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

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Zhang Y

2016-01-01

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

Histogram analysis of apparent diffusion coefficient at 3.0 T in urinary bladder lesions: correlation with pathologic findings.

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Suo, Shi-Teng; Chen, Xiao-Xi; Fan, Yu; Wu, Lian-Ming; Yao, Qiu-Ying; Cao, Meng-Qiu; Liu, Qiang; Xu, Jian-Rong

2014-08-01

To investigate the potential value of histogram analysis of apparent diffusion coefficient (ADC) obtained at standard (700 s/mm(2)) and high (1500 s/mm(2)) b values on a 3.0-T scanner in the differentiation of bladder cancer from benign lesions and in assessing bladder tumors of different pathologic T stages and to evaluate the diagnostic performance of ADC-based histogram parameters. In all, 52 patients with bladder lesions, including benign lesions (n = 7) and malignant tumors (n = 45; T1 stage or less, 23; T2 stage, 7; T3 stage, 8; and T4 stage, 7), were retrospectively evaluated. Magnetic resonance examination at 3.0 T and diffusion-weighted imaging were performed. ADC maps were obtained at two b values (b = 700 and 1500 s/mm(2); ie, ADC-700 and ADC-1500). Parameters of histogram analysis included mean, kurtosis, skewness, and entropy. The correlations between these parameters and pathologic results were revealed. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of histogram parameters. Significant differences were found in mean ADC-700, mean ADC-1500, skewness ADC-1500, and kurtosis ADC-1500 between bladder cancer and benign lesions (P = .002-.032). There were also significant differences in mean ADC-700, mean ADC-1500, and kurtosis ADC-1500 among bladder tumors of different pathologic T stages (P = .000-.046). No significant differences were observed in other parameters. Mean ADC-1500 and kurtosis ADC-1500 were significantly correlated with T stage, respectively (ρ = -0.614, P Histogram analysis of ADC-1500 at 3.0 T can be useful in evaluation of bladder lesions. A combination of mean ADC-1500 and kurtosis ADC-1500 may be more beneficial in the differentiation of benign and malignant lesions. Mean ADC-1500 was the most promising parameter for differentiating low- from high-stage bladder cancer. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

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Primdahl, Hanne; von der Maase, Hans; Sørensen, Flemming Brandt

2002-01-01

PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors.METHODS: The tissue material consisted of bladder tumors from three groups of patients......; group 1, 23 patients with recurrent stage Ta (non-invasive) tumors; group 2, 22 patients presenting at their first admission with T2-4 (muscle invasive) tumors; group 3, 24 patients who experienced disease progression from Ta or T1 (invasive in connective tissue) to a higher stage...

Utility of early dynamic and delayed post-diuretic 18F-FDG PET/CT SUVmax in predicting tumour grade and T-stage of urinary bladder carcinoma: results from a prospective single centre study.

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Sharma, Abhishek; Mete, Uttam K; Sood, Ashwani; Kakkar, Nandita; Gorla, Arun K R; Mittal, Bhagwant R

2017-04-01

Accurate pre-treatment grading and staging of bladder cancer are vital for better therapeutic decision and prognosis. The aim of the present study was to evaluate the correlation between maximum standardized uptake value (SUV max ) calculated during early dynamic and post-diuretic fluorine-18 fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT studies with grade and pT-stage of bladder cancer. 39 patients with suspected/proven bladder carcinoma underwent 10-min early dynamic pelvic imaging and delayed post-diuretic whole-body FDG PET/CT imaging. SUV max of the lesions derived from both studies was compared with grade and pT-stage. Relationship of SUV max with grade and pT-stage was analyzed using independent sample t-test and analysis of variance. SUV max of the early dynamic imaging showing tumour perfusion was independent from the SUV max of delayed imaging. High-grade tumours showed higher SUV max than low-grade tumours in the early dynamic imaging (5.4 ± 1.4 vs 4.7 ± 1.6; p-value 0.144) with statistically significant higher value in Stage pT1 tumours (6.8 ± 0.8 vs 5.5 ± 1.2; p-value 0.04). Non-invasive pTa tumours had significantly less SUV max than higher stage tumours during early dynamic imaging [F(4,29) = 6.860, p 0.001]. Early dynamic imaging may have a role in predicting the grade and aggressiveness of the bladder tumours and thus can help in treatment planning and prognostication. Advances in knowledge: Dynamic PET/CT is a limitedly explored imaging technique. This prospective pilot study demonstrates the utility of this modality as a potential adjunct to standard FDG PET/CT imaging in predicting the grade and aggressiveness of the bladder tumours and thus can impact the patient management.

Computed tomography in staging of bladder carcinoma (Prospective study)

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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

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

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Egerod, Frederikke N S Lihme; Bartels, Annette; Fristrup, Niels

2009-01-01

bladder cancer. RESULTS: The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling...... than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling...

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

International Nuclear Information System (INIS)

Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

2009-01-01

Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

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Primdahl, Hanne; von der Maase, Hans; Sørensen, Flemming Brandt

2002-01-01

; group 1, 23 patients with recurrent stage Ta (non-invasive) tumors; group 2, 22 patients presenting at their first admission with T2-4 (muscle invasive) tumors; group 3, 24 patients who experienced disease progression from Ta or T1 (invasive in connective tissue) to a higher stage......PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors.METHODS: The tissue material consisted of bladder tumors from three groups of patients......(kip1) ( P=0.03), Rb ( P=0.00002), and L-myc ( P=0.00000007) in muscle invasive tumors compared to noninvasive tumors. Tumors presenting as muscle invasive at first diagnosis had significantly lower levels of p16/CDKN2A ( P=0.01) when compared to muscle invasive tumors that followed Ta or T1 precursor...

Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder, NCI Retrospective Case Series

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FAKHR, I.; EL-HOSSIENY, H.; SALAMA, A.

2008-01-01

Aim: We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma. Patients and Methods: In a retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free survival were analyzed. Results: Thirty-three patients were included, 29 were males and 4 were females. The mean age was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68 months, mean 18 months) for survival. Eleven (33.3%) patients had multi- focal tumors. Associated schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of 34 (30.3%) patients received post- cystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II, 6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had post-cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three (60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced locoregional disease and another patient died from post- operative complications. Among those patients who received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of T1G3 than that reported by some authors

Comparison of ultrasound and computed tomography in staging of bladder cancer

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Suyama, Bunzo

1982-01-01

Preoperative staging of bladder cancer is very important for decision of treating methods and prognostication. The present author used ultrasound via the abdominal wall in the diagnosis of 83 patients with bladder cancer. I estimated the extent of bladder tumor infiltration by ultrasound via the abdominal wall according to Shiraishi's criteria. Ultrasound scans, pelvic angiograms and CT scans were reviewed to determine their accuracy in staging of bladder tumors. Ultrasound scans were excellent in staging of non-infiltrated bladder tumors, while pelvic angiograms and CT scans were excellent in staging of infiltrated bladder tumors. (author)

Stage of urinary bladder cancer at first presentation

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AlBazzaz Pishtewan H

2009-01-01

The stage of urinary bladder cancer is an important factor in determining prognosis of the disease. This prospective study was performed to determine the stage of bladder cancer at first presentation at the Rizgary Hospital in the Erbil governorate in Iraqi Kurdistan. We evaluated 72 patients with bladder cancer. The grades and stages of bladder cancer of these patients were determined through physical examination and investigations. We found that 47.2% of patients had superficial cancer, 19.4% had tumor with invasion into the lamina propria and 30.6% of patients had tumor with invasion to muscle wall. Regional or distant metastases were found in 2.8% of patients. Well differentiated tumor was seen in 44.4% of the patients, moderately differentiated tumor was found in 38.9% and poorly differentiated tumor was found in 16.7% of the patients. Our study suggests that bladder cancer is diagnosed at a relatively early stage in the Erbil governorate. However, the situation can be further improved by adopting proper screening programs and performing appropriate investigations. (author)

Stage of urinary bladder cancer at first presentation

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Al-Bazzaz Pishtewan

2009-01-01

Full Text Available The stage of urinary bladder cancer is an important factor in determining prognosis of the disease. This prospective study was performed to determine the stage of bladder cancer at first presentation at the Rizgary Hospital in the Erbil governorate in Iraqi Kurdistan. We evaluated 72 patients with bladder cancer. The grades and stages of bladder cancer of these patients were determined through physical examination and investigations. We found that 47.2% of patients had superficial cancer, 19.4% had tumor with invasion into the lamina propria and 30.6% of patients had tumor with invasion to muscle wall. Regional or distant metastases were found in 2.8% of patients. Well differentiated tumor was seen in 44.4% of the patients, moderately differentiated tumor was found in 38.9% and poorly differentiated tumor was found in 16.7% of the patients. Our study suggests that bladder cancer is diagnosed at a relatively early stage in the Erbil governorate. However, the situation can be further improved by adopting proper screening programs and performing appropriate investigations.

Optimal management of high-risk T1G3 bladder cancer: a decision analysis.

