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Sample records for bladder urothelial carcinoma

  1. Chromium in urothelial carcinoma of the bladder.

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    Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

    2017-12-23

    Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

  2. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder.

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    Han, Yonghua; Liu, Yuchen; Gui, Yaoting; Cai, Zhiming

    2013-04-01

    Long intergenic non-coding RNAs (lincRNAs) are a class of non-coding RNAs that regulate gene expression via chromatin reprogramming. Taurine Up-regulated Gene 1 (TUG1) is a lincRNA that is associated with chromatin-modifying complexes and plays roles in gene regulation. In this study, we determined the expression patterns of TUG1 and the cell proliferation inhibition and apoptosis induced by silencing TUG1 in urothelial carcinoma of the bladder. The expression levels of TUG1 were determined using Real-Time qPCR in a total of 44 patients with bladder urothelial carcinomas. Bladder urothelial carcinoma T24 and 5637 cells were transfected with TUG1 siRNA or negative control siRNA. Cell proliferation was evaluated using MTT assay. Apoptosis was determined using ELISA assay. TUG1 was up-regulated in bladder urothelial carcinoma compared to paired normal urothelium. High TUG1 expression levels were associated with high grade and stage carcinomas. Cell proliferation inhibition and apoptosis induction were observed in TUG1 siRNA-transfected bladder urothelial carcinoma T24 and 5637 cells. Our data suggest that lincRNA TUG1 is emerging as a novel player in the disease state of bladder urothelial carcinoma. TUG1 may have potential roles as a biomarker and/or a therapeutic target in bladder urothelial carcinoma. Copyright © 2012 Wiley Periodicals, Inc.

  3. Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

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    Flezar, Margareta Strojan

    2010-01-01

    Light microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer. Characteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma

  4. Urothelial Carcinoma of the Urinary Bladder in Young Adults — Clinical Experience at Taipei Veterans General Hospital

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    Yu-Ching Wen

    2005-06-01

    Conclusion: Urothelial carcinoma of the urinary bladder in young adults is usually associated with low grade and low stage. Invasive bladder cancer had no worse a survival rate than superficial bladder cancer.

  5. Vaginal metastasis of bladder urothelial carcinoma: Description of a case and revision of literature.

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    Di Franco, Carmelo A; Porru, Daniele; Giliberto, Giovanni; Viglio, Alessandra; Rovereto, Bruno

    2017-06-30

    Vaginal metastases from urothelial cancer are a rare entity and in literature, few cases are described. We report a case of a 68 year-old woman with history of bladder urothelial carcinoma underwent to radical cystectomy who came in our department after 5 months for pelvic pain and vaginal bleeding. Objective examination revealed an ulcerative, solid vaginal lesion in the upper vaginal wall. We performed a vaginal biopsy that showed urothelial carcinoma compatible with the primitive bladder cancer. The patient underwent to surgery and was sent to oncological evaluation.

  6. Sarcomatoid urothelial carcinoma of the bladder: a contemporary clinicopathologic analysis of 37 cases.

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    Fatima, Nazneen; Canter, Daniel J; Carthon, Bradley C; Kucuk, Omer; Master, Viraj A; Nieh, Peter T; Ogan, Kenneth; Osunkoya, Adeboye O

    2015-06-01

    Sarcomatoid urothelial carcinoma is a dedifferentiated biphasic tumor that exhibits morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. In this series, we analyzed the clinicopathologic features of this rare variant of urothelial carcinoma. A search was made through our surgical pathology files and consultation files of the senior author for cases of sarcomatoid urothelial carcinoma of the bladder from 2005-2014. All the slides were retrieved and re-reviewed, and clinical data was also obtained including follow up. Thirty-seven cases of sarcomatoid urothelial carcinoma of the bladder were identified. Mean patient age was 71 years (range: 51 to 88 years). Twenty-six of 37 (70%) patients were male and 11/37 (30%) patients were female. Twenty-five cases were from cystectomy/cystoprostatectomy specimens, 8 cases from transurethral resection of bladder tumor specimens and 4 cases were from biopsy specimens. The mean tumor size was 5 cm (range: 1.4 cm to 13.0 cm). Four of 37 (10%) cases had focal heterologous components; 1 case with both chondroid and osteoid, 2 cases with chondroid and 1 case rhabdoid elements. Twenty-one of 37 (56%) patients died within a year of presentation. Sarcomatoid urothelial carcinoma of the bladder is more prevalent in males, with the mean age of 71 years in our series. Smoking is an important risk factor. Sarcomatoid urothelial carcinoma is an aggressive variant of urothelial carcinoma which commonly presents at an advanced stage, and over 50% of patients in our series died of disease within 1 year of presentation.

  7. Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site.

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    Agarwal, Poojan; Pasricha, Sunil; Gupta, Gurudutt; Sharma, Anila; Mehta, Anurag

    2018-01-01

    Urothelial carcinoma of urinary bladder with divergent differentiation into rhabdomyosarcoma (RMS) is an extremely uncommon aggressive phenomenon. We present a case of a 74-year-old male with bladder carcinoma which metastasized to the abdominal wall as epithelioid RMS. To the best knowledge of our literature searches, an oligometastasis of exclusive heterologous component has not been described before. The clinical, radiological, and immunohistochemistry profile of the patient supported the monoclonal nature of the tumor.

  8. Status of Her2 over expression in muscle invasive urothelial bladder carcinoma: Report of 21 cases

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    Nesrine Mejri

    2014-01-01

    Four patients died from disease, one of them had Her2 3+ score. Conclusion: Her2 overexpression can be observed in muscle invasive urothelial bladder carcinoma in an important number of patients. Evaluation criteria must be standardized, especially with heterogeneous cases. Metastases tests can also readdress the expression of Her2, which gives the patient a supplementary therapeutic tool.

  9. Evaluation of her-2/neu expression by immunohistochemistry in urothelial carcinoma of urinary bladder

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    Nasim, A.; Salim, B.; Niazi, S.; Fatima, N.

    2015-01-01

    The objective of this study is to determine the HER-2/NEU expression by immunohistochemistry in Urothelial carcinoma of urinary bladder. Study Design: Cross sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from 15th August 2011 to 14th August 2012. Patients and Methods: Bladder cancer tissue specimens from 70 patients were selected in one year as per the inclusion criterion. Immunohistochemistry results were interpreted on light microscope using high power field objective and Her 2/ neu expression was recorded. Mean and standard deviation were calculated for quantitative variables. Frequencies and percentages were calculated for qualitative variables. Results: Out of 70 cases of urothelial carcinoma, Her 2/ neu expression was found to be positive in 24 cases, out of which 5 were of low grade and 19 were of high grade while 16 were invasive and 8 were non invasive. The expression of Her 2/neu was detected in 16 out of 33 cases of invasive carcinoma (48.4%) and in 8 out of 37 cases of non invasive carcinoma (21.6%). As far as grade is concerned, Her 2/ neu was found to be positive in 5 out of 30 cases of low grade carcinoma (16.6%) and 19 out of 40 cases of high grade carcinoma (47.5%). Conclusion: The expression of Her 2/neu has been shown to be related to the stage and grade of urothelial carcinoma. Her 2/neu expression is increased in high grade and invasive urothelial carcinoma. Molecular targeted therapy targeting Her 2/neu can be beneficial in patients after assessment of Her 2/neu expression. (author)

  10. Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature.

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    Knez, Virginia M; Barrow, Willis; Lucia, M Scott; Wilson, Shandra; La Rosa, Francisco G

    2014-08-14

    The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diagnosis are tumors of Müllerian origin and metastatic lesions, such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear cell urothelial carcinoma is exceedingly rare, with only nine clinical cases described in the literature. We report the case of a 75-year-old Caucasian man who presented with intermittent hematuria, in whom a bladder tumor was identified. A final histopathology examination of a cystoprostatectomy specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder tumor consisted of sheets of malignant cells with severe nuclear atypia and abundant clear cytoplasm; no glandular or tubular structures were identified. Tumor cells were periodic acid-Schiff positive and negative after diastase treatment; additional mucicarmine and oil red O stains were negative. Immunohistochemical stains showed the tumor cells positive for cytokeratin 7 (CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45 (HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP), prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25 (CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all negative. The tumor marker profile was consistent with clear

  11. Expression profiles of variation integration genes in bladder urothelial carcinoma.

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    Wang, J M; Wang, Y Q; Gao, Z L; Wu, J T; Shi, B K; Yu, C C

    2014-04-30

    Bladder cancer is a common cancer worldwide and its incidence continues to increase. There are approximately 261,000 cases of bladder cancer resulting in 115,000 deaths annually. This study aimed to integrate bladder cancer genome copy number variation information and bladder cancer gene transcription level expression data to construct a causal-target module network of the range of bladder cancer-related genomes. Here, we explored the control mechanism underlying bladder cancer phenotype expression regulation by the major bladder cancer genes. We selected 22 modules as the initial module network to expand the search to screen more networks. After bootstrapping 100 times, we obtained 16 key regulators. These 16 key candidate regulatory genes were further expanded to identify the expression changes of 11,676 genes in 275 modules, which may all have the same regulation. In conclusion, a series of modules associated with the terms 'cancer' or 'bladder' were considered to constitute a potential network.

  12. New therapeutic targets in the management of urothelial carcinoma of the bladder

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    Sverrisson, Einar F; Espiritu, Patrick N; Spiess, Philippe E

    2013-01-01

    Urothelial carcinoma of the bladder, despite the myriad of treatment approaches and our progressively increasing knowledge into its disease processes, remains one of the most clinically challenging problems in modern urological clinical practice. New therapies target biomolecular pathways and cellular mediators responsible for regulating cell growth and metabolism, both of which are frequently overexpressed in malignant urothelial cells, with the intent of inducing cell death by limiting cellular metabolism and growth, creating an immune response, or selectively delivering or activating a cytotoxic agent. These new and novel therapies may offer a potential for reduced toxicity and an encouraging hope for better treatment outcomes, particularly for a disease often refractory or not amenable to the current therapeutic approaches. PMID:24400235

  13. New therapeutic targets in the management of urothelial carcinoma of the bladder

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    Sverrisson EF

    2013-03-01

    Full Text Available Einar F Sverrisson, Patrick N Espiritu, Philippe E SpiessDepartment of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Urothelial carcinoma of the bladder, despite the myriad of treatment approaches and our progressively increasing knowledge into its disease processes, remains one of the most clinically challenging problems in modern urological clinical practice. New therapies target biomolecular pathways and cellular mediators responsible for regulating cell growth and metabolism, both of which are frequently overexpressed in malignant urothelial cells, with the intent of inducing cell death by limiting cellular metabolism and growth, creating an immune response, or selectively delivering or activating a cytotoxic agent. These new and novel therapies may offer a potential for reduced toxicity and an encouraging hope for better treatment outcomes, particularly for a disease often refractory or not amenable to the current therapeutic approaches.Keywords: targeted therapy, intravesical agents, systemic therapies

  14. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

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    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  15. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

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    2017-12-04

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  16. A Case of Early Stage Bladder Carcinosarcoma in Late Recurrence of Urothelial Carcinoma after Transurethral Resection

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    Daisaku Hirano

    2018-01-01

    Full Text Available Carcinosarcomas of the urinary bladder are rare biphasic neoplasms, consisting of both malignant epithelial and malignant mesenchymal components, and the prognosis of this tumor is unfavorable in most patients with even possibility of resection of disease. A 77-year-old male with a history of transurethral resection (TUR of urothelial carcinoma (UC of the bladder and adjuvant intravesical chemotherapy with pirarubicin 10 years ago revisited our department with a gross hematuria. Cystoscopy demonstrated an approximately 2.5 cm nonpapillary tumor on the right wall of the bladder. Pelvic MRI showed the tumor without extending the base of the bladder wall. The tumor could be completely removed with TUR. The malignant epithelial elements consisted of high-grade UC and the majority of mesenchymal components were fibrosarcomatous differentiation based on immunohistochemical studies. The tumor could be pathologically also suspected to be an early stage on TUR specimens. Although he has received no additional intervention due to the occurrence of myocardial infarction at three weeks after the TUR, he has been alive with no evidence of recurrence of the disease 27 months after the TUR. Some early stages of bladder carcinosarcoma might have a favorable prognosis without aggressive treatments.

  17. 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.

  18. Resolution of hypercalcemia of malignancy following radical cystectomy in a patient with paraneoplastic syndrome associated with urothelial carcinoma of the bladder

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    Alfredo Harb-De La Rosa

    2015-01-01

    Full Text Available Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.

  19. 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.

  20. Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder.

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    Kim, Philip H; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Zabor, Emily C; Scott, Sasinya N; Ostrovnaya, Irina; Ramirez, Ricardo; Sun, Arony; Shah, Ronak; Yee, Alyssa M; Reuter, Victor E; Bajorin, Dean F; Rosenberg, Jonathan E; Schultz, Nikolaus; Berger, Michael F; Al-Ahmadie, Hikmat A; Solit, David B; Bochner, Bernard H

    2015-02-01

    Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node-positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-altered tumors experienced worse RFS (HR: 5.76; pHR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  1. 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

  2. Metabolic syndrome and the risk of urothelial carcinoma of the bladder: a case-control study

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    Montella, Maurizio; Di Maso, Matteo; Crispo, Anna; Grimaldi, Maria; Bosetti, Cristina; Turati, Federica; Giudice, Aldo; Libra, Massimo; Serraino, Diego; La Vecchia, Carlo; Tambaro, Rosa; Cavalcanti, Ernesta; Ciliberto, Gennaro; Polesel, Jerry

    2015-01-01

    The Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB. Between 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders. Patients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS. This study supports a positive association between the MetS and bladder cancer risk

  3. 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.

  4. Plasmacytoid urothelial carcinoma of the bladder with extensive scrotal wall invasion

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    Yong Gang Wang

    2016-01-01

    Full Text Available Plasmacytoid urothelial carcinoma (PUC is an extremely rare and aggressive variant of urothelial carcinoma. We report a case of a 62-year-old male who presented with a rapid spread of PUC to involve his entire scrotal wall after failed surgery and chemotherapy. The second course of chemotherapy was effective in providing symptom control. We believe this is the first case report of PUC causing such rapid and extensive scrotal invasion. This case highlights the important features of PUC including the pattern of tumor spread along fascial planes, the tendency for initial understaging, and the rapid recurrence after initially response to chemotherapy.

  5. 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.

  6. 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.

  7. Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

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    Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

    2018-02-01

    Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (pinflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Molecular Characterization of Urothelial Carcinoma of the Bladder and Upper Urinary Tract

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    Ji Yun Lee

    2018-02-01

    Full Text Available PURPOSE: A better understanding of the molecular basis of urothelial carcinoma (UC is needed to refine the clinical decision-making process. METHODS AND MATERIALS: We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC and urinary bladder UC (UBUC were compared. RESULTS: Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P = .137. In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%. Frequently detected somatic mutations included TP53 (68.5%, KDR (41.3%, and PIK3CA (17.4%. Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P = .020. The most common types of CNVs included amplifications (56/62, 90.3%: 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4 fusion. CONCLUSION: Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.

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

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    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

  10. 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.

  11. Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma.

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    Washino, Satoshi; Hirai, Masaru; Matsuzaki, Atsushi; Kobayashi, Yutaka

    2011-01-01

    To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated. Copyright © 2011 S. Karger AG, Basel.

  12. Urinary pH Levels are Strongly Associated with Bladder Recurrence After Nephroureterectomy in Upper Tract Urothelial Carcinoma Patients with a Smoking History.

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    Ide, Hiroki; Kikuchi, Eiji; Hagiwara, Masayuki; Hayakawa, Nozomi; Hongo, Hiroshi; Miyajima, Akira; Oya, Mototsugu

    2016-12-01

    Aromatic amines, well-known bladder carcinogens, derived from cigarette smoke are activated by acidic urine. We herein determined whether urinary pH levels are associated with bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history. A total of 256 upper tract urothelial carcinoma patients who were surgically treated at our institution between 1990 and 2013 were included. Urinary pH levels were defined as the median of at least two consecutive measurements within 1 month of surgery. Ninety-six patients (37.5 %) had pH pH ≥5.5, and urinary pH levels were identified as one of the significant predictors for bladder recurrence in univariate but not multivariate Cox regression analysis in overall. In patients with a positive smoking history among those without a history of bladder tumor (N = 110), the 5-year bladder recurrence-free survival rate was 52.5 % in patients with pH ≥5.5, which was significantly higher than that in those with pH pH pH pH for urine alkalization may prevent bladder recurrence.

  13. The effect of photochemical internalization of bleomycin in the treatment of urothelial carcinoma of the bladder: an in vitro study.

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    Arentsen, Harm C; Falke, Johannes; Høgset, Anders; Oosterwijk, Egbert; Alfred Witjes, J

    2014-01-01

    In this in vitro study, we determined whether meso-tetraphenyl chlorin disulphonate (TPCS2a)-based photochemical delivery of bleomycin was able to potentiate the cytotoxicity of bleomycin on bladder cancer cells. The human RT4, RT112, 253J, T24, and rat AY-27 urothelial carcinoma cell lines were used. Cells were seeded in 96-well plates. TPCS2a was added to the growth medium and the plates were incubated overnight. Cells were then resuspended in TPCS2a-free culture medium and incubated for 3 hours. Subsequently, cells were treated for 60 minutes with increasing doses of epirubicin, gemcitabine, mitomycin C, or bleomycin followed by illumination for different periods. Cell viability was measured with a colorimetric assay after 72 hours. For the single treatments, in all 5 cell lines a dose-dependent inhibition of cell proliferation was observed. This was seen both after treatment with TPCS2a-based photodynamic therapy (PDT), as well as after treatment with either bleomycin or one of the control chemotherapeutic agents. After treatment with PDT (240-s illumination), bleomycin 9.0 µM, and the combination of these treatments, relative survival percentages were 89.2 ± 13.0, 70.2 ± 8.9, and 30.5 ± 6.1, respectively, in the T24 cell line. After treatment with PDT (120-s illumination), bleomycin 27 µM and the combination of these treatments, relative survival percentages were 93.6 ± 15.7, 74.7 ± 9.6, and 30.0 ± 11.1, respectively, in the AY-27 cell line. In both cell lines, PDT combined with bleomycin showed significantly (Pinternalization effect. TPCS2a-based photochemical internalization of bleomycin showed a significant, at least, additive antiproliferative activity against human and rat urothelial carcinoma cells in vitro. Thus, photochemical internalization may have therapeutic potential as an intravesical strategy against bladder cancer. As the effect is heterogeneous, biomarker studies are warranted to be able to predict the effects of a photochemical

  14. A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

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    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage ≥pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage ≥pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk (≤pT2), intermediate-risk (≥pT3 and ≥10 nodes removed), and high-risk (≥pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in

  15. 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

  16. Crude mortality and loss of life expectancy of patients diagnosed with urothelial carcinoma of the urinary bladder in Norway.

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    Andreassen, Bettina K; Myklebust, Tor Å; Haug, Erik S

    2017-02-01

    Reports from cancer registries often lack clinically relevant information, which would be useful in estimating the prognosis of individual patients with urothelial carcinoma of the urinary bladder (UCB). This article presents estimates of crude probabilities of death due to UCB and the expected loss of lifetime stratified for patient characteristics. In Norway, 10,332 patients were diagnosed with UCB between 2001 and 2010. The crude probabilities of death due to UCB were estimated, stratified by gender, age and T stage, using flexible parametric survival models. Based on these models, the loss in expectation of lifetime due to UCB was also estimated for the different strata. There is large variation in the estimated crude probabilities of death due to UCB (from 0.03 to 0.76 within 10 years since diagnosis) depending on age, gender and T stage. Furthermore, the expected loss of life expectancy is more than a decade for younger patients with muscle-invasive UCB and between a few months and 5 years for nonmuscle-invasive UCB. The suggested framework leads to clinically relevant prognostic risk estimates for individual patients diagnosed with UCB and the consequence in terms of loss of lifetime expectation. The published probability tables can be used in clinical praxis for risk communication.

  17. Preoperative anemia is associated with adverse outcome in patients with urothelial carcinoma of the bladder following radical cystectomy.

    Science.gov (United States)

    Gierth, M; Mayr, R; Aziz, A; Krieger, S; Wullich, B; Pycha, A; Lodde, M; Salvadori, U; Bründl, J; Fritsche, H M; Hofstädter, F; Pawlik, M T; Otto, W; May, M; Burger, M; Denzinger, S

    2015-10-01

    Radical cystectomy (RC) can be associated with significant blood loss, whereas many patients are presenting with anemia preoperatively. To date, there is a lack of data addressing the impact of preoperative anemia (PA) on survival of patients undergoing RC for urothelial carcinoma of the bladder (UCB). This retrospective multicenter study includes 684 patients with UCB undergoing RC with pelvic lymph node dissection. The median follow-up was 50 (IQR 29,78) months. Anemia was defined in line with the WHO classification (hemoglobin (Hb): male ≤13 g/dL, female ≤12 g/dL) and based on contemporary gender- and age-adjusted classification (Hb: white male aged classification versus contemporary classification. Age, increased ECOG performance status, advanced tumor stages, lymph node metastasis, positive surgical margin and anemia were associated with disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM). In multivariable analysis, anemia was an independent predictor of DR, CSM and ACM (WHO and/or contemporary classification). Blood transfusion was significantly associated with ACM in both classifications of anemia. PA is significantly associated with worse oncological outcome in patients undergoing RC. Based on the additional unfavorable influence of blood transfusion, this emphasizes the importance of early diagnosis and correction of anemia and implementation of alternative methods of blood volume management.

  18. Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis.

    Science.gov (United States)

    Lee, Song-Tay; Lu, Min-Hua; Chien, Lan-Hsiang; Wu, Ting-Feng; Huang, Li-Chien; Liao, Gwo-Ing

    2013-12-21

    Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action. Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract. This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell. The analytical results of this study help to provide insight into the molecular mechanism

  19. Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

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    Wu, Pengjie; Liu, Shengjie; Zhang, Wei; Zhang, Yaoguang; Zhu, Gang; Wei, Dong; Wan, Ben; Wang, Jianye

    2015-12-01

    To evaluate the association of molecular markers and conventional clinicopathological factors with bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. The expressions of Ki-67 and P53 were measured by immunohistochemical staining prospectively in 115 consecutive patients with primary upper tract urothelial carcinoma from March 2004 to February 2014. The Cox proportional hazards regression model was used to identify independent predictors. The association between Ki-67 expression and clinicopathological variables was assessed by the χ(2) test. Intravesical recurrence occurred in 13 out of 115 (11.3%) patients with a mean follow-up of 54.2 months (range: 7-130). Low-level Ki-67 expression (P = 0.010), older age (>65, P = 0.040) and lower ureter tumour (P = 0.001) were independent predictors of bladder tumour recurrence in Cox regression analysis. Ki-67 expression was elevated with the progression of tumour grade (P = 0.004) but not with stage (P = 0.186). Ki-67 overexpression was also significantly higher in aggressive pathological types (P = 0.008), but only shows an inclination towards poor oncologic outcomes in the cancer-specific survival rate (P = 0.107) and the overall survival rate (P = 0.063). Low-level Ki-67 expression was an independent predictor for bladder tumour recurrence, while Ki-67 overexpression was associated with adverse clinicopathological parameters and poor prognosis in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Long non-coding RNA urothelial carcinoma-associated 1 as a tumor biomarker for the diagnosis of urinary bladder cancer.

    Science.gov (United States)

    Wang, Zichun; Wang, Xiaoxiong; Zhang, Daming; Yu, Yongchun; Cai, Licheng; Zhang, Cheng

    2017-06-01

    To investigate the diagnostic value of urothelial carcinoma-associated 1 as a urine biomarker in urinary bladder cancer patients by performing a comprehensive meta-analysis. A comprehensive literature search was conducted by the databases PubMed, Embase, Cochrane Library, China Knowledge Resource Integrated, and Web of Science. The quality of eligible studies was scored with the Quality Assessment of Diagnostic Accuracy Studies. The bivariate meta-analysis model was used to pool the sensitivity, specificity, likelihood ratio, and diagnostic odds ratio. Receiver operating characteristic curves and hierarchical summary receiver operating characteristic models were employed to check the overall test performance in this meta-analysis. Seven publications involving 678 patients and 563 controls were included in this meta-analysis. The pooled sensitivity was 0.84 (95% confidence interval: 0.80-0.88), specificity was 0.87 (95% confidence interval: 0.75-0.94), positive likelihood ratio was 6.5 (95% confidence interval: 3.10-13.62), negative likelihood ratio was 0.18 (95% confidence interval: 0.13-0.25), and diagnostic odds ratio was 36 (95% confidence interval: 13-99). The area under the summary receiver operating characteristic curve was 0.89 (95% confidence interval: 0.86-0.91). Our results indicated that urothelial carcinoma-associated 1 was a potential diagnostic biomarker with good specificity and sensitivity in urinary bladder cancer. Further prospective studies with larger cohorts are necessary to evaluate the diagnostic accuracy of urothelial carcinoma-associated 1 for urinary bladder cancer.

  1. Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?

    Directory of Open Access Journals (Sweden)

    Simone Bier

    2018-01-01

    Full Text Available Objectives. To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT for diagnosis of UUT urothelial carcinoma (UC. Patients and Methods. The study comprised 758 urine samples either collected from the bladder (n=373 or UUT (n=385. All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH, immunocytology (uCyt+, and nuclear matrix protein 22 (NMP22 were performed. Results. UUT UC was diagnosed in 59 patients (19.1% (UUT urine and 27 patients (7.2% (bladder-derived urine. For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions. Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.

  2. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

    Science.gov (United States)

    Keay, Susan K.; Birder, Lori A.; Chai, Toby C.

    2014-01-01

    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. PMID:24900993

  3. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

  5. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Li, Zhengkun; Chen, Wei

    2014-07-01

    Urothelial carcinoma associated 1 (UCA1) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in bladder cancer progression and acts as a diagnostic biomarker for bladder carcinoma. Here, we studied the expression and function of lncRNA-UCA1 in the hypoxic microenvironment of bladder cancer. The expression and transcriptional activity of lncRNA-UCA1 were measured by quantitative real-time polymerase chain reaction and luciferase assays. Cell proliferation and apoptosis were evaluated by MTT assays and flow cytometry. Cell migration and invasion were detected by wound healing, migration, and invasion assays. The binding of hypoxia-inducible factor-1α (HIF-1α) to hypoxia response elements (HREs) in the lncRNA-UCA1 promoter was confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. HRE mutations were generated by using a site-directed mutagenesis kit, and HIF-1α knockdown was mediated by small interfering RNA. The effect of HIF-1α inhibition by YC-1 on lncRNA-UCA1 expression was also examined. LncRNA-UCA1 was upregulated by hypoxia in bladder cancer cells. Under hypoxic conditions, lncRNA-UCA1 upregulation increased cell proliferation, migration, and invasion and inhibited apoptosis. The underlying mechanism of hypoxia-upregulated lncRNA-UCA1 expression was that HIF-1α specifically bound to HREs in the lncRNA-UCA1 promoter. Furthermore, HIF-1α knockdown or inhibition could prevent lncRNA-UCA1 upregulation under hypoxia. These findings revealed the mechanism of lncRNA-UCA1 upregulation in hypoxic bladder cancer cells and suggested that effective blocking of lncRNA-UCA1 expression in the hypoxic microenvironment of bladder cancer could be a novel therapeutic strategy.

  6. Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies.

    Science.gov (United States)

    Liem, Esmee Iml; Freund, Jan Erik; Baard, Joyce; de Bruin, D Martijn; Laguna Pes, M Pilar; Savci-Heijink, C Dilara; van Leeuwen, Ton G; de Reijke, Theo M; de la Rosette, Jean Jmch

    2018-02-07

    Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions. The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology. In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations. Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018. For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma. Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central

  7. Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma

    International Nuclear Information System (INIS)

    Geynisman, Daniel M.; Handorf, Elizabeth; Wong, Yu-Ning; Doyle, Jamie; Plimack, Elizabeth R.; Horwitz, Eric M.; Canter, Daniel J.; Uzzo, Robert G.; Kutikov, Alexander; Smaldone, Marc C.

    2015-01-01

    To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer (aSCBC) patients and compare to those with urothelial carcinoma (UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups (P < 0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy (MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients (P < 0.0001). Median overall survival (OS) for aSCBC patients was 8.6 months; 13.0 months in N+M0 versus 5.3 months in NxM1 patients (P < 0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8 months vs. 12.1 months, P = 0.15). Urothelial carcinoma patients (n = 27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3 months vs. 13.0 months, P = 0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease

  8. Peristomal pagetoid spread of urothelial carcinoma of the ureter

    Directory of Open Access Journals (Sweden)

    Fumio Ito

    2013-09-01

    Full Text Available Patients with ostomy including urinary stoma often develop peristomal complications, especially skin damage. The patient in this case was a 69-year old female with a history of urothelial carcinoma of the bladder and left ureter who underwent transurethral resection of a bladder tumor, nephroureterectomy and cystectomy combined with ureterocutaneostomy. Later, she had recurrence of urothelial carcinoma in the remaining ureter that spread to the peristomal epidermis, with a skin appearance resembling Paget’s disease. We report this case based on its clinical significance since we believe it is the first description of this condition in the literature.

  9. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  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

  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. Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuh-Shyan Tsai

    2012-01-01

    Full Text Available The prognostic importance of examining ErbB receptor family expression in human bladder cancer remains uncertain. Using published evidence, we examined the clinical value and the updated results of clinical trials targeting ErbB receptor family members. Twenty-seven articles from 65 references related to ErbB receptor expression assessment in bladder cancer were reviewed. The estimates included the association significance, hazard ratios, and 95% confidence intervals (CIs from actuarial curves and survival analyses. A meta-analysis was done on those reports using univariate log-rank tests or a Cox-regression model. The methods of analysis and study subjects chosen varied widely among studies. The overall risks of disease progression for patients with EGFR or ErbB2 overexpression were 4.5 (95% CI: 2.5–8.4 and 1.1 (95% CI: 0.6–1.9, and the risks of mortality were 3.0 (95% CI: 1.6–5.9 and 1.1 (95% CI: 1.0–1.2, respectively. However, the significance of coexpression patterns of the ErbB receptor family remains controversial. None of six clinical trials yielded convincing results for blockading ErbB receptor signaling in urothelial carcinoma. The results of this analysis suggest that assessing co-expression patterns of the ErbB family may provide better prognostic information for bladder cancer patients.

  13. Reduced immunohistochemical PTEN staining is associated with higher progression rate and recurrence episodes in non-invasive low-grade papillary urothelial carcinoma of the bladder.

    Science.gov (United States)

    Kulac, Ibrahim; Arslankoz, Sehbal; Netto, George J; Ertoy Baydar, Dilek

    2018-01-24

    Non-invasive low-grade papillary urothelial carcinoma (NILGPUC) of the bladder is regarded as a relatively indolent disease. However, its propensity for frequent recurrences constitutes a major clinical problem. Additionally, there is a progression risk of 10-15% to either a higher grade and/or a higher stage disease in these tumors. The molecular factors that will predict recurrence and progression in low-grade pTa bladder carcinoma have not yet been elucidated. Herein, we investigated the association of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) alterations with recurrence and progression in NILGPUC using immunohistochemistry. Eighty-one cases of bladder cancer initially diagnosed as NILGPUC in a single institution with follow-up were encountered after searching medical records. Tissue microarrays (TMA) that contained both tumor and non-neoplastic mucosa from each case were constructed using paraffin blocks of transurethral resections. Sections from TMA blocks were stained immunohistochemically for PTEN protein and were evaluable in 76 cases. Any absence of staining was recorded and correlated with clinical findings. Ten patients (13.2%) showed progression and 41 (53.9%) showed recurrence. Reduced PTEN expression was observed in 29 cases (38.1%). Cases with reduced PTEN had higher progression rate compared to cases with intact PTEN (p = 0.026). Tumor relapse was more frequent in cases with reduced PTEN (65.5 vs 46.8%), but this difference was not statistically significant (p = 0.112). On the other hand, decreased PTEN expression was associated with higher number of recurrence episodes (p = 0.002). PTEN seems to have a link with the disease course in NILGPUC of the bladder.

  14. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994)

    DEFF Research Database (Denmark)

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

    2015-01-01

    carcinoma of the bladder. METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy......; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment...

  15. ABO Blood Group and Rhesus Factor Are Not Associated with Outcomes After Radical Cystectomy for Non-metastatic Urothelial Carcinoma of the Bladder.

    Science.gov (United States)

    D'Andrea, David; Moschini, Marco; Soria, Francesco; Gust, Kilian M; Briganti, Alberto; Karakiewicz, Pierre I; Rouprêt, Morgan; Shariat, Shahrokh F

    2017-10-01

    To investigate the role of ABO blood group and Rhesus factor as a predictor of outcome in patients undergoing radical cystectomy (RC) for non-metastatic urothelial carcinoma of the bladder. Data of 463 consecutive patients treated with RC between 1988 and 2003 were retrospectively analyzed. The effect on recurrence-free survival, and cancer-specific and overall mortality were assessed using the Kaplan-Meier and multivariable Cox regression methods. Overall, 185 (41.3%), 190 (42.4%), 46 (10.3%) and 27 (6%) patients expressed O, A, B and AB phenotypes, respectively; 65 (14.5%) were Rhesus-negative. Median follow-up was 14.2 years (interquartile range=10.2-17.1 years). No individual blood group was associated with any clinicopathological characteristics whereas Rhesus-positive patients had a higher rate of pT4 disease (11% vs. 22%; p=0.02). ABO blood groups were not associated with outcomes. Rhesus-positive patients had an increased risk of shorter recurrence-free survival, and of cancer-specific and overall mortality compared to Rhesus-negative patients (all pABO blood group nor Rhesus factor are associated with oncological outcomes. The clinical relevance of blood groups and Rhesus factor in bladder cancer remains questionable. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Knockdown of long non-coding RNA Taurine Up-Regulated 1 inhibited doxorubicin resistance of bladder urothelial carcinoma via Wnt/β-catenin pathway.

    Science.gov (United States)

    Xie, Dalong; Zhang, Hui; Hu, Xuanhao; Shang, Chao

    2017-10-24

    In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed in several malignant tumors, including BC. In this study, over-expression of TUG1 was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox in T24/Dox cells. TUG1 knockdown also depressed the Wnt/β-catenin pathway, and the activation the Wnt/β-catenin pathway partly reversed the inhibitory effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up-regulation of lncRNA TUG1 was related with the poor response of BUC patients to Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via Wnt/β-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for BUC, thereby improve the effects of clinical treatment in patients.

  17. Low Grade Lymphoma Mimicking Metastatic Urothelial Carcinoma: When Do We Need Further Histologic Staging?

    Directory of Open Access Journals (Sweden)

    Azka Ali

    2016-01-01

    Full Text Available Introduction. Patients with urothelial carcinoma of the bladder often present with metastases to regional lymph nodes, with lymphadenopathy on physical examination or radiographic imaging. Case Presentation. We present the case of a 73-year-old Caucasian man with presumed metastatic urothelial carcinoma of the bladder to regional pelvic and retroperitoneal lymph nodes. He underwent systemic chemotherapy for treatment of urothelial carcinoma and was discovered on restaging to have findings suggestive of disease progression but ultimately was found to have a concurrent secondary malignancy. Conclusion. Our case suggests that in patients with urothelial carcinoma, the concurrent presentation of regional lymphadenopathy may not be metastatic urothelial carcinoma and may warrant further investigation.

  18. Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems

    NARCIS (Netherlands)

    Oosterhuis, J. W. A.; Schapers, R. F. M.; Janssen-Heijnen, M. L. G.; Pauwels, R. P. E.; Newling, D. W.; ten Kate, F.

    2002-01-01

    AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were

  19. The association of ABO blood type with disease recurrence and mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

    Science.gov (United States)

    Gershman, Boris; Moreira, Daniel M; Tollefson, Matthew K; Frank, Igor; Cheville, John C; Thapa, Prabin; Tarrell, Robert F; Thompson, Robert Houston; Boorjian, Stephen A

    2016-01-01

    To evaluate the association of ABO blood type with clinicopathologic outcomes and mortality among patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). We identified 2,086 consecutive patients who underwent RC between 1980 and 2008. Postoperative recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to evaluate the association of ABO blood type with outcomes. A total of 913 (44%), 881 (42%), 216 (10%), and 76 (4%) patients had blood type O, A, B, and AB, respectively. Median postoperative follow-up among survivors was 11.0 years (interquartile range: 7.7-15.9y). Overall, 1,561 patients died, with 770 deaths attributable to bladder cancer. Non-O blood type was associated with significantly worse 5-year RFS (65% vs. 69%; P = 0.04) and/or CSS (64% vs. 70%; P = 0.02). In particular, among patients with≤pT2N0 disease, the 5-year RFS for those with non-O vs. O blood type was 75% vs. 82%, respectively (P = 0.002), whereas the 5-year CSS was 77% vs. 85%, respectively (P = 0.001). Moreover, on multivariable analysis, blood type A remained independently associated with an increased risk of cancer-specific mortality (hazard ratio = 1.22; P = 0.01). Non-O blood type, particularly blood type A, is associated with a significantly increased risk of death from bladder cancer among patients undergoing RC. If validated, the utility of a multimodal therapy approach, including perioperative chemotherapy, or more frequent postoperative surveillance in this cohort warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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.

  1. Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy.

    Science.gov (United States)

    Zhang, Shiqiang; Wang, Jun; Zhang, Xinyu; Zhou, Fangjian

    2017-01-01

    Tumor-infiltrating lymphocytes (TILs) are associated with better clinical outcomes in many tumors. TILs represent a cell-mediated immune response against the carcinoma. CD8+ TILs are a crucial component of cell-mediated immunity. The significance of CD8+ TILs has not been reported respectively in organ- and non-organ-confined urothelial carcinoma (UC) of the bladder. We explored the prognostic value of CD8+ TILs in the two groups. The presence of CD8+ TILs was assessed by immunohistochemical staining of whole tissue sections from 75 organ and 51 non-organ-confined disease patients with long-term follow-up, and its correlation with clinicopathological features and overall survival (OS) was determined. The CD8+ TIL immunohistochemical staining score was 0 (CD8 negative if the score was 0. There were no associations between CD8+ TILs and age, sex, nuclear grade, and adjuvant or neoadjuvant chemotherapy in organ- and non-organ-confined disease. The presence of CD8+ TILs was seen more frequently in pTa- 1 than pT 2 stage ( p  = 0.033) in organ-confined disease. No associations between CD8+ TILs and pT stage, pN stage were found in non-organ-confined disease. CD8+ TILs were associated with better OS (log-rank test, P  = 0.036) in non-organ-confined disease, but with poorer OS (log-rank test, P  = 0.040) in organ-confined disease by the Kaplan-Meier method. In multivariate analysis, CD8+ TILs were an independent favorable prognostic factor in non-organ-confined disease, but were an independent unfavorable prognostic factor in organ-confined disease. These results suggest that CD8+ TILs have clinically significant anti-tumor activity in non-organ-confined disease, but may have pro-tumor activity in organ-confined disease. Therefore, we should be cautious if CD8+ TILs are aimed to be exploited in the treatment of bladder cancer.

  2. Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

    OpenAIRE

    Wallard, M J; Pennington, C J; Veerakumarasivam, A; Burtt, G; Mills, I G; Warren, A; Leung, H Y; Murphy, G; Edwards, D R; Neal, D E; Kelly, J D

    2006-01-01

    The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and ...

  3. The effect of photochemical internalization of bleomycin in the treatment of urothelial carcinoma of the bladder: an in vitro study

    NARCIS (Netherlands)

    Arentsen, H.C.; Falke, J.; Hogset, A.; Oosterwijk, E.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this in vitro study, we determined whether meso-tetraphenyl chlorin disulphonate (TPCS2a)-based photochemical delivery of bleomycin was able to potentiate the cytotoxicity of bleomycin on bladder cancer cells. MATERIALS AND METHODS: The human RT4, RT112, 253J, T24, and rat AY-27

  4. Precystectomy serum levels of carbohydrate antigen 19-9, carbohydrate antigen 125, and carcinoembryonic antigen: prognostic value in invasive urothelial carcinoma of the bladder.

    Science.gov (United States)

    Ahmadi, Hamed; Djaladat, Hooman; Cai, Jie; Miranda, Gus; Daneshmand, Siamak

    2014-07-01

    To evaluate the prognostic value of precystectomy carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), and carcinoembryonic antigen (CEA) levels in invasive urothelial carcinoma of the bladder (UCB). Preoperatively collected serum samples from patients with invasive UCB who underwent radical cystectomy between 2004 and 2009 were used to measure CA 19-9, CA 125, and CEA levels. Laboratory cutoff points were used to define elevated marker levels (CA 19-9>37 U/ml, CA 125>35 U/ml, and CEA>3.8 U/ml). The Cox regression model was used to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). A total of 186 patients with the mean age of 69 years (range: 36-89) and median follow-up of 4 years (range: 0.1-7.2) were included in the study. Overall, 94 (51%) patients had pathologic organ-confined disease (≤T2) and 92 (49%) had pathologic locally advanced UCB (pT3-T4 or positive lymph node or both). The mean CA 19-9, CA 125, and CEA levels were 11.6 U/ml (range:<0.6-111), 11.5 U/ml (range: 3-56), and 2.2 ng/ml (range: 0.3-30.2), respectively. Levels of CA 19-9, CEA, and CA 125 were elevated in 7 (3%), 25 (13%), and 3 (1%) patients, respectively. Median 3-year RFS and OS were 72%. Using the multivariate Cox regression model, elevated levels of CA 19-9 and CEA were found to be independent predictors of worse 3-year OS (hazard ratio [HR] = 2.7, P = 0.05 and HR = 2, P = 0.03, respectively), and an elevated level of CA 19-9 was an independent predictor of worse 3-year RFS (HR = 2.8, P = 0.05). Precystectomy CA 125 level was not associated with oncological outcome. Elevated precystectomy serum levels of CA 19-9 and CEA are independent predictors of worse oncological outcome in patients with invasive UCB. Further studies are needed to elucidate the role of these markers in the management of UCB. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The potential effect of age on the natural behavior of bladder cancer: Does urothelial cell carcinoma progress differently in various age groups?

