a diagnostic challenge in urine cytology due to the relatively low nuclear-to-cytoplasmic ratio; however, it could definitively be diagnosed using histological specimens. UC diagnosis is based on the presence of papillary architecture and widespread p53 nuclear accumulation, suggesting malignancy. An oncocytic tumor is generally considered to be not actively dividing, as shown by the low Ki-67 labeling index in this case. In spite of the low proliferative activity, the possibility of intravesicle recurrence (IVR) should be considered since positive preoperative cytology of upper tract UC is a risk factor for IVR after nephroureterectomy.

  6. XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Chien-I [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Chen, Wei-Jen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-09-15

    The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on

  7. Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis

    Science.gov (United States)

    Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

    2017-01-01

    The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83–2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59–2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76–2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction. PMID:28182725

  8. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten;

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and SOX4-induced pathways, we used a time-course global expression study of the overexpressed SOX4. Analysis of the microarray data showed 130 novel SOX4-related genes, some involved in signal transduction (MAP......2K5), angiogenesis (NRP2), and cell cycle arrest (PIK3R3) and others with unknown functions (CGI-62). Among the genes regulated by SOX4, 25 contained at least one SOX4-binding motif in the promoter sequence, suggesting a direct binding of SOX4. The gene set identified in vitro was analyzed...

  9. A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma.

    Science.gov (United States)

    Wang, Liqin; Šuštić, Tonći; Leite de Oliveira, Rodrigo; Lieftink, Cor; Halonen, Pasi; van de Ven, Marieke; Beijersbergen, Roderick L; van den Heuvel, Michel M; Bernards, René; van der Heijden, Michiel S

    2017-01-17

    Activating mutations and translocations of the FGFR3 gene are commonly seen in urothelial cell carcinoma (UCC) of the bladder and urinary tract. Several fibroblast growth factor receptor (FGFR) inhibitors are currently in clinical development and response rates appear promising for advanced UCC. A common problem with targeted therapeutics is intrinsic or acquired resistance of the cancer cells. To find potential drug targets that can act synergistically with FGFR inhibition, we performed a synthetic lethality screen for the FGFR inhibitor AZD4547 using a short hairpin RNA library targeting the human kinome in the UCC cell line RT112 (FGFR3-TACC3 translocation). We identified multiple members of the phosphoinositide 3-kinase (PI3K) pathway and found that inhibition of PIK3CA acts synergistically with FGFR inhibitors. The PI3K inhibitor BKM120 acted synergistically with inhibition of FGFR in multiple UCC and lung cancer cell lines having FGFR mutations. Consistently, we observed an elevated PI3K-protein kinase B pathway activity resulting from epidermal growth factor receptor or Erb-B2 receptor tyrosine kinase 3 reactivation caused by FGFR inhibition as the underlying molecular mechanism of the synergy. Our data show that feedback pathways activated by FGFR inhibition converge on the PI3K pathway. These findings provide a strong rationale to test FGFR inhibitors in combination with PI3K inhibitors in cancers harboring genetic activation of FGFR genes.

  10. A rare bladder cancer - small cell carcinoma: review and update

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

  11. Contemporary Evaluation and Management of Upper Tract Urothelial Cancer.

    Science.gov (United States)

    Mandalapu, Rao S; Matin, Surena F

    2016-08-01

    Radical nephroureterectomy with en bloc bladder cuff excision and regional lymphadenectomy is the gold standard for the management of high-grade and high-risk upper tract urothelial carcinomas. There are a few prospective randomized controlled studies in this uncommon and often aggressive disease to support level-1 management guidelines. However, recent developments in imaging, minimally invasive techniques, lymphatic dissemination, and bladder cancer prevention raise the hope for improved risk stratification and treatments without compromising, and hopefully improving, oncological outcomes. Multimodality approaches in terms of neoadjuvant, adjuvant topical, and systemic chemotherapeutic regimens are promising, with 2 prospective trials either open or in development.

  12. Expression and Clinicopathologic Significance of EpCAM and E-Cadherin in Urothelial Carcinoma of Renal Pelvis%肾盂癌中EpCAM和E-Cadherin的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    单立平; 卜仁戈; 张墨; 李波; 吴斌; 宋永胜

    2012-01-01

    Objective To investigate the pmgnostic value of EpCAM and E-Cadherin in urothelial carcinoma of rpnal pelvis. Methods Ep-CAM and E-Cadherin were analyzed by immunohistochemistry using monoclonal antiliodies in 50 cases of normal mucosa and 76 cases of urothelial carcinoma of renal pelvis. Results The positive rate of EpCAM in urothelial carcinoma of renal pelvis was 60.5% .which was significantly higher than in para-cancerous mucosa of 27.6%. The expression of EpCAM was significantly related with the differential clinical stage,pathological degree,distant metastasis and bladder tumor recurrence (all P< 0.05). The expression of E-Cadherin was significantly re-lated with the differential clinical stage,pathological degree and distant metastasis (all P < 0.05). There was negative correlation between the expression of EpCAM and E-Cadherin in urothelial carcinoma of renal pelvis ( r =-0.425,P < 0.01). Conclusion The expression EpCAM and E-Cadherin are highly related to occurrence,development,infiltration and metastasis of urothelial carcinoma of renal pelvis,and evaluation of the two proteins could be a very applicable guidance for the diagnosis of metastasis and invasion of urothelial carcinoma of renal pelvis.%目的 探讨EpCAM和E-Cadherin的表达与肾盂癌病理分级和临床分期的关系.方法 应用免疫组织化学SP法检测76例不同级别肾盂癌和50例癌旁正常组织中EpCAM和E-Cadherin的表达.结果 EpCAM在肾盂癌阳性表达率为60.5%(46/76),明显高于癌旁组织27.6%(21/76),差异具有统计学意义(P<0.05);EpCAM的表达与肾盂癌不同临床分期、病理分级、远处转移及继发膀胱肿瘤相关(P<0.05);EpCAM与E-Cadherin在肾盂癌中表达呈负相关(r=-0.425,P< 0.01).结论 EpCAM及E-Cadherin的表达变化与肾盂癌的发生发展、浸润转移有良好的相关性,同步检测二者在肾盂癌组织中的表达并综合分析两者之间的关系对评价肾盂癌的侵袭转移能力判断具有一定价值.

  13. Pathology of epithelial tumors & carcinoma in situ of bladder.

    Science.gov (United States)

    Mostofi, F K; Sesterhenn, I A

    1984-01-01

    We have reviewed the World Health Organization International Histological Classification of Tumors of Urinary Bladder. The classification recognizes papilloma as a distinct entity, which, although histologically benign, has a definite increased risk of progression to carcinoma. The classification further characterizes carcinomas of bladder in terms of certain features which have considerable influence on treatment, recurrence and prognosis. These are: the patterns of growth, the histology of the tumor, the grade, the pathological stage, the mode and location of spread, and the status of the remaining mucosa. We have called attention to the need for proper recognition of nonpapillary, noninvasive superficial mucosal lesions which have hitherto been dismissed as atypia and dysplasia. We have demonstrated that these lesions present a high risk for development of invasive carcinoma and recommended that the term "intraepithelial neoplasia" be employed and graded one to three to eliminate the use of terms atypia, dysplasia and CIS. We have emphasized the need for development of technics to demonstrate invasive and metastatic potential of epithelial tumors of bladder.

  14. A retrospective study of post-operative gall bladder pathology with special reference to incidental carcinoma of the gall bladder

    OpenAIRE

    Jagannath Dev Sharma; Indrajit Kalita; Tonmoy Das; Papari Goswami; Manigreeva Krishnatreya

    2014-01-01

    Background: Surgical removal of gall bladder for its diseases is common. However, not much is known about the incidence of incidental carcinoma in such patients in our population. Objective of current study was to analyze the different pathological entities of post-operative gall bladder specimen with particular emphasis on incidental carcinoma. Methods: This retrospective study was carried out at a multi-specialty hospital in eastern India from the pathology records for the period from Au...

  15. Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

    Directory of Open Access Journals (Sweden)

    Chai Karl X

    2009-10-01

    Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

  16. 荧光原位杂交应用于尿路上皮癌尿液早期诊断的研究进展%Advances of Early Diagnosis of Urothelial Carcinoma Urine by Fluorescence in Situ Hybridization

    Institute of Scientific and Technical Information of China (English)

    邱晓拂; 胡卫列

    2011-01-01

    Urothelial carcinoma is one of the most common urinary malignant tumors. Early diagnosis is important for its treatment. FISH diagnoses UC by urine, which is a fast, no traumatic, and high sensitivity and specificity. This article reviews the clinical application research reports about fish in bladder UC, upper urinary tract UC and monitoring after transurethral resection of bladder tumor. Authors make some conclusions, Fish increases the sensitivity and specificity of urinary cytology in lower grade or superficial bladder UC and decreases false positive caused by hematuria, urinary tract infection and perfusion bladder. FISH has higher the sensitivity and specificity in upper urinary tract UC. The loss of p16 anti-oncogene in 9 chromosome is related to recurrence of the bladder UC. FISH not only predict the recurrence but also monitor the recurrence, and it needs large and multicenter prospective study.%尿路上皮癌(urothelial carcinoma,UC)是泌尿系统最常见恶性肿瘤之一,早期诊断是提高该类疾病疗效的关键所在,荧光原位杂交(fluorescence in situ hybrization,FISH)通过尿液来检测UC,具有快速、无创伤性、敏感度高和特异性强等优点.FISH提高了尿细胞学在低级别或浅表性膀胱UC诊断的敏感性,且减少了血尿、尿路感染及膀胱内灌注治疗等对细胞形态的影响而引起的假阳性,提高检测的特异性.对于诊断上尿路UC,FISH的敏感性与特异性更高.膀胱UC患者9号染色体p16抑癌基因丢失与复发明显相关,FISH既能预测膀胱UC的复发性,更能监测UC的复发,但仍需大样本、多中心的前瞻性研究.本文将FISH在膀胱UC、上尿路 UC早期诊断以及膀胱UC术后监测等方面的临床应用研究报道进行综述.

  17. Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients.

    Directory of Open Access Journals (Sweden)

    Alyaa M Abdel-Haleem

    Full Text Available Urinary bladder cancer (UBC ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1 is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; P<0.0001 in bladder tumor specimens relative to normal bladder mRNA. RFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; p<0.05 where median RFC mRNA expression was significantly (p<0.05 higher in the urothelial (∼14-fold compared to the non-urothelial (∼4-fold variant. This may account for the variation in response to antifolate-containing regimens used in the treatment of either type. RFC mRNA levels were not associated with tumor grade (I, II and III or stage (muscle-invasive vs. non-muscle invasive implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas.

  18. Primary osteosarcoma of bladder diverticulum mimicking intradiverticular calculus: a case report

    OpenAIRE

    2011-01-01

    Abstract There is a well-documented relationship between urinary bladder diverticula and intradiverticular neoplasms. The great majorities of these tumors are urothelial carcinomas, but may also be of glandular or squamous type. Sarcomas occurring within bladder diverticula are exceptionally rare and highly malignant lesions, with only 20 well documented cases published in the literature to date (including carcinosarcomas). We report a case of osteosarcoma of the bladder diverticulum in a 68-...

  19. Genome-wide methylation profiling and the PI3K-AKT pathway analysis associated with smoking in urothelial cell carcinoma

    NARCIS (Netherlands)

    Brait, Mariana; Munari, Enrico; LeBron, Cynthia; Noordhuis, Maartje G.; Begum, Shahnaz; Michailidi, Christina; Gonzalez-Roibon, Nilda; Maldonado, Leonel; Sen, Tanusree; Guerrero-Preston, Rafael; Cope, Leslie; Parrella, Paola; Fazio, VitoMichele; Ha, Patrick K.; Netto, George J.; Sidransky, David; Hoque, Mohammad O.

    2013-01-01

    Urothelial cell carcinoma (UCC) is the second most common genitourinary malignant disease in the USA, and tobacco smoking is the major known risk factor for UCC development. Exposure to carcinogens, such as those contained in tobacco smoke, is known to directly or indirectly damage DNA, causing muta

  20. Gall bladder carcinoma with ampullary carcinoma: A rare case of double malignancy

    Directory of Open Access Journals (Sweden)

    Praveer Rai

    2013-01-01

    Full Text Available Simultaneous double cancers in the biliary system are rare. Most are associated with pancreaticobiliary maljunction (PBM. However, it can occur in patients without PBM. Differentiation between these events is important since these two mechanistic origins imply different stages of disease, as well as different subsequent treatments and prognoses. Herein, we report a case of ampullary carcinoma associated with gall bladder carcinoma diagnosed nonoperatively and palliated with biliary metal stenting.

  1. Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3-CK20/CD44s/p53) and α-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia.

    Science.gov (United States)

    Aron, Manju; Luthringer, Daniel J; McKenney, Jesse K; Hansel, Donna E; Westfall, Danielle E; Parakh, Rugvedita; Mohanty, Sambit K; Balzer, Bonnie; Amin, Mahul B

    2013-12-01

    Urothelial carcinoma in situ (CIS) is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions especially in the setting of prior therapy. Various markers including CK20, CD44s, and p53 have been used as an adjunct in making this distinction; however, the utility of these markers in the posttreatment scenario is not fully established. α-Methylacyl-CoA racemase (AMACR) is a tumor-associated marker that is expressed in a subset of high-grade urothelial carcinomas but has not been studied in CIS. This study was undertaken to evaluate the immunoreactivity of CK20, CD44s, and p53 as a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3) in distinguishing CIS from its mimics and to compare its utility with AMACR in the diagnosis of CIS. A total of 135 specimens (7 benign ureters and 128 bladder biopsies-28 reactive, 33 posttherapy reactive, 43 CIS, 24 CIS posttherapy) were included in this study. Immunostaining for p53 (brown, nuclear), CD44s (brown, membranous), and CK20 (red, cytoplasmic and membranous) was performed as a cocktail, and the staining pattern was further classified as: malignant (full-thickness CK20 and/or full-thickness p53 with CD44s negativity), reactive/benign (CK20 limited to the umbrella cell layer, p53 negative, and CD44s positivity ranging from basal to full thickness), and indeterminate (CK20 and p53 positive but not full thickness and/or CD44s positive). AMACR staining was performed in 50 cases. Cytoplasmic staining for AMACR was graded as negative (absent to weak focal staining [<5% cells]) and positive (≥5%). The "IUN-3 malignant" pattern was observed in 84% of cases of CIS without a history of prior therapy and in 71% of the cases of CIS with a history of prior therapy. Cases with posttherapy reactive atypia showed an "IUN-3 reactive" pattern in 84% cases and "IUN-3 indeterminate" pattern in 16% of the cases; the IUN-3 malignant pattern was not identified in any of the

  2. Productive infection of bovine papillomavirus type 2 in the urothelial cells of naturally occurring urinary bladder tumors in cattle and water buffaloes.

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    Sante Roperto

    Full Text Available BACKGROUND: Papillomaviruses (PVs are highly epitheliotropic as they usually establish productive infections within squamous epithelia of the skin, the anogenital tract and the oral cavity. In this study, early (E and late (L protein expression of bovine papillomavirus type 2 (BPV-2 in the urothelium of the urinary bladder is described in cows and water buffaloes suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. METHODS AND FINDINGS: E5 protein, the major oncoprotein of the BPV-2, was detected in all tumors. L1 DNA was amplified by PCR, cloned and sequenced and confirmed to be L1 DNA. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection was detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the neoplastic urothelium. Finally, the early protein E2, required for viral DNA replication and known to be a pivotal factor for both productive and persistent infection, was detected by Western blot and immunohistochemically. Electron microscopic investigations detected electron dense particles, the shape and size of which are consistent with submicroscopic features of viral particles, in nuclei of neoplastic urothelium. CONCLUSION: This study shows that both active and productive infections by BPV-2 in the urothelium of the bovine and bubaline urinary bladder can occur in vivo.

  3. Transitional cell carcinoma of the bladder in children: radiologic appearance and differential diagnosis.

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    Quillin, S P; McAlister, W H

    1991-01-01

    Primary epithelial tumors of the bladder are rare in children. We report a case of transitional cell carcinoma (TCCa) of the bladder in a 10-year-old boy who was evaluated with intravenous urography, ultrasonography, and computed tomography (CT). The radiographic appearance and a differential diagnosis are discussed. The literature of TCCa of the bladder in children is reviewed.

  4. Meningeal carcinomatosis: an extremely rare involvement of urinary bladder carcinoma.

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    Uncu, Dogan; Arpaci, Fikret; Beyzadeoglu, Murat; Gunal, Armagan; Surenkok, Serdar; Ozturk, Mustafa; Ozet, Ahmet

    2010-01-01

    Meningeal carcinomatosis (MC) is a rare presentation of solid tumors, particularly breast cancer, lung cancer, and malignant melanoma. Recently, the incidence of MC has been reported to be increasing. It has a bad prognosis despite aggressive therapy. The usual clinical presentation is multifocal involvement of the neuraxis, with headache and radicular pain being the most common initial symptoms. The most frequent signs are motor deficits, altered mental status, and cranial nerve involvement. The treatment of MC remains controversial and no straightforward guidelines exist in the literature. MC from urinary bladder tumors is rare. In this case report, we present a 52-year-old male patient with meningeal metastasis from a primary urinary bladder carcinoma along with a review of the related literature. Free full text available at www.tumorionline.it

  5. Recurrence patterns of bladder transitional cell carcinoma after radical cystectomy

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    Kim, Bohyun; Choi, Hyuck Jae; Kim, Mi-hyun; Cho, Kyung-Sik [Dept. of Radiology, Asan Medical Center, Univ. of Ulsan, Seoul (Korea, Republic of); E-mail: choihj@amc.seoul.kr

    2012-10-15

    Background Multidetector computed tomography (MDCT) is widely accepted as an effective imaging modality in monitoring for bladder cancer recurrence after radical cystectomy. Elucidating the pattern of bladder cancer recurrence on CT can increase the diagnostic accuracy. Purpose To evaluate the recurrence patterns of transitional cell carcinoma of the bladder and the factors associated with cancer recurrence. Material and Methods One hundred and forty-nine consecutive patients (mean age, 66.55 years; range, 32-86 years) who underwent preoperative contrast-enhanced CT and radical cystectomy were included in this study. The presence, site, and time of tumor recurrence were recorded retrospectively by two radiologists in a consensus fashion. The association of tumor recurrence and tumor factors (T stage, lymph node metastasis, nuclear grade, and tumor diameter) were also evaluated using multiple logistic regression analysis and Kaplan-Meier statistics. Results Tumor recurrence occurred in 60 patients (40.3%) with a mean time of 14 months (range, 1-64 months). The sites of recurrence included the operation site (n = 20), lymph node (n = 20), bone (n = 11), liver (n = 6), lung (n = 5), upper urinary tract (n = 4), colon (n = 3), adrenal gland (n = 2), peritoneum (n = 1), abdominal wall (n = 1), psoas muscle (n = 1), and penile skin (n = 1). Tumor recurrence was found to be associated with advanced T stage (P = 0.002) and lymph node metastasis (P < 0.001). Conclusion Transitional cell carcinomas of the bladder recur more frequently at the operation site and lymph node, and T-stage and lymph node metastasis are closely associated with tumor recurrence.

  6. Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells.

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    Imani, Roghayeh; Veranič, Peter; Iglič, Aleš; Kreft, Mateja Erdani; Pazoki, Meysam; Hudoklin, Samo

    2015-03-01

    The differentiation of urothelial cells results in normal terminally differentiated cells or by alternative pathways in low-grade or high-grade urothelial carcinomas. Treatments with traditional surgical and chemotherapeutical approaches are still inadequate and expensive, as bladder tumours are generally highly recurrent. In such situations, alternative approaches, using irradiation of the cells and nanoparticles, are promising. The ways in which urothelial cells, at different differentiation levels, respond to UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and nanoparticles (photocatalytic treatment), are unknown. Here we tested cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii) human low-grade urothelial cancer cells (RT4), and (iii) human high-grade urothelial cancer cells (T24). The results have shown that 1 minute of UV-irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as determined by the live/dead viability assay. On the other hand, the majority of T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV-irradiation for 30 minutes killed TiO2 microbeads and then UV-irradiated, the viability of these high-grade urothelial cancer cells was reduced to TiO2 photocatalysis. Using electron microscopy, we confirmed that the mesoporous TiO2 microbeads were internalized into T24 cells, and that the cell's ultrastructure was heavily compromised after UV-irradiation. In conclusion, our results show major differences in the sensitivity to UV-irradiation among the urothelial cells with respect to cell differentiation. To achieve an increased cytotoxicity of urothelial cancer cells, the photocatalytic approach is recommended.

  7. Nonmuscle invasive bladder cancer:a primer on immunotherapy

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    Mahir Maruf; Sam J. Brancato; Piyush K. Agarwal

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer.

  8. Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.

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    Alexander S Baras

    Full Text Available The 5-year cancer specific survival (CSS for patients with muscle invasive urothelial carcinoma of the bladder (MIBC treated with cystectomy alone is approximately 50%. Platinum based neoadjuvant chemotherapy (NAC plus cystectomy results in a marginal 5-10% increase in 5-year CSS in MIBC. Interestingly, responders to NAC (

  9. HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

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    Liang Peir-In

    2012-12-01

    Full Text Available Abstract Background HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs. Methods In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS, metastasis-free survival (MeFS, urinary bladder recurrence-free survival (UBRFS, and various clinicopathological factors. Results HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005. Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p p p = 0.0370 in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS. Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035 and MeFS (p = 0.0015 in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015. Conclusions HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive

  10. Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.

    Science.gov (United States)

    Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K

    2014-05-01

    Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.

  11. Relationship of Ki67, TP53, MDM-2 and BCL-2 expressions with WHO 1973 and WHO/ISUP grades, tumor category and overall patient survival in urothelial tumors of the bladder.

    Science.gov (United States)

    Gönül, Ipek Işik; Akyürek, Nalan; Dursun, Ayşe; Küpeli, Bora

    2008-01-01

    Using the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) (2004 WHO), 1999 WHO/ISUP, and 1973 WHO classifications, we examined Ki67, BCL-2, TP53, and MDM-2 expressions in invasive and noninvasive urothelial neoplasias of the bladder of 72 patients, and compared the results regarding tumor category and grade with clinical outcome to determine the clinicopathological relevance of these classifications. Ki67 and TP53 expressions were correlated with tumor grades of the 1973 WHO classification, and they also distinguished "papillary urothelial neoplasm with low malignant potential" from other WHO/ISUP grades (p ISUP grades (p > 0.05). Neither tumor grade nor tumor category correlated with MDM-2 or BCL-2 expressions (p > 0.05). WHO/ISUP classifications are obviously not superior to the 1973 WHO classification for grading urothelial neoplasia of the bladder. However, if the "papillary urothelial neoplasm with low malignant potential" is distinguished from grade 1 tumors of the 1973 WHO classification, more precise prognostic information may be obtained.

  12. Changing trends in the management of small cell carcinoma of urinary bladder

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    Anshuma Bansal

    2015-01-01

    Full Text Available Small cell carcinoma (SCC of the urinary bladder is a rare presentation, accounting for <1% of all bladder carcinomas. It has been considered as an aggressive variant of bladder carcinoma, with high incidence of distant relapse. Though cisplatin-based chemotherapy is considered the gold standard approach for this variety of bladder tumor, the role of radical cystectomy and radiotherapy cannot be neglected, due to its frequent association with transitional cell carcinoma. Different management strategies have been adopted by oncologists worldwide, in an effort to obtain survival benefits. Recently, neoadjuvant chemotherapy before surgery has been tried and the results are encouraging. This review article particularly focuses on the treatment evolution of SCC of bladder, various treatment options and their effects on the outcome, so that an optimal management can be planned for individual cases.

  13. Lymphoepithelioma - like carcinoma of the bladder in a North African man: A case report

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    Amel Trabelsi

    2009-01-01

    Full Text Available Context: Lymphoepithelioma - like carcinoma of the bladder is an extremely rare tumour. We discuss through a new case and a review of the literature the pathological pattern and the management of this uncommon entity. Case report: We report the case of a 58 year-old man who presented with a macroscopic hematuria. Transurethral bladder resection was consistent with the diagnostic of a poorly differentiated carcinoma infiltrating the bladder′s muscle. A radical cysto-prostatectomy was performed. The pathological examination revealed an EBV negative lymphoepithelioma-like carcinoma of the bladder. Conclusion : Lymphoepithelioma-like carcinoma of the bladder is a rare bladder cancer that is important to recognize since it has a favourable prognosis.

  14. OPIUM USE IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER

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    A. Nourbakhsh

    2006-08-01

    Full Text Available Opium use is one of the most common forms of substance abuse in Iran and there are some evidence indicating it is a risk factor of transitional cell carcinoma (TCC of the urinary bladder. The majority of opium users are also cigarette smokers, so consideration of the high prevalence of smoking which is the most important risk factor of TCC of the urinary bladder among opium users is essential to assess the role of opium use as a possible risk factor of TCC. This study was done to evaluate the role of opium as a risk factor of TCC. A case-control study was performed on 255 individuals diagnosed with TCC of the urinary bladder by pathologic light microscopic examination of the tumor biopsies. Control population was chosen from individuals who had no history or presenting signs or symptoms of urinary problems. Case and control groups were matched by sex and age and also by cigarette smoking habits. Forty-one (18.1% of the cases and 12 (5% of controls were recognized to be opium users. Mantel-Haenszel analysis showed an odds ratio of 3.88, with 95% confidence interval of 1.99-7.57 and P value of < 0.001. Results indicate that opium use is a risk factor for TCC. The majority of opium users are also cigarette smokers, which is another important risk factor for TCC. Routine urine cytology and early evaluation in the patients presenting with any of the symptoms of urinary bladder malignancy by means of cystoscopy and urine cytology are highly recommended.

  15. Chinese herbs containing aristolochic acid associated with renal failure and urothelial carcinoma: a review from epidemiologic observations to causal inference.

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    Yang, Hsiao-Yu; Chen, Pau-Chung; Wang, Jung-Der

    2014-01-01

    Herbal remedies containing aristolochic acid (AA) have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure in Taiwan, occupational exposure in Chinese herbalists, and food contamination in farming villages in valleys of the Danube River. Such an association is corroborated by detecting specific DNA adducts in the tumor tissue removed from affected patients. Preventive actions of banning such use and education to the healthcare professionals and public are necessary for the safety of herbal remedies.

  16. Chinese Herbs Containing Aristolochic Acid Associated with Renal Failure and Urothelial Carcinoma: A Review from Epidemiologic Observations to Causal Inference

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    Hsiao-Yu Yang

    2014-01-01

    Full Text Available Herbal remedies containing aristolochic acid (AA have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure in Taiwan, occupational exposure in Chinese herbalists, and food contamination in farming villages in valleys of the Danube River. Such an association is corroborated by detecting specific DNA adducts in the tumor tissue removed from affected patients. Preventive actions of banning such use and education to the healthcare professionals and public are necessary for the safety of herbal remedies.

  17. Expression of pRb, p53, p16 and cyclin D1 and their clinical implications in urothelial carcinoma.

    Science.gov (United States)

    Lee, Kyungji; Jung, Eun Sun; Choi, Young-Jin; Lee, Kyo Young; Lee, Ahwon

    2010-10-01

    The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.

  18. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  19. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-08-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  20. A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer.

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    Jialou Zhu

    Full Text Available BACKGROUND: DNA methylation aberration and microRNA (miRNA deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. METHODOLOGY/PRINCIPAL FINDINGS: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17 by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. CONCLUSIONS/SIGNIFICANCE: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.

  1. The bladder carcinoma secondary to schistosoma mansoni infection: A case report with review of the literature

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    Murat Can Kiremit

    2015-01-01

    Conclusion: Regarding the increasing travels all around the world, clinicians should remember that Schistosoma infection is certainly a part of the differential diagnosis of bladder carcinoma, even if the patients are not from endemic regions.