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Girish S Kulkarni

2007-09-01

Full Text Available BACKGROUND: Controversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3 bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE and quality-adjusted life expectancy (QALE for both of these treatments for men and women of different ages and comorbidity levels. METHODS AND FINDINGS: We evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1 Immediate cystectomy with neobladder creation versus (2 conservative management with intravesical bacillus Calmette-Guérin (BCG and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients

Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers

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Miyake, Makito; Lawton, Adrienne; Goodison, Steve; Urquidi, Virginia; Gomes-Giacoia, Evan; Zhang, Ge; Ross, Shanti; Kim, Jeongsoon; Rosser, Charles J

2013-01-01

Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), may regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Studies have linked CXCL1 expression to gastric, colon and skin cancers, but limited studies to date have described CXCL1 protein expression in human bladder cancer (BCa). CXCL1 protein expression was examined in 152 bladder tissue specimens (142 BCa) by immunohistochemical staining. The expression of CXCL1 was scored by assigning a combined score based on the proportion of cells staining and intensity of staining. CXCL1 expression patterns were correlated with clinicopathological features and follow-up data. CXCL1 protein expression was present in cancerous tissues, but was entirely absent in benign tissue. CXCL1 combined immunostaining score was significantly higher in high-grade tumors relative to low-grade tumors (p = 0.012). Similarly, CXCL1 combined immunostaining score was higher in high stage tumors (T2-T4) than in low stage tumors (Ta-T1) (p < 0.0001). An increase in the combined immunostaining score of CXCL1 was also associated with reduced disease-specific survival. To date, this is the largest study describing increased CXCL1 protein expression in more aggressive phenotypes in human BCa. Further studies are warranted to define the role CXCL1 plays in bladder carcinogenesis and progression

Bladder Involvement in Stage I Endometriosis.

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Brady, Paula C; Missmer, Stacey A; Laufer, Marc R

2017-08-01

Endometriosis-the ectopic implantation of endometrial-like tissue-affects 10% of adolescent females and adults. Bladder involvement, causing dysuria and hematuria, occurs in a very small number of endometriosis patients. The patient presented at age 12 years with dysuria and pelvic pain. Laparoscopy revealed stage I endometriosis. Postoperatively, she reported persistent dysuria and passage of tissue in her urine. Cystoscopy showed diffuse erythema; urine cytology revealed glandular and spindle cells suggestive of endometriosis. She was transitioned from oral contraceptives to an intranasal gonadotropin-releasing hormone agonist, with symptom resolution. Intravesicular endometriosis coinciding with stage I disease supports a mechanism of endometriosis dissemination other than direct bladder infiltration. Patients with endometriosis who complain of urinary symptoms warrant assessment, because intravesicular bladder involvement cannot be excluded using pelviscopy. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Impaired swim bladder inflation in early-life stage fathead ...

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The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior swim bladders were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Incidence of inflation and length of anterior swim bladder in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, sig

Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR spectroscopic imaging.

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Zhang, Jingbo; Hricak, Hedvig; Shukla-Dave, Amita; Akin, Oguz; Ishill, Nicole M; Carlino, Lauren J; Reuter, Victor E; Eastham, James A

2009-11-01

To assess the diagnostic accuracy of endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging for prediction of the pathologic stage of prostate cancer and the presence of clinically nonimportant disease in patients with clinical stage T1c prostate cancer. The institutional review board approved-and waived the informed patient consent requirement for-this HIPAA-compliant study involving 158 patients (median age, 58 years; age range, 40-76 years) who had clinical stage T1c prostate cancer, had not been treated preoperatively, and underwent combined 1.5-T endorectal MR imaging-MR spectroscopic imaging between January 2003 and March 2004 before undergoing radical prostatectomy. On the MR images and combined endorectal MR-MR spectroscopic images, two radiologists retrospectively and independently rated the likelihood of cancer in 12 prostate regions and the likelihoods of extracapsular extension (ECE), seminal vesicle invasion (SVI), and adjacent organ invasion by using a five-point scale, and they determined the probability of clinically nonimportant prostate cancer by using a four-point scale. Whole-mount step-section pathology maps were used for imaging-pathologic analysis correlation. Receiver operating characteristic curves were constructed and areas under the curves (AUCs) were estimated nonparametrically for assessment of reader accuracy. At surgical-pathologic analysis, one (0.6%) patient had no cancer; 124 (78%) patients, organ-confined (stage pT2) disease; 29 (18%) patients, ECE (stage pT3a); two (1%) patients, SVI (stage pT3b); and two (1%) patients, bladder neck invasion (stage pT4). Forty-six (29%) patients had a total tumor volume of less than 0.5 cm(3). With combined MR imaging-MR spectroscopic imaging, the two readers achieved 80% accuracy in disease staging and AUCs of 0.62 and 0.71 for the prediction of clinically nonimportant cancer. Clinical stage T1c prostate cancers are heterogeneous in pathologic stage and volume. MR imaging may

A combined analysis of European Organization for Research and Treatment of Cancer, and Medical Research Council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer. European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council Working Party on Superficial Bladder Cancer

NARCIS (Netherlands)

Pawinski, A.; Sylvester, R.; Kurth, K. H.; Bouffioux, C.; van der Meijden, A.; Parmar, M. K.; Bijnens, L.

1996-01-01

The use of prophylactic agents after primary resection can decrease the incidence of tumor recurrence in patients with stage TaT1 bladder cancer. However, the long-term impact on progression to muscle invasive disease as well as on duration of survival is unknown. A combined analysis of individual

Multiple imaging procedures including MRI for the bladder cancer

International Nuclear Information System (INIS)

Mikata, Noriharu; Suzuki, Makoto; Takeuchi, Takumi; Kunisawa, Yositaka; Fukutani, Keiko; Kawabe, Kazuki

1986-01-01

Endoscopic photography, double contrast cystography, transurethral echography, X-ray CT scan, and MRI (magnetic resonance imaging) were utilized for the staging diagnosis of the four patients with carcinoma of the bladder. In the first case, a 70-year-old man, since all of the five imaging procedures suggested a superficial and pedunculated tumor, his bladder cancer was considered T1. The classification of stage T3 carcinoma was made for the second 86-year-old male. Because all of his imaging examinations showed a tumor infiltrating deep muscle and penetrating the bladder wall. The third case was a 36-year-old male. His clinical stage was diagnosed as T2 or T3a by cystophotography, double contrast cystogram, ultrasonography, and X-ray CT scan. However, MRI showed only thickened bladder wall and the infiltrating tumor could not be distinguished from the hypertrophic wall. The last patient, a 85-year-old female, had a smaller Ta cancer. Her double contrast cystography revealed the small tumor at the lateral bladder wall. But, the tumor could not be detected by transaxial, sagittal and coronal scans. Multiple imaging procedures combining MRI and staging diagnosis of the bladder carcinoma were discussed. (author)

Impact of complications and bladder cancer stage on quality of life in patients with different types of urinary diversions.

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Prcic, Alden; Aganovic, Damir; Hadziosmanovic, Osman

2013-12-01

Determine correlation between complications and stage of the disease and their impact on quality of life in patients with different types of ileal urinary derivation after radical cystectomy, and upon estimation of acquired results, to suggest the most acceptable type of urinary diversion. In five year period a prospective clinical study was performed on 106 patients, to whom a radical cystectomy was performed due to bladder cancer. Patients were divided into two groups, 66 patients with ileal conduit derivation and 40 patients with orthotopic derivation, whereby in each group a comparison between reflux and anti-reflux technique of orthotopic bladder was made. All patients from both groups filled the Sickness Impact Profile score six months after the operation. All patients had CT urography or Intravenous urography performed, as well as standard laboratory, vitamin B12 blood values, in order to evaluate early (ileus or subileus, wound dehiscence, bladder fistula, rupture of orthotopic bladder, urine extravazation) and late complications (VUR, urethral stricture, ureter stenosis, metabolic acidosis, mineral dis-balance, hypovitaminosis of vitamin B12, increased resorption of bone calcium, urinary infection, kidney damage, relapse of primary disease), so as disease stage and it's impact on quality of life. From gained results we observe that each category of SIP score correlates with different rate of correlation with the type of operation, group, T, N, and R grade, except work category. Average value of SIP score rises depending on the type of operation and T stage. It is notable that there is no difference in T1 stage, no matter the type of operation. So the average value of SIP score in T1 stage for conduit was 20.3, for Abol-Enein and Ghoneim 17.25 and Hautmann 18.75 respectively. Average value of SIP score in T2 stage for conduit was 31, for Abol-Enein and Ghoneim 19.1 and Hautmann 17.8. Average value of SIP score in T3 stage for conduit was 38.03, for Abol

Are prostate carcinoma clinical stages T1C and T2 similar?

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Athanase Billis

2006-04-01

Full Text Available PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c tumors is similar to T2 tumors, indicating a need for further refinement of clinical staging system. To test this finding we compared clinicopathologic characteristics and the time to PSA progression following radical retropubic prostatectomy of patients with clinical stage T1c tumors to those with stage T2, T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45% stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age, preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical margins, extraprostatic extension (pT3a, seminal vesicle invasion (pT3b, and time to PSA progression. Tumor extent was evaluated by a point-count method. RESULTS: Patients with clinical stage T1c were younger and had the lowest mean preoperative PSA. In the surgical specimen, they had higher frequency of Gleason score < 7 and more organ confined cancer. In 40.54% of the patients with clinical stage T2b tumors, there was extraprostatic extension (pT3a. During the study period, 54 patients (30.68% developed a biochemical progression. Kaplan-Meier product-limit analysis revealed no significant difference in the time to PSA progression between men with clinical stage T1c versus clinical stage T2 (p = 0.7959, T2a (p = 0.6060 or T2b (p = 0.2941 as well as between men with clinical stage T2a versus stage T2b (p = 0.0994. CONCLUSION: Clinicopathological features are not similar considering clinical stage T1c versus clinical stages T2, T2a or T2b.

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.

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX and Sirtuin1 (SIRT1

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Ming-Hung Lin

2016-06-01

Full Text Available Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1 in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.

Predictive value of excretory urography, ultrasonography, computerized tomography, and liver and bone scan in the staging of bilharzial bladder cancer in Saudi Arabia

International Nuclear Information System (INIS)

Hanash, K.A.; Bissada, N.K.; Abla, A.; Esmail, D.; Dowling, A.