    Science.gov (United States)

    Gunlusoy, Bulent; Ceylan, Yasin; Degirmenci, Tansu; Aydogdu, Ozgu; Bozkurt, Ibrahim Halil; Yonguc, Tarik; Sen, Volkan; Kozacioglu, Zafer

    2016-05-01

    We aimed to evaluate the potential effect of age on the natural behavior of bladder cancer and to compare these findings between different age groups. The clinical and pathologic data of 239 patients treated at our institution between 1994 and 2014 were analyzed. The patients were classified into three groups according to age: ≤ 40 years (Group 1), 41-59 years (Group 2), and ≥ 60 years (Group 3). The following data were collected: characteristics of the patients, initial pathological findings after transurethral resection, tumor stage and grade, tumor size and multiplicity, and disease recurrence and progression. The mean age of the patients at initial diagnosis was 34.2±5.5 years, 53±5.1 years, and 71.1±7 years in Groups 1, 2, and 3, respectively. There were 207 (86.6%) patients with nonmuscle-invasive urothelial bladder cancer and 32 (13.4%) patients with muscle-invasive disease. Tumor recurrence was significantly lower in Group 1 than in Group 2 (p=0.001) and Group 3 (p=0.001). Although the time to tumor recurrence was significantly different between the three groups (p=0.001), no significant difference was noted in the time to progression (p=0.349). Patients with urothelial cancer younger than 40 years tend to have single and small tumors. The tumor recurrence rate is lower in the younger age group, but tumor progression is similar in older and younger patients. Therefore, the findings indicate that clinicians should be careful when assessing the invasiveness of urothelial tumors in younger patients and start treatment as soon as possible. Copyright © 2016. Published by Elsevier Taiwan.

  6. 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.

  7. Alterations of mTOR and PTEN protein expression in schistosomal squamous cell carcinoma and urothelial carcinoma.

    Science.gov (United States)

    Makboul, Rania; Refaiy, Abeer; Abdelkawi, Islam F; Hameed, D A; Elderwy, Ahmad A; Shalaby, Mahmoud M; Merseburger, Axel S; Hussein, Mahmoud Rezk Abdelwahed

    2016-05-01

    mTOR signaling pathway is commonly activated in cancer. PTEN, a tumor suppressor gene, is a potent inhibitor of this pathway. To date the expression pattern of mTOR and PTEN in schistosomal bladder squamous cell carcinoma and urothelial carcinoma was not investigated. Also, whether alterations of these proteins are associated with pathological parameters was not established. We hypothesize that "expression of mTOR and/or PTEN will be altered in schistosomal-related urothelial and squamous cell carcinomas". To test our hypothesis we examined the expression pattern of mTOR and PTEN in normal and hyperplastic urothelium, squamous metaplasia, schistosomal urothelial carcinomas (70 cases) and squamous cell carcinomas (47 cases) using immunohistochemical methods. mTOR protein expression was absent in the normal, hyperplastic urothelium and metaplastic squamous epithelium. mTOR was over-expressed in muscle invasive urothelial and high grade squamous cell carcinomas. In contrast, PTEN protein expression was seen in the normal and hyperplastic urothelium. The expression was reduced (metaplastic squamous epithelium) or lost in muscle invasive urothelial and high grade squamous carcinomas. Alterations of these proteins were associated with some clinicopathological features. mTOR expression was negatively correlated with PTEN expression in urothelial carcinoma only. We report, for the first time, altered expression of mTOR and PTEN proteins in schistosomal urothelial and squamous cell carcinomas. Alterations of these proteins may contribute to the progression and aggressive behavior of schistosomal bladder carcinoma. Targeting mTOR, may be a promising therapeutic strategy in these tumors. Copyright © 2016 Elsevier GmbH. All rights reserved.

  8. Paraneoplastic syndrome in urothelial carcinoma of the kidney: difficulty in diagnosis and deterioration in prognosis

    Directory of Open Access Journals (Sweden)

    I. E. Mamaev

    2015-01-01

    Full Text Available Paraneoplastic syndrome is not a common concomitance of urothelial tumors. The literature describes a few tens of clinical cases in which urothelial cancer has become a cause of marked nonspecific tumor-associated reactions, associated with the presence of the tumor. Bladder tumors are at stake in all cases. The given clinical observation describes paraneoplastic manifestations in high-grade urothelial carcinoma of the kidney. It demonstrates difficulties in differential diagnosis and gives a retrospective estimate of diagnostic and therapeutic tactics.

  9. Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Illemann, Martin; Høyer-Hansen, Gunilla

    2015-01-01

    during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia. MATERIALS AND METHODS: The expression-and localization pattern of u......PAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages...... comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020). CONCLUSIONS: The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly...

  10. Expression profile of urothelial transcription factors in bladder biopsies with interstitial cystitis.

    Science.gov (United States)

    Kaga, Kanya; Inoue, Ken-Ichi; Kaga, Mayuko; Ichikawa, Tomohiko; Yamanishi, Tomonori

    2017-08-01

    To characterize interstitial cystitis pathology based on the expression profile of urothelial tissue-specific master transcription factors. Bladder carcinoma cell lines derived from the urothelial stem cells (epithelial or mesenchymal) were used to identify candidate urothelial master transcription factors. Gene expression was measured with quantitative reverse transcription polymerase chain reaction. From the initial screening of 170 transcription factors (human homologs of Drosophila segmentation genes and known master transcription factors from a database), 28 transcription factors were selected. Subsequently, messenger ribonucleic acid from bladder biopsies of interstitial cystitis patients was purified, and gene expression levels of known urothelial marker genes and candidate master transcription factors were measured. Multivariate expression data were analyzed with spss software. Factor analysis decomposed the expression profile into four axes: principal axis 1 included retinoic acid receptors and 17 candidate master transcription factors. Principal axis 2 included KRT5 and five candidates. Principal axis 3 included transcription factor TP63 and two candidates. Principal axis 4 included SHH and two candidates. Principal component analysis segregated biopsies from Hunner's lesion in the principal component 1 (retinoic acid)/principal component 2 (SOX13)/principal component 3 (TP63) space. Urothelial master transcription factors could serve as novel diagnostic markers and potentially explain the molecular pathology of interstitial cystitis. © 2017 The Japanese Urological Association.

  11. Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy

    Science.gov (United States)

    Sun, Tengfei; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.; Piao, Daqing

    2017-02-01

    In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic AY-27 rat bladder urothelial cell carcinoma model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder tumor cells were intravesically instilled in four rats and allowed to implant and grow for one week, with two additional rats as the control. A total of 107 SfRS measurements were taken from 27 sites on two control bladders and 80 from four AY-27 treated bladders. The spectral profiles obtained from AY-27 treated bladders revealed various levels of a methemoglobin (MetHb) characteristic spectral feature around 635nm. A multisegment spectral analysis method estimated concentrations of five chromophore compositions including oxyhemoglobin, deoxyhemoglobin, MetHb, lipid and water. The total hemoglobin concentration ([HbT]), the MetHb proportion in the total hemoglobin and the lipid volume content showed possible correlations. The 80 measurements from the AY-27 treated bladders could separate to three sub-sets according to the MetHb proportion. Specifically, 72 were in subset 1 with low proportion (5.3%30%). When grouped according to [MetHB], the [HbT] increased from 368 μM of subset 1 to 488 μM of subset 2 to 541 μM of subset 3, in comparison to the 285 μM of the control. The increased total hemoglobin and the elevation of MetHb proportion may signify angiogenesis and degradation in hemoglobin oxygen-transport. Additionally, the lipid volume content decreased from 2.58% in the control to <0.2% in the tumor groups, indicating disruption of subepithelium tissue architecture.

  12. Nuclear E-cadherin expression is associated with the loss of membranous E-cadherin, plasmacytoid differentiation and reduced overall survival in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Keck, Bastian; Wach, Sven; Kunath, Frank; Bertz, Simone; Taubert, Helge; Lehmann, Jan; Stöckle, Michael; Wullich, Bernd; Hartmann, Arndt

    2013-07-01

    Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy. A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan-Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher's exact test. Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p Nuclear accumulation was found in 47.6 % of PUCs, 10 % of MPCs, and 1.8 % of UCs. Sixty-two percent of all tumors with negative membranous E-cadherin expression and nuclear accumulation were PUCs (p = 0.035). In a Kaplan-Meier analysis, mean survival with nuclear E-cadherin expression was 31.9 months [95 % confidence interval (CI) 16.1-47.6] of patients without nuclear staining 61 months (95 % CI 53.5-67.7; p = 0.045). A univariate Cox regression analysis showed that nuclear E-cadherin accumulation was associated with a 2-fold increase in risk of death (95 % CI 1.03-4.06; p = 0.04). In multivariate Cox regression analysis adjusted to type of chemotherapy, tumor stage, and tumor grade, the hazard ratio for patients with nuclear E-cadherin was 2.03 (95 % CI 1.00-4.121; p = 0.050). Nuclear E-cadherin is associated with PUCs and is suggested to be an independent prognostic factor in advanced UC.

  13. 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

  14. Giant urothelial carcinoma of unknown origin invading the sigmoid mesocolon - a case report

    International Nuclear Information System (INIS)

    Kolacinska, A.; Howaniec, J.; Stanczyk, M.; Pawlak, M.; Morawiec, Z.; Rykala, J.

    2007-01-01

    Background: Transitional cell carcinoma, also called urothelial carcinoma, is the most common malignancy of the urinary bladder. Additionally, it can develop in the lining of the renal pelvis, ureter, prostate and urethra. Exceptionally, cancer can arise from the urachus. Also primary transitional cell carcinoma of the endometrium or ovary is a rare entity. Aim: The aim of this article was to present a case of giant urothelial carcinoma of unknown origin invading the sigmoid mesocolon. We report a rare case of urothelial carcinoma invading the sigmoid mesocolon in a 60-year-old female admitted to our department. The patient presented with a 25-cm intra-abdominal mass and 6-cm ulcerated lesion at the top of the umbilicus. Laparotomy was performed which demonstrated a huge polycystic and solid tumour of the sigmoid mesentery infiltrating the sigmoid colon and appendix. Appendectomy and resection of the tumour with an infiltrated sigmoid loop were performed. A right ovarian cyst - not contiguous to the aforementioned tumour - was found at the time of the operation and excised. We also removed the 6-cm skin lesion in the umbilical area. Histopathological examination revealed urothelial carcinoma with squamous cell metaplasia of the sigmoid mesocolon with bowel and umbilical invasion. Concurrent desmoid cyst (mature teratoma) of the right ovary was found. In conclusion, this patient with a sigmoid mesocolon invasion from urothelial carcinoma of unknown origin posed a diagnostic dilemma. (authors)

  15. 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.

  16. 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.

  17. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

    International Nuclear Information System (INIS)

    Kitamura, Hiroshi; Tsukamoto, Taiji

    2011-01-01

    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

  18. Urothelial Carcinoma in a 22-Year-Old Female with Angelman Syndrome

    Directory of Open Access Journals (Sweden)

    Jessica Pugh

    2017-01-01

    Full Text Available A 22-year-old nulligravid white female with Angelman syndrome was noted to have a 4-month history of premenstrual nausea, vomiting, and abdominal pain. She had an echogenic focus in her bladder noted on ultrasound. She was diagnosed with low grade urothelial carcinoma after cystoscopic evaluation with biopsy and was sent to urology for further treatment. Urothelial carcinoma is rare in individuals younger than age 40. Patients may present with gross hematuria. There is often a delay in diagnosis in younger individuals with different genetic mutations noted upon diagnosis.

  19. 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

    In a consecutive series of 500 unselected patients with primary urinary bladder tumours the influence of urothelial atypia on the 5 years survival-rate was examined. All tumours were transitional-cell tumours categorized according to the T-classification. Mucosal biopsies from 7 pre-selected sites...... 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...... worse than those with normal bladder mucosa (5 years survival 42% versus 62%). This difference in survival-rate became apparent first after two years of observation. Grade II atypia in the bladder mucosa and grade III (carcinoma in situ) had equal significance assessed by the survival-rates....

  20. Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

    Science.gov (United States)

    Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

    2017-01-01

    Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

  1. Review of Topical Treatment of Upper Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  2. Angiogenesis in urinary bladder carcinoma as defined by ...

    African Journals Online (AJOL)

    Background: Among the patients with bladder cancer, a group is still at risk of disease recurrence, progression, and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial carcinoma and is a potential therapeutic target. Objectives: To quantify tumor ...

  3. Immunohistochemical Differentiation between Urothelial Papillomas and Papillary Neoplasms of Low Malignant Potential of the Urinary Bladder.

    Science.gov (United States)

    Alrashidy, Mohammed; Atef, Aliaa; Baky, Tarek Abdel

    2016-01-01

    Urothelial papilloma and non-invasive papillary carcinoma are common neoplasms of the urinary bladder. Distinguishing papillomas and papillary carcinomas, especially the low grade type, is often debatable on the basis of histological features alone. We investigated immunohistochemical expression of cytokeratin 20 (CK20), p53, and Ki-67 in a group of 20 urothelial papilloma cases and 30 noninvasive papillary neoplasms of low malignant potential (PNLMP) of the urinary bladder. Whole tissue sections were examined. Among the 30 carcinoma cases, 12 (40%) showed strong reactivity for the whole panel, 16 (53%) reacted positively for two markers, and 2 (7%) reacted just to one of them. Ki-67 was considered positive in 27 cases (90%) and p53 in 24 (80%), CK20 showed positive reactivity in 21 cases (70%). Only small percentages of papillomas were positive, and then only weakly. We concluded that the intense positivity of suspicious cells for at least one of these markers would confirm the presence of malignant changes and favours the diagnosis of carcinoma.

  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. Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional.

    Science.gov (United States)

    Chess-Williams, R

    2002-06-01

    1. The parasympathetic nervous system is responsible for maintaining normal bladder function, contracting the bladder smooth muscle (detrusor) and relaxing the bladder outlet during micturition. 2. Contraction of the bladder involves direct contraction via M3 receptors and an indirect 're-contraction' via M2-receptors whereby a reduction in adenylate cyclase activity reverses the relaxation induced by beta-adrenoceptor stimulation. 3. Muscarinic receptors are also located on the epithelial lining of the bladder (urothelium) where they induce the release of a diffusible factor responsible for inhibiting contraction of the underlying detrusor smooth muscle. The factor remains unidentified but is not nitric oxide, a cyclooxygenase product or adenosine triphosphate. 4. Finally, muscarinic receptors are also located prejunctionally in the bladder on cholinergic and adrenergic nerve terminals, where M1-receptors facilitate transmitter release and M2 or M4-receptors inhibit transmitter release. 5. In pathological states, changes may occur in these receptor systems resulting in bladder dysfunction. Muscarinic receptor antagonists are the main therapeutic agents available for treatment of the overactive bladder, but whether their therapeutic effect involves actions at all three locations (detrusor, prejunctional, urothelial) has yet to be established.

  6. Urothelial cancer of bladder in young versus older adults: clinical and pathological characteristics and outcomes.

    Science.gov (United States)

    Telli, Onur; Sarici, Hasmet; Ozgur, Berat Cem; Doluoglu, Omer Gokhan; Sunay, Mehmet Melih; Bozkurt, Selen; Eroglu, Muzaffer

    2014-09-01

    Bladder urothelial carcinoma is rare in young adults and occurs more commonly in older individuals. The aim of this study was to compare the clinical behavior, pathologic characteristics, and prognosis of urothelial carcinoma of urinary bladder in young versus older adults. A retrospective review of our records between 2007 and 2013 identified 56 patients (42 males and 14 females) with transitional cell carcinoma of the bladder who were less than 40 years old. Clinical and pathological parameters of patients who were less than 40 years of age were compared with those of a series of patients older than 40 years of age (the control group) during the same period. 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 clinical outcomes. The mean age was 29.21 years (range, 5-40 years) for patients less than 40 years old and 61.66 years (range, 41-75) for those older than 40 years. The mean follow-up was 40.26 months (range, 12-65 months) for young patients and 42.57 months (range, 12-72 months) for the older patients. Young bladder cancer patients had smaller-sized tumors (less than 3 cm), less high-grade cancers, higher papillary urothelial neoplasms of low malignant potential, and low-grade tumors than patients older than 40 years. Multivariate logistic regression analysis predicted tumor recurrence in young patients with high-grade tumors [odds ratio (OR), 1.959; 95% confidence interval (CI), 1.235-2.965; p = 0.046] and tumors larger than 3 cm (OR, 1.772; 95% CI, 1.416-1.942; p = 0.032). The 5-year overall survival rate was 100% for young patients and 88.1% for older patients. No difference was observed in the recurrence-free (p = 0.321) and progression-free (p = 0.422) survival rates between the two groups. We concluded that although the clinical stage distribution, natural history, and outcomes of bladder urothelial cancer in young adults are

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

    Science.gov (United States)

    Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

    2016-03-01

    In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001). Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American

  10. The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.

    Science.gov (United States)

    Earl, Julie; Rico, Daniel; Carrillo-de-Santa-Pau, Enrique; Rodríguez-Santiago, Benjamín; Méndez-Pertuz, Marinela; Auer, Herbert; Gómez, Gonzalo; Grossman, Herbert Barton; Pisano, David G; Schulz, Wolfgang A; Pérez-Jurado, Luis A; Carrato, Alfredo; Theodorescu, Dan; Chanock, Stephen; Valencia, Alfonso; Real, Francisco X

    2015-05-22

    Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.

  11. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    Science.gov (United States)

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a.

    Science.gov (United States)

    May, Matthias; Bastian, Patrick J; Brookman-May, Sabine; Fritsche, Hans-Martin; Tilki, Derya; Otto, Wolfgang; Bolenz, Christian; Gilfrich, Christian; Trojan, Lutz; Herrmann, Edwin; Moritz, Rudolf; Tiemann, Arne; Müller, Stefan C; Ellinger, Jörg; Buchner, Alexander; Stief, Christian G; Wieland, Wolf F; Höfner, Thomas; Hohenfellner, Markus; Haferkamp, Axel; Roigas, Jan; Zacharias, Mario; Nuhn, Philipp; Burger, Maximilian

    2013-10-01

    Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage. Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping. Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53-0.68, P < 0.001). Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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

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

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    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.

  15. Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2011 consensus guidelines for curative radiotherapy for urothelial carcinoma of the bladder

    International Nuclear Information System (INIS)

    Hindson, Benjamin R.; Turner, Sandra L.; Millar, Jeremy L.

    2012-01-01

    Curative radiotherapy, with or without concurrent chemotherapy, is recognized as a standard treatment option for muscle-invasive bladder cancer. It is commonly used for two distinct groups of patients: either for those medically unfit for surgery, or as part of a 'bladder preserving' management plan incorporating the possibility of salvage cystectomy. However, in both situations, the approach to radiotherapy varies widely around the world. The Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recognised a need to develop consistent, evidence-based guidelines for patient selection and radiotherapy technique in the delivery of curative radiotherapy. Following a workshop convened in May 2009, a working party collated opinions and conducted a wide literature appraisal linking each recommendation with the best available evidence. This process was subject to ongoing re-presentation to the Faculty of Radiation Oncology Genito-Urinary Group members prior to final endorsement. These Guidelines include patient selection, radiation target delineation, dose and fractionation schedules, normal tissue constraints and investigational techniques. Particular emphasis is given to the rationale for the target volumes described. These Guidelines provide a consensus-based framework for the delivery of curative radiotherapy for muscle-invasive bladder cancer. Widespread input from radiation oncologists treating bladder cancer ensures that these techniques are feasible in practice. We recommend these Guidelines be adopted widely in order to encourage a uniformly high standard of radiotherapy in this setting, and to allow for better comparison of outcomes.

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

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    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

  17. Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations.

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    McLatchie, L M; Young, J S; Fry, C H

    2014-07-01

    The aim of this study was to quantify and characterize the mechanism of non-neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti-muscarinic drugs. A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release. Minimal mechanical stimulus achieved full ACh release, indicating a small dynamic range and possible all-or-none signal. ACh release involved a mechanism dependent on the anion channel CFTR and intracellular calcium concentration, but was independent of extracellular calcium, vesicular trafficking, connexins or pannexins, organic cation transporters and was not affected by botulinum-A toxin. Stimulating ACh receptors increased ATP production and antagonizing them reduced ATP release, suggesting a link between ACh and ATP release. These results suggest that release of non-neuronal ACh from the urothelium is large enough and well located to act as a modulator of ATP release. It is hypothesized that this pathway may contribute to the actions of anti-muscarinic drugs in reducing the symptoms of lower urinary tract syndromes. Additionally the involvement of CFTR in ACh release suggests an exciting new direction for the treatment of these conditions. © 2014 The British Pharmacological Society.

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

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    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.

  19. Neoadjuvant chemotherapy improves survival rate in advanced urothelial carcinoma

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    Chia-Chun Tsai

    2013-04-01

    Full Text Available Radical surgery (RS with adjuvant chemotherapy (AC or radiotherapy has been conventionally used for patients with advanced urothelial carcinoma (AUC. Recent research has indicated that systemic neoadjuvant chemotherapy (NC with RS yields better outcomes than RS alone for patients with locally advanced bladder cancer. However, there are no reports indicating whether NC or AC would be beneficial for patients with AUC. The present study compared the survival rate for AUC patients receiving NC or AC. A retrospective analysis was conducted using data for 64 patients with AUC who underwent RS and systemic chemotherapy at our institution between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS and 34 received RS followed by systemic AC. Pathologic stages (p=0.002, grades (p=0.018 and lymphovascular invasion (p=0.047 were significantly lower in the patients who received NC first than in those who received RC first. Furthermore, analysis of the surgical specimens revealed that 26.7% of patients who received NC before RS had complete remission. There were no significant differences in demographic data, surgical complications, and chemotoxicity between the two patient groups. The progression-free survival (PFS and overall survival (OS of patients who received initial NC were significantly better than those of patients who received initial RC (p=0.002 and 0.018, respectively. Our results indicate that NC administration before RS significantly improved the PFS and OS of AUC patients, without increasing surgical complications and chemotoxicity. Further prospectively controlled trials need to be conducted to confirm the effectiveness of NC for AUC patients.

  20. The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma.

    Science.gov (United States)

    Momota, Masaki; Hatakeyama, Shingo; Tokui, Noriko; Sato, Tendo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Narita, Satoshi; Kawaguchi, Toshiaki; Ohyama, Chikara

    2018-03-13

    The impact of preoperative renal impairment severity on prognosis in urothelial carcinoma remains unelucidated. To evaluate the impact of severe preoperative renal insufficiency on oncological outcomes in patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy. A total of 1066 patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy at six medical centres from February 1995 to November 2017 were retrospectively examined. Oncological outcomes, stratified using preoperative estimated glomerular filtration rate (eGFR≥60, 45≤eGFRpreoperative eGFR on prognosis. Of 610 patients with muscle-invasive bladder cancer (MIBC), 80 (13%) had severe renal insufficiency (eGFRpreoperative eGFR≥60, 45≤eGFRpreoperative eGFRpreoperative eGFRpreoperative severe renal insufficiency (estimated glomerular filtration rate<45ml/min/1.73m 2 ) had higher risk for relapse and lower survival probability. Close attention is necessary when urothelial carcinoma patients have severe renal insufficiency before radical cystectomy or nephroureterectomy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  1. CEA-producing urothelial cell carcinoma with metastasis presenting as a rectal adenocarcinoma

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    Ming-Hsin Yang

    2012-11-01

    Full Text Available This is a case study of a 61-year-old male who presented with difficult defecation for 1 month. A circumferential submucosal rectal tumor was noted on a digital rectal examination and colonoscopy. Laboratory examination revealed high serum levels of carcinoembryonic antigen (CEA; 43.75 ng/mL and carbohydrate antigen 19-9 (CA19-9; 11,790 U/mL. In addition, tumor biopsies revealed a poorly differentiated adenocarcinoma of the rectum with intact mucosa. The patient had history of advanced stage-T2 urothelial cell carcinoma of bladder, which had been downstaged to T0 by neoadjuvant chemotherapy followed by radical cystectomy 1 year prior. After investigating the initial bladder tumor specimens, a small portion of the tumor with high CEA expression comparable to the submucosal rectal tumor was found. The size of the tumor was reduced and the levels of the tumor markers decreased after administering FOLFIRI chemotherapy targeted at the adenocarcinoma. Although neoadjuvant chemotherapy may have a selective pressure to eliminate most urothelial cell carcinoma, physicians should be aware that it can lead to rectal metastasis via CEA-producing components.

  2. Vulvar Metastasis from Bladder Cancer

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    Fouad Aoun

    2015-01-01

    Full Text Available Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity; few cases are reported in the English literature. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of a patient with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief review of the reported cases in the literature.

  3. CD73 Predicts Favorable Prognosis in Patients with Nonmuscle-Invasive Urothelial Bladder Cancer

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    Marian S. Wettstein

    2015-01-01

    Full Text Available Aims. CD73 is a membrane associated 5′-ectonucleotidase that has been proposed as prognostic biomarker in various solid tumors. The aim of this study is to evaluate CD73 expression in a cohort of patients with primary bladder cancer in regard to its association with clinicopathological features and disease course. Methods. Tissue samples from 174 patients with a primary urothelial carcinoma were immunohistochemically assessed on a tissue microarray. Associations between CD73 expression and retrospectively obtained clinicopathological data were evaluated by contingency analysis. Survival analysis was performed to investigate the predictive value of CD73 within the subgroup of pTa and pT1 tumors in regard to progression-free survival (PFS. Results. High CD73 expression was found in 46 (26.4% patients and was significantly associated with lower stage, lower grade, less adjacent carcinoma in situ and with lower Ki-67 proliferation index. High CD73 immunoreactivity in the subgroup of pTa and pT1 tumors (n=158 was significantly associated with longer PFS (HR: 0.228; p=0.047 in univariable Cox regression analysis. Conclusion. High CD73 immunoreactivity was associated with favorable clinicopathological features. Furthermore, it predicts better outcome in the subgroup of pTa and pT1 tumors and may thus serve as additional tool for the selection of patients with favorable prognosis.

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

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    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.

  5. Human Epidermal Growth Factor Receptor 2 Overexpression in Micropapillary and Other Variants of Urothelial Carcinoma.

    Science.gov (United States)

    Behzatoğlu, Kemal; Yörükoğlu, Kutsal; Demir, Hale; Bal, Nebil

    2016-06-21

    Human epidermal growth factor receptor 2 (HER2) protein overexpression or gene amplification has been shown in urothelial bladder cancer. This could be helpful when using targeted anti-HER2 therapy on these tumors. To evaluate HER2 immunohistochemical expression in conventional urothelial carcinoma (UC), in situ UC, and UC variants primarily in micropapillary urothelial carcinoma (MPUC). The study evaluated 60 MPUC cases; 25 invasive, 20 low-grade noninvasive, and 10 high-grade noninvasive UC cases; 8 in situ UC cases; and 69 UC variant cases. The immunohistochemistry staining was scored according to recommendations of the American Society of Clinical Oncology/College of American Pathologists 2013 HER2 test guideline established for breast cancer and only 3+ staining was considered HER2 overexpression. HER2 overexpression was determined by 3+ staining. 34 of 60 MPUC cases (56%) showed HER2 overexpression (3+ staining). We observed 3+ staining HER2 overexpression in nine of 25 conventional invasive UC cases (36%), four of eight in situ UC cases (50%), and three of six lipid cell variant cases (50%). 3+ staining HER2 overexpression was not seen in eight glandular, six small cell, and five sarcomatoid variant cases. HER2 overexpression was negative in the 20 low-grade noninvasive UC cases but positive in two of the 10 high-grade noninvasive UC cases (20%). We observed HER2 overexpression most commonly in MPUC cases. We also found HER2 overexpression in conventional invasive and in situ UC cases. Pure in situ UC and conventional invasive UC, especially MPUC, could be candidate tumors for treatment with anti-HER2 antibody (trastuzumab therapy). Targeted therapy has a limited place in treatment of bladder cancer. In this study, human epidermal growth factor receptor 2 (HER2) overexpression in bladder carcinomas was evaluated in a large number of cases. Anti-HER2 therapy could be used in bladder cancers, as in breast and gastric cancers. Copyright © 2016 European

  6. 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.

  7. The nested variant of urothelial carcinoma arising in a fibroepithelial polyp: Report of a case and review of literature

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    Nadira Mamoon

    2014-01-01

    Full Text Available The nested variant of urothelial carcinoma is a rare but very important histological entity due to its deceptively bland-looking appearance and aggressive behavior. We present a case of a 30-year-old man who was found to have a solitary polypoid growth in the bladder. It was resected and found to be a fibroepithelial polyp; a rare entity in itself, harboring the above tumor. The lesion also showed a second population of scattered bizarre stromal cells. To our knowledge, this is the first instance of a nested variant of urothelial carcinoma arising in a fibroepithelial polyp. The presence of atypical stromal cells has also not been described previously.

  8. Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma

    NARCIS (Netherlands)

    Mandalapu, Rao S.; Remzi, Mesut; de Reijke, Theo M.; Margulis, Vitaly; Palou, J.; Kapoor, A.; Yossepowitch, Ofer; Coleman, Jonathan; Traxer, Olivier; Anderson, J. Kyle; Catto, James; de la Rosette, Jean; O'Brien, Timothy; Zlotta, Anthony; Matin, Surena F.

    2017-01-01

    The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups.

  9. Bladder carcinoma. Apport MR imaging

    International Nuclear Information System (INIS)

    Roy, C.; Spittler, G.; Jacqmin, D.; Morel, M.

    1991-01-01

    Bladder carcinoma is the second most commun cause of urogenital tumor. It is suspected by abdominal ultrasound and prouved by cystoscopy with biopsy. At present, MR Imaging is the most accurate diagnostic modality for loco-regional staging. Urography is still useful to appreciate urinary tract [fr

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

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    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.

  11. An uncommon manifestation of paraneoplastic cerebellar degeneration in a patient with high grade urothelial, carcinoma with squamous differentiation: A case report and literature review

    International Nuclear Information System (INIS)

    Zhu, Yaofeng; Chen, Shouzhen; Chen, Songyu; Song, Jing; Chen, Fan; Guo, Hu; Shang, Zhenhua; Wang, Yong; Zhou, Changkuo; Shi, Benkang

    2016-01-01

    Paraneoplastic neurological syndromes (PNS) are rare disorders associated with malignant tumours, which are triggered by autoimmune reactions. Paraneoplastic cerebellar degeneration (PCD) is the PNS type most commonly associated with ovarian and breast cancer. Two bladder cancers manifesting in PCD were previously reported. However, the cancers in these cases had poor outcomes. Here, we present a 68-year old man with history of high-grade papillary urothelial carcinoma of the bladder. The patient suffered from persistent cerebellar ataxia accompanied by bladder cancer recurrence five months after transurethral resection of the bladder tumour (TURBt). Laboratory screening for the specific antibodies of paraneoplastic neurological syndromes revealed no positive results. Symptoms were not remitted after a 7-day-course of high-dose glucocorticoid therapy. To our surprise, the patient recovered fully after laparoscopic radical cystectomy. Postoperative pathology revealed that surgical specimens were urothelial carcinoma in situ (CIS) and squamous cell carcinoma of the bladder. The patient remained asymptomatic and there was no evidence of recurrence after the followup period of 11 months. To our knowledge, this is the third report of PCD in a patient with bladder cancer. This case showed that tumour resection cured the PCD. To assist clinical evaluation and management, literature regarding basic PNS characteristics and bladder cancers was reviewed

  12. Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma.

    Science.gov (United States)

    Mandalapu, Rao S; Remzi, Mesut; de Reijke, Theo M; Margulis, Vitaly; Palou, J; Kapoor, A; Yossepowitch, Ofer; Coleman, Jonathan; Traxer, Olivier; Anderson, J Kyle; Catto, James; de la Rosette, Jean; O'Brien, Timothy; Zlotta, Anthony; Matin, Surena F

    2017-03-01

    The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups. This report updates the conservative management of the low-risk group. The ICUD for low-risk UTUC working group performed a thorough review of the literature with an assessment of the level of evidence and grade of recommendation for a variety of published studies in this disease space. We update these publications and provide a summary of that original report. There are no prospective randomized controlled studies to support surgical management guidelines. A risk-stratified approach based on clinical, endoscopic, and biopsy assessment allows selection of patients who could benefit from kidney-preserving procedures with oncological outcomes potentially similar to radical nephroureterectomy with bladder cuff excision, with the added benefit of renal function preservation. These treatments are aided by the development of high-definition flexible digital URS, multi-biopsies with the aid of access sheaths and other tools, and promising developments in the use of adjuvant topical therapy. Recent developments in imaging, minimally invasive techniques, multimodality approaches, and adjuvant topical regimens and bladder cancer prevention raise the hope for improved risk stratification and may greatly improve the endoscopic treatment for low-risk UTUC.

  13. A STUDY OF P53 EXPRESSION IN UROTHELIAL NEOPLASMS OF URINARY BLADDER

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    G. Sathish Kumar

    2017-07-01

    Full Text Available BACKGROUND Urothelial Cell Carcinoma (UCC of urinary bladder is the seventh commonest cancer wordwide.1 At initial diagnosis, 30% of UCC display solid and invasive growth patterns and are locally advanced or metastatic at the time of diagnosis. 70% of tumours are noninvasive papillary UCC confined to the epithelium and subepithelial connective tissue,2 which can be managed by endoscopic resection. A significant number of post-resected cases, progress for recurrence of tumour and infiltration to muscle layers. Invasive bladder cancer has high morbidity and uniform mortality when it is metastatic. There are no effective tools to predict aggressiveness of tumour, so that these cases can be managed more successfully. Mutated Tp53/p53 is the genetic abnormality most frequently associated with UCC and related to cell transformation, malignancy and high recurrence rates.2 MATERIALS AND METHODS This is a descriptive study conducted in the departments of urology and pathology and during the period of March 2014 to February 2015. All consecutive cystoscopic biopsies, Trans urethral resection of bladder tumour (TURBT and radical cystectomy specimens histopathologically diagnosed as UCC were included in the study. p53 expression was assessed by immunohistochemistry. Positive and negative controls were used. Bivariate analysis was done using Chi-square test in all cases. RESULTS A total of 80 cases were analysed. Significant association of p53 expression was found in higher grades of tumour. Also, noted relation of p53 mutation with tumour size, multifocality, multiplicity, muscle invasion and tumour stage, which were statistically not significant. CONCLUSION Bladder tumour grade shows significant association to p53 expression. Papillary neoplasm of low malignant potential (PUNLMP tumours are negative for p53, and in the present study, there was significant difference in p53 over expression low-grade papillary UCC compared with PUNLMP. 90% of low

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

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    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.

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

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    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.

  16. Increased Risks of Upper Tract Urothelial Carcinoma in Male and Female Chinese Herbalists

    Directory of Open Access Journals (Sweden)

    Hsiao-Yu Yang

    2011-03-01

    Conclusion: The significant risk of urothelial carcinoma noted in male herbalists increases our suspicion that this is an occupational disease that renders regular health assessment of herbalists an urgent necessity.

  17. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; de Wit, Ronald; Vaughn, David J

    2017-01-01

    .005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1......BACKGROUND: Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. METHODS: In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred...... points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10...

  18. Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients.

    Science.gov (United States)

    Sooriakumaran, Prasanna; Chiocchia, Virginia; Dutton, Susan; Pai, Aakash; Ayres, Benjamin E; Le Roux, Pieter; Swinn, Michael; Bailey, Michael; Perry, Matthew J A; Issa, Rami

    2016-01-01

    Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy. A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed. The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study. High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM. © 2015 S. Karger AG, Basel.

  19. 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. Copyright © 2010 Wiley-Liss, Inc.

  20. NEOADJUVANT RADIOTHERAPY FOR BLADDER CARCINOMA IN ...

    African Journals Online (AJOL)

    Objective To evaluate the impact of preoperative accelerated hyperfractionated radiotherapy in the management of bladder carcinoma in Egyptian patients. Patients and Methods Between December 1996 and February 2000, 104 Egyptian patients with pathologically proven infiltrative bladder carcinoma were enrolled in ...

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

    Directory of Open Access Journals (Sweden)

    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

  2. Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer.

    Science.gov (United States)

    Bertz, Simone; Otto, Wolfgang; Denzinger, Stefan; Wieland, Wolf F; Burger, Maximilian; Stöhr, Robert; Link, Stefan; Hofstädter, Ferdinand; Hartmann, Arndt

    2014-01-01

    The prognostic value of CK20, Ki-67, and p53 has been investigated for non-muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of pT1 bladder cancers. To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers. Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected. Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4-8 wk. A total of 76 patients underwent cystectomy. We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95% confidence interval [CI], 1.44-24.15; p=0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45-5.43, p=0.002). Ki-67 (HR: 3.83; 95% CI, 1.59-9.26; p=0.003), and CK20 (HR: 8.44; 95% CI,1.16-61.34; p=0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS (p=0.026), PFS (p=0.003), and CSS (plimitation of this study. Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas. Copyright © 2012 European Association of Urology. Published by

  3. A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

    Science.gov (United States)

    Leow, Jeffrey J; Orsola, Anna; Chang, Steven L; Bellmunt, Joaquim

    2015-04-01

    Upper tract urothelial carcinoma (UTUC) accounts for management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Small cell carcinoma of the urinary bladder diverticulum: A case report and review of the literature

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    Wu Xu Dong

    2013-01-01

    Full Text Available Small cell carcinoma of the urinary bladder is very rare. Small cell carcinoma of the urinary bladder is a mass with swiftly aggressive and metastatic, and with a poor prognosis. Due to its scarcity, no forward-looking researches assessing the most effective treatment have been issued in the medical literature. It can happen either in connection with urothelial (transitional cell carcinoma or in a pure form. Its treatment should include surgery, chemotherapy and radiotherapy. In this article,we report a case occurring in a mixed form in the urinary bladder diverticulum and we concisely review the published literature with respect to the clinical manifestation, pathology,differential diagnosis, treatment and prognosis.

  5. Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer.

    Science.gov (United States)

    Koti, Madhuri; Xu, Amanda Shou; Ren, Kevin Yi Mi; Visram, Kash; Ren, Runhan; Berman, David M; Siemens, D Robert

    2017-10-27

    Urothelial bladder cancer (UBC) is a highly prevalent disease in North America, however its optimal management remains elusive. The contribution of B cell associated responses is poorly understood in bladder cancer. Lymphoid neogenesis is a hallmark of an active immune response at tumor sites that sometimes leads to formation of tertiary lymphoid structures (TLS) that resemble germinal centers formed in secondary lymphoid organs. This study was conducted with an aim to investigate the presence and characteristics of TLS in UBC with a focus to compare and contrast the TLS formation in treatment naive low grade non-muscle invasive (NMIBC) and muscle invasive bladder cancers (MIBC). The study cohort consisted of transurethral bladder resection tumour (TURBT) specimens from 28 patients. Sections showing lymphoid aggregates in hematoxylin and eosin (H&E) stained TURBT specimens were further subjected to multi-color immunohistochemistry using immune cell markers specific to CD20 + B cells, CD3 + and CD8 + T cells, PNAd + high endothelial venules, CD208 + mature dendritic cells, CD21 + follicular dendritic cells to confirm the hallmarks of classical germinal centers. Our pilot study investigating the presence of TLS in bladder cancer patients is the first to demonstrate that well-formed TLS are more common in aggressive high grade MIBC tumors compared to low grade NIMBC. These novel findings suggest B cell mediated anti-tumour humoral immune responses in bladder cancer progression.

  6. Urothelial Functional Protein and Sensory Receptors in Patients With Interstitial Cystitis/Bladder Pain Syndrome With and Without Hunner's Lesion.

    Science.gov (United States)

    Jhang, Jia-Fong; Hsu, Yung-Hsiang; Kuo, Hann-Chorng

    2016-12-01

    To investigate the urothelium function and sensory receptors difference between interstitial cystitis/bladder pain syndrome (IC/BPS) patients with or without Hunner's lesion. Fourteen female IC/BPS patients with Hunner's lesion (Hunner IC) and 14 age-matched IC/BPS patients without Hunner's lesions (non-Hunner IC) were enrolled. Bladder mucosa biopsies were obtained. Bladder inflammation, eosinophil infiltration, and urothelial denudation were graded on a 4-point scale after staining with hematoxylin and eosin. Adhesive protein E-cadherin, tryptase, and zonula occuldens-1 in the bladder tissues were assessed with immunofluorescence staining. Urothelial muscarinic receptors M2, M3, endothelial nitric oxide synthase (eNOS), and purinergic receptor P2X3 were evaluated by Western blotting. Hunner IC patients had a significantly higher mean visual analog scale pain score and smaller cystometric bladder capacity than non-Hunner IC patients. The Hunner IC bladder specimens showed more severe or moderate eosinophilic infiltration and urothelial denudation than the non-Hunner IC bladder specimens did. The E-cadherin expression was significantly lower, and eNOS expression was significantly higher in the Hunner IC bladder samples than in the non-Hunner IC samples. The other functional proteins or sensory receptors did not differ between groups. Bladder inflammation and urothelial cell adhesion defects were more severe in the Hunner IC than that in the non-Hunner IC patients. eNOS was significantly higher in the Hunner IC than in the non-Hunner IC bladder samples, suggesting that eNOS expression difference may implicate different pathogenesis in 2 types of IC. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. NFATc1 Expression as a Prognosticator in Urothelial Carcinoma of the Upper Urinary Tract

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    Takashi Kawahara

    2017-06-01

    Full Text Available We recently found that NFATc1, a member of the NFAT family and a key regulator of the immune response, could induce bladder carcinogenesis and cancer progression. In this study, we immunohistochemically stained for NFATc1 in upper urinary tract urothelial carcinoma (UUTUC specimens and paired nonneoplastic urothelial tissues. NFATc1 was positive in 51 [52%; 40 (40% weak (1+, 9 (9% moderate (2+, and 2 (2% strong (3+] of 99 UUTUCs, which was significantly higher than in benign urothelium [30 (36% of 83; 28 (34% weak and 2 (2% moderate] (0 vs 1+/2+/3+, P = .038; 0/1+ vs 2+/3+, P = .023. There were no significant associations between NFATc1 expression pattern and tumor grade or pT stage. However, the positive rates of NFATc1 expression tended to be higher in renal pelvic tumors (60% than in ureteral tumors (42%; P = .080 as well as in pN+ tumors (75% than in pN0 tumors (49%; P = .089. Kaplan-Meier and log-rank tests revealed that moderate (2+ to strong (3+ NFATc1 expression correlated with lower progression-free survival (P = .032 and cancer-specific survival (P = .005 rates in the 99 cases. Patients with high (2+/3+ NFATc1 muscle-invasive tumor (n = 9 also had a significantly higher risk of cancer-specific mortality (P = .021 compared to those with low (0/1+ NFATc1 muscle-invasive tumor (n = 53. Thus, compared with nonneoplastic urothelium, a significant increase in the expression of NFATc1 in UUTUC was seen, implying the involvement of NFATc1 signals in the development of UUTUC. The current results further suggest that NFATc1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.