  2. Small cell carcinoma of the urinary bladder: Virtual CT cystoscopic findings

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    Tsili A

    2009-01-01

    Full Text Available A 74-year-old man underwent multidetector CT virtual cystoscopy due to macroscopic hematuria. A large, irregularly-surfaced, solid bladder mass was detected, infiltrating the perivesical fat, the seminal vesicles and the prostate. CT examination of the chest and abdomen showed no distant metastases. Radical cystectomy was performed and pathology reported pure small cell carcinoma of the urinary bladder.

  3. Expression of Hpa and CD222 in bladder carcinoma and analysis of clinico-pathologic correlation

    Institute of Scientific and Technical Information of China (English)

    Shuhong Shi; Hui Zhang

    2014-01-01

    Objective:Our study aimed to investigate the relationships between the clinico-pathologic features and the hepa-ranase (Hpa) and CD222 expressions in bladder carcinoma. Methods:The expressions of Hpa and CD222 in 95 bladder carcinoma specimens and 20 paraneoplastic bladder tissues (controls) were assessed using the immunohistochemical stain-ing method. Results:The positive expression rates of Hpa and CD222 in bladder carcinoma were 68.42%and 61.05%, respectively. The positive rate of Hpa was significantly higher in the carcinoma specimens than in the control specimens (P<0.01). Similarly, the Hpa expression in the invasive bladder carcinoma was significantly higher than that in the non-invasive bladder carcinoma (P<0.01). A positive correlation was observed between the expressions of Hpa and CD222 (P<0.05). The expressions of Hpa and CD222 were significantly correlated with lymphatic invasion and TNM staging (P<0.05). The 5-year survival rate was significantly higher in negative expression of the Hpa group than that in the positive expression group (P<0.05). Compared with the non-co-positive expression group, the 5-year survival rate in the co-positive expression of Hpa and CD222 group was significantly lower (P<0.05). Conclusion:High Hpa and CD222 expressions in tumor tissues were associated with the occurrence and development of bladder carcinoma. Our results provide helpful information for the further diagnosis and therapy of bladder carcinoma.

  4. MicroRNA expression signatures of bladder cancer revealed by deep sequencing.

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    Yonghua Han

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression. They are aberrantly expressed in many types of cancers. In this study, we determined the genome-wide miRNA profiles in bladder urothelial carcinoma by deep sequencing. METHODOLOGY/PRINCIPAL FINDINGS: We detected 656 differentially expressed known human miRNAs and miRNA antisense sequences (miRNA*s in nine bladder urothelial carcinoma patients by deep sequencing. Many miRNAs and miRNA*s were significantly upregulated or downregulated in bladder urothelial carcinoma compared to matched histologically normal urothelium. hsa-miR-96 was the most significantly upregulated miRNA and hsa-miR-490-5p was the most significantly downregulated one. Upregulated miRNAs were more common than downregulated ones. The hsa-miR-183, hsa-miR-200b ∼ 429, hsa-miR-200c ∼ 141 and hsa-miR-17 ∼ 92 clusters were significantly upregulated. The hsa-miR-143 ∼ 145 cluster was significantly downregulated. hsa-miR-182, hsa-miR-183, hsa-miR-200a, hsa-miR-143 and hsa-miR-195 were evaluated by Real-Time qPCR in a total of fifty-one bladder urothelial carcinoma patients. They were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium (p < 0.001 for each miRNA. CONCLUSIONS/SIGNIFICANCE: To date, this is the first study to determine genome-wide miRNA expression patterns in human bladder urothelial carcinoma by deep sequencing. We found that a collection of miRNAs were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium, suggesting that they might play roles as oncogenes or tumor suppressors in the development and/or progression of this cancer. Our data provide novel insights into cancer biology.

  5. Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation

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    John D. Terrell

    2011-12-01

    Full Text Available OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331, 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1 and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668 patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta. The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.

  6. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

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    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  7. Anterior urethra sparing cystoprostatectomy for bladder cancer: a 10-year, single center experience

    OpenAIRE

    Hayakawa, Nozomi; Kikuno, Nobuyuki; Ishihara, Hiroki; Ryoji, Osamu; Tanabe, Kazunari

    2015-01-01

    Purpose Decision making regarding the urethra before and after radical cystectomy due to urothelial carcinoma has always been controversial. To determine whether anterior urethra sparing cystoprostatectomy for bladder cancer is an oncologically-safe procedure, we evaluated the long-term oncologic clinical outcome. Patients and methods A total of 51 male patients with cTa-4N0-2M0 bladder cancer were treated with anterior urethra sparing cystoprostatectomy and simultaneous urinary diversion bet...

  8. Well-differentiated gall bladder hepatoid carcinoma producing alpha-fetoprotein: a case report

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    Kao Ching-Yun

    2009-06-01

    Full Text Available Abstract Introduction Gall bladder carcinoma is rare, and metastatic gall bladder carcinoma from hepatocellular carcinoma has been reported in only a few patients. Case presentation We present a 73-year-old man with a history of hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma. He received transcatheter arterial chemoembolization, and was diagnosed to have an alpha-fetoprotein producing gall bladder tumor with intraluminal growth. Open cholecystectomy was performed. Pathologic examination of the lesion revealed a well-differentiated hepatoid carcinoma. The lesion was thought most likely to be a metastatic lesion from previous hepatocellular carcinoma. His alpha-fetoprotein level dropped to normal levels five months after the surgery. Conclusion This unusual intraluminal growing tumor proved to be a well-differentiated hepatoid carcinoma, most likely a metastatic lesion from previous hepatocellular carcinoma. This case reminds clinicians that in looking for likely hepatocellular carcinoma recurrence, when no detectable hepatic lesion can account for an elevated alpha-fetoprotein level, the gall bladder should be included in the search for the site of metastasis.

  9. Superficial Urothelial Cancer in the Prostatic Urethra

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    Ziya Kirkali

    2006-01-01

    Full Text Available Transitional cell carcinoma (TCC is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU. The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12—40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.

  10. Superficial urothelial cancer in the prostatic urethra.

    Science.gov (United States)

    Kirkali, Ziya; Canda, A Erdem

    2006-02-28

    Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12-40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS) in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG) seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.

  11. Enhanced oxidative stress and the glycolytic switch in superficial urothelial carcinoma of urinary bladder

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    Yu-Wei Lai

    2016-12-01

    Conclusions: UC of the UB manifested that the glycolytic phenotype would reflect the Warburg effect. We suggest that the molecular mechanism in the regulation of glycolytic switch in UC of the UB might provide a specific biomarker for the future development of cancer diagnosis.

  12. External Validation of Models for Prediction of Lymph Node Metastasis in Urothelial Carcinoma of the Bladder.

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    Ja Hyeon Ku

    Full Text Available To externally validate models to predict LN metastsis; Karakiewicz nomogram, clinical nodal staging score (cNSS, and pathologic nodal staging score (pNSS using a different cohort.Clinicopathologic data from 500 patients who underwent radical cystectomy and pelvic lymphadenectomy were analyzed. The overall predictive values of models were compared with the criteria of overall performance, discrimination, calibration, and clinical usefulness.Presence of pN+ stages was recorded in 117 patients (23.4%. Agreement between clinical and pathologic stage was noted in 174 (34.8%. Based on Nagelkerke's peudo-R2 and brier score, pNSS demonstrated best overall performance. Area under the receiver operating characteristics curve, showed that pNSS had the best discriminatory ability. In all models, calibration was on average correct (calibration-in-the-large coefficient = zero. On decision curve analysis, pNSS performed better than other models across a wide range of threshold probabilities.When compared to pNSS, current precystectomy models such as the Karakiewicz nomogram and cNSS cannot predict the probability of LN metastases accurately. The findings suggest that the application of pNSS to Asian patients is feasible.

  13. Cytologic diagnosis of low-grade papillary urothelial neoplasms (low malignant potential and low-grade carcinoma) in the context of the 1998 WHO/ISUP classification.

    Science.gov (United States)

    Whisnant, Richard E; Bastacky, Sheldon I; Ohori, N Paul

    2003-04-01

    The 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms introduced a category called papillary neoplasm of low malignant potential (LMP) and separated it from low-grade papillary urothelial carcinoma (LGPUC), which was thought to yield abnormal cells in cytology specimens. The objective of our study was to evaluate the effectiveness of urine cytology in diagnosing these lesions. Eighty-six paired transurethral surgical biopsy and corresponding urine cytology specimens representing the spectrum of urothelial papillary lesions were examined. Consensus diagnosis on each biopsy was made, and the distribution was as follows: 16 benign urothelium, 27 LMP, 28 LGPUC, and 15 high-grade papillary urothelial carcinoma (HGPUC). This was followed by a blinded independent review of the urine cytology specimens by three observers. Each cytology case was marked as negative, atypical, suspicious, or positive for malignant cells by using previously published cytologic criteria. When the negative and atypical diagnoses were grouped together as "benign" and the suspicious and malignant diagnoses as "malignant," the detection rate of "malignancy" of the lesions was as follows: LMP, 37%; LGPUC, 25%; and HGPUC, 53%. The false positive rate was 6%, and the positive predictive value (PPV) was 94%. Detection rates of cells that were at least "atypical" were as follows: LMP, 74%; LGPUC, 79%; and HGPUC, 100%. While most of the LMP and LGPUC cases yielded cells that were at least "atypical," there was no significant difference in the distribution of cytologic diagnoses for LMP and LGPUC cases (P > 0.05). Urine cytology in the context of the 1998 WHO/ISUP classification appears to be useful as a screening tool but does not appear to discriminate LMP effectively from LGPUC.

  14. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung.

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    Chang, Alex; Amin, Ali; Gabrielson, Edward; Illei, Peter; Roden, Richard B; Sharma, Rajni; Epstein, Jonathan I

    2012-10-01

    Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult. The differential diagnosis includes high-grade prostatic adenocarcinoma, spread from an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC. In terms of metastatic UC, the most common problem is differentiating spread of UC to the lung from a primary pulmonary SCC. Immunohistochemical analysis (IHC) for GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas, representative tissue sections from 15 invasive anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition, GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC, respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining. Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high-grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was present in occasional basal cells of benign prostate glands, in a few benign atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2 (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining. Weak staining was also rarely

  15. Types of HLA in the bladder transitional cell carcinoma (TCC).

    Science.gov (United States)

    Yılmaz, Erkan; Uğur Özalp, Ali; Cekmen, Arman; Eren, Bülent; Onal, Bülent; Akkuş, Emre; Erdoğan, Ergun

    2013-02-01

    HLA plays a complementary role in the interaction between tumor and body immunology. The aim of this study was to determine the existence of the association between the HLA system and transitional cell carcinoma (TCC). Using standard micro-lymphocytotoxic method of Terasaki, HLA-A, B, DR and DQ antigen types of 30 patients with TCC of the bladder were compared with the control group (30 healthy people). In the TCC patient group, HLA -DQ6(1) and HLA -DQ7(3) antigens were detected with a significantly higher frequency than in the control group (p=0.018 and p=0.038, respectively), whereas HLA-A10, B4, DR53 and DQ1 antigens were detected with significantly higher frequency in the control group (p less 0.05 in all). It suggests that patients who had the antigens detected were at higher risk of TCC, and the ones who had the antigens displaying protective features as were detected in the control group, were at lesser risk.

  16. p53 and H-ras mutations and microsatellite instability in renal pelvic carcinomas of NON / Shi mice treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine: different genetic alteration from urinary bladder carcinoma.

    Science.gov (United States)

    Gen, H; Yamamoto, S; Morimura, K; Min, W; Mitsuhashi, M; Murai, T; Mori, S; Hosono, M; Oohara, T; Makino, S; Wanibuchi, H; Fukushima, S

    2001-12-01

    We previously reported p53 mutations to be frequent (greater than 70%), whereas both H-ras mutations and microsatellite instability (MSI) were infrequent (about 10%), in urinary bladder carcinomas (UBCs) and their metastatic foci in the N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse urothelial carcinogenesis model. In the present study, an analysis of p53 and H-ras mutations as well as MSI was performed on 12 renal pelvic carcinomas (RPCs) and 8 metastatic or invading foci produced by the same experimental procedure. Histologically, 10 of the RPCs were transitional cell carcinomas and the remaining 2 were squamous cell carcinomas. p53 mutations were infrequent and only found in one primary RPC (8%), its metastatic foci and an invading lesion in another animal (in a total 2 of 12; 17%). H-ras mutations were slightly more frequent (found in 3 of 12 animals; 25%), 4 of 5 involving codon 44, GTG to GCG, not a hot-spot reported for human cancers. In two cases, H-ras mutations were confined to lung metastasis and not detectable in their primary RPCs. MSI analysis was available for 6 pairs of primary RPCs and their metastatic foci, and 4 animals (67%) had MSI at one or more microsatellite loci. Overall, the distribution of genetic alterations differed from that in UBCs produced by the same experimental protocol. The results thus suggest that different genetic pathways may participate in carcinogenesis of the upper and lower urinary tract due to BBN.

  17. Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

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    Otto Wolfgang

    2012-10-01

    Full Text Available Abstract Background Treatment of patients with stage pT1 urothelial bladder cancer (UBC continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG. Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months. Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS, progression-free (PFS and cancer-specific survival (CSS. RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020. This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025. Conclusions Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.

  18. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

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    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  19. Transitional Cell Carcinoma of the Urinary Bladder in a Beluga Whale (Delphinapterus leucas).

    Science.gov (United States)

    Martineau, D; Lagacé, A; Massé, R; Morin, M; Béland, P

    1985-10-01

    A transitional cell carcinoma of the urinary bladder was found in a beluga whale stranded in the St. Lawrence middle estuary. Various organs of this animal were submitted to high resolution gas chromatography coupled with mass spectrometry analysis. High frequency of urinary bladder cancer in the human population of the same area and the presence of carcinogenic compounds in the marine environment of this animal are discussed.Concurrent isolation of Edwardsiella tarda from various organs of this whale is also reported.

  20. Transitional Cell Carcinoma of the Urinary Bladder in a Beluga Whale (Delphinapterus leucas)

    OpenAIRE

    Martineau, D.; Lagacé, A.; Massé, R; Morin, M.; Béland, P

    1985-01-01

    A transitional cell carcinoma of the urinary bladder was found in a beluga whale stranded in the St. Lawrence middle estuary. Various organs of this animal were submitted to high resolution gas chromatography coupled with mass spectrometry analysis. High frequency of urinary bladder cancer in the human population of the same area and the presence of carcinogenic compounds in the marine environment of this animal are discussed.

  1. An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine

    OpenAIRE

    Maldonado, Leonel; Brait, Mariana; Michailidi, Christina; Munari, Enrico; Driscoll, Tina; Schultz, Luciana; Bivalacqua, Trinity; Schoenberg, Mark; Sidransky, David; George J Netto; Hoque, Mohammad Obaidul

    2014-01-01

    By a candidate gene approach, we analyzed the promoter methylation (PM) of 8 genes (ARF, TIMP3, RAR-β2, NID2, CCNA1, AIM1, CALCA and CCND2) by quantitative methylation specific PCR (QMSP) in the DNA of 17 non-recurrent and 19 recurrent noninvasive low grade papillary urothelial cell carcinoma (LGPUCC) archival tissues. Among the genes tested, by establishing an empiric cutoff value, CCND2, CCNA1, NID2, and CALCA showed higher frequency of methylation in recurrent than in non-recurrent LGPUCC:...

  2. Primary Intramural Vesical Endometriosis Mimicking Urothelial Carcinoma in a Middle Aged Female

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    Shirazi N

    2015-10-01

    Full Text Available Endometriosis is the presence of ectopic endometrial tissue outside the uterus. Presence of endometrial glands and/or stroma may interfere with the normal physiological process by their infiltrative nature or by forming adhesions. Endometriosis occurs in 15-20% of women of child bearing age and commonly involves the ovaries, utero-sacral ligaments, fallopian tubes, rectum, scar sites and cervico-vaginal regions. Incidence of urinary tract involvement is estimated to be 1%. We report a case of a 38 year female presenting with low back pain, single episode of haematuria and burning during micturition. Urine culture was negative. There was no past history of pelvic surgery. On cystoscopy, a growth was visualised in the posterior urinary bladder wall suspicious of neoplastic origin. Tansurethral resection of bladder nodule was done and sent for histopathology, on which it was diagnosed as endometriosis. The case merits interest due to its atypical clinical presentation and the rarity of the lesion at this site.

  3. A systematic study of gene mutations in urothelial carcinoma; inactivating mutations in TSC2 and PIK3R1.

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    Gottfrid Sjödahl

    Full Text Available BACKGROUND: Urothelial carcinoma (UC is characterized by frequent gene mutations of which activating mutations in FGFR3 are the most frequent. Several downstream targets of FGFR3 are also mutated in UC, e.g., PIK3CA, AKT1, and RAS. Most mutation studies of UCs have been focused on single or a few genes at the time or been performed on small sample series. This has limited the possibility to investigate co-occurrence of mutations. METHODOLOGY/PRINCIPAL FINDINGS: We performed mutation analyses of 16 genes, FGFR3, PIK3CA, PIK3R1 PTEN, AKT1, KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, TSC1, TSC2, APC, CTNNB1, and TP53, in 145 cases of UC. We show that FGFR3 and PIK3CA mutations are positively associated. In addition, we identified PIK3R1 as a target for mutations. We demonstrate a negative association at borderline significance between FGFR3 and RAS mutations, and show that these mutations are not strictly mutually exclusive. We show that mutations in BRAF, ARAF, RAF1 rarely occurs in UC. Our data emphasize the possible importance of APC signaling as 6% of the investigated tumors either showed inactivating APC or activating CTNNB1 mutations. TSC1, as well as TSC2, that constitute the mTOR regulatory tuberous sclerosis complex were found to be mutated at a combined frequency of 15%. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a significant association between FGFR3 and PIK3CA mutations in UC. Moreover, the identification of mutations in PIK3R1 further emphasizes the importance of the PI3-kinase pathway in UC. The presence of TSC2 mutations, in addition to TSC1 mutations, underlines the involvement of mTOR signaling in UC.

  4. Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Ying-Ting [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2011-02-15

    Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: {yields} Plasma alpha-tocopherol levels were significantly inversely related to UC risk. {yields} There were no correlations between plasma micronutrients and urinary 8-OHdG. {yields} People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

  5. Verrucous carcinoma of the bladder with koilocytosis unassociated with vesical schistosomiasis

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    Fabio Lewin

    Full Text Available CONTEXT: Verrucous carcinoma of the bladder is a very rare malignant neoplasm, histologically similar to condyloma acuminatum. Usually it shows association with vesical schistosomiasis (bilharziasis. Only 13 cases unrelated to bilharziasis have been reported to date, and none of them reported koilocytosis, a typical finding in human papillomavirus infection. CASE REPORT: We report a case of verrucous carcinoma of the bladder that was unrelated to bilharziasis, with koilocytosis and absence of human papillomavirus. The literature relating to the topic is discussed.

  6. 荧光原位杂交技术在尿路上皮癌诊断中应用%Application of fluorescence in situ hybridization in Urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴丽华; 姚锋; 黄华

    2015-01-01

    Objective:To evaluate the diagnostic efficiency of urinary cytology and fluorescence in situ hybridization in the diagnosis of urothelial carcinoma. Methods:Fresh urine samples from 121 volunteers who were suspected of suffering from malignant urothelial tumors with pathological diagnosis results were collected,and the specimens were detected by uri-nary cytology and fluorescence in situ hybridization. Result:When urothelial carcinoma was detected by urinary cytology, the sensitivity was 81.82%(54/66).The specificity was 100%(55/55).The positive predictive value was 100%(54/54).And the negative predictive value was 96.49%(55/57).While when detecting the low grade tumors,the sensitivity was 68.42%(13/19).And when detecting the high grade tumors,the sensitivity was 87.23%(41/47).When detecting urothelial carcino-ma by fluorescence in situ hybridization,the sensitivity was 53.03%(35/66).The specificity was 92.73%(51/55).The posi-tive predictive value was 89.74%(35/39).And the negative predictive value was 62.20%(51/82).While when detecting the low grade tumors,the sensitivity was 10.53%(2/19).And when detecting the high grade tumors,the sensitivity was 70.21%(33/47). When detecting urothelial carcinoma by combined diagnosis,the sensitivity was 93.94%(62/66).The specificity was 100%(55/55).The positive predictive value was 100%(5/5).And the negative predictive value was 92.73%(51/55). When the low grade tumors were detected,the sensitivity was 78.95%(15/19).And when the high grade tumors were detect-ed,the sensitivity was 100%(47/47). Conclusion: According to the results, the sensitivity of FISH for the detection of urothelial bladder cancer was superior to that of cytology. The sensitivity of combined diagnosis by urinary cytology and flu-orescence in situ hybridization was superior to that of any single method.%目的:评估荧光原位杂交技术和液基脱落细胞学在尿路上皮癌诊断中应用价值.方法:收集临床疑为尿路上皮癌

  7. Effects of curcumin in an orthotopic murine bladder tumor model

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    Katia R. M. Leite

    2009-10-01

    Full Text Available Cigarette smoking (CS is the main risk factor for bladder cancer development. There are more than 100 carcinogens present in cigarette smoke. Among the potential mediators of CS-induced alterations is nuclear factor-kappa (NF-κB, which is responsible for the transcription of genes related to cell transformation, tumor promotion, angiogenesis, invasion and metastasis. Curcumin is a polyphenol compound derived from Curcuma longa that suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis by down regulating NF-κB and its regulated genes. The aim of our study was to assess the effects of curcumin in bladder urothelial carcinoma. We studied the effects of curcumin in vitro and in vivo using the orthotropic syngeneic bladder tumor animal model MB49. Curcumin promotes apoptosis of bladder tumor cells in vitro. In vivo tumors of animals treated with curcumin were significantly smaller as compared to controls. Using immunohistochemistry, we demonstrated a decrease in the expression of Cox-2 by 8% and Cyclin D1 by 13% in the animals treated with curcumin; both genes regulated by NF-κB and related to cell proliferation. In this study, we showed that curcumin acts in bladder urothelial cancer, possibly dowregulating NF-κB-related genes, and could be an option in the treatment of urothelial neoplasms. The results of our study suggest that further research is warranted to confirm our findings.

  8. Plasmacytoid Transitional Cell Carcinoma of Bladder: A Clinico-pathological Study and Review of Literatures

    Institute of Scientific and Technical Information of China (English)

    FENG Xiaoli; ZHANG Hongtu; SUN Yuntian; LIU Xiuyun

    2006-01-01

    Objective: To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods: Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results: A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion: The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

  9. Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients.

    Science.gov (United States)

    Abdel-Haleem, Alyaa M; El-Zeiry, Maha I; Mahran, Laila G; Abou-Aisha, Khaled; Rady, Mona H; Rohde, Jan; Mostageer, Marwa; Spahn-Langguth, Hilde

    2011-01-01

    Urinary bladder cancer (UBC) ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1) is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; PRFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; pRFC mRNA expression was significantly (pRFC mRNA levels were not associated with tumor grade (I, II and III) or stage (muscle-invasive vs. non-muscle invasive) implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas.

  10. Application value of fluorescence in situ hybridization in patients with urothelial bladder cancer%荧光原位杂交技术在膀胱尿路上皮癌诊断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    余义; 刘飞; 黄永辉; 陆文宝; 黄红卫

    2012-01-01

    Objective:To evaluate the application value of fluorescence in situ hybridization(FISH)technique in the diagnosis of urothelial bladder cancer. Method: Urine samples from 60 patients suspected of having bladder cancer were collected before cystoscopy for immediate urine cytology and FISH analysis. The criteria for FISH abnormality were determined by evaluating the urine specimens from 20 subjects without urogenital neoplasm. Result; The overall sensitivity of cytology and FISH was 42. 0% and 82. 2% ,and their specificity was 93. 3% and 86. 7% , respectively. The differences between FISH and cytology showed statistical significance in the sensitivity of low grade and non-muscle-invasive cancer(P<0. 05). Conclusion: FISH can improve remarkablely the detection rate of urothelial bladder cancer,especially for the low stage and low grade tumors,and will be a new noninvasive screening method for urothelial bladder cancer.%目的:评估荧光原位杂交技术(FISH)在膀胱尿路上皮癌诊断中的应用价值.方法:收集60例疑似膀胱癌的血尿患者的尿液标本,分别作尿细胞学检测和荧光原位杂交分析.20例正常人尿液标本,用于建立FISH阀值,作为阳性判断的标准.结果:细胞学和FISH的总敏感性分别为42.0%、82.2%,特异性分别为:93.3%、86.7%.细胞学和FISH在低级别及非肌层浸润性肿瘤等敏感性的均差异有统计学意义(P<0.05).结论:FISH技术能明显提高膀胱尿路上皮癌的检出率,尤其是早期和低级别病变,可以成为筛查膀胱尿路上皮癌的一种新的无创性检查方法.

  11. Bladder Cancer in an Inguinoscrotal Vesical Hernia

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    Lucas Regis

    2012-01-01

    Full Text Available We present the case of a 79-year-old male who, due to hematuria, underwent cystoscopy that showed a lesion in the bladder dome. Transurethral resection was attempted, but access to the tumor by this route was impossible. Given the findings, a body CT scan was performed showing an inguinoscrotal hernia with vesical carcinoma contained. Open surgical treatment of the vesical carcinoma contained within the inguinoscrotal hernia was performed in conjunction with the hernia repair. The anatomical pathology report confirmed a high-grade urothelial carcinoma (stage pT2b with a free resection margin of <1 mm. Adjuvant radiotherapy was selected for subsequent treatment. The presence of bladder tumor in an inguinoscrotal hernia is an uncommon finding and a diagnostic delay can be assumed. The initial therapeutic plan may need to be changed from the usual approaches due to the atypical presentation.

  12. Methylation of a CpG Island within the Uroplakin Ib Promoter: A Possible Mechanism for Loss of Uroplakin lb Expression in Bladder Carcinoma

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    Andrea E. Varga

    2004-03-01

    Full Text Available Uroplakin Ib is a structural protein on the surface of urothelial cells. Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell carcinomas (TCCs but molecular mechanisms underlying loss of expression remain to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1. This study examined the hypothesis that methylation of this CpG island regulates uroplakin Ib expression. Uroplakin Ib mRNA levels were determined by reverse transcription polymerase chain reaction and CpG methylation was assessed by bisulfite modification of DNA, PCR, and sequencing. A correlation was demonstrated in 15 TCC lines between uroplakin Ib mRNA expression and lack of CpG methylation. In support of a regulatory role for methylation, incubating uroplakin Ib-negative lines with 5-aza-2′ -deoxycytidine reactivated uroplakin Ib mRNA expression. A trend between uroplakin Ib mRNA expression and CpG methylation was also observed in normal urothelium and bladder carcinomas. In particular, loss of uroplakin Ib expression correlated with methylation of a putative Spi/NFκB binding motif. The data are consistent with the hypothesis that methylation of specific sites within the uroplakin Ib promoter may be an important factor in the loss of uroplakin Ib expression in TCCs.

  13. Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: pathological implications in diagnosis.