1984-01-01

The role of ultrasonography, computed tomography (CT), and radioisotopic scanning in the staging of bilharzial bladder cancer has not been reported previously. Forty patients with invasive bladder cancer seen at the King Faisal Specialist Hospital and Research Centre between January 1978 and June 1981 underwent complete preoperative workup for staging of their tumors prior to radical cystectomy. The preoperative radiologic investigations included excretory urography (IVP), ultrasonography (US), CT of the pelvis, and liver and bone scans. The results of these investigations were compared with the operative and pathologic staging. Ninety-three percent of the patients with bilharzial cancer had evidence of ureteric obstruction on IVP compared with 22% of the nonbilharzial cancer patients. The presence of ureteric obstruction in these patients did not correlate with the stage of the disease with 83% of the patients with superficial tumors (T1 and T2) having hydroureteronephrosis. Ultrasonography and CT had an 83% accuracy in the staging of superficial tumors. Stage T3 tumors were understaged in 14% of the cases. Ultrasonography did not differentiate Stages T3 and T4 tumors while CT scan differentiated these two stages in 57% of the cases. Bone scan failed to reveal evidence of metastatic disease in any of the bilharzial cancer patients. Liver scan was suspicious for liver metastases in two patients with bilharzial cancers in whom open liver biopsy revealed only hepatic bilharziasis. Of all the radiographic studies, US or preferably CT scan seem to be of some value in the staging of bilharzial tumors localized to the bladder. Bone and liver scans are probably of no cost effective benefit

The effect of chemotherapy with or without radiation on the accuracy of MR imaging for evaluating tumor infiltration into the bladder wall in cases of advanced bladder cancer

International Nuclear Information System (INIS)

Nishimura, Kazushige; Satou, Yuji; Nannri, Masaharu

2004-01-01

Staging of tumor infiltration into the bladder wall is one of the critical points in decision-making for optimal treatment of invasive bladder cancer. We studied the correlation of MR findings with pathological diagnosis in cases of invasive bladder cancer which had been treated with chemotherapy, with or without radiation. Twenty-one patients (14 men and 7 women) with invasive bladder tumors who underwent either partial cystectomy or radical cystectomy were entered into the study. Eight cases had received chemotherapy after staging biopsy (Group A), 6 cases had undergone chemo-radiation therapy following staging biopsy (Group B), and 7 cases had received no adjuvant therapy except for staging biopsy preoperatively (Group C). All cases had MR imaging study before surgical treatment. The pathological stage was assessed by examining the whole layer of the resected bladder wall. Pathological diagnosis was pT0 in 4 cases, pT1 in 2 cases, pT2b in 5 cases, pT3a in 2 cases and pT3b in 8 cases. Staging with MR imaging was consistent with pathological findings in 14 of the 21 cases (66.7%), while MR imaging produced over-staging in 6 cases and under-staging in 1 case. Of the 6 cases with over-staging, 2 cases had received chemo-radiation therapy, 2 cases had received chemotherapy, and 2 cases had received staging biopsy alone preoperatively. The one case with under-staging had received chemo-radiation therapy preoperatively. The accuracy in staging with MR imaging was 75.0% (6/8), 50.0% (3/6), and 71.4% (5/7) in Groups A, B, and C, respectively. Imaging study with MR is useful for the staging of invasive bladder cancer. However, care should be taken in the staging of invasive bladder tumors which have been treated with chemotherapy, with or without radiation therapy, because inflammatory infiltration and/or fibrous change caused by the chemo-radiation make accurate staging with MR imaging difficult. (author)

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

Science.gov (United States)

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.

Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

International Nuclear Information System (INIS)

Abe, Toyofumi; Yoshioka, Toshiaki; Sato, Mototaka; Mori, Naoki; Sekii, Ken-Ichiro; Itatani, Hiroaki

2011-01-01

We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

Diagnosis of clinical staging of bladder cancer by CT and angiography

International Nuclear Information System (INIS)

Kobayashi, Isao; Igawa, Mikio; Ohnishi, Yoshio; Nakano, Hiroshi; Nihira, Hiromi; Mori, Masaki; Okada, Mitsuo.

1984-01-01

The preoperative staging of bladder cancer is of fundamental importance for prognostic evaluation and surgical indication. We studied the accuracy of computed tomography (CT) and angiography in defining the extent of local invasion in 16 patients with surgically proven carcinoma of the bladder. The overall accuracy of CT and angiographic staging in these cases was 75 % and 50 % respectively. In low stage, the accuracy was 90 % in CT and 70 % in angiography. In high stage, the accuracy was 50 % in CT and 16.7 % in angiography. Our results seems to indicate lower accuracy in high stage bladder cancer compared with other research. Data from a much larger series are required to ascertain whether the additional information provided by CT and angiography will produce any improvement in patient management. (author)

Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

Directory of Open Access Journals (Sweden)

Marija G Matic

Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

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Reddy, Abhinav V. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Pariser, Joseph J.; Pearce, Shane M. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Weichselbaum, Ralph R. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Smith, Norm D.; Steinberg, Gary D. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States)

2016-04-01

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined using follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.

Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer

DEFF Research Database (Denmark)

Andersen, JB; Jensen, Mads Aaboe; Borden, EC

2006-01-01

Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours...... at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage...... component of bladder cancer-associated gene expression....

PKC α regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer

International Nuclear Information System (INIS)

Liu, Jiao; Kong, Chui-ze; Gong, Da-xin; Zhang, Zhe; Zhu, Yu-yan

2014-01-01

Netrin-1 and its receptor UNC5B play important roles in angiogenesis, embryonic development, cancer and inflammation. However, their expression patttern and biological roles in bladder cancer have not been well characterized. The present study aims to investigating the clinical significance of PKC α, netrin-1 and UNC5B in bladder cancer as well as their association with malignant biological behavior of cancer cells. Netrin-1 and UNC5B expression was examined in 120 bladder cancer specimens using immunohistochemistry and in 40 fresh cancer tissues by western blot. Immunofluorescence was performed in cancer cell lines. PKC α agonist PMA and PKC siRNA was employed in bladder cancer cells. CCK-8, wound healing assays and flow cytometry analysis were used to examine cell proliferation, migration and cell cycle, respectively. Netrin-1 expression was positively correlated with histological grade, T stage, metastasis and poor prognosis in bladder cancer tissues. Immunofluorescence showed elevated netrin-1 and decreased UNC5B expression in bladder cancer cells compared with normal bladder cell line. Furthermore, cell proliferation, migration and cell cycle progression were promoted with PMA treatment while inhibited by calphostin C. In addition, PMA treatment could induce while calphostin C reduce netrin-1 expression in bladder cancer cells. The present study identified netrin-1/UNC5B, which could be regulated by PKC signaling, was important mediators of bladder cancer progression

Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.

Science.gov (United States)

Sweeney, Sean K; Luo, Yi; O'Donnell, Michael A; Assouline, Jose

Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm. To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent

CT in the diagnosis of squamous cell carcinoma of urinary bladder

International Nuclear Information System (INIS)

Narumi, Yoshifumi; Mitani, Takashi; Kuriyama, Keiko

1988-01-01

CT findings of 8 operated cases with squamous cell carcinoma of urinary bladder were reviewed. All of them had advanced stage tumor with invasion into perivesical fat or organs (≥ T3b), and with or without lymphnode involvement. We compared them with 15 operated cases with advavced transitional cell carcinoma of urinary bladder (≥ T3b) especially in regard to the direction of tumor growth, and the frequency of invasion into perivesical organs and lymphnode involvement. Futhermore, we studied a relation between CT findings and histopathological stages of the squamous cell carcinoma of urinary bladder. Squamous cell carcinoma of urinary bladder showed predominant extravesical growth as the stage advanced, while transitional cell carcinoma generally showed predominant intravesical growth. Squamous cell carcinoma invaded into perivesical organs and metastasized to lymphnodes more frequently than transitional cell carcinoma of control group. Accuracy of CT staging of squamous cell carcinoma of urinary bladder was found to be 100 % in T stage and 75 % in N stage. (author)

Effect of sirolimus on urinary bladder cancer T24 cell line

Directory of Open Access Journals (Sweden)

Oliveira Paula A

2009-01-01

Full Text Available Abstract Background Sirolimus is recently reported to have antitumour effects on a large variety of cancers. The present study was performed to investigate sirolimus's ability to inhibit growth in T24 bladder cancer cells. Methods T24 bladder cancer cells were treated with various concentrations of sirolimus. MTT assay was used to evaluate the proliferation inhibitory effect on T24 cell line. The viability of T24 cell line was determined by Trypan blue exclusion analysis. Results Sirolimus inhibits the growth of bladder carcinoma cells and decreases their viability. Significant correlations were found between cell proliferation and sirolimus concentration (r = 0.830; p Conclusion Sirolimus has an anti-proliferation effect on the T24 bladder carcinoma cell line. The information from our results is useful for a better understanding sirolimus's anti-proliferative activity in the T24 bladder cancer cell line.

Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

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Chen, Junxing, E-mail: Junxingchen@hotmail.com; Yao, Zhijun, E-mail: yaozhijun1985@qq.com; Qiu, Shaopeng, E-mail: qiushp@mail.sysu.edu.cn; Chen, Lingwu, E-mail: chenlingwu@hotmail.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Urology (China); Wang, Yu, E-mail: zsyyjr@163.com; Yang, Jianyong, E-mail: yangjianyong_2011@163.com; Li, Jiaping, E-mail: jpli3s@126.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Interventional Oncology (China)

2013-12-15

Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3 weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31

Intra-arterial chemotherapy for locally advanced bladder cancer

International Nuclear Information System (INIS)

Aota, Yasuhiro; Yoshida, Kazuhiko

1999-01-01

A total of 83 patients with locally advanced bladder cancer (T1, n=5; T2, n=28; T3a, n=21; T3b, n=21; T4, n=8) were treated with intra-arterial (i.a.) cisplatin and adriamycin (or epirubicin) chemotherapy. In 51 of the 83 cases, we combined this treatment with radiotherapy. The pathological complete response (CR) rate was 68% for all patients, 84% for i.a. chemotherapy combined with radiotherapy and only 41% for i.a. chemotherapy. The 5-year survival rate was 57% for all patients, 71% for i.a. chemotherapy combined with radiotherapy and only 44% for i.a. chemotherapy. The 5-year survival as a function of the clinical stage was 82% for T1+T2, 66% for T3a, 28% for T3b, 25% for T4 (T1+T2 vs. T3b: p<0.001, T1+T2 vs. T4: p<0.0001, T3a vs. T3b: p<0.0263, T3a vs. T4: p<0.0214, T3b vs. T4: p<0.029). In 46% of all patients, we succeeded in preserving the bladder; especially noteworthy, is that in 65% of the patients undergoing i.a. chemotherapy combined with radiotherapy, we succeeded in preserving the bladder. These results demonstrate that i.a. chemotherapy combined with radiotherapy is a useful method for locally advanced bladder cancer which may make preservation of the bladder function feasible. (author)

Evaluation of transurethral ultrasonography and computed tomography in the staging of bladder tumors

International Nuclear Information System (INIS)

Yamakawa, Kensuke; Hoshina, Akira; Tochigi, Hiromi; Kawamura, Juichi

1987-01-01

A definitive pathologic diagnosis was made in 47 patients with bladder tumors from cystectomy specimens or by surgical exploration. The tumor was staged in 35 cases by transurethral ultrasonography and in 39 cases by computed tomography. We obtained the following results : the accuracy was 83 % using transurethral sonography, 77 % using computed tomography. Although transurethral ultrasonography is more advantageous than computed tomography in the low stage in regard to accuracy, computed tomography is excellent method to obtain information about the tumor invasion and/or metastases. Of 25 cases combind with computed tomography and transurethral sonography. tumors were correctly staged by both methods in 18 cases (72 %). Histopathological stage was consistent with neither ultrasonographic stage nor computed tomographic stage in 2 cases, and any of these tumors was correctly staged by either of these methods. Although transurethral ultrasonography and computed tomography improve the clinical stage of the bladder tumors separately, some limitations and problems was recognized on using together with these methods for staging the bladder tumors. (author)

Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease

International Nuclear Information System (INIS)

Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

2014-01-01

Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran–Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III–IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not

Future strategies in the diagnosis, staging and treatment of bladder cancer.

NARCIS (Netherlands)

Heijden, A.G. van der; Witjes, J.A.

2003-01-01

PURPOSE OF REVIEW: In this review new modalities in the diagnosis, staging and treatment of superficial and invasive bladder cancer are reviewed. RECENT FINDINGS: Urinary markers still cannot replace cystoscopy in diagnosing bladder cancer. However, DNA micro-array has shown promise for diagnosis.

Long-term results of radiation combined with cisplatin in localized muscle invasive bladder cancer

International Nuclear Information System (INIS)

Hara, Takahiro; Nishijima, Jun; Miyachika, Yoshihiro; Yamamoto, Yoshiaki; Nagao, Kazuhiro; Sakano, Shigeru; Matsuyama, Hideyasu; Naito, Katsusuke

2011-01-01

Although radical cystectomy is the standard treatment for localized muscle invasive-bladder cancer, bladder preservation therapies have been tried for selective patients in several institutes. However, the indication of bladder preservation therapy remains controversial. To select patients who are good candidates for bladder preservation therapy, we evaluated our long-term experience with radiation therapy (conformal radiotherapy (CRT)) combined with cisplatin. Between 1994 and 2009, 90 patients with bladder cancer (clinical stage T2-4N0M0) with no evidence of upper urinary tract cancer were treated with CRT. The response was evaluated by transurethral resection (TUR) of the tumor, urine cytology and CT scan. Thirty-seven cases (41.1%) achieved pathological complete response (CR) which was defined as no microscopic residual tumor in the bladder. After TUR, 74 cases (82.2%) achieved local control of the cancer that was considered as clinical CR. Among 16 patients for whom clinical CR was not achieved, 8 cases were treated with immediate radical cystectomy. We evaluated the long-term results of CRT in 82 cases with bladder preservation. The median follow-up was 36.6 months (range, 4.1-155.1). The five-year overall survival rate and the 5-year progression-free survival rate were 73.0% and 59.2%, respectively. Clinical T stage and type of tumor (primary or recurrent) were prognostic factors for overall survival (p=0.003 and p=0.017). Likewise, clinical T stage and type of tumor were prognostic factors for progression-free survival (p=0.022 and p=0.033). In addition, primary cT2 cases had a significantly better prognosis than those with other T stage and recurrence in overall survival and progression-free survival (p=0.007 and p=0.018). Based on these data, we concluded that primary cT2 tumors were good candidates for radiation combined with cisplatin for bladder preservation therapy. (author)

CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

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Zheng, Jiajia [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China); Zhu, Xi [Department of Urology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing (China); Zhang, Jie, E-mail: zhangjiebjmu@163.com [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China)

2014-03-28

Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.

CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

International Nuclear Information System (INIS)

Zheng, Jiajia; Zhu, Xi; Zhang, Jie

2014-01-01

Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy

Microsatellite instability in bladder cancer

DEFF Research Database (Denmark)

Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K

1993-01-01

Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X...... or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis....

Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

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Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg; He, Jiwei [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Malkowicz, S. Bruce [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John, E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-03-01

Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” if a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

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Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

2018-04-01

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

Survival benefit of adjuvant radiotherapy in stage III and IV bladder cancer: results of 170 patients

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Bayoumi Y

2014-11-01

Full Text Available Yasser Bayoumi,1 Tarek Heikal,2 Hossam Darweish2 1Radiation Oncology, National Cancer Institute, Cairo University, Giza, Egypt; 2Medical Oncology, Damietta Cancer Institute, Ministry of Health, Damietta, Egypt Background: Radical cystectomy (RC with or without neoadjuvant chemotherapy is the standard treatment for muscle-invasive bladder cancers. However, the locoregional recurrence rate is still significantly higher for locally advanced cases post-RC. The underuse of postoperative radiotherapy (PORT in such cases after RC is related mainly to a lack of proven survival benefit. Here we are reporting our long-term Egyptian experience with bladder cancer patients treated with up-front RC with or without conformal PORT. Patients and methods: This retrospective study included 170 locally advanced bladder cancer (T3–T4, N0/N1, M0 patients who had RC performed with or without PORT at Damietta Cancer Institute during the period of 1998–2006. The treatment outcomes and toxicity profile of PORT were evaluated and compared with those of a non-PORT group of patients. Results: Ninety-two patients received PORT; 78 did not. At median follow-up of 47 months (range, 17–77 months, 33% locoregional recurrences were seen in the PORT group versus 55% in the non-PORT group (P<0.001. The overall distant metastasis rate in the whole group was 39%, with no difference between the two groups. The 5-year disease-free survival for the whole group of patients was 53%±11%, which was significantly affected by additional PORT, and 65%±13% compared with 40%±9% for the non-PORT group (P=0.04. The pathological subtypes did not affect 5-year disease-free survival significantly (P=0.9. The 5-year overall survival was 44%±10%. Using multivariate analysis, PORT, stage, and extravesical extension (positive surgical margins were found to be important prognostic factors for locoregional control. Stage and lymph node status were important prognosticators for distant metastasis

Survival after cystectomy in infiltrating bladder cancer

International Nuclear Information System (INIS)

Mandron, E.; Desrez, G.; Chatelain, C.

1998-01-01

We reviewed the results of infiltrating bladder cancer treated by radical cystectomy to evaluate cancer treated by radical cystectomy to evaluate survival. Between January 1989 and December 1992, a total of 58 consecutive cystectomies or anterior pelvic exenterations performed on 48 men and 10 women (mean age 63.2 years) in our department were retrospectively evaluated. Four patients were lost to follow-up and the mean follow-up was 72 months. Pathologic staging was as follows: stage pTO,A,1: 13.5%, stage pT2: 17.5%, stage pT3a: 12%, stage pT3b: stage pT4: 21%. The year probability of the overall survival was 60% for pT2-p T3a patients, 15% for pT3b patients, and 9% for pT4 patients, respectively. Overall, 53.5% of patients died of cancer, 7.5% of intercurrent disease, and 39% were alive. The cancer related death rate was 12% for pT2-pT3a patients, and 82% for pT3b-pT4 patients. The 5- year probability of specific survival was 80% for pT2-pT3a patients, 15% for pT3b patients and 9% for pT4 patients, respectively. Infiltrating bladder cancer still has a high mortality rate. Radical cystectomy may be considered to be a curative procedure for stages pT2 and pT3a. Adjuvant chemotherapy and/or radiotherapy seem necessary at stages pT3 and pT4. Preoperative criteria need to be better defined to reduce understanding. (authors)

Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.

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Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

2014-12-01

Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran-Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥ 2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥ 2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III-IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not

Clinico-pathological pattern, classification and staging of urinary bladder carcinomas - a five years experience at a tertiary care hospital in central punjab

International Nuclear Information System (INIS)

Naeem, A.