  8. Squamous cell carcinoma in bladder extrophy

    OpenAIRE

    Cabral-Ribeiro, J; Silva, C; Sousa, L; Pérez García, D; Ribeiro dos Santos, A

    2005-01-01

    Bladder extrophy is a rare congenital malformation that nowadays is surgically corrected in neonatal period. We present a case report of a 71-year-old male with a verrucous squamous cell carcinoma arising in a classical uncorrected form of bladder extrophy.

  9. Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Stroh, M; Winter, H; Marchand, M; Claret, L; Eppler, S; Ruppel, J; Abidoye, O; Teng, S L; Lin, W T; Dayog, S; Bruno, R; Jin, J; Girish, S

    2017-08-01

    Atezolizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human programmed death-ligand 1 (PD-L1), is US Food and Drug Administration (FDA) approved in metastatic urothelial carcinoma (MUC) and is being investigated in various malignancies. This analysis based upon 906 patients from two phase I and one phase II MUC studies, is the first report of the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of atezolizumab. Atezolizumab exhibited linear PK over a dose range of 1-20 mg/kg, including the labeled 1,200 mg dose. The clearance, volume of distribution, and terminal half-life estimates from population pharmacokinetic (PopPK) analysis of 0.200 L/day, 6.91 L, and 27 days, respectively, were as expected for an IgG1. Exposure-response analyses did not identify statistically significant relationships with either objective response rate or adverse events of grades 3-5 or of special interest. None of the statistically significant covariates from PopPK (body weight, gender, antitherapeutic antibody, albumin, and tumor burden) would require dose adjustment. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  10. 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.

  11. 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.

  12. Matched-pair analysis of open versus laparoscopic nephroureterectomy for upper urinary tract urothelial cell carcinoma.

    Science.gov (United States)

    Blackmur, James P; Stewart, Grant D; Egong, Eric A; Cutress, Mark L; Tolley, David A; Riddick, Anthony C P; McNeill, S Alan

    2015-01-01

    Laparoscopic nephroureterectomy (LNU) offers a superior morbidity profile compared with open nephroureterectomy (ONU) in treating upper urinary tract urothelial cell carcinoma. Evidence of oncological equivalence between LNU and ONU is limited. We compare operative and oncological outcomes for LNU and ONU using matched-pair analysis. Of 159 patients who underwent a nephroureterectomy at a single institution between April 1992 and April 2010, 13 pairs of ONU and LNU patients were matched for gender, age, tumour location, tumour grade and stage. Operative details, post-operative characteristics and recurrences were collated and survival rates analysed using the Kaplan-Meier method. There was no significant difference in mean operation time between LNU (191 min) and ONU (194 min, p=0.92). There was no significant difference in the 5-year survival rate between LNU and ONU (overall survival 59.1% vs. 73.5%, p=0.18; progression-free survival 24.0% vs. 56.0%, p=0.14; cancer-specific survival 60.9% vs. 73.5%, p=0.56; bladder cancer recurrence-free survival 8.7% vs. 0.0%, p=0.09). Amidst limited RCT and comparative studies, this study presents further evidence of oncological equivalence between LNU and ONU. There was a trend towards poorer outcomes following LNU though, which merits further study. © 2014 S. Karger AG, Basel.

  13. 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.

  14. Quantitative molecular grading of bladder tumours: a tool for objective assessment of the biological potential of urothelial neoplasias.

    Science.gov (United States)

    Bollmann, Daniel; Bollmann, Magdolna; Bankfalvi, Agnes; Heller, Hildegard; Bollmann, Reinhard; Pajor, Gabor; Hildenbrand, Ralf

    2009-01-01

    The present study aimed to assess whether patients with bladder urothelial tumours can be more objectively stratified into low- and high-risk groups for recurrence and progression using a 2-tired molecular grading scheme, than by subjective histopathological grading alone. Biopsy material from 45 consecutive patients with urothelial bladder neoplasias (2 papillary urothelial neoplasm of low malignant potentials, 18 pTa, 1 pTis, 19 pT1 and 5 pT2) was analysed for immunohistochemical Ki-67 and p53 expression. Labelling indices were assessed by automated cellular image analysis. UroVysion FISH test results were evaluated by automated signal counting, and DNA ploidy of single nuclei preparations were measured by image cytometry. Sixty-nine percent of cases showed >10% Ki-67 LI, 64% had >10% p53 LI, 53% revealed DNA aneuploidy and 56% expressed a high-risk FISH pattern. Based on a combination of single molecular markers, 75% of neoplasias were classified as high molecular grade. Tumour stage and histopathological grade were significantly associated with FISH pattern, DNA ploidy and MIB1 LI. Stage was also related with molecular grade. Clinical outcome showed a significant correlation with MIB1 LI and molecular grade. P53 had neither diagnostic nor prognostic relevance, nor was there any correlation between histological and molecular grade. Our preliminary data strongly suggest that the combination of quantitative biomarkers provides superior and objective prognostic tools in bladder urothelial neoplasias compared to classic clinicopathological features and indices.

  15. Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

    Science.gov (United States)

    Harper, Holly L; McKenney, Jesse K; Heald, Brandie; Stephenson, Andrew; Campbell, Steven C; Plesec, Thomas; Magi-Galluzzi, Cristina

    2017-01-01

    Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial

  16. Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

    Science.gov (United States)

    Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

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

    Directory of Open Access Journals (Sweden)

    Smolensky D

    2016-10-01

    Full Text Available Dmitriy Smolensky,1,2 Kusum Rathore,1 Maria Cekanova1,2 1Department of Small Animal Clinical Sciences, College of Veterinary Medicine, 2UT-ORNL Graduate School of Genome Science and Technology, The University of Tennessee, Knoxville, TN, USA Abstract: 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. Keywords: bladder cancer, transitional cell carcinoma, signaling pathways, clinical trials

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Percutaneous Nephrostomy Infusion: Nursing Considerations for Treatment of Upper Urinary Tract Urothelial Carcinoma.

    Science.gov (United States)

    Draganski, Eryn; Sterman, Ellen; Morris, Kathy

    2017-12-01

    An intrarenal approach using a percutaneous nephrostomy tube is a novel method to deliver chemotherapy and biotherapy to patients with upper urinary tract urothelial carcinoma. A paucity of evidence exists regarding basic nursing implications for this unique treatment option. This column will provide suggested guidelines to administer intrarenal treatment via a percutanous nephrostomy tube.
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  20. External Beam Radiotherapy for Focal Lymphoepithelioma-Like Carcinoma in the Urinary Bladder: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    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.

  1. Combined effects of GSTO1 and SULT1A1 polymorphisms and cigarette smoking on urothelial carcinoma risk in a Taiwanese population

    OpenAIRE

    Min-Che Tung; Yuan-Hung Wang; Shauh-Der Yeh; Chia-Chang Wu; Kuan-Chou Chen; Zhon-Min Huang; Ming-Te Huang; Hung-Yi Chiou

    2014-01-01

    Cigarette smoking is the main risk factor for urothelial carcinoma of the bladder (UCB). Glutathione S-transferase omega 1 (GSTO1) and sulfotransferase 1A1 (SULT1A1) have been reported to be associated with the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. The aim of the present study was to investigate the combined effects of polymorphisms in GSTO1 and SULT1A1 genes and cigarette smoking on UCB risk in a Taiwanese population. Methods: A total of 300 patients w...

  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. Incidental Detection of Perinephric Urinary Leak on Bone Scintigraphy in a Patient with Urinary Bladder Carcinoma.

    Science.gov (United States)

    Vadi, Shelvin Kumar; Dasagrandhi, Vaishnavi; Bhattacharya, Anish; Singh, Shrawan Kumar; Mittal, Bhagwant Rai

    2018-01-01

    A 71-year-old male patient with urothelial carcinoma of the bladder was referred for 99m Tc-methylene diphosphonate bone scintigraphy to assess for skeletal metastasis. While the bone scan showed no abnormal skeletal uptake, tracer activity was detected in the extrarenal region of the left renal fossa on the planar image; single photon emission computed tomography-computed tomography (CT) demonstrated tracer pooling in the perirenal collection. In addition, the CT detected nontracer-avid parenchymal lung nodules and hypodense liver lesions consistent with metastatic disease. The perinephric urinary leak was drained by percutaneous drainage, confirmed by diuretic renography the following day.

  4. Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder.

    Science.gov (United States)

    Srivastava, A K; Singh, P K; Rath, S K; Dalela, D; Goel, M M; Bhatt, M L B

    2014-11-01

    Initial diagnosis of carcinoma of the urinary bladder remains to be a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Urothelial cancer associated 1 (UCA1) is a novel non-coding RNA gene, which plays a pivotal role in bladder cancer progression. Our aim is to investigate the significance of urinary UCA1 for the non-invasive diagnosis of transitional cell carcinoma (TCC) of the urinary bladder. We examined UCA1 expression in a bladder cancer cell line (T24) and in urine of 28 healthy individuals, 46 patients of non-malignant disorders, and 117 cases (69 primary and 48 recurrent cases) of histologically proven TCC prior to transurethral resection by using real-time PCR and compared it with voided urinary cytology. UCA1 expression was found in T24 cell line and also found to be significantly higher in the cancer group as compared to the controls (p0.05). UCA1 can be used as a non-invasive diagnostic biomarker for TCC bladder as an adjunct to cytology in the early diagnosis of primary urinary bladder cancer.

  5. Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

    Science.gov (United States)

    Rava, Marta; Czachorowski, Maciej J; Silverman, Debra; Márquez, Mirari; Kishore, Sirish; Tardón, Adonina; Serra, Consol; García-Closas, Montse; Garcia-Closas, Reina; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Kogevinas, Manolis; Malats, Núria

    2018-02-01

    Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis. © 2017 UICC.

  6. Durvalumab: an investigational anti-PD-L1 monoclonal antibody for the treatment of urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Faiena I

    2018-01-01

    Full Text Available Izak Faiena,1,2 Amy L Cummings,3 Anna M Crosetti,3 Allan J Pantuck,1,2 Karim Chamie,1,2 Alexandra Drakaki1–3 1Department of Urology, 2Institute of Urologic Oncology, 3Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA, USA Abstract: Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1 and its ligand programmed cell death ligand-1 (PD-L1. Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4 monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. One of the latest inhibitors is durvalumab, which is a high-affinity human immunoglobulin G1 kappa monoclonal antibody and blocks the interaction of PD-L1 with PD-1 and CD80. Currently, there are a number of ongoing trials in advanced urothelial carcinoma both using durvalumab monotherapy and in combination with other targeted therapies. In addition, durvalumab is being investigated in the non-muscle-invasive urothelial carcinoma, which is centered around intravenous formulations. These exciting developments have added a significant number of therapies in a previously limited treatment landscape. Keywords: durvalumab, checkpoint inhibitors, metastatic urothelial carcinoma

  7. Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.

    OpenAIRE

    Lindgren, David; Sjödahl, Gottfrid; Lauss, Martin; Staaf, Johan; Chebil, Gunilla; Lövgren, Kristina; Gudjonsson, Sigurdur; Liedberg, Fredrik; Patschan, Oliver; Månsson, Wiking; Fernö, Mårten; Höglund, Mattias

    2012-01-01

    Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes...

  8. Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

    Science.gov (United States)

    2018-03-20

    Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Msaouel, Pavlos; Koutsilieris, Michael

    2011-01-01

    The diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26). CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests

  11. Corticotropin-releasing factor family peptide signaling in feline bladder urothelial cells.

    Science.gov (United States)

    Hanna-Mitchell, Ann T; Wolf-Johnston, Amanda; Roppolo, James R; Buffington, Tony C A; Birder, Lori A

    2014-07-01

    Corticotropin-releasing factor (CRF) plays a central role in the orchestration of behavioral and neuroendocrine responses to stress. The family of CRF-related peptides (CRF and paralogs: urocortin (Ucn)-I, -II, and -III) and associated receptors (CRFR1 and CRFR2) are also expressed in peripheral tissues such as the skin and gastrointestinal tract. Local signaling may exert multiple effects of stress-induced exacerbation of many complex syndromes, including psoriasis and visceral hypersensitivity. Interstitial cystitis/painful bladder syndrome (IC/PBS), a chronic visceral pain syndrome characterized by urinary frequency, urgency, and pelvic pain, is reported to be exacerbated by stress. Functional changes in the epithelial lining of the bladder, a vital blood-urine barrier called the urothelium, may play a role in IC/PBS. This study investigated the expression and functional activity of CRF-related peptides in the urothelium of normal cats and cats with feline interstitial cystitis (FIC), a chronic idiopathic cystitis exhibiting similarities to humans diagnosed with IC/PBS. Western blots analysis showed urothelial (UT) expression of CRFR1 and CRFR2. Enzyme immunoassay revealed release of endogenous ligands (CRF and Ucn) by UT cells in culture. Evidence of functional activation of CRFR1 and CRFR2 by receptor-selective agonists (CRF and UCN3 respectively) was shown by i) the measurement of ATP release using the luciferin-luciferase assay and ii) the use of membrane-impermeant fluorescent dyes (FM dyes) for fluorescence microscopy to assess membrane exocytotic responses in real time. Our findings show evidence of CRF-related peptide signaling in the urothelium. Differences in functional responses between FIC and normal UT indicate that this system is altered in IC/PBS. © 2014 Society for Endocrinology.

  12. The nested variant of bladder transitional cell carcinoma: Review of 12 cases and review of the literature.

    Science.gov (United States)

    Carrion-Ballardo, C J; Gala-Solana, L; Portillo-Martin, J A; Azueta-Etxebarria, A; Truan-Cacho, D; Campos-Juanatey, F

    2015-01-01

    The nested variant of bladder transitional cell carcinoma is extremely rare and has a different biological behavior to other bladder tumors. The aim of this study is to analize if their behavior is as aggressive as has been described in the literature. Review of 12 diagnosed cases with nested variant of bladder transitional cell carcinoma and analysis of demographic characteristics, clinical presentation, tumor characteristics, treatment options, analysis of recurrence and cancer-specific survival between January 1997 and December 2010 in our hospital. 50% of the cases had a pathologic stage ≥T2, with grade of differentiation G2 (50%) or G3 (50%). After the pathological result of the TUR (transurethral resection) Bladder, 5 cases underwent radical cystoprostatectomy, 3 a second TUR bladder and 4 cases with treatment chemotherapy and/or radiotherapy (RT). Five out of 12 cases (41.7%) died due to bladder cancer and 3 died (25%) of other causes (urinary sepsis, respiratory failure, renal failure). With a median follow up of 40 months, the overall survival was 50% and cancer-specific survival of 65.6%. The nested variant of bladder transitional cell carcinoma is a disease with an advanced-stage presentation, with high recurrence and mortality rates despite the use of different treatments. So far there is not a clinical practice guideline for this variety of urothelial tumor. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Olaparib in Treating Patients With Metastatic or Advanced Urothelial Cancer With DNA-Repair Defects

    Science.gov (United States)

    2018-03-02

    Abnormal DNA Repair; ATM Gene Mutation; ATR Gene Mutation; BAP1 Gene Mutation; BARD1 Gene Mutation; BLM Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; BRIP1 Gene Mutation; CHEK1 Gene Mutation; CHEK2 Gene Mutation; FANCC Gene Mutation; FANCD2 Gene Mutation; FANCE Gene Mutation; FANCF Gene Mutation; MEN1 Gene Mutation; Metastatic Urothelial Carcinoma; MLH1 Gene Mutation; MSH2 Gene Mutation; MSH6 Gene Mutation; MUTYH Gene Mutation; NPM1 Gene Mutation; PALB2 Gene Mutation; PMS2 Gene Mutation; POLD1 Gene Mutation; POLE Gene Mutation; PRKDC Gene Mutation; RAD50 Gene Mutation; RAD51 Gene Mutation; SMARCB1 Gene Mutation; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; STK11 Gene Mutation; Urothelial Carcinoma

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Pathologic Pattern of Invasive Bladder Carcinoma: Impact of ...

    African Journals Online (AJOL)

    Objective: To describe the pathologic pattern of invasive bladder carcinoma in cystectomy specimens in relation to bilharziasis. Patients and Methods: Between April 2002 and October 2006, 148 consecutive patients with invasive bladder cancer were subjected to radical cystectomy and orthotopic sigmoid bladder ...

  16. 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.

  17. MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma.

    Science.gov (United States)

    Matsuzaki, Kyosuke; Fujita, Kazutoshi; Jingushi, Kentaro; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Ueda, Yuko; Tanigawa, Go; Yoshioka, Iwao; Ueda, Koji; Hanayama, Rikinari; Uemura, Motohide; Miyagawa, Yasushi; Tsujikawa, Kazutake; Nonomura, Norio

    2017-04-11

    Extracellular vesicles are lipid bilayer vesicles containing protein, messengerRNA and microRNA. Cancer cell-derived extracellular vesicles may be diagnostic and therapeutic targets. We extracted extracellular vesicles from urine of urothelial carcinoma patients and the control group to identify cancer-specific microRNAs in urinary extracellular vesicles as new biomarkers. microRNA from urinary extracellular vesicles extracted from 6 urothelial carcinoma patients and 3 healthy volunteers was analyzed. We verified candidate microRNAs in an independent cohort of 60 urinary extracellular vesicles samples. To normalize the microRNA expression level in extracellular vesicles, we examined the following in extracellular vesicles: protein concentration, CD9 intensity, amounts of whole miRNAs, RNA U6B small nuclear expression and the creatinine concentration of original urine correlating with the counts of extracted extracellular vesicles measured by the NanoSight™ system. From the microarray results 5 microRNAs overexpressed in urinary extracellular vesicles of urothelial carcinoma patients were identified. Creatinine concentration of original urine correlated most with particle counts of extracellular vesicles, indicating that creatinine could be a new tool for normalizing microRNA expression. MiR-21-5p was the most potent biomarker in urinary extracellular vesicles (sensitivity, 75.0%; specificity, 95.8%) and was also overexpressed in urinary extracellular vesicles from urothelial carcinoma patients with negative urine cytology. For the subgroup with negative urine cytology, the sensitivity was 75.0% and specificity was 95.8%. MiR-21-5p in urinary extracellular vesicles could be a new biomarker of urothelial carcinoma, especially for urothelial carcinoma patients with negative urine cytology.

  18. Oncologic Results of Retroperitoneoscopic Versus Open Surgery for T2 Upper Tract Urothelial Carcinoma.

    Science.gov (United States)

    Shan, Hongli; Wang, Xiaoqing; Sun, Qingnian; Chen, Qihui; Xu, Bo; Hao, Yuanyuan; Xu, Wei

    2015-12-01

    The present study was designed to compare oncologic outcomes of T2 upper tract urothelial carcinoma patients treated with retroperitoneoscopic nephroureterectomy (RNU) or open radical nephroureterectomy (ONU). T2 upper tract urothelial carcinoma patients were treated with RNU (n = 110) or ONU (n = 118) and followed-up for > 5 years. Demographic and clinical data, including preoperative indexes, intraoperative indexes, and oncological outcomes, were retrospectively compared to determine the efficacy of the 2 procedures. The RNU and ONU groups were statistically similar in age, sex, tumor location, and tumor pathologic grade. The original surgery time required for RNU and ONU was statistically similar, but RNU was associated with a significantly smaller volume of intraoperative estimated blood loss and shorter length of postoperative hospital stay. Follow-up (average: 43.2 months; range, 6-72 months) revealed that the estimated 5-year overall survival rate and the estimated 5-year disease-specific survival rate after RNU was slightly worse than after ONU (66.0% vs. 67.1%, and 80.8% vs. 83.8%, respectively), and the estimated 5-year recurrence-free survival rate and the estimated 5-year intravesical recurrence-free survival rates were slightly better than ONU (79.5% vs. 77.9%, and 68.3% vs. 65.6%, respectively). However, none of these differences were statistically significant. The open surgery strategy and the RNU strategy are equally effective for treating T2 upper tract urothelial carcinoma. However, the RNU procedure is safer, less invasive, and requires a shorter duration of postoperative hospitalized care; thus, RNU is recommended as the preferred strategy. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Impact of preoperative anemia on oncologic outcomes of upper tract urothelial carcinoma treated with radical nephroureterectomy.

    Science.gov (United States)

    Rink, Michael; Sharifi, Nasim; Fritsche, Hans-Martin; Aziz, Atiqullah; Miller, Florian; Kluth, Luis A; Ngamsri, Theofanis; Dahlem, Roland; Chun, Felix K; Shariat, Shahrokh F; Stenzl, Arnulf; Fisch, Margit; Gakis, Georgios

    2014-02-01

    We evaluated the impact of preoperative anemia on oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. A total of 282 patients with upper tract urothelial carcinoma underwent radical nephroureterectomy. Preoperatively measured hemoglobin values were stratified into normal and anemia based on the WHO classification of 13 gm/dl or less and 12 or less considered anemia in males and females, respectively. We performed sensitivity analysis based on contemporary anemia classifications adjusted for the impact of age, gender and race with anemia considered a hemoglobin value of 13.7 gm/dl or less and 13.2 or less in white males younger than 60 and 60 years old or older, respectively, and 12.2 gm/dl or less in white females of all ages. Univariable and multivariable Cox regression analyses were done to assess the effects of anemia on oncologic outcomes. Median preoperative hemoglobin was 13.2 gm/dl (IQR 11.7, 14.3). A total of 112 patients (39.7%) were anemic by the WHO classification vs 129 (45.7%) by the contemporary classification. Anemia was associated with lymph node metastasis, lymphovascular invasion, sessile tumor architecture, tumor necrosis, advanced age and a higher ECOG (Eastern Cooperative Oncology Group) performance score using the WHO and/or the contemporary definition (p ≤0.044). At a median 30-month followup anemia was associated with decreased recurrence-free (p ≤0.008) and cancer specific (p contemporary classifications, respectively. Preoperative anemia is an independent predictor of disease recurrence and cancer specific mortality. It is associated with aggressive tumor features in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. Hemoglobin is a promising marker for patient counseling and risk stratification for additional treatment decision making. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc

  20. 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.

  1. Long-term outcome of hand-assisted laparoscopic nephroureterectomy for pathologic T3 upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Chung, Shiu-Dong; Chen, Shyh-Chyan; Wang, Shuo-Meng; Chueh, Shih-Chieh; Lai, Ming-Kuen; Huang, Chao-Yuan; Pu, Yeong-Shiau; Huang, Kuo-How; Yu, Hong-Jeng

    2009-01-01

    To determine the feasibility and long-term outcomes of hand-assisted laparoscopic nephroureterectomy (HALNU) compared with open nephroureterectomy (ONU) in the management of pT(3)N0 upper urinary tract urothelial carcinoma (UUT-UC). Between January 1994 and December 2005, 21 patients who underwent HALNU for stage pT(3)N0 UTT-UC were matched and compared with 31 patients who underwent ONU. The oncologic out-comes, including bladder recurrence, recurrence-free survival, cancer-specific survival, and overall survival, were statistically analyzed. The median follow-up period in the HALNU group was 72 months (range 33-111 months) and 115 months in the ONU group (range 24-161 months). Patient age, sex, body mass index, tumor size, specimen weight, and American Society of Anesthesiologists classification showed no significant difference between the two groups. The HALNU group had statistically less blood loss than the ONU group (113 mL versus 487 mL; P = 0.02). The average hospital stay and doses of narcotic analgesics were significantly less in the HALNU group than the ONU group. The complication and bladder recurrence rates were similar between the two groups. The 5-year recurrence-free survival, cancer-specific survival, and overall survival were also comparable in both groups. HALNU is a safe and efficacious procedure with comparable long-term oncologic outcomes in comparison with ONU in treating patients with locally advanced pT(3)N0UUT-UC.

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

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    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.

  3. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

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    Ajjai Alva

    2015-07-01

    Full Text Available Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  4. Loss of BCG Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to BCG Exposure

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    Shah, Gopitkumar; Zhang, Guangjian; Chen, Fanghong; Cao, YanLi; Kalyanaraman, Balaraman; See, William

    2018-01-01

    INTRODUCTION The attenuated mycobacterium Bacille Calmette Guerin (BCG) is widely utilized as intravesical “immunotherapy” for the treatment of non-muscle invasive urothelial carcinoma. Previous studies have demonstrated that in both the laboratory and clinical setting, BCG viability is a variable that correlates with anti-tumor efficacy. This study evaluated how loss of BCG viability impacted a number of molecular and phenotypic intermediate endpoints that characterize, and/or contribute to, the direct effect of BCG on Urothelial carcinoma (UC) cells. MATERIALS AND METHODS Two human UC cell lines were used to study the effect of loss of BCG viability on the tumor cell response to BCG. The cellular response to BCG rendered non-viable by heat killing (hk) was compared to the response to viable BCG. The response endpoints evaluated included the induction of oxidative stress, activation of intracellular signaling pathways, gene transactivation, and phenotypic changes. RESULTS Loss of viability resulted in a quantitative decrease in the tumor cell response, relative to viable BCG, for all of the measured endpoints. The decrease in response varied by cell line, ranging from 15% to 100% of the response to viable BCG. While quantitatively different, non-viable BCG continued to induce responses that were qualitatively similar to BCG relative to untreated controls. CONCLUSIONS BCG viability is an important variable influencing the direct tumor cell response to BCG. Although the magnitude of it effects are attenuated, hkBCG remains active for the induction of BCG responsive biologic endpoints. PMID:24035882

  5. Evaluation of Bladder Carcinoma Risk of the Workers Exposed to Industrial Chemicals

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    Serpil Oguztuzun

    2010-12-01

    Full Text Available AIM: The aim of this study is to evaluate the ratios of bladder carcinoma of workers exposed to industrial chemicals in Kirikkale, Turkey by urinary cytology method. METHOD: Urinary cytology preparations for a total of 63 workers in the gun powder production plant was prepared using Papanicolaou staining and evaluated by light microscopy. The relationship between Papanicolaou staining results and workers’ exposure time to chemicals was evaluated statistically by Post Hoc Test method. RESULTS: For the cytological diagnoses of voided urine in all 63 workers, 16 workers as control group had negative cytologic findings. 47 workers exposed to industrial chemicals more than 20 years had two metaplasic and two dysplasic cells in their urine cytology samples. Moreover, a worker exposed to industrial chemicals more than 30 years had urothelial carcinoma cells. CONCLUSION: That the workers’ risk of developing bladder carcinoma increases with their exposure time to chemicals in their work environment has been found statistically significant (p<0,05. [TAF Prev Med Bull 2010; 9(6.000: 597-604

  6. 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...

  7. Low Grade Micropapillary Urothelial Carcinoma, Does It Exist? - Analysis of Management and Outcomes from the Surveillance, Epidemiology and End Results (SEER) Database.

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    Vourganti, Srinivas; Harbin, Andrew; Singer, Eric A; Shuch, Brian; Metwalli, Adam R; Agarwal, Piyush K

    2013-01-01

    To elucidate the oncologic behavior of Micropapillary Urothelial Bladder Carcinoma (MPBC), a rare aggressive variant histology. All MPBC patients in SEER 17 database were compared with those with traditional urothelial carcinoma (UC). Kaplan-Meier curves were used to determine OS and CSS. A Cox proportional hazards model (CPH) was constructed to test the effect of covariates on outcomes. From 2001-2008, 120 MPBC patients were identified, 0.1% of all bladder cancer. MPBC presented with more high grade (86.1% vs. 38.7%, p<0.0001) and more high stage disease (40.8% NMI vs. 90.4% NMI, p < 0.0001) than UC. Low grade (LG) NMI MPBC had worse OS and CSS compared to LG UC (p=0.0037, p<0.0001 respectively), and did no better than high grade (HG) NMI MPBC. No difference was detected between HG NMI MPBC and HG NMI UC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. UC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 patients underwent definitive therapy, of whom none died of disease. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). Controlling for stage and grade, no survival difference could be detected between MPBC and UC. Low grade NMI MPBC behaved similarly to both high grade MPBC and high grade UC. We propose that all MPBC (regardless of grade) be managed as high grade disease, and that strong consideration for definitive therapy should be given in all cases.

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

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    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.

  9. The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

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    Gudjónsson, Sigurdur; Bläckberg, Mats; Chebil, Gunilla; Jahnson, Staffan; Olsson, Hans; Bendahl, Pär-Ola; Månsson, Wiking; Liedberg, Fredrik

    2012-07-01

    It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now. By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable. To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder

  10. Risk factors and prognosis of intravesical recurrence after surgical management of upper tract urothelial carcinoma: A 30-year single centre experience

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    Mohamed Mohamed Elawdy

    2017-09-01

    Conclusions: In our present series, bladder cancer recurrence of urothelial malignancy occurred in nearly half of the patients after surgical management of UTUC. Ureteric tumour was the only identifiable risk factor, thus patients with ureteric tumours may benefit from prophylactic intravesical chemoimmunotherapy. Bladder recurrence does not appear to affect the cancer-specific survival after surgical management of UTUC.

  11. 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...

  12. Transitional Cell Carcinoma within a Portion of Inguinally Herniated Bladder

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    Matthew A. Uhlman

    2013-01-01

    Full Text Available Bladder herniation within the inguinal canal is a relatively uncommon finding. We report an even less-common occurrence of transitional cell carcinoma located within a portion of inguinally herniated bladder. Fewer than 20 reports exist in the literature describing this scenario.

  13. Serum Cystatin C Level Is Not a Promising Biomarker for Predicting Clinicopathological Characteristics of Bladder Urothelial Tumors

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    Hui Wang

    2018-01-01

    Full Text Available The role of cystatin C (Cys-C in tumorigenesis and progression of bladder urothelial tumors (BUT is still indefinite. We retrospectively collected the clinical information from the records of 425 BUT patients. Pretreatment serum Cys-C levels were compared across the various groups. Then we subgroup the patients with GFR ≥ 90 mg/min/1.73 m2, to exclude the effects of lower renal function on cystatin C. No statistically significant differences in the levels of serum Cys-C were found among the tumor characteristics (all P>0.05. In conclusion, circulating Cys-C was not a reliable predictor for clinicopathological characteristics of BUT patients.

  14. Urothelial dysfunction and sensory protein expressions in patients with urological or systemic diseases and hypersensitive bladder

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    Hueih-Ling Ong

    2017-09-01

    Conclusion: Patients with OAB or HSB showed increased urothelial inflammation and lower barrier protein expression. Increased M3/β3-AR or M2/β3-AR in the urothelium was associated with OAB, whereas decreased M3/β3-AR or M2/β3-AR was associated with poor voiding efficiency and large PVR in LUTD.

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

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    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.

  16. Review: Application of Nanoparticles in Urothelial Cancer of the Urinary Bladder

    OpenAIRE

    Chen, Chieh-Hsiao; Chan, Tzu-Min; Wu, Yi-Jhen; Chen, Jia-Jin

    2015-01-01

    Bladder cancer is a common malignancy of the urinary tract, which generally develops in the epithelial lining of the urinary bladder. The specific course of treatment depends on the stage of bladder cancer; however, therapeutic strategies typically involve intravesical drug delivery to reduce toxicity and increase therapeutic effects. Recently, metallic, polymeric, lipid, and protein nanoparticles have been introduced to aid in the treatment of bladder cancer. Nanoparticles are also commonly ...

  17. 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

  18. Thin-section CT with air insufflation technique for bladder carcinoma: CT findings of superficial bladder carcinoma

    International Nuclear Information System (INIS)

    Kim, Hyun; Song, Ha Hun; Kim, Mi Hye; Lee, Eun Ja; Kim, Young Sin; Kang, Si Won; Shinn, Kyung Sub

    1994-01-01

    The staging of bladder carcinoma is a major determinant of operative management CT of bladder carcinoma has been widely used to diagnose external extension (pT3b and over), but tumors confined to the bladder wall (from pT1 to pT3a) are poorly delineated. The authors describe CT findings of the superficial bladder carcinoma (below T1, stage A) in thin-section CT with air insufflation technique (air insufflation-CT) to facilitate early detection and to aid correct staging of the superficial bladder carcinoma. The materials consisted of proved 24 cases (19 patients, single tumor: 16 patients, multiple tumors: 3 patients) of stage A bladder carcinomas. Air insufflation-CT was performed by the infusion of approximately 200 mL of air into the bladder via a Foley catheter. After the routine pelvic CT, bladder tumors were re-scanned with 1.5 to 5 mm thickness and intervals. The superficial bladder carcinoma were detected as nodular(5 cases, 20.8%), papillary(15 cases, 62.5%), pyramida(2 cases, 8.3%), and domed(2 cases, 8.3%) forms on air insufflation-CT. These tumors were classified into three types according to the size of the tumoral neck: type I(pedundulated polypoid tumor: 4 cases, 16.6%), type II(polypid tumor with short neck: 13 cases, 54.2%), and type III(sessile tumor: 7 cases, 29.2%). The mean size(tumoral width x height x base c neck/stalk) of the tumors was 22 x 20 x 16mm. The average tumoral sizes according to each type of the superficial tumors were type I: 22 x 25 x 6mm, type II: 23 x 22 x 18mm, and type III: 18 x 15 x 18mm. The mean width of the type I-II tumoral necks was 15mm. The mean length of the type I tumoral neck(pedicle) was 2.5mm. Papillary fronds of the tumors were seen in 10 cases(41.7%) of 24 superficial tumors. Outer margin of the involved bladder wall was smooth in all cases. Thin-section CT with air insufflation technique for bladder carcinoma was useful in tumoral demonstration, and characteristics of the superficial bladder carcinomas were

  19. Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

    Science.gov (United States)

    Tsai, Hsin-Lin; Chang, Jei-Wen; Wu, Tsai-Hun; King, Kuang-Liang; Yang, Ling-Yu; Chan, Yu-Jiun; Yang, An-Hang; Chang, Fu-Pang; Pan, Chin-Chen; Yang, Wu-Chang; Loong, Che-Chuan

    2014-07-15

    To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

  20. Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.

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    David Lindgren

    Full Text Available Similar to other malignancies, urothelial carcinoma (UC is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21, and BCL2L1 (20q11. We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development.

  1. Dietary intake of nutrients involved in one-carbon metabolism and risk of urothelial cell carcinoma: A prospective cohort study.

    Science.gov (United States)

    Dugué, Pierre-Antoine; Brinkman, Maree T; Hodge, Allison M; Bassett, Julie K; Bolton, Damien; Longano, Anthony; Hopper, John L; Southey, Melissa C; English, Dallas R; Milne, Roger L; Giles, Graham G

    2018-02-15

    Nutrients involved in one-carbon metabolism may play a role in carcinogenesis through DNA replication, repair and methylation mechanisms. Most studies on urothelial cell carcinoma (UCC) have focused on folate. We sought to examine the association between B-group vitamins and methionine intake and UCC risk, overall and by subtype, and to test whether these associations are different for population subgroups whose nutritional status may be compromised. We followed participants in the Melbourne Collaborative Cohort Study (N = 41,513) for over 20 years and observed 500 UCC cases (89% originating in the bladder; superficial: 279, invasive: 221). Energy-adjusted dietary intakes of B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12) and methionine were estimated from a 121-item food frequency questionnaire administered at baseline (1990-1994), using the residuals method. We used Cox regression models to compute hazard ratios (HRs) of UCC risk per standard deviation (SD) of log-transformed nutrient intakes and 95% confidence intervals, adjusted for potential confounders. We investigated associations by tumor subtype, and tested interactions with sex, country of birth, smoking and alcohol drinking. The risk of UCC appeared not to be associated with intake of B-group vitamins or methionine, and findings were consistent across tumor subtypes and across demographic and lifestyle characteristics of the participants. A potential interaction between vitamin B1 and alcohol drinking was observed (all participants: HR per 1 SD = 0.99 (0.91-1.09), never drinkers: HR = 0.81 (0.69-0.97), p-interaction = 0.02), which needs to be confirmed by other studies. Our findings do not indicate that dietary intake of nutrients involved in one-carbon metabolism are associated with UCC risk. © 2018 UICC.

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

    International Nuclear Information System (INIS)

    Fischer, Nicolas; Göke, Friederike; Splittstößer, Vera; Lankat-Buttgereit, Brigitte; Müller, Stefan C.; Ellinger, Jörg

    2012-01-01

    Highlights: ► The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. ► We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. ► 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.

  3. 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.

  4. Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.

    Science.gov (United States)

    Rieken, Malte; Shariat, Shahrokh F; Karam, Jose A; Foerster, Beat; Khani, Francesca; Gust, Kilian; Abufaraj, Mohammad; Wood, Christopher G; Weizer, Alon Z; Raman, Jay D; Guo, Charles C; Rioux-Leclercq, Nathalie; Haitel, Andrea; Bensalah, Karim; Lotan, Yair; Bachmann, Alexander; De Marzo, Angelo M; Robinson, Brian D; Margulis, Vitaly

    2017-12-01

    To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. PTEN staining was absent in 45 cases (7.4%). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95% CI 1.09-2.61, p = 0.02). In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. CT Urography for Diagnosis of Upper Urinary Tract Urothelial Carcinoma: Are Both Nephrographic and Excretory Phases Necessary?

    Science.gov (United States)

    Takeuchi, Mitsuru; Konrad, Aaron J; Kawashima, Akira; Boorjian, Stephen A; Takahashi, Naoki

    2015-09-01

    The objective of our study was to compare the diagnostic performance of nephrographic phase only, excretory phase only, and both nephrographic and excretory phases of CT urography (CTU) for the detection of upper tract urothelial carcinoma. Forty-nine consecutive patients with pathologically proven upper tract urothelial carcinoma who underwent a single-bolus CTU examination were evaluated. Forty-nine control patients with normal findings on two CTU examinations performed at a 1-year interval were included. Two radiologists independently reviewed the 98 CTU examinations at three different sessions (nephrographic phase only, excretory phase only, and both nephrographic and excretory phases simultaneously) and rated the likelihood of the presence of a urothelial carcinoma in each segment of the renal collecting system and ureter using a 5-point scale. Sensitivity, specificity, and AUC of ROC curve were calculated per segment and per patient. A total of 314 segments, 56 of which contained tumors, were evaluated. In the per-segment analysis for reviewers 1 and 2, the sensitivity, specificity, and AUC, respectively, were as follows: 88%, 98%, and 0.95 and 84%, 97%, and 0.94 for the nephrographic phase; 79%, 98%, and 0.91 and 89%, 98%, and 0.95 for the excretory phase; and 88%, 99%, and 0.95 and 89%, 99%, and 0.96 for the combined nephrographic and excretory phases. The AUC of the combined nephrographic and excretory phases was significantly higher than that of the nephrographic phase (per-patient analysis, reviewer 2) and that of excretory phase (per-segment analysis, reviewer 1) but was not significantly different in any other comparisons. The nephrographic and excretory phases are complementary for the detection of upper tract urothelial carcinoma.

  6. Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

    NARCIS (Netherlands)

    Bevers, R. F. M.; Kurth, K.-H.; Schamhart, D. H. J.

    2004-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been

  7. Hydronephrotic urine in the obstructed kidney promotes urothelial carcinoma cell proliferation, migration, invasion through the activation of mTORC2-AKT and ERK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Chi-Hao Chang

    Full Text Available Obstructive nephropathy is the most common presentation of urothelial carcinoma. The role of the urine in the obstructed kidney namely "hydronephrotic urine" in urothelial carcinoma has not been extensively explored. This study aims to evaluate whether hydronephrotic urine in the obstructed kidney could promote urothelial carcinoma. The hydronephrotic urine was collected from the obstructed kidneys of Sprague-Dawley rats induced by different periods of unilateral ureteral obstruction (UUO. By the inhibition of LY294002 and PD184352, we confirm that hydronephrotic urine promotes urothelial carcinoma cell (T24 and immortalized normal urothelial cells (E6 proliferation, migration and invasion in a dose-dependent manner through the activation of the mTORC2-AKT and ERK signaling pathways. Hydronephrotic urine also increases the expression of cyclin-D2, cyclin-B and CDK2. It also decreases the expression of p27 and p21 in both urothelial carcinoma cells and normal urothelial cells. By the protein array study, we demonstrate that many growth factors which promote tumor cell survival and metastasis are over-expressed in a time-dependent manner in the hydronephrotic urine, including beta-FGF, IFN-γ, PDGF-BB, PIGF, TGF-β, VEGF-A, VEGF-D and EGF. These results suggest that hydronephrotic urine promotes normal and malignant urothelial cells proliferation, migration and invasion, through the activation of the mTORC2-AKT and ERK signaling pathways. Further investigation using live animal models of tumor growth may be needed to clarify aspects of these statements.

  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...... in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease....... the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P bladder cell line HU609, SOX4...