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    Sukhwinder Kaur

    Full Text Available Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines.Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting.MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC. MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12 to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001. In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28, both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06. However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9.The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

  14. The use of fluorescence in situ hybridization in the detection of urothelial bladder cancer%荧光原位杂交技术在膀胱癌检测中的临床应用研究

    Institute of Scientific and Technical Information of China (English)

    刘跃新; 刘小超; 康雯婷; 陈山; 王伟; 闫伟

    2013-01-01

    Objective We determine the relative sensitivities and specificities of cytology and fluorescencx in situ hybridization (FISH) for the detection of urothelial bladder cancer in order to evaluate the clinical utility of FISH in the screening of urothelial bladder cancer. Methods From December 2007 to June 2008, the fresh urine voided by 20 healthy volunteers was obtained. A mixture of fluorescxntly labeled Probes were targeted to the chromosomes 3, land 17 and p16. FISH was performed on exfoliated urothelial cells in the urine to get the threshold value of healthy adults. Urine voided by 93 patients with hematuria was collected and examined by cytology and FISH simultaneously before cystoscopy. The McNemar test was used to determine the statistical significance between the yields of different tests. Results The sensitivities of FISH and cytology were 90.78%% (69/76), 48.10%% (38/79). The specificities of FISH and cytology were 82.35% (13/17) and 92.85% (13/14). Conclusion According to this study, the sensitivity of FISH for the detection of urothelial bladder is superior to that of cytology,and the specificities of FISH and cytology for the detection of urothelial bladder cancer are not significantly different.%目的 分析比较荧光原位杂交技术(FISH)与尿液脱落细胞学在膀胱尿路上皮肿瘤检测中灵敏性与特异性的差异.方法 2007年6月至2008年12月,收取20例健康人群的新鲜尿液,应用荧光标记的3号、7号、17号染色体着丝粒探针及p16位点探针,对尿液脱落细胞进行FISH检测,建立正常人群的阈值;留取临床确诊的93例膀胱上皮肿瘤患者的尿液标本,同时进行尿液脱落细胞学检查及FISH检测,对比尿液脱落细胞学检查及FISH检测结果,对FISH、尿液脱落细胞学检查检测膀胱尿路上皮癌的敏感性和特异性进行统计学分析.结果 FISH、尿液脱落细胞学检测膀胱尿路上皮癌总的敏感性分别为90.78%% (69/76)和48.10%%(38

  15. Clinico-pathological features of bladder carcinoma in women in Pakistan and smokeless tobacco as a possible risk factor

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    Rafique Muhammad

    2005-08-01

    Full Text Available Abstract Background Bladder carcinoma is one of the common urological malignancies occurring worldwide in both sexes. Use of smokeless tobacco by women is common in rural areas of Pakistan. The clinico-pathological features of bladder carcinoma in women and association of smokeless tobacco as a possible risk factor for bladder carcinoma has not been well described in the literature. The objective of the study was to determine the clinico-pathological features of histologically confirmed bladder carcinoma in women and to investigate the role of smokeless tobacco use as a possible risk factor for its development. Patients and methods Of the 204 patients (160 male and 44 female M:F ratio 3.6:1 of newly diagnosed bladder carcinoma treated at Nishtar Medical College Hospital Multan from January 1998 to December 2004, the 44 female patients were evaluated with respect to age, clinical presentation, cystoscopic findings, histopathological reports and possible etiological factors. Data were collected and prospectively updated at the time of discharge from hospital and during follow-up in urology out-patient clinic. Results Transitional cell carcinoma accounted for all of the bladder carcinoma in women. Median age of the patients was 55 years and 68% patients were under 60 years of age. Majority of patients (88% presented with hematuria. Eleven (25% patients had superficial (pTa/pT1 while 33 (75% patients had muscle invasive (T2–T4 bladder carcinoma. Most (81% superficial tumors were papillary while muscle invasive tumors had solid configuration at cystoscopy. Of these, 21 (47% patients had long history of smokeless tobacco use (chewable or moist snuff. Conclusion Transitional cell carcinoma is the most common bladder malignancy in women in Pakistan. Many women with bladder carcinoma had long history of use of smokeless tobacco. Majority of patients presented with hematuria and were under 60 years of age. At the time of diagnosis 75% women had muscle

  16. Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder

    DEFF Research Database (Denmark)

    Sasaki, M; Sørensen, Flemming Brandt; Fukuzawa, S

    1993-01-01

    BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible...

  17. Squamous Cell Carcinoma of the Bladder Mimicking Interstitial Cystitis and Voiding Dysfunction

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    Colton Prudnick

    2013-01-01

    Full Text Available Squamous cell carcinoma (SCC of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

  18. CT findings of primary localized amyloidosis of the urinary bladder: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwan; Kim, See Hyung; Kim, Mi Jeong; Kim, Sang Pyo [Keimyung Univ. College of Medicine/Dongsan Hospital, Daegu (Korea, Republic of)

    2012-08-15

    Primary localized amyloidosis is a rare disease that impairs the organs and tissue function, caused by extracellular deposition of amyloid protein. Although amyloid proteins can be deposited in localized or systemic organs, the bladder is a rare site. CT showed diffuse infiltrative mass in the left urinary bladder wall, and the left ureterovesical junction with enhancement and perivesical invasion, which mimics urothelial carcinoma. However, pathological diagnosis was localized primary amyloidosis. We report here on the CT findings of a rare case of primary localized amyloidosis of the urinary bladder with brief review of the literature.

  19. Spontaneous rupture of bladder diverticulum after postoperative radiotherapy for carcinoma of the uterine cervix. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tetsuo; Suzuki, Kazunori; Iijima, Mitsuharu; Nozue, Masashi; Imai, Michiko; Suzuki, Sachiko; Sakahara, Harumi; Ohta, Nobutaka; Kasami, Masako [Hamamatsu Univ. School of Medicine, Shizuoka (Japan)

    2000-08-01

    We present a case of spontaneous rupture of bladder diverticulum three years after postoperative whole pelvic irradiation (50.4 Gy) for carcinoma of the uterine cervix. The patient had suffered from a neurogenic bladder after hysterectomy, but excretory urography revealed no abnormalities. Bladder diverticulum was found two years later. Spontaneous rupture of the urinary bladder is one of the late complications associated with radiotherapy, although it is very rare. Postoperative neurogenic bladder may also be associated with rupture. We should be aware of this rare complication in patients who receive pelvic irradiation. (author)

  20. Muscle-invasive bladder cancer in a young adult: a case report and a review of the literature.

    Science.gov (United States)

    Nabbout, Philippe; Eldefrawy, Ahmed; Engles, C Dirk; Culkin, Daniel J; Slobodov, Gennady

    2013-01-01

    The peak incidence of bladder cancer (BC) is in the sixth decade of life. Muscle-invasive bladder cancer (MIBC) in young adults is extremely rare. We report a case of MIBC in a 28-year-old smoking male patient. The patient presented with hematuria and flank pain for which he underwent a computerized tomography (CT) scan of the abdomen and pelvis with and without contrast. The CT scan showed a 6 cm mass on the left side of the trigone extending to the left urteric orifice and left hydronephrosis, but no lymphadenopathy was noted. The patient then underwent a left nephrostomy tube placement followed by trans-urethral resection of bladder tumor (TURBT). The tumor involved both ureteric orifices and extended to the prostatic urethra. Complete resection was not feasible. Pathology showed high-grade T1 urothelial carcinoma. CT scan of the chest showed no distant lung metastasis. The patient then elected to undergo radical cystectomy with ileal conduit urinary diversion. Final pathology revealed T2a N0 urothelial carcinoma of the bladder. Our aim is to present our experience and review the literature for the natural history and oncological and quality of life outcomes of urothelial carcinoma of the bladder in young patients.

  1. Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

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    Deepika Kanojia

    Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

  2. Cytokeratin-20 immunocytochemistry in voided urine cytology and its comparison with nuclear matrix protein-22 and urine cytology in the detection of urothelial carcinoma.

    Science.gov (United States)

    Srivastava, Ruchi; Arora, Vinod Kumar; Aggarwal, Seema; Bhatia, Arati; Singh, Navjeevan; Agrawal, Vivek

    2012-09-01

    This study was done on 59 subjects (42 urinary bladder carcinoma patients and 17 non-neoplastic controls). Urine cytology and bladder chek NMP22 test was done on all cases. CK20 immunostaining was performed on archived papanicolaou stained urine cytology smears in 34 cases (27 bladder carcinoma and 7 negative controls). Results of all three tests (cytology, NMP22, and CK20 immunostaining) were compared with histopathology to evaluate the accuracy of individual test. The combination of cytology and NMP22 was compared with combination of cytology and CK20 immunostaining for detection of bladder carcinoma. NMP22 had sensitivity of 92.9% and specificity of 70.6%, as compared with voided urine cytology (sensitivity of 76.2% and specificity of 76.5%) and CK20 immunostaining (sensitivity of 70.4% and specificity of 71.4%). Combination of cytology and NMP22 gave better results (sensitivity of 88.1% and specificity of 88.2%) than combination of cytology and CK20 immunostaining or any other test in isolation.

  3. Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

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    Enrique Redondo-Gonzalez

    2015-01-01

    Full Text Available Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC. A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH, muscle invasive bladder carcinoma (MIBC, carcinoma in situ (CIS, and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR. A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

  4. Divergent effects of taurolidine as potential anti-neoplastic agent: inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo.

    Science.gov (United States)

    Abramjuk, Claudia; Bueschges, Michael; Schnorr, Jörg; Jung, Klaus; Staack, Andrea; Lein, Michael

    2009-08-01

    We investigated taurolidine (TRD) against various human bladder cell lines and the AY-27 rat bladder carcinoma cells. In vitro we tested the effect of TRD in ascending concentrations depending on different incubation times on cell proliferation by the XTT-test. Taurolidine had an inhibitory effect on all tested cell lines. Increasing concentrations and longer incubation times decreased the proliferation depending on the primary quantities of cells. For in vivo studies, an orthotopic rat bladder carcinoma was used. The animals were treated intravenously or intravesically and the tumors were harvested and weighted after the study. In contrast to other authors we could not find any anti-proliferative effect, we actually showed that instillation into the rat urinary bladder enhanced tumor growth.

  5. Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring...

  6. The Differential Expression of EphB2 and EphB4 Receptor Kinases in Normal Bladder and in Transitional Cell Carcinoma of the Bladder

    OpenAIRE

    Xiuqing Li; Choi, Wesley W.; Rui Yan; Haiyang Yu; Valery Krasnoperov; S Ram Kumar; Anne Schuckman; Klumpp, David J.; Chong-Xian Pan; David Quinn; Gill,Inderbir S.; Gill, Parkash S.; Ren Liu

    2014-01-01

    Effective treatment of transitional cell carcinoma (TCC) of the bladder requires early diagnosis. Identifying novel molecular markers in TCC would guide the development of diagnostic and therapeutic targets. Ephrins mediate signals via tyrosine kinase activity that modulates diverse physiologic and developmental processes, and ephrins are increasingly implicated in carcinogenesis. The aim of our study was to examine the differential regulation of EphB4 and EphB2 in normal bladder and in TCC o...

  7. Selective arterial embolization for control of haematuria secondary to advanced or recurrent transitional cell carcinoma of the bladder.

    LENUS (Irish Health Repository)

    Halpenny, D

    2014-05-02

    Haematuria is a common symptom in patients with advanced transitional cell carcinoma of the bladder. We report our experience of selective pelvic embolization using gelfoam as an embolic agent to treat intractable haematuria in these patients.

  8. NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation.

    NARCIS (Netherlands)

    Smakman, N.; Schaap, N.P.M.; Snijckers, C.M.; Rinkes, M.J.; Kranenburg, O.

    2005-01-01

    OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess its effect on tumor cell proliferation and survival and tumor vascularization. COX-2 overexpression is frequently observed in bladder carcinom

  9. Detection of chromosomal aberrations of bladder carcinoma by fluorescence in situ hybridization%荧光原位杂交技术检测膀胱癌染色体畸变的研究

    Institute of Scientific and Technical Information of China (English)

    李晓娟; 符生苗; 刘元晓; 邓立群

    2012-01-01

    Objective To detect the common chromosomal aberrations from (he bladder transitional cell carcinoma by using M-FISH. Methods 50 urine samples were detected by FISH with centromeric probes of chromosome 17,7,3 and band probe of 9p2 l,and then the results were analyzed. Results There were four chromosomes showing a high distortion in 50 cases of bladder carcinoma group,showing significant association between chromosome 17,7,3,9p2 1 aberrations and pathological stage,grade (P<0.01). Conclusion Fluorescence in situ hybridization is an effective way for detection of chromosomal aberrations of urothelial tumors, as well as the early diagnosis of urothelial cancer.%目的 用多色荧光原位杂交(M-FISH)检测膀胱移行细胞癌中常见的染色体畸变. 方法 50例尿液标本采用FISH技术检测9p21区带及17、7、3号染色体的畸变情况,并对结果进行相应的统计学分析. 结果 50例膀胱癌病人组中,4个染色体均显示较高的畸变率.9p21以及17、7和3号染色体畸变率与病理分期、分级均有显著相关性(P<0.01).结论 用荧光原位杂交技术是检测尿路上皮肿瘤染色体畸变的有效方法,可作为早期诊断尿路上皮肿瘤的重要途径.

  10. Fire fighters, combustion products, and urothelial cancer.

    Science.gov (United States)

    Golka, Klaus; Weistenhöfer, Wobbeke

    2008-01-01

    Urothelial cancer may be induced by different workplace chemicals, including carcinogenic aromatic amines, coke oven fumes, and cigarette smoking. The general impact of combustion products on urothelial cancer risk of exposed persons is still controversial. This raises the question whether fire fighters may have an increased risk for urothelial cancer. The present review compiles the literature on combustion products, possibly relevant for fire fighters, and the available studies on urinary bladder cancer risk in fire fighters. Chemical analyses of smoke from experimental fires as well as from fires in cities, wildlands, and industry do not indicate a generally elevated risk of bladder cancer in fire fighters. This is supported by studies on bladder cancer in fire fighters. Based on mortality studies, studies on exposures, and cancer incidence, we conclude that an elevated risk of urothelial cancer in fire fighters, in general, is not confirmed. Only in professional fire fighters more severely exposed for decades, having started their career some decades before, occupational exposure might be discussed as causative for urothelial cancer.

  11. Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival

    Directory of Open Access Journals (Sweden)

    Fujimoto Kiyohide

    2011-05-01

    Full Text Available Abstract Background Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo. Methods COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells. Results Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA, resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes. Conclusions COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.

  12. Carcinoma-in-situ bladder -an early indication for cystectomy?

    Directory of Open Access Journals (Sweden)

    V Kumar

    2002-01-01

    All patients diagnosed to have CIS bladder histolo-gically in Harrogate District Hospital from August 94 to August 99 were included in the study. All data con-cerning the management, treatment and subsequent fol-low-up were collected from the patients′ records and analysed in a systematic way. A total of 20 patients were included in the study. Analysis showed that there was no age or sex predilection and the age group ranged from 36 to 75. It occurs either alone or with papillary bladder tumour. It is found to be poor prognostic indi-cator for subsequent ttunour recurrence. Mitomvcin was the least effective and BCG is the most effective form of intravesical treatment. Failure on BCG therapy is an earlvpredictorforaggressive treatment i.e. Radical Cys-tectomy. Eventually 1/3 of all patients diagnosed to have CIS progressed to muscle invasive disease requiring radical treatment.

  13. Long-term oncologic outcomes of laparoscopic nephroureterectomy versus open nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis

    Science.gov (United States)

    Zhang, Su; Luo, You; Wang, Cheng; Fu, Sheng-Jun

    2016-01-01

    Background. Several factors have been validated as predictors of disease recurrence in upper tract urothelial carcinoma. However, the oncological outcomes between different surgical approaches (open nephroureterectomy versus laparoscopic nephroureterectomy, ONU vs LNU) remain controversial. Therefore, we performed a meta-analysis to evaluate the oncological outcomes associated with different surgical approaches. Methods. We conducted an electronic search of the PubMed, Embase, ISI Web of Knowledge and Cochrane Library electronic databases through November 2015, screened the retrieved references, collected and evaluated the relevant information. We extracted and synthesized the corresponding hazard ratios (HRs) and 95% confidence intervals (95% CI) using Stata 13. Results. Twenty-one observational studies were eligible for inclusion in the meta-analysis. The results of the meta-analysis showed no differences in the intravesical recurrence-free survival (IRFS), unspecified recurrence-free survival (UnRFS) and overall survival (OS) between LNUandONU. However, improvements in the extravesical recurrence free survival (ExRFS) and cancer specific survival (CSS) were observed inLNU. The pooled hazard ratios were 1.05 (95% CI [0.92–1.18]) for IRFS, 0.80 (95% CI [0.64–0.96]) for ExRFS, 1.10 (95% CI [0.93–1.28]) for UnRFS, 0.91 (95% CI [0.66–1.17]) for OS and 0.79 (95% CI [0.68–0.91]) for CSS. Conclusion. Based on current evidence, LNU could provide equivalent prognostic effects for upper tract urothelial carcinoma, and had better oncological control of ExRFS and CSS compared to ONU. However, considering all eligible studies with the intrinsic bias of retrospective study design, the results should be interpreted with caution. Prospective randomized trials are needed to verify these results. PMID:27280069

  14. Long-term oncologic outcomes of laparoscopic nephroureterectomy versus open nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Su; Luo, You; Wang, Cheng; Fu, Sheng-Jun; Yang, Li

    2016-01-01

    Background. Several factors have been validated as predictors of disease recurrence in upper tract urothelial carcinoma. However, the oncological outcomes between different surgical approaches (open nephroureterectomy versus laparoscopic nephroureterectomy, ONU vs LNU) remain controversial. Therefore, we performed a meta-analysis to evaluate the oncological outcomes associated with different surgical approaches. Methods. We conducted an electronic search of the PubMed, Embase, ISI Web of Knowledge and Cochrane Library electronic databases through November 2015, screened the retrieved references, collected and evaluated the relevant information. We extracted and synthesized the corresponding hazard ratios (HRs) and 95% confidence intervals (95% CI) using Stata 13. Results. Twenty-one observational studies were eligible for inclusion in the meta-analysis. The results of the meta-analysis showed no differences in the intravesical recurrence-free survival (IRFS), unspecified recurrence-free survival (UnRFS) and overall survival (OS) between LNUandONU. However, improvements in the extravesical recurrence free survival (ExRFS) and cancer specific survival (CSS) were observed inLNU. The pooled hazard ratios were 1.05 (95% CI [0.92-1.18]) for IRFS, 0.80 (95% CI [0.64-0.96]) for ExRFS, 1.10 (95% CI [0.93-1.28]) for UnRFS, 0.91 (95% CI [0.66-1.17]) for OS and 0.79 (95% CI [0.68-0.91]) for CSS. Conclusion. Based on current evidence, LNU could provide equivalent prognostic effects for upper tract urothelial carcinoma, and had better oncological control of ExRFS and CSS compared to ONU. However, considering all eligible studies with the intrinsic bias of retrospective study design, the results should be interpreted with caution. Prospective randomized trials are needed to verify these results.

  15. Identification of differentially expressed genes in two new human bladder carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To screen and identify differentially expressed genes in two new human urothelial carcinoma cell lines, BLS-211 and BLX. Methods Suppression subtractive hybridization (SSH) was used to createa subtracted library, and clones were sequenced. Results Totally 13 over-expressed genes in BLX and 9 in BLS-211 cells were obtained, respectively. Among them, 18 were known genes and 4 were new ESTs (Expressed Sequence Tag), and were collected by GenBank dbEST database (The access number was EB390424-7). Conclusion SSH is a powerful method for the identification of differentially expressed genes. The differential expression of some BCG-associated genes in different cells may be related to the different responses to clinical BCG therapy. The identified new ESTs can be cloned for full length to further study their functions.

  16. [Transitional cell carcinoma of the bladder in adolescents: a diagnosis to bear in mind].

    Science.gov (United States)

    Ruiz, Eduardo; Alarcón Caba, Martín; Toselli, Luzia; Moldes, Juan; Ormaechea, María; de Badiola, Francisco; Christiansen, Silvia

    2009-02-01

    Transitional cell carcinoma of the bladder has a high incidence in adults, but it is uncommon in children and adolescents. Hematuria is the most common symptom of presentation and vesical ecography the preferred diagnostic method. The diagnosis and treatment is performed with cystoscopy and endoscopic resection. We describe two patients: an 18 years old male, who presented with a pediculated tumor on the posterior bladder wall and a 15 years old female with a 1 cm long tumor on the posterior wall too; both were removed under endoscopic control. In both patients superficial transitional cell carcinoma was the final diagnosis and are disease free 3 and 5 years later. A review of the available literature was performed to clarify if this type of tumors must be considered malignant and try to define how long and by which way these patients must be controlled.

  17. Concurrent Testicular and Bladder Cancer in a 57-year-old Man

    Directory of Open Access Journals (Sweden)

    Esther Han

    2015-09-01

    Full Text Available We present a rare finding of concurrent right testis non-seminomatous mixed germ cell tumor and muscle invasive urothelial carcinoma of the bladder in a 57-year-old homeless man. The socioeconomic factors and the disease presentation caused a treatment dilemma in terms of the appropriate type of neoadjuvant chemotherapy. The patient ultimately underwent upfront surgery with retroperitoneal lymph node dissection and radical cystoprostatectomy followed by adjuvant cisplatin-based chemotherapy.

  18. Concurrent Testicular and Bladder Cancer in a 57-year-old Man

    OpenAIRE

    Esther Han; Stein, Daniel M.; Dongping Shi; Ranko Miocinovic

    2015-01-01

    We present a rare finding of concurrent right testis non-seminomatous mixed germ cell tumor and muscle invasive urothelial carcinoma of the bladder in a 57-year-old homeless man. The socioeconomic factors and the disease presentation caused a treatment dilemma in terms of the appropriate type of neoadjuvant chemotherapy. The patient ultimately underwent upfront surgery with retroperitoneal lymph node dissection and radical cystoprostatectomy followed by adjuvant cisplatin-based chemotherapy.

  19. Bladder squamous cell carcinomas express psoriasin and externalize it to the urine

    DEFF Research Database (Denmark)

    Celis, J E; Rasmussen, H H; Vorum, H;

    1996-01-01

    PURPOSE: To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), a calcium binding protein which is expressed largely by stratified squamous epithelia and is externalized to the urine of bladder squamous cell carcinoma (SCC) bearing patients. MATERIALS AND METHODS: Protein expression profiles...... identified from 100 samples of patients with suspected transitional cell carcinoma (TCC). The protein profiles of the 4 SCCs (56-1, grade III, T4; 181-1, grade I, T3; 219-1, grade III, T3 and 239-1, grade not determined, T2-4) resembled that of keratinocytes, suggesting that these cells express an early...

  20. Small cell carcinoma of the urinary bladder: KIT and PDGFRA gene mutations

    Directory of Open Access Journals (Sweden)

    Nuket Eliyakin

    2015-12-01

    Full Text Available Primary small cell carcinoma of the urinary bladder is very rare. A 72-year-old was admitted to our hospital because of hematuria and dysuria. Cystoscopy revealed a bladder full of multiple, solid and papillary tumors. Biopsies from the deep and papillary tumors were taken. Histologically, tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, neuron-specific enolase, CD56, CD117 and Ki67 (labeling 70%. The tumor cells were negative for CK7, CK20, CD3, CD20, LCA, CDX2, uroplakin, thyroid transcription factor 1, PSA and p63. Metastatic workup was performed an no primary or metastatic lung lesions were noted. Due to the clinical, radiologic and immunohistochemical findings, the patient was diagnosed as primary small cell carcinoma of bladder. A molecular genetic analysis for KIT (exons 9, 11, 13 and 17 and PDGFRA (exons 12 and 18 genes was performed, in paraffin micro dissection specimens, by the PCR-direct sequencing method. According to the sequencing analyses, two mutations were found at positions 558 (p.K558N and 562 (p.E562D in KIT gene exon 11 in our case. The another hand the same case presented two mutations in PDGFRA gene exon 14 at position 631 (p.P631A and 638 (p.638Q_639AinsC. The disease process was fulminant and the patient was lost due to several complications prior to any chemotherapy.

  1. THE INHIBITORY EFFECT OF MELATONIN ON THE GROWTH OF HUMAN BLADDER CARCINOMA T24 CELL LINE

    Institute of Scientific and Technical Information of China (English)

    白艳红; 慕慧; 赵晏; 蔡晓宏; 王中秋; 郭瑗

    2004-01-01

    Objective To study the inhibitory effects of melatonin and its inhibitory mechanism on the growth of human bladder carcinoma T24. Methods The inhibitory effects of melatonin with various concentrations on the human bladder carcinoma T24 lines in vitro were determined by MTT assay. The mechanism of the inhibition was observed by flow cytometry (FCM) and transmission electron microscopy (TEM). Results The 30% inhibition concentration (IC30) value was 0.71mmol·L-1 and the 50% inhibition concentration (IC50) value was 1.20mmol·L-1. The population doubling time of T24 cells treated with melatonin at 0.71mmol·L-1 was 43.2 hours, which was significant different from that of 34.6 hours of the control group. Using FCM, we found that the cell percentage increased during the G1 phase, but decreased during the S stage. The degenerated ultra-structure of the cell treated with melatonin was also observed by TEM. Conclusion The results suggest that melatonin can inhibit the growth of human bladder carcinoma T24. The inhibitory effects of melatonin might be the prolonging of the staging from G1 to S in the cell cycle.

  2. Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells.

    Science.gov (United States)

    Tsui, Ke-Hung; Lin, Yu-Hsiang; Chung, Li-Chuan; Chuang, Sung-Ting; Feng, Tsui-Hsia; Chiang, Kun-Chun; Chang, Phei-Lang; Yeh, Chi-Ju; Juang, Horng-Heng

    2016-05-28

    Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells.

  3. Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development

    DEFF Research Database (Denmark)

    Zieger, Karsten; Marcussen, Niels; Borre, Michael

    2009-01-01

    Bladder cancer develops through different pathways, provisionally entitled "papillary" and "invasive." Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions, and the relations......Bladder cancer develops through different pathways, provisionally entitled "papillary" and "invasive." Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions......, and the relationship between chromosomal alterations and the different pathways. We laser-microdissected 12 CIS and 4 dysplasia samples concomitant to invasive bladder cancer. We determined genome-wide chromosome copy number changes and loss of heterozygosity (LOH) using Mapping 10K SNP microarrays. We further......3 mutations mutually exclusive. No FGFR3 mutations were found in 23 CIS and dysplasia samples. Based on this, we classified high-risk non-muscle-invasive bladder tumors according to FGFR3 mutations and chromosomal changes into papillary and CIS-type tumors with high correlation to CIS status (p = 0...

  4. Expression of X-linked Inhibitor of Apoptosis Protein and Its Effect on Chemotherapeutic Sensitivity of Bladder Carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Liang; BI Yalan; ZENG Fuqing; ZHENG Liduan; TONG Qiangsong

    2007-01-01

    The expression of X-linked inhibitor of apoptosis protein (XIAP) gene and its effect on chemotherapeutic sensitivity in bladder carcinoma was explored. By using immunohistochemistry,the expression of XIAP was detected in 47 bladder carcinomas and 5 normal bladder tissues. The XIAP gene was transfected into bladder cancer cell line T24 by liposome and the positive clone was screened by G418. Cellular XIAP mRNA level was detected by RT-PCR. Low-dose mitocycin C was administered to induce the apoptosis of T24 cells. The in vitro growth of bladder carcinoma cells was analyzed by MTT colorimetry, and the apoptosis rate was assayed by TUNEL methods. It was found XIAP was moderately expressed in bladder carcinomas with the the positive rate being 78.73% (37/47), but the positive rate was not correlated with carcinoma stages and grades (P<0.05). XIAP mRNA level in transfected T24 cells was significantly increased by 3.8 times as compared with that in the cells not transfected with XIAP. After treatment with low-dose mitomycin C (0.005 and 0.05 mg/mL), the growth rate in XIAP no-transfected control group was increased by (11.60±0.25)% and (16.51±0.87)% (P<0.05), and the apoptosis rate was decreased by (10.1±0.2)% and (11.9±0.2%) (P<0.05) respectively as compared with XIAP transfected group. It was concluded that XIAP was expressed in most of bladder carcimoma samples. Overexpression of XIAP in T24 could significantly reduce the MMC-induced apoptosis of bladder carcinoma, suggesting its effect on the chemotherapeutic sensitivity of T24 cells.

  5. Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kerem Okutur

    2015-01-01

    Full Text Available Although signet-ring cell (SRC adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer.

  6. [A case of small cell carcinoma in the urinary bladder responding to gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].