2015-01-01

In Pakistan, urinary bladder carcinoma is the 8th commonest malignancy while being the fourth commonest cancer in men. The relative occurrence of a particular histological type of bladder carcinoma depends on the clinical setting. Both grade and stage of these cancers are highly correlated with recurrence, progression and patient survival rates. Methods: This cross-sectional study comprised of 122 patients with newly diagnosed operable primary bladder carcinomas who underwent cystoscopy associated transurethral resection of bladder tumour at the Urology Department of Punjab Employees Social Security Hospital, Lahore. All participants completed a detailed questionnaire and underwent an in-depth interview to obtain data. The surgical specimens were referred to the Pathology department. Gross observations of the tumour recorded. Result: A total of 114 cases, classified according to WHO/ISUP criteria, low-grade papillary lesions, comprising Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) and Papillary Low Grade carcinomas, accounted for 43% of tumours. Male to female ratio being 5.3:1 (74%). Lateral walls were involved in 44%, posterior wall in 25.3%, trigone in 10.7%, bladder neck in 7.2%, dome in 5.8%, ureteric orifice in 4.13%, anterior wall in 2% and left ureter in 0.87% cases. Tumour staging revealed an overall 11.5% of tumours with stage Ta and 31.5% with stage T3-4. About 29% tumours were non invasive. About n=13 of low-grade carcinomas and n=68 of high-grade carcinomas were invasive. For tumours classified by WHO/ISUP criteria, the percentage of women was larger for PUNLMP than for the other categories of urothelial tumours (p-value 0.006); no statistically significant difference was found by age or gender with respect to tumour stage (p-value 0.138 and 0.452). Conclusion: Transitional Cell Carcinoma (TCC) is the commonest among middle aged men. (author)

Expression of Bmi-1 is a prognostic marker in bladder cancer

International Nuclear Information System (INIS)

Qin, Zi-Ke; Zeng, Mu-Sheng; Yang, Jian-An; Ye, Yun-lin; Zhang, Xing; Xu, Li-Hua; Zhou, Fang-Jian; Han, Hui; Liu, Zuo-Wei; Song, Li-Bing

2009-01-01

The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer. We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis. Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P < 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (P < 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (P < 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, P < 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, P > 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P < 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (P < 0.05), but not with tumor number (P > 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P < 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer

PET/CT staging of T1-stage non-small cell lung cancer

International Nuclear Information System (INIS)

Salman, K. A.; Steinmann, C. H.; Von Schulthess, G. K.; Steinert, H. C.; Sukumar, V. P.

2009-01-01

Full text:Purpose: To evaluate the value of PET/CT in detecting occult metastases in patients with T 1 -stage non-small cell lung cancer (NSCLC). Method: Patients with proven NSCLC and T 1 -stage ( c m) were retrospectively analyzed. In all patients a whole-body 18 F-FDG PET/CT scan for initial staging was performed. The PET/CT findings were compared with all available clinical information, intra-operative findings and the histopathological results. Results: 95 patients (39 men, 56 women; age range, 19-85 years) were analyzed in our study. PET/CT in 68-95 patients correctly excluded mediastinal and distant metastases. In 17/95 patients (18%) mediastinal lymph-node metastases were proven (N 2 n=15; N 3 n=2). PET/CT correctly detected in 10/17 patients (58.8%) mediastinal nodal disease. The smallest mediastinal lymph-node metastasis detected by PET/CT had a size of 0.7 c m. In 7 patients PET/CT missed N 2 -stage. In three of these patients the SUVmax of the primary was c m. Only in one missed N 2 -stage metastasis was sized > 1.0 c m. The tumor histology (adenocarcinoma, squamous cell carcinoma) and location of the primary (central, periphery) did not influence the missed N 2 -stage by PET/CT. PET/CT diagnosed correctly N 3 -stage in 2 patients. 10/95 patients (10.5%) had distant metastases. PET/CT detected unknown M 1 -stage in 4/10 patients. In one patient a metastasis of the parietal pleura was missed by PET/CT. Conclusion: In our study, 28% patients with T 1 -stage NSCLC showed mediastinal or distant metastases. PET/CT was efficient in the detection of occult metastases. However, the sensitivity of PET/CT in mediastinal staging was only 64%.

Contrast-enhanced dynamic and diffusion-weighted MR imaging at 3.0 T to assess aggressiveness of bladder cancer

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Zhou, Guoxing, E-mail: sheasthospital@163.com [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Chen, Xiao, E-mail: chx_win@163.com [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029 (China); Zhang, Jianhua [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Zhu, Jingqi, E-mail: zjh1830@easthospital.cn [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Zong, Genlin, E-mail: zgl0577@easthospital.cn [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Wang, Zhongqiu, E-mail: zhq2001us@163.com [Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029 (China)

2014-11-15

Highlights: • Wash out rate is associated with the aggressiveness of bladder cancer (BC). • Apparent diffusion coefficient (ADC) value could be used to assess the aggressiveness of BC. • The diagnostic accuracy of aggressiveness of BC using ADC was better than semi-quantitative parameters. • Our data showed a good diagnostic performance of ADC and wash-out together in assessing BC aggressiveness. - Abstract: Background: Diffusion weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have been considered useful for pathological staging and histological grading in bladder cancer. To our knowledge, no study has combined the two imaging modalities together to assess aggressiveness of bladder cancer. Objective: To assess the clinical aggressiveness of bladder cancer with DCE MRI and DWI at 3.0 T. Materials and methods: A total of 59 patients with 69 pathologically confirmed tumor lesions were included in this study. All patients underwent MR examination at 3.0 T basing on DWI and DCE imaging. Tumor staging and histological grade were evaluated. The aggressiveness of bladder cancer was classified as low-, intermediate-, or high-aggressiveness according to its pathological phenotype. Apparent diffusion coefficient (ADC) value and semi-quantitative parameters (wash-in rate and wash-out rate) were determined. The correlation between clinical aggressiveness and ADC value, wash-in rate and wash-out rate were analyzed. In addition, the diagnostic accuracy of the diffusion and semi-quantitative parameters were estimated using receiver operating characteristic curve (ROC). Results: Aggressiveness of bladder cancer is negatively correlated with ADC value (r = −0.705, p < 0.0001) and wash-out rate (r = −0.719, p < 0.0001). The tumor ADC value is positively correlated with wash-out rate (r = 0.555, p < 0.0001). The diagnostic specificity and accuracy using tumor ADC value and wash-out for the tumor with size <24 mm were better than that

Contrast-enhanced dynamic and diffusion-weighted MR imaging at 3.0 T to assess aggressiveness of bladder cancer

International Nuclear Information System (INIS)

Zhou, Guoxing; Chen, Xiao; Zhang, Jianhua; Zhu, Jingqi; Zong, Genlin; Wang, Zhongqiu

2014-01-01

Highlights: • Wash out rate is associated with the aggressiveness of bladder cancer (BC). • Apparent diffusion coefficient (ADC) value could be used to assess the aggressiveness of BC. • The diagnostic accuracy of aggressiveness of BC using ADC was better than semi-quantitative parameters. • Our data showed a good diagnostic performance of ADC and wash-out together in assessing BC aggressiveness. - Abstract: Background: Diffusion weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have been considered useful for pathological staging and histological grading in bladder cancer. To our knowledge, no study has combined the two imaging modalities together to assess aggressiveness of bladder cancer. Objective: To assess the clinical aggressiveness of bladder cancer with DCE MRI and DWI at 3.0 T. Materials and methods: A total of 59 patients with 69 pathologically confirmed tumor lesions were included in this study. All patients underwent MR examination at 3.0 T basing on DWI and DCE imaging. Tumor staging and histological grade were evaluated. The aggressiveness of bladder cancer was classified as low-, intermediate-, or high-aggressiveness according to its pathological phenotype. Apparent diffusion coefficient (ADC) value and semi-quantitative parameters (wash-in rate and wash-out rate) were determined. The correlation between clinical aggressiveness and ADC value, wash-in rate and wash-out rate were analyzed. In addition, the diagnostic accuracy of the diffusion and semi-quantitative parameters were estimated using receiver operating characteristic curve (ROC). Results: Aggressiveness of bladder cancer is negatively correlated with ADC value (r = −0.705, p < 0.0001) and wash-out rate (r = −0.719, p < 0.0001). The tumor ADC value is positively correlated with wash-out rate (r = 0.555, p < 0.0001). The diagnostic specificity and accuracy using tumor ADC value and wash-out for the tumor with size <24 mm were better than that

The influence of the level of lamina propria invasion and the prevalence of p53 nuclear accumulation on survival in stage T1 transitional cell bladder cancer

DEFF Research Database (Denmark)

Hermann, G G; Horn, T; Steven, K

1998-01-01

and routinely grouped according to the level of lamina propria invasion. Invasion of the tumor stalk was defined as stage T1a, invasion of the lamina propria proper superficial to the level of muscularis mucosa as stage T1b and into or deeper than the muscularis mucosa as stage T1c. The p53 nuclear...

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.

Treatment options for high-risk T1 bladder cancer. Status quo and future perspectives of radiochemotherapy

International Nuclear Information System (INIS)

Weiss, C.; Roedel, C.; Ott, O.J.; Wittlinger, M.; Fietkau, R.; Sauer, R.; Krause, S.F.

2008-01-01

Purpose: to review the standards and new developments in diagnosis and management of high-risk T1 bladder cancer with emphasis on the role of radiotherapy (RT) and radiochemotherapy (RCT). Material and methods: a systematic review of the literature on developments in diagnosis and management of high-risk T1 bladder cancer was performed. Results: first transurethral resection (TUR), as radical as safely possible, supported by fluorescence cystoscopy, shows higher detection and decreased recurrence rates. An immediate single postoperative instillation with a chemotherapeutic drug reduces the relative risk of recurrence by 40%. A second TUR is recommended to assess residual tumor. For adjuvant intravesical therapy, bacille Calmette-Guerin (BCG) demonstrated the highest efficacy. Early cystectomy should be reserved for selected patients. A recent phase III trial comparing RT versus conservative treatment in T1 G3 tumors could not show any advantage for RT. Data from Erlangen, Germany, using combined RCT in 80% of the patients, compare favorably with most of the contemporary BCG series. Conclusion: results of intravesical therapy are still unsatisfying and early cystectomy is associated with morbidity and mortality. RT alone proved not superior to other conservative treatment strategies. However, data on RCT are promising and demonstrate an alternative to intravesical therapy and radical cystectomy. (orig.)