  9. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. A Modified Single Mini-Incision Complete Urinary Tract Exenteration for Urothelial Carcinoma in Dialysis Patients

    Directory of Open Access Journals (Sweden)

    I-Hsuan Chen

    2014-01-01

    Full Text Available Objective. To present our experience with single mini-incision complete urinary tract exenteration (CUTE for female dialysis patients suffering from urothelial carcinoma (UC. Patients and Methods. Institutional review board approval was obtained. From 2005 through 2012, 14 female dialysis patients with UC underwent single mini-incision CUTE, in combination with radical hysterectomy and bilateral salpingo-oophorectomy. All were placed in the modified dorsal lithotomy position without repositioning. An infraumbilical midline mini-incision was made. Bilateral nephroureterectomy was first performed entirely extraperitoneally, followed by radical cystectomy with removal of the uterus and ovaries transperitoneally. Results. All procedures were done successfully without major complications. The median operative time was 242.5 minutes, and estimated blood loss was 500 mL. The median time to oral intake was 2 postoperative days; the median hospital stay was 11 days. Ten patients remained cancer-free at a median follow-up of 46.5 months; six patients were confirmed as having preoperatively undetectable UC or renal cell carcinoma, even after reviewing preoperative computed tomography. Conclusions. This modified technique provides a time-saving complete urinary tract extirpation to eliminate preoperatively undetectable malignancy, reduce metachronous recurrences, and avert perioperative complications associated with pneumoperitoneum and repositioning. Good cancer control and early convalescence can mutually be achieved in experienced hands.

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

    Directory of Open Access Journals (Sweden)

    Shian-Shiang Wang

    Full Text Available 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.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.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.

  12. 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

  13. The role of polymer nanosurface roughness and submicron pores in improving bladder urothelial cell density and inhibiting calcium oxalate stone formation

    Science.gov (United States)

    Chun, Young Wook; Khang, Dongwoo; Haberstroh, Karen M.; Webster, Thomas J.

    2009-02-01

    Synthetic polymers have been proposed for replacing resected cancerous bladder tissue. However, conventional (or nanosmooth) polymers used in such applications (such as poly(ether) urethane (PU) and poly-lactic-co-glycolic acid (PLGA)) often fail clinically due to poor bladder tissue regeneration, low cytocompatibility properties, and excessive calcium stone formation. For the successful reconstruction of bladder tissue, polymer surfaces should be modified to combat these common problems. Along these lines, implementing nanoscale surface features that mimic the natural roughness of bladder tissue on polymer surfaces can promote appropriate cell growth, accelerate bladder tissue regeneration and inhibit bladder calcium stone formation. To test this hypothesis, in this study, the cytocompatibility properties of both a non-biodegradable polymer (PU) and a biodegradable polymer (PLGA) were investigated after etching in chemicals (HNO3 and NaOH, respectively) to create nanoscale surface features. After chemical etching, PU possessed submicron sized pores and numerous nanometer surface features while PLGA possessed few pores and large amounts of nanometer surface roughness. Results from this study strongly supported the assertion that nanometer scale surface roughness produced on PU and PLGA promoted the density of urothelial cells (cells that line the interior of the bladder), with the greatest urothelial cell densities observed on nanorough PLGA. In addition, compared to respective conventional polymers, the results provided evidence that nanorough PU and PLGA inhibited calcium oxalate stone formation; submicron pored nanorough PU inhibited calcium oxalate stone formation the most. Thus, results from the present study suggest the importance of nanometer topographical cues for designing better materials for bladder tissue engineering applications.

  14. A low psoas muscle volume predicts longer hospitalization and cancer recurrence in upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Tsutsumi, Sohgo; Kawahara, Takashi; Teranishi, Jun-Ichi; Yao, Masahiro; Uemura, Hiroji

    2018-02-01

    The aging population is becoming a primary global problem. The most important alteration that occurs in the body with age, is the loss of skeletal muscle. Previously, sarcopenia, which is associated with the loss of skeletal muscle, has been reported to be associated with the prognosis of cancer and complications. The present study investigated the importance of sarcopenia with regard to the prognosis or postoperative complications of upper urothelial cancer patients who underwent nephro-ureterectomy. A total of sixty patients (male, n=44; female, n=16) underwent nephro-ureterectomy for upper urothelial carcinoma. The psoas muscle volume was calculated at the level of the umbilicus using axial computed tomography images obtained prior to nephro-ureterectomy. The psoas muscle index (PMI) was calculated by the following formula: (right side psoas muscle area at the level of the umbilicus mm 2 )/(body height m) 2 . The median and mean (± standard deviation) ages of the 44 patients were 71 and 68.0 years (± 12.2 years). The lower PMI group demonstrated a significantly poorer recurrence-free survival compared with the higher PMI group (634 vs. 2,317 days, P=0.005). In terms of the duration of postoperative admission, the long-admission group (≥13 days) demonstrated a significantly lower PMI compared with the short-admission group (≤12 days) (383.0 vs. 433.1, P=0.039). Although the overall survival of the two groups did not differ significantly, the lower PMI group tended to have a shorter survival period compared with the higher PMI group (P=0.080). Of the patients with upper urothelial carcinoma, the lower PMI group exhibited a longer postoperative admission period and poorer recurrence-free survival compared with the higher PMI group. The present findings suggest that sarcopenia is a meaningful factor that should be considered when selecting therapy for upper urothelial carcinoma.

  15. 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.

  16. Urothelial mucosal signaling and the overactive bladder-ICI-RS 2013.

    Science.gov (United States)

    Birder, Lori A; Andersson, Karl-Erik; Kanai, Anthony J; Hanna-Mitchell, Ann T; Fry, Chris H

    2014-06-01

    There is abundant evidence that the lower urinary tract (LUT) mucosal layer is involved both in mechanosensory functions that regulate bladder contractile activity and in urethral sensation. Changes to the mucosa can be associated with a number of bladder pathologies. For example, alterations of the urothelium and underlying lamina propria at both the molecular and structural levels have been reported in both patients and animals associated with disorders such as bladder pain syndrome and diabetic cystopathy. In contrast to the urinary bladder, much less is known about the urothelium/lamina propria of the bladder neck/proximal urethra. There are important gender differences in the outflow region both anatomically and with respect to innervation, hormonal sensitivity, and location of the external urethral sphincter. There is reasonable evidence to support the view that the mucosal signaling pathway in the proximal urethra is important for normal voiding, but it has also been speculated that the proximal urethra can initiate bladder overactivity. When dysfunctional, the proximal urethra may be an interesting target, for example, botulinum toxin injections aiming at eliminating both urgency and incontinence due to detrusor overactivity. © 2014 Wiley Periodicals, Inc.

  17. Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

    International Nuclear Information System (INIS)

    Rogler, Anja; Lehmann, Jan; Petsch, Sabrina; Hartmann, Arndt; Stoehr, Robert; Hoja, Sabine; Giedl, Johannes; Ekici, Arif B; Wach, Sven; Taubert, Helge; Goebell, Peter J; Wullich, Bernd; Stöckle, Michael

    2014-01-01

    Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be

  18. Isolated Meningeal Recurrence of Transitional Cell Carcinoma of the Bladder

    Directory of Open Access Journals (Sweden)

    Catherine Butchart

    2010-06-01

    Full Text Available Meningeal carcinomatosis occurs in 1–18% of patients with solid tumours, most commonly carcinomas of the breast and lung or melanomas. There are relatively few reports of meningeal carcinomatosis in transitional cell carcinoma of the bladder. Isolated meningeal recurrence is particularly uncommon, and we present an unusual case of this in a 58-year-old man. The case was further complicated by the somewhat atypical presentation with a confirmed ischaemic stroke. The patient died one month after presentation.

  19. Molecular markers in transitional cell carcinoma of the bladder: New insights into mechanisms and prognosis

    Directory of Open Access Journals (Sweden)

    Behfar Ehdaie

    2008-01-01

    Full Text Available Urothelial carcinoma is potentially life-threatening and expensive to treat since for many patients, the diagnosis entails a lifetime of surveillance to detect recurrent disease. Advancements in technology have provided an understanding of the molecular mechanisms of carcinogenesis and defined distinct pathways in tumorigenesis and progression. At the molecular level, urothelial carcinoma is being seen as a disease with distinct pathways of carcinogenesis and progression and thus markers of these processes should be used as both diagnostics and predictors of progression and patient outcome. Herein we present a selective overview of the molecular underpinning of urothelial carcinogenesis and progression and discuss the potential for proteins involved in these processes to serve as biomarkers. The discovery of biomarkers has enabled the elucidation of targets for novel therapeutic agents to disrupt the deregulation underlying the development and progression of urothelial carcinogenesis.

  20. Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer

    Directory of Open Access Journals (Sweden)

    Wojciech Krajewski

    2014-03-01

    Full Text Available Bladder cancer (BCA is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines – IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

  1. Transitional cell carcinoma developing in a bladder diverticulum ...

    African Journals Online (AJOL)

    Computed tomography confirmed a left-sided narrow neck urinary bladder diverticulum, with wall thickening, in a 56-year-old man. These findings were initially detected on ultrasonographic investigation. Transitional cell carcinoma was confirmed histologically. There is an increased incidence of neoplastic transformation in ...

  2. Management of transitional cell carcinoma of the urinary bladder at ...

    African Journals Online (AJOL)

    Management of transitional cell carcinoma of the urinary bladder at Kenyatta National Hospital, Nairobi. C G Waihenya, P N Mungai. Abstract. No Abstract. East African Medical Journal Vol. 83 (12) 2006: pp. 679-683. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  3. Carcinoma of Urinary Bladder in a Region of Low Schistosomiasis ...

    African Journals Online (AJOL)

    Aim: To study the geographical pathology of carcinoma of the urinary bladder as regards both its association with endemic schistosomiasis and the variable proportions of its histological types. Methods: A 30-year retrospective analysis was carried out with regard to Igbo patients who inhabit a region of low incidence of ...

  4. Predictive models and prognostic factors for upper tract urothelial carcinoma: a comprehensive review of the literature.

    Science.gov (United States)

    Mbeutcha, Aurélie; Mathieu, Romain; Rouprêt, Morgan; Gust, Kilian M; Briganti, Alberto; Karakiewicz, Pierre I; Shariat, Shahrokh F

    2016-10-01

    In the context of customized patient care for upper tract urothelial carcinoma (UTUC), decision-making could be facilitated by risk assessment and prediction tools. The aim of this study was to provide a critical overview of existing predictive models and to review emerging promising prognostic factors for UTUC. A literature search of articles published in English from January 2000 to June 2016 was performed using PubMed. Studies on risk group stratification models and predictive tools in UTUC were selected, together with studies on predictive factors and biomarkers associated with advanced-stage UTUC and oncological outcomes after surgery. Various predictive tools have been described for advanced-stage UTUC assessment, disease recurrence and cancer-specific survival (CSS). Most of these models are based on well-established prognostic factors such as tumor stage, grade and lymph node (LN) metastasis, but some also integrate newly described prognostic factors and biomarkers. These new prediction tools seem to reach a high level of accuracy, but they lack external validation and decision-making analysis. The combinations of patient-, pathology- and surgery-related factors together with novel biomarkers have led to promising predictive tools for oncological outcomes in UTUC. However, external validation of these predictive models is a prerequisite before their introduction into daily practice. New models predicting response to therapy are urgently needed to allow accurate and safe individualized management in this heterogeneous disease.

  5. Regional differences in practice patterns and associated outcomes for upper tract urothelial carcinoma in Canada.

    Science.gov (United States)

    Metcalfe, Michael; Kassouf, Wassim; Rendon, Ricardo; Bell, David; Izawa, Jonathan; Chin, Joseph; Kapoor, Anil; Matsumoto, Edward; Lattouf, Jean-Baptiste; Saad, Fred; Lacombe, Louis; Fradet, Yves; Fairey, Adrian; Jacobson, Niels-Eric; Drachenberg, Darryl; Cagiannos, Ilias; So, Alan; Black, Peter

    2012-12-01

    : We delineated Canadian regional differences in practice patterns in the management of upper tract urothelial carcinoma (UTUC) after nephroureterectomy and relate these to patient outcomes. : A database was created with 1029 patients undergoing radical nephroureterectomy for UTUC between 1994 and 2009 at 10 Canadian centres. Demographic, clinical and pathological variables were collected from chart review. Practice pattern variables were defined as: open versus laparoscopic nephroureterectomy, management strategy for the distal ureter, performance of lymphadenectomy and administration of chemotherapy and/or radiation therapy. The outcome measures were overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). The centres were divided into three regions (West, Central, East). Cox proportional multivariable linear regression analysis was used to determine the association between regional differences in practice patterns and clinical outcomes. : There was a significant difference in practice patterns between regions within Canada for: time from diagnosis to surgery (p = 0.001), type of surgery (open vs. laparoscopic, p analysis demonstrated that the differences in survival were independent of region OS (p = 0.78), DSS (p = 0.30) or RFS (p = 0.43). : There is significant disparity in practice patterns between regions within Canada, but these do not appear to have an effect on survival. We believe that the variability in practice is a reflection of the lack of standardized treatments for UTUC and underlines the need for multi-institutional studies in this disease.

  6. Utilization and Outcomes of Nephroureterectomy for Upper Tract Urothelial Carcinoma by Surgical Approach.

    Science.gov (United States)

    Rodriguez, Joseph F; Packiam, Vignesh T; Boysen, William R; Johnson, Scott C; Smith, Zachary L; Smith, Norm D; Shalhav, Arieh L; Steinberg, Gary D

    2017-07-01

    To compare outcomes and survival of open-, robotic-, and laparoscopic nephroureterectomy (ONU, RNU, LNU) using population-based data. Using the National Cancer Database, we identified patients who underwent nephroureterectomy for localized upper tract urothelial carcinoma between 2010 and 2013. Demographic and clinicopathologic characteristics were compared among the three operative approaches. Multivariate regression analyses were used to determine the impact of approach on performance of lymphadenectomy (LND), positive surgical margins (PSM), and overall survival (OS). In total, there were 9401 cases identified for analysis, including 3199 ONU (34%), 2098 RNU (22%), and 4104 LNU (44%). From 2010 to 2013, utilization of RNU increased from 14% to 30%. On multivariate analysis, LND was more likely in RNU (odds ratio [OR] 1.52; p ONU. RNU was associated with decreased PSM compared with ONU (OR = 0.73; p = 0.04). After adjusting for other factors, OS was not significantly associated with surgical approach. RNU utilization doubled over the study period. While RNU was associated with greater likelihood of LND performance as well as lower PSM rates when compared with ONU and LNU, surgical approach did not independently affect OS.

  7. Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Lim, Ju Hyun; Jeong, In Gab; Park, Jong Yeon; You, Dalsan; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

    2015-07-01

    The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.

  8. Mutational profiles of Brenner tumors show distinctive features uncoupling urothelial carcinomas and ovarian carcinoma with transitional cell histology.

    Science.gov (United States)

    Pfarr, Nicole; Darb-Esfahani, Silvia; Leichsenring, Jonas; Taube, Eliane; Boxberg, Melanie; Braicu, Ioana; Jesinghaus, Moritz; Penzel, Roland; Endris, Volker; Noske, Aurelia; Weichert, Wilko; Schirmacher, Peter; Denkert, Carsten; Stenzinger, Albrecht

    2017-10-01

    Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in-situ hybridization (FISH) and quantitative PCR-based copy number assays. Additionally, we analyzed the TERT promotor region by conventional Sanger sequencing. We identified 25 different point mutations in 23 of the analyzed genes in BTs and 10 mutations in 8 genes in TCCs. About 57% percent of mutations occurred in genes involved in cell cycle control, DNA repair, and epigenetic regulation processes. All TCC cases harbored TP53 mutations whereas all BTs were negative and none of the mutations observed in BTs were present in TCCs. CNV analysis revealed recurrent MDM2 amplifications in 3 out of 4 of the malignant BT cases with one case harboring a concomitant amplification of CCND1. No mutations were observed in the TERT promoter region in BTs and TCCs, which is mutated in about 50%-75% of urothelial carcinoma and in 16% of ovarian clear-cell carcinomas. In conclusion, our study highlights distinct genetic features of BTs, and detection of the triplet phenotype MDM2 amplification/TP53 wt/TERT wt may aid diagnosis of malignant BT in difficult cases. Moreover, selected genetic lesions may be clinically exploitable in a metastatic setting. © 2017 Wiley Periodicals, Inc.

  9. Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer

    International Nuclear Information System (INIS)

    Kumari, N.; Saxena, S.; Agrawal, U.

    2015-01-01

    Background: Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients. Objective: The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy. Methods: The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n = 248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ ontoexpress). Results: Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2. Conclusions: The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin - an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis

  10. Aggressive bladder carcinoma in an HIV-positive man with tetraplegia and neurogenic bladder.

    Science.gov (United States)

    Benabdallah, Justin O; Collins, Clinton W; Carucci, Laura R; Moores, Kenneth E; Gater, David R; Klausner, Adam P

    2011-01-01

    Patients with neurogenic bladder secondary to spinal cord injury who are managed long term with an indwelling catheter are known to be at increased risk for transitional cell carcinoma of the bladder. Immunosuppression is a known risk factor for malignancies that often are more aggresSive than those seen in normal populations. Case report and discussion of management recommendations. We summarize the case of a 44-year-old HIV-positive C5-C6 incomplete tetraplegic male (date of injury 1980), who was diagnosed with transitional cell carcinoma of the bladder and succumbed to disease within 6 months of diagnosis. The patient was a non-smoker who was never managed with an indwelling catheter. There has been no such case reported in the literature. HIV infection in the presence of a neurogenic bladder may carry an increased risk of aggressive bladder malignancy. More studies are warranted to determine whether routine annual screening with cystoscopy in all patients with HIV and neurogenic bladder is indicated.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Predictive and Prognostic Value of Preoperative Thrombocytosis in Upper Tract Urothelial Carcinoma.

    Science.gov (United States)

    Foerster, Beat; Moschini, Marco; Abufaraj, Mohammad; Soria, Francesco; Gust, Kilian M; Rouprêt, Morgan; Karakiewicz, Pierre I; Briganti, Alberto; Rink, Michael; Kluth, Luis; Mathieu, Romain; Margulis, Vitaly; Lotan, Yair; Aziz, Atiqullah; John, Hubert; Shariat, Shahrokh F

    2017-12-01

    The purpose of this study was to evaluate the predictive and prognostic role of preoperative thrombocytosis (TC) in upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) in a large multi-institutional cohort of patients. Records of 2492 patients undergoing RNU for non-metastatic UTUC between 1990 and 2008 were retrospectively analyzed. Preoperative TC was defined as a platelet count > 400 × 10 9 /L, irrespective of gender type. Logistic regression analyses were performed to evaluate its association with pathologic features. Cox proportional hazards regression was used for estimation of recurrence-free survival, cancer-specific survival, and overall survival. Preoperative TC was found in 309 (12.4%) patients and was associated with advanced tumor stage and grade, lymph node metastasis, lymphovascular invasion, tumor architecture, necrosis, and concomitant carcinoma in situ (P-values ≤ .027). Preoperative TC independently predicted ≥ pT2 (P preoperative model that adjusted for the effects of age, gender, location, multifocality, and tumor architecture. Within a median follow-up of 45 months, recurrence occurred in 663 (26.6%) patients with 545 (21.9%) dying of UTUC. In univariable Cox proportional hazard regression analysis, TC was significantly associated with recurrence-free survival (hazard ratio [HR], 1.32; P = .015) and overall survival (HR, 1.4; P Preoperative TC is associated with adverse clinicopathologic features and predicts worse pathology at RNU. Among other serum biomarkers, TC could benefit preoperative risk stratification and help guide treatment decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Incidental Gynecologic Tract Neoplasms in Women Undergoing Anterior Pelvic Exenteration for Urothelial Carcinoma.

    Science.gov (United States)

    Tran, Lily; Antic, Tatjana; Lastra, Ricardo R

    2017-12-18

    Urothelial carcinoma (UC) invasive into the muscularis propria or tumors unresponsive to treatment are indications for cystectomy. In females, with the goal of achieving complete cancer eradication and for concerns of UC extension into the adjacent pelvic organs, this may also warrant resection of the gynecologic organs. This study is aimed to assess the prevalence of unanticipated gynecologic neoplasms in anterior pelvic exenteration specimens. A retrospective review of pathology reports to identify women undergoing anterior pelvic exenteration for UC was performed (N=221), and incidentally discovered gynecologic tract neoplasms were recorded. Concomitant malignant or premalignant lesions of the gynecologic tract were identified in 8 patients (3.6%). These included endometrial adenocarcinoma [endometrioid type, International Federation of Gynecology and Obstetrics grade 1 (n=2, 0.9%)], cervical high-grade squamous intraepithelial lesion (n=2, 0.9%), Sertoli-Leydig cell tumor of intermediate differentiation (n=1, 0.5%), endometrioid adenocarcinoma of the ovary (n=1, 0.5%), and high-grade serous carcinoma of the ovary (n=1, 0.5%) and fallopian tube (n=1, 0.5%). Benign uterine neoplasms included leiomyomas (n=81, 37%), adenomyoma (n=3, 1.4%), and adenomatoid tumors (n=2, 0.9%). Benign ovarian neoplasms included serous cystadenoma (n=7, 3%), serous cystadenofibroma (n=4, 2%), benign Brenner tumor (n=5, 2.3%), mature teratoma (n=4, 2%), stromal luteoma (n=2, 0.9%), mucinous cystadenoma (n=1, 0.5%), thecoma (n=1, 0.5%), and endometrioid cystadenoma (n=1, 0.5%). Involvement of the gynecologic tract by UC was identified in 11 patients (5%). Spread of UC to the reproductive organs is rare in anterior pelvic exenteration specimens. Coexisting neoplasms of the gynecologic tract are occasionally identified, therefore careful evaluation of these organs is necessary.

  14. 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

  15. Diagnosis and kidney-sparing treatments for upper tract urothelial carcinoma: state of the art.

    Science.gov (United States)

    Territo, Angelo; Foerster, Bear; Shariat, Shahrokh F; Rouprêt, Morgan; Gaya, Jose M; Palou, Joan; Breda, Alberto

    2018-02-01

    Conservative management of upper tract urothelial cancer (UTUC) is becoming increasingly popular: the key to success is correct selection of patients with low-risk UTUC based on size (≤ 2 cm), focality (single lesion), stage (state of the art" in the diagnosis and conservative treatment of UTUC, a systematic review of the literature was performed. A PubMed, Scopus, and Cochrane search for peer-reviewed studies was performed using the keywords "upper tract urothelial carcinoma" OR "UTUC" OR "upper urinary tract" AND "biopsy" OR "diagnosis" OR "endomicroscopy" OR "imaging" AND "URS" OR "ureteroscopy" OR "kidney-sparing surgery" OR "laser ablation" OR "ureterectomy". We considered as relevant comparative prospective studies (randomized, quasi-randomized, no randomized), retrospective studies, meta-analyses, systematic reviews, and case report series written in the English language. Letters to the editor and contributions written in languages other than English were not considered of value for this review. Eligible articles were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Two hundred and sixty-three (263) records were identified using the above-mentioned keywords. Overall, 30 studies were considered relevant for the purpose of this systematic review and for the evidence evaluation process during qualitative synthesis. The outcomes evaluated in this review were the current diagnostic methods and the KSS approaches in UTUC. Furthermore, we included in the review the emerging technology for distinguishing between normal tissue, low-grade UTUC, and high-grade UTUC. Conclusive diagnosis is fundamental to the decision-making process in patients who could benefit from conservative treatment of UTUC. The most relevant diagnostic modalities are computed tomography urography, local urine cytology, and ureteroscopy with acquisition of an adequate biopsy sample for histology. KSS includes the endourological

  16. FLUORESCENCE DIAGNOSIS FOR RECURRENT BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    R. V. Ulyanov

    2017-01-01

    Full Text Available The clinical case of successful use of local fluorescence spectroscopy combined with fluorescence imaging during cystoscopy for diagnosis of recurrent bladder cancer is represented in the article. Histological study of fluorescent foci confirmed tumor growth (urothelial carcinoma in all areas with high levels of diagnostic parameter. In the fluorescent focus with low diagnostic parameter inflammation was detected.

  17. Computed tomography in staging of bladder carcinoma (Prospective study)

    International Nuclear Information System (INIS)

    Lee, Kyung Soo; Choi, Byung Ihn; Han, Man Chung

    1985-01-01

    Staging of carcinoma of the urinary bladder is important for the choice of therapy and also has prognostic implications. Hitherto the staging has been based upon cystoscopy with biopsy, transurethral resection, and palpation with complementary radiographic examinations such as cystography, urography, lymphangiography, ultrasound and angiography. However, with all these methods, the staging of bladder carcinomas still uncertain and inferior to CT. Authors analyzed CT staging of bladder cancers and compared with pathologic staging of laparotomy results. The results are as following: 1. Overall accuracy of CT staging in bladder carcinoma was 72 percent. 2. Overstaging was 20 percent (5/25) and understaging was 8 percent (2/25). 3. All of CT stage B cancers were proven to be stage B, pathologically. 4. In 6 cases of CT static cancers, only one was correct, 3 were overstaged and 2 were understaged. 5. In 7 cases of CT stage D cancers, 5 were correct and 2 were overstaged. 6. CT detected only 2 cases of pelvic lymph node involvement in 4 of pathologically proven lymphadenopathy

  18. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model.

    Science.gov (United States)

    Alexiev, Borislav A; Randhawa, Parmjeet; Vazquez Martul, Eduardo; Zeng, Gang; Luo, Chunqing; Ramos, Emilio; Drachenberg, Cinthia B; Papadimitriou, John C

    2013-05-01

    Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for "rare" carcinogenic events. The BK polyomavirus-induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus-related urothelial malignancies in transplant recipients. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. 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".

  20. Forkhead box protein P3 (Foxp3) expression serves as an early chronic inflammation marker of squamous cell differentiation and aggressive pathology of urothelial carcinomas in neurological patients.

    Science.gov (United States)

    Phé, Véronique; Rouprêt, Morgan; Cussenot, Olivier; Chartier-Kastler, Emmanuel; Gamé, Xavier; Compérat, Eva

    2015-04-01

    To establish whether the expression of forkhead box protein P3 (Foxp3) provides specific diagnostic information about neurological patients with urothelial carcinoma of the bladder (UCB). UCB tissue samples from neurological patients were retrieved and compared with control samples. The expression of Foxp3 was analysed via immunohistochemistry of microarray tissue sections. The correlation between Foxp3 expression, histological parameters and tumour stage was assessed. Overall, 20 UCB tissue samples and 20 others without UCB from neurological patients, and 46 UCB tissue samples from non-neurological patients were analysed. The distribution of pT of UCB in the neurological patients was as follows: one low-grade pTa (5%), three high-grade pTa (15%), three pT1(15%), one pT2(5%), seven pT3(35%) and five pT4(25%). Squamous cell differentiation was seen in nine UCB samples (45%). Foxp3 expression was detected in tumour tissues, including one pTa high grade, one pT1, one pT2, five pT3 and five pT4 tumours. Foxp3 was expressed in 11/13 muscle-invasive tumours. All tumours displaying squamous cell differentiation expressed Foxp3. Foxp3 was not expressed in the pT3 tumours that displayed sarcomatoid and micropapillary properties. Among the bladder samples without UCB from neurological patients, no expression of Foxp3 was observed. Among the UCB samples from the non-neurological patients, only seven displayed squamous cell differentiation. All tumours that displayed squamous cell differentiation expressed Foxp3, including one pTa high grade, four pT3 and two pT4 tumours. Other tumours displaying urothelial differentiation did not express Foxp3. The expression of Foxp3 correlated to squamous cell differentiation in neurological (P = 0.004) and non-neurological UCB tissue (P differentiation. Targeting Foxp3 may represent a novel strategy to improve anti-tumour immunotherapy for UCB. © 2015 The Authors. BJU International © 2015 BJU International.

  1. Tolerability of Repeat Use of Blue Light Cystoscopy with Hexaminolevulinate for Patients with Urothelial Cell Carcinoma.

    Science.gov (United States)

    Lane, Giulia I; Downs, Tracy M; Soubra, Ayman; Rao, Amrita; Hemsley, Lauren; Laylan, Christopher; Shi, Fangfang; Konety, Badrinath

    2017-03-01

    Hexaminolevulinate hydrochloride with blue light cystoscopy is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy for the detection of urothelial cell carcinoma. In this study we examined the tolerability of the repeat use of white light cystoscopy with blue light cystoscopy. We retrospectively reviewed the records of all patients who underwent white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride during a 34-month period at 2 institutions. We compared the incidence of adverse events after initial and subsequent procedures. We grouped, graded and assigned the degree of attribution for all adverse events. A total of 180 patients underwent 269 white light cystoscopy with blue light cystoscopy procedures. Of those 180 patients 118 (65%) underwent white light cystoscopy with blue light cystoscopy only 1 time. The other 62 (35%) patients underwent white light cystoscopy with blue light cystoscopy 2 or more times, including 43 (24%) 2 times and 19 (10%) 3 or more times. We noted 89 adverse events out of 269 procedures (33%), of which 66 (74%) occurred after the first white light cystoscopy with blue light cystoscopy; 14 (16%) after the second time and 9 (10%) after the third time or more. We found no statistically significant difference in adverse events between those patients undergoing 1 vs 2 or more white light cystoscopy with blue light cystoscopy procedures (p=0.134). We observed 1 grade 3 adverse event and no grade 4 or 5 adverse events. None of the adverse events were classified as probably or definitely related to hexaminolevulinate hydrochloride. In this retrospective study we found no statistically significant difference in the frequency or the grade of adverse events between first and repeat use of white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier

  2. Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu-Li Su

    Full Text Available We developed a novel inflammation-based model (NPS, which consisted of a neutrophil to lymphocyte ratio (NLR and platelet count (PC, for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC.We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS.In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001 or PC (P < .0001. The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001. Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002.The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

  3. Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

    International Nuclear Information System (INIS)

    Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.; Su, C.-T.; Huang, Y.-K.; Chen, Y.-T.; Hsueh, Y.-M.

    2008-01-01

    Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 ± 2.98 μg/g creatinine, for UC patients than for healthy controls of 21.10 ± 0.79 μg/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 ± 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 ± 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 ± 0.75 than those of males at 5.76 ± 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic

  4. Imaging of urinary bladder tumors

    International Nuclear Information System (INIS)

    Hadjidekov, G.

    2015-01-01

    Full text: Primary bladder neoplasms account for 2%-6% of all tumors, with urinary bladder cancer ranked as the fourth most common cancer in males. Transitional cell carcinoma (TCC) is the most common subtype of urothelial tumour accounting for approximately 90% of all urothelial cancers. It is typically observed in men aged 50-70 years with history of smoking or occupational exposure to carcinogens. Most urothelial neoplasms are low-grade papillary tumors, with high incidence of recurrence, requires rigorous follow-up but have a relatively good prognosis. Other bladder neoplasm include squamous cell carcinoma accounts for 2%-15% mainly according to geographic location; adenocarcinoma - less than 2% /both occurring in the context of chronic bladder infection and irritation/; mesenchymal tumors in 5%, with the most common examples being rhabdomyosarcoma in children and leiomyosarcoma in adults. More rare mesenchymal tumors include paraganglioma, lymphoma, leiomyoma and solitary fibrous tumor which have no specific typical imaging findings to be differentiated. Multidetector computed tomography urography is an efficient tool for diagnosis and follow-up in patients with transitional cell carcinoma and it can be considered the primary radiologic method for detection, staging and assessment of the entire urothelium regarding the multicentric nature of TCC. MRI is rapidly expanding modality of choice especially in locally staging the tumor and in controversies. Accurate TNM staging is primordial in choosing treatment and prognosis for patients with bladder carcinoma. Correct interpretation and classification of the tumour is helpful for the urologists to determine further management in these cases. The learning objectives of the presentation are: to illustrate the spectrum of CT and MRI findings and to assess their clinical value in patients with transitional cell carcinoma and some other bladder neoplasm; to discuss the TNM staging based on the imaging findings; to be

  5. PDT-induced apoptosis in bladder carcinoma cells

    Science.gov (United States)

    Bachor, Ruediger; Reich, Ella D.; Kleinschmidt, Klaus; Repassy, Denes; Hautmann, Richard E.

    1999-02-01

    Photodynamic therapy (PDT) is a highly efficient inducer of apoptosis in EY-28 bladder carcinoma cells, resulting in extensive DNA fragmentation. Bladder carcinoma cells EY-28 (Tumorbank Heidelberg, Germany) were incubated for 1 h with 1 (mu) g AamTPPn/ml or 2 (mu) g AamTPPn/ml. After incubation cells were refed with complete medium and irradiated with 0.75 J/cm2. To identify apoptotic cells, a in situ cell death detection kit POD (Boehringer Mannheim, Germany) was used. The chromatin condensation characteristic to apoptotic cells was detected by transmission electron microscopy. Using 1 (mu) g AamTPPn/ml and 2 (mu) g AamTPPn/ml (9-Acetamido-2,7,12,17- tetra-n-Porpylporphycene), respectively, and irradiation at 0.75 J/cm2, a percentage of 36.9% and 54.7%, respectively, of apoptotic cells was detected.

  6. Laparoscopic versus open nephroureterectomy to treat localized and/or locally advanced upper tract urothelial carcinoma: oncological outcomes from a multicenter study.

    Science.gov (United States)

    Liu, Jian-Ye; Dai, Ying-Bo; Zhou, Fang-Jian; Long, Zhi; Li, Yong-Hong; Xie, Dan; Liu, Bin; Tang, Jin; Tan, Jing; Yao, Kun; He, Le-Ye

    2017-01-17

    Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T 1-4 /N 0-X ). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T 1-4 /N 0-X UTUC. We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T 1-4 /N 0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for univariate and multivariate analysis. The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46-3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54-1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616-3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81-3.17, P = 0.17). The results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the laparoscopy and the open groups. Thus, LNU can be an alternative to the open procedure for T 1-4 /N 0-X UTUC. Further studies, including a multi-institutional, prospective study are required to confirm these findings.

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

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    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.

  8. [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

    Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

  9. Bladder hemorrhage after radiotherapy for carcinoma of the cervix uteri

    International Nuclear Information System (INIS)

    Matsuyama, Toshitake; Tsukamoto, Naoki; Sugimori, Hajime; Yoshino, Teruo; Kashiwamura, Masamichi.

    1979-01-01

    The relationship among the incidence, the time of occurrence, and radiation dose was studied in regard to hemorrhagic cystitis after radiotherapy for carcinoma of the cervix uteri. Of 1004 patients with carcinoma of the cervix uteri observed between 1961 and 1974, 28 (2.8%) had bladder hemorrhage seemingly due to radiation injury (0.7% were serious). Incidences varied every year. The radiation dose was increased from 4000 to 6000 rad after 1971. In addition to this external dose, because the depth-dose has also increased, the rate of bladder hemorrhage has become high. Seven patients with serious bladder hemorrhage were exposed to more than 5000 rad of 60 Co. Bladder hemorrhage occurred comparatively frequently in patients in whom two hila were irradiated. It usually occurred a few years after irradiation (about 1 year after initial rectal hemorrhage). It continued for approximately 1 year in 21 patients, for approximately 3 years in 4 patients, and for approximately 4 years in 3 patients. Adrenochrome (a hemostatic agent) and antiplasmin were used as therapeutic agents. Serious patients improved remarkably when a large amount of diluted formaline solution or conjugated estrogen was administered intravenously. (Namekawa, K.)

  10. Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

    Science.gov (United States)

    Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

    2017-07-27

    The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

  11. The merits of cytology in the workup for upper tract urothelial carcinoma - a contemporary review of a perplexing issue

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    E.F. Sverrisson

    2014-08-01

    Full Text Available Introduction The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC at a single tertiary care referral center. Materials and Methods 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population. Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. Results 57% (68/119 had preoperative upper tract cytology collected. 73% (50/68 patients had abnormal cytology (positive, suspicious with a sensitivity of 74% (which increased to 90% if atypical included, specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade. Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. Conclusions Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients.

  12. Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal pelvis: identification in human tumors and confirmation in animal models.

    Science.gov (United States)

    Qian, Chao-Nan; Furge, Kyle A; Knol, Jared; Huang, Dan; Chen, Jindong; Dykema, Karl J; Kort, Eric J; Massie, Aaron; Khoo, Sok Kean; Vanden Beldt, Kristin; Resau, James H; Anema, John; Kahnoski, Richard J; Morreau, Hans; Camparo, Philippe; Comperat, Eva; Sibony, Mathilde; Denoux, Yves; Molinie, Vincent; Vieillefond, Annick; Eng, Charis; Williams, Bart O; Teh, Bin Tean

    2009-11-01

    Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.

  13. 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

  14. Nomogram-based Prediction of Overall Survival in Patients with Metastatic Urothelial Carcinoma Receiving First-line Platinum-based Chemotherapy

    DEFF Research Database (Denmark)

    Necchi, Andrea; Sonpavde, Guru; Lo Vullo, Salvatore

    2017-01-01

    BACKGROUND: The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of cisplatin-treated patients. OBJECTIVE: To develop a new model based on real-world patients. DESIGN, SETTING, AND PARTICI...

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

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    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.

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

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    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.

  17. Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.

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    Johanna Droop

    Full Text Available Many long noncoding RNAs (lncRNAs are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC, several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1 was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106. Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252, and correlation to overall survival (OS. All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could

  18. Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.

    Science.gov (United States)

    Droop, Johanna; Szarvas, Tibor; Schulz, Wolfgang A; Niedworok, Christian; Niegisch, Günter; Scheckenbach, Kathrin; Hoffmann, Michèle J

    2017-01-01

    Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to

  19. [Disseminated BCG infection in patients with urinary bladder carcinoma].

    Science.gov (United States)

    Korać, Milos; Milosević, Branko; Lavadinović, Lidija; Janjić, Aleksandar; Brmbolić, Branko

    2009-01-01

    Bacillus Calmette-Guërin--a live, attenuated strain of Mycobacterium bovis has been used in immunotherapy of patients with superficial urinary bladder carcinoma. Some patients develop complications after intravesical instillation of BCG: high temperature followed by hematuria or granulomatous prostatits, epidydimoorchitis, urethral obstruction, and less than 1% have a systemic disease followed by dissemination of bacteria into other organs. A 50-year-old man underwent transurethral resection of a bladder tumor. One month after the operation BCG intravesical installations were administered for three weeks. After the fourth installation, our patient developed high fever, fatigue, vomiting, dark urine, light stools, and jaundice. On admission he was jaundiced with a high fever, enlarged liver and spleen and laboratory findings which included high erythrocyte sedimentation rate, pancytopenia, elevated liver enzymes, especially alkaline phosphatase and aminotranspherases. The bone-marrow biopsy showed granulomatous inflamation suggesting mycobacterial spread in the bone marrow, liver and spleen and sepsis. The patient was initially treated with antituberculous therapy, but his state did not improve until corticosteroids were added to the antituberculous treatment regimen. Although dissemination of BCG is a rare complication of intravesical BCG treatment of the bladder carcinoma, it may result in prolonged fever and granulomatous inflamation of the liver, spleen, lungs, bone marrow and BCG sepsis. Antituberclous agents in combination with corticosteroids comprise the treatment of choice for disseminated BCG infection.

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

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    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.

  1. Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions

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    Shilpa Gupta

    2017-01-01

    Full Text Available Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC. Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1 inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.

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

    International Nuclear Information System (INIS)

    Liang, Peir-In; Shiue, Yow-Ling; Huang, Hsuan-Ying; Hsu, Han-Ping; Chen, Li-Tzon; Lin, Ching-Yih; Tai, Chein; Lin, Chun-Mao; Li, Chien-Feng; Li, Wei-Ming; Wang, Yu-Hui; Wu, Ting-Feng; Wu, Wen-Ren; Liao, Alex C; Shen, Kun-Hung; Wei, Yu-Ching; Hsing, Chung-Hsi

    2012-01-01

    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). 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. 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 < 0.0001), MeFS (p < 0.0001), and UBRFS (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). HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in

  3. 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.

  4. 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.

  5. iNOS EXPRESSION AND NO PRODUCTION CONTRIBUTE TO THE DIRECT EFFECTS OF BCG ON UROTHELIAL CARCINOMA CELL BIOLOGY

    Science.gov (United States)

    Shah, Gopitkumar; Zhang, Guangjian; Chen, Fanghong; Cao, YanLi; Kalyanaraman, Balaraman; See, William A.

    2018-01-01

    OBJECTIVES Evidence suggests that oxidative stress occurring as a consequence of inducible nitric oxide synthase/nitric oxide (iNOS/NO) contributes to the biologic effects of Bacille Calmette Guérin (BCG). Objective of the current study is to examine iNOS expression, NO production and the biologic impact of NO, on established intermediate end points for the human urothelial carcinoma cell response to BCG. MATERIALS AND METHODS Quantitative rt-PCR and real time measurement of NO was used to assess iNOS and NO production respectively, in two human urothelial carcinoma (UC) cell lines, in response to BCG. The effect of blocking NO production using the specific iNOS inhibitor 1400W was determined for multiple intermediate end points characterizing BCGs direct effects on tumor cell biology. Activation of NF-κB and NRF2 signaling pathways, transactivation of genes including p21, CD54, IL6, IL8, CXCL1, CXCL3, CCL20 and cytotoxicity as measured by vital dye exclusion, lactate dehydrogenase (LDH) release and MTT assay were measured in response to BCG with and without iNOS inhibition. RESULTS Exposure of UC cells to BCG significantly increased both iNOS expression and NO production. Inhibition of iNOS activity with 1400W significantly inhibited BCG’s direct biologic effect on UC cells for all of the end points evaluated. CONCLUSIONS iNOS expression, NO production and the associated oxidative stress play a central role in the response of UC cells to BCG exposure. Manipulation of oxidative stress may afford an opportunity to enhance the antitumor effects of BCG. PMID:24054867

  6. Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma

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    Gilhyang Kim

    2016-11-01

    Full Text Available Background Human epidermal growth factor receptor 2 (HER2 is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP criteria and compare their prognostic significance in UUTUC. Methods HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+ and high (2+, 3+ groups. Results Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001. The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004, but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161 in cancer-specific survival. Conclusions HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

  7. Long-term comparative outcomes of open versus laparoscopic nephroureterectomy for upper urinary tract urothelial-cell carcinoma after a median follow-up of 13 years*.