    Science.gov (United States)

    Shirato, Akitomi; Shimamoto, Kenji; Ozawa, Akira; Tanji, Nozomu; Yokoyama, Masayoshi

    2006-12-01

    We report a case of primary small cell carcinoma of the urinary bladder. A 79-year-old man with the chief complaints of macrohematuria and pollakisuria was admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was small cell carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission. Total cystectomy with ileal conduit was performed following 3 courses of chemotherapy. Microscopic examination revealed that the small cell carcinoma had disappeared and the converted squamous cell carcinoma remained only in a small part of the specimens. The patient was carefully followed for 10 months after operation, with no tumor recurrence.

  7. Upper tract urinary cytology to detect upper tract urothelial carcinoma: Using the Johns Hopkins Hospital template and evaluation of its feasibility

    Directory of Open Access Journals (Sweden)

    Longwen Chen

    2015-01-01

    Full Text Available Introduction: Primary upper urinary tract (UT urothelial carcinoma (UC is rare. UT washing cytology is often used during UT surveillance. The Johns Hopkins Hospital template (JHHT is primarily designed to use on lower tract urine cytology and the data on applying JHHT on UT cytology is limited. We herein study the value of UT cytology in detecting UTUC using JHHT in a cohort. Materials and Methods : One hundred UT cytologic specimens were retrieved from our database during a 10-year period (2001-2011. For each patient, the cytology specimen with the highest degree of abnormality was selected. Histologic sections of these cases were also studied. Results: Seventy-six cases of UT cytology had histologic follow-up by either serial (>2 endoscopic biopsies or nephroureterectomy or ureterectomy. Among them, the cytologic diagnosis of positive or suspicious for high-grade UC (HGUC was made in 15 cases; suspicious for low-grade UC (LGUC in 3 cases; atypical urothelial cells (AUCs of undetermined significance in 19 cases; and negative in 39 cases. Of the 15 cases with diagnosis of positive for HGUC or AUC-HGUC (AUC-H, 10 had histologically confirmed HGUC, 1 had LGUC, and 4 had benign histology. All 3 cases of cytologically suspicious for LGUC had LGUC on concomitant histology. Among the 19 washings with AUCs with unknown significance, 7 were LGUC, 1 was HGUC, and 11 were benign on histology. Six of 39 cases with negative cytology had UC (3 low-grade and 3 high-grade on histology. Combining positive and AUC-H for UC diagnoses, sensitivity, and specificity for detecting HGUC were 71.4% and 91.9%, while for LGUC were 21.4% and 100%, respectively. Conclusions: UT washing cytology has high specificity for detecting UC, especially HGUC. Using JHHT on UT washing cytology is feasible, but the category of LGUC may need modification.

  8. [Clinical use of the ImmunoCyt/uCyt+ and fluorescence in situ hybridisation (FISH) tests for urothelial carcinomas].

    Science.gov (United States)

    Lodde, Michele; Mian, Christine

    2013-01-01

    In recent decades years, we have witnessed the propagation and marketing of numerous diagnostic tests capable of detecting, in the urine of patients, the presence of urothelial tumor markers. Among None of the different markers studied to date , no one has been able to meet all the requirements of the ideal marker. We present and discuss below we discuss the results reported in the literature of about two tests approved by the Food and Drug Administration [ImmunoCyt/uCyt+ and Fluorescence In Situ Hybridisation (FISH)], which have been and commercially available for about 10 years., ImmunoCyt/uCyt + and Fluorescence In Situ Hybridisation (FISH).

  9. Evaluation of {sup 11}C-choline PET/CT for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Sassa, Naoto; Yamamoto, Tokunori; Gotoh, Momokazu [Nagoya University Graduate School of Medicine, Department of Urology, Nagoya (Japan); Kato, Katsuhiko; Ikeda, Mitsuru; Shimamoto, Kazuhiro; Yamamoto, Seiichi [Nagoya University Graduate School of Medicine, Department of Radiological and Medical Laboratory Sciences, Nagoya (Japan); Abe, Shinji [Nagoya University Hospital, Department of Radiological Technology, Nagoya (Japan); Iwano, Shingo; Ito, Shinji; Naganawa, Shinji [Nagoya University Graduate School of Medicine, Department of Radiology, Nagoya (Japan)

    2014-12-15

    We conducted a pilot study to prospectively evaluate the efficacy of PET/CT with {sup 11}C-choline (choline PET/CT) for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract (UUT-UC). Enrolled in this study were 16 patients (9 men, 7 women; age range 51 - 83 years, mean ± SD 69 ± 10.8 years) with suspected UUT-UC. The patients were examined by choline PET/CT, and 13 underwent laparoscopic nephroureterectomy and partial cystectomy. Lymphadenectomy and chemotherapy were also performed as necessary in some of the patients. Of the 16 patients, 12 were confirmed to have UUT-UC (7 renal pelvis carcinoma and 5 ureteral carcinoma), 1 had malignant lymphoma (ureter), 1 had IgG4-related disease (ureter), and 2 had other benign diseases (ureter). Of the 16 study patients, 13 showed definite choline uptake in urothelial lesions, and of these, 11 had UUT-UC, 1 had malignant lymphoma, and 1 had IgG4-related disease. Three patients without choline uptake comprised one with UUT-UC and two with benign diseases. Of the 12 patients with UUT-UC, 3 had distant metastases, 2 had metastases only in the regional lymph nodes, and 7 had no metastases. Distant metastases and metastases in the regional lymph nodes showed definite choline uptake. The outcome in patients with UUT-UC, which was evaluated 592 - 1,530 days after surgery, corresponded to the patient classification based on the presence or absence of metastases and locoregional or distant metastases. Choline uptake determined as SUVmax 10 min after administration was significantly higher than at 20 min in metastatic tumours of UUT-UC (p < 0.05), whereas there was no statistically significant difference between the SUVmax values at 10 and those at 20 min in primary tumours of UUT-UC. This study suggests that choline PET/CT is a promising tool for the primary diagnosis and staging of UUT-UC. (orig.)

  10. Lymphography and percutaneous fine needle node aspiration biopsy in the staging of bladder carcinoma.

    Science.gov (United States)

    Boccon-Gibod, L; Katz, M; Cochand, B; Le Portz, B; Steg, A

    1984-01-01

    Forty-two patients with infiltrating bladder tumor were submitted to pedal lymphography with percutaneous fine needle node aspiration biopsy on an out patient basis. Of 41 evaluable patients, 59% had a positive lymphangiogram. Adequate material was obtained in 81% of the patients. Of 12 patients with a normal lymphography, none had a positive aspiration whereas 40% of the positive lymphangiograms correlated with a positive aspiration. The high rate of positive lymphangiogram negative aspirate is attributed to inflammatory changes due to previous TUR of the tumor. Twenty-one patients were submitted to radical cystectomy: 12 negative aspirations correlated with 11 negative lymphadenectomies, and 4 positive aspirations with 4 positive lymphadenectomies. There was no mortality and only mild morbidity in this series. Lymphography with fine needle percutaneous node aspiration biopsy has a role in the pre-operative staging of bladder carcinoma. Positive pelvic wall lymph nodes upgrade bladder carcinoma from a local to a systemic disease that is no longer amenable to any form of local treatment. Nodal assessment is therefore critical to treatment planning in order to spare the N+ patients unnecessary radical surgery. Pelvic lymph nodes have been evaluated, in the past, radiologically by bipedal lymphography or C.A.T. scanning. The high false positive and negative rates of these procedures (Benson et al., 1981; Boccon-Gibod et al., 1982) preclude their routine use (Correa 1982; Walsh et al., 1980).(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Differential expression of microRNA clusters in bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Zhifeng Wei; Zhengyu Zhang; Jingping Ge; Peng Xie; Hongqing Ma; Jianping Gao; Wen Cheng

    2013-01-01

    Objective: The aim of the study was to investigate the differential expression of microRNAs (miRNAs) in bladder transitional cell carcinoma (BTC). Methods: Fresh tissues were obtained from patients with BTC (9 cases; 3 cases with grade I, 3 cases with grade II, 3 cases with grade III) and those with normal bladder mucosa (3 cases) and stored in liquid nitrogen. Total RNA was extracted using TRizol reagent and RNA was quantified and quality control was performed. miRNA probes were labeled with Hy3TM fluorescence, then hybridized with a miRCURYTM array labeling kit. miRNA arrays were scanned and analyzed and the scanned result was validated using reverse transcription-polymerase chain reaction (RT-PCR). Results: In four groups of differentially expressed genes obtained from grade I, grade II, grade III, and grade I + grade II + grade III BTC tissues compared with normal bladder mucosa, hsa-miR-29b-1* was upregulated, and hsa-miR-923 and hsa-miR-300 were downregulated. The hsa-miR-29b-1*, hsa-miR-300, and hsa-miR-923 findings were confirmed by real-time RT-PCR. Conclusion: Genes that were differentially expressed between BTC and normal bladder mucosa may be involved in the pathogenesis and development of BTC, and may be useful for further studies of BTC-related genes.

  12. Clinical analysis of bladder inverted urothelial papilloma: Report of 43 cases%膀胱内翻性乳头状瘤临床诊疗分析(附43例报告)

    Institute of Scientific and Technical Information of China (English)

    宋彦; 宋永胜

    2012-01-01

    Objective: To investigate the clinical features, pathology, diagnosis and treatment of Inverted urothelial papilloma. Methods; A total of 43 cases of urothelial inverted papilloma were analyzed retrospectively,of these cases,35 were male and 8 were female,with a mean age of 57 years old. Most patients complained of painless gross he-maturia. The diagnosis could be established mainly by ultrasonic, cystoscope and pathology. 41 were treated by tran-surethral bladder tumor resection (TURBT) , among which 4 cases accompanying benign prostatic hyperplasia were treated by transurethral prostatic resection, 1 by partial cystectomy, 1 by cyst irrigation. Results: 35 cases were followed up for 12 months to 64 months ( mean 25 months). Intravesical recurrence was found in 5 cases,of them 4 cases underwent TURBT,and 1 case underwent total cystectomy. Conclusion; Bladder inverted urothelial papilloma is a benign tumor. TURBT is the preferred treatment choice for inverted papilloma of the bladder, Although this disease has a good prognosis, regular follow - up observations are necessary. Irrigation therapy could not reduce the risk of recurrence.%目的:探讨膀胱内翻性乳头状瘤的临床表现、病理类型及临床诊治方法.方法:回顾性分析2004年3月至2011年6月,我院收治膀胱内翻性乳头状瘤43例,其中男35例,女8例,平均年龄57岁.临床表现主要为无痛性肉眼血尿,下尿路症状及体检发现.诊断依据泌尿系超声,膀胱镜检及病理检查,41例行经尿道膀胱肿瘤切除(TURBT),其中4例合并良性前列腺增生者同时行经尿道前列腺切除术,膀胱部分切除术1例,未手术治疗仅行膀胱灌注1例.结果:35例随访12个月- 64个月,平均25个月.5例复发,其中4例再次行TURBT术,1例行膀胱全切治疗.结论:膀胱内翻性乳头状瘤是良性肿瘤,多见于男性,TURBT是膀胱内翻性乳头状瘤的首选治疗方法,预后良好,复发率低,膀胱灌注未见明显降低其复发率.但需定期随访.

  13. A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine

    OpenAIRE

    2013-01-01

    Background: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. Objective: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. Meth...

  14. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    OpenAIRE

    Liss, Michael A.; Noguchi, Jonathan; Lee, Hak J.; Vera, David R.; Kader, A. Karim

    2015-01-01

    A sentinel lymph node (SLN) is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND); its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assesse...

  15. Prognostic significance of 5-fluorouracil metabolism-relating enzymes and enhanced chemosensitivity to 5-fluorouracil by 5-chloro 2,4-dihydroxy-pyridine in urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Ide Hiroki

    2012-09-01

    Full Text Available Abstract Background Recently, S-1, a novel 5-fluorouracil (5-FU-based agent containing the strong dihydropyrimidine dehydrogenase (DPD inhibitor, 5-chloro-2,4-dihydropyrimidine (CDHP has been clinically used to treat various non-urothelial carcinomas (UC. High levels of thymidylate synthase (TS, the target enzyme of 5-FU and DPD which degrades the majority of 5-FU, are associated with poor prognosis in some cancers. However, only a few reports have dealt with this in UC. The aim of this study was to investigate the clinical significance of TS and DPD in upper tract urothelial carcinoma (UTUC and evaluate the role of TS and DPD on the sensitivity of 5-FU in UC cell lines and the anti-tumor effect of S-1 in UC xenograft model. Methods Firstly, we evaluated the immunohistochemical expression of TS and DPD in 176 patients with UTUC to determine their prognostic significance. Secondly, the levels of TS and DPD in UC cell lines were measured by ELISA and real-time PCR. Furthermore, the association between their levels and the sensitivity to 5-FU was examined using the small interfering RNA (siRNA specific for TS and DPD. Thirdly, the anti-tumor effect of S-1 was evaluated in UC xenograft model. Results Immunohistochemical evaluation of TS and DPD in UTUC human samples revealed that TS expression was significantly associated with stage, grade, and lymphovascular invasion and DPD expression was significantly associated with grade. Multivariate analysis revealed that high TS expression was an independent predictor of disease-specific survival in them. In in vitro study using UC cell lines, high levels of TS and DPD were associated with low response to 5-FU and these associations were confirmed with siRNA specific for TS and DPD. In in vivo study using UC xenograft model, S-1 treatment dramatically inhibited tumor growth compared to controls, tegafur, or UFT in UC tumor with a high level of DPD. Conclusions TS plays an important role in the prognosis of

  16. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    Science.gov (United States)

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Antecedentes: el carcinoma neuroendocrino de células pequeñas primario de vejiga es una lesión maligna muy poco frecuente. Caso clínico: paciente masculino de 68 años de edad, que tuvo hematuria macroscópica de 24 horas de evolución. Estudios de imagen mostraron tumoración vesical de 218 cc, que en 20 días alcanzó un volumen de 426 cc. A la tinción con hematoxilina-eosina, histológicamente se apreció: placa sólida infiltrante de bordes irregulares, compuesta por células neoplásicas con claro predominio de núcleo y escaso citoplasma (células pequeñas). A la tinción inmunohistoquímica con cromogranina parecía difusamente positivo en células neoplásicas, en un patrón granular citoplasmático. A la tinción con citoqueratina de alto peso molecular se observó patrón negativo en células neoplásicas con control interno positivo en el urotelio acompañante en espécimen. De igual manera, la tumoración fue positiva para sinaptofisina y CD-56 y negativa para CK-7 y CK-20. El paciente recibió tratamiento a base de radioterapia y quimioterapia. Conclusión: el carcinoma neuroendocrino de células pequeñas primario de vejiga representa de 0.35 a 0.70% de los tumores vesicales primarios. Su diagnóstico se basa en el reconocimiento histológico e inmunohistoquímico. El tratamiento se fundamenta en quimioterapia con cisplatino más cistectomía radical, excepto cuando existe enfermedad metastásica.

  17. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

  18. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Kruhøffer, Mogens; Andersen, Thomas Thykjær

    2004-01-01

    The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (s...... urothelium and urothelium with CIS lesions from the same urinary bladder revealed that the gene expression found in sTCC with surrounding CIS is found also in CIS biopsies as well as in histologically normal samples adjacent to the CIS lesions. Furthermore, we also identified similar gene expression changes...

  19. Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Sasaki, M; Fukuzawa, S

    1994-01-01

    BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of morphologic examination in transitional cell carcinomas of the urinary bladder (TCC) may be subject to observer variation, resulting in a reduced level of reproducibility. This may confound comparisons of treatment...... results. Using objective, unbiased stereologic techniques and ordinary histomorphometry, such problems may be solved. EXPERIMENTAL DESIGN: A study of 110 patients with papillary or solid transitional cell carcinomas of the urinary bladder in stage Ta through T4 was carried out, addressing reproducibility...

  20. Mincle, an Innate Immune Receptor, Is Expressed in Urothelial Cancer Cells of Papillomavirus-Associated Urothelial Tumors of Cattle.

    Directory of Open Access Journals (Sweden)

    Sante Roperto

    Full Text Available Mincle, macrophage-inducible C-type lectin, is a member of C-type lectin receptors. It plays an important role in anti-mycobacterial and anti-fungal immunity. Furthermore it senses dead cells through its primary ligand SAP130.We examined ten urothelial tumors of the urinary bladder of cattle. Eight of them expressed E5 cDNA of bovine papillomaviruses type 2 (BPV-2 and type 13 (BPV-13 that belong to Deltapapillomavirus genus. Two of them were not examined for detection of E5 cDNA. Mincle expression appeared to occur in urothelial neoplastic cells only. No mincle expression was detected in urothelial cells from healthy cattle. Mincle expression was characterized by a membranous pattern in papillary urothelial cancers; isolated and/or clustered urothelial cells showing a strong cytoplasmic immunoreactivity were primarily seen in invasive urothelial cancers.This is the first study about the expression of mincle in veterinary oncology and the first report which describes the expression of functional mincle receptor in neoplastic cells in medical literature. As it has been shown that urothelial cancer cells have the ability to function as antigen-presenting cells (APCs, it is conceivable that mincle expression is involved in the presentation of cancer cell antigens to cells of the immune system. Furthermore, since expression of mincle contributes to the control of Mycobacterium bovis BCG infection, this study has exciting clinical implications in comparative medicine keeping in mind that Bacillus Calmette-Guérin (BCG immunotherapy is currently the most effective treatment of non-muscle invasive bladder cancer in man. Mincle expression in urothelial tumor cells warrants further study to better understand the role, if any, of this receptor in bladder cancer. Future studies will provide insights in the role of mincle receptor of urothelial cancer cells in antitumor immunotherapy.

  1. A phase II trial of R115777, an oral farnesyl transferase inhibitor, in      patients with advanced urothelial tract transitional cell carcinoma

    DEFF Research Database (Denmark)

    Rosenberg, Jonathan E.; Maase, Hans von der; Seigne, John D.;

    2005-01-01

    BACKGROUND: R115777 is a potent farnesyl transferase inhibitor and has       significant antitumor effects in vitro and in vivo. METHODS: The objective       of the current study was to determine the objective response proportion in       patients with metastatic transitional cell carcinoma (TCC......) of the       urothelial tract who received treatment with R115777 at a dose of 300 mg       orally given twice daily for 21 days followed by 7 days of rest for every       4-week cycle. Thirty-four patients with TCC were enrolled in this Phase II       study. Patients were allowed to have received a maximum of one prior......       observed. CONCLUSIONS: The objective response rate of R115777 was not       sufficient to warrant future investigation in TCC as a single agent.       Preliminary evidence of the activity of R115777 in 2 chemotherapy-naive       patients may warrant further investigation in combination with first...

  2. Identification of "tumor-associated" nucleolar antigens in human urothelial cancer.

    Science.gov (United States)

    Yu, D; Pietro, T; Jurco, S; Scardino, P T

    1987-09-01

    Nucleoli isolated from HeLa S3 cells were used to produce rabbit antisera capable of binding nucleoli of transitional cell carcinomas (TCCa) of the bladder. Cross-reactivity of the rabbit antiserum with normal nucleoli was reduced by absorption with fetal calf serum, normal human serum, and human placental nucleoli. This antinucleolar antiserum exhibited strong reactivity in immunoperoxidase assays performed on specimens of human bladder cancer. In frozen tissue sections of 24 patients with TCCa and eight individuals without tumor, nucleolar staining was observed in all malignant specimens, but was not observed in seven of the normal specimens. Cytologic examination of bladder washing specimens from 47 normal individuals showed absence of nucleolar staining in 43 (91%) of 47 normal specimens while 12 (86%) of 14 specimens from patients with TCCa were positive. These results suggest that there are antigens associated with the nucleoli of HeLa cells and transitional cell carcinomas which are generally absent (or in low concentration) in normal human urothelial cells, and that antisera to these antigens may be useful in the cytologic diagnosis of human transitional cell carcinoma.

  3. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2012-01-01

    Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

  4. Staphylococcus saprophyticus ATCC 15305 is internalized into human urinary bladder carcinoma cell line 5637.

    Science.gov (United States)

    Szabados, Florian; Kleine, Britta; Anders, Agnes; Kaase, Martin; Sakinç, Türkân; Schmitz, Inge; Gatermann, Sören

    2008-08-01

    Invasion of bacteria into nonphagocytic host cells is an important pathogenicity factor for escaping the host defence system. Gram-positive organisms, for example Staphylococcus aureus and Listeria monocytogenes, are invasive in nonphagocytic cells, and this mechanism is discussed as an important part of the infection process. Uropathogenic Escherichia coli and Staphylococcus saprophyticus can cause acute and recurrent urinary tract infections as well as bloodstream infections. Staphylococcus saprophyticus shows strong adhesion to human urinary bladder carcinoma and Hep2 cells and expresses the 'Microbial Surface Components Recognizing Adhesive Matrix molecule' (MSCRAMM)-protein SdrI with collagen-binding activity. MSCRAMMs are responsible for adhesion and collagen binding in S. aureus and are discussed as an important pathogenicity factor for invasion. To investigate internalization in S. aureus, several fluorescence activated cell sorting (FACS) assays have been described recently. We used a previously described FACS assay, with slight modifications, in addition to an antibiotic protection assay and transmission electron microscopy to show that S. saprophyticus ATCC 15305 and the wild-type strain 7108 were internalized into the human urinary bladder carcinoma cell line 5637. The discovery of the internalization of S. saprophyticus may be an important step for understanding the pathogenicity of recurrent infections caused by this organism.

  5. Transitional cell carcinoma arising from a bladder diverticulum: computed tomography findings - case report; Carcinoma de celulas transicionais em um diverticulo de bexiga: achados na tomografia computadorizada - relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Almeida Junior, Jose Guiomar de; Santos, Maria Lucia de Oliveira; Vabo, Telmo Pimentel do; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia]. E-mail: edmarchiori@zipmail.com.br; Torres Neto, Gilberto [Hospital Universitario Pedro Ernesto, Rio de Janeiro, RJ (Brazil). Dept. de Radiologia; Silva, Klezer Gaspar Carvalho da [Hospital de Clinicas de Niteroi, RJ (Brazil)

    2003-03-01

    We report the case of a patient with a transitional cell carcinoma arising from a bladder diverticulum that was diagnosed by computed tomography. Although there is a greater incidence of neoplasms in bladder diverticula, its occurrence is uncommon and the diagnosis is at times difficult. The role, the importance and limitations of computed tomography in the diagnosis of transitional cell carcinoma arising from a bladder diverticulum are discussed. (author)

  6. Immunohistochemical Expression of Cyclooxygenase-2 in Urinary Bladder Transitional Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    F Niki

    2012-07-01

    Full Text Available Background: Transitional Cell Carcinoma (TCC is the most common type of urinary bladder cancer. Cyclooxygenase-2 (COX-2, a key enzyme in prostaglandins biosynthesis, has been introduced as a new candidate for targeted therapy in this cancer. In this study, we investigated the expression of COX-2 in urinary bladder TCCs and its relationship with clinicopathological parameters such as tumor grade and stage. Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Pathology reports of patients with definite diagnosis of urinary bladder TCCs who had undergone Transurethral Resection (TUR were reviewed and 40 cases were selected. Subsequently, COX-2 expression was assessed immunohistochemically by the examination of paraffin embedded tissue blocks. Staining in more than 5% of tumor cells was considered as positive expression. Results: COX-2 was expressed in 52.5% of the patients. High-grade tumors revealed a higher (87.5% COX-2 expression versus other grades of the lesions and there was a statistically significant difference in COX-2 expression between them (P<0.001. Patients age was also related to the expression of this marker (P=0.03. In contrast, this marker did not correlate with other characteristics including gender, lymphatic invasion or tumor stage. In addition, perineurial or vascular invasions were not detected in any of the patients. Conclusion: COX-2 expression was seen in more than half of our patients and it had a marked relation to tumor differentiation. Accordingly, this molecule may be a useful tumor marker in the assessment of urinary bladder cancers.

  7. Targeting of alpha-v integrins reduces malignancy of bladder carcinoma.

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    Full Text Available Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.

  8. Genetics of Bladder Malignant Tumors in Childhood

    Science.gov (United States)

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-01-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  9. Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.

    Science.gov (United States)

    Jou, Yeong-Chin; Shen, Cheng-Huang; Cheng, Ming-Chin; Lin, Chang-Te; Chen, Pi-Che

    2012-02-01

    Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.

  10. Lymphoepithelioma-like carcinoma of the urinary bladder: A case report and review of systemic treatment options

    Directory of Open Access Journals (Sweden)

    Nicholas M Pantelides

    2012-01-01

    Full Text Available Lymphoepithelioma-like carcinoma (LELC of the urinary bladder is a rare variant, which can occur in a pure form or in conjunction with transitional cell carcinoma. Owing to the scarcity of reported cases, the optimum treatment is yet to be defined, although the benefits of chemotherapy are increasingly recognised. We present a case of a 64-year-old man with pure LELC, treated with trans-urethral resection of the bladder tumor (TURBT and primary gemcitabine and platinum-based chemotherapy. He remained free of disease at six-month follow-up cystoscopy. The case adds to the growing evidence for the efficacy of chemotherapy, coupled with TUR, as part of a bladder-preserving treatment option for LELC.

  11. Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

    2007-01-01

    and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic...

  12. Defect in lectin-induced interleukin 2 production by peripheral blood lymphocytes of patients with invasive urinary bladder carcinoma

    DEFF Research Database (Denmark)

    Bubeník, J; Kieler, J; Tromholt, V

    1988-01-01

    The production of interleukin 2 (IL-2) by phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 21 patients with transitional cell carcinoma of the urinary bladder (BTCC) and 16 control blood donors was measured with a solid phase enzyme immunoassay based on the dual...

  13. Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Jacobsen, F

    1991-01-01

    Primary, flat carcinoma in situ of the urinary bladder is rare and its behaviour is unpredictable. The aim of this retrospective study was to obtain base-line data and investigate the prognostic value of unbiased, stereological estimates of the volume-weighted mean nuclear volume, nuclear vv, in 78...

  14. EXPRESSION OF A MUTANT hTERT IN HUMAN BLADDER CARCINOMA CELL LINE T24 AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    符伟军; 洪宝发; 黄君健; 徐兵; 高江平; 王晓雄; 黄翠芬

    2004-01-01

    Objective: To construct a mutant pEGFP- hTERT expression vector, to observe its steady expression in transfected human bladder carcinoma cell line T24 and its role in molecular regulatory mechanisms of telomerase, and to provide a new target gene for bladder cancer. Methods: PCR amplification was performed by using primers based on the known gene sequence of hTERT. PCR production was cloned into plasmid pGEMT-T easy and the sequence of mutant hTERT gene was analyzed. A recombinant mutant hTERT vector (pEGFP-hTERT) was constructed at the EcoR I and Sal I sites of the pEGFP-C1 vector. After transfecting the fusion gene into bladder carcinoma cell line T24 by calcium phosphate-DNA coprecipitation, the steady expression of GFP-hTERT fusion protein was tested by fluorescent light microscopy. The proliferation changes of bladder carcinoma cell line T24 were detected by light microscopy and senescence correlated β-galactosidase staining. Results: Identification of pEGFP-hTERT by enzyme digestion showed that mutant hTERT fragment had been cloned into EcoR I and Sal I sites of the pEGFP-C1 vector. The steady expression of GFP-hTERT fusion protein was localized in the nucleus of transfected cells. Expression of senescence-associated β-galactosidase in transfected cells gradually increased with extended cultured time and cell growth was suppressed. Conclusion: The mutant-type hTERT gene suppresses the proliferation of bladder carcinoma cell line T24 by competitive effect on telomerase activity. This suggests that hTERT gene might be a suitable gene target for bladder cancer therapy.