Esophageal motion characteristics in thoracic esophageal cancer: Impact of clinical stage T4 versus stages T1-T3

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Yuta Kobayashi, MS

2016-10-01

Conclusions: The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.

Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion

International Nuclear Information System (INIS)

Lee, Minsu; Oh, Young Taik; Jung, Dae Chul; Park, Sung Yoon; Shin, Su-Jin; Cho, Nam Hoon; Choi, Young Deuk

2017-01-01

To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. (orig.)

Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion

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Lee, Minsu; Oh, Young Taik; Jung, Dae Chul; Park, Sung Yoon [Yonsei University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Shin, Su-Jin [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Hanyang University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Cho, Nam Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Choi, Young Deuk [Yonsei University College of Medicine, Department of Urology, Seoul (Korea, Republic of)

2017-09-15

To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. (orig.)

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

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

1995-01-15

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.

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

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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

Prospective evaluation of MRI, 11C-acetate PET/CT and contrast-enhanced CT for staging of bladder cancer

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Vargas, H.A.; Akin, O.; Schöder, H.; Olgac, S.; Dalbagni, G.; Hricak, H.; Bochner, B.H.

2012-01-01

Purpose: To prospectively evaluate the diagnostic performance of magnetic resonance imaging (MRI), 11 C-acetate positron emission tomography/computed tomography (PET/CT) and contrast-enhanced CT for bladder cancer staging, using whole-mount pathologic review of radical cystectomy and pelvic lymph node specimens as the reference standard. Materials and methods: The institutional review board approved this prospective study, which was compliant with the Health Insurance Portability and Accountability Act. Written informed consent was obtained from 16 patients with histologically confirmed bladder cancer who underwent MRI, 11 C-acetate PET/CT and contrast-enhanced CT before radical cystectomy and pelvic lymph node dissection. Before imaging 4/16 patients had received intravesical Bacillus Calmette-Guérin treatment, 6 had received systemic chemotherapy, 3 had received both and 3 had received neither. Measures of diagnostic performance including accuracy, sensitivity and specificity were estimated separately for each imaging modality. Results: MRI correctly staged 56% of patients (9/16), overstaged 38% (6/16) and understaged 6% (1/16). CT correctly staged 50% of patients (8/16), overstaged 44% (7/16) and understaged 6% (1/16). In 9 patients, 11 C-acetate PET/CT showed uptake within the bladder wall; the uptake was true-positive in 7 patients and false-positive in 2 patients. Of the remaining 7 patients, 5 had true-negative and 2 had false-negative PET/CT results for cancer in the bladder wall. For all modalities, staging accuracy was reduced in patients with a history of prior intravesical and/or systemic chemotherapy. Conclusion: In staging bladder cancer, MRI, 11 C-acetate PET/CT and CT displayed similar levels of accuracy. For all modalities, a history of intravesical and/or systemic chemotherapy affected staging accuracy.

Pathology outcomes in patients with transurethral bladder tumour resection in a Turkish population: A retrospective analysis

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Salih Budak

2018-03-01

Full Text Available Objectives: Transurethral bladder tumour resection (TURBT is the common surgical method used in the diagnosis, staging and treatment of patients with bladder tumour. Most of the rare tumours other than the urothelial carcinomas of the bladder are in advanced stage on diagnosis and necessitate aggressive treatment. In our study, we aimed to the histologic types of bladder cancer and to determine the regional incidence of rare bladder cancer types in our region. Materials and methods: We retrospectively evaluated 815 patients who underwent TURBT surgery between January 2010 and March 2016 in our clinic with a diagnosis of bladder cancer and at least 1 year follow-up. Patients with tumour histopathological examination including histological tumour type, grade and were reported. Thirty-nine patients with an unclear pathology report (neighboring organ invasion, cautery artifact, etc and 17 patients whose data could not be accessed were excluded from the study. The patients who had received chemotherapy or radiotherapy due to any type of malignancy (23 were also excluded from the study. Results: The outcomes of 736 patients operated in our clinics due to bladder tumour were evaluated. The mean age was 65.2 ± 8.4; 135 were female and 601 were male. Among them 711 patients with urothelial carcinoma were reported (94.2%. According to TNM classification, stage Ta was observed in 270 patients (37.9%, stage T1 in 297 (41.7%, and stage T2 in 144 (20.3%. Non-urothelial cancers were reported in 25 cases (3.3%. Conclusion: The incidence of bladder carcinoma varies between regions. The results of our study are similar to those of the western countries. Increased smoking and exposure to environmental carcinogenetic agents may lead to altered incidences and histological types of bladder tumours. Revision of regional tumour records may be useful to develop and evaluate future treatment strategies.

Prospective evaluation of MRI, {sup 11}C-acetate PET/CT and contrast-enhanced CT for staging of bladder cancer

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Vargas, H.A., E-mail: vargasah@mskcc.org [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Akin, O.; Schöder, H. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Olgac, S. [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Dalbagni, G. [Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Hricak, H. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Bochner, B.H. [Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

2012-12-15

Purpose: To prospectively evaluate the diagnostic performance of magnetic resonance imaging (MRI), {sup 11}C-acetate positron emission tomography/computed tomography (PET/CT) and contrast-enhanced CT for bladder cancer staging, using whole-mount pathologic review of radical cystectomy and pelvic lymph node specimens as the reference standard. Materials and methods: The institutional review board approved this prospective study, which was compliant with the Health Insurance Portability and Accountability Act. Written informed consent was obtained from 16 patients with histologically confirmed bladder cancer who underwent MRI, {sup 11}C-acetate PET/CT and contrast-enhanced CT before radical cystectomy and pelvic lymph node dissection. Before imaging 4/16 patients had received intravesical Bacillus Calmette-Guérin treatment, 6 had received systemic chemotherapy, 3 had received both and 3 had received neither. Measures of diagnostic performance including accuracy, sensitivity and specificity were estimated separately for each imaging modality. Results: MRI correctly staged 56% of patients (9/16), overstaged 38% (6/16) and understaged 6% (1/16). CT correctly staged 50% of patients (8/16), overstaged 44% (7/16) and understaged 6% (1/16). In 9 patients, {sup 11}C-acetate PET/CT showed uptake within the bladder wall; the uptake was true-positive in 7 patients and false-positive in 2 patients. Of the remaining 7 patients, 5 had true-negative and 2 had false-negative PET/CT results for cancer in the bladder wall. For all modalities, staging accuracy was reduced in patients with a history of prior intravesical and/or systemic chemotherapy. Conclusion: In staging bladder cancer, MRI, {sup 11}C-acetate PET/CT and CT displayed similar levels of accuracy. For all modalities, a history of intravesical and/or systemic chemotherapy affected staging accuracy.

The management of non-invasive bladder tumours with Doxorubicin intravesical instillation after transurethral resection.

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Al-Gallab, Musa I; Naddaf, Louai A; Kanan, Mohamad R

2009-04-01

Evaluation of the intravesical instillation of doxorubicin for its effect on disease recurrence for patients with non-invasive bladder tumour. The study was performed at Al Assad University Hospital in Lattakia, Syria and included patients with non-invasive bladder tumours who were managed with transurethral resection and induction and maintenance therapy with intravesical doxorubicin. They were followed up by cystoscopy every 3 months for 2 years and every 6 months thereafter with special emphasis on recurrence rates. The study included 85 patients with non-invasive bladder tumours: 23 with non-invasive papillary carcinoma (Stage Ta), 62 with tumour invading subepithelial connective tissue (Stage T1). Twelve patients had well differentiated tumours (Grade 1), 48 had moderately differentiated (Grade 2), 25 had poorly differentiated (Grade 3) tumours. The total recurrence rate was 23%. The rates of recurrence were 56% in Grade 3 and 0% in Grade 1. The recurrence rate was 41% in patients with large tumours versus 17% in those with small tumours; 44% in those with multiple tumours compared to 18% in those with solitary tumours; 30% of Stage Ta tumours recurred and 21% of Stage T1 tumours. In short term follow-up, our rate of recurrence was 23%. Adjuvant intravesical doxorubicin was shown to reduce the recurrence of superficial bladder cancer. Tumour grade, size and number were shown to be prognostic factors for recurrence.

Clinical outcome of primary small cell carcinoma of the urinary bladder

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Hou CP

2013-08-01

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

Automatic T1 bladder tumor detection by using wavelet analysis in cystoscopy images

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Freitas, Nuno R.; Vieira, Pedro M.; Lima, Estevão; Lima, Carlos S.

2018-02-01

Correct classification of cystoscopy images depends on the interpreter’s experience. Bladder cancer is a common lesion that can only be confirmed by biopsying the tissue, therefore, the automatic identification of tumors plays a significant role in early stage diagnosis and its accuracy. To our best knowledge, the use of white light cystoscopy images for bladder tumor diagnosis has not been reported so far. In this paper, a texture analysis based approach is proposed for bladder tumor diagnosis presuming that tumors change in tissue texture. As is well accepted by the scientific community, texture information is more present in the medium to high frequency range which can be selected by using a discrete wavelet transform (DWT). Tumor enhancement can be improved by using automatic segmentation, since a mixing with normal tissue is avoided under ideal conditions. The segmentation module proposed in this paper takes advantage of the wavelet decomposition tree to discard poor texture information in such a way that both steps of the proposed algorithm segmentation and classification share the same focus on texture. Multilayer perceptron and a support vector machine with a stratified ten-fold cross-validation procedure were used for classification purposes by using the hue-saturation-value (HSV), red-green-blue, and CIELab color spaces. Performances of 91% in sensitivity and 92.9% in specificity were obtained regarding HSV color by using both preprocessing and classification steps based on the DWT. The proposed method can achieve good performance on identifying bladder tumor frames. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis.