    Science.gov (United States)

    Stewart, Grant D; Humphries, Katie J; Cutress, Mark L; Riddick, Antony C P; McNeill, S Alan; Tolley, David A

    2011-08-01

    Open nephroureterectomy (ONU) rather than laparoscopic nephroureterectomy (LNU) is still regarded as the standard of care for extirpative surgical management of upper urinary tract urothelial-cell carcinoma (UUT-UCC). The longest published follow-up of LNU is 7 years. We report outcomes for patients having surgery ≥10 years ago. Consecutive patients with UUT-UCC who were treated with ONU (n=39) or LNU (n=23) between April 1992 to September 2000 were included. Preoperative, tumor, operative and postoperative characteristics, recurrence, and outcomes were collated. Survival was estimated using the Kaplan-Meier method. Median follow-up of censored patients was 163 months (13.6 y). Estimated mean overall survival (OS) was 111 months for ONU and 103 months for LNU. Mean progression free survival (PFS) was 175 months for ONU and 143 months for LNU. Probability of PFS at 10 years was 79% for ONU and 76% for LNU and was unchanged at 15 years. There was no significant difference between ONU and LNU in terms of OS (P=0.51, log-rank test), PFS (P=0.70) or cancer-specific survival (CSS; P=0.43). There were no prognostic differences between ONU and LNU after correcting for confounding variables. There was no increase in the probability of a bladder cancer recurrence from 10 to 15 years postoperation. Long-term follow-up of patients who were operated on more than 10 years ago suggests that LNU has oncologic equivalence to ONU because there were no significant differences in OS, PFS, or CSS between ONU and LNU patients followed for a median of 13 years.

  8. Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association.

    Science.gov (United States)

    Miyazaki, Jun; Nishiyama, Hiroyuki; Fujimoto, Hiroyuki; Ohyama, Chikara; Koie, Takuya; Hinotsu, Shiro; Kikuchi, Eiji; Sakura, Mizuaki; Inokuchi, Junichi; Hara, Tomohiko

    2016-05-01

    Open nephroureterectomy (ONU) is the current standard for muscle-invasive upper tract urothelial carcinoma (UTUC) in the European Association of Urology/Japanese Urological Association (JUA) guidelines. In this study, we compared the postsurgical survival of muscle-invasive UTUC patients treated with ONU or with laparoscopic nephroureterectomy (LNU), using the multi-institutional national database of the JUA. The 1509 patients with UTUC who were diagnosed at 348 Japanese institutions in 2005 were registered. We collected the clinical data of the patients in 2011. The muscle-invasive UTUC patients who underwent ONU or LNU were identified, and survival curves were estimated using the Kaplan-Meier method. Overall, 749 pT2≥cNxM0 patients underwent a nephroureterectomy (ONU, n = 527 and LNU, n = 222). The overall survival and cause-specific survival rates were not significantly different between the ONU and LNU groups (p = 0.1263 and p = 0.0893, respectively). In addition, 459 of the 749 (61.3%) patients experienced disease recurrence (bladder recurrence, local recurrence, or distant metastasis), with no significant difference between the ONU and LNU groups. Even when patients were stratified by pT3/pT4 and/or pN+, overall survival was not significantly different between the ONU and LNU groups (p = 0.2876). The results of a univariate analysis showed that lymphovascular invasion was an independent prognostic factor for overall survival, but the surgical approaches were not found to be associated with overall survival. Our data suggest that there is no evidence that the oncologic outcome of LNU is inferior to that of ONU in muscle-invasive UTUC, when the appropriate patients are selected.

  9. The small conductance calcium-activated potassium channel 3 (SK3) is a molecular target for Edelfosine to reduce the invasive potential of urothelial carcinoma cells.

    Science.gov (United States)

    Steinestel, Konrad; Eder, Stefan; Ehinger, Konstantin; Schneider, Juliane; Genze, Felicitas; Winkler, Eva; Wardelmann, Eva; Schrader, Andres J; Steinestel, Julie

    2016-05-01

    Metastasis is the survival-determining factor in urothelial carcinoma (UC) of the urinary bladder. The small conductance calcium-activated potassium channel 3 (SK3) enhances tumor cell invasion in breast cancer and malignant melanoma. Since Edelfosine, a glycerophospholipid with antitumoral properties, effectively inhibits SK3 channel activity, our goal was to evaluate SK3 as a potential molecular target to inhibit the gain of an invasive phenotype in UC. SK3 protein expression was analyzed in 208 tissue samples and UC cell lines. Effects of Edelfosine on SK3 expression and intracellular calcium levels as well as on cell morphology, cell survival and proliferation were assessed using immunoblotting, potentiometric fluorescence microscopy, and clonogenic/cell survival assay; furthermore, we analyzed the effect of Edelfosine and SK3 RNAi knockdown on tumor cell migration and invasion in vitro and in vivo. We found that SK3 is strongly expressed in muscle-invasive UC and in the RT112 cellular tumor model. Higher concentrations of Edelfosine have a strong antitumoral effect on UC cells, while 1 μM effectively inhibits migration/invasion of UC cells in vitro and in vivo comparable to the SK3 knockdown phenotype. Taken together, our results show strong expression of SK3 in muscle-invasive UC, consistent with the postulated role of the protein in tumor cell invasion. Edelfosine is able to effectively inhibit migration and invasion of UC cells in vitro and in vivo in an SK3-dependent way, pointing towards a possible role for Edelfosine as an antiinvasive drug to effectively inhibit UC cell invasion and metastasis.

  10. Localized inhibition of P2X7R at the spinal cord injury site improves neurogenic bladder dysfunction by decreasing urothelial P2X3R expression in rats.

    Science.gov (United States)

    Munoz, Alvaro; Yazdi, Iman K; Tang, Xiufeng; Rivera, Carolina; Taghipour, Nima; Grossman, Robert G; Boone, Timothy B; Tasciotti, Ennio

    2017-02-15

    Reestablishment of bladder function in patients with spinal cord injury (SCI) is a clinical priority. Our objectives were to determine whether SCI-localized inhibition of purinergic P2X7 receptors (P2X7R) improve bladder function by decreasing afferent signals mediated by urothelial P2X3R. Systemic inhibition of P2X7R may improve locomotion in rodent SCI models; however, beneficial effects on bladder function and its physiological mechanisms have not been evaluated. We designed a thermosensitive nanohydrogel (NHG) consisting of the P2X7R antagonist brilliant blue-G (BBG) loaded into silica nanoparticles, embedded with poly(d,l-lactic-co-glycolic) acid, and resuspended in 20% pluronic acid. Female Sprague-Dawley rats with a bilateral dorsal lesion at the thoracic T8/T9 region received either 100μl of an empty NHG, or a NHG containing BBG (BBG-NHG) on top of the spinal tissue. Cystometric properties, spinal immunohistochemistry for P2X7R, and bladder immunohistochemistry for P2X3R were evaluated at four weeks post-SCI. After SCI animals recovered hind-legs use but neurogenic bladder dysfunction remained. SCI rats treated with BBG-NHG for a period of at least two weeks post-SCI experienced fewer non-voiding contractions. The localized inhibition of P2X7R decreased microglia activation. At the lower urinary tract level we observed, unexpectedly, a concomitant reduction of urothelial P2X3 receptors, which are involved in initiation of bladder afferent transmission to start micturition. Localized inhibition of P2X7R for two weeks can be associated with reduced number of microglia and attenuated bladder hyperexcitability mediated by downregulation of urothelial P2X3R in rats with neurogenic bladder dysfunction and independently of locomotor improvements. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma.

    Science.gov (United States)

    Kaye, M E; Thamm, D H; Weishaar, K; Lawrence, J A

    2015-12-01

    The goal of this study was to evaluate the anti-tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m(-2) IV) was administered intravenously along with concurrent oral anti-inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1-16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20-239 days). Median survival time for all dogs was 187 days; median survival for 13 pre-treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study. © 2013 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Neoadjuvant Chemotherapy for Patients with Muscle-invasive Urothelial Bladder Cancer Candidates for Curative Surgery: A Prospective Clinical Trial Based on Cisplatin Feasibility.

    Science.gov (United States)

    Schinzari, Giovanni; Monterisi, Santa; Pierconti, Francesco; Nazzicone, Giulia; Marandino, Laura; Orlandi, Armando; Racioppi, Marco; Cassano, Alessandra; Bassi, Pierfrancesco; Barone, Carlo; Rossi, Ernesto

    2017-11-01

    Neoadjuvant chemotherapy demonstrated a survival benefit versus cystectomy alone in muscle-invasive urothelial bladder cancer. Despite this advantage, preoperative chemotherapy is not widely employed. When patients are unfit for cisplatin-based regimen, they are often candidates for immediate surgery. In our study, patients with muscle-invasive bladder cancer were treated with neoadjuvant chemotherapy. The principal objective was the rate of complete pathological response (pCR). Secondary end-points were disease-free survival (DFS), overall survival (OS) and toxicity. Patients (n=72) with Eastern Cooperative Oncology Group (ECOG) performance status 0-1, clinical stage cT3-4, and/or N+ muscle-invasive bladder cancer were enrolled. The chemotherapy regimen was established according to the cisplatin feasibility. Thirty patients were treated with cisplatin/gemcitabine (Gem) and 42 with carboplatin/Gem. The rate of pCR was 29.2%, 36% with cisplatin-based treatment and 23.8% with carboplatin (p=0.3574). DFS and OS were longer in pCR patients, while no difference was reported between cisplatin/Gem and Carboplatin/Gem groups. Our results confirm the prognostic value of pCR in neoadjuvant chemotherapy for muscle-invasive bladder cancer. When the patients are not fit for cisplatin, a carboplatin/Gem regimen represents a valid option because of comparable long-term outcome. When cisplatin is not feasible, the exclusion of a preoperative treatment is not justified. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. A phase II monocentric study of oxaliplatin in combination with gemcitabine (GEMOX) in patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.

    Science.gov (United States)

    Theodore, C; Bidault, F; Bouvet-Forteau, N; Abdelatif, M; Fizazi, K; di Palma, M; Wibault, P; de Crevoisier, R; Laplanche, A

    2006-06-01

    The aim of the study was to evaluate the activity and the safety of the gemcitabine-oxaliplatin (GEMOX) combination as first-line treatment in advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract. Patients with metastatic or unresectable TCC, PS TCC with minimal toxicity and needs to be evaluated in a selected population of unfit patients and compared with other non-cisplatin-containing regimens.

  16. [Cardiorespiratory arrest due to acute pulmonary thromboembolism during chemotherapy for female urothelial carcinoma of urethra: a case report].

    Science.gov (United States)

    Nakazawa, Shigeaki; Uemura, Motohide; Matsuzaki, Kyosuke; Yoshida, Takahiro; Takao, Tetsuya; Tsujimura, Akira; Nonomura, Norio

    2013-05-01

    We report a case of deep vein thrombosis and acute pulmonary thromboembolism that occurred during chemotherapy for urethral carcinoma. A 68-year-old woman suffered from dysuria for a period of 2 years. When the symptoms worsened, a urethral catheter was placed and she was referred to our hospital for further examinations. Imaging analysis revealed a urethral tumor with multiple metastases. Pathological diagnosis on a specimen obtained from transurethral resection of the urethral mucosa was urothelial carcinoma and combined chemotherapy with gemcitabine and cisplatin was administered. On day 6 of the second course, the patient collapsed and was found to be in cardiorespiratory arrest. Cardiopulmonary resuscitation was successful and she received percutaneous cardiopulmonary support. Computed tomography at that time revealed a pulmonary embolism and deep vein thrombosis in the right popliteal vein. After her condition improved, an inferior vena cava filter was inserted to avoid further thromboembolism. The patient decided to continue the chemotherapy despite this episode. After the fourth course of combined chemotherapy, the urethral tumor and metastatic tumors were downsized, and she could urinate as she did before.

  17. Chronic thrombotic microangiopathy secondary to chemotherapy for urothelial carcinoma in a patient with a history of Wegener granulomatosis.

    Science.gov (United States)

    Thomas, Jacob G; Sethi, Sanjeev; Norby, Suzanne M

    2011-05-01

    We present the case of a 62-year-old man with a history of Wegener granulomatosis who developed chronic thrombotic microangiopathy attributed to gemcitabine chemotherapy. Wegener granulomatosis had been diagnosed 15 years earlier, and the patient was treated using cyclophosphamide and prednisone, then maintained on mycophenolate mofetil and prednisone. Four years previously, he had been treated with mitomycin C for urothelial carcinoma and at the time of presentation had developed significant anemia and thrombocytopenia after a course of gemcitabine and carboplatin due to metastasis of the carcinoma. He was managed using red blood cell and platelet transfusions but then developed acute kidney injury, along with progressive dyspnea and pulmonary infiltrates. Imaging studies showed bilateral ureteral obstruction requiring placement of nephrostomy tubes. Because of concern about a flare of Wegener granulomatosis after withdrawing maintenance immunosuppression in the context of the malignancy, a kidney biopsy was performed that showed chronic thrombotic microangiopathy, likely secondary to gemcitabine chemotherapy. Clinical, laboratory, and pathologic findings of this case are discussed to illustrate the natural history of thrombotic microangiopathy associated with gemcitabine chemotherapy. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  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. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

    2014-01-01

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  1. Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

    Science.gov (United States)

    Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

    2015-11-01

    Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Transitional cell carcinoma of the bladder in childhood: radiological findings and differential diagnosis

    International Nuclear Information System (INIS)

    Casado, L.; Mansilla, F.; Mansilla, M.D.; Marin, A.

    1998-01-01

    We present a case of transitional cell carcinoma of the bladder in an 11-year-old boy. The rarity of these tumors during childhood is pointed out. The radiological and ultrasonographic findings are described and the differential diagnosis is discussed with respect to other bladder tumors occurring in childhood. (Author) 11 refs

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

    Directory of Open Access Journals (Sweden)

    Jialou Zhu

    Full Text Available 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.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.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.

  4. Commentary on: "Clonal evolution of chemotherapy-resistant urothelial carcinoma." Faltas BM, Prandi D, Tagawa ST, Molina AM, Nanus DM, Sternberg C, Rosenberg J, Mosquera JM, Robinson B, Elemento O, Sboner A, Beltran H, Demichelis F, Rubin MA.: Nat Genet. 2016 Oct 17. http://dx.doi.org/10.1038/ng.3692.

    Science.gov (United States)

    Lee, Byron H

    2017-09-01

    Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights that are as follows: (1) chemotherapy-treated urothelial carcinoma is characterized by intrapatient mutational heterogeneity, and most mutations are not shared; (2) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (3) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell-adhesion molecule and integrin signaling pathways; and (4) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Modulation of intra-epithelial expansion of human T24 bladder-carcinoma cells in murine urothelium by growth factors and extracellular-matrix components

    NARCIS (Netherlands)

    J.M.J. Rebel (Annemarie); C.D.E.M. Thijssen (C. D E M); M. Vermey; E.C. Zwarthoff (Ellen); Th.H. van der Kwast (Theo)

    1995-01-01

    textabstractThe high recurrence rate of bladder cancer is probably due to an efficient repopulation of the bladder by residual transformed cells after resection of the tumour. However, the regenerating capacity of the normal urothelial cells is very high. To study the balance between regenerating

  6. Paclitaxel with Cisplatin as Salvage Treatment for Patients with Previously Treated Advanced Transitional Cell Carcinoma of the Urothelial Tract

    Directory of Open Access Journals (Sweden)

    Ji Eun Uhm

    2007-01-01

    Full Text Available BACKGROUND: This study was performed to evaluate the safety and efficacy of paclitaxel with cisplatin as salvage therapy in patients previously treated with gemcitabine and cisplatin (G/C for advanced transitional cell carcinoma (TCC of the urothelial tract. METHODS: Twenty-eight patients with metastatic or locally advanced TCC who had received prior G/C chemotherapy were enrolled. All patients received paclitaxel (175 mg/m2 and cisplatin (60 mg/m2 every 3 weeks for eight cycles or until disease progression. RESULTS: The median age was 61 years (range, 43–83 years, and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2. The overall response rate was 36% [95% confidence interval (95% CI = 18–54], with three complete responses and seven partial responses. The median time to progression was 6.2 months (95% CI = 3.9–8.5, and the median overall survival was 10.3 months (95% CI = 6.1–14.1. The most common Grade 3/4 nonhematologic and hematologic toxicities were emesis (10 of 28 patients; 36% and neutropenia (5 of 110 cycles; 5%. CONCLUSIONS: Salvage chemotherapy with paclitaxel and cisplatin displayed promising results with tolerable toxicity profiles in patients with metastatic or locally advanced TCC who had been pretreated with G/C.

  7. Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma.

    Science.gov (United States)

    Simhan, Jay; Smaldone, Marc C; Egleston, Brian L; Canter, Daniel; Sterious, Steven N; Corcoran, Anthony T; Ginzburg, Serge; Uzzo, Robert G; Kutikov, Alexander

    2014-08-01

    To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset. Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities. © 2013 The Authors. BJU International © 2013 BJU International.

  8. Nuclear, but not cytoplasmic, localization of survivin as a negative prognostic factor for survival in upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Kitamura, Hiroshi; Torigoe, Toshihiko; Hirohashi, Yoshihiko; Asanuma, Hiroko; Inoue, Ryuta; Nishida, Sachiyo; Tanaka, Toshiaki; Masumori, Naoya; Sato, Noriyuki; Tsukamoto, Taiji

    2013-01-01

    Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p nuclear expression of survivin vs. 73 % for those without nuclear expression of survivin (hazard ratio = 2.19; 95 % confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67 %, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.

  9. Genotyping of high-risk human papillomaviruses in p16/Ki-67-positive urothelial carcinoma cells: even a worm will turn.

    Science.gov (United States)

    Advenier, A-S; Casalegno, J-S; Mekki, Y; Decaussin-Petrucci, M; Mège-Lechevallier, F; Ruffion, A; Piaton, E

    2015-04-01

    Co-expression of p16INK4a protein and Ki-67 (p16/Ki-67) is noted in almost all high-grade urothelial lesions. However, the aetiological role or, conversely, the absence of causative effect of high-risk human papillomaviruses (hr-HPVs) has not been documented. The purpose of this study is to evaluate HPV DNA in p16/Ki-67-positive, high-grade urothelial tumour cells. Fifty-seven urine samples collected from 50 patients, including 55 histologically proven high-grade proliferations and two cases with clinical evidence of malignancy, were analysed for p16/Ki-67. Immunolabelling was performed in destained Papanicolaou-stained slides after ThinPrep(®) processing. HPV genotyping was performed by polymerase chain reaction (PCR) using a DNA microarray for 35 HPV types. Confirmation of the presence (or absence) of HPV in tissue samples was verified using a reasoned approach combining PCR and in situ hybridization (ISH) for hr-HPVs. Co-expression of p16/Ki-67 was noted in 43 of 57 (75.4%) cases. In these, hr-HPVs 16, 31 and 70, and low risk HPV 84, were detected in the urine in four patients (8%). Upregulation of p16INK4a protein was confirmed on bladder biopsy or transurethral resection specimens, but PCR and ISH for hr-HPVs were both negative on the tissue sections. Our results show a low prevalence of HPV infection in the urinary tract of patients with p16/Ki-67-positive urothelial malignancy. The study confirms that the deregulated cell cycle, as demonstrated by p16/Ki-67 dual labelling, is independent of the oncogenic action of hr-HPVs in high-grade urothelial proliferations. © 2014 John Wiley & Sons Ltd.

  10. Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies.

    Science.gov (United States)

    Ni, Shaobin; Tao, Weiyang; Chen, Qiyin; Liu, Lianxin; Jiang, Hongchi; Hu, Hailong; Han, Ruifa; Wang, Chunyang

    2012-06-01

    Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited. Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma. A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages. Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p>0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p>0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p>0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics. Our data suggest

  11. Response and toxicity of photodynamic therapy for canine bladder carcinoma

    International Nuclear Information System (INIS)

    Beck, E.R.; Dunstan, R.W.

    1992-01-01

    This investigation was to determine PDT efficacy and tolerance (both short term and long term) in dogs with spontaneously occurring transitional cell carcinoma of the urinary bladder. All patients were T2-T3, N x , M o . 27 dogs were given Photofrin II at 3.0 mg/kg IV, and 72 hours later doses of 632 nm light from 5-25 J/cm 2 . In 25/27 dogs, PDT resulted in complete remission of stranguria, hematuria and pollackiuria within one week of treatment. Gross hematuria increased in 7 dogs for the first 2 days following treatment, but then disappeared completely. Duration of clinical remission varied from 5-25 weeks after single treatment, within a median duration of 10 weeks. Doses of light from 5-10 J/cm 2 were well tolerated, with only mild toxicity for 1-3 days. Moderate toxicity showed in some dogs given 10-15 J/cm 2 . In all dogs given 25 J/cm 2 and 46% of those given 15 J/cm 2 , severe abdominal cramping, fecal incontinence, perforations and sepsis was seen. A second PDT treatment of 10-15 J/cm 2 following recurrence of clinical signs was administered to 9 dogs, without an increase in toxicity beyond that seen following the first treatment. Median duration of this second remission was 8 weeks, with a range of 5-12 weeks. 4-5 multiple PDT treatments were given to 4 dogs without any clinical symptoms of decreased bladder function. Each treatment produced an additional remission of variable length. (author). 14 refs., 1 fig., 1 tab

  12. A rare case of synchronous renal cell carcinoma of the bladder presenting with gross hematuria

    Directory of Open Access Journals (Sweden)

    Stephan Kruck

    2013-05-01

    Full Text Available A 57-year old man was referred to the Urology Department due to gross hematuria; abdominal ultrasound revealed an unspecific solid tumor of the left bladder wall. Ultrasound, transurethral resection of the bladder mass with subsequent histological analysis, thoracic and abdominal computed tomography-scan and brain magnetic resonance imaging were performed. He was diagnosed with a bladder metastasis of clear cell renal cell carcinoma (RCC with concomitant bone, pulmonary, and cerebral metastatic disease of a primary RCC of the right kidney. Management: Transurethral resection of the bladder mass, cerebral and bone radiotherapy, removal of the primary tumor, targeted systemic therapy with mTOR followed by tyrosine kinase inhibition.

  13. Lymph node dissection during laparoscopic (LRC) and open (ORC) radical cystectomy due to muscle invasive bladder urothelial cancer (pT2-3, TCC).

    Science.gov (United States)

    Chlosta, Piotr; Drewa, Tomasz; Siekiera, Jerzy; Jaskulski, Jarosław; Petrus, Andrzej; Kamecki, Krzysztof; Mikołajczak, Witold; Obarzanowski, Mateusz; Wronczewski, Andrzej; Krasnicki, Krzysztof; Jasinski, Milosz

    2011-09-01

    The aim of the study was to compare the number of nodes dissected during laparoscopic and open radical cystoprostatectomy in men or anterior exenteration in women due to muscle invasive bladder urothelial cancer (IBC). Fifty-one patients treated with laparoscopic radical cystectomy (LRC) and 63 with open radical cystectomy (ORC) were compared. The LRC group consisted of 47 pT2 tumours and 4 pT3, while the ORC group was composed of 27 pT2 tumours and 36 pT3. During ORC external, internal, common iliac and obturator lymph nodes were removed separately, but were added and analysed together for each side. Nodes dissected from one side during ORC were compared to en bloc dissected nodes in the LRC group. There were no complications associated with extended pelvic lymph node dissection during LRC or ORC. There were significant differences in the mean number of resected lymph nodes between LRC and ORC for pT2 tumours. The laparoscopic approach allowed about 8-9 more lymph nodes to be removed than open surgery in the pT2 group. In 15% of patients with pT2 disease treated with open radical cystectomy node metastases were observed. Active disease was detected in 18% of nodes resected laparoscopically due to pT2 disease. Fourty-seven percentage of patients with pT3 disease treated with open surgery were diagnosed as harbouring metastatic lymph nodes. The laparoscopic group with pT3 disease was too small to analyse. We have found that laparoscopic radical cystectomy can be performed without any compromise in lymph node dissection. The technique of lymph node dissection (LND) during laparoscopic cystectomy (LRC) resulted in sufficient resected lymphatic tissue, especially in patients with bladder-confined tumours with a low volume of lymph nodes.

  14. Lymph node dissection during laparoscopic (LRC and open (ORC radical cystectomy due to muscle invasive bladder urothelial cancer (pT2-3, TCC

    Directory of Open Access Journals (Sweden)

    Krzysztof Krasnicki

    2011-09-01

    Full Text Available Aim: The aim of the study was to compare the number of nodes dissected during laparoscopic and open radical cystoprostatectomyin men or anterior exenteration in women due to muscle invasive bladder urothelial cancer (IBC.Material and methods: Fifty-one patients treated with laparoscopic radical cystectomy (LRC and 63 with open radicalcystectomy (ORC were compared. The LRC group consisted of 47 pT2 tumours and 4 pT3, while the ORC groupwas composed of 27 pT2 tumours and 36 pT3. During ORC external, internal, common iliac and obturator lymphnodes were removed separately, but were added and analysed together for each side. Nodes dissected from one sideduring ORC were compared to en bloc dissected nodes in the LRC group.Results: There were no complications associated with extended pelvic lymph node dissection during LRC or ORC.There were significant differences in the mean number of resected lymph nodes between LRC and ORC for pT2tumours. The laparoscopic approach allowed about 8-9 more lymph nodes to be removed than open surgery in thepT2 group. In 15% of patients with pT2 disease treated with open radical cystectomy node metastases were observed. Active disease was detected in 18% of nodes resected laparoscopically due to pT2 disease. Fourty-seven percentageof patients with pT3 disease treated with open surgery were diagnosed as harbouring metastatic lymph nodes. Thelaparoscopic group with pT3 disease was too small to analyse.Conclusions: We have found that laparoscopic radical cystectomy can be performed without any compromise inlymph node dissection. The technique of lymph node dissection (LND during laparoscopic cystectomy (LRC resultedin sufficient resected lymphatic tissue, especially in patients with bladder-confined tumours with a low volume oflymph nodes.

  15. 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.

  16. TREATMENT EFFECTS OF WST11 VASCULAR TARGETED PHOTODYNAMIC THERAPY IN UROTHELIAL CELL CARCINOMA AND FEASIBILITY, SAFETY, AND LONG TERM OUTCOMES IN THE UPPER URINARY TRACT OF SWINE

    Science.gov (United States)

    Murray, Katie S; Winter, Ashley G; Corradi, Renato Beluco; LaRosa, Stephen; Jebiwott, Sylvia; Somma, Alexander; Takaki, Haruyuki; Srimathveeravalli, Govindarajan; Lepherd, Michelle; Monette, Sebastien; Kim, Kwanghee; Scherz, Avigdor; Coleman, Jonathan A

    2016-01-01

    Purpose Surgical management of upper tract urothelial carcinoma requires removal of kidney and ureter, compromising renal function. Non-surgical alternatives have potentially prohibitive safety concerns. We examine the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular-targeted photodynamic therapy in a porcine model and report efficacy of WST11 vascular-targeted photodynamic therapy in a murine model. Materials and Methods Following approval, we performed 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4mg/kg) followed by laser illumination (10 minutes) was performed via percutaneous access or retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology was evaluated at several post-ablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. Results At 24 hours, 50 mW/cm laser fluence produced superficial necrosis of the ureter and deeper necrosis (penetrating the muscularis propria or adventitia) was produced by treatment with 200 mW/cm in the ureter and renal pelvis. At 4 weeks, superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis, or abnormality of lab testing was noted up to 4 weeks. In mice, 80% had no evidence of tumor at 19 days after WST11 vascular-targeted photodynamic therapy. Conclusions Urothelial cell carcinoma appears to be sensitive to WST11 vascular-targeted photodynamic therapy. Depth of WST11 vascular-targeted photodynamic therapy treatment effects can be modulated in a dose-dependent manner by titration of light intensity. Moreover, this treatment modality, applied to the porcine upper urinary tract, is feasible via antegrade and retrograde access. PMID:26860792

  17. DNA Damage Response and Repair Gene Alterations Are Associated with Improved Survival in Patients with Platinum-Treated Advanced Urothelial Carcinoma.

    Science.gov (United States)

    Teo, Min Yuen; Bambury, Richard M; Zabor, Emily C; Jordan, Emmet; Al-Ahmadie, Hikmat; Boyd, Mariel E; Bouvier, Nancy; Mullane, Stephanie A; Cha, Eugene K; Roper, Nitin; Ostrovnaya, Irina; Hyman, David M; Bochner, Bernard H; Arcila, Maria E; Solit, David B; Berger, Michael F; Bajorin, Dean F; Bellmunt, Joaquim; Iyer, Gopakumar; Rosenberg, Jonathan E

    2017-07-15

    Purpose: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in DNA damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy. Experimental Design: Patients with diagnosis of locally advanced and metastatic urothelial carcinoma treated with platinum-based chemotherapy who had exon sequencing with the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay were identified. Patients were dichotomized based on the presence/absence of alterations in a panel of 34 DDR genes. DDR alteration status was correlated with clinical outcomes and disease features. Results: One hundred patients were identified, of which 47 harbored alterations in DDR genes. Patients with DDR alterations had improved progression-free survival (9.3 vs. 6.0 months, log-rank P = 0.007) and overall survival (23.7 vs. 13.0 months, log-rank P = 0.006). DDR alterations were also associated with higher number mutations and copy-number alterations. A trend toward positive correlation between DDR status and nodal metastases and inverse correlation with visceral metastases were observed. Different DDR pathways also suggested variable impact on clinical outcomes. Conclusions: Somatic DDR alteration is associated with improved clinical outcomes in platinum-treated patients with advanced urothelial carcinoma. Once validated, it can improve patient selection for clinical practice and future study enrollment. Clin Cancer Res; 23(14); 3610-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. 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.

  19. INCREASED URINARY ALBUMIN INDICATING UROTHELIAL LEAKAGE FOLLOWING INTRAVESICAL BACILLUS-CALMETTE-GUERIN THERAPY FOR SUPERFICIAL BLADDER-CANCER

    NARCIS (Netherlands)

    de Boer, E. C.; de Reijke, T. M.; Schamhart, D. H.; Vos, P. C.; Kurth, K. H.

    1993-01-01

    This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guerin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type

  20. A Systematic Review of the Diagnostic and Prognostic Value of Urinary Protein Biomarkers in Urothelial Bladder Cancer

    Science.gov (United States)

    D’Costa, Jamie J.; Goldsmith, James C.; Wilson, Jayne S.; Bryan, Richard T.; Ward, Douglas G.

    2016-01-01

    For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting. As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation. PMID:27500198

  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; Netto, George J; 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

    Directory of Open Access Journals (Sweden)

    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. Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma.

    Science.gov (United States)

    Chung, Chi-Jung; Chang, Chao-Hsiang; Liou, Saou-Hsing; Liu, Chiu-Shong; Liu, Huei-Ju; Hsu, Li-Ching; Chen, Jhih-Sheng; Lee, Hui-Ling

    2017-02-01

    Cigarette smoking and environmental exposure to heavy metals are important global health issues, especially for urothelial carcinoma (UC). However, the effects of cadmium and lead exposure, as well as the levels of DNA hypomethylation, on UC risk are limited. We evaluated the possible exposure sources of Cd and Pb and the relationship among DNA hypomethylation, urinary Cd and Pb levels, and UC risk. We recruited 209 patients with UC and 417 control patients for a hospital-based case-control study between June 2011 and August 2014. We collected environmental exposure-related information with questionnaires. Blood and urine samples were analyzed to measure the Cd and Pb exposure and 5-methyl-2'-deoxycytidine levels as a proxy for DNA methylation. Multivariate logistic regression and 95% confidence intervals were applied to estimate the risk for UC. Study participants with high Cd and Pb exposure in blood or urine had significantly increased risk of UC, especially among the smokers. After adjusting for age and gender, the possible connections of individual cumulative cigarette smoking or herb medicine exposure with the increased levels of Cd and Pb were observed in the controls. Participants with 8.66%-12.39% of DNA hypomethylation had significantly increased risk of UC compared with those with ≥12.39% of DNA hypomethylation. Environmental factors including cigarette smoking and herb medicine may contribute to the internal dose of heavy metals levels. Repeat measurements of heavy metals with different study design, detailed dietary information, and types of herb medicine should be recommended for exploring UC carcinogenesis in future studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  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. Clinical and prognostic value of preoperative hydronephrosis in upper tract urothelial carcinoma: a systematic review and meta-analysis

    Science.gov (United States)

    Wang, Zhiping

    2016-01-01

    Background. Epidemiological studies have reported various results relating preoperative hydronephrosis to upper tract urothelial carcinoma (UTUC). However, the clinical significance and prognostic value of preoperative hydronephrosis in UTUC remains controversial. The aim of this study was to provide a comprehensive meta-analysis of the extent of the possible association between preoperative hydronephrosis and the risk of UTUC. Methods. We searched PubMed, ISI Web of Knowledge, and Embase to identify eligible studies written in English. Summary odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Results. Nineteen relevant studies, which had a total of 5,782 UTUC patients enrolled, were selected for statistical analysis. The clinicopathological and prognostic relevance of preoperative hydronephrosis was evaluated in the UTUC patients. The results showed that all tumor stages, lymph node status and tumor location, as well as the risk of cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were significantly different between UTUC patients with elevated preoperative hydronephrosis and those with low preoperative hydronephrosis. High preoperative hydronephrosis indicated a poor prognosis. Additionally, significant correlations between preoperative hydronephrosis and tumor grade (high grade vs. low grade) were observed in UTUC patients; however, no significant difference was observed for tumor grading (G1 vs. G2 + G3 and G1 + G2 vs. G3). In contrast, no such correlations were evident for recurrence status or gender in UTUC patients. Conclusions. The results of this meta-analysis suggest that preoperative hydronephrosis is associated with increased risk and poor survival in UTUC patients. The presence of preoperative hydronephrosis plays an important role in the carcinogenesis and prognosis of UTUC. PMID:27366646

  6. Involvement of p38 mitogen-activated protein kinase in acquired gemcitabine-resistant human urothelial carcinoma sublines

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    Yu-Ting Kao

    2014-07-01

    Full Text Available Resistance to chemotherapeutic drugs is one of the major challenges in the treatment of cancer. A better understanding of how resistance arises and what molecular alterations correlate with resistance is the key to developing novel effective therapeutic strategies. To investigate the underlying mechanisms of gemcitabine (Gem resistance and provide possible therapeutic options, three Gem-resistant urothelial carcinoma sublines were established (NG0.6, NG0.8, and NG1.0. These cells were cross-resistant to arabinofuranosyl cytidine and cisplatin, but sensitive to 5-fluorouracil. The resistant cells expressed lower values of [hENT1 × dCK/RRM1 × RRM2] mRNA ratio. Two adenosine triphosphate-binding cassette proteins ABCD1 as well as multidrug resistance protein 1 were elevated. Moreover, cyclin D1, cyclin-dependent kinases 2 and 4 were upregulated, whereas extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase (MAPK activity were repressed significantly. Administration of p38 MAPK inhibitor significantly reduced the Gem sensitivity in NTUB1 cells, whereas that of an extracellular signal-regulated kinase MAPK inhibitor did not. Furthermore, the Gem-resistant sublines also exhibited higher migration ability. Forced expression of p38 MAPK impaired the cell migration activity and augmented Gem sensitivity in NG1.0 cells. Taken together, these results demonstrate that complex mechanisms were merged in acquiring Gem resistance and provide information that can be important for developing therapeutic targets for treating Gem-resistant tumors.

  7. Interleukin-17-positive mast cells influence outcomes from BCG for patients with CIS: Data from a comprehensive characterisation of the immune microenvironment of urothelial bladder cancer.

    Directory of Open Access Journals (Sweden)

    Alexander C Dowell

    Full Text Available The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS, p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the context of patient outcome, following intravesical BCG immunotherapy which is the standard of care; higher numbers of IL-17+ cells were associated with improved event-free survival (p = 0.0449, HR 0.2918, 95% CI 0.08762-0.9721 in patients with primary and concomitant CIS (n = 41, we propose a model of IL-17+ Mast cells mechanism of action. Thus, in the context of bladder CIS, IL-17+ mast cells predict favourable outcome following BCG immunotherapy indicative of a novel mechanism of BCG immunotherapy in UBC and could form the basis of a stratified approach to treatment.

  8. [Micropapillary carcinoma of the bladder: case report and review of the literature].

    Science.gov (United States)

    Ripa Saldías, L; Guarch Troyas, R; Hualde Alfaro, A; De Pablo Cárdenas, A; Pinós Paul, M; Santiago González de Garibay, A

    2005-04-01

    Micropapillary carcinoma is an uncommon pathologic variant of bladder carcinoma with aggressive behavior. Its usual presentation is like a high grade and high stage carcinoma and associated with other histologic types in different proportion. It doesn't differ clinically from normal transitional cell carcinoma of the bladder. Studies of molecular markers are still contradictories. Treatment should be early and aggresive, based on surgical therapy as radiotherapy and chemotherapy have shown limited results. We report a 72 year old man suffering from low urinary tract symptoms for years and recently presented gross hematuria. He was diagnosed as high stage micropapillary carcinoma. One year after radical cystectomy and subsequent chemotherapy based on carboplatin and gemcitabine, progression of the disease was shown on CT and the patient died 14 months after the diagnosis.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Mameghan, Hedy; Fisher, Richard; Mameghan, Jill; Brook, Susan

    1995-01-01

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy

  11. Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer.

    Science.gov (United States)

    Suriano, Francesca; Santini, Daniele; Perrone, Giuseppe; Amato, Michela; Vincenzi, Bruno; Tonini, Giuseppe; Muda, Andrea; Boggia, Sara; Buscarini, Maurizio; Pantano, Francesco

    2013-11-05

    To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy. Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann-Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method. CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively). M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.

  12. Intravesicular taxane-induced dermatotoxicity in a 78-year-old man with urothelial carcinoma and primary cutaneous anaplastic large cell lymphoma.

    Science.gov (United States)

    Pelletier, Daniel; O'Donnell, Michael; Stone, Mary Seabury; Liu, Vincent

    2018-02-27

    Patients treated with intravesical bacillus Calmette-Guerin therapy for urothelial carcinoma often become refractory and experience recurrent disease, thus necessitating alternative intravesical treatment modalities if the patient is to be spared the morbidities associated with radical cystectomy. Intravesical treatment with taxane-based chemotherapy, such as docetaxel, has gained traction in urologic oncology, proving to be an effective salvage therapy in such patients. Systemic taxane-based chemotherapeutic regimens have long been used in several advanced malignancies, and their systemic side effects and associated histologic correlates have been extensively documented. In contrast to adverse effects associated with systemic administration, intravesical taxane administration has thus far proven to be well-tolerated, with little to no systemic absorption. To our knowledge, features of taxane-induced systemic effects have not been reported in this setting. Herein, we report a case of a patient with recurrent urothelial carcinoma treated with intravesical docetaxel, along with primary cutaneous anaplastic large cell lymphoma, who developed characteristic dermatotoxic histologic findings associated with intravenous taxane administration. As such histopathologic findings often represent close mimickers of neoplastic and infectious etiologies, knowledge of the potential for systemic manifestations of taxane therapy in patients treated topically may prevent potentially costly diagnostic pitfalls. This article is protected by copyright. All rights reserved.

  13. Preoperative controlling nutritional status (CONUT) score as a novel predictive biomarker of survival in patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy.

    Science.gov (United States)

    Ishihara, Hiroki; Kondo, Tsunenori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Tanabe, Kazunari

    2017-09-01

    The purpose of this study was to investigate the correlation between the controlling nutritional status (CONUT) score and survival of patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy (RNU). We retrospectively enrolled 107 patients. CONUT score was calculated based on the serum albumin concentration, lymphocyte count, and total cholesterol concentration. Patients were classified into 2 groups based on CONUT score. Relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU were compared between the 2 groups, and predictors of survival were analyzed using Cox proportional hazards regression models. For CONUT score, the area under the curve was 0.588 and the optimal cutoff value was 3. Twenty-four patients (22.4%) had high CONUT scores. The patients with high CONUT scores had significantly shorter 5-year RFS, CSS, and OS than did those with low CONUT scores (RFS: 50.1% vs. 66.0%; CSS: 28.1% vs. 71.7%; OS: 26.4% vs. 66.8%; all PHR] = 5.44, P = 0.0016) and OS (HR = 2.90, P = 0.0214) and showed marginal significance for predicting RFS (HR = 2.26, P = 0.0581). Preoperative CONUT score helps predict survival in patients with localized urothelial carcinoma of the upper urinary tract treated with RNU. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A Modified Direct-Smear Processing Technique Employing Two-Step Centrifugation/Fixation Is Useful for Detecting High-Grade Urothelial Carcinoma.

    Science.gov (United States)

    Toyonaga, Yasuhiro; Yamazaki, Kazuto; Koyama, Yoshinori; Yamada, Masatoshi; Ishida, Yasuo

    2017-01-01

    To demonstrate the usefulness of a direct-smear processing technique employing two-step centrifugation/fixation processing (TSCFP) in the cytoscreening of high-grade urothelial carcinoma (HGUC). Using the T24 HGUC cell line, we compared the cell yield and the morphological preservation of preparations concurrently processed by direct-smear, SurePath, ThinPrep, and TSCFP techniques. A total of 287 urine cytology cases subjected to TSCFP over a period of 6 years were reviewed and reclassified according to the Paris System for Reporting Urinary Cytology (PSRUC) and correlated with histology results. TSCFP of T24 cells demonstrated good cell yield with a recovery rate of about 70%. Diagnostic features of HGUC, such as a high nuclear/cytoplasmic ratio and irregular/hyperchromatic chromatin, were better discovered in TSCFP smears than in smears prepared with the other methods. Cytological evaluation of 287 voided urine specimens revealed that the rate of unsatisfactory preparations was quite low (0.30%) and the overall sensitivity, specificity, and positive and negative predictive values for urothelial carcinoma were 0.719, 0.923, 0.973, and 0.462, respectively. TSCFP was able to provide adequate preparations for detecting HGUC in urine cytology and could be considered as a promising processing method according to the principal purpose of PSRUC. © 2017 S. Karger AG, Basel.