  15. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)

    2013-01-01

    textabstractEpidemiologyBladder cancer (BC) is the most prevalent type of urothelial cancer and is associated with thehighest costs of all cancer types due to intensive patient surveillance. Because bladder tumorsfrequently recur, patients need to be monitored extensively [1-4]. Incidence increases

  16. Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

    Science.gov (United States)

    Dyrskjøt, L; Zieger, K; Kissow Lildal, T; Reinert, T; Gruselle, O; Coche, T; Borre, M; Ørntoft, T F

    2012-01-01

    Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. Methods: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy (P=0.02, χ2-test). Conclusion: Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival. PMID:22596240

  17. Prostatic Adenocarcinoma Coexist with Transitional Cell Carcinoma of the Bladder and Prostate-A Case Report and Review of the Literature

    Institute of Scientific and Technical Information of China (English)

    TongZhang; YongXu; ShuminZhang

    2004-01-01

    Prostatic adenocarcinoma(PAC) with transitional cell carcinoma(TCC) of the bladder and prostate is a rare clinicopathological entity, presentation is usually late. We report a case with obstructive voiding symptoms and lumbago. Prostatic and cystic biopsy revealed PAC and TCC of bladder. Bone scan showed multiple bone metastases. He underwent transurethral resection of the prostate and bladder tumor and was found to have PAC with TCC of the bladder and prostate. We discuss the cases of PAC with TCC of the bladder and prostate.

  18. Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

    Science.gov (United States)

    2017-03-09

    Bladder Urothelial Carcinoma; Distal Urethral Carcinoma; Infiltrating Bladder Urothelial Carcinoma Associated With Urethral Carcinoma; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Proximal Urethral Carcinoma; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urethra Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Prostate Cancer; Stage IV Urethral Cancer; Ureter Carcinoma

  19. Feasibility of organ preservation in muscle-invasive transitional cell carcinoma bladder: A single institutional approach

    Directory of Open Access Journals (Sweden)

    Chhaya Roy

    2015-01-01

    Full Text Available Background: Trimodality treatment initial transurethral resection of the bladder tumor [TURBT] followed by concurrent chemotherapy and radiation and organ preservation have been gradually replacing the radical cystectomy in muscle-invasive transitional cell carcinoma (TCC of bladder. Aims: The aims of this study is to determine the clinical effectiveness, safety and protocol completion rate of trimodality treatment in muscle-invasive TCC of the bladder. Settings and Design: Prospective randomized and open-labeled study. Subjects and Methods: Patients with TCC of bladder, American Joint Committee on Cancer tumor node metastasis (TNM Bladder Cancer Staging (2002 T2-3, N0, M0. Were underwent TURBT followed by three cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin regimen. The patients were then randomized to receive either concurrent cisplatin 75 mg/m 2 in week 1 and 4 (arm-A or no cisplatin (arm-B along with external beam radiation therapy (EBRT 45 Gy, in 25 fractions over 5 weeks. 4 weeks after completion of the initial phase of treatment, all patients were re-evaluated with TURBT. Those with complete remission (CR received additional 15 Gy of EBRT in 8 fractions, while patients with residual disease were recommended for immediate radical cystectomy. All the patients of arm-B received boost dose of 15 Gy of EBRT. Statistical Analysis Used: The major statistical endpoints of this study were the CR rate at 8 weeks post-concurrent chemoradiotherapy (CCRT and only radiotherapy. Statistical significance was accepted at the P < 0.05 (two-sided level. Statistical analysis was performed entirely using the Statistical Package for the Social Sciences for Windows, version 17 (SPSS Inc., Chicago, IL, U.S.A.. Results: 8 weeks after completion of treatment 13/16 (81% patients were in CR in CCRT arm (arm-A compare to 6/15 (40% patients receiving radiation only (arm-B. Conclusions: Patients, after TURBT receiving CCRT

  20. CD82/KAI1在膀胱尿路上皮癌中的表达%Expression and significance of CD82/KAI1 in Bladder Urothelial Cancer

    Institute of Scientific and Technical Information of China (English)

    唐甜; 陕光; 陈小希

    2013-01-01

    Objective To investigate the expression and significanceof CD82/KAI1in bladder urotheli-alcancer tissues. Methods Parafflin-embeded specimens of 50 cases of bladder urothelialcancer and 5 normal tissues near the cancer, which were all filed in full pathological and clinical data, were collected from the pathology department of the Renmin Hospital of Wuhan University between 2006 and 2010. The expression of CD82/KAI1 was detected by immunohistochemical S-P method. Quantitative analysis of CD82/ KAI1 was conducted by a high-definitionpathological graphics context report system (HPIAS-1000). Oneway analysis of variance and SNK(q) tests were usedto analyse the mean density and the positive area rate of the immunohistochemical results. All data were processed by SPSS13. 0. Results The expression of CD82/KAI1 was higher in normal paracancerous tissues, than in bladder urothelialcancer tissues, with a statistically significant difference (P<0. 05). Conclusion The anomalous expression of CD82/KAI1 in bladder urothelialcancer tissues may play an important role in the occurrence and development of bladder urothelial cancer.%目的 探讨膀胱尿路上皮癌中CD82/KAI1的表达及临床意义.方法 收集武汉大学人民医院病理科2006-2010年有完整临床和病理资料的膀胱尿路上皮癌存档蜡块50例和5例癌旁组织,采用免疫组织化学S-P法检测50例膀胱尿路上皮癌和5例癌旁组织中CD82/KAI1的表达水平.采用HPIAS-1000 高清晰度彩色病理图文报告管理系统,对CD82/KAI1的表达进行定量分析,并用SPSS13.0 软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验.结果 CD82/KAI1在膀胱尿路上皮癌中呈低表达,癌旁组织中呈高表达.膀胱尿路上皮癌与癌旁组织相比,差异有显著性 (P<0.05).结论 CD82/KAI1在膀胱尿路上皮癌中的表达异常可能在膀胱尿路上皮癌的发生和发展中发挥了重要作用.

  1. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2013-01-15

    Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.

  2. Intraoperative prognostic factors and atypical patterns of recurrence in patients with upper urinary tract urothelial carcinoma treated with laparoscopic radical nephroureterectomy.

    Science.gov (United States)

    Carrion, Albert; Huguet, Jorge; García-Cruz, Eduard; Izquierdo, Laura; Mateu, Laura; Musquera, Mireia; Ribal, Maria José; Alcaraz, Antonio

    2016-08-01

    Objective The aims of this study were to identify clinical, intraoperative and pathological prognostic factors for predicting extraurothelial recurrence and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone laparoscopic radical nephroureterectomy (LRNU), and to investigate the site-specific patterns of recurrence and the associated outcomes. Materials and methods A retrospective revision was undertaken of 117 consecutive patients who had undergone transperitoneal LRNU for UTUC between 2007 and 2012. Univariate and multivariate Cox regression analyses were used to identify prognostic factors and Kaplan-Meier was used to estimate CSS. Results With a median follow-up of 20 months, 36 patients (30%) developed extraurothelial recurrence (local and/or distant). In the multivariate analysis, entering the urinary tract during LRNU was related to local recurrence (p = 0.04), management of the distal ureter to CSS (p = 0.003), pathological stage and positive margins to local (p = 0.001, p = 0.013), distant (p = 0.028, p = 0.009) and global recurrence (p = 0.05, p = 0.012) and CSS (p = 0.011, p = 0.042), and multifocality to distant recurrence (p = 0.024). Median time to recurrence was 11.4 months after LRNU. Of 36 patients with progression, 23 (64%) had simultaneous local and distant recurrence and eight had atypical metastases: two port-site metastases, five peritoneal, two subcutaneous and two abdominal wall implants. The 5 year CSS was 61% for all patients with UTUC and 9% for those with recurrence. Conclusions Intraoperative events could have a negative impact on the oncological outcomes of patients with UTUC treated with LRNU. The use of laparoscopy for advanced UTUC may be related to atypical ways of spreading.

  3. Research on the diagnostic values of the detection of urine exfoliated cells by FISH and cytologic technology in bladder urothelial tumor%FISH技术及细胞学技术检测尿脱落细胞对膀胱尿路上皮肿瘤诊断价值研究

    Institute of Scientific and Technical Information of China (English)

    陈伟; 伊惠霞; 张睿

    2014-01-01

    目的:比较荧光原位杂交(FISH)技术及细胞学技术检测尿脱落细胞对膀胱尿路上皮肿瘤诊断价值。方法采用CSP3/CSP7组合探针和GLPp16/CSP17组合探针对膀胱尿路上皮肿瘤疑似患者的尿脱落细胞进行FISH检测,同时采用细胞学技术检测尿脱落细胞,比较2种方法的灵敏度和特异度。结果FISH技术筛查膀胱尿路上皮肿瘤的灵敏度和特异度分别为92.5%和85.0%,细胞学技术的灵敏度和特异度分别为27.5%和90.0%。FISH技术的灵敏度显著高于细胞学技术(P<0.05),但2种方法的特异度差异无统计学意义(P>0.05)。结论FISH技术有望成为筛查膀胱尿路上皮肿瘤的新方法。%Objective To compare the diagnostic values of the detection of urine exfoliated cells by FISH and cytology technolo‐gy in bladder urothelial tumor .Methods The combination probes of CSP3/CSP7 and GLPp16/CSP17 were both used in the FISH detection of urine exfoliated cells from suspected patients with bladder urothelial tumor .The urine exfoliated cells were detected by cytology technology at the same time .The sensitivity and the specificity of the two methods were compared .Results The sensitivi‐ty and specificity of FISH for bladder urothelial tumor screening were 92 .5% and 85 .0% respectively ,and those of cytology tech‐nology were 27 .5% and 90 .0% respectively .The sensitivity of FISH was significantly higher than that of cytology technology (P0 .05) .Conclusion FISH is expected to become a new method for the screening of bladder urothelial tumor .

  4. The prognostic meaning of marker chromosomes in human urinary bladder carcinoma.

    Science.gov (United States)

    Burk, K; Harbott, J

    1984-01-01

    In summary, only a chromosome analysis of directly extracted tumour tissue seems to be of prognostic value, because this allows one to exclude alterations that are conditioned by cultures. The number of chromosomes does not give an indication of the malignancy and invasiveness of the tumour. The presence of marker chromosomes in superficial bladder carcinoma seems to worsen the prognosis of those patients significantly. Further observation of the previously investigated patients and new studies are aimed at determining whether the reported tendency proves to be valid. If the presence of marker chromosomes really enables us to predict an unfavourable prognosis, a timely cystectomy, i.e. cystectomy in the preinvasive stage, should decisively ameliorate the poor prognosis of these patients.

  5. RECURRENCE RISK FACTORS IN PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF BLADDER

    Institute of Scientific and Technical Information of China (English)

    YUE Xiang-hui; YANG Xiao-hong; ZHENG Fu-qing

    2005-01-01

    Objective: To study recurrence factors and set up a model to evaluate the prognosis of patients with bladder cancer.Methods: An analysis on recurrence-related factors was made by Cox's proportional hazards model analysis and logistic multiple linear regression model analysis in 212 patients with transitional cell carcinoma treated surgically from 1995~2001.These factors included clinical and pathologic figures. Results: The most important factor is metastasis to the regional lymph nodes, the Hazards ratio is 6.6 (P=0.0004), followed by multiple tumors (Hr=2.255, P<0.0001), tumor in trigone and bladder neck (Hr=2.053, P<0.0001), stage (Hr=2.057, P<0.0001), grade (Hr=1.569, P=0.0081), intravesical chemotherapeutic instillations (Hr-0.559, P=0.0011) and hematuria (Hr=0.762, P=0.0076). A predicting equation was established, and the predicting values were calculated according to the individual features of patients. The predicting and actual values were compared, and the sensitivity, specificity and overall concordance were 83.5%, 67.6% and 80.1% respectively. Conclusion:The evaluation of prognosis could be made quite accurately based on these factors.

  6. Survival Analysis in Patients with Non- metastatic Squamous Cell Carcinoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Ahmed M. Abdel-Rahim

    2011-04-01

    Full Text Available Background: We conducted a retrospective analysis to evaluate overall survival(OAS and disease free survival (DFS rates in patients with squamous cell carcinoma of the urinary bladder according to different prognostic factors. Methods: This retrospective study analyzed the medical records of patients with non-metastatic squamous cell carcinoma of the urinary bladder. All men underwent radical cystectomy and women underwent anterior pelvic exentration. Most patients had postoperative radiation therapy. The log-rank test examined differences in OASand DFS rates. Results: The medical records of 106 patients were analyzed. The median follow-up from the date of enrollment was 30 months and ranged from 2 to 73 months. For the entire group, three-year OAS rates were 46.9% and DFS rates were 44%. For patients with P2 (tumor invasion into the muscularis propria the three-year OAS rate was 53%, for P3 (tumor invasion into perivesical fat it was 45% and 9% for P4 (tumor invasion into adjacent organs, pelvic wall or abdominal wall The OAS rate was statistically significant in favor of P2 disease (P=0.0041. The three-year DFS rate was 50% for P2, 45% for P3 and 9% for P4 disease (P=0.0125. Administration of post-operative radiotherapy did not result in statistically significant improvement in three-year OASand DFS rates. Conclusion: Survival rates were statistically significant and higher in patients with P2 and P3 disease compared to P4 disease. Adjuvant radiotherapy did not result in statistically significant survival improvement.

  7. Concomitant Urothelial Cancer and Renal Tuberculosis

    Directory of Open Access Journals (Sweden)

    Sheray N. Chin

    2014-01-01

    Full Text Available We report a case of coexisting urothelial cancer and renal tuberculosis in the same kidney. The patient is a 72-year-old female with a remote history of treated pulmonary tuberculosis who presented with haematuria, initial investigation of which elucidated no definitive cause. Almost 1 year later, a diagnosis of metastatic urinary tract cancer was made. The patient received chemotherapy for advanced collecting duct type renal cell carcinoma, based on histological features of renal biopsy. Subsequent confirmatory immunostains however led to a revised diagnosis of urothelial cancer, necessitating a change in chemotherapy regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR testing of renal biopsy tissue and anti-TB therapy was coadministered with chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial cancer.

  8. Preoperative lymph-node staging of invasive urothelial bladder cancer with 18F-fluorodeoxyglucose positron emission tomography/computed axial tomography and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Jensen, Thor Knak; Holt, Per; Gerke, Oke

    2011-01-01

    investigated the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed axial tomography (¹⁸F-FDG PET/CT) and magnetic resonance imaging (MRI) for preoperative N staging of bladder cancer. Material and methods. From June 2006 to January 2008, 48 consecutive patients diagnosed with bladder...... cancer were referred to preoperative staging including MRI and ¹⁸F-FDG PET/CT. Eighteen out of 48 patients underwent radical cystoprostatectomy including removal of lymph nodes for histology, and were included in the study. Values of ¹⁸F-FDG PET/CT and MRI for regional N staging were compared...... to histopathology findings, the gold standard. Results. ¹⁸F-FDG PET/CT and MRI were performed in 18 patients. The specificities for detection of lymph-node metastases for MRI and ¹⁸F-FDG PET/CT were 80% (n = 15) and 93.33% (n = 15), respectively. The negative predictive values were 80% (n = 15) and 87.5% (n = 16...

  9. The positron emission tomography coupled with the tomography (PET-CT) {sup 18}F-fluoro-deoxy-glucose ([{sup 18}F]-FDG) in diagnostic imaging evaluation of urinary bladder cancer with bladder dilution. About four cases; La tomographie par emission de positons couplee a la tomodensitometrie (TEP-TDM) au {sup 18}F-fluoro-desoxy-glucose ([{sup 18}F]-FDG), avec dilution vesicale dans l'imagerie des tumeurs urotheliales. A propos de quatre cas

    Energy Technology Data Exchange (ETDEWEB)

    Godbert, Y.; Clermont, H. de; Laffon, E.; Allard, M.; Fernandez, P. [CHU de Bordeaux, Service de Medecine Nucleaire, 33 (France); Wallerand, H.; Ferriere, M. [CHU de Bordeaux, Service d' Urologie, 33 (France); Clermont, H.; Ferriere, J.M.; Ravau, A.; Allard, M.; Fernandez, P. [CHU de Bordeaux, Service d' Oncologie-Radiotherapie, 33 (France); Clermont, H. de; Laffon, E.; Ferriere, M.; Ravau, A.; Allard, M.; Fernandez, P. [Bordeaux-2 Univ. Victor-Segalen, 33 (France)

    2009-02-15

    This article illustrates, by means of four demonstrative case reports of urothelial carcinomas, the potential role of PET-CT using {sup 18}F-fluoro-deoxy-glucose ([{sup 18}F]-F.D.G.) with delayed images after diuretic. These patients were referred to the PET centre of the University Hospital in Bordeaux for the initial staging of a known bladder cancer or for the characterization of residual mass after radical treatment by surgery and radiotherapy. Analysing recent published results this preliminary study underlines the good performances of forced diuresis for the interpretation of bladder wall and thus enables to assess the potential clinical impact of [{sup 18}F]-F.D.G. PET-CT in the staging of urothelial carcinoma. (authors)

  10. Diagnosing the Location of Carcinoma in situ (CIS) of the Urinary Bladder Using Pirarubicin Hydrochloride%吡柔比星在膀胱原位癌定位诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    胡汪; 颜小平; 李成文; 王晨亮; 李志坚; 杨少鸿

    2010-01-01

    目的 探讨吡柔比星在膀胱原位癌(CIS)定位诊断中的效果.方法 在经尿道膀胱肿瘤电切(TUR-BT)术前膀胱内灌注吡柔比星(THP),术中在普通膀胱镜下能清楚地看见肿瘤组织及周围部分膀胱黏膜组织被染色,分别切除并送检.结果 在15例移行细胞癌患者中,11例于肿瘤周边区域或膀胱其他部位均发现有小的橙色区域.这些组织电切病理结果:2例移行细胞癌,3例原位癌,2例不典型增生,4例慢性膀胱炎.肿瘤旁未染色的膀胱粘膜组织病理切片均未发现膀胱尿路上皮癌.结论 通过经尿道膀胱肿瘤电切术前灌注吡柔比星,能肉眼发现膀胱微小癌灶及原位癌,方便而快速,能较好的指导电切,对减少肿瘤的遗漏有较大的临床意义.%Objectives To discuss the effect of pirarubicin hydrochloride(THP) on niveau diagnosis of bladder carcinoma in situ( CIS).Methods We dissolved 50 mg of THP in 50 ml of distilled water,and instilled the resulting solution into the urinary bladder.After 5 min,the urinary bladder is examined using a cystoscope.The study group consisted of 15 subjects.Results THP uptake was seen in 11 flat ( nontumorous) areas of the bladder mucosa in 11 patients.Of these,11 lesions in 3 patients were confirmed to be CIS.THP uptake was also seen in flat malignant lesions such as bladder cancer invasion into the prostatic urethra,and in benign lesions such as chronic cystitis and urothelial hyperplasia.Conclusions The present method can be useful to fi nd easily and macroscopically the location of flat malignant lesions such as CIS.

  11. Implementation of adaptive radiation therapy for urinary bladder carcinoma - Imaging, planning and image guidance

    Energy Technology Data Exchange (ETDEWEB)

    Tuomikoski, Laura; Collan, Juhani; Keyrilaeinen, Jani; Saarilahti, Kauko; Tenhunen, Mikko [Dept. of Oncology, Helsinki Univ. Central Hospital, Helsinki (Finland)], e-mail: laura.tuomikoski@hus.fi; Korhonen, Juha [Dept. of Oncology, Helsinki Univ. Central Hospital, Helsinki (Finland); Clinical Research Inst. Helsinki Univ. Central Hospital Ltd, Helsinki (Finland); Visapaeae, Harri [Dept. of Oncology, Helsinki Univ. Central Hospital, Helsinki (Finland); Dept. of Urology, Helsinki Univ. Central Hospital, Helsinki (Finland); Sairanen, Jukka [Dept. of Urology, Helsinki Univ. Central Hospital, Helsinki (Finland)

    2013-10-15

    Background: Adaptive radiation therapy (ART) for urinary bladder cancer has emerged as a promising alternative to conventional RT with potential to minimize radiation-induced toxicity to healthy tissues. In this work we have studied bladder volume variations and their effect on healthy bladder dose sparing and intra fractional margins, in order to refine our ART strategy. Material and methods: An online ART treatment strategy was followed for five patients with urinary bladder cancer with the tumors demarcated using Lipiodol. A library of 3-4 predefined treatment plans for each patient was created based on four successive computed tomography (CT) scans. Cone beam CT (CBCT) images were acquired before each treatment fraction and after the treatment at least weekly. In partial bladder treatment the sparing of the healthy part of the bladder was investigated. The bladder wall displacements due to bladder filling were determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment planning CT scans. An ellipsoidal model was applied in order to find the theoretical maximum values for the bladder wall displacements. Moreover, the actual bladder filling rate during treatment was evaluated using the CBCT images. Results: In partial bladder treatment the volume of the bladder receiving high absorbed doses was generally smaller with a full than empty bladder. The estimation of the bladder volume and the upper limit for the intra fractional movement of the bladder wall could be represented with an ellipsoidal model with a reasonable accuracy. Observed maximum growth of bladder dimensions was less than 10 mm in all three orthogonal directions during 15 minute interval. Conclusion: The use of Lipiodol contrast agent enables partial bladder treatment with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder model can be used for the estimation of the bladder volume changes and the upper limit of the bladder wall movement during the treatment

  12. Carcinoma In Situ Is Significantly Underdetected by Prenephroureterectomy Ureteroscopy in the Management of Upper Tract Urothelial Cancers

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    Angela Gillan

    2015-01-01

    Full Text Available Objective. Diagnostic reliability of prenephroureterectomy ureteroscopy (PNU for the detection of upper tract carcinoma in situ (CIS remains unproven in particular and underreported in general. Methods. Patients who underwent radical nephroureterectomy (RNU in a large multicentre retrospective study for upper tract transitional cell carcinoma (UT-TCC between January 2002 and December 2013 were identified from our hospitals databases. PNU appearances, stage, and grade of ureteroscopic biopsy were compared with final histology results of RNU to assess the diagnostic reliability of PNU for carcinoma in situ (CIS. Results. Three hundred patients underwent RNU for UT-TCC. 106 (106/300; 35.3% of the cohort had PNU using white light with biopsies taken in most (92/106; 86.7%. Postnephroureterectomy histology of the cohort showed CIS in 65 (65/300; 21.6% patients. Thirty nine of patients with CIS (39/65; 60% had prenephroureterectomy ureteroscopy biopsies. Out of ten patients with CIS on ureteroscopic biopsies, six did not show CIS on final histopathology (6/10; 60%. Moreover, grading and staging on PNU biopsies of obvious tumours showed a significant nonconcordance with final histopathology of RNU specimen (P=0.02. Overall survival was also shorter in patients with CIS compared with those without; this showed strong statistical significance (P=0.004. Conclusions. There is a high incidence of CIS in upper tract with significant underdetection and discordance rate between the histopathology of biopsy samples obtained by white light PNU and resected specimen of radical nephroureterectomy. The presence of concomitant CIS and high stage disease in the upper tract TCC carried a poor prognosis following radical nephroureterectomy.

  13. Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, K; Kissow Lildal, T;

    2012-01-01

    Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. Methods: We used specific q-RT-PCR assays to analyse...... the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed...... PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter...

  14. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature

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    Giannikaki Elpida

    2005-07-01

    Full Text Available Abstract Background The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. Case presentation We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year. The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. Conclusion It is important for the clinicians to keep in mind the possibility of a metachronous (successive or a synchronous (simultaneous malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.

  15. Antiproliferative factor regulates connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells

    Science.gov (United States)

    Matika, Christina A.; Wasilewski, Melissa; Arnott, John A.; Planey, Sonia Lobo

    2012-01-01

    Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis (IC)—a chronic, painful bladder disease of unknown etiology. APF inhibits the proliferation of normal bladder epithelial and T24 bladder carcinoma cells in vitro by binding to cytoskeleton-associated protein 4 (CKAP4) and altering the transcription of genes involved in proliferation, cellular adhesion, and tumorigenesis; however, specific molecular mechanisms and effector genes that control APF's antiproliferative effects are unknown. In this study, we found that there was a 7.5-fold up-regulation of connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells treated with APF. Western blot revealed a dose-dependent increase in CCN2 protein levels, with secretion into the culture medium after APF treatment. CCN2 overexpression enhanced APF's antiproliferative activity, whereas CCN2 knockdown diminished APF-induced p53 expression. Using a luciferase reporter construct, we found that APF treatment resulted in fivefold activation of the CCN2 proximal promoter and, of importance, that small interfering RNA–mediated knockdown of CKAP4 inhibited CCN2 upregulation. In addition, we demonstrate that CKAP4 translocates to the nucleus and binds to the CCN2 proximal promoter in an APF-dependent manner, providing evidence that CCN2 regulation by APF involves CKAP4 nuclear translocation and binding to the CCN2 promoter. PMID:22438586

  16. 薄层细胞学检查对诊断尿路上皮肿瘤的临床评价%Clinical evaluation of the value of thinprep cytologic test in diagnosis of urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    翁潭潭; 魏辉; 程志刚; 黄英; 李国; 罗旭杰; 方少洪

    2012-01-01

    Objective To evaluate the value of urine thinprep cylologic lesl(TCT)in the diagnosis of urothelial carcinoma. Methods 53 cases of urothelial carcinoma were delecled by TCT and conventional urinary cylology. Sensilivily and specificity of ihe urinary TCT were compared with that of the urinary cylology. The relationship belween TCT sensilivily and pathological grade and stage of urolhelial carcinoma were analyzed. Results The positive rale of urine TCT was 79. 2% (42/53 ) , which was significantly higher than those in conventional urinary cylology ( 58. 5% ) ( 31/53 ) ( P 0. 05 ]. Conclusions Urine TCT is more sensitive lhan conventional urinary cylology and may be an ideal method for no ninvasive diagnosis of urothelial carcinoma.%目的 评估应用薄层细胞学检查技术(TCT)检测尿脱落细胞在诊断尿路上皮肿瘤中的临床价值.方法 从2006年12月至2011年12月,对53例尿路上皮癌患者,分别进行常规的尿脱落细胞学检查和TCT检查,比较两种诊断性试验的敏感性、特异性以及不同尿路上皮肿瘤分级、分期与尿TCT之间的关系.结果 尿脱落细胞TCT检查的阳性率为79.2%(42/53),明显高于常规尿细胞学检查组的58.5%(31/53),差异有统计学意义(P0.05).结论 TCT避免了传统的细胞学检查阳性率低和假阴性率高的缺点,可作为尿路上皮癌的无创性诊断方法.