  15. Small cell carcinoma of the urinary bladder without gross hematuria: a case report.

    Science.gov (United States)

    Huang, Wanqiu; Luan, Yang; Jin, Lu; Wang, Tao; Chen, Ruibao; Liu, Zheng; Chen, Zhiqiang; Lan, Ruzhu

    2015-09-01

    Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking.

  16. A Stratified Meta-Analysis of the Association between Exposure to Environmental Tobacco Smoke during Childhood and Adulthood and Urothelial Bladder Cancer Risk

    Directory of Open Access Journals (Sweden)

    Frits H. M. van Osch

    2018-03-01

    Full Text Available Background: Active smoking is a major risk factor for urothelial bladder cancer (UBC. However, the evidence that exposure to environmental tobacco smoke (ETS either in childhood or adult life is also associated with UBC risk is ambiguous. With this meta-analysis, we aim to summarise how exposure to ETS is associated with UBC risk. Methods: In total, 11 studies (3 cohort studies, 8 case-control studies were included in this meta-analysis and summary odds ratios (SORs for UBC risk were calculated for never smokers who were exposed to ETS during childhood at home, during adulthood at home, or during adulthood in a work environment compared to never smokers who were never exposed to ETS. Sensitivity analyses were conducted to test the robustness of findings. Results: Never smokers exposed to ETS during childhood (SOR = 1.04, 95% confidence interval (CI = 0.82–1.26, during adulthood at work (SOR = 0.98, 95% CI = 0.78–1.18 or at home (SOR = 0.99, 95% CI = 0.83–1.15 were at a similar risk of UBC compared to never smokers who were never exposed to ETS. Results for males and females were similar. Also, when pooling all estimates during both childhood and adulthood, no effect was observed (SOR = 1.00, 95% CI = 0.89–1.10. Conclusions: Although measurement of exposure to ETS was imprecise, there does not seem to be an association between UBC risk and exposure to ETS during childhood or adulthood. However, the current body of evidence mostly overlooks the duration and intensity of exposure to ETS.

  17. 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

    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.......Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we...

  18. TERT Promoter Mutations Occur Early in Urothelial Neoplasia and are Biomarkers of Early Disease and Disease Recurrence in Urine

    Science.gov (United States)

    Kinde, Isaac; Munari, Enrico; Faraj, Sheila F.; Hruban, Ralph H.; Schoenberg, Mark; Bivalacqua, Trinity; Allaf, Mohamad; Springer, Simeon; Wang, Yuxuan; Diaz, Luis A.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Netto, George J.

    2014-01-01

    Activating mutations occur in the promoter of the telomerase reverse transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To explore their role in bladder cancer development, and to assess their utility as urine markers for early detection, we sequenced the TERT promoter in 76 well-characterized papillary and flat noninvasive urothelial carcinomas, including 28 pTa low-grade (pTa LG) transitional cell carcinomas (TCC), 31 pTa high-grade (pTa HG) TCCs, and 17 pTis carcinoma in situ (CIS) lesions. We also evaluated the sequence of the TERT promoter in a separate series of 14 early bladder neoplasms and matched follow-up urine samples to determine if urine TERT status was an indicator of disease recurrence. A high rate of TERT promoter mutation was observed in both papillary and flat lesions, as well as in low- and high-grade noninvasive urothelial neoplasms (mean: 74%). Additionally, among patients whose tumors harbored TERT promoter mutations, the same mutations were present in follow-up urines in seven of eight patients that recurred but in none of 6 patients that did not recur (P <0.001). TERT promoter mutations occur in both papillary and flat lesions, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. These provocative results suggest that TERT promoter mutations may offer a useful urinary biomarker, for both early detection and monitoring of bladder neoplasia. PMID:24121487

  19. Urinary bladder adenocarcinoma arising in a spina bifida patient.

    Science.gov (United States)

    Bitar, Mireille; Mandel, Edmund; Kirschenbaum, Alexander M; Unger, Pamela D

    2007-12-01

    Urinary bladder adenocarcinomas are rare malignancies accounting for approximately 2.5% of all urothelial neoplasms. Intestinal metaplasia of the urothelium indicates the presence of intestinal-type goblet cells and was generally observed to coexist with or to precede the diagnosis of bladder adenocarcinomas. Controversy continues of whether intestinal metaplasia is an acquired precancerous lesion, secondary to different insults to the urothelium, or a concomitant lesion in glandular carcinogenesis. Patients with neurogenic bladders are particularly at risk for developing bladder cancer, mostly squamous cell carcinoma and rarely adenocarcinoma. In these patients, chronic irritation of the urothelium as well as long-term indwelling urinary catheters were the most significant risk factors. Spina bifida is a congenital developmental abnormality that may result in neurogenic bladder. There is only one previously reported case of urothelial carcinoma with associated squamous metaplasia of the bladder occurring in a spina bifida patient. We report the first case of bladder adenocarcinoma associated with intestinal metaplasia occurring in a spina bifida occulta patient. The patient had a complicated clinical course and suffered recurrent urinary tract infections, renal calculi, and urinary incontinence and was managed with intermittent as well as indwelling catheterization.

  20. UBC®Rapid Test for detection of carcinoma in situ for bladder cancer.

    Science.gov (United States)

    Ecke, Thorsten H; Weiß, Sarah; Stephan, Carsten; Hallmann, Steffen; Barski, Dimitri; Otto, Thomas; Gerullis, Holger

    2017-05-01

    UBC ® Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC ® Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC ® Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC ® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC ® Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.

  1. Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Meijer, Richard P.; Meinhardt, Wim; Poel, Henk G. van der; Rhijn, Bas W. van; Kerst, J. Martijn; Pos, Floris J.; Horenblas, Simon; Bex, Axel

    2013-01-01

    The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

  2. Autopsy findings in surgical-radiotherapeutically treated bladder carcinoma - conclusions for optimization of radiotherapy

    International Nuclear Information System (INIS)

    Fueller, J.; Kob, D.; Fritzsche, V.

    1989-01-01

    Autopsy findings in patients with bladder carcinoma, treated by combined operation and radiotherapy, revealed tendencies of tumor spread as well as complications and late effects of radiotherapy. In 24.5% of the cases tumor tissue was found within the bladder and in 30.5% within the minor pelvis. Metastases were found in 24.1% in iliac lymph nodes, in 21.3% in abdominal lymph nodes. Liver, lungs, bones, and kidneys are main organs for hematological metastasizing. Little or undifferentiated carcinomas and squamous cell carcinomas showed a greater tendency to metastasize than highly and medium-differentiated ureteral carcinomas. The least radiotherapeutical complications and late effects were found in a fractionation with daily 1.5 Gy and a total dose of 60 Gy. (author)

  3. Role of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma.

    Science.gov (United States)

    Lenis, Andrew T; Donin, Nicholas M; Faiena, Izak; Salmasi, Amirali; Johnson, David C; Drakaki, Alexandra; Gollapudi, Kiran; Blumberg, Jeremy; Belldegrun, Arie; Pantuck, Allan; Chamie, Karim

    2018-01-01

    With increasing utilization of robot-assisted surgery in urologic oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of choice for patients with upper tract urothelial carcinoma (UTUC). The role of surgical approach on lymph node dissection (LND) and lymph node (LN) yield is unclear, and potential therapeutic effects are unknown. Here we analyze the effects of surgical approach on LN yield, performance of LND, and overall survival (OS). Patients with UTUC who underwent nephroureterectomy from 2010 to 2013 were identified in the National Cancer Database. Outcomes of interest included rate of LND, LN yield, and OS. Logistic regression analyses were used to predict performance of LND. Negative binomial regression was used to derive incidence rate ratios for LN yield. Cox proportional hazards models were used to quantify survival outcomes. A total of 3,116 patients met inclusion criteria. LND was performed in 41% (314/762) of RNU, 27% (380/1385) of LNU cases, and 35% (340/969) of ONU (PONU, patients who underwent a LNU had significantly lower odds of receiving a LND (OR = 0.70, 95% CI: 0.55-0.87) and had fewer LNs removed (IRR = 0.69, 95% CI: 0.60-0.80), while RNU trended toward increased LN yield (IRR = 1.14, 95% CI: 0.98-1.33). In a Cox proportional hazards model, increasing LN yield was associated with improved OS in patients with pN0 disease (HR = 0.97 per 1 unit increase in LN yield, 95% CI: 0.95-0.99). Compared with an ONU, RNU does not compromise performance of a LND and may be associated with improved LN yield. LNU is associated with the lowest rates of LND and LN yield. Increasing LN yield is associated with improved OS in patients with pN0 disease. Despite differential rates of LND and LN yield, surgical approach did not independently affect OS. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature

    International Nuclear Information System (INIS)

    Kumaran, D.; Anamalai, M.; Velu, U.; Julka, P.K.; Nambirajan, A.

    2016-01-01

    Background: Gall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature. Methods: This report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis. Case report: A 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2 2 cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired. Conclusion: There are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer

  6. 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.

  7. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection.

    Science.gov (United States)

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio

    2015-02-01

    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  8. Expression of cathepsin D in bladder carcinoma: correlation with pathological features and serum cystatin C levels.

    Science.gov (United States)

    Tokyol, Cidğem; Köken, Tülay; Demirbas, Murat; Dilek, Fatma Hüsniye; Yörükoglu, Kutsal; Mungan, Ugur; Kirkali, Ziya

    2006-01-01

    The aim of this study is to evaluate the expression of cathepsin D in primary bladder cancer and to determine its relationship with conventional pathological features and serum cystatin C levels. The immunohistochemical cathepsin D expression and staining patterns of epithelial and stromal cells were investigated in 21 patients with primary bladder carcinoma. Serum cystatin C levels were determined by immunoturbidimetry and compared with matched controls. There were 7 papillary neoplasms of low malignant potential, 7 low-grade and 7 high-grade carcinomas. Six tumors were invasive. Statistical analysis showed a significant inverse relationship between cathepsin D expression of the tumor cells and tumor grade and stage (P = 0.018 and P = 0.046, respectively). Serum cystatin C levels of the controls and patients varied between 0.39 mg/L and 1.99 mg/L (P > 0.05). There was no significant relation between cathepsin D expression in tumor tissue and serum cystatin C levels. Loss of cathepsin D expression in bladder carcinomas may be associated with high-grade and invasive tumors. Thus, increased cathepsin D expression by tumor cells may be related to local tumor invasion at an early stage, but it seems that extracellular cystatin C is not affected by cathepsin D expression of tumor or stromal cells, and cystatin C concentrations are not directly correlated with the progression of primary bladder carcinomas.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Lymphoepithelioma-like carcinoma of the urinary bladder: A case report.

    Science.gov (United States)

    Laforga, Juan B; Gasent, Joan M

    We report a case of lymphoepithelioma-like carcinoma of the urinary bladder in an elderly female patient. A 97-year old woman presented with hematuria, and an ultrasonographic urinary study showed a localized tumor in the trigone region of the urinary bladder. A transurethral resection revealed a mixed tumor formed by high-grade transitional carcinoma and lymphoepithelioma-like carcinoma that had infiltrated into the muscular propria. We describe the clinicopathological, morphological and immunohistochemical features of this tumor and briefly discuss its differential diagnosis and biological behavior. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Expression of cell cycle regulators, 14-3-3σ and p53 proteins, and vimentin in canine transitional cell carcinoma of the urinary bladder.

    Science.gov (United States)

    Suárez-Bonnet, Alejandro; Herráez, Pedro; Aguirre, Maria; Suárez-Bonnet, Elena; Andrada, Marisa; Rodríguez, Francisco; Espinosa de Los Monteros, Antonio

    2015-07-01

    The study of the expression of 14-3-3σ, p53, and vimentin proteins in canine transitional cell carcinoma (TCC) evaluating differences with normal bladder tissues, and the association with clinicopathological variables. We analyze by immunohistochemistry in 19 canine TCCs the expression of 14-3-3σ, p53, and vimentin using monoclonal antibodys. A semiquantitative scoring method was employed and statistical analysis was performed to display relationships between variables. In contrast to normal urinary bladder epithelium, which showed high levels of 14-3-3σ, its expression was decreased in 53% of the studied tumors (P = 0.0344). The 14-3-3σ protein was expressed by neoplastic emboli and by highly infiltrative neoplastic cells. The p53 protein was expressed in 26% of TCCs, but no significant association between 14-3-3σ and p53 was detected. Neoplastic epithelial cells displayed vimentin immunoreactivity in 21% of TCCs, and a positive correlation with mitotic index was observed (P = 0.042). Coexpression of vimentin and 14-3-3σ by highly infiltrative neoplastic cells was also observed. 14-3-3σ is deregulated in canine TCCs and its expression by highly infiltrative tumor cells may be related to the acquisition of aggressive behavior. Furthermore, this article reinforce the role of canine TCC as relevant model of human urothelial carcinoma and we suggest 14-3-3σ as a potential therapeutic target. Further studies are necessary to clarify the role of 14-3-3σ in canine TCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 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)

  13. Prognostic factors in non-muscle-invasive bladder tumors - I. Clinical prognostic factors: A review of the experience of the EORTC genito-urinary group - II. Biologic prognostic markers

    NARCIS (Netherlands)

    Kurth, Karl-Heinz; Sylvester, Richard J.

    2007-01-01

    Objectives: To summarize the most important clinical prognostic factors of non-muscle-invasive bladder cancer, as assessed by the European organization for Research and Treatment of Cancer (EORTC) Genito-Urinary Group, to present biologic markers involved in urothelial cell carcinoma, and to address

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Carcinoma Of The Urinary Bladder In Maiduguri, Nigeria: A ...

    African Journals Online (AJOL)

    Simple statistical analysis was used in analyzing the cases. RESULTS: Squamous cell carcinoma was the commonest tumour and accounted for 70% of the cases. Transitional cell carcinoma constituted 22%. The least common tumours were embryonal rhabdomyosarcoma and carcinosarcoma contributing one case each.

  19. Impact of ABO blood type on outcomes in patients with primary nonmuscle invasive bladder cancer.

    Science.gov (United States)

    Klatte, Tobias; Xylinas, Evanguelos; Rieken, Malte; Kluth, Luis A; Rouprêt, Morgan; Pycha, Armin; Fajkovic, Harun; Seitz, Christian; Karakiewicz, Pierre I; Lotan, Yair; Babjuk, Marko; de Martino, Michela; Scherr, Douglas S; Shariat, Shahrokh F

    2014-05-01

    ABO blood type is an established prognostic factor for several malignancies but its role in bladder urothelial carcinoma is largely unknown. We determined whether ABO blood type is associated with the outcome of transurethral resection of nonmuscle invasive bladder urothelial carcinoma. We retrospectively studied ABO blood types in 931 patients with primary nonmuscle invasive bladder urothelial carcinoma treated with transurethral bladder resection with or without intravesical instillation therapy. Disease recurrence and progression were analyzed with univariable and multivariable competing risks regression models. Median followup was 67 months. Discrimination was evaluated by the concordance index. The ABO blood type was O, A, B and AB in 414 (44.5%), 360 (38.7%), 103 (11.1%) and 54 patients (5.8%), respectively. ABO blood type was significantly associated with outcome on univariable and multivariable analysis. Overall, patients with blood type O had worse recurrence and progression rates than those with A (p = 0.015 and 0.031) or B (p = 0.004 and 0.075, respectively). The concordance index of multivariable base models increased after including ABO blood type. In patients with nonmuscle invasive bladder urothelial carcinoma the ABO blood type may predict the outcome. Those with blood type O showed the highest recurrence and progression rates. Including ABO blood type in multivariable models increases the accuracy of standard prognostic factors. Since the ABO blood type is available for most patients, it may represent an ideal adjunctive marker to predict recurrence and progression. The biological explanation and prognostic value of this finding must be further elucidated. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma

    NARCIS (Netherlands)

    Sonneveld, P.; Kurth, K. H.; Hagemeyer, A.; Abels, J.

    1990-01-01

    Two cases are reported of patients who developed a hematologic malignancy several years after intravesical chemotherapy of superficial bladder cancer with etoglucid, doxorubicin, and mitomycin C. In one patient, karyotypic abnormalities (-5, 7q-) typical of a therapy induced malignancy were

  1. Seminal vesicle cyst associated with ipsilateral renal agenesis and papillary carcinoma of the bladder

    Energy Technology Data Exchange (ETDEWEB)

    Gorrea, M.; Lorente, R.; Roel, J. [Dept. of Radiology, Hospital Gomez Ulla, Madrid (Spain)

    2001-12-01

    We report a case of seminal vesicle cyst associated with ipsilateral renal agenesis in a 37-year-old patient with papillary carcinoma of the bladder. Ultrasonography showed absence of the right kidney, a bladder tumour and a round retrovesical hypoechogenic mass with posterior acoustic enhancement. It showed low attenuation on CT, low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted MR images. Intravenous urography (IVU) and cystoscopy were also performed. After surgery, it proved to be a seminal vesicle cyst. The embryology, imaging characteristics and differential diagnosis of seminal vesicle cysts are discussed. Associated findings are also described. (orig.)

  2. Forced diuresis 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced in detection of carcinoma of urinary bladder diverticulum

    International Nuclear Information System (INIS)

    Soundararajan, Ramya; Singh, Harmandeep; Arora, Saurabh; Nayak, Brusabhanu; Shamim, Shamim Ahmed; Bal, Chandrasekhar; Kumar, Rakesh

    2015-01-01

    Urinary bladder diverticular carcinomas are uncommon with a lesser incidence of 0.8–10% and its diagnosis still remains a challenge. Cystoscopy is the most reliable method, but evaluating diverticulum with narrow orifices is difficult. Before the initiation of appropriate treatment, proper detection of bladder diverticular carcinoma and its locoregional and distant sites of involvement is necessary. Here, we present a case of 48-year-old male with urinary bladder diverticular carcinoma detected by forced diuretic 18 F-fluorodeoxyglucose positron emission tomography/computerized tomography ( 18 F-FDG PET/CT). This case also highlights the significance of forced diuretic 18 F-FDG PET/CT in the detection, staging, and response evaluation of bladder diverticular carcinoma

  3. 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.

  4. 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...

  5. Risk factors for transitional cell carcinoma of urinary bladder: a hospital based study

    International Nuclear Information System (INIS)

    Fayyaz, A.; Ilyas, M.; Qayyum, A.

    2011-01-01

    Objective: The objective of the study was to determine the role of various known risk factors for the development of Transitional cell carcinoma (TCC) of urinary bladder in our set up. Study design: Case control study Place and duration of the study: Department of Radiology CMH Rawalpindi, from March 2007 to December 2007. Material and methods: 70 patients with TCC urinary bladder were included in the study. 70 controls were included. The patients were enquired about the risk factors. The data was analysed on SPSS version 12. Odds ratio for each factor was carried out. p value of < 0.05 was considered statistically significant. Results: Smoking was the most important factor in the development of TCC of urinary bladder with odds ratio of 3:1. Driving was the next common factor. Low socioeconomic conditions appear to be an important factor in our set up. The role of chemicals in industrial work could not be established. Conclusion: Differences from the West exist regarding the etiological factors for the development of TCC of urinary bladder. Males outnumber the females by a significant ratio. Smoking is an important factor in the development of TCC of urinary bladder. Most bladder cancers arise in low socioeconomic group in our set up. (author)

  6. Langerhans cell histiocytosis of the urinary bladder in a patient with bladder cancer previously treated with intravesical Bacillus Calmette-Guérin therapy.

    Science.gov (United States)

    Numakura, Satoe; Morikawa, Teppei; Ushiku, Tetsuo; Toyoshima, Toyoaki; Fukayama, Masashi

    2014-02-01

    We report an extremely rare case of Langerhans cell histiocytosis (LCH) of the urinary bladder. A 68-year-old man presented with gross hematuria. Cystoscopy showed multiple papillary tumors in the urinary bladder, and transurethral resection was performed. Pathological diagnosis was high-grade papillary urothelial carcinoma with lamina propria invasion. The patient received six treatments with intravesical Bacillus Calmette-Guérin (BCG) therapy. Seven months after surgery, follow-up cystoscopy showed three elevated lesions in the urinary bladder, two of which were identified histologically as recurrent urothelial carcinoma. Microscopic examination of the lesion at the anterior wall revealed diffuse infiltration of medium to large histiocytoid cells in the lamina propria, many of which had distorted nuclei and nuclear grooves. Dense eosinophilic infiltration was also observed. Immunohistochemically, the histiocytoid cells were diffusely positive for S-100 and CD1a, but negative for cytokeratin AE1/AE3 and melanosome-associated antigen recognized by HMB-45. Based on the histological and immunohistochemical features, we diagnosed the lesion as LCH of the urinary bladder. There was no evidence of recurrence of either bladder cancer or LCH after an 18-month follow-up. To avoid misdiagnosis, urologists and pathologists should be aware that LCH may develop in the urinary bladder after intravesical BCG therapy for bladder cancer. Copyright © 2013 Elsevier GmbH. All rights reserved.

  7. A Case of Giant Bladder Carcinosarcoma without Submucosal Invasion

    Directory of Open Access Journals (Sweden)

    Masayoshi Zaitsu

    2011-01-01

    Full Text Available Carcinosarcoma is a rare biphasic neoplasia containing both malignant mesenchymal and epithelial elements. Bladder carcinosarcoma commonly presented as high-grade, advanced stage, and aggressive behavior with a poor prognosis. An 83-year-old male presented with painless gross hematuria to our hospital. Cystoscopy revealed massive nonpapillary bladder tumor on the right wall. The 91 g tumor could be completely removed with transurethral resection. Histology of the tumor was diagnosed as carcinosarcoma with no submucosal invasion composed of biphasic malignant epithelial and mesenchymal cells. Epithelial malignancy was urothelial cancer and mesenchymal one was chondrosarcoma and leiomyosarcoma. The specimens taken at the second-look TUR-Bt revealed that carcinoma in situ (urothelial cancer but not sarcoma existed at the mucosa surrounding the previous tumor site. 80 mg of BCG instillation intravesically every week for six weeks was successfully administered to the patient. There is no tumor recurrence for 6 months after treatments.

  8. 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.

  9. Clinical significance of the VEGF level in urinary bladder carcinoma.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Abhishek, Amar; Rajender, Singh

    2015-01-01

    To investigate the correlation of Vascular Endothelial Growth Factor (VEGF) and micro-vessel density (MVD) with urinary bladder tumor and its stage. The study was conducted between January 2010 and December 2012. The study included screening of 122 patients at elevated risk for bladder cancer, of which 35 patients were finally enrolled in the study. Diagnosis was made on the basis of urine cytology, radiological investigation (ultrasound KUB, and CT-scan) and histopathology. Thirty-five normal cancer-free individuals were enrolled as controls. Human VEGF levels were measured using an enzyme linked immunoassay and protein content (pg/mg protein) by Lowry method. SPSS for Windows version 10.0.7 (SPSS, Chicago, IL, USA) was used for statistical analysis of the data. Mean urine VEGF level in the cases was significantly higher in comparison to the control group. There was a direct correlation between VEGF level and tumor stage. Mean urine VEGF values were minimum in the control group (22.75 ± 15.41 pg/mg creatinine) and maximum in stage IV patients (180.15 ± 75.93 pg/mg creatinine). Tissue VEGF levels also showed a similar trend of increase with increase in stage. Urine VEGF level also showed a correlation with tissue VEGF level. Similarly, MVD showed a significant increase with increase in tumor stage. A correlation between bladder cancer and MVD and VEGF suggest that the latter can serve as markers for therapeutic guidance. This is the first study from India on clinical and pathological correlation among urine VEGF, tumor tissue VEGF levels, and Micro Vessel Density (MVD) in urinary bladder cancer patients.

  10. IFN Alfa-2B and BCG Therapy Is An Effective Method In Superficial Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmet Ozdemir

    2012-04-01

    Full Text Available Aim: The initial therapy for superficial bladder carcinoma is the transurethral resection of the tumor. In spite of successful resections, there are 60-79% recurrence and 15% progression rates. Additional therapies are suggested for the treatment of superficial bladder carcinoma. We compared the efficacy of interferon alfa-2b monotherapy with interferon alfa-2b plus Bacillus Calmette Guerin (BCG combination therapy with urine interleukin (IL 2, 6 and 10 levels of patients with superficial bladder carcinoma. Material and Method: The patients who underwent TUR-BT for superficial bladder tumor (pathological staging Ta-T1 between 2004 and 2007 at our hospital included in this prospective study. Intravesical immunotherapy was administered once a week for 6 weeks and there after a month for 6 months, starting 4 weeks after TUR-BT. IL levels were measured. Results: IL-2, IL-6 and IL- 10 levels in urine samples were taken at 2nd and 4th hours of intravesical therapy. A statistically significant difference was observed between mean urine IL-2 levels of patients treated with IFN%u03B1-2b monotherapy and IFN%u03B1- 2b plus BCG combination both at 2nd and 4th hours. (p=0.05 In IFN%u03B1-2b plus BCG combination group, there was a statistical significant difference between stages regarding IL-2 and IL-6 levels (p=0.05. Among patients with G3 tumors, IL-2 levels were higher at 2 and 4 hours (p=0.05 but there was no significant difference in IL-6 and IL-10 levels in this group of patients regardless of intravesical therapy received (p=0.05. Discussion: IFN%u03B1-2b and BCG combination therapy is a reliable and effective therapy in the management of superficial bladder tumors.

  11. Simultaneous Penile and Signet Ring Cell Bladder Carcinoma in Renal Transplant Recipient: A First Case

    Directory of Open Access Journals (Sweden)

    Francesca Manassero

    2009-01-01

    Full Text Available The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder. The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma, the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up.

  12. [Small cell bladder carcinoma in age extremes: Report of two cases.

    Science.gov (United States)

    Vallejo-Benítez, Ana; Rodríguez-Zarco, Enrique; Pabón-Carrasco, Sara; Espinal, Paula Sofía

    2018-03-01

    We report 2 cases of small cell neuroendocrine carcinomas (CCP) of the urinary bladder in patients aged 37 and 80 years. CCP is a malignancy with poor prognosis. We review the literature, under the current WHO classification (2016). Paraffin blocks were cut for HE staining and immunohistochemistry to analyze the expression of neuroendocrine differentiation. The main diagnosis was based on histopathologic features, which revealed a diffuse growth pattern of small cells with scant cytoplasm and hyperchromatic nuclei. The result of the additional technical immunoreaction was positive for synaptophysin and CD56. Our cases have been reviewed with the literature to discuss the evolution and differential diagnosis of small cell carcinoma of the urinary bladder. This is a rare tumor with very aggressive behavior and its diagnosis lies in its morphology, and immunohistochemical profile.

  13. [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.

  14. Chemotherapy by M-VAC protocol in progressive bladder carcinoma treatment.

    Science.gov (United States)

    Janicic, A; Tulic, C; Radosevic-Jelic, Lj; Dzamic, Z; Acimovic, M; Hadzi-Djokic, J

    2007-01-01

    Treatment of invasive bladder carcinoma is complex therapy procedure which means surgical and non-surgical treatment appliance. In spite of radical surgical treatment conduction, the gold standard in invasive bladder tumor therapy, about 30-40% patients spread metastasis in further disease course. The system chemotherapy in invasive bladder tumors treatments is marked with accent. Its fundamental aim is to correct results of surgical treatment. This therapy option very often means the only modality in bladder carcinoma treatment, for instance, in the diseminal disease faze. The adjuvant chemotherapy imposes a task to correct surgical treatments results in case where the high risk of recidive breaking out exists. As risks for recidive breaking out cite are: a) lymphatic and vascular invasion into the primary tumor; b) extravezical tumor extension-T3b; c) tumor invasion neighboring structures-T4; d) positive lgl findings-N+. After radical cystectomy caused by high level malignancy tumors - T3b,T4, is founded frequency of positive IgI of about 40-60%. Patients with positive lgl have badly prognosis. Only 17% they survive longer than two years, and 7% have surviving of five years.

  15. 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.

  16. An updated review on primary signet-ring cell carcinoma of the urinary bladder and report of a case

    DEFF Research Database (Denmark)

    Lendorf, Maria Elisabeth; Dohn, Line Hammer; Á Dunga, Bara

    2018-01-01

    OBJECTIVE: The aim of the present study was to emphasize the critical importance of the clinician's awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity. MATERIALS AND METHODS: A review of the current literature was conducted and a classic case...... of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC. RESULTS: The prognosis for patients with SRCC of the urinary bladder is poor...

  17. Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

    International Nuclear Information System (INIS)

    Matos, Tadeja; Cufer, Tanja; Cervek, Jozica; Borstnar, Simona; Kragelj, Borut; Zumer-Pregelj, Mirjana

    2000-01-01

    Purpose: The results of bladder sparing approach for the treatment of muscle-invasive bladder cancer, using a combination of transurethral resection (TUR), chemotherapy, and radiotherapy, are encouraging. The survival of patients treated by this method is similar to the survival of patients treated by radical cystectomy. The aim of our study was to find out which pretreatment characteristics influence the survival of patients treated by organ sparing approach that would enable us to identify the patients most suitable for this type of treatment. Methods and Materials: The prognostic value of different factors, such as age, gender, performance status, hemoglobin level, clinical stage, histologic grade, presence of obstructive uropathy, and completeness of TUR, has been studied in 105 patients with invasive bladder cancer, who received a bladder sparing treatment in the period from 1988 to 1995. They were treated with a combination of TUR, followed by 2-4 cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders the treatment was completed by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas nonresponders underwent cystectomy whenever feasible. Results: Our study has confirmed an independent prognostic value of performance status, histologic grade, and obstructive uropathy, for the disease-specific survival (DSS) of bladder cancer patients treated by a conservative approach. We believe that performance status best reflects the extent of disease and exerts significant influence on the extent and course of treatment, while obstructive uropathy is a good indicator of local spread of the disease, better than clinical T-stage. Our finding that histologic grade is one of the strongest prognostic factors shows that tumor biology also is a very important prognostic factor in patients treated by conservative approach. Conclusion: Patients with muscle-invasive bladder cancer who are most likely to benefit

  18. Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract.

    Science.gov (United States)

    Novara, Giacomo; De Marco, Vincenzo; Dalpiaz, Orietta; Gottardo, Fedra; Bouygues, Vianney; Galfano, Antonio; Martignoni, Guido; Patard, Jean Jacques; Artibani, Walter; Ficarra, Vincenzo

    2008-06-01

    To identify the prognostic factors predictive of metachronous bladder transitional cell carcinoma (TCC) in a multi-institutional dataset of patients who had undergone nephroureterectomy (NU) for nonmetastatic upper urinary tract (UUT) TCC. The clinical and pathological data of 231 patients who had had NU for UUT-TCC from 1989 to 2005 in three European centres were collected retrospectively, and analysed for clinical and pathological variables. The median follow-up was 38 months; during the follow-up, bladder TCC was detected in 109 patients (47.2%), and was significantly more common in patients who had UUT-TCC after previous bladder TCC (P TCC (P = 0.017). On multivariate analysis, a previous history of bladder TCC was the only independent predictor of metachronous bladder TCC (hazard ratio 2.825; P TCC was 45.5%. A history of bladder TCC (P TCC (hazard ratio 2.226; P TCC (1.562; P = 0.036) were independent predictors of the probabilities of being free from metachronous bladder TCC. In this multi-institutional study of patients who had had NU for UUT-TCC, a history of bladder TCC was the only independent predictor of metachronous bladder TCC, while both a history of bladder TCC and the presence of ureteric tumours were predictive of the probabilities of being free from metachronous bladder TCC.

  19. Paraganglioma of the urinary bladder: a clinicopathologic spectrum of a series of 14 cases emphasizing diagnostic dilemmas.

    Science.gov (United States)

    Menon, Santosh; Goyal, Pankaj; Suryawanshi, Pallavi; Tongaonkar, Hemant; Joshi, Amit; Bakshi, Ganesh; Desai, Sangeeta

    2014-01-01

    Paraganglioma (PG) of the urinary bladder is a rare neuroendocrine neoplasm, accounting for bladder tumours. Distinction from urothelial carcinoma is imperative as management and prognosis vary markedly. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. All cases of PG of urinary bladder diagnosed at our institute from 2002-2012 were retrieved and diagnosis confirmed in accordance with WHO classification. Clinical and treatment details were obtained from hospital medical records. Fourteen cases of PG of urinary bladder including 5 consult cases were analysed. These included 11 transurethral resections ± partial cystectomies, 2 partial cystectomies and 1 radical cystectomy. Two out of the 5 consult cases had been submitted with a diagnosis of urothelial carcinoma and 1 with that of a rhabdomyosarcoma. Age ranged from 15-84 years (median, 43 years) with a male to female ratio of 1:2.5. Presenting symptoms were haematuria, dysuria and flank pain; only 1 case had antecedent hypertension. Histologically, typical 'zellballen' (72%), diffuse (21%) and ribbon-like (7%) growth patterns amidst a richly vascularised stroma were seen. Muscularis propria invasion and necrosis was present in 72% and 21%, respectively. Substantial cautery artifacts led to misdiagnosis in the 3 erroneous cases. Tumour cells were positive for chromogranin, synaptophysin; sustentacular cells were S-100 positive. Follow up was available in 6 patients; median follow-up was 29 months (8-120 months). One patient developed distant metastasis in cervical lymph node 10 years after diagnosis; remaining were alive without evidence of disease. Paraganglioma of the urinary bladder is a rare tumor and may be misdiagnosed as urothelial cancer

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

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    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.

  1. Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.

    Science.gov (United States)

    Apolo, Andrea B; Infante, Jeffrey R; Balmanoukian, Ani; Patel, Manish R; Wang, Ding; Kelly, Karen; Mega, Anthony E; Britten, Carolyn D; Ravaud, Alain; Mita, Alain C; Safran, Howard; Stinchcombe, Thomas E; Srdanov, Marko; Gelb, Arnold B; Schlichting, Michael; Chin, Kevin; Gulley, James L

    2017-07-01

    Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged

  2. Histopathological characterization of a syngeneic orthotopic murine bladder cancer model

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    Daher C. Chade

    2008-03-01

    Full Text Available PURPOSE: We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line. MATERIALS AND METHODS: Bladder tumor implantation was achieved by intravesical instillation of 5 x 10(5 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3. After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7, carcinoembrionic antigen (Dako-CEA, p53 and c-erbB2 oncoprotein (Her2/neu. RESULTS: Twenty-nine out of 30 animals (96.7% developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g, 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model. CONCLUSIONS: High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

  3. Clinical evaluation of intra-operative radiotherapy combined with subtotal cystectomy for invasive bladder carcinoma

    International Nuclear Information System (INIS)

    Ozawa, Kazunori; Nakagomi, Kazuaki; Yonese, Junzi

    1996-01-01

    From 1981 to 1994, intra-operative radiotherapy after subtotal cystectomy was performed on 22 patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. All the patients received 25 to 30 Gy of radiotherapy focused on trigonum and internal urethral orifice after subtotal cystectomy with uretero-cutaneostomy. Of 22 patients, 15 patients died. Five patients died of bladder cancer, one died of gastic cancer, one died of rectal cancer and the others died of pneumonia, heart failure, sepsis and senility. The five-year survival rate was 41% and the cause-specific five-year survival rate was 75%. Local recurrence was seen only in one patient, who received second intra-operative radiotherapy and recovered well in complete remission. We believe that intra-operative radiotherapy after subtotal cystectomy is useful for patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. (author)

  4. Thrombomodulin expression regulates tumorigenesis in bladder cancer

    International Nuclear Information System (INIS)

    Wu, Chun-Te; Chang, Ying-Hsu; Lin, Paul- Yang; Chen, Wen-Cheng; Chen, Miao-Fen

    2014-01-01

    The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer

  5. Sarcopenia predicts survival outcomes among patients with urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy: a retrospective multi-institution study.

    Science.gov (United States)

    Ishihara, Hiroki; Kondo, Tsunenori; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Hashimoto, Yasunobu; Tanabe, Kazunari

    2017-02-01

    We aimed to evaluate the effect of sarcopenia, a condition of low muscle mass, on the survival among patients who were undergoing radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUT). We retrospectively reviewed consecutive patients with UCUT (cT[any]N0M0) who underwent RNU between 2003 and 2013 at our department and its affiliated institutions. Preoperative computed tomography images were used to calculate each patient's skeletal muscle index, an indicator of whole-body muscle mass. Sarcopenia was defined according to the sex-specific consensus definitions, based on the patient's skeletal muscle and body mass indexes. We analyzed the relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU to identify factors that predicted patient survival. A total of 137 patients were included, and 90 patients (65.7 %) were diagnosed with sarcopenia. Compared to the non-sarcopenic patients, the sarcopenic patients had a significant inferior 5-year RFS (48.8 vs. 79.6 %, p = 0.0002), CSS (57.1 vs. 92.6 %, p sarcopenia was an independent predictor of shorter RFS, CSS, and OS (all, p Sarcopenia was an independent predictor of survival among patients with UCUT who were undergoing RNU.

  6. Carcinoma of the renal pelvis and ureter

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    Fernando Korkes

    2006-12-01

    Full Text Available OBJECTIVE: To assess the occurrence of upper urinary tract urothelial tumors (UUTT in Brazil. MATERIALS AND METHODS: We performed a clinical and histopathologic study of 33 patients who were diagnosed with a malignant neoplasm in the renal pelvis or ureter in the period of 1994 to 2004, in a single institution. RESULTS: Among the patients with upper urinary tract carcinoma, 70% were males and 30% females, with mean age of 65 ± 16 years (ranging from 31 to 91 years. Nineteen patients presented renal pelvis tumor (58%, 9 ureteral tumor (27% and 5 synchronic pelvic and ureteral tumors (15%. Renal pelvis tumors represented 2.8% of all the urothelial neoplasms, and 11.4% of all renal neoplasms treated in the same period. Ureteral tumors represented 1.6% of all the urothelial malignancies surgically managed in these 11 years. Tobacco smoking was the most common risk factor, and analgesic abuse was not reported by those patients. Most carcinomas were high-grade and muscle-invasive. Mean time to diagnosis was 7 months, being hematuria the most common symptom. CONCLUSIONS: A high association was also found between UUTT and bladder urothelial carcinoma. UUTT were mostly seen in men in their seventies and related to a high overall and cancer-related mortality rate. The overall disease-specific survival was 40%, much lower than found in most of the reported series.

  7. Hexavalent chromium induces chromosome instability in human urothelial cells

    International Nuclear Information System (INIS)

    Wise, Sandra S.; Holmes, Amie L.; Liou, Louis; Adam, Rosalyn M.; Wise, John Pierce Sr.

    2016-01-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.

  8. Ureteral Involvement Is Associated with Poor Prognosis in Upper Urinary Tract Urothelial Carcinoma Patients Treated by Nephroureterectomy: A Multicenter Database Study.

    Science.gov (United States)

    Waseda, Yuma; Saito, Kazutaka; Ishioka, Junichiro; Matsuoka, Yoh; Numao, Noboru; Fujii, Yasuhisa; Sakai, Yasuyuki; Koga, Fumitaka; Okuno, Tetsuo; Arisawa, Chizuru; Kamata, Shigeyoshi; Nagahama, Katsuji; Masuda, Hitoshi; Yonese, Junji; Kageyama, Yukio; Noro, Akira; Tsujii, Toshihiko; Morimoto, Shinji; Gotoh, Shuichi; Kihara, Kazunori

    2016-08-01

    The prognostic significance of tumor location for patients with upper urinary tract urothelial carcinoma (UUT-UC) has been disputed. Several papers have reported that ureteral cancer is associated with worse prognosis. To investigate the prognostic significance of the presence of ureteral tumors in UUT-UC patients who underwent radical nephroureterectomy (RNU). In this multicenter retrospective study, 1068 eligible patients (median follow-up: 40 mo [interquartile range: 17-77 mo]) were divided into three groups based on tumor location: renal pelvic, ureteral, and both-regional (having both renal pelvic and ureteral tumors). The ureteral and both-regional groups were subsequently integrated into the ureteral involvement group to evaluate its prognostic impact. All patients underwent RNU. The prognostic impact of tumor location on survival was analyzed. The renal pelvic, ureteral, and both-regional groups consisted of 507 (47.5%), 430 (40.3%), and 131 (12.3%) patients, respectively. The ureteral and both-regional groups had a higher rate of lymphovascular invasion and lymph node metastasis compared with the renal pelvic group. The renal pelvic and both-regional tumors presented more frequently with locally advanced stages (pT3/T4) compared with the ureteral tumors. The 5-yr cancer-specific survival (CSS) and progression-free survival (PFS) rates of patients in the ureteral (70.5% and 66.7%, respectively) and both-regional groups (64.8% and 57.8%, respectively) were significantly worse than those in the renal pelvic group (81.9% and 78.1%, respectively). In a multivariate analysis, the presence of ureteral involvement was a significant prognostic factor for CSS (hazard ratio [HR]: 1.50; p=0.006) and PFS (HR: 1.35; p=0.023). This study is inherently limited by the biases associated with its retrospective and multicenter design. The presence of ureteral involvement had a significant impact on the survival of surgically treated UUT-UC patients associated with a poor

  9. Urology and nephrology update: bladder and kidney cancer.

    Science.gov (United States)

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

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

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    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.

  11. Studies on the cellular immune response in patients with upper urinary tract carcinoma compawed with those in patients with bladder carcinoma and it's postoperative change

    International Nuclear Information System (INIS)

    Sakai, Shunsuke

    1980-01-01

    Non-specific cellular immunity of patients with upper urinary tract carcinoma was studied by PPD reaction (in vivo or in vitro), lymphocytes subpopulation and macrophage migration inhibition test and the results were compared with those of patients with bladder carcinoma or benign urological diseases. 1) The preoperative cellular immunity of the malignant tumor group gave low values as compared to that in the benign disease group. Although the cellular immunity of patients with renal cell carcinoma showed no difference in the points of their grade and stage, significant differences were noted in patients with bladder carcinoma. The patients with renal pelvic and ureter carcinoma appeared to be similar to the patients with bladder carcinoma in the aspects of immune reactions. 2) In the majority of patients with upper urinary tract and bladder carcinoma, the cellular immunity after complete removal of the carcinoma gave an increased value of each marker as compared to the preoperative value. 3) The cellular immunity after irradiation decreased in the majority of the cases in terms of PPD reaction and T-cell ratio in lymphocyte subpopulation. Irradiation of 4000 - 6000 Rad. showed greater influence on T-cell than on B-cell, but influence of irradiation on cellular immunity was not different by irradiation dose. 4) The cellular immunity indicated decreased values for one to two months after discontinuation of irradiation, but then it showed a tendency to increase in terms of PPD and lymphocytes subpopulation in the patients with satisfactory postoperative courses. 5) Through the pre and postoperative courses, the immunity of the carcinomatous stage seems to be reflected better by the T-cell ratio than by the absolute number of T-cell. It is likely that macrophage migration inhibition test shows much sharper reaction than PPD reaction. (author)

  12. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

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    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.

  13. Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

    Science.gov (United States)

    Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

    2006-05-01

    We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

  14. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; Théodore, Christine; Demkov, Tomasz

    2009-01-01

    PURPOSE: Vinflunine (VFL) is a new microtubule inhibitor that has activity against transitional cell carcinoma of urothelial tract (TCCU). We conducted a randomized phase III study of VFL and best supportive care (BSC) versus BSC alone in the treatment of patients with advanced TCCU who had......) subsequently escalated to 320 mg/m(2)) or BSC. RESULTS: Three hundred seventy patients were randomly assigned (VFL + BSC, n =253; BSC, n = 117). Both arms were well balanced except there were more patients with PS more than 1 (10% difference) in the BSC arm. Main grade 3 or 4 toxicities for VFL + BSC were...

  15. 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...

  16. Characteristics of Patients With Transitional Cell Carcinoma of the Urinary Bladder in Kermanshah Province, Iran.

    Science.gov (United States)

    Payandeh, Mehrdad; Sadeghi, Masoud; Sadeghi, Edris

    2015-12-01

    In Iran, bladder cancer is one of the most common malignancy sites among men, ranking as the fifth with age-specific incidence rate of about 11.2 per 100,000 males. It causes 8% of all malignancies in men and 3% of all malignancies in women. The aim of this study was to report the epidemiological, clinical, and pathological features of bladder cancer in Western Iran compared to other studies. This is a retrospective study between 2003 and 2014 when forty-four patients with bladder cancer referred to Hematology Clinic of Kermanshah, Kermanshah, Iran. Transitional cell carcinoma (TCC) was in 39 patients. In the patients with TCC, the mean age in diagnosis for them was 65.43 years (± 11.64), range of age 42 to 88 years , thirty-three patients (84.6%) were male, and six patients (15.4%) were female. Of 39 patients with TCC, 16 patients (41%) had metastasis. 21 patients (53.8%) were smoker and 16 patients (41%) had muscle invasive. 35 patients (89.7%) were histological high grade and the rest of patients were low grade. In the TCC patients with increasing age, metastasis and muscle invasive increased. The age presentation of TCC in West Iran was similar to other studies. Percentage of patients with high grade is more than other studies, and also the number of patients with bladder cancer has increased during last 4 years. For better results, studies must be conducted with more patients in this area, and other areas of Iran with checking of genetics, race and environmental factors.

  17. Immunohistochemical Expression of Cyclooxygenase-2 in Urinary Bladder Transitional Cell Carcinomas

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    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.

  18. Primary signet-ring cell carcinoma of the urinary bladder successfully managed with cisplatin and gemcitabine: a case report

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    El Ammari Jalal Eddine

    2013-02-01

    Full Text Available Abstract Introduction Primary signet-ring cell carcinoma of the urinary bladder is a rare variant of mucus-producing adenocarcinoma constituting approximately 0.5% to 2.0% of all primary carcinomas of the bladder. This tumor initially presents as a high-grade, high-stage lesion and diffusely invades the bladder wall without forming intraluminal growth. The patients have no specific symptoms, which leads to delayed diagnosis and poor prognosis. Case presentation We report the case of a 51-year-old Moroccan Berber man consulting for gross hematuria. Ultrasonography and a computed tomography scan found a bladder tumor diffusely invading the bladder wall. A histopathological examination of the tumor chips from a transurethral resection of the bladder revealed signet-ring cell adenocarcinoma. The gastrointestinal tract exploration did not reveal any other tumor localization. A radical cystectomy and adjuvant cisplatin and gemcitabine chemotherapy were therefore performed resulting in 18 months of survival without metastasis and a good quality of life within that time. Conclusion The rarity and the successful management with carboplatin and gemcitabine as adjuvant chemotherapy of this entity, which is rarely reported in the literature, are two remarkable characteristics described in this case report.

  19. Evaluation of the Clinical Utility of Renin-Angiotensin System Inhibitors in Patients Undergoing Radical Surgery for Urothelial Carcinoma of the Upper Urinary Tract.

    Science.gov (United States)

    Yoshida, Takashi; Matsuzaki, Tomoaki; Murota, Takashi; Kawa, Gen; Matsuda, Tadashi; Kinoshita, Hidefumi

    2017-12-01

    Renin-angiotensin system (RAS) inhibitors are effective for treating patients with cancer. The present study evaluated the impact of RAS inhibitors, including angiotensin-2 converting enzyme inhibitors and angiotensin 2 receptor blockers, after patients underwent radical surgery for upper urinary tract urothelial carcinoma (UTUC). This retrospective study included 312 patients with nonmetastatic UTUC who underwent radical surgery. The oncological outcomes of patients treated or not treated with RAS inhibitors following surgery were evaluated. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method and Cox regression analysis. The median follow-up duration after radical surgery was 44.7 months. The 5-year RFS, CSS, and OS rates of patients who did or did not receive RAS inhibitors were 82.3% versus 68.9% (P = .018), 88.9% versus 71.8% (P = .0044), and 68.7% versus 61.8% (P = .047), respectively. Multivariable analyses revealed that the use of RAS inhibitors was an independent prognostic factor for RFS, CSS, and OS (hazard ratio [HR] 0.48, P = .013; HR 0.31, P = .002; and HR 0.52, P = .01, respectively). Moreover, patients treated with RAS inhibitors versus untreated patients had better 5-year RFS compared with those in the pT2 and < pN1 subgroups (pT2: 100.0% vs. 62.2%, P = .014 and < pN1: 87.2% vs. 74.7%, P = .034). RAS inhibitors significantly improved RFS, CSS, and OS of patients with UTUC who underwent radical surgery. These agents may be particularly beneficial for patients with stage pT2 or < pN1 disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. H2O2 generation by BCG induces the cellular oxidative stress response required for BCG’s direct effects on urothelial carcinoma tumor biology

    Science.gov (United States)

    Shah, Gopitkumar; Zielonka, Jacek; Chen, Fanghong; Zhang, Guangjian; Cao, YanLi; Kalyanaraman, Balaraman; See, William

    2018-01-01

    INTRODUCTION Exposure of urothelial carcinoma (UC) cells to Bacille Calmette Guerin (BCG) affects cellular redox status and tumor cell biology but mechanism(s) remains unclear. This study examined free radical production by BCG, and in tumor cells in response to BCG, using global profiling of Reactive oxygen species/reactive nitrogen species (ROS/RNS). The relationship between free radical generation and downstream cellular events was evaluated. MATERIALS AND METHODS Using fluorescent probes, global profiling of ROS/RNS was carried out in Heat killed (hk) BCG, viable BCG, and in two UC cell lines post BCG exposure (253J and T24). Inhibition of BCG internalization and pharmacologic scavenging of H2O2 was studied for their effect on cellular ROS/RNS generation and various physiological end points. RESULTS Viable BCG produced H2O2 (Hydrogen peroxide) and O2− (Superoxides) but did not show NO (Nitric oxide) generation. Loss of viability decreased production of H2O2 by 50% compared to viable BCG. BCG internalization was necessary for BCG induced ROS/RNS generation in UC cells. Pharmacologic H2O2 scavenging reversed the ROS/RNS mediated signaling in UC cells. BCG dependent alterations in tumor biology including intracellular signaling, gene expression and cytotoxicity were dependent on free radical generation. CONCLUSIONS This study demonstrates the importance of free radical generation by BCG, and intracellular generation of Cellular oxidative stress (COS), on the UC cell response to BCG. Manipulation of the BCG induced COS represents a potential target for increasing BCG efficacy. PMID:24928267

  1. Trends in utilisation, perioperative outcomes, and costs of nephroureterectomies in the management of upper tract urothelial carcinoma: a 10-year population-based analysis.

    Science.gov (United States)

    Tinay, Ilker; Gelpi-Hammerschmidt, Francisco; Leow, Jeffrey J; Allard, Christopher B; Rodriguez, Dayron; Wang, Ye; Chung, Benjamin I; Chang, Steven L

    2016-06-01

    To perform a population-based study to evaluate contemporary utilisation trends, morbidity, and costs associated with nephroureterectomies (NUs), as contemporary data for NUs are largely derived from single academic institution series describing the experience of high-volume surgeons and it is unclear if the same favourable results occur at a national level. Using the Premier Hospital Database, we captured patients undergoing a NU with diagnoses of renal pelvis or ureteric neoplasms from 2004 to 2013. We fitted regression models, adjusting for clustering by hospitals and survey weighting to evaluate 90-day postoperative complications, operating-room time (OT), prolonged length of stay (pLOS), and direct hospital costs among open (ONU), laparoscopic (LNU) and robotic (RNU) approaches. After applying sampling and propensity weights, we derived a final study cohort of 17 254 ONUs, 13 317 LNUs and 3774 RNUs for upper tract urothelial carcinoma (UTUC) in the USA between 2004 and 2013. During that period, minimally invasive NU (miNU) increased from 36% to 54%, while the total number of NUs decreased by nearly 20%. No differences were noted in perioperative outcomes between the three surgical approaches, including when the analysis was restricted to the highest-volume hospitals and highest-volume surgeons. The OT was longer for LNU and RNU (P ONU for UTUC with a recent surge in RNU, along with a concurrent reduction in total NUs performed. Despite not being associated with a clinically significant improvement in perioperative outcomes, the costs for miNUs were consistently higher. However, higher hospital volumes suggest a potential cost containment strategy when performing miNUs. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  2. Diagnostic Role of F-18 Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Restaging of Upper Urinary Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Hakan Öztürk

    2017-09-01

    Full Text Available Objective: To retrospectively evaluate contribution of F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (18FDG-PET/CT to re-staging of upper urinary tract urothelial carcinoma (UTUC. Materials and Methods: This study included a total of 17 patients (12 males and 5 females, who underwent nephroureterectomy due to UTUC and 18FDG-PET/CT between July 2007 and April 2015. The mean age of the patients was 64.3±9.96 years (range: 45-79. 18FDG-PET/CT was performed for re-staging 6-24 months after nephroureterectomy (mean: 18 months. Nearly 1 hour after intravenous injection of 555 MBq of F-18 FDG, the patients underwent whole-body PET scanning from the skull base to the upper thighs after 6 hours of fasting, and nearly 1 hour after all body CT scanning performed in the craniocaudal direction. By using CT data for attenuation correction, FDG-PET images were reconstructed. Results: 18FDG-PET/CT scans proved negative findings in three patients (17.7% and positive findings in 14 patients (82.3%. Suspicious recurrent or metastatic lesions were confirmed by histopathology or clinical follow-up. Sensitivity of 18FDG-PET/CT was 93% and the specificity was 75%. Conclusion: 18FDG-PET/CT defines local recurrence and far metastases with high specificity in re-staging of operated UTUC. It is thought that the procedure could play an important role in decisions regarding radiotherapy or chemotherapy and post-operative follow-up after the operation and could affect the whole decision-making process.

  3. 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.

  4. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

    International Nuclear Information System (INIS)

    Chung, Chi-Jung; Huang, Chao-Yuan; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Su, Chien-Tien; Hsueh, Yu-Mei

    2013-01-01

    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.

  5. Clinical Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Upper Tract Urothelial Carcinoma: Impact on Detection of Metastases and Patient Management.

    Science.gov (United States)

    Tanaka, Hajime; Yoshida, Soichiro; Komai, Yoshinobu; Sakai, Yasuyuki; Urakami, Shinji; Yuasa, Takeshi; Yamamoto, Shinya; Masuda, Hitoshi; Koizumi, Mitsuru; Kohno, Atsushi; Fukui, Iwao; Yonese, Junji; Fujii, Yasuhisa; Kihara, Kazunori

    2016-01-01

    To determine the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis and its impact on patient management with upper tract urothelial carcinoma (UTUC). Consecutive patients with UTUC underwent 18F-FDG PET/CT after CT for initial staging (n = 47) and for restaging at recurrence (n = 9). Diagnostic accuracy for detecting metastases with PET/CT and CT was compared statistically. The impact of PET/CT on patient management was assessed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. In the lesion-based analysis, 142 lesions were diagnosed as metastases. The sensitivity of PET/CT was significantly better than that of CT (85 vs. 50%, p = 0.0001). In the patient-based analysis, 22 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy of PET/CT tended to be superior to those of CT, but these values were not significantly different (95, 91, and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, and 0.063, respectively). The clinicians changed their assessments of disease extent and management plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. The diagnostic accuracy of PET/CT for detecting metastasis was superior to that of CT. PET/CT provided additional information to the CT-based staging, which had an impact on patient management. © 2015 S. Karger AG, Basel.

  6. 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 r...

  7. Total cystectomy for treatment of transitional cell carcinoma of the urethra and bladder trigone in a dog.

    Science.gov (United States)

    Boston, Sarah; Singh, Ameet

    2014-03-01

    To report total cystectomy with reimplantation of the ureters in the proximal aspect of the vagina. Case report. An 11-year-old female spayed Vizsla with spontaneously occurring transitional cell carcinoma of the urethra and bladder. After initial treatment for transitional cell carcinoma of the bladder trigone with urethral stent placement and chemotherapy, the dog developed urinary incontinence 2 months after stent placement. Eleven months after initial diagnosis, the dog developed pulmonary metastasis and local progression, leading to bilateral ureteral dilatation. After palliative radiation, total cystectomy was performed. The owners elected euthanasia 442 days after original presentation and 92 days after total cystectomy. Euthanasia was unrelated to the surgical procedure, but was related to the primary disease. Total cystectomy is a technically feasible procedure that should be considered for the treatment of bladder cancer in dogs. © Copyright 2014 by The American College of Veterinary Surgeons.

  8. 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.

  9. Bladder cancer and schistosomiasis

    International Nuclear Information System (INIS)

    Zaghloul, M.S.

    2012-01-01

    Schistosoma-associated bladder cancer was believed, for several decades, to be a completely unique entity of disease, different from urothelial cancer. This was probably due to its distinct clinico pathologic and demographic features that varied from those of urothelial entity. The carcinogenesis is an extremely complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation regulation process. In bladder cancer, many of these carcinogenic cascades were not fully documented or somewhat conflicting. In spite of the efforts performed, much is still needed to explore the presence or absence of the carcinogenic difference with a different etiology. The control of schistosomiasis in certain countries and the subsequent decrease in the intensity of infestation showed changing of features approaching that of urothelial tumors. However the schistosoma-associated bladder cancer presented in more advanced stages than schistosoma-non associated urothelial cancer. More recently, data are gathered that, upon applying the same treatment protocol and management care, stage by stage comparison of the treatment end-results were found to be similar in bladder cancer patients with a different etiology. All treatment options; including radical cystectomy with or without adjuvant or neoadjuvant chemo- or radiotherapy or tri modality bladder preserving treatment seem to lead to similar end-results regardless of etiologic factor(s) implicated in bladder cancer development.

  10. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Sager, E.M.

    1991-01-01

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  11. Intravesical chemotherapy in non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Sima P Porten

    2015-01-01

    Full Text Available Non-muscle-invasive bladder cancer (NMIBC is characterized by a tendency for recurrence and capacity for progression. Intravesical instillation therapy has been employed in various clinical settings, which are summarized within this review. Several chemotherapeutic agents have shown clinical efficacy in reducing recurrence rates in the post-transurethral resection of bladder tumor (TURBT setting, including mitomycin C (MMC, doxorubicin, and epirubicin. Mounting evidence also supports the use of intravesical MMC following nephroureterectomy to reduce later urothelial bladder recurrence. In the adjuvant setting, bacillus Calmette-Guérin (BCG immunotherapy is an established first-line agent in the management of carcinoma in situ (CIS and high-grade non muscle invasive urothelial carcinoma (UC. Among high and intermediate-risk patients (based on tumor grade, size, and focality improvements in disease-free intervals have been seen with adjunctive administration of MMC prior to scheduled BCG dosing. Following failure of first-line intravesical therapy, gemcitabine and valrubicin have demonstrated modest activity, though valrubicin remains the only agent currently Food and Drug Administration (FDA-approved for the treatment of BCG-refractory CIS. Techniques to optimize intravesical chemotherapy delivery have also been explored including pharmacokinetic methods such as urinary alkalization and voluntary dehydration. Chemohyperthermia and electromotive instillation have been associated with improved freedom from recurrence intervals but may be associated with increased urinary toxicity. Improvements in therapeutic selection may be heralded by novel opportunities for genomic profiling and refinements in clinical risk stratification.

  12. Polyps and masses of the pediatric urinary bladder: a 21-year pathology review.

    Science.gov (United States)

    Huppmann, Alison R; Pawel, Bruce R

    2011-01-01

    Although not uncommon in adults, bladder tumors are rare in children. In addition, the histologic types of tumors seen in the pediatric population differ from those seen in adults. Although rhabdomyosarcoma is the most common pediatric bladder tumor, many other benign, malignant, and reactive lesions can be encountered. All may present clinically as a mass or polyp in the bladder. This study was designed to describe the pathology and patient demographics of pediatric bladder masses, because there are few studies describing these entities. Retrospectively reviewing our experience over a 21-year period, we identified 98 specimens from 65 patients with polyps or masses in the urinary bladder. As expected, the most frequent diagnosis was rhabdomyosarcoma. This was followed by fibroepithelial polyp and a variety of additional nonurothelial tumors. Only 7 urothelial tumors were identified, including 1 low-grade papillary urothelial carcinoma. Inflammatory lesions, such as cystitis cystica and nephrogenic adenoma, were invariably associated with an irritating factor when a history was provided. Our findings emphasize that diagnoses made in the pediatric urinary bladder are distinct from those in adults, although a wide variety of lesions may still be seen.

  13. Clinical significance of determination of changes of serum SE-cad, SF and TSGF levels after operation in patients with carcinoma of urinary bladder

    International Nuclear Information System (INIS)

    Zhang Jibang; Qin Wenjing

    2008-01-01

    Objective: To explore the clinical significance of changes of serum SE-cad, SF and TSGF levels after operation in patients with carcinoma of urinary bladder. Methods: Serum SE-cad ( with ELISA), SF (with RIA) and TSGF levels (with biochemistry) levels were measured in 36 patients with carcinoma of urinary bladder both before and 3 months after operation as well as in 30 controls. Results: Before operation, in the patients, the serum SE-cad, SF and TSGF levels were significantly higher than those in the controls (P 0.05). Conclusion: Serum SE-cad, SF and TSGF were useful markers for detection of carcinoma of urinary bladder. (authors)

  14. Lectin immunohistochemical evaluation of human bladder carcinomas. A comparison of Carnoy's and formalin fixation.

    Science.gov (United States)

    Okamura, T; Ueda, K; Ohtaguro, K; Inoue, K; Washida, H; Mori, M; Tatemoto, Y; Fukushima, S

    1993-10-01

    A lectin immunohistochemical analysis of 51 human bladder carcinomas, including 44 cases of transitional cell carcinoma (TCC) (G1, 15 cases; G2, 17 cases; G3, 12 cases) and 7 cases of squamous cell carcinoma (SCC), was performed. Tissues were obtained by cold punch biopsies, fixed in Carnoy's or 10% formalin solution, stained for binding of 10 different lectins, and evaluated under the light microscope. The lectins used were concanavalin agglutinin (Con A), soybean agglutinin (SBA), Lotus tetragonolobus agglutinin (LTA), Dolichos biflorusa agglutinin (DBA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA1), Ulex europaeus agglutinin I, II (UEA-I, II), wheat germ agglutinin (WGA), and Pisum sativum agglutinin (PEA). TCC prepared with Carnoy's fixation tended to show moderately positive Con A, UEA-I, and WGA reactions for G1, and strongly positive reactions for G2 and G3 lesions. UEA-II was mainly negative in G1, but tended to increase to become moderate in G3. DBA tended to show a moderately positive reaction in G1 and G2, but was mainly negative in G3. With formalin fixation, only RCA1 demonstrated grade specific variation, tendency to react moderately in the G1 and G2 cases, and strongly in G3. There were no further differences among the histopathological grades of TCC for other lectins. Thus, Carnoy's fixation appears superior for distinguishing between grades of lesions. SCC tended to react more strongly than TCC with all the various lectins except PEA, independent of fixation.

  15. Rhodamine dyes as potential agents for photochemotherapy of cancer in human bladder carcinoma cells

    International Nuclear Information System (INIS)

    Shea, C.R.; Chen, N.; Wimberly, J.; Hasan, T.

    1989-01-01

    The phototoxicity in vitro of rhodamine 123 and tetrabromo rhodamine 123 (TBR) was compared, in order to assess their photochemotherapeutic potential. Exposure to 514.5-nm radiation from an argon ion laser caused phototoxicity in MGH-U1 bladder carcinoma cells previously treated with either dye at 10 microM for 30 min. As assessed by colony formation and cellular morphology, TBR was markedly more phototoxic than rhodamine 123, reflecting increased intersystem crossing of TBR to the triplet manifold via spin-orbital coupling induced by the heavy bromine atoms. Photoreactions of TBR very efficiently generated singlet oxygen ( 1 O 2 ) in solution; furthermore, irradiation of TBR-treated cells was significantly more toxic when performed in the presence of deuterium oxide, an enhancer of damage caused by 1 O 2 . Retention of fluorescence in TBR-treated cells was enhanced by irradiation, indicating that a stable photoproduct may be formed in reaction with cellular components

  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......, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction......, estimates of nuclear mean profile area (aH(nuc)), nuclear profile density index (NI), and mitotic profile density index (MI) were obtained by stereologic and morphometric techniques. RESULTS: The T-stage and morphologic grade of malignancy were closely cross-correlated (+0.63

  17. 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......, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction...... of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC....

  18. 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...

  19. Total retroperitoneal laparoscopic nephroureterectomy with bladder-cuff resection for upper urinary tract transitional cell carcinoma.

    Science.gov (United States)

    Fang, Zhenqiang; Li, Longkun; Wang, Xiangwei; Chen, Wei; Jia, Weisheng; He, Fan; Shen, Chongxing; Ye, Gang

    2014-12-01

    Open nephroureterectomy (ONU) and bladder cuff resection (ONU-BCR) has been the gold standard of surgical treatment for upper urinary tract transitional cell carcinoma (UUT-TCC). The aim of this study is to introduce a modified total retroperitoneal laparoscopic nephroureterectomy (LNU) with bladder-cuff resection (LNU-BCR) method for treating UUT-TCC and compare its clinical efficacy with ONU-BCR. Sixty-five patients with UUT-TCC, who underwent ONU-BCR (n = 36) or LNU-BCR (n = 29) between January 2008 and June 2012, were analyzed in this retrospective study. Perioperative data as well as incidence of disease recurrence at the primary site or distant metastasis was compared in patients with at least 6 months follow-up. As compared with patients with ONU-BCR, the patients with LNU-BCR had significantly shorter operative time, lower estimated blood loss, shorter time to oral intake, lower analgesic dose, shorter duration of analgesic use, shorter duration of incision drainage tube, shorter time to ambulation out of bed and reduced postoperative hospital stay (all, p ONU-BCR with the advantages of reduced invasiveness, bleeding and hospitalization.

  20. Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

    Science.gov (United States)

    Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu

    2017-09-01

    The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G 1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Blood tests and prognosis in bladder carcinomas treated with definitive radiotherapy

    International Nuclear Information System (INIS)

    Hannisdal, E.; Fossa, S.D.; Host, H.

    1993-01-01

    The value of some commonly recorded blood tests as prognostic factors in patients with bladder carcinomas treated with definitive radiotherapy has been assessed. This study included 202 consecutive patients (T2, n=46; T3, n=82 and T4, n=74) treated during the period 1980-1987. The median total dose received was 56 Gy [50-67] and the median cumulative radiation effect was 1750 reu (radiation effect unit) (1515-1823). The blood tests examined in survival analyses were erythrocyte sedimentation rate (ESR), hemoglobin (Hb), leucocyte and thrombocyte count, alkaline phosphatase (ALP), γ-glutamyltransferase (GT), lactate dehydrogenase (LD), creatinine and albumin. In the univariate survival analyses six blood tests were significant prognostic factors (ESR, albumin, creatinine, Hb, ALP and GT). In the multivariate analysis of all 202 patients, the following five variables were significantly associated with shorter survival: T4 tumors, ESR > 30 mm/h, albumin 400 U/I and age >75 years. Our conclusion is that several commonly recorded blood tests are powerful prognostic factors in bladder cancer treated with definitive radiotherapy. These tests can replace other more expensive laboratory investigations used for prognostication. (author). figs. tabs

  2. Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Diagnostic Evaluation of Carcinoma Urinary Bladder: Comparison with Computed Tomography

    International Nuclear Information System (INIS)

    Chakraborty, Dhritiman; Mittal, Bhagwant Rai; Kashyap, Raghava; Mete, Utham Kumar; Narang, Vikram; Das, Ashim; Bhattacharya, Anish; Khandelwal, Niranjan; Mandal, Arup K.

    2014-01-01

    Bladder carcinoma is the most frequent tumor of the urinary tract and accounts 7% of all malignancies in men and 2% of all malignancies in women. This retrospective study was carried out to assess the diagnostic utility of F18-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the imaging evaluation of bladder carcinoma. Seventy-seven consecutive patients diagnosed to have carcinoma urinary bladder referred for F18-FDG PET/CT were included in this study. Thirty-four patients were for initial staging after transurethral biopsy and remaining 43 patients were for restaging. All patients also underwent CT scan of the abdomen and pelvis. PET/CT findings were correlated with diagnostic CT scan and histopathological findings. In 30 of the 34 patients for initial staging, both PET/CT and CT confirmed the primary lesion in the bladder. Histopathology report was available in 23 patients. Lymph nodes FDG uptake reported to be metastatic in 10/23 patients while CT detected lymph node metastasis in 12 patients. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy have been calculated to be 87.5%, 80%, 70%, 92%, 82% for PET/CT and 66%, 57%, 50%, 72%, 60% for CT respectively. PET/CT detected metastatic disease in 8 patients whereas CT detected in 4 patients. Of the 43 patients for restaging, local recurrence was detected in 24 patients on both PET/CT and CT. Histopathology report was available in 17 patients. Sensitivity, specificity, PPV, NPV and accuracy were 85%, 60%, 60%, 85%, 70% for PET/CT and 80%, 50%, 40%, 85%, 58% for CT respectively. Nineteen patients were detected to have metastatic disease by PET/CT, whereas CT detected metastases in 11 patients. F-18 FDG PET/CT is a very useful modality in pre-operative staging and monitoring after surgery, chemotherapy or radiotherapy of patients with carcinoma urinary bladder

  3. Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis

    International Nuclear Information System (INIS)

    Xie, Q.; Zhang, J.; Wu, P.-H.; Jiang, X.-Q.; Chen, S.-L.; Wang, Q.-L.; Xu, J.; Chen, G.-D.; Deng, J.-H.

    2005-01-01

    AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p<0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r=0.938, p<0.001) and histological grade (Spearman rank correlation; r=0.734, p<0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r=0.087, p=0.410) and MVD (Spearman rank correlation, r=0.103, p=0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer

  4. 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

  5. CYTOKINE PRODUCTION BY THE HUMAN BLADDER-CARCINOMA CELL-LINE T24 IN THE PRESENCE OF BACILLUS-CALMETTE-GUERIN (BCG)

    NARCIS (Netherlands)

    de Reijke, T. M.; Vos, P. C.; de Boer, E. C.; Bevers, R. F.; de Muinck Keizer, W. H.; Kurth, K. H.; Schamhart, D. H.

    1993-01-01

    The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T 24 treated with BCG was investigated. A 24-h treatment of

  6. Hypofractionated Whole-Brain Radiotherapy for Multiple Brain Metastases From Transitional Cell Carcinoma of the Bladder

    International Nuclear Information System (INIS)

    Rades, Dirk; Meyners, Thekla; Veninga, Theo; Stalpers, Lukas J.A.; Schild, Steven E.

    2010-01-01

    Purpose: Brain metastases in bladder cancer patients are extremely rare. Most patients with multiple lesions receive longer-course whole-brain radiotherapy (WBRT) with 10 x 3 Gy/2 weeks or 20 x 2 Gy/4 weeks. Because its radiosensitivity is relatively low, metastases from bladder cancer may be treated better with hypofractionated radiotherapy. This study compared short-course hypofractionated WBRT (5 x 4 Gy/1 week) to longer-course WBRT. Methods and Materials: Data for 33 patients receiving WBRT alone for multiple brain metastases from transitional cell bladder carcinoma were retrospectively analyzed. Short-course WBRT with 5 x 4 Gy (n = 12 patients) was compared to longer-course WBRT with 10 x 3 Gy/20 x 2 Gy (n = 21 patients) for overall survival (OS) and local (intracerebral) control (LC). Five additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, and extracranial metastases. The Bonferroni correction for multiple tests was used to adjust the p values derived from the multivariate analysis. p values of <0.025 were considered significant. Results: At 6 months, OS was 42% after 5 x 4 Gy and 24% after 10 x 3/20 x 2 Gy (p = 0.31). On univariate analysis, improved OS was associated with less than four brain metastases (p = 0.021) and almost associated with a lack of extracranial metastases (p = 0.057). On multivariate analysis, both factors were not significant. At 6 months, LC was 83% after 5 x 4 Gy and 27% after 10 x 3/20 x 2 Gy (p = 0.035). Improved LC was almost associated with a KPS of ≥70 (p = 0.051). On multivariate analysis, WBRT regimen was almost significant (p = 0.036). KPS showed a trend (p = 0.07). Conclusions: Short-course WBRT with 5 x 4 Gy should be seriously considered for most patients with multiple brain metastases from bladder cancer, as it resulted in improved LC.

  7. Preoperative C-reactive protein as a prognostic predictor for upper tract urothelial carcinoma: A systematic review and meta-analysis.

    Science.gov (United States)

    Luo, You; Fu, Sheng Jun; She, Dong Li; Xiong, H U; Yang, L I

    2015-07-01

    Upper tract urothelial carcinoma (UTUC) is a relatively rare and highly aggressive tumor. However, the prognosis of UTUC is rarely predicted accurately due to the lack of reliable biomarkers. C-reactive protein (CRP) has been found to be correlated with several types of cancer. In this study, we performed a systematic review and meta-analysis to determine the association between CRP levels and prognosis in UTUC. A computerized search was conducted through PubMed, Embase, Web of Science, the Cochrane Library and CBM databases to identify clinical studies that have evaluated the association between preoperative CRP levels and prognosis of UTUC. The prognostic outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). We extracted and synthesized corresponding hazard ratios (HRs) and confidence intervals (CIs) using Review Manager 5.3 software. We identified 7 retrospective cohort studies including a total of 1,919 patients and analyzed these studies using univariate and multivariate models. Our meta-analysis results revealed that RFS and CSS were significantly different between patients with elevated CRP levels and those with low CRP levels (P<0.0001 and P<0.00001, respectively); however, that was not the case for OS (P=0.22) in the multivariate or the univariate model. The pooled HR of RFS was 2.90 (95% CI: 1.87-4.51, P<0.00001) in the univariate analysis and 1.57 (95% CI: 1.26-1.97, P<0.0001) in the multivariate analysis. The pooled HRs of CSS were 2.78 (95% CI: 1.75-4.43, P<0.0001) and 1.64 (95% CI: 1.32-2.03, P<0.00001) in the univariate and multivariate analysis, respectively. However, the pooled HRs of OS were not significant in the univariate [1.24 (95% CI: 0.72-2.15, P=0.43)] or the multivariate analysis [1.24 (95% CI: 0.88-1.75, P=0.22)]. In conclusion, our meta-analysis results suggested that CRP level may be a prognostic predictor in UTUC.

  8. Responses of NBT-II bladder carcinoma cells to conditioned medium from normal fetal urogenital sinus.

    Science.gov (United States)

    Rowley, D R; Tindall, D J

    1987-06-01

    In vitro studies were conducted to determine whether conditioned medium from rat fetal urogenital sinus explants would affect phenotypic characteristics of NBT-II urinary bladder carcinoma cells in culture. NBT-II cells were exposed to medium (30%, v/v) conditioned for 48 h by intact urogenital sinus explants derived from 18-day fetal rats. Upon exposure for 23 h the [3H]thymidine incorporation by NBT-II cells was decreased by 40.3% relative to control cultures. This effect was paralleled by a similar decrease in proliferation. NBT-II cultures decreased in cell number by 32.1 and 45.8% on days 2 and 4, respectively, after exposure to conditioned medium. Although cell proliferation was inhibited, conditioned medium acted to induce an increase in protein secretion. An increase of 18.6% was observed in the incorporation of [35S]methionine into newly synthesized, secreted proteins by NBT-II cells exposed to conditioned medium for 23 h. Morphologically the NBT-II cells exposed to conditioned medium were larger, more spread out, and exhibited a greater array of lamellipodia and filopodia, although [35S]methionine incorporation into cellular proteins was decreased by 11.1%. These results suggest that diffusable factors produced by fetal urogenital sinus explants can induce changes in proliferation, protein synthesis, protein secretion, and phenotypic morphology of NBT-II carcinoma cells in culture.

  9. Initial Results of Bladder Preserving Approach by Chemo-Radiotherapy in Patients with Muscle Invading Transitional Cell Carcinoma

    International Nuclear Information System (INIS)

    Aboziada, M.A.; Hamza, H.; Abdlrahem, A.M.

    2009-01-01

    This study was conducted to test the efficacy and tolerability of trimodality treatment for invasive bladder cancer and to test the possibility of bladder sparing. Methods: This study had been carried out on 50 patients with transitional cell carcinoma (TCC) stage T2- T3 tumors with adequate performance status and renal function. All patients were subjected to maximum transurethral resection of bladder tumors (TURBT). Patients were then subjected to chemo-radiation that was executed in two treatment phases. Phase I was external radiotherapy in the form of 46 Gy /23 fractions /5 weeks to whole pelvis with concurrent cisplatin 40 mg/m 2 weekly. Phase II was 20 Gy /10 fractions /2 weeks to the bladder tumor with concurrent cisplatin 40 mg/m2 weekly. After phase I, patients who had complete response (CR) or partial response (PR) were subjected to phase II and patients who had stationary disease (SD) were subjected to salvage cystectomy. After the end of treatment, patients who had CR were subjected to bladder preservation. Radiological and cystoscopic reevaluation was done to assess the tumor response after phase I and phase II. After completion of the scheduled treatment, patients were under follow up for clinical examination, radiological, and cystoscopic assessment. Results: The treatment schedule was tolerable and was associated with infrequent incidence of moderate toxicity that was easily controlled without interruption of treatment. Bladder preservation was achieved in 72% of patients. The actuarial relapse free survival and overall survival at a median follow up 18 months for patients who were candidate for bladder preservation were 81% and 100%; respectively. Invasive recurrence (16%) sal-Jvaged with cystectomy and superficial recurrence (6%) successfully treated with Bacilles bilie de Calmette- Guerin. Conclusions: This study indicates that in spite of a relatively small number of patients and short follow-up period; the trimodality treatment could be an

  10. The forecasting of radiation injuries of the urinary bladder and rectum in patients with uterine cervix carcinoma

    International Nuclear Information System (INIS)

    Zharinov, G.M.; Gabelov, A.A.

    1984-01-01

    The frequency and degree of severity of radiation in unjuries of the urinary bladder and rectum after combined treatment of 725 patients with uterine cercix carcigoma are analysed. A quantitative index was worked out permi-- tting one to give an ob ective evaluation of the degree of early radiation reactions of the ad acent organs. The determination of the ''radiation injuries prognosis index'' (RIPI) makes it possible to forecast the occurence and degree of severity of late radiation injuries of the urinary bladder and rectum. The evaluation of RIPI mean values in the patients' groups provides an opportunity to oompare the damaging effect of different methods and regiment directly in the process of radiation therapy. The above method improves the potentialities of the forecasting of radiation injuries of the urinary bladder and rectum in patients with uterine cervix carcinoma

  11. Dual effects of radiation bystander signaling in urothelial cancer: purinergic-activation of apoptosis attenuates survival of urothelial cancer and normal urothelial cells.

    Science.gov (United States)

    Bill, Malgorzata A; Srivastava, Kirtiman; Breen, Conor; Butterworth, Karl T; McMahon, Stephen J; Prise, Kevin M; McCloskey, Karen D

    2017-11-14

    Radiation therapy (RT) delivers tumour kill, directly and often via bystander mechanisms. Bladder toxicity is a dose limiting constraint in pelvic RT, manifested as radiation cystitis and urinary symptoms. We aimed to investigate the impact of radiation-induced bystander signaling on normal/cancer urothelial cells. Human urothelial cancer cells T24, HT1376 and normal urothelial cells HUC, SV-HUC were used. Cells were irradiated and studied directly, or conditioned medium from irradiated cells (CM) was transferred to naïve, cells. T24 or SV-HUC cells in the shielded half of irradiated flasks had increased numbers of DNA damage foci vs non-irradiated cells. A physical barrier blocked this response, indicating release of transmitters from irradiated cells. Clonogenic survival of shielded T24 or SV-HUC was also reduced; a physical barrier prevented this phenomenon. CM-transfer increased pro-apoptotic caspase-3 activity, increased cleaved caspase-3 and cleaved PARP expression and reduced survival protein XIAP expression. This effect was mimicked by ATP. ATP or CM evoked suramin-sensitive Ca 2+ -signals. Irradiation increased [ATP] in CM from T24. The CM-inhibitory effect on T24 clonogenic survival was blocked by apyrase, or mimicked by ATP. We conclude that radiation-induced bystander signaling enhances urothelial cancer cell killing via activation of purinergic pro-apoptotic pathways. This benefit is accompanied by normal urothelial damage indicating RT bladder toxicity is also bystander-mediated.

  12. Bioinformatic identification of FGF, p38-MAPK, and calcium signalling pathways associated with carcinoma in situ in the urinary bladder

    International Nuclear Information System (INIS)

    Herbsleb, Malene; Christensen, Ole F; Thykjaer, Thomas; Wiuf, Carsten; Borre, Michael; Ørntoft, Torben F; Dyrskjøt, Lars

    2008-01-01

    Carcinoma in situ (CIS) is believed to be a precursor of invasive bladder cancer. Identification of CIS is a valuable prognostic factor since radical treatment strategies can be offered these patients before the disease becomes invasive. We developed a pathway based classifier approach to predict presence or absence of CIS in patients suffering from non muscle invasive bladder cancer. From Ingenuity Pathway Analysis we considered four canonical signalling pathways (p38 MAPK, FGF, Calcium, and cAMP pathways) with most coherent expression of transcription factors (TFs) across samples in a set of twenty-eight non muscle invasive bladder carcinomas. These pathways contained twelve TFs in total. We used the expression of the TFs to predict presence or absence of CIS in a Leave-One-Out Cross Validation classification. We showed that TF expression levels in three pathways (FGF, p38 MAPK, and calcium signalling) or the expression of the twelve TFs together could be used to predict presence or absence of concomitant CIS. A cluster analysis based on expression of the twelve TFs separated the samples in two main clusters: one branch contained 11 of the 15 patients without concomitant CIS and with the majority of the genes being down regulated; the other branch contained 10 of 13 patients with concomitant CIS, and here genes were mostly up regulated. The expression in the CIS group was comparable to the expression of twenty-three patients suffering from muscle-invasive bladder carcinoma. Finally, we validated our results in an independent test set and found that prediction of CIS status was possible using TF expression of the p38 MAPK pathway. We conclude that it is possible to use pathway analysis for molecular classification of bladder tumors

  13. Spinal tuberculosis with severe neurological symptoms as a complication of intravesical BCG therapy for carcinoma of the bladder.

    Science.gov (United States)

    Białecki, Jerzy; Nowak-Misiak, Mirosława; Rąpała, Kazimierz; Marczyński, Wojciech; Suchodolski, Gracjan; Truszczyńska, Aleksandra

    2016-01-01

    Non-invasive bladder cancer is effectively treated with intravesical BCG therapy. The administration of the BCG vaccine is to destroy the neoplastic lesion or prevent further recurrences. The activity of the vaccine involves boosting the immune system through the stimulation of the inflammation in the bladder. Adverse reactions after this immunotherapy are rare. The aim of the study was to present complications in the form of spinal tuberculosis and serious neurological symptoms that occurred during intravesical BCG immunotherapy for carcinoma of the bladder. The manuscript also describes a method for neurosurgical spinal cord decompression of the thoracic spine. In the first patient, aged 66, after intravesical BCG therapy for bladder carcinoma, back pain and spastic paralysis of the lower limbs were observed. The MRI and CT revealed destruction of the intervertebral disc and vertebral endplates Th11-Th12. Mycobacterium tuberculosis complex bacilli were cultured from the material obtained by puncture aspiration. In the second patient, aged 35 years, during intravesical BCG immunotherapy for carcinoma of the bladder, girdle thoracic spine pain was observed. The MRI and CT of the spine showed visible lesions characteristic of tuberculosis. Immobilization in a plaster corset and implementation of antituberculous treatment resulted in quick relief of the pain and healing of the tuberculosis focus in the spine. The cases described in the work are the first documented reports in the Polish literature of spinal tuberculosis which occurred as a complication of intravesical administration of bacilli Calmette-Guérin. The diagnosis was based on the finding of BCG vaccine bacillus with molecular methods or PCR. Full antimycobacterial treatment was implemented. Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Late effects of radiation therapy for prostate carcinoma: The patient's perspective of bladder, bowel and sexual morbidity

    International Nuclear Information System (INIS)

    Franklin, C.I.V.; Parker, C.A.; Morton, K.M.