  17. Clinical Significance of Early Changes in Circulating Tumor Cells from Patients Receiving First-Line Cisplatin-Based Chemotherapy for Metastatic Urothelial Carcinoma1

    Science.gov (United States)

    Fina, Emanuela; Necchi, Andrea; Giannatempo, Patrizia; Colecchia, Maurizio; Raggi, Daniele; Daidone, Maria Grazia; Cappelletti, Vera

    2016-01-01

    Background: The therapeutic paradigm of metastatic urothelial carcinoma (UC) is rapidly shifting and new biomarkers are needed to enhance patient selection. Objective: Early identification of dynamic predictors of outcome may be a key to optimize the sequence of effective therapies in metastatic UC patients. Methods: Blood samples from patients receiving first-line MVAC chemotherapy were collected at baseline (T0) and after 2 cycles (T2). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of EPCAM, MUC1 and ERBB2 was studied using multiplex-PCR. Circulating tumor cell (CTC) positivity and cutoffs, obtained by receiver operator characteristic (ROC) curve analysis in healthy donors, were: ≥1 positive marker among EPCAM (≥0.40 ng/μl), MUC1 (≥0.10 ng/μl) and ERBB2 (≥0.20 ng/μl). CTC variation (T0/T2) was split in favorable (+/–, –/–, –/+) and unfavorable groups (+/+). Cox regression analyses evaluated associations with clinical factors. Results: In this pilot study to assess a new CTC detection method, among 31 evaluable patients, 17 (54.8%) were CTC-positive at T0. No association was found between CTC and objective response to MVAC. CTC dynamic changes better predicted 3-year progression-free (PFS) and overall survival (OS) compared to CTC status assessed at single time points. Unfavorable trend was univariably detrimental on 3-year PFS (10% vs. 49.2%, p = 0.006) and OS (20% vs. 63.5%, p = 0.017). Significance was maintained after controlling for liver metastases (p = 0.031 and p = 0.025 for PFS and OS) and MSKCC score (p = 0.014 and 0.025). Conclusions: Newly described early CTC changes during chemotherapy might be useful to improve our prognostic ability. Pending validation, these results could fulfill the promise to help accelerating therapeutic sequences. PMID:28035320

  18. Combined modality program with possible organ preservation for invasive bladder carcinoma: Results of RTOG protocol 85-12

    Energy Technology Data Exchange (ETDEWEB)

    Tester, W.; Porter, A.; Asbell, S.; Coughlin, C.; Heaney, J.; Krall, J.; Martz, K.; Venner, P.; Hammond, E. (Radiation Therapy Oncology Group, Philadelphia, PA (United States))

    1993-04-02

    This Phase 2 study was designed to test the tolerance and effectiveness of concurrent cisplatin-radiotherapy in the treatment of invasive bladder cancer. Objectives were to determine toxicity, complete response rate, bladder preservation rate, and survival. Patients with invasive bladder cancer, clinical Stages T2--4, NO-2 or NX, MO were treated with pelvic radiotherapy 40 Gy in 4 weeks and cisplatin 100 mg/m[sup 2] on days 1 and 22. Complete responders were given an additional 24 Gy bladder boost plus a third dose of cisplatin; patients with residual tumor after 40 Gy were assigned radical cystectomy. The complete remission rate following cisplatin and 40 Gy for evaluable cases was 31/47 (66%). Acute toxicity was acceptable with only two patients not completing induction therapy. Patients with poorly differentiated tumors were more likely to achieve complete remission. Of fully evaluable patients, 28/42 (67%) achieved complete remission with induction therapy, 11 remain continuously in remission, and eight have relapsed with bladder as the only site of failure. Five of these eight cases relapsed with noninvasive tumor. Of the 14 patients who failed to achieve complete remission, only three remain disease-free. Median survival is not reached, with 17/42 (19/48) deaths reported. Actuarial survival is 64% at 3 years. This combined cisplatin-radiotherapy regime was moderately well-tolerated and associated with tumor clearance in 66% of patients treated. Isolated bladder recurrences with invasive carcinoma are infrequent. Better definition of pretreatment selection criteria is needed if combined modality treatment is to achieve disease control and organ preservation for patients with bladder cancer. 37 refs., 3 figs., 5 tabs.

  19. Polycomb Repressor Complex 1 Member, BMI1 Contributes to Urothelial Tumorigenesis through p16-Independent Mechanisms

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    Lia E. De Faveri

    2015-10-01

    Full Text Available Urothelial carcinoma (UC causes significant morbidity and remains the most expensive cancer to treat because of the need for repeated resections and lifelong monitoring for patients with non–muscle-invasive bladder cancer (NMIBC. Novel therapeutics and stratification approaches are needed to improve the outlook for both NMIBC and muscle-invasive bladder cancer. We investigated the expression and effects of B Lymphoma Mo-MLV Insertion Region 1 (BMI1 in UC. BMI1 was found to be overexpressed in most UC cell lines and primary tumors by quantitative real-time polymerase chain reaction and immunohistochemistry. In contrast to some previous reports, no association with tumor stage or grade was observed in two independent tumor panels. Furthermore, upregulation of BMI1 was detected in premalignant bladder lesions, suggesting a role early in tumorigenesis. BMI1 is not located within a common region of genomic amplification in UC. The CDKN2A locus (which encodes the p16 tumor suppressor gene is a transcriptional target of BMI1 in some cellular contexts. In UC cell lines and primary tissues, no correlation between BMI1 and p16 expression was observed. Retroviral-mediated overexpression of BMI1 immortalized normal human urothelial cells (NHUC in vitro and was associated with induction of telomerase activity, bypass of senescence, and repression of differentiation. The effects of BMI1 on gene expression were identified by expression microarray analysis of NHUC-BMI1. Metacore analysis of the gene expression profile implicated downstream effects of BMI1 on α4/β1 integrin-mediated adhesion, cytoskeleton remodeling, and CREB1-mediated transcription.

  20. Influence of late-stage chronic kidney disease on overall survival in patients with upper tract urothelial carcinoma following radical nephroureterectomy

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    Sheng-Chen Wen

    2015-06-01

    Conclusion: Patients with late-stage CKD had a higher risk of having poor OS. Patients with concomitant bladder tumor had a greater risk of having bladder cancer recurrence despite primary tumor stage. Concomitant bladder tumor, however, had no effect on OS and CSS in this study.

  1. An in vitro model of intra-epithelial expansion of transformed urothelial cells

    NARCIS (Netherlands)

    Rebel, J.M.J.; Boer, de W.I.; Thijssen, C.D.; Vermey, M.; Zwarthoff, E.C.; Kwast, van der T.H.

    1993-01-01

    Replacement of normal urothelium by pre-cancerous epithelium may explain the high recurrence rate of human bladder cancer. An in vitro model was designed in order to study the mechanisms of expansion of transformed urothelial cells at the expense of normal urothelium. For this purpose, mouse bladder

  2. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

    DEFF Research Database (Denmark)

    Holten Andersen, MN; Brunner, N; Nielsen, HJ;

    2006-01-01

    Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  3. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

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    Keck Bastian

    2013-02-01

    Full Text Available Abstract Background Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. Methods We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC and 9 micropapillary (MPC carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Results Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis. Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters showed a hazard ratio of 3.2 (p=0.045 for PUC in contrast to patients suffering from MPC. Conclusions Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

  4. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

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    Michael A Liss

    2015-01-01

    Full Text Available A sentinel lymph node (SLN is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND; its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assessed a variety of imaging techniques to identify SLNs in patients with urothelial carcinoma of the bladder. Eight studies investigated human patients while one looked at animal (dog models. Seven studies representing 156 patients noted the negative predictive value of the SLN to predict a metastasis free state was 92% (92/100. The SLN biopsy was less accurate in metastatic patients with a positive predictive value of only 77% (43/56 with a false negative range of in individual studies of 0-19%. Clinically, positive nodes routinely do not take up the pharmaceutical agent for SLN. Therefore, SLN biopsy is a promising concept with a 92% negative predictive value; however, the false negative rates are high which may be improved by standardizing populations and indications. Novel technologies are improving the detection of SLN and may provide the surgeon with an improved ability to detect micrometastasis, guide surgery, and reduce patient morbidity.

  5. SPARING CYSTECTOMY IN PATIENTS WITH TRANSITIONAL-CELL CARCINOMA OF THE URINARY BLADDER

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    V. B. Matveyev

    2014-07-01

    Full Text Available Objective: to study the results of sparing cystectomy in patients with urinary bladder cancer (UBC.Subjects and methods. The study has covered 82 patients with transitional-cell UBC (T1-4aN0M0 who received radiotherapy (RT and thenunderwent radical cystectomy at the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, in 1980 to2007. Among them there were 76 (92.7% males and 6 (7.3% females. The median age was 55.2±10.8 years. Superficial (T1 and inva-sive (Т2—4а carcinomas were detected in 33 (40.2% and 49 (59.8% patients, respectively. Category N+ was identified in 3 (3.7% patients.All the patients received RT to the bladder area (median total focal dose (TFD 56±12.3 Gy and regional metastatic zones (median TFD40.0±0.0 Gy. A full effect of irradiation was achieved in 44 (53.7% patients, of whom 41 (93.2% developed local relapses. All the 82patients underwent radical cystectomy: that with ureterostomy in 28 (34.1% cases, Bricker’s operation in 45 (54.4%, Studer’s operationin 4 (4.9%, and rectal urinary bladder in 5 (6.1%. The median follow-up was 32.7±31.9 months.Results. The median interval between RT and cystectomy was 12.5±5.1 months; the median time of surgery was 360 (60—480 min; themedian blood loss was 1515.2±1227.8 ml. Intraoperative and postoperative complications developed in 10 (12.2% and 40 (48.6%patients, respectively. Repeated operations were performed in 7 (8.4% cases. Mortality was 4.9%. A urinary derivation technique failed toaffect the incidence of complications and the rates of mortality (p > 0.05. Histological studies revealed transitional-cell carcinoma in thedistant specimens in 80 (97.6% cases. Recurrences developed in 40 (48.8% of the 82 patients following an average of 32.9 (1—150months of cystectomy: local relapses in 5 (6.1% cases; distant metastases in 29 (35.4%; a local relapse and distant metastases in 5 (6.1%;urethral recurrence in 1 (1.2% patient. Five-year overall

  6. SPARING CYSTECTOMY IN PATIENTS WITH TRANSITIONAL-CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    V. B. Matveyev

    2009-01-01

    Full Text Available Objective: to study the results of sparing cystectomy in patients with urinary bladder cancer (UBC.Subjects and methods. The study has covered 82 patients with transitional-cell UBC (T1-4aN0M0 who received radiotherapy (RT and thenunderwent radical cystectomy at the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, in 1980 to2007. Among them there were 76 (92.7% males and 6 (7.3% females. The median age was 55.2±10.8 years. Superficial (T1 and inva-sive (Т2—4а carcinomas were detected in 33 (40.2% and 49 (59.8% patients, respectively. Category N+ was identified in 3 (3.7% patients.All the patients received RT to the bladder area (median total focal dose (TFD 56±12.3 Gy and regional metastatic zones (median TFD40.0±0.0 Gy. A full effect of irradiation was achieved in 44 (53.7% patients, of whom 41 (93.2% developed local relapses. All the 82patients underwent radical cystectomy: that with ureterostomy in 28 (34.1% cases, Bricker’s operation in 45 (54.4%, Studer’s operationin 4 (4.9%, and rectal urinary bladder in 5 (6.1%. The median follow-up was 32.7±31.9 months.Results. The median interval between RT and cystectomy was 12.5±5.1 months; the median time of surgery was 360 (60—480 min; themedian blood loss was 1515.2±1227.8 ml. Intraoperative and postoperative complications developed in 10 (12.2% and 40 (48.6%patients, respectively. Repeated operations were performed in 7 (8.4% cases. Mortality was 4.9%. A urinary derivation technique failed toaffect the incidence of complications and the rates of mortality (p > 0.05. Histological studies revealed transitional-cell carcinoma in thedistant specimens in 80 (97.6% cases. Recurrences developed in 40 (48.8% of the 82 patients following an average of 32.9 (1—150months of cystectomy: local relapses in 5 (6.1% cases; distant metastases in 29 (35.4%; a local relapse and distant metastases in 5 (6.1%;urethral recurrence in 1 (1.2% patient. Five-year overall

  7. The Implicaiton of the Expression of Three Cytokines in Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    YANGWeimin

    2002-01-01

    Objective To explore the expression of CK19,CK20 and bFGF in transitional cell carcinoma of the bladder(TCC) and their biological implication. Methods Samples from 54 patients with TCC were examined for expression of CK19, CK20 and Bfgf. Results There was a significant difference in CK19 expression between relapse and non-relapse groups(P0.05).There were significant differences in CD20 expression among groups with different pathological grades (P<0.05) and clinical stages (P<0.01) and between the relapse and non-relapse groups (P<0.0001).The expression of bFGF was significantly different among groups with different pathological grades and clini-cal stages and between the relapse and non-relapse groups(P<0.05).Conclusion The expression of CK19 ,CK20 and bFGF is closely associated with their biological behavior and among them bFGF is pri-marily secreted by TCC tumor tissues.

  8. Bilateral symmetrical corneal melting following intravesical Bacille Calmette-Guerin therapy for bladder carcinoma

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    Chandana Chakraborty

    2012-01-01

    Full Text Available A 63-year-old man with unremarkable previous ocular history presented with bilateral symmetrical corneal ulceration along with mucopurulent conjunctivitis and dry eye 10 days after the fourth dose of intravesical Bacille Calmette-Guerin (BCG instillation for treatment of bladder carcinoma. Slit lamp examination revealed thinning of the cornea at the base of the ulcer in both eyes. Conjunctival swab and scraping from ulcer sent for Gram and acid fast bacilli stain and culture were negative. On the basis of history, clinical examination, and laboratory investigations, we diagnosed it as bilateral immune mediated sterile corneal ulceration along with mucopurulent conjunctivitis and dry eye. He was treated with topical antibiotics, cycloplegics, cyclosporine, lubricant gel, and bandage contact lens. There was progressive stromal melting, descemetocele formation, and perforation in the inferior part of cornea in both the eyes. He was treated with pulse steroid and paramedian tarsorraphy in both eyes. The patient was subsequently lost to follow-up. We report this case to highlight this rare complication of BCG therapy, in order to improve their management protocol in patients with similar clinical profile. We could not find a similar case after thorough PubMed search.

  9. Mechanical characterization of benign and malignant urothelial cells from voided urine

    Science.gov (United States)

    Shojaei-Baghini, Ehsan; Zheng, Yi; Jewett, Michael A. S.; Geddie, William B.; Sun, Yu

    2013-03-01

    This study investigates whether mechanical differences exist between benign and malignant urothelial cells in voided urine. The Young's modulus of individual cells was measured using the micropipette aspiration technique. Malignant urothelial cells showed significantly lower Young's modulus values compared to benign urothelial cells. The results indicate that Young's modulus as a biomechanical marker could possibly provide additional information to conventional urinary cytology. We hope that these preliminary results could evoke attention to mechanical characterization of urine cells and spark interest in the development of biomechanical approaches to enhance non-invasive urothelial carcinoma detection.

  10. Synchronous dual primary malignancy of urinary bladder and hypopharynx in a 62-year-old male patient: An extremely rare phenomenon

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    Kuna J

    2016-04-01

    Full Text Available The diagnosis of multiple primary malignancy (MPM is not uncommon. Nevertheless synchronous MPM involving urinary bladder and hypopharynx is an extremely unusual event.No such cases have been reported so far in English literature to our review. We report the case of 62-year-old male patient who presented with haematuria and later dysphagia to solids. Whole body 18F-fluro deoxy glucose positron emission tomography- computed tomography (18FFDG PET-CT revealed two distinct lesions one in hypopharynx and another in urinary bladder. Biopsy from the urinary bladder mass and the hypopharyngeal lesion were suggestive of urothelial carcinoma and poorly differentiated squamous cell carcinoma respectively. The patient was treated with concurrent chemo-radiotherapy to hypopharynx. Following treatment he had improvement of dysphagia. Haematuria had also stopped. Because of severe comorbidities the planned radical cystectomy or radiotherapy were deferred. Currently the patient is in symptomatic remission six months following treatment.

  11. Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

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    Kamel Nermen A

    2011-01-01

    Full Text Available Abstract Background Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. Methods The study prospectively included 71 patients, (47 males, 24 females with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0 who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1, while 33 patients did not receive adjuvant radiotherapy (group 2. Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. Results The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03. The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p Conclusions Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

  12. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

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    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  13. New and promising strategies in the management of bladder cancer.

    Science.gov (United States)

    Apolo, Andrea B; Vogelzang, Nicholas J; Theodorescu, Dan

    2015-01-01

    Bladder cancer is a complex and aggressive disease for which treatment strategies have had limited success. Improvements in detection, treatment, and outcomes in bladder cancer will require the integration of multiple new approaches, including genomic profiling, immunotherapeutics, and large randomized clinical trials. New and promising strategies are being tested in all disease states, including nonmuscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and metastatic urothelial carcinoma (UC). Efforts are underway to develop better noninvasive urine biomarkers for use in primary or secondary detection of NMIBC, exploiting our genomic knowledge of mutations in genes such as RAS, FGFR3, PIK3CA, and TP53 and methylation pathways alone or in combination. Recent data from a large, randomized phase III trial of adjuvant cisplatin-based chemotherapy add to our knowledge of the value of perioperative chemotherapy in patients with MIBC. Finally, bladder cancer is one of a growing list of tumor types that respond to immune checkpoint inhibition, opening the potential for new therapeutic strategies for treatment of this complex and aggressive disease.

  14. Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

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    Kari T. Syvänen

    2014-05-01

    Full Text Available Neoadjuvant chemotherapy (NAC in muscle-invasive bladder cancer was introduced several years ago. Despite the evidence supporting its use in clinical practice, only a minority of patients who undergo radical cystectomy receive preoperative chemotherapy. In addition, recommendations and methods to detect patients who would benefit the most from NAC are still unclear. The European Association of Urology (EAU guidelines panel on muscle-invasive and metastatic bladder cancer recommends the use of cisplatin-based NAC for T2-T4a, cN0 M0 bladder cancer if the patient has a performance status ≥2 and if the renal function is not impaired, but the American Urological Association, for example, does not have any guideline recommendations on this topic at all. In this review we describe the current literature supporting NAC in association with radical cystectomy in muscle-invasive urothelial carcinoma of the bladder. Evidence acquisition was made searching the Medline database for original articles published before 1st February 2014, with search terms: “neoadjuvant chemotherapy”, “radical cystectomy”, and “invasive bladder cancer”.

  15. Immunohistochemical detection of hTERT in urothelial lesions: a potential adjunct to urine cytology

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    Khalbuss Walid

    2006-08-01

    Full Text Available Abstract Background Urine cytology has a critical role in evaluation for bladder carcinoma. Due to the low sensitivity of this technique, ancillary modalities such as the detection of markers of malignancy by immunochemistry are desirable. Promising factors in this context are components of the human telomerase enzyme complex. Telomerase repairs and extend telomeres, which when eroded beyond a critical limit trigger a senescence checkpoint. Accordingly, while absent in normal somatic cells, telomerase activity has been detected in the great majority of malignant tumor specimens tested, and so has potential value for the recognition of malignant cells in clinical specimens. Methods In this study, we investigated whether the immunohistochemical detection of the catalytic subunit of telomerase (hTERT can aid cytology in the diagnosis of bladder lesions. Findings from the retrospective evaluation of over 100 cell blocks, including urine sediments from confirmed malignant and benign conditions, were compared with routine urine cytology data. Results The presence of hTERT protein was indicative of the transformation of urothelia to a malignant phenotype. Nucleolar hTERT was expressed in 27 (93% of 29 samples obtained from patients with confirmed primary bladder cancer. Conversely, hTERT was detectable in only 3 (0.8% of 39 samples from benign conditions. The hTERT assay showed higher diagnostic sensitivity (84.8% than published urine cytology data (~65% for confirmed bladder carcinoma, however, the hTERT assay was less specific than cytology (65.2% vs. ~95% respectively. Conclusion As a highly sensitive marker, immunohistochemical hTERT detection in urine sediments represents a reliable adjunct to cytology in the accurate diagnosis of urothelial neoplasms.

  16. Keystone Symposia "ncRNAs in Development and Cancer", Vancouver, Canada: Increased release of exosomes and export of invasion-modulating miRNAs miR921, -23b, -and -224 from metastatic urothelial carcinoma cells

    DEFF Research Database (Denmark)

    Ostenfeld, Marie Stampe; Jeppesen, Dennis Kjølhede; Laurberg, Jens Reumert

    2013-01-01

    Cancer cells secrete soluble factors and various extracellular vesicles, including exosomes, into their tissue microenvironment. The secretion of exosomes is speculated to facilitate local invasion and increase the propensity of tumors to form distant metastases. Here we present a characterization...... of exosome vesicles from isogenic urothelial carcinoma cell lines, with different metastatic propensity by western blotting, electron microscopy, nanoparticle tracking analysis, dynamic light scattering, and profiling of 671 miRNAs by qRT-PCR. An increase in the number of multivesicular bodies and exosomes...... was observed for metastatic FL3 cells compared to isogenic non-metastatic T24 cells. The release was significantly inhibited by knockdown of Rab27b and pharmacological inhibition of nsmase2 by GW4869. miRNA profiling was conducted on parental cells and their secreted exosomes. Here, selective export of miR921...

  17. 液基薄层细胞学技术在尿路上皮癌患者术后随访中的应用%Application of Thinprep Cytologic Test in Urothelial Carcinoma Patients' Following-up after Operation

    Institute of Scientific and Technical Information of China (English)

    陈卓; 金伟

    2011-01-01

    Objective:To study the clinical value of Thinprep cytologic test(TCT) in urothelial carcinoma patients' following-up after operation. Methods: A total of 74 cases of UC were followed up regularly by urine examination of TCT and traditional manual smear method. Urine tumor cells were determined and the tumor recurrence events were monitored. Results: In this group of 74 cases of patients, 25 cases of high grade urothelial carcinoma patients, followed up for one year, recurrence of 13 cases, urine examination of TCT found the tumor cells is 11, the sensitivity rate was 84. 6 % , and 6 patients with urine examination of TCT earlier than for cystoscopy found tumor recurrence. The urine examination of traditional manual smear method found tumor cells is 7, the sensitivity rate was 53. 8%. All the 41 cases of low grade urothelial carcinoma patients were followed up for one year, recurrence events were found in cases. Urine examination of TCT found the tumor cells was 4, the sensitivity rate was 66. 7 %. The urine examination of traditional manual smear method found the tumor cells was 2, and the sensitivity rate was 33. 3%. Conclusions: Urine TCT check more sensitive than manual smear method and can be used in the urothelial carcinoma patients were followed up for tumor recurrence, and can play the early detection and early diagnosis function.%目的:探讨尿液膜式液基薄层细胞学技术(TCT)在尿路上皮癌患者术后随访中应用的临床价值.方法:对74例尿路上皮癌患者进行术后随访,定期行尿液TCT和手工涂片法找尿中肿瘤细胞和监测肿瘤复发,并对结果进行分析.结果:在本组74例患者之中,25例高级别尿路上皮癌患者,随访近1年,复发13例,其中尿液TCT找到肿瘤细胞11例,灵敏度84.6%,且有6例患者尿液TCT检查要早于膀胱镜检查发现肿瘤复发;手工涂片法尿中找到肿瘤细胞7例,灵敏度为53.8%.41例低级别尿路上皮癌患者中,随访近1年,复发6例,其

  18. Application of fluorescence in situ hybridization in the diagnosis of urothelial carcinoma%荧光原位杂交技术在尿路上皮癌诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    张卫兵; 刘波; 王行环; 程忠源; 郑新民; 李世文

    2012-01-01

    目的 探讨荧光原位杂交技术( FISH)在尿路上皮癌诊断中的应用价值.方法 采用FISH检测100例血尿患者尿脱落细胞中第3、7、17号染色体和第9号染色体p16位点异常,以组织病理学确诊尿路上皮癌为金标准,评估FISH诊断的敏感度和特异度,并与尿细胞学检查结果进行比较.结果 FISH检测和尿细胞学检查诊断尿路上皮癌的敏感度分别为82.5%和49.2%, 差异有统计学意义(P<0.05);特异度分别为86.7%和96.6%,差异无统计学意义(P>0.05).结论 与尿细胞学比较,FISH诊断尿路上皮癌具有较高的敏感度和相似的特异度.%Objective To evaluate the results of fluorescence in situ hybridization (FISH) for detecting urothelial carcinoma.Methods Voided urine samples from 100 patients with haematuria were analyzed by FISH and cytology; labeled probes for chromosomes 3,7,17 and 9 p16 were used to assess chromosomal abnormalities.The gold standard was pathology diagnosis.The overall sensitivity and specificity of FISH were evaluated and compared with cytology.Results The sensitivity of FISH and cytology in detection urothelial cancer were 82.5% and 49.2% respectively,and the specificity was 86.7% and 96.6% respectively.There was a significant difference between the sensitivity( P < 0.05 ),and the different between the specificity was not significant ( P > 0.05 ).Conclusion Compared with urine cytology,FISH diagnosis of urothelial carcinoma with high sensitivity and a similar specificity.

  19. Screening differentially expressed genes of urine exfoliated urothelial cells in transitional cell carcinoma by SSH%膀胱癌患者尿脱落细胞抑制消减文库的构建及差异基因的初步筛选

    Institute of Scientific and Technical Information of China (English)

    张冲; 郭柏鸿; 张志华; 吏葆光; 车团结; 陈一戎

    2009-01-01

    目的 应用抑制性消减杂交方法 筛选膀胱移行细胞癌患者与正常人尿脱落细胞差异表达基因.方法 分离膀胱移行细胞癌患者与正常人尿液中总mRNA,用SMART技术反转录成cDNA,经过酶切、接头连接、两轮消减杂交及两轮抑制性PCR,使得差异表达的DNA片段得以富集.PCR产物与T/A载体连接并转化大肠杆菌XL-blue构建差异表达基因的cDNA消减文库.文库扩增后随机挑取克隆进行酶切、测序及同源性分析.结果 PCR鉴定有317个克隆载有主要在200~900bp之间呈随机分布的插入片段,片段插入率达93.2%,证实建库成功.对20个质粒测序结果 经同源性比对分析,其中20个片段源于17个已知基因,1个克隆在GenBank中未检索到与其有相似性的基因序列,表明它们可能为BTCC差异表达的新基因.结论 该消减杂交文库质量町靠,它的成功构建为进一步筛选、克隆膀胱肿瘤差异表达基因提供了依据.也为膀胱肿瘤诊断基因芯片的研究与开发奠定了基础.%Objectives To Screening transitional" differentially suppression subtractive eDNA library in transitional cell carcinoma of bladder (BTCC) and normal urine exfoliated urothelial cells. Methods Total mRNA was isolated from BTCC and normal exfoliatod urothelial calls in urine, respectively. Then double-strand eDNA was synthesized and restricted by Hae Ⅲ. eDNA of BTCC was divided into two groups and ligated with either adaptor Ⅰ or adaptor 2. After hybridized twice normal exfoliated urothelial cells eDNA underwent nested PCR, the PCR products were cloned into PGM-T vector and transformed to E. Eoli JM109. Some pesitive clones were randomly picked up, digested, sequenced and homologous analyzed. Results The SSH library contained about 400 positive clones. Random analysis of 384 clones with enzyme restriction showed that 317clones contained cDNA fragments which were mainly between 200~900bp. The inserted rate reached to 82

  20. Survivin mRNA expression in urine as a biomarker for patients with transitional cell carcinoma of bladder

    Institute of Scientific and Technical Information of China (English)

    HOU Jian-quan; HE Jun; WEN Duan-gai; CHEN Zi-xing; ZENG Jian

    2006-01-01

    @@ Transitional cell carcinoma (TCC) of bladder is the most common malignant tumor in uropoiesis system. Up to date, there is still lack of an ideal marker for the diagnosis of TCC except CT and MRI imaging and cystoscopy. Cystoscopy is an invasive examination, which increases the possibility of urinary tract infection. Urine cytology has low sensitivity (21%-40%) in diagnosis of bladder cancer, especially for those with medium or high differentiation. The specificity is often affected by factors such as specimen collection, urinary tract infection, etc. Detecting the expression of survivin mRNA in urine by real time-PCR is simple in specimen collection and is sensitive and relatively specific, which provides a simple and noninvasive diagnostic method for TCC. Moreover it allows comparing the gene expression levels at different stages and grades of TCC, which can help define malignancy degree of TCC.

  1. Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of {sup 99m}Tc-MDP

    Energy Technology Data Exchange (ETDEWEB)

    Damle, Nishikant A; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar; Subbarao, Kiran; Singh, Prabhjot [All India Institute of Medical Sciences, New Delhi (India); Mishra, Rohini; Das, Nitendra Lal; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar [B. L. Kapur Memorial Hospital, New Delhi (India)

    2012-06-15

    A bone scan was per-formed using 740 MBq (29 mCi) {sup 99}mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). Soft tissue uptake of {sup 99}mTc-MDP is described in various benign and malignant conditions. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The postulated causes of {sup 99}mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man.

  2. Hedgehog pathway activation in human transitional cell carcinoma of the bladder

    OpenAIRE

    2012-01-01

    Background: The Hedgehog (Hh) signalling pathway functions as an organiser in embryonic development. Recent studies have shown constitutive activation of this pathway in various malignancies, but its role in bladder cancer remains poorly studied. Methods: Expression levels of 31 genes and 9 microRNAs (miRNAs) involved in the Hh pathway were determined by quantitative real-time RT–PCR in 71 bladder tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC) bladder cancers), a...

  3. The new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification for TA, T1 bladder tumors: is it an improvement?

    Science.gov (United States)

    Epstein, Jonathan I

    2003-08-01

    The World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of urothelial neoplasms of the urinary bladder was developed in an attempt to both improve upon prior classification systems as well as to adopt a classification system that would have widespread acceptance. Prior to this classification system, numerous diverse grading schemes for bladder cancer existed whereby the same lesion seen by different pathologists would result in very different diagnoses solely based on definitional differences of lesions. Another strength of the consensus classification system is that it provides detailed histological criteria for papillary urothelial lesions. In contrast, prior grading systems for bladder tumors were vague and subjective. The current classification system allows for designation of a lesion (papillary urothelial neoplasm of low malignant potential), which biologically has a very low risk of progression, yet is not entirely benign. In the past, these lesions were a source of controversy, as some experts in the field required very restrictive criteria for the diagnosis of papilloma and would label such lesions as malignant. Other experts in the field, not wanting to label a patient with such a low-grade papillary lesion as having carcinoma, would diagnose these lesions as papilloma. This intermediate category allows both schools of thought to diagnose a lesion as not fully malignant, yet still documents need for additional follow-up. Since its inception, several studies have been published documenting the relationship of tumors classified using the WHO/ISUP system to prognosis. These articles are summarized within this review.

  4. Clonal, self-renewing and differentiating human and porcine urothelial cells, a novel stem cell population.

    Directory of Open Access Journals (Sweden)

    Hans M Larsson

    Full Text Available Although urothelial progenitor-like cells have been described in the human urinary tract, the existence of stem cells remains to be proven. Using a culture system that favors clonogenic epithelial cell growth, we evaluated and characterized clonal human urothelial cells. We isolated human urothelial cells that were clonogenic, capable of self-renewal and could develop into fully differentiated urothelium once re-implanted into the subcapsular space of nude mice. In addition to final urothelial cell differentiation, spontaneous formation of bladder-like microstructures was observed. By examining an epithelial stem cell signature marker, we found p63 to correlate with the self-renewal capacity of the isolated human urothelial clonal populations. Since a clinically relevant, long-term model for functional reconstitution of human cells does not exist, we sought to establish a culture method for porcine urothelial cells in a clinically relevant porcine model. We isolated cells from porcine ureter, urethra and bladder that were clonogenic and capable of self-renewal and differentiation into fully mature urothelium. In conclusion, we could isolate human and porcine cell populations, behaving as urothelial stem cells and showing clonogenicity, self-renewal and, once re-implanted, morphological differentiation.

  5. Effect of Cerium on Expression and Activity of MMP-9 from Human Carcinoma of Bladder Cell Line

    Institute of Scientific and Technical Information of China (English)

    李瑾; 胡国武; 欧阳砥; 牛瑞芳; 周永洽; 申泮文

    2004-01-01

    The effects of Ce4+ on cell survival,expression and activity of matrix metalloproteinase-9(MMP-9)with MTT colorimetry and gelatin zymography assays in human bladder carcinoma cell line was studied.The results indicate that the lower concentration of Ce4+(0.01 mmol*L-1)has no influence on cell growth,but inhibits extremely expression of MMP-9 and increases its activity,whereas the higher concentration of Ce4+(1.0 mmol*L-1)can inhibit all of them.The results raise the possibility that Ce4+ may have beneficial effects in attenuating invasion and metastasis of malignant tumors.

  6. Cystectomy with orthotopic ileal neobladder reconstruction for treatment of bladder contracture after intravesical bacillus Calmette-Guerin therapy.

    Science.gov (United States)

    Vetorazzo Filho, José Eduardo; Bahia, Leandro Augusto Costa; Vedovato, Bruno César; Maron, Paulo Eduardo Goulart; Esteves, Paulo Ebert; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2014-01-01

    Bladder cancer is an important health problem worldwide due to high prevalence rates and costs related to treatment. A reduction in recurrence rates has been observed since the introduction of adjuvant intravesical immunotherapy with bacillus Calmette-Guerin. There are mild complications that are easily solved by local measures and orientations. Bladder contracture, a rare and severe local complication, in some cases leading to disability, is observed primarily in patients in a maintenance program. In this article we reported the case of a male patient who underwent transurethral resection of the bladder because of a high-grade T1 urothelial carcinoma and developed this complication during treatment with bacillus Calmette-Guerin. For this reason he was submitted to cystoprostatectomy with orthotopic ileal neobladder reconstruction.

  7. A retrospective study of post-operative gall bladder pathology with special reference to incidental carcinoma of the gall bladder

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    Jagannath Dev Sharma

    2014-06-01

    Methods: This retrospective study was carried out at a multi-specialty hospital in eastern India from the pathology records for the period from August 2005 to July 2008. The records were analyzed for gender, age group distribution, and pathological types with different histology. Results: Out of 863 records, chronic cholecystitis 51.2% was the most common histology and malignancy was seen in 2.7% (23/863 both pre-operative and post-operative diagnosis. In the neoplastic group incidental carcinoma was diagnosed in 1.9% (17/23 of cases Conclusion: Histopathological examination of gallbladder specimen helps to identify non-neoplastic conditions with its complications and also, for the detection of incidental carcinoma. Thorough sampling of all gallbladder specimens is a must to detect focal neoplastic changes. [Int J Res Med Sci 2014; 2(3.000: 1050-1053

  8. Expression of monocyte chemoattractant protein and MCP-1 gene in urothelial carcinoma of renal pelvis and its clinical significance%单核细胞趋化蛋白在肾盂尿路上皮癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    白鑫; 高健刚; 侯四川; 孙小庆; 朱磊一

    2011-01-01

    Objective To investigate the monocyte chemoattractant protein (MCP-1) gene expression of urothelial carcinoma of renal pelvis and adjacent normal tissues and the correlation of the incidence and pathological grading of urothelial carcinoma of renal pelvis.Methods Twenty cases of patients with urothelial carcinoma of renal pelvis( 12 cases of male, 8 cases of female) were taken the blood, carcinoma tissues and adjacent normal tissues.Thirty cases of non-cancer patients( 18 cases of male, 12 cases of female) as control group were taken blood samples.Expression of MCP-1 in plasma were detected by ELISA method quantitative determination,and the expression of MCP-1 in urothelial carcinoma of renal pelvis and adjacent normal tissues were investigated by immunohistochemical method.Real-time quantitative PCR was used to detect the expression of MCP-1 RNA.Results MCP-1 in plasma of urothelial carcinoma patients of renal pelvis was(173.4 ±82.1)pg/ml, higher than that of non-tumor group (91.8 ±34.6) pg/ml (P <0.05).Expression of MCP-1 in high-grade urothelial carcinoma of renal pelvis was(254.1 ± 125.8)pg/ml,while in low-grade urothelial carcinoma of renal pelvis was( 151.3 ± 79.5 ) pg/ml.Immunohistochemistry showed that MCP-1 positive rate in urothelial carcinoma of renal pelvis was 90.0% ( 18/20), and in adjacent normal tissues was 65.0% ( 13/20), with significant differences ( P < 0.01 ).Positive expression rate of MCP-1 in high-grade urothelial carcinoma of renal pelvis was 100.0% (4/4) , while in low-grade urothelial carcinoma of renal pelvis was 87.5% ( 14/16 ).Total RNA and mRNA levels of MCP-1 in the urothelial carcinoma of renal pelvis were statistically significant different compared with adjacent normal tissues group (P < 0.05).Conclusion The upregulation of MCP-1 gene expression is likely to play an important role in the incidence and metastasis of the urothelial carcinoma of renal pelvis.%目的 探讨肾盂尿路上皮癌组

  9. Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

    Directory of Open Access Journals (Sweden)

    Chen C

    2003-01-01

    Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

  10. 荧光原位杂交在尿路上皮癌诊断中的应用%Application of Fluorescence in situ Hybridization in the Diagnosis of Urothelial Carcinoma

    Institute of Scientific and Technical Information of China (English)

    王一; 孙光; 刘晓强; 孙岩; 李晨光; 吴长利; 王凡

    2011-01-01

    Objective: To detect chromosomal aneuploidy in the urine cells of patients with urothelial carcinoma and to evaluate the results of fluorescence in situ hybridization ( FISH ) as a non-invasive diagnostic method for detecting urothelial carcinoma.Methods: Fresh urine samples from 100 patients suspected of having urothelial carcinoma and 20 healthy subjects ( controls ) were collected, and urine cytology and FISH were conducted.Abnormalities on chromosome 3, 7, 17 and 9p21 ( p160 ) were found by FISH.Through the comparison and statistical analysis of the experimental results and pathology, the sensitivity and specificity of the two methods were established, as well as a threshold for the difference between high and low-grade carcinoma.Results: Urine samples of patients with urothelial carcinoma have many more chromosomal abnormalities than samples from the control group.The sensitivity and specificity of urine cytology were 71% and 80%, respectively.The sensitivity and specificity of FISH were 88% and 80%, respectively ( P < 0.01 ).The sensitivity of FISH was higher than urine cytology.The receiver operating characteristic ( ROC ) curve was drawn using the sensitivity and specificity data.The areas under the curve were 0.758 for urine cytology and 0.842 for FISH.Conclusion: FISH is a valuable and non-invasive detecting method for patients suspected of having urothelial carcinoma.The overall sensitivity of FISH is higher than that of urine cytology, but the specificity of the two methods is similar.%目的:检测尿路上皮肿瘤患者尿液脱落细胞染色体的缺失和非整倍异常,探讨FISH技术作为尿路上皮肿瘤患者无创诊断方法的价值.方法:收集可疑尿路上皮肿瘤患者和健康对照人群的新鲜尿液,同步进行细胞形态学分析及荧光原位杂交(Fluorescencein situ hybridization,FISH)检测3号、7号及17号染色体、9号染色体p16位点异常.共入选可疑尿路上皮肿瘤患者100

  11. Screening for Bladder and Other Urothelial Cancers

    Science.gov (United States)

    ... from a well that has high levels of arsenic . Drinking water that has been treated with chlorine . ... trials also are meant to show whether early detection (finding cancer before it causes symptoms ) decreases a ...

  12. 肾盂尿路上皮癌患者尿 NMP22、TPS、CYFRA21-1、CA19-9的检测与评估%Evaluation of NMP22,TPS,CYFRA21-1 and CA19-9 in the urine of patients for the diagnosis of urothelial carcinoma of renal pelvis

    Institute of Scientific and Technical Information of China (English)

    李志斌; 陈惠庆; 米振国; 宋继文; 韩雪冰; 韩存芝

    2016-01-01

    urothelial carcinoma of renal pelvis. Methods The study was a retrospective analysis with clinical data of cases of urothelial carcinoma of renal pelvis in Shanxi Provincial Tumor Hospital from 2010 January to 201 5 December,including 238 urine samples from 63 cases with urothelial car-cinoma of the renal pelvis (group A),46 cases with urothelial carcinoma of the urinary bladder (group B),62 cases with other urological diseases (group C),47 cases with no recurrence after radi-cal resection from the renal pelvis group for at least 2 years (group D),20 volunteers from our hos-pital (group E).Voided urine samples were collected before cystoscopies or surgeries.NMP22, TPS,CYFRA21-1,CA1 9-9 were measured by chemiluminescent immunoassays.We evaluated their concentration of urine and draw receiver operating characteristic cutoffs curves,and calulated the are-as under the ROC curves for further statistical analysis.Results The urine concentration of NMP22 in group A was higher than that in group B,the difference was statistically significant (P =0.001). There was no significant difference in the urine concentrations of TPS,CYFRA21-1 and CA1 9-9 between group A and group B (P >0.05).The urine concentrations of CA1 9-9,NMP22,CYFRA21-1 and TPS in group A were higher than that in group C, group D and group E,and the differences were statistically significant (P 0.05).The urine concentrations of NMP22,TPS,CYFRA21-1,CA1 9-9 in the group A were not statistically significant (P >0.05)between group of different pathological grades,clinical stages,tumor size, and whether there was hydronephrosis or not.The diagnostic accuracy of NMP22,TPS,CYFRA21-1 and CA1 9-9 were higher than that of urine cytology in group A by paired sample McNemar tests,and the differences were statistically significant (P <0.05).The areas under the ROC curves of the four tumor markers were all in 0.7-0.9,and the diagnostic efficacies were moder-ate,with the highest one was the combination of NMP22 and CYFRA21-1,which

  13. Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yi Luo

    2012-01-01

    Full Text Available Problem statement: Bladder cancer is a common urologic cancer and intravesical Mycobacterium bovis Bacillus Calmette-Guerin (BCG is the mainstay in the treatment of superficial bladder cancer. However, the current BCG therapy is not desirable with respect to its efficacy and side effects. Interleukin (IL-10, a T helper type (Th 2 cytokine, plays an important regulatory role in bladder cancer immunosurveillance and BCG immunotherapy. Therefore, blocking IL-10 activity could be beneficial for bladder cancer patients undergoing BCG therapy. Approach: Treatment with intravesical BCG in combination with systemic IL-10 monoclonal antibody (mAb specific for IL-10 neutralization or IL-10 receptor (IL-10R blockage has been evaluated in preclinical bladder cancer models. Results: Addition of anti-IL-10 neutralizing mAb or anti-IL-10R1 mAb enhances BCG induction of Th1 immune responses and anti-bladder cancer immunity. Conclusion/Recommendations: BCG immunotherapy of bladder cancer can be enhanced by addition of IL-10 blocking mAb. Future studies should aim to explore the mechanisms underlying the induction of enhanced antitumor immunity by BCG combination therapy and develop therapeutic regimens for clinical evaluation of the safety and efficacy of BCG combination therapy.

  14. TGF-β1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.

    Science.gov (United States)

    Zhang, Naiwen; Bi, Xiaojun; Zeng, Yu; Zhu, Yuyan; Zhang, Zhe; Liu, Yang; Wang, Jianfeng; Li, Xuejie; Bi, Jianbin; Kong, Chuize

    2016-08-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-β1 and test whether fascin1 is an important mediator of the tumor response to TGF-β1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-β1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-β1 treatment (pTGF-β1. The findings suggested that TGF-β1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-β1.

  15. A systematic experimental evaluation of microRNA markers of human bladder cancer

    Directory of Open Access Journals (Sweden)

    Anastasia eZabolotneva

    2013-11-01

    Full Text Available Background: MicroRNAs (miRNAs are a class of small RNAs that regulate gene expression. They are aberrantly expressed in many human cancers and are potential therapeutic targets and molecular biomarkers. Methods: In this study, we for the first time validated the reported data on the entire set of published differential miRNAs (102 in total through a series of transcriptome-wide experiments. We have conducted genome-wide miRNA profiling in 17 urothelial carcinoma bladder tissues and in nine normal urothelial mucosa samples using three methods: 1 An Illumina HT-12 microarray hybridization (MA analysis 2 a suppression-subtractive hybridization (SSH assay followed by deep sequencing (DS and 3 DS alone. Results: We show that DS data correlate with previously published information in 87% of cases, whereas MA and SSH data have far smaller correlations with the published information (6% and 9% of cases, respectively. qRT-PCR tests confirmed reliability of the DS data.Conclusions: Based on our data, MA and SSH data appear to be inadequate for studying differential miRNA expression in the bladder. Impact: We report the first comprehensive validated database of miRNA markers of human bladder cancer.

  16. Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma

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    Wang Shixin

    2011-04-01

    Full Text Available Abstract Background Bladder transitional cell carcinoma (BTCC is the fourth most frequent neoplasia in men, clinically characterized by high recurrent rates and poor prognosis. Availability of urinary tumor biomarkers represents a convenient alternative for early detection and disease surveillance because of its direct contact with the tumor and sample accessibility. Results We tested urine samples from healthy volunteers and patients with low malignant or aggressive BTCC to identify potential biomarkers for early detection of BTCC by two-dimensional electrophoresis (2-DE coupled with mass spectrometry (MS and bioinformatics analysis. We observed increased expression of five proteins, including fibrinogen (Fb, lactate dehydrogenase B (LDHB, apolipoprotein-A1 (Apo-A1, clusterin (CLU and haptoglobin (Hp, which were increased in urine samples of patients with low malignant or aggressive bladder cancer. Further analysis of urine samples of aggressive BTCC showed significant increase in Apo-A1 expression compared to low malignant BTCC. Apo-A1 level was measured quantitatively using enzyme-linked immunosorbent assay (ELISA and was suggested to provide diagnostic utility to distinguish patients with bladder cancer from controls at 18.22 ng/ml, and distinguish patients with low malignant BTCC from patients with aggressive BTCC in two-tie grading system at 29.86 ng/ml respectively. Further validation assay showed that Apo-A1 could be used as a biomarker to diagnosis BTCC with a sensitivity and specificity of 91.6% and 85.7% respectively, and classify BTCC in two-tie grading system with a sensitivity and specificity of 83.7% and 89.7% respectively. Conclusion Taken together, our findings suggest Apo-A1 could be a potential biomarker related with early diagnosis and classification in two-tie grading system for bladder cancer.

  17. Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian.

    Science.gov (United States)

    Wang, Hongkun; Wang, Ying; Kota, Krishna K; Kallakury, Bhaskar; Mikhail, Nabiel N; Sayed, Douaa; Mokhtar, Ahmed; Maximous, Doaa; Yassin, Etemad H; Gouda, Iman; Sobitan, Adebiyi; Sun, Bing; Loffredo, Christopher A; Zheng, Yun-Ling

    2015-11-01

    Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.

  18. Performance of computed tomographic urography in diagnosis of upper urinary tract urothelial carcinoma, in patients presenting with hematuria: Systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chlapoutakis, Konstantinos [Department of Radiology, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003 Iraklion, Crete (Greece); Theocharopoulos, Nicholas [Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003 Iraklion, Crete (Greece); Department of Natural Sciences, Technological Education Institute of Crete, P.O. Box 140, 71004 Iraklion, Crete (Greece); Yarmenitis, Spyros [Department of Radiology, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003 Iraklion, Crete (Greece); Damilakis, John [Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003 Iraklion, Crete (Greece)], E-mail: damilaki@med.uoc.gr

    2010-02-15

    Computed tomographic urography (CTU) is a relatively new diagnostic imaging technique, which combines the diagnostic advantages introduced by helical tomographic imaging, with the established technique of imaging during the renal excretory phase, into one single examination. Increasing availability of multidetector computed tomography (MDCT) units, further promotes the technique as the 'one-stop-shop' for the imaging investigation of patients with haematuria. We reviewed and meta-analyzed published literature, in order to evaluate the performance of CTU for the detection of upper urinary tract urothelial tumors. CTU proved to be a very sensitive and specific method for the detection of urothelial malignancy, with sensitivity ranging between 88% and 100%, and specificity between 93% and 100%. Pooled sensitivity was 96% (95% CI: 88-100%) and pooled specificity was 99% (95% CI: 98-100%). Direct comparison of the method with intravenous urography (IVU), confirmed the superiority of CTU over IVU in terms of sensitivity and specificity. Major drawbacks of CTU are increased radiation risk, injection of iodinated contrast media which may potentially be accompanied by serious side effects and increased cost, estimated as roughly three times that of IVU. According to our study, CTU is the method of choice for the detection of pathology in 'high risk' haematuria patients, i.e. patients older than 40 years of age presenting with gross haematuria.

  19. ImmunoCytTM and cytology for diagnosis of bladder carcinoma:a meta analysis

    Institute of Scientific and Technical Information of China (English)

    Yang Minggen; Zheng Zhouda; Zhuang Zhiming; Zhao Xiaokun; Xu Zhenqiang; Lin Haili

    2014-01-01

    Background Currently,cystoscopy and urine cytology are standard modalities in therapy monitoring and follow-up of bladder carcinoma (BC).Cystoscopy is an invasive and uncomfortable procedure while cytology has a limited value because it is operator-dependent and has low sensitivity.This study was to assess the accuracy of ImmunoCyt in detecting BC by comparing it with cytology using systemic analyses of studies published in both English and Chinese.Methods Cochrane systematic evaluation was used to search through MEDLINE,EMBASE,Cochrane Library,CMCC,and CNKI for studies regarding ImmunoCyt and cytology for detection of BC.Data were extracted and analyzed by the software MetaDiSc 1.4.Results In total 42 relevant studies were searched,of which 15 were enrolled and 12 491 patients were included.Heterogeneity,except for threshold effects,was found within these studies.A meta-analysis was performed using the random effect model.Pooled accuracy indicators like sensitivity,specificity,and diagnostic odds ratio of ImmunoCytTM and cytology were 0.75 (0.73-0.77) vs.0.45 (0.43-0.48),0.73 (0.72-0.74) vs.0.97 (0.96-0.97),and 10.97 (7.53-15.99) vs.16.40 (10.57-25.46),respectively.The sensitivity of both was increased with the increase of tumor grade and stage.The area under summary receiver operating characteristics curve was 0.834 4 and 0.853 4 and the Q index 0.766 7 and 0.785 3 for ImmunoCyt and cytology,respectively.Combination of both can obviously improve the accuracy of diagnosis.Conclusions ImmunoCyt has a high sensitivity in detecting BC,but its specificity is low.As an important adjunct,ImmunoCytTM can not replace cytology,but combined with cytology it could improve sensitivity with high specificity in the detection and postoperative monitoring of BC.

  20. Neoadjuvant chemotherapy and hyperfractionated radiation therapy for the urinary bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ishibashi, Ryochi; Shigematsu, Naoyuki; Kawada, Tetsuya; Nakayama, Toshitake; Andou, Yutaka; Kubo, Atsushi; Tachibana, Masaaki [Keio Univ., Tokyo (Japan). School of Medicine; Ito, Hisao

    1997-06-01

    The standard treatment for an invasive bladder cancer is radical surgery; however, the quality of life of the patients who undergo total cystectomy is unfavorable even when the ileal conduits were constructed. We carried out a bladder-conserving treatment for 8 bladder cancer patients by using a hyperfractionated radiotherapy together with low dose of cis-platinum or carboplatinum daily as a radiosensitizer following trans-urethral tumor resection and neoadjuvant chemotherapy. Cystoscopic findings and biopsies at one month after completing radiation showed complete remission (CR) and partial response (PR) for 5 and 3 patients, respectively. All of the PR cases had T4 tumors and the patients with tumors smaller than T3 and without lymph node metastasis achieved CR. All patients completed radiotherapy without acute severe complications. Six patients have remained alive for more than 10 months and radiation induced late complications such as bladder or intestinal insufficiency have not been observed thus far. (author)

  1. Remarkable Response to Neoadjuvant Therapy with Methotrexate, Vinblastine, Adriamycin, and Cisplatin for Undifferentiated Bladder Carcinoma: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Kenji Numahata

    2014-11-01

    Full Text Available We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.

  2. Long-term survival after gemcitabine and cisplatin in patients with locally advanced transitional cell carcinoma of the bladder: focus on supplementary treatment strategies

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Sengelov, Lisa; von der Maase, Hans

    2007-01-01

    OBJECTIVE: The objective was to evaluate response and survival, as well as efficacy of subsequent supplementary treatment and follow-up strategy in patients with locally advanced transitional cell carcinoma of the bladder following combination chemotherapy with gemcitabine and cisplatin (GC...

  3. Multiple skeletal muscle metastases in a case of transitional cell carcinoma of bladder detected by F-18 FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava; Mittal, Bhagwant Rai; Chakraborty, Dhritiman; Bhattacharya, Anish; Singh, Baljinder [Institute of Medical Education and Research, Chandigarh (India)

    2010-12-15

    We present a case of poorly differentiated muscle invasive transitional cell carcinoma in a 64-year-old male diagnosed with FDG-avid mass in the urinary bladder wall and multiple skeletal muscles visualised on F-18 FDG PET/CT

  4. Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Folio, Les Roger, E-mail: Les.folio@nih.gov [Lead Radiologist for CT, NIH Radiology and Imaging Sciences, 10 Center Drive, Bethesda, MD 20892 (United States); Turkbey, Evrim B., E-mail: evrimbengi@yahoo.com [Johns Hopkins University, Baltimore, MD 21218 (United States); Steinberg, Seth M., E-mail: steinbes@mail.nih.gov [Head, Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, 9609 Medical Center Drive, Room 2W334, MSC 9716, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892 (United States)

    2015-09-15

    Highlights: • It is clear that 2D axial measurements are incomplete assessments in metastatic disease; especially in light of evolving antiangiogenic therapies that can result in tumor necrosis. • Our pilot study demonstrates that taking volumetric density into account can better predict overall survival when compared to RECIST, volumetric size, MASS and Choi. • Although volumetric segmentation and further density analysis may not yet be feasible within routine workflows, the authors believe that technology advances may soon make this possible. - Abstract: Objectives: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. Materials and methods: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan–Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. Results: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2–14 months. Only the VTV criteria demonstrated a statistical association with OS (p = 0.019; median OS 9.7 vs. 3.5 months). Conclusion: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to

  5. Hemodynamic analysis of bladder tumors using T{sub 1}-dynamic contrast-enhanced fast spin-echo MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kanazawa, Yuki, E-mail: yukikanazawa@me.com [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80, Kodatsuno, Kanazawa, Ishikawa 920-0942 (Japan); Department of Radiology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto (Japan); Miyati, Tosiaki [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80, Kodatsuno, Kanazawa, Ishikawa 920-0942 (Japan); Sato, Osamu [Department of Radiology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto (Japan)

    2012-08-15

    Objectives: To evaluate the hemodynamics of bladder tumors, we developed a method to calculate change in R{sub 1} value ({Delta}R{sub 1}) from T{sub 1}-dynamic contrast-enhanced fast spin-echo magnetic resonance imaging (T{sub 1}DCE-FSE-MRI). Materials and methods: On a 1.5-T MR system, T{sub 1}DCE-FSE-MRI was performed. This study was applied to 12 patients with urinary bladder tumor, i.e. urothelial carcinoma. We compared {Delta}R{sub 1}-time and {Delta}SI-time between a peak in the {Delta}R{sub 1}-time and {Delta}SI-time curve occurred during the first pass within 60 s. Next, we assessed the slope of increase for 180 s after CA injection (Slope{sub 0-180}). Results: The mean slope of the first pass was significantly higher for bladder tumors on both the {Delta}R{sub 1}-time and the {Delta}SI-time curve compared with normal bladder walls. Moreover, a significant difference was apparent between bladder tumors and normal bladder walls on the mean Slope{sub 0-180} in the {Delta}R{sub 1}-time curve. However, no significant difference in the mean Slope{sub 0-180} was observed on the {Delta}SI-time curve between bladder tumors and normal bladder walls. Conclusion: T{sub 1}DCE-FSE-MRI offers three advantages: quantitative analysis; high-quality (i.e., artifact-free) images; and high temporal resolution even for SE images. Use of {Delta}R{sub 1} analysis with T{sub 1}DCE-FSE-MRI allows more detailed information on the hemodynamics of bladder tumors to be obtained and assists in differentiation between bladder tumors and the normal bladder wall.

  6. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

    Directory of Open Access Journals (Sweden)

    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  7. MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype

    Science.gov (United States)

    Lenherr, Sara M.; Tsai, Sheaumei; Silva Neto, Brasil; Sullivan, Travis B.; Cimmino, Cara B.; Logvinenko, Tanya; Gee, Jason; Huang, Wei; Libertino, John A.; Summerhayes, Ian C.; Rieger-Christ, Kimberly M.