    1998-01-01

    The patients' perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire (included as an appendix) which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity. Copyright (1998) Blackwell Science Pty Ltd

  15. 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...... in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present...

  16. 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

    bladder biopsies from 22 patients with primary flat carcinoma in situ (Bergkvist grades III-IV). On average, nuclear vv was 77 microns 3 in nine biopsies with morphologically normal urothelium, 292 microns 3 in 56 isolated primary lesions and 266 microns 3 in lesions of luminal urothelium in 13 biopsies...... carcinoma in situ (nuclear vv = 261 microns 3), the survival was the same in patients with nuclear vv above and below the cut-off point (2P = 0.16). However, the survival curves showed a tendency to differ in the first 2-8 years of observation. Stereological estimates of nuclear vv provide objective...

  17. Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma.

    Science.gov (United States)

    Bahria-Sediki, Islem Ben; Yousfi, Nadhir; Paul, Catherine; Chebil, Mohamed; Cherif, Mohamed; Zermani, Rachida; El Gaaied, Amel Ben Ammar; Bettaieb, Ali

    2016-05-30

    The aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients. Expression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity. T-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2-T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p T-bet expression. Our results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.

  18. TP53 modulating agent, CP-31398 enhances antitumor effects of ODC inhibitor in mouse model of urinary bladder transitional cell carcinoma.

    Science.gov (United States)

    Madka, Venkateshwar; Mohammed, Altaf; Li, Qian; Zhang, Yuting; Kumar, Gaurav; Lightfoot, Stan; Wu, Xueru; Steele, Vernon; Kopelovich, Levy; Rao, Chinthalapally V

    2015-01-01

    Mutations of the tumor suppressor p53 and elevated levels of polyamines are known to play key roles in urothelial tumorigenesis. We investigated the inhibition of polyamines biosynthesis and the restoration of p53 signaling as a possible means of preventing muscle invasive urothelial tumors using DFMO, an ODC-inhibiting agent, and CP-31398 (CP), a p53 stabilizing agent. Transgenic UPII-SV40T male mice at 6weeks age (n=15/group) were fed control diet (AIN-76A) or experimental diets containing DFMO (1000 and 2000 ppm) or 150 ppm CP or both. At 40 weeks of age, all mice were euthanized and urinary bladders were evaluated to determine tumor weight and histopathology. Low-dose DFMO had a moderate significant inhibitory effect on tumor growth (38%, P0.05). CP at 150 ppm alone had a strong inhibitory effect on tumor growth by 80% (PCP (150 ppm) led to significant decrease in tumor weight (70%, PCP and DFMO appears to be a promising strategy for urothelial TCC prevention.

  19. Influence of late-stage chronic kidney disease on overall survival in patients with upper tract urothelial carcinoma following radical nephroureterectomy

    Directory of Open Access Journals (Sweden)

    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.

  20. Polycomb Repressor Complex 1 Member, BMI1 Contributes to Urothelial Tumorigenesis through p16-Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    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.

  1. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.

    Science.gov (United States)

    Petrylak, Daniel P; de Wit, Ronald; Chi, Kim N; Drakaki, Alexandra; Sternberg, Cora N; Nishiyama, Hiroyuki; Castellano, Daniel; Hussain, Syed; Fléchon, Aude; Bamias, Aristotelis; Yu, Evan Y; van der Heijden, Michiel S; Matsubara, Nobuaki; Alekseev, Boris; Necchi, Andrea; Géczi, Lajos; Ou, Yen-Chuan; Coskun, Hasan Senol; Su, Wen-Pin; Hegemann, Miriam; Percent, Ivor J; Lee, Jae-Lyun; Tucci, Marcello; Semenov, Andrey; Laestadius, Fredrik; Peer, Avivit; Tortora, Giampaolo; Safina, Sufia; Del Muro, Xavier Garcia; Rodriguez-Vida, Alejo; Cicin, Irfan; Harputluoglu, Hakan; Widau, Ryan C; Liepa, Astra M; Walgren, Richard A; Hamid, Oday; Zimmermann, Annamaria H; Bell-McGuinn, Katherine M; Powles, Thomas

    2017-11-18

    Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m 2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96-4·47] vs 2·76 months [2·60-2·96]; hazard ratio [HR] 0·757, 95% CI 0·607-0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8-30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4-18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1

  2. Is radical cystectomy mandatory in every patient with variant histology of bladder cancer

    Directory of Open Access Journals (Sweden)

    Ofer N Gofrit

    2011-04-01

    Full Text Available Urothelial carcinomas have an established propensity for divergent differentiation. Most of these "variant tumors" are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%, 57 patients (72% of them had muscle-invasive disease or extensive non-muscle invasive tumors and 22 patients (28% were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (p=0.02. The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (p=0.33. 5 patients (22.7% of variant group and 13 patients (9.03% of conventional group underwent cystectomy during follow-up (p=0.068. Patients with non-muscle invasive variants of bladder cancers can be managed with intra-vesical immunotherapy if tumor is not bulky (>4cm. Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients. Life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.

  3. Urothelial cancers following radiation therapy for cervical cancer

    International Nuclear Information System (INIS)

    Nakata, Seiji; Hasumi, Masaru; Sato, Jin; Mayuzumi, Takuji; Kumasaka, Fuminari; Shimizu, Toshihiro.

    1996-01-01

    Some reports have indicated that bladder cancer is induced by radiation therapy for cervical cancer. We encountered 6 cases of urothelial cancer (5 cases of bladder cancer and 1 case of ureter cancer) following radiation therapy for cervical cancer. Age at the time of diagnosis of cervical cancer ranged from 38 to 66 years, and the average was 51.2±11.0 (S.D.) years old. Age at the time of diagnosis of urothelial cancer ranged from 53 to 83 years, and the average was 67.5±10.3 years old. The interval between the diagnosis of cervical cancer and urothelial cancer ranged from 3 to 25 years, averaging 16.3 years. It is impossible to evaluate the risk of development of urothelial cancer after radiation therapy based on our data. However, it is important to make an effort to diagnose urothelial cancer at an early stage by educating patients (e.g., advising regular urine tests) after the follow-up period to cervical cancer. (author)

  4. Bladder afferent hyperexcitability in bladder pain syndrome/interstitial cystitis.

    Science.gov (United States)

    Yoshimura, Naoki; Oguchi, Tomohiko; Yokoyama, Hitoshi; Funahashi, Yasuhito; Yoshikawa, Satoru; Sugino, Yoshio; Kawamorita, Naoki; Kashyap, Mahendra P; Chancellor, Michael B; Tyagi, Pradeep; Ogawa, Teruyuki

    2014-04-01

    Bladder pain syndrome/interstitial cystitis is a disease with lower urinary tract symptoms, such as bladder pain and urinary frequency, which results in seriously impaired quality of life of patients. The extreme pain and urinary frequency are often difficult to treat. Although the etiology of bladder pain syndrome/interstitial cystitis is still not known, there is increasing evidence showing that afferent hyperexcitability as a result of neurogenic bladder inflammation and urothelial dysfunction is important to the pathophysiological basis of symptom development. Further investigation of the pathophysiology will lead to the effective treatment of patients with bladder pain syndrome/interstitial cystitis. © 2014 The Japanese Urological Association.

  5. 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.

  6. A Smac mimetic augments the response of urothelial cancer cells to gemcitabine and cisplatin.

    Science.gov (United States)

    Lee, Eugene K; Jinesh G, Goodwin; Laing, Naomi M; Choi, Woonyoung; McConkey, David J; Kamat, Ashish M

    2013-09-01

    Cisplatin-based chemotherapy is considered the gold standard for patients with advanced bladder cancer. However, despite initial response, many patients will relapse; therefore, novel salvage treatment strategies are desperately needed. Herein, we studied a mechanism based treatment combination using a Smac mimetic with standard chemotherapy. Using a panel of 10 urothelial cancer cell lines, we exposed them to a combination of gemcitabine, cisplatin, and a Smac mimetic. Sensitivity was determined using a DNA fragmentation assay. We determined that three cell lines (UMUC-3, UMUC-13, and RT4v6) were considered sensitive to the combination of gemcitabine and cisplatin and an additional three cell lines were sensitized to gemcitabine and cisplatin with the addition of the Smac mimetic (UMUC-6, UMUC-12, and UMUC-18). We next explored the constitutive expression of selected members of the IAP family (XIAP, cIAP-1, cIAP-2, and Survivin), the BCL family (BCL-2, BCLXL, and BAX) and Smac using gene expression profiling and western blotting. We determined that RNA and protein expression of SMAC, selected members of the IAP family and members of the BCL family did not correlate to drug sensitivity. Lastly, using an in vivo mouse model, we determined that treatment with the Smac mimetic in combination with gemcitabine and cisplatin resulted in increased apoptosis, decreased microvessel density and decreased cellular proliferation. This novel treatment strategy may be effective in patients with advanced urothelial carcinoma and warrants further investigation.

  7. Therapy-relevant aberrant expression of MRP3 and BCRP mRNA in TCC-/SCC-bladder cancer tissue of untreated patients.

    Science.gov (United States)

    Rady, Mona; Mostageer, Marwa; Rohde, Jan; Zaghloul, Ashraf; Knüchel-Clarke, Ruth; Saad, Shady; Attia, Deena; Mahran, Laila; Spahn-Langguth, Hilde

    2017-07-01

    Multidrug resistance (MDR) is a critical factor, which results in suboptimal outcomes in cancer chemotherapy. One principal mechanism of MDR is the increased expression of ATP-binding cassette (ABC) transporters. Of these, multidrug resistance-associated protein 3 (MRP3) and breast cancer resistance protein (BCRP) confer MDR when overexpressed in cancer cell lines. We measured the mRNA expression of MRP3 and BCRP in primary untreated bladder cancer specimens using reverse transcription-quantitative PCR (RT-qPCR) in comparison to normal bladder tissue. The MRP3 and BCRP expression in the two major histotypes of bladder cancer; transitional cell carcinoma (TCC; urothelial type of bladder cancer) and squamous cell carcinoma (SCC; 'Schistosoma-induced' bladder cancer) were compared. Furthermore, the association between MRP3 and BCRP expression and tumor grade and stage were investigated. MRP3 mRNA expression in bladder cancer specimens was increased ~13-fold on average compared to normal bladder tissue (n=36, PTCC showed significantly increased MRP3 mRNA expression compared to SCC of the bladder (PTCC and SCC of the bladder (P=0.1072). The increased MRP3 mRNA expression was not related to bladder tumor grade (P=0.3465) but was, however, significantly higher in superficial than in invasive bladder tumors (P=0.0173). The decreased expression of BCRP was not related to bladder tumor grade (P=0.1808) or stage (P=0.8016). The current data show that bladder cancer is associated with perturbed expression of MRP3 and BCRP. Representing drug resistance factors, determining the expression of these transporters in native tumors may be predictive of the outcome of chemotherapy based-treatment of bladder cancer.

  8. Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells.

    Science.gov (United States)

    Nirmal, J; Wolf-Johnston, A S; Chancellor, M B; Tyagi, P; Anthony, M; Kaufman, J; Birder, L A

    2014-10-01

    To study the protection offered by empty liposomes (LPs) alone against acrolein-induced changes in urothelial cell viability and explored uptake of LPs by primary (rat) urothelial cells. Acrolein was used as a means to induce cellular damage and reduce urothelial cellular viability. The effect of acrolein or liposomal treatment on cellular proliferation was studied using 5-bromo-2'-deoxy-uridine assay. Cytokine release was measured after urothelial cells were exposed to acrolein. Temperature-dependent uptake study was carried out for fluorescent-labeled LPs using confocal microscopy. Liposome pretreatment protected against acrolein-induced decrease in urothelial cell proliferation. LPs also significantly affected the acrolein-induced cytokine (interferon-gamma) release offering protection to the urothelial cells against acrolein damage. We also observed a temperature-dependent urothelial uptake of fluorescent-labeled LPs occurred at 37 °C (but not at 4 °C). Empty LPs alone provide a therapeutic efficacy against acrolein-induced changes in urothelial cell viability and may be a promising local therapy for bladder diseases. Hence, our preliminary evidence provides support for liposome-therapy for urothelial protection and possible repair.

  9. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    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.

  10. Micropapillary bladder cancer: current treatment patterns and review of the literature.

    Science.gov (United States)

    Willis, Daniel L; Flaig, Thomas W; Hansel, Donna E; Milowsky, Matthew I; Grubb, Robert L; Al-Ahmadie, Hikmat A; Plimack, Elizabeth R; Koppie, Theresa M; McConkey, David J; Dinney, Colin P; Hoffman, Vanessa A; Droller, Michael J; Messing, Edward; Kamat, Ashish M

    2014-08-01

    No guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature. A survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network-sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review. Most survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease. The management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Recurrent and multiple bladder tumors show conserved expression profiles

    International Nuclear Information System (INIS)

    Lindgren, David; Fioretos, Thoas; Månsson, Wiking; Höglund, Mattias; Gudjonsson, Sigurdur; Jee, Kowan Ja; Liedberg, Fredrik; Aits, Sonja; Andersson, Anna; Chebil, Gunilla; Borg, Åke; Knuutila, Sakari

    2008-01-01

    Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors

  13. Bladder cancer--the neglected tumor: a descriptive analysis of publications referenced in MEDLINE and data from the register ClinicalTrials.gov.

    Science.gov (United States)

    Kunath, Frank; Krause, Steffen F; Wullich, Bernd; Goebell, Peter J; Engehausen, Dirk G; Burger, Maximilian; Meerpohl, Joerg J; Keck, Bastian

    2013-10-24

    Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem. The aim of this study was to evaluate research activity in uro-oncology over the last decade. We searched MEDLINE and ClinicalTrials.gov systematically for studies on prostatic, urinary bladder, kidney, and testicular neoplasms. The increase in newly published reports per year was analyzed using linear regression. The results are presented with 95% confidence intervals, and a p value <0.05 was considered statistically significant. The number of new publications per year increased significantly for prostatic, kidney and urinary bladder neoplasms (all <0.0001). We identified 1,885 randomized controlled trials (RCTs); also for RCTs, the number of newly published reports increased significantly for prostatic (p = 0.001) and kidney cancer (p = 0.005), but not for bladder (p = 0.09) or testicular (p = 0.44) neoplasms. We identified 3,114 registered uro-oncological studies in ClinicalTrials.gov. However, 85% of these studies are focusing on prostatic (45%) and kidney neoplasms (40%), whereas only 11% were registered for bladder cancers. While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms, urothelial carcinomas of the bladder seem to be neglected despite their important clinical role. Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported.

  14. Transurethral resection versus open bladder cuff excision in patients undergoing nephroureterectomy for upper urinary tract carcinoma: Operative and oncological results.

    Science.gov (United States)

    Fragkoulis, Charalampos; Pappas, Athanasios; Papadopoulos, Georgios I; Stathouros, Georgios; Fragkoulis, Aristodimos; Ntoumas, Konstantinos

    2017-03-01

    To evaluate the impact of distal ureter management on oncological results after open nephroureterectomy (ONU) comparing transurethral resection of the intramural ureter to conventional open excision, as controversy still exists about the method of choice for managing the distal ureter and bladder cuff during ONU. We retrospectively collected data from 378 patients who underwent ONU for upper urinary tract transitional cell carcinoma (UUT-TCC) from 1988 to 2009. Patients were divided into two subgroups according to the type of operation performed. Group A comprised 192 patients who had ONU with open resection of the bladder cuff from 1988 to 1997. Group B comprised 186 patients in whom transurethral resection of the intramural ureter plus single incision ONU was performed between 1998 and 2009. The mean operative time, hospital stay, duration of catheterisation, bladder recurrence rates, and cancer-specific survival (CSS) were assessed. The total operative time was statistically significantly less in the endoscopic group (Group B). For catheterisation, patients treated with an open approach (Group A) had a statistically significantly shorter duration of postoperative catheterisation. There was no statistical difference between Groups A and B for the bladder recurrence rate (Group A 24% vs 27% in Group B, P  = 0.51). There was no difference in CSS at the 5-year follow-up. ONU with transurethral resection of the intramural ureter up to the extravesical fat followed by ureter extraction is an oncologically safe and technically feasible operation.

  15. Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.

    Science.gov (United States)

    Da Rocha, Mitscheli Sanches; Arnold, Lora L; De Oliveira, Maria Luiza Cotrim Sartor; Catalano, Shadia M Ihlaseh; Cardoso, Ana Paula Ferragut; Pontes, Merielen G N; Ferrucio, Bianca; Dodmane, Puttappa R; Cohen, Samuel M; De Camargo, João Lauro V

    2014-05-01

    Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

  16. Immunohistochemical detection of hTERT in urothelial lesions: a potential adjunct to urine cytology

    Directory of Open Access Journals (Sweden)

    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.

  17. Macrophage Migration Inhibitory Factor Mediates PAR-Induced Bladder Pain.

    Directory of Open Access Journals (Sweden)

    Dimitrios E Kouzoukas

    Full Text Available Macrophage migration inhibitory factor (MIF, a pro-inflammatory cytokine, is constitutively expressed in urothelial cells that also express protease-activated receptors (PAR. Urothelial PAR1 receptors were shown to mediate bladder inflammation. We showed that PAR1 and PAR4 activator, thrombin, also mediates urothelial MIF release. We hypothesized that stimulation of urothelial PAR1 or PAR4 receptors elicits release of urothelial MIF that acts on MIF receptors in the urothelium to mediate bladder inflammation and pain. Thus, we examined the effect of activation of specific bladder PAR receptors on MIF release, bladder pain, micturition and histological changes.MIF release was measured in vitro after exposing immortalized human urothelial cells (UROtsa to PAR1 or PAR4 activating peptides (AP. Female C57BL/6 mice received intravesical PAR1- or PAR4-AP for one hour to determine: 1 bladder MIF release in vivo within one hour; 2 abdominal hypersensitivity (allodynia to von Frey filament stimulation 24 hours after treatment; 3 micturition parameters 24 hours after treatment; 4 histological changes in the bladder as a result of treatment; 5 changes in expression of bladder MIF and MIF receptors using real-time RT-PCR; 6 changes in urothelial MIF and MIF receptor, CXCR4, protein levels using quantitative immunofluorescence; 7 effect of MIF or CXCR4 antagonism.PAR1- or PAR4-AP triggered MIF release from both human urothelial cells in vitro and mouse urothelium in vivo. Twenty-four hours after intravesical PAR1- or PAR4-AP, we observed abdominal hypersensitivity in mice without changes in micturition or bladder histology. PAR4-AP was more effective and also increased expression of bladder MIF and urothelium MIF receptor, CXCR4. Bladder CXCR4 localized to the urothelium. Antagonizing MIF with ISO-1 eliminated PAR4- and reduced PAR1-induced hypersensitivity, while antagonizing CXCR4 with AMD3100 only partially prevented PAR4-induced hypersensitivity.Bladder

  18. 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.

  19. Intravesical BCG therapy in bladder carcinoma. Effect on cytotoxicity, IL-2 production and phenotype of peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Zeuthen, J

    1991-01-01

    The purpose of the study was to examine the effects of intravesical BCG treatment on the cytotoxicity, interleukin-2 (IL-2) production and distribution of the subsets of peripheral blood mononuclear cells (PBMC) in patients with carcinoma in situ of the bladder. Treatments were made in 6 patients...... during a conventional BCG treatment schedule. Four patients showed a complete response, one a partial response and one had a progressive disease after BCG treatment. Intravesical BCG did not induce significant changes in the cytotoxicity of PBMC. The distribution of NK-cells and T-cells also remained...... unchanged and so did the lectin induced production of IL-2. The results suggest that the effects of intravesical BCG on the immune system should be studied in lymphocytes isolated from the bladder....

  20. GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder.

    Science.gov (United States)

    Djukic, Tatjana; Simic, Tatjana; Radic, Tanja; Matic, Marija; Pljesa-Ercegovac, Marija; Suvakov, Sonja; Coric, Vesna; Pekmezovic, Tatjana; Novakovic, Ivana; Dragicevic, Dejan; Savic-Radojevic, Ana

    2015-04-01

    To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Case-control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found that carriers of mutant GSTO2*G/G genotype were at increased risk of the development of TCC (OR 2.6, 95% CI 1.2-5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk (p = 0.450). According to smoking status, smokers with GSTO2*G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95% CI 1.6-11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1/GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) (D' = 0.309, p = 0.001). The study subjects with GSTO1*C/GSTO2*G (GSTO1 wild-type/GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95% CI 1.5-5.2, p = 0.002). Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2*G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.

  1. [Influence of hepatocyte cell adhesion molecule on gene expression profile of human bladder transitional cell carcinoma cell line].

    Science.gov (United States)

    Wang, Qiu-ju; Lv, Chang-kun; Tao, Jia; Du, Hong-fei; Fan, Yan-ru; Song, Xue-dong; Luo, Chun-li

    2013-04-01

    To investigate the changes of gene expression file in transitional cell carcinoma of bladder after hepatocyte cell adhesion molecule(hepaCAM) overexpression. Affymetrix Human Genome U133 Plus 2.0 Array was used to investigate the changes of gene expression profile between adenovirus-green fluorescent protein(GFP) -hepaCAM group and GFP group in transitional cell carcinoma of bladder EJ cells.Significant Analysis of Microarray(SAM) was used to screen the differentially expressed genes, DAVID software was used to conduct gene ontology analysis and wikiPathway analysis based on the differentially expressed genes. Reverse transcription-polymerase chain reaction and Western blot were applied to verify microarray data. Compared with the GFP group, a total of 2469 genes were up-regulated or down-regulated by more than 2 times in the GFP-hepaCAM group. Among these genes, 1602 genes were up-regulated and 867 were down-regulated.Most of the differentially expressed genes were involved in the function of cell proliferation and cell cycle regulation. The mRNA expressions of nibrin, liver kinase B1, and cyclin D1 detected by reverse transcription-polymerase chain reaction in three different bladder cancer cell lines were consistent with the microarray data.The protein expressions of nibrin and liver kinase B1 in these three cell lines measured by Western blot were consistent with the mRNA expression. HepaCAM can alter the gene expression profile of bladder cancer EJ cells. The well-known anti-tumor effect of hepaCAM may be mediated by regulating the gene expression via multiple pathways.

  2. Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

    Science.gov (United States)

    Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

    2017-08-01

    Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74

  3. Radical Scavenging and Anti Proliferative Activity of Woodfordia Fruticosa Kurz on Human Bladder Carcinoma, 5637 Cell Lines

    OpenAIRE

    Manggau, Marianti; gemini, alam; Wahyudin, Elly; ulrike, lindequest

    2013-01-01

    Antiproliferative effect of ethanol extract from a plant used in folk medicine, Woodfordia fruticosa Kurz to human bladder carcinoma, 5637 cell lines. After incubation for 72 h with varying concentration of extract (0,343, 1,029, 3,086, 9.259, 27.78, 83.33 dan 250 mg/ml), anti proliferative effect was determined by the neutral red assay and reported in terms of cell viability. The ethanol extract, had a significant anti proliferation against 5637 cell lines with IC50 values of 10,8 mg/ml. A h...

  4. Commentary on: "Comprehensive transcriptional analysis of early-stage urothelial carcinoma." Hedegaard J, Lamy P, Nordentoft I, Algaba F, Høyer S, Ulhøi BP, Vang S, Reinert T, Hermann GG, Mogensen K, Thomsen MB, Nielsen MM, Marquez M, Segersten U, Aine M, Höglund M, Birkenkamp-Demtröder K, Fristrup N, Borre M, Hartmann A, Stöhr R, Wach S, Keck B, Seitz AK, Nawroth R, Maurer T, Tulic C, Simic T, Junker K, Horstmann M, Harving N, Petersen AC, Calle ML, Steyerberg EW, Beukers W, van Kessel KE, Jensen JB, Pedersen JS, Malmström PU, Malats N, Real FX, Zwarthoff EC, Ørntoft TF, Dyrskjøt L. Cancer Cell. 2016 Jul 11;30(1):27-42.

    Science.gov (United States)

    Lee, Byron H

    2017-09-01

    Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into 3 major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Prophylactic yttrium 90 instillation in the case of bladder carcinomas Jewett 0

    International Nuclear Information System (INIS)

    Donn, F.; Becker, H.; Kaufmann, J.; Montz, H.R.

    1982-01-01

    We performed in a prospective pilot study the treatment of bladder cancer Jewett 0 by 90-Yttrium-instillation. The chief aim is to prevent recurrent tumour formation. Our technique delivers an average dose of ca. 3000 rad to the surface of the bladder. The complication rate was moderate. The results were encouraging because the recurrent tumour formation was distinctly reduced. (orig.) [de

  6. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer ...

    Indian Academy of Sciences (India)

    Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness forpreventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activityof silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial ...

  7. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer

    Indian Academy of Sciences (India)

    Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness forpreventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activityof silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial ...

  8. Detection of bladder cancer using proteomic profiling of urine sediments.

    Directory of Open Access Journals (Sweden)

    Tadeusz Majewski

    Full Text Available We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer, and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer. Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival.

  9. serum beta human chorionic gonadotrophin in human urothelial ...

    African Journals Online (AJOL)

    95 years) with urothelial carcinoma at the time of diagnosis of the tumors and at follow-up. For control purposes radioimmunosassay for B-HCG was performed in2 ' groups of patients: Group A: 30 patients with benign conditions who came for operations like hernia repair and Group B: 70 patients who previously had had.

  10. Cytologic diagnosis of transitional cell carcinoma of the urinary bladder. Comparison with endoscopical and pathological findings on 538 cases.

    Science.gov (United States)

    Raica, M; Minciu, R; Miclea, F; Botoca, M; Drăgan, P; Ioiart, I

    1997-01-01

    There were investigated 583 cases with tumors of the urinary bladder and 612 patients with non-malignant diseases of the urinary tract. Samples of voided urine were taken from all cases and direct smears fixed by drying were stained by rapid blue polychrome-tanin Drăgan method Cytological results were compared with endoscopical and pathological findings. The overall rate of real positive results was 91.7% and false negative results were noticed in 8.3% of cases. A direct relationship between real positive results and histological "G" was found. Causes for false negative results were: tumor developed in a bladder diverticulum, calcified tumor, irradiated tumor, insufficient quantity of voided urine, chronic urinary infections and underestimation of cytological criteria of cellular malignancy. There were 9 false positive results in patients with nonmalignant diseases, due to lithiasis, chronic renal failure and chronic urinary infections. The cytological grade of differentiation was performed by the method purposed by Friedman and Ash, and concordance with the standard histological finding was 76.4%. Urine cytology is thought to be a useful method in the primary diagnosis and recurrences of transitional cell carcinoma of the urinary bladder, in all patients with hematuria, recurrent infections of the urinary tract and neglected lithiasis.

  11. Image Analysis Based Grading of Bladder Carcinoma. Comparison of Object, Texture and Graph Based Methods and Their Reproducibility

    Directory of Open Access Journals (Sweden)

    Heung‐Kook Choi

    1997-01-01

    Full Text Available The possibility that computerized image analysis could increase the reproducibility of grading of bladder carcinoma as compared to conventional subjective grading made by pathologists was investigated. Object, texture and graph based analysis were carried out from Feulgen stained histological tissue sections. The object based features were extracted from gray scale images, binary images obtained by thresholding the nuclei and several other images derived through image processing operations. The textural features were based on the spatial gray‐tone co‐occurrence probability matrices and the graph based features were extracted from the minimum spanning trees connecting all nuclei. The large numbers of extracted features were evaluated in relation to subjective grading and to factors related to prognosis using multivariate statistical methods and multilayer backpropagation neural networks. All the methods were originally developed and tested on material from one patient and then tested for reproducibility on entirely different patient material. The results indicate reasonably good reproducibility for the best sets of features. In addition, image analysis based grading showed almost identical correlation to mitotic density and expression of p53 protein as subjective grading. It should thus be possible to use this kind of image analysis as a prognostic tool for bladder carcinoma.

  12. Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Elzein, Fatehi; Albogami, Nada; Saad, Mustafa; El Tayeb, Nazik; Alghamdi, Abdullah; Elyamany, Ghaleb

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) remains a first-line treatment for superficial transitional cell carcinoma of the bladder. Although its use is relatively safe, severe complications such as granulomatous hepatitis, osteomyelitis, pneumonitis, and sepsis occur in few patients. Complications of intravesical instillation of BCG can be local or systemic, with early or late presentation. Here, we report an 88-year-old man who developed fever, rigors, and episodes of syncope following fourth intravesical BCG instillation for the treatment of superficial transitional cell carcinoma of the bladder. Pancytopenia, disseminated intravascular coagulation, ground glass appearance on computerized tomography of the chest scan in addition to multiple bone marrow granulomas, suggested the diagnosis of disseminated BCG infection. All these features recovered on antituberculosis treatment. Our case study highlights the importance of early recognition and prompt treatment of patients with disseminated BCG infection following intravesical instillation. Although isolation of mycobacterium is desirable to make the diagnosis, it is not unusual to have negative smears and cultures and this should not be used to dismiss the possibility of BCG infection.

  13. Alterations to the protein profile of bladder carcinoma cell lines induced by plant extract MINA-05 in vitro.

    Science.gov (United States)

    Nguyen-Khuong, Terry; White, Melanie Y; Hung, Tzong-Tyng; Seeto, Shona; Thomas, Melissa L; Fitzgerald, Anna M; Martucci, Carlos E; Luk, Sharon; Pang, Shiu-Fu; Russell, Pamela J; Walsh, Bradley J

    2009-04-01

    Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48 h then treated for 72 h with concentrations of MINA-05 reflecting 1/2 IC(50), IC(50) and 2 x IC(50) (n = 3) or with vehicle, (0.5% DMSO). Dose-dependant changes in protein abundance were detected and characterised using 2-dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA-05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA-05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment.

  14. Fibroblast growth factor-10 is a mitogen for urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Bagai, Shelly; Rubio, Eric; Cheng, Jang-Fang; Sweet, Robert; Thomas, Regi; Fuchs, Elaine; Grady, Richard; Mitchell, Michael; Bassuk, James A.

    2002-02-01

    Fibroblast Growth Factor (FGF)-10 plays an important role in regulating growth, differentiation, and repair of the urothelium. This process occurs through a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the epithelium (urothelium). In situ hybridization analysis demonstrated that (i) fibroblasts of the human lamina propria were the cell type that synthesized FGF-10 RNA and (ii) the FGF-10 gene is located at the 5p12-p13 locus of chromosome 5. Recombinant (r) preparations of human FGF-10 were found to induce proliferation of human urothelial cells in vitro and of transitional epithelium of wild-type and FGF7-null mice in vivo. Mechanistic studies with human cells indicated two modes of FGF-10 action: (i) translocation of rFGF-10 into urothelial cell nuclei and (ii) a signaling cascade that begins with the heparin-dependent phosphorylation of tyrosine residues of surface transmembrane receptors. The normal urothelial phenotype, that of quiescence, is proposed to be typified by negligible levels of FGF-10. During proliferative phases, levels of FGF-10 rise at the urothelial cell surface and/or within urothelial cell nuclei. An understanding of how FGF-10 works in conjunction with these other processes will lead to better management of many diseases of the bladder and urinary tract.

  15. Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Donatella Conconi

    2016-02-01

    Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

  16. Companied P16 genetic and protein status together providing useful information on the clinical outcome of urinary bladder cancer.

    Science.gov (United States)

    Pu, Xiaohong; Zhu, Liya; Fu, Yao; Fan, Zhiwen; Zheng, Jinyu; Zhang, Biao; Yang, Jun; Guan, Wenyan; Wu, Hongyan; Ye, Qing; Huang, Qing

    2018-04-01

    SPEC P16/CEN3/7/17 Probe fluorescence-in-situ-hybridization (FISH) has become the most sensitive method in indentifying the urothelial tumors and loss of P16 has often been identified in low-grade urothelial lesions; however, little is known about the significations of other P16 genetic status (normal and amplification) in bladder cancer.We detected P16 gene status by FISH in 259 urine samples and divided these samples into 3 groups: 1, normal P16; 2, loss of P16; and 3, amplified P16. Meanwhile, p16 protein expression was measured by immunocytochemistry and we characterized the clinicopathologic features of cases with P16 gene status.Loss of P16 occurred in 26.2%, P16 amplification occurred in 41.3% and P16 gene normal occurred in 32.4% of all cases. P16 genetic status was significantly associated with tumor grade and primary tumor status (P = .008 and .017), but not with pathological tumor stage, overall survival, and p16 protein expression. However, P16 gene amplification accompanied protein high-expression has shorter overall survival compared with the overall patients (P = .023), and P16 gene loss accompanied loss of protein also had the tendency to predict bad prognosis (P = .067).Studies show that the genetic status of P16 has a close relation with the stages of bladder cancer. Loss of P16 is associated with low-grade urothelial malignancy while amplified P16 donotes high-grade. Neither P16 gene status nor p16 protein expression alone is an independent predictor of urothelial bladder carcinoma, but combine gene and protein status together providing useful information on the clinical outcome of these patients.

  17. Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Alongi, Pierpaolo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Gentile, Roberta; Baldari, Sergio [University of Messina, Nuclear Medicine Unit, Department of Biomedical Sciences and Morphological and Functional Images, Messina (Italy); Stefano, Alessandro; Russo, Giorgio; Gilardi, Maria Carla [IBFM-CNR, Cefalu (Italy); Albano, Domenico [Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy)

    2017-02-15

    A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for

  18. Urinary Bladder Cancer in Egypt: Are There Gender Differences in Its Histopathological Presentation?

    Directory of Open Access Journals (Sweden)

    Fiorina Kyritsi

    2018-01-01

    Full Text Available We investigated gender differences in the histopathologic presentation of bladder cancer cases in Egypt, where both urothelial cell carcinoma (UC and squamous cell carcinoma (SCC types are highly prevalent. We used logistic regression to estimate the unadjusted (OR and adjusted odds ratio (AOR and 95% confidence interval (CI of the associations between gender and different histopathologic and sociodemographic parameters of 2,186 confirmed cases of primary bladder cancer (1,775 males and 411 females; 784 SCC and 1,402 UC. There were no statistically significant gender differences in tumor grade, stage, mucosal ulcer, or inflammatory cystitis, regardless of the cancer type, but men were less likely than women to have undergone cystectomy with pelvic lymphadenectomy. Having Schistosoma haematobium (SH ova in the bladder tissue was significantly associated with male gender in the fully adjusted model of either SCC (AOR (95% CI = 2.12 (1.15–3.89 or UC cases (3.78 (1.89–7.55. Compared to females, male cases were significantly older at time of diagnosis and smokers. In Egypt, regardless of the type of bladder cancer (SCC or UC, male more than female cases had evidence of SH infection, but not other histopathologic differences, in bladder tissue specimens.

  19. Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  20. Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells

    Directory of Open Access Journals (Sweden)

    Zhang Chen-Ou

    2010-12-01

    β-catenin changed in response to APF in these cells. In addition, the changes in cell proliferation, MMP2/p53 mRNA and protein expression, and Akt/GSK3β/β-catenin phosphorylation in response to APF treatment were all specifically abrogated following CKAP4 siRNA knockdown. Conclusions Synthetic as-APF inhibits cell proliferation in T24 bladder carcinoma cells via the CKAP4 receptor. The mechanism for this inhibition involves regulating phosphorylation of specific cell signaling molecules (Akt, GSK3β, and β-catenin plus mRNA and protein expression of p53 and MMP2.

  1. In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

    Science.gov (United States)

    Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

    2017-02-01

    Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (pbladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

  2. The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

    Directory of Open Access Journals (Sweden)

    Meyer Hellmuth-Alexander

    2008-12-01

    Full Text Available Abstract Background The three far-upstream element (FUSE binding proteins (FBP1, FBP2, and FBP3 belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. Methods FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. Results High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p Conclusion The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors.

  3. 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...

  4. Association of PAX5 Expression with Clinical Outcome in Patients with TaT1 Transitional Cell Carcinoma of the Bladder

    Czech Academy of Sciences Publication Activity Database

    Babjuk, M.; Soukup, V.; Mareš, J.; Dušková, J.; Pecen, Ladislav; Pešl, M.; Pavlík, I.; Dvořáček, J.

    2006-01-01

    Roč. 67, č. 4 (2006), s. 756-761 ISSN 0090-4295 R&D Projects: GA MZd NR8095; GA MZd NR8934 Institutional research plan: CEZ:AV0Z10300504 Keywords : bladder carcinoma * PAX5 expression Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.130, year: 2006

  5. 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

  6. Significance of pigmented urothelial and non-urothelial cells in voided urine specimens: A case report and review

    Directory of Open Access Journals (Sweden)

    Joseph Alan Kagan

    2017-01-01

    Full Text Available We present a case of metastatic malignant melanoma to the urinary bladder diagnosed on a voided urinary cytology specimen in a patient who visited the emergency department complaining of right flank pain, and dark urine. The patient reported having previous episodes of kidney stones. Additionally, more detailed clinical history obtained after the cytological diagnosis, revealed a previous excision of malignant melanoma on the back 10 years ago. The diagnosis of metastatic malignant melanoma was based solely on voided urine cytology. While metastases of malignant melanoma to urinary bladder are well known, the significance of pigmented cells in voided urine specimens is not well documented. In this article we provide a discussion as well as a review of the literature about possible disease entities associated with pigment containing urothelial as well as non-urothelial cells.

  7. A systematic experimental evaluation of microRNA markers of human bladder cancer

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    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.

  8. Can urologists introduce the concept of "oligometastasis" for metastatic bladder cancer after total cystectomy?

    Science.gov (United States)

    Ogihara, Koichiro; Kikuchi, Eiji; Watanabe, Keitaro; Kufukihara, Ryohei; Yanai, Yoshinori; Takamatsu, Kimiharu; Matsumoto, Kazuhiro; Hara, Satoshi; Oyama, Masafumi; Monma, Tetsuo; Masuda, Takeshi; Hasegawa, Shintaro; Oya, Mototsugu

    2017-12-19

    We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014. We extracted independent predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria which were independently associated with cancer-specific death was defined as oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3 or less; the largest diameter of metastatic foci of 5cm or less; and no liver metastasis. We evaluated differences in clinical outcomes between patients with oligometastasis (oligometastasis group) and those without oligometastasis (non-oligometastasis group). Overall, there were 43 patients in the oligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 53.3%, which was significantly higher than that in the non-oligometastasis group (16.1%, poligometastasis (poligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 55.0%, which was significantly higher than that in the non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the only independent risk factor for cancer-specific death. We presented that urothelial carcinoma with oligometastasis had a favorable prognosis and responded to systemic chemotherapy. Oligometastasis may be treated as a separate entity in the field of metastatic urothelial carcinoma.

  9. Can urologists introduce the concept of “oligometastasis” for metastatic bladder cancer after total cystectomy?

    Science.gov (United States)

    Ogihara, Koichiro; Kikuchi, Eiji; Watanabe, Keitaro; Kufukihara, Ryohei; Yanai, Yoshinori; Takamatsu, Kimiharu; Matsumoto, Kazuhiro; Hara, Satoshi; Oyama, Masafumi; Monma, Tetsuo; Masuda, Takeshi; Hasegawa, Shintaro; Oya, Mototsugu

    2017-01-01

    We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014. We extracted independent predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria which were independently associated with cancer-specific death was defined as oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3 or less; the largest diameter of metastatic foci of 5cm or less; and no liver metastasis. We evaluated differences in clinical outcomes between patients with oligometastasis (oligometastasis group) and those without oligometastasis (non-oligometastasis group). Overall, there were 43 patients in the oligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 53.3%, which was significantly higher than that in the non-oligometastasis group (16.1%, poligometastasis (poligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 55.0%, which was significantly higher than that in the non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the only independent risk factor for cancer-specific death. We presented that urothelial carcinoma with oligometastasis had a favorable prognosis and responded to systemic chemotherapy. Oligometastasis may be treated as a separate entity in the field of metastatic urothelial carcinoma. PMID:29340094

  10. A Comparison of 30-Day Perioperative Outcomes in Open Versus Minimally Invasive Nephroureterectomy for Upper Tract Urothelial Carcinoma: Analysis of 896 Patients from the American College of Surgeons-National Surgical Quality Improvement Program Database.

    Science.gov (United States)

    Hanske, Julian; Sanchez, Alejandro; Schmid, Marianne; Meyer, Christian P; Abdollah, Firas; Feldman, Adam S; Kibel, Adam S; Sammon, Jesse D; Menon, Mani; Eswara, Jairam R; Noldus, Joachim; Trinh, Quoc-Dien

    2015-09-01

    Minimally invasive surgery for nephroureterectomy (MINU) in patients with upper tract urothelial carcinoma (UTUC) is increasingly used among urologists with reported equivalent oncologic outcomes compared with open nephroureterectomy (ONU). Population-level data comparing perioperative outcomes between these approaches remain limited, however. We sought to compare perioperative outcomes between MINU and ONU in a prospectively collected national cohort of patients. Between 2006 and 2012, patients who underwent nephroureterectomy for UTUC within the American College of Surgeons-National Surgical Quality Improvement Program database were categorized into MINU or ONU. Our primary outcome of interest was 30-day perioperative complications. Secondary outcomes included use of lymph node dissection (LND), transfusion, reintervention and readmission rate, operative time, length of stay (LOS), and perioperative mortality. Multivariable logistic regression analyses were used to examine the association between outcomes and surgical approach. A total of 599 (66.9%) and 297 (33.1%) patients underwent MINU and ONU, respectively. Overall, 12.7% of patients experienced a complication within 30 days postoperatively, and the rate did not differ among surgical approaches. Patients in the MINU group, however, had a decreased LOS (PONU. MINU, however, was associated with a decreased risk of blood transfusions, thromboembolic events, reintervention, and overall LOS compared with ONU. MINU should be considered as a primary approach in select groups of patients with UTUC.

  11. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

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    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.

  12. 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

    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.......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...

  13. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

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    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 significan