    2017-01-01

    The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3–T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease. PMID:28218662

  8. The time from diagnosis of bladder cancer to radical cystectomy in Polish urological centres – results of CysTiming Poland study

    Science.gov (United States)

    Poletajew, Sławomir; Lisiński, Janusz; Moskal, Karol; Ornat, Jacek; Renk, Kacper; Szlaga, Michał; Tworkiewicz, Jakub; Wojtkowiak, Dominik; Wołyniec, Paweł; Woźniak, Krzysztof; Radziszewski, Piotr

    2014-01-01

    Introduction The aim of the study was to assess the waiting time, from establishing the indications for radical cystectomy to surgery, in patients with urothelial carcinoma of the bladder at different Polish urological centres and to determine its influencing factors. Material and methods Retrospective analysis of data was performed on all consecutive radical cystectomies, performed in 2008–2012, at 10 Polish urological centres. The waiting time of patients from establishing the indications for radical cystectomy to surgery, as well as factors potentially influencing this time, were assessed. University (3), provincial (3) and regional (4) hospitals were defined as the 3rd, 2nd and 1st level referral hospitals, respectively. Results A total of 575 patients qualified for radical cystectomy due to muscle invasive urothelial carcinoma of the bladder (MIBC, 68% of cases) or failure of previous treatment of non–muscle invasive urothelial carcinoma of the bladder (NMIBC, 32%) were included in the analysis. The average time after the establishment of indications to surgery was 73.4 days, with a median of 56 days. In the case of 121 patients (22.1%), the waiting time exceeded 90 days. Significant differences in waiting time were found when the hospital referral levels were taken into consideration. In the 3rd level referral hospitals the median time for cystectomy was 61.5 days (p = 0.035), in the 2nd level referral hospitals – 45 days (p = 0.000) and, in the 1st level referral hospitals – 58 days (p = 0.051). Conclusions The waiting time from establishing the indications for radical cystectomy to surgery for most cases in Poland does not exceed 90 days. PMID:25667748

  9. 30. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to MMC

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AND AIM: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50-to 70- year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection. So drug resistance, especially in its multiple type forms, remains a major and difficult problem to resolve in bladder cancer therapy. This phenomenon has often been ascribed to strictly pharmacolo-gic factors, such as the overexpression of multidrug transporters P-glycoprotein, multidrug resistance related protein (MRP), and other variables closely implicated DNA repair and induction/modulation of apoptosis, such as P53 and the Bcl-protein family. Furthermore, it has been recently shown that certain growth factors(IGFs etc) may be involved in the mechanism of drug resistance. Clearly, these findings suggest the design of new strategies that might improve bladder tumor response to chemotherapy. Results have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. The acquirement of autonomous growth capacity was likely to be an important element in the oncogenesis of bladder tumors. Furthermore, criss-cross experiments showed that supernatants stimulated not only proliferation of the autologous cell line of bladder cancer, but also growth of the other bladder cancer cell lines, suggesting the production of common autocrine factors in bladder tumor cells. Some factors or their receptors involved in autocrine loop mechanism of bladder tumor cells have been confirmed, such as IL-6, the epidermal growth factor receptor, IFN-beta, transferrins-like substance etc. But certain factors which may

  10. Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer.

    Science.gov (United States)

    Miyake, Makito; Nakai, Yasushi; Anai, Satoshi; Tatsumi, Yoshihiro; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

    2014-05-01

    Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named "Cellular Fluorescence Analysis Unit" (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68-80% sensitivity) than conventional urine cytology, BTA and NMP22 (8-20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.

  11. Schistosomiasis-induced squamous cell bladder carcinoma in an HIV-infected patient

    DEFF Research Database (Denmark)

    Marbjerg, Lis Høy; Øvrehus, Anne Lindebo Holm; Johansen, Isik Somuncu

    2015-01-01

    The burden of Schistosoma haematobium-associated bladder cancer is very high in Africa; nevertheless the disease can pose considerable diagnostic challenges in low prevalence countries. We present the case of a 40-year-old HIV co-infected woman, originally from Mozambique, who had persisting...... haematuria for more than a year. Investigations revealed invasive S. haematobium-associated squamous cell bladder cancer. If her origin had been taken into account, the diagnosis might have been made earlier. Awareness of the disease prevalence among HIV co-infected patients from endemic areas and timely...... screening of such patients is important for the early diagnosis of schistosomiasis and related complications, such as S. haematobium-associated squamous cell bladder cancer....

  12. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

    Directory of Open Access Journals (Sweden)

    Hiroki Ide

    2015-01-01

    Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

  13. Schistosomiasis-induced squamous cell bladder carcinoma in an HIV-infected patient

    DEFF Research Database (Denmark)

    Marbjerg, Lis Høy; Øvrehus, Anne Lindebo Holm; Johansen, Isik Somuncu

    2015-01-01

    The burden of Schistosoma haematobium-associated bladder cancer is very high in Africa; nevertheless the disease can pose considerable diagnostic challenges in low prevalence countries. We present the case of a 40-year-old HIV co-infected woman, originally from Mozambique, who had persisting...... haematuria for more than a year. Investigations revealed invasive S. haematobium-associated squamous cell bladder cancer. If her origin had been taken into account, the diagnosis might have been made earlier. Awareness of the disease prevalence among HIV co-infected patients from endemic areas and timely...

  14. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

    DEFF Research Database (Denmark)

    Gui, Yaoting; Guo, Guangwu; Huang, Yi;

    2011-01-01

    discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more...... frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer....

  15. Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classification system.

    Science.gov (United States)

    Miyamoto, Hiroshi; Miller, Jeremy S; Fajardo, Daniel A; Lee, Thomas K; Netto, George J; Epstein, Jonathan I

    2010-01-01

    The classification and grading of papillary urothelial neoplasms has been a long-standing subject of controversy. Previously, numerous diverse grading schemes for bladder tumor, including the 1973 World Health Organization (WHO) classification, existed whereby one of the major limitations was poor inter-observer reproducibility among pathologists. The WHO/International Society of Urological Pathology (ISUP) consensus classification system of urothelial neoplasms of the urinary bladder was developed in 1998 and was revised most recently in 2003 (published in 2004). Importantly, the current classification system provides detailed histological criteria for papillary urothelial lesions and allows for designation of a lesion (papillary urothelial neoplasm of low malignant potential) with a negligible risk of progression. Thus, the latest system is designed to be a universally acceptable one for bladder tumors that not only could be effectively used by pathologists, urologists, and oncologists, but also stratifies the tumors into prognostically significant categories. This article outlines the 2004 WHO/ISUP classification system regarding the specific histological criteria for non-invasive papillary urothelial neoplasms and the clinical significance of each category.

  16. High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma

    Science.gov (United States)

    Luo, Yihuan; Zhang, Xin; Mo, Meile; Tan, Zhong; Huang, Lanshan; Zhou, Hong; Wang, Chunqin; Wei, Fanglin; Qiu, Xiaohui; He, Rongquan; Chen, Gang

    2016-01-01

    Abstract Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623–4.127, P < 0.001), 2.697 (95%CI: 1.874–3.883, P < 0.001), 2.649 (95%CI: 1.632–4.300, P < 0.001), 3.506 (95%CI: 2.231–5.508, P < 0.001), and 1.792 (95%CI: 1.409–2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343–2.597, P < 0.001), 2.626 (95%CI: 2.089–3.301, P < 0.001), 1.104 (95%CI: 1.008–1.209, P = 0.032), 1.518 (95%CI: 1.299–1.773, P < 0.001), and 1.294 (95%CI: 1.203–1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly

  17. Cloning of Human Uroplakin Ⅱ Gene from Chinese Transitional Cell Carcinoma of Bladder and Construction of Its Eukaryotic Expression Vector

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To clone Uroplakin Ⅱ gene from Chinese transitional cell carcinoma (TCC) of bladder and construct its eukaryotic expression vector, the molecular cloning method was used to extract total RNA from a GⅢ/ T3N0M0 tissue sample of the bladder TCC patients. The primers were designed by Primer 5.0 software. Full length cDNA of Uroplakin Ⅱ gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), assayed by nucleic acid sequencing and then inserted between Xba Ⅰ and HindⅢ restrictive sites of eukaryotic expression vector pcDNA3.0. The recombinant was assayed by restricted enzyme digestion. Under the induction of Lipofectamine 2000, the recombinant was transfected into Uroplakin Ⅱ negative bladder cancer cell line EJ. Cellular expression levels of Uroplakin Ⅱ were detected by RT-PCR. The nucleic acid sequencing results indicated that Chinese Uroplakin Ⅱ cDNA (555 bp) was successfully cloned. The BLAST analysis demonstrated that the cloned sequence is 100 % homologous with sequences reported overseas. The GenBank accession number AY455312 was also registered. The results of restricted enzyme digestion indicated that eukaryotic vector pcDNA-UP Ⅱ for Uroplakin Ⅱ was successfully constructed.After being transferred with pcDNA-UPⅡ for 72 h, cellular Uroplakin Ⅱ mRNA levels were significantly improved (P<0.01). It is concluded that human Uroplakin Ⅱ gene was successfully cloned from Chinese TCC tissues, which provided a basis for further exploration of the roles of Uroplakin Ⅱ gene in TCC biological behaviors and potential strategies for targeted biological therapy of TCC.

  18. Porcelain gall bladder in a case of papillary renal cell carcinoma: A rare occurrence and its impact on treatment verdict

    Directory of Open Access Journals (Sweden)

    Raghavan V. Sugi Subramaniam

    2012-01-01

    Full Text Available Multiple primary malignant neoplasms (MPMN is a rare clinical entity in which two primary malignancies are encountered in the same individual which can be synchronous (second primary within 6 months or metachronous (beyond 6 months. We present a case of a 41-year-old male who underwent left partial nephrectomy for suspected renal cell carcinoma and it was confirmed based on histopathology. The gallbladder was normal on contrast-enhanced computed tomogram (CECT abdomen. Follow-up CECT done 1 year later showed no enhancing masses in both kidneys, but incidentally porcelain gallbladder was detected. An elective open cholecystectomy was done for acalculous porcelain gall bladder owing to its premalignant nature. We report this case to highlight the relative risk of second primaries in patients treated for primary malignancies and that relevant premalignant conditions should be managed as possible second malignancies to avoid potential complications.

  19. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

    Science.gov (United States)

    Ali, Maged M.; El Shorbagy, Shereen; Abdelbary, Abeer M.; Abdelaziz, Lobna A.; Salim, Reham A.; Abdel Wahab, Khaled M.

    2017-01-01

    Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p < 0.001), number of tumors, lymph node metastasis, and tumor size (p < 0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively). High NEDD9 and p38 detection had a worse 3-year OS (p = 0.041 and <0.001, respectively). By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients' outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC. PMID:28194179

  20. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ola A. Harb

    2017-01-01

    Full Text Available Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC. Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9 is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p<0.001, number of tumors, lymph node metastasis, and tumor size (p<0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively. High NEDD9 and p38 detection had a worse 3-year OS (p=0.041 and <0.001, respectively. By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients’ outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

  1. 荧光原位杂交技术在膀胱尿路上皮癌术后复发的早期检测中的临床应用价值%Clinical value of fluorescence in situ hybridization in early detection of postoperative recurrence of bladder urothelial cancer

    Institute of Scientific and Technical Information of China (English)

    闫伟; 康雯婷; 陈山; 刘跃新

    2014-01-01

    目的:应用荧光原位杂交技术(fluorescence in situ hybridization,FISH)对膀胱尿路上皮肿瘤患者术后复发进行早期评估预测。方法2009年1月至2011年11月,选取首都医科大学附属北京同仁医院40例临床诊断的高危膀胱尿路上皮癌患者,术后第3,6,9,12,18个月行尿细胞学检查、膀胱镜检查,并行尿液 FISH 检查,记录膀胱肿瘤复发的时间。观察 FISH 对于膀胱尿路上皮肿瘤患者术后复发的早期预测价值。结果60%(12/20)的 FISH 阳性者膀胱肿瘤复发,FISH 阴性者无1例出现膀胱肿瘤复发。 FISH 阳性者膀胱尿路上皮癌复发率高于 FISH 阴性者(60% vs 0%,P<0.05)。6例(50%)肿瘤复发患者 FISH 阳性先于膀胱镜检查及尿细胞学检查。结论 FISH 对膀胱肿瘤检测的阳性率高于细胞学检测,FISH 对膀胱肿瘤的诊断早于膀胱镜和细胞学。 FISH 技术可作为膀胱尿路上皮肿瘤术后复发的监测指标之一。%Objective To early diagnose postoperative recurrence of bladder urothelial cancer with fluorescence in situ hybridization (FISH). Methods Forty patients with bladder urothelial cancer were chosen between January, 2009 and November, 2011. Urine cytologic examination, cystoscopy, and FISH were performed in these patients at 3, 6, 9, 12, and 18 months post-operation, and tumor recurrence was recorded. Results Among the 40 patients tested, 12 of 20 FISH-positive patients developed tumor recurrence within the follow-up period, while none of the FISH-negative patients developed recurrence during the same period. The recurrence rate in FISH-positive patients(60% ) was significantly higher than that of FISH-negative patients(P<0. 05). The sensitivity to detect tumor recurrence by FISH analysis was higher than that by cystoscopy and urine cytologic examination. Conclusion FISH analysis is effective in early detection of postoperative recurrence of bladder urothelial cancer.

  2. Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder

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    Bedeir Ali-El-Dein

    2011-01-01

    Conclusions: Cancer-specific survival is statistically comparable for primary and deferred cystectomy in T1 bladder cancer, although there is a non-significant difference in favor of primary cystectomy. In the deferred cystectomy group, the number of TURBTs beyond three is associated with lower survival. Conservative treatment should be adopted for most cases in this category.

  3. Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling.

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    Hiromitsu Negoro

    Full Text Available Urothelial cells respond to bladder distension with ATP release, and ATP signaling within the bladder and from the bladder to the CNS is essential for proper bladder function. In other cell types, pannexin 1 (Panx1 channels provide a pathway for mechanically-induced ATP efflux and for ATP-induced ATP release through interaction with P2X7 receptors (P2X7Rs. We report that Panx1 and P2X7R are functionally expressed in the bladder mucosa and in immortalized human urothelial cells (TRT-HU1, and participate in urothelial ATP release and signaling. ATP release from isolated rat bladders induced by distention was reduced by the Panx1 channel blocker mefloquine (MFQ and was blunted in mice lacking Panx1 or P2X7R expression. Hypoosmotic shock induced YoPro dye uptake was inhibited by MFQ and the P2X7R blocker A438079 in TRT-HU1 cells, and was also blunted in primary urothelial cells derived from mice lacking Panx1 or P2X7R expression. Rinsing-induced mechanical stimulation of TRT-HU1 cells triggered ATP release, which was reduced by MFQ and potentiated in low divalent cation solution (LDPBS, a condition known to enhance P2X7R activation. ATP signaling evaluated as intercellular Ca2+ wave radius was significantly larger in LDPBS, reduced by MFQ and by apyrase (ATP scavenger. These findings indicate that Panx1 participates in urothelial mechanotransduction and signaling by providing a direct pathway for mechanically-induced ATP release and by functionally interacting with P2X7Rs.

  4. From clinical trials to the front line: Vinflunine for Treatment of UrothelialCell Carcinoma at the National Cancer Institute of Naples

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    GAETANO eFACCHINI

    2016-05-01

    Full Text Available BACKGROUND: the efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, ‘real life’ experiences are very helpful to verify the efficacy of a new therapy. METHODS: this was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. RESULTS: 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months respectively. CONCLUSION: our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2-3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug.

  5. Clinical value of urine liquid-based cytology test in the diagnosis of urothelial carcinoma%尿液基细胞学在诊断尿路上皮癌中的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    赵焕; 李旻; 郭会芹; 曹箭; 马建辉; 李长岭; 潘秦镜

    2008-01-01

    Objective To explore the diagnostic accuracy of urine liquid-based cytology(LBC)for diagnosis of urothelial carcinoma(UC).Methods A total of 603 cases in our department from January 2005 to July 2007 were subject to urine liquid-based cytology test(LBC)and followed by histological examination.Using the histological appearance as the gold standard,the accuracy of LBC test was evaluated.Results A total of 436 cases with histological diagnoses were selected.There were 274 cases of UC and 61 cases of other malignant tumors of urinary system.The sensitivity,specificity and accuracy of urine LBC test for malignant tumors were 61.5%,86.5% and 67.1%,respectively.The positive predictive value and negative predictive value were 94.1% and 39.2%,respectively.The sensitivity of urine LBC test for UC and non-urothelial malignant tumors were 68.6% and 29.5%,respectively.The sensitivity for UC Was significantly higher than that for non-urothelial malignant tumors.The diagnostic sensitivity of urine LBC test for UC G1,G1-2;G2,G2-3 and G3 was 53.3%,74.5% and 90.6%,respectively.The diagnostic sensitivity of urine LBC was increased with the increacment of histological grade of UC.Conclusions The sensitivity of urine LBC test for high grade UC is high and has a good clinical value.However,for the diagnosis of low grade UC,the sensitivity of LBC test is low and adjuvant test is needed to improve it.%目的 评估尿液基细胞学(LBC)对尿路上皮癌(UV)诊断的准确性.方法 对2005年1月至2007年7月在本院细胞学室做尿LBC检查的603例患者标本和组织学诊断标本进行对照.以细胞学诊断的可疑癌(SUCA)为切入点,组织学诊断为金标准,计算尿液基细胞学的诊断效能.结果 在有组织学随访结果的436例患者中,274例为UC、其他恶性肿瘤61例.尿LBC诊断恶件肿瘤的敏感度、特异度和准确性分别为61.5%、86.5%和67.1%.阳性预测值和阴性预测值分别为94.1%和39.2%.对UC和非尿路上皮恶性肿瘤

  6. Analysis of prognostic factors in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

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    Antunes Alberto A.

    2006-01-01

    Full Text Available OBJECTIVE: To analyze the results of the treatment of transitional cell carcinoma (TCC of the bladder with radical cystectomy and determine which prognostic factors can be utilized as disease-free survival and cancer-specific survival independent variables. MATERIALS AND METHODS: Medical records of 113 patients submitted to radical cystectomy and bilateral iliac lymphadenectomy between 1993 and 2005 were reviewed. The risk factors analyzed were age, sex, pathological stage, tumor grade, presence of carcinoma in situ and the presence of lymph nodes involvement. RESULTS: After a mean follow-up of 31.7 ? 28.5 months, 46 patients (40.7% presented recurrence and 24 patients (21.2% died due to cancer. Only pathological stage and the lymph nodes involvement became independent variables for recurrence and survival. Patients with T4 stage presented 9.6 times the risk of recurrence of the disease when compared with stage T0 patients (p = 0.010 and the patients with lymph node involvement presented 2.5 times the risk of recurrence (p = 0.047 and 3.1 times the risk of death (p = 0.022 when compared to patients without lymph nodes involvement. CONCLUSIONS: Pathological stage and the involvement of lymph nodes represented more important prognostic variables, and in the presence of advanced stage tumors (T3/T4 and involvement of lymph nodes, the institution of adjuvant treatment should be considered.

  7. Correlation of urine cytology with ABO(H) antigenicity in transitional cell carcinoma of the bladder.

    OpenAIRE

    1988-01-01

    Cell surface ABO(H) antigenicity of superficial bladder tumours was assessed by the indirect immunoperoxidase test in 49 patients. Good correlation was obtained between surface antigenicity of tumours and the results of urine cytology. Malignant cells were detected cytologically in 22(56%) of cases with ABO(H) antigen negative tumours which are known to behave more aggressively than ABO(H) antigen positive ones. In contrast, malignant cells were found in the urine cytology of only one (10%) o...

  8. Management of Bladder Cancer following Solid Organ Transplantation

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    Jeffrey J. Tomaszewski

    2011-01-01

    Full Text Available Objective. Present our experience managing bladder cancer following liver and renal transplantation. Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC following solid organ transplantation between January 1992 and December 2007. Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2% following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease. Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients.

  9. The Treatment of Recurrent Urothelial Tumors of the Upper Urinary System and at Urostomy Site following Radical Cystectomy with Intraureteral Bacillus Calmette-Guérin and Cryotherapy

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    Abdullah Demirtaş

    2013-01-01

    Full Text Available Urinary bladder carcinoma is the second most common cancer of the urinary system. The recurrence rate in the upper urinary system (UUS for urothelial cancers is around 3% following radical cystectomy. The followup generally consists of imaging studies and urinary cytology, although there are no prospective data on the frequency, the mode, and the duration of followup. In patients carefully selected according to risk factors, kidney-sparing minimally invasive methods (ureteroscopic procedures, percutaneous approach, and local drug instillation appear as contemporary alternatives for low-grade and low-stage primary UUS. In this paper, we present the patient who underwent radical cystectomy with urinary diversion ureterocutaneostomy, was diagnosed with widespread bilateral UUS tumors and recurrent tumor at the urostomy site at active followup, for which he was given local Bacillus Calmette-Guérin (BCG and cryotherapy, and was followed by disease-free for 2 years thereafter.

  10. Peripheral primitive neuroectodermal tumor of the urinary bladder in an Arab woman with history of squamous cell carcinoma: a case report

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    Al Meshaan Mohd Khaled

    2009-04-01

    Full Text Available Abstract Introduction Peripheral primitive neuroectodermal tumors of the urinary bladder are rare and tend to occur in an older age group than do their counterparts in bones and soft tissue. Case presentation We report a case of peripheral primitive neuroectodermal tumor of the urinary bladder in a 67-year-old woman of Arab origin. She had undergone transurethral resection followed by chemotherapy because of pulmonary metastasized muscle-invasive squamous cell carcinoma of the bladder in 2005. One year later, she first presented with a history of repeated hematuria in our institution. Performing cystoscopy any tumor could be detected. Control cystoscopy two months later showed a tumor mass of 3 cm in diameter at another location than described for the first tumor. After perforating by transurethral resection partial bladder resection had to be done. Tissue specimen after pathological analysis revealed a peripheral primitive neuroectodermal tumor with tumor cells reactive to cluster of differentiation 99, neuron-specific enolase and S100 protein and stained negative for other markers such as cytokeratins, epithelial membrane antigen, desmin, smooth muscle actin, chromogranin and leucocyte common antigen. Staging computerized tomography was especially free from any hint on organ metastasis, but the patient died due to a cardiac problem only a few months later. Conclusions To the best of our knowledge, we report the eighth case of bladder peripheral primitive neuroectodermal tumors in literature and the first concerning an Arab patient. It is also the first presentation of a peripheral primitive neuroectodermal tumor patient with a history of squamous cell carcinoma of the bladder. As in other cases, expression of single-chain-type 1 glycoprotein and neural markers was positive and the disease was at an advanced stage at the time of diagnosis.

  11. Pathology of bilharzial bladder cancer.

    Science.gov (United States)

    Godwin, J T; Hanash, K

    1984-01-01

    Retrospective review of bladder carcinoma at this institution has revealed a high incidence of squamous cell carcinoma associated with bilharzia infection as has been found in other Mideast and African countries. Associated inflammatory and epithelial metaplastic changes were commonly noted and apparently represent early changes in the development of carcinoma, particularly in view of the progression from squamous metaplasia to in situ and infiltrating carcinoma observed in both bladder and ureter. The relationship between bilharzia infection and the development of bladder carcinoma has been postulated to be related to several factors; however, as yet the specific etiologic relationship and pathogenesis have not been defined.

  12. Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells

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    Shigeru Kihira

    2012-08-01

    Our previous study demonstrated that tyrosine phosphorylation of p145met/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD serve as a structural platform for signaling events involving p145met, EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa, an urothelium-specific protein. Results obtained so far revealed: 1 UPIIIa undergoes partial proteolysis in serum-starved cells; 2 a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3 knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP, inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells.

  13. Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis

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    Karen Y.R. Nakagaki

    2015-01-01

    Full Text Available This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis, from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil.

  14. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development.

    Science.gov (United States)

    Knapp, Deborah W; Ramos-Vara, José A; Moore, George E; Dhawan, Deepika; Bonney, Patty L; Young, Kirsten E

    2014-01-01

    Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC.

  15. Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Academic Radiation Oncology Department, Centre Oscar Lambret, Lille (France); Barney, Brandon [Mayo Clinic, Rochester, Minnesota (United States); Sundar, Santhanam [Department of Oncology, Nottingham University Hospitals National Health Service Trust, Nottingham (United Kingdom); Poortmans, Philip [Department of Radiation Oncology, Radboud university medical center, Nijmegen (Netherlands); Villa, Salvador [Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona (Spain); Nasrallah, Haitam [Division of Oncology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ghadjar, Pirus [Department of Radiation Oncology, Bern University Hospital, Bern (Switzerland); Lassen-Ramshad, Yasmin [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Senkus, Elżbieta [Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk (Poland); Oar, Andrew [Genesis Cancer Care, Southport (Australia); Roelandts, Martine [Institut Jules Bordet, Brussels (Belgium); Amichetti, Maurizio [Provincial Agency for Proton Therapy, Trento (Italy); Vees, Hansjoerg [Department of Radiation Oncology, Hopital de Sion, Sion (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

    2015-07-15

    Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

  16. Usefulness of the UBC{sup TM} (urinary bladder cancer) test compared to urinary cytology for transitional cell carcinoma of the bladder in patients with hematuria

    Energy Technology Data Exchange (ETDEWEB)

    Gil, Myung Cheol; Kang, Do Young; Seong, Youl Koon [School of Medicine, Donaga Univ., Busan (Korea, Republic of)] [and others

    2001-06-01

    Urinary cytology and cystoscopic exam are effective methods for diagnosis of transitional cell carcinoma (TCC). But the former shows drawbacks such as the need for a well-trained examiner, and wide imprecision related to the variability of microscopic exam; the latter is a invasive method. UBC{sup TM} test detects the epitope on specific cytokeratin fragments released from epithelium of bladder cancer by immunoradiometric assay. We compared UBC{sup TM} test with urinary cytology for diagnosis of TCC to evaluate the utility of UBC{sup TM} test. Eighty-four patients with hematuria were included in our study, UBC{sup TM} tests (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. Nineteen patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC{sup TM} concentration was greater than 12 {mu}g/L. UBC{sup TM} levels were significantly different between group A (95.9 {+-}166.4 {mu}g/L) and group B (19.2 {+-} 85.6 {mu}g/L)(p<0.001). Sensitivity for diagnosis of TCC was 89.5% (17/19) in UBC test and 47.4% (9/19) in cytology (p<0.05). Specificity for diagnosis of TCC was 81.5% (53/65) in UBC{sup TM} test and 100% (65/65) in cytology. UBC{sup TM} test was significantly more sensitive in stage Ta, T{sub 1} tumors (84.6 vs 38.5%, p<0.05) and in grade I (83.3% vs 16.7%, p<005) than cytology. UBC{sup TM} test showed a tendency to be more sensitive as the grade was higher (83.3% in Grade 1, 90% in Grade II and 100% in Grade III). UBC{sup TM} test could be a useful method in distinguishing TCC from other benign genitourinary diseases. Moreover, UBC{sup TM} test could be an especially valuable marker for diagnosis of TCC in patients with early TCC of low grade TCC compared to urinary cytology. Therefore, mbined use of UBC{sup TM} test in association with cytology is helpful to

  17. Overactive bladder – 18 years – Part II

    OpenAIRE

    Jose Carlos Truzzi; Cristiano Mendes Gomes; Bezerra, Carlos A.; Ivan Mauricio Plata; Jose Campos; Gustavo Luis Garrido; Almeida, Fernando G. [UNIFESP; Marcio Augusto Averbeck; Alexandre Fornari; Anibal Salazar; Arturo Dell’Oro; Caio Cintra; Carlos Alberto Ricetto Sacomani; Juan Pablo Tapia; Eduardo Brambila

    2016-01-01

    ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afferenc...

  18. Vinflunine–gemcitabine versus vinflunine–carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1)†

    Science.gov (United States)

    De Santis, M.; Wiechno, P. J.; Bellmunt, J.; Lucas, C.; Su, W.-C.; Albiges, L.; Lin, C.-C.; Senkus-Konefka, E.; Flechon, A.; Mourey, L.; Necchi, A.; Loidl, W. C.; Retz, M. M.; Vaissière, N.; Culine, S.

    2016-01-01

    Background There is no standard first