Prostanoid-dependent bladder pain caused by proteinase-activated receptor-2 activation in mice: Involvement of TRPV1 and T-type Ca2+ channels

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Maho Tsubota

2018-01-01

Full Text Available We studied the pronociceptive role of proteinase-activated receptor-2 (PAR2 in mouse bladder. In female mice, intravesical infusion of the PAR2-activating peptide, SLIGRL-amide (SL, caused delayed mechanical hypersensitivity in the lower abdomen, namely ‘referred hyperalgesia’, 6–24 h after the administration. The PAR2-triggered referred hyperalgesia was prevented by indomethacin or a selective TRPV1 blocker, and restored by a T-type Ca2+ channel blocker. In human urothelial T24 cells, SL caused delayed prostaglandin E2 production and COX-2 upregulation. Our data suggest that luminal PAR2 stimulation in the bladder causes prostanoid-dependent referred hyperalgesia in mice, which involves the activation of TRPV1 and T-type Ca2+ channels.

Computerized tomography and staging of bladder tumors

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Wozniak, A.; Luongo, A.; Nogueira, A.

1982-01-01

Computed Tomography (CT) has been employed in 13 patients with bladder tumors; 8 of them subsequently underwent surgery. Concordance between CT and pathological staging ranged in 90% of accurate results. Our data are discussed and compared to those of other authors in the literature. Staging was carried out according to the International Union Against Cancer. CT proved to be very accurate in the assessment of local and regional spread of tumor, limphatic progression and early detection of ureteral obstruction, as well as diagnosis of distant metastasis in selected patients. In poor candidates for surgery CT provided invaluable data to be used for localizing fields of radiation therapy. CT is a very well tolerated procedure, it is therefore suitable in subsequent treatment control. (Author) [pt

Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

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Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

2015-11-01

Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in

Preoperative radiation therapy for muscle-invading bladder carcinoma

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Cox, J.A.; Greven, K.M.; Anscher, M.S.; Morgan, T.M.; Scott, J.

1991-01-01

This paper reports on low-dose and high-dose radiation therapy (RT) followed by cystectomy for bladder carcinoma that was evaluated for survival, failure patterns, and complications as these outcomes have been incompletely documented in the past. One hundred five patients with clinical stages T2-T4 (muscle-invading) transitional cell carcinoma of the bladder who completed preoperative RT followed by total cystectomy were evaluated. Eighty-five patients received 20-27 Gy in 4-7 fractions (group A). Twenty patients received 40-50 Gy in 20-28 fractions (group B). Actuarial 5-year survival was 45% and 29% (P = .06) for groups A and B, respectively; 6% of group A was stage T4 compared with 30% of group B. Five-year actuarial survival for patients with stages T2-T3 in groups A and B was 46% and 42%, respectively, while that for T4 was 33% and 0% in groups A and B, respectively. Multivariate analysis revealed that stage, grade, and presence of hydronephrosis independently affected survival. Five-year actuarial local control rates for T2, T3, and T4 were 93%, 93%, and 22%, respectively, with no significant difference between RT groups. Rates of distant metastasis and complications versus preoperative regime and stage were similar

Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse

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Wu Li-Li

2011-07-01

Full Text Available Abstract Background Since transitional cell carcinoma (TCC of the upper urinary tract is a relatively uncommon malignancy, the role of adjuvant radiotherapy is unknown. Methods We treated 133 patients with TCC of the renal pelvis or ureter at our institution between 1998 and 2008. The 67 patients who received external beam radiotherapy (EBRT following surgery were assigned to the radiation group (RT. The clinical target volume included the renal fossa, the course of the ureter to the entire bladder, and the paracaval and para-aortic lymph nodes, which were at risk of harbouring metastatic disease in 53 patients. The tumour bed or residual tumour was targeted in 14 patients. The median radiation dose administered was 50 Gy. The 66 patients who received intravesical chemotherapy were assigned to the non-radiation group (non-RT. Results The overall survival rates for the RT and non-RT groups were not significantly different (p = 0.198. However, there was a significant difference between the survival rates for these groups based on patients with T3/T4 stage cancer. A significant difference was observed in the bladder tumour relapse rate between the irradiated and non-irradiated bladder groups (p = 0.004. Multivariate analysis indicated that improved overall survival was associated with age grade 3 hematologic symptoms also occurred. Conclusion EBRT may improve overall survival for patients with T3/T4 cancer of the renal pelvis or ureter and delay bladder tumour recurrence in all patients.

TGFβ1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases

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Al-Azayzih, Ahmad; Gao, Fei; Goc, Anna; Somanath, Payaningal R.

2012-01-01

Highlights: ► TGFβ induced apoptosis in invasive prostate cancer and bladder cancer cells. ► TGFβ inhibited prostate/bladder cancer cell proliferation and colony/foci formation. ► TGFβ induced prostate/bladder cancer cell apoptosis independent of Akt inhibition. ► TGFβ inhibited ERK1/2 phosphorylation in prostate/bladder cancer cells. ► TGFβ induced p38 MAPK and JNK-mediated activation of caspases-9, -8 and -3. -- Abstract: Recent findings indicate that advanced stage cancers shun the tumor suppressive actions of TGFβ and inexplicably utilize the cytokine as a tumor promoter. We investigated the effect of TGFβ1 on the survival and proliferation of invasive prostate (PC3) and bladder (T24) cancer cells. Our study indicated that TGFβ1 decreased cell viability and induced apoptosis in invasive human PC3 and T24 cells via activation of p38 MAPK-JNK-Caspase9/8/3 pathway. Surprisingly, no change in the phosphorylation of pro-survival Akt kinase was observed. We postulate that TGFβ1 pathway may be utilized for specifically targeting urological cancers without inflicting side effects on normal tissues.

[(18)F]Fluorodeoxyglucose - positron emission tomography/computed tomography improves staging in patients with high-risk muscle-invasive bladder cancer scheduled for radical cystectomy.

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Kollberg, Petter; Almquist, Helen; Bläckberg, Mats; Cronberg, Carin; Garpered, Sabine; Gudjonsson, Sigurdur; Kleist, Jakob; Lyttkens, Kerstin; Patschan, Oliver; Liedberg, Fredrik

2015-01-01

The aim of this study was to evaluate the clinical use of [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in addition to conventional preoperative radiological investigations in a defined group of patients with high-risk muscle-invasive bladder cancer. In total, 103 patients with high-risk muscle-invasive bladder cancer defined as stage T3/T4 disease or as stage T2 with hydronephrosis or high-risk histological features, who were provisionally scheduled to undergo cystectomy, were prospectively recruited to the study. The patients were referred to FDG-PET/CT in addition to standard preoperative investigation with computed tomography (CT). The final treatment decision was reached at a multidisciplinary conference based on all available information including the FDG-PET/CT findings. Compared to CT alone, FDG-PET/CT provided more supplemental findings suggesting malignant manifestations in 48 (47%) of the 103 patients. The additional FDG-PET/CT findings led to an altered provisional treatment plan in 28 out of 103 patients (27%), detection of disseminated bladder cancer and subsequent cancellation of the initially intended cystectomy in 16 patients, and identification of disseminated disease and treatment with induction chemotherapy before radical cystectomy in 12 patients. Preoperative FDG-PET/CT changed the treatment plan for a considerable proportion (27%) of the present patients. Accordingly, such examination can potentially improve the preoperative staging of cystectomy patients with high-risk features, and may also reduce the number of futile operations in patients with advanced disease who are beyond cure.

Thrombomodulin expression regulates tumorigenesis in bladder cancer

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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

Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in patients with T1 bladder tumours: clinical implications and prognostic significance.

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Blanca Pedregosa, A M; Sánchez-González, Á; Carrasco Valiente, J; Ruiz García, J M; Gómez Gómez, E; López Beltrán, A; Requena Tapia, M J

2017-04-01

To determine the differential protein expression of biomarkers FGFR3, PI3K (subunits PI3Kp110α, PI3KClassIII, PI3Kp85), AKT, p21Waf1/Cip1 and cyclins D1 and D3 in T1 bladder cancer versus healthy tissue and to study their potential role as early recurrence markers. This is a prospective study that employed a total of 67 tissue samples (55 cases of T1 bladder tumours that underwent transurethral resection and 12 cases of adjacent healthy mucosa). The protein expression levels were assessed using Western blot, and the means and percentages were compared using Student's t-test and the chi-squared test. The survival analysis was conducted using the Kaplan-Meier method and the log-rank test. Greater protein expression was detected for FGFR3, PI3Kp110α, PI3KClassIII, cyclins D1 and D3 and p21Waf1/Cip1 in the tumour tissue than in the healthy mucosa. However, these differences were not significant for PI3Kp85 and AKT. We observed statistically significant correlations between early recurrence and PI3Kp110α, PI3KClassIII, PI3Kp85 and AKT (P=.003, P=.045, P=.050 and P=.028, respectively), between the tumour type (primary vs. recurrence) and cyclin D3 (P=.001), between the tumour size and FGFR3 (P=.035) and between multifocality and cyclin D1 (P=.039). The survival analysis selected FGFR3 (P=.024), PI3Kp110α (P=.014), PI3KClassIII (P=.042) and AKT (P=.008) as markers of early-recurrence-free survival. There is an increase in protein expression levels in bladder tumour tissue. The overexpression of FGFR3, PI3Kp110α, PI3KClassIII and AKT is associated with increased early-recurrence-free survival for patients with T1 bladder tumours. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Survivin Expression as a Predictive Marker for Local Control in Patients With High-Risk T1 Bladder Cancer Treated With Transurethral Resection and Radiochemotherapy

International Nuclear Information System (INIS)

Weiss, Christian; Roemer, Felix von; Capalbo, Gianni; Ott, Oliver J.; Wittlinger, Michael; Krause, Steffen F.; Sauer, Rolf; Roedel, Claus; Roedel, Franz

2009-01-01

Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results: Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.

Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer : An international validation in primary tumours

NARCIS (Netherlands)

M.M. Vedder (Moniek); M. Márquez (Mirari); E.W. de Bekker-Grob (Esther); M.L. Calle (Malu); L. Dyrskjot (Lars); M. Kogevinas (Manolis); U. Segersten (Ulrika); P.-U. Malmström (Per-Uno); F. Algaba (Ferran); W. Beukers (Willemien); T.F. Orntoft (Torben); E.C. Zwarthoff (Ellen); F.X. Real (Francisco); N. Malats (Núria); E.W. Steyerberg (Ewout)

2014-01-01

textabstractObjective: We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. Methods: We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who

Bladder preservation for locally advanced bladder cancer by transurethral resection, systemic chemotherapy and radiation

International Nuclear Information System (INIS)

Honda, Masahito; Satoh, Mototaka; Tujimoto, Yuichi; Takada, Tuyoshi; Matsumiya, Kiyomi; Fujioka, Hideki

2006-01-01

Twenty-three out of 31 patients with clinical T2-4a N0 M0 bladder cancer and given a trial of trimodality therapy including transurethral resection (TUR), systemic chemotherapy and radiation between 1991 and 2002 completed this therapy. The other 8 dropped out because of insufficient clinical effect. Local bladder recurrence was seen in 3 patients and the bladder preservation rate was 64.5%. Nineteen of the 23 patients showed a complete histological response on a subsequent TUR specimen, the other 4 were not examined for histological response. Thirteen of the 19 patients showed a complete histological response after maximal TUR and systemic chemotherapy, while 6 did after TUR, chemotherapy and radiotherapy. Bladder cancer was T2 in, 15, T3 in 1, and T4a in 3 patients. The CR rate for T2 cancer was significantly higher than that for T3-4a cancer. The 5-year disease-specific survival of the 23 patients treated with preservation therapy was 67.1%. Some of the patients with locally advanced bladder cancer may benefit from this preservation therapy. (author)

Diagnosis of preoperative staging of bladder cancer by CT and angiography

International Nuclear Information System (INIS)

Munechika, Hirotsugu; Saito, Kazuhiko; Tanaka, Osamu; Tomiie, Fumitaka; Aihara, Toshinori

1982-01-01

The accuracy of computed tomography (CT) and angiography in defining the extent of local invasion was studied retrospectively in 19 patients with surgically proven carcinoma of the bladder. The overall accuracy of CT and angiographic staging in these cases was 54 percent and 47 percent respectively. The diagnosis of carcinoma of the bladder by CT tended to do overstaging rather than understaging. A tangential view of the tumor-bearing area by the selective internal iliac arteriography allows an accurate estimation of the perivesical tumor extension. The topographic diagnosis should be made by CT prior to the angiographic study. (author)

Selective bladder preservation by combined modality therapy for invasive bladder cancer

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Kachnic, L A; Kaufman, D S; Zietman, A L; Dallow, K C; Griffin, P P; Heney, N M; Althausen, A F; Shipley, W U

1995-07-01

intravesical drug therapy. Only 4 of these required subsequent cystectomy for failure of conservative management with 13 to 97 months of follow-up. Multivariate analysis showed that the probability of local tumor control was independently predicted by increasing T-stage but not by tumor grade 1-2 vs. 3. The probability of local tumor control was highest in those who had a complete response following TURBT and MCV. No patient has required cystectomy for treatment related bladder morbidity. Conclusions: The use of TURBT with chemotherapy, radiation, and selection for organ-conservation by response should now be a standard treatment option for muscle-invading transitional cell cancer of the bladder. Overall survival is comparable to the published results of radical cystectomy-based series and the majority of the long-term survivors retain fully functional bladders.

Selective bladder preservation by combined modality therapy for invasive bladder cancer

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Kachnic, L. A.; Kaufman, D. S.; Zietman, A. L.; Dallow, K. C.; Griffin, P. P.; Heney, N. M.; Althausen, A. F.; Shipley, W. U.

1995-01-01

intravesical drug therapy. Only 4 of these required subsequent cystectomy for failure of conservative management with 13 to 97 months of follow-up. Multivariate analysis showed that the probability of local tumor control was independently predicted by increasing T-stage but not by tumor grade 1-2 vs. 3. The probability of local tumor control was highest in those who had a complete response following TURBT and MCV. No patient has required cystectomy for treatment related bladder morbidity. Conclusions: The use of TURBT with chemotherapy, radiation, and selection for organ-conservation by response should now be a standard treatment option for muscle-invading transitional cell cancer of the bladder. Overall survival is comparable to the published results of radical cystectomy-based series and the majority of the long-term survivors retain fully functional bladders

Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.

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Lamm, Donald; Persad, Raj; Brausi, Maurizio; Buckley, Roger; Witjes, J Alfred; Palou, Joan; Böhle, Andreas; Kamat, Ashish M; Colombel, Marc; Soloway, Mark

2014-01-01

Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

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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

Invasive bladder cancer treated by radical external radiotherapy

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Corcoran, M.O.; Thomas, D.M.; Lim, A.; Berry, R.J.; Milroy, E.J.G.

1985-01-01

Fifty-three consecutive unselected patients with invasive bladder cancer, Stage T2 to T3, treated by radical radiotherapy have been reviewed. Cystectomy was reserved for patients with significant worsening of disease during treatment, histologically confirmed persistent or recurrent invasive tumour after treatment, or patients with intolerable symptoms due to radiation cystitis. In 64% of our patients a favourable tumour response to radiotherapy was seen, while a further 31% showed disease progression either during or on completion of radiotherapy. Cystectomy was performed on 22% of patients, mainly for radiation cystitis, and was not associated with a significant operative mortality rate. The crude 5-year survival rate was 42%. We conclude that radical radiotherapy is as effective as other forms of treatment for invasive bladder cancer, but that there remains a need to identify those bladder tumours destined to respond poorly to radiotherapy at an earlier stage. (author)

Differential diagnosis and staging of urological tumors by magnetic resonance imaging compared with computed tomography

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Nishimura, Kazuo; Okada, Yusaku; Takeuchi, Hideo; Miyakawa, Mieko; Okada, Kenichiro; Yoshida, Osamu; Nishimura, Kazumasa

1987-01-01

Magnetic resonance imaging (MRI) was performed on 49 urological tumors (11 renal cell carcinomas, 3 renal pelvic cancers, 2 renal angiomyolipomas, 1 renal leiomyosarcoma, 1 large renal cvst, 4 adrenal tumors, 11 bladder cancers, 2 bone metastasis from bladder cancer, 10 prostatic cancers, 1 prostatic sarcoma, 1 urethral cancer, 1 penile cancer and 1 perivesical granuloma) since October 1985 to September 1986. MRI was performed using a Signa (G.E.) with a 1.5 T superconductive magnet and 3 images, including T1 weighted image, T2 weighted image, and proton density image, were obtained. In conclusion MRI is a noninvasive examination and gives more information than computed tomography despite its high cost. In renal cell carcinoma, the chemical shift in MRI and clear visualization of tumor thrombus enable accurate staging. Differential diagnosis from other renal mass lesions may be possible by the T2 weighted image. In adrenal disease, most of the adrenal masses can be differentiated, but in some cases it is impossible. In bladder cancer, wall invasion of tumor may be evaluated in T2 weighted image, and MRI is suitable for staging of locally advanced tumor. In prostatic cancer, visualization of periprostatic plexus and differentiation between internal and external gland may enable local staging and identification of low stage tumors. (author)

Detection Of Aneuploidy In Chromosomes 3,7,9 And 17 In Bladder Cancer Patients Using Urovysion Assay

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Abd-Elsattar, N.A.; Yossef, M.F.; Saleh, S.A.R.; Shahin, R.S.; Ali, H.H.; Kotb, Y.M.

2012-01-01

Background: Cystoscopy is considered up till now the gold standard as well as urine cytology for diagnosis and follow up of urinary bladder cancer patients. Cystoscopy is an invasive inconclusive technique while cytology have low sensitivity. Therefore search for a more sensitive, non-invasive highly reliable method is important. Aim of the study: To assess the diagnostic sensitivity and specificity of Urovysion to be used as a non-invasive tool for early detection of bladder cancer patients. Furthermore, to assess its relationship with histopathological stages and grades of the disease. Subjects and methods: This study was conducted on 30 patients with urinary bladder cancer( Group I) which were subdivided according to cancer stages and grades into subgroups and 15 diseased control patients (Group II). One urine sample was taken from each patient for Urovysion assay and another sample taken for urine cytology. Results: Urovysion showed higher positive results in (Group I) than urine cytology. In (Group II) the latter did not miss any negative case while urovysion showed only one false positive case. Moreover, Urovysion results revealed significant association with both bladder cancer histopathological stages and grades while urine cytology showed significant association with tumor grades only. Conclusion: Urovysion; both by itself and in combination with urine cytology; offers a sensitive, reliable and non invasive approach to bladder cancer diagnosis. Urovysion is associated with invasiveness of bladder cancer from stage Tis, T1 to T4 and from grades G1 to G3. Thus, urovysion assay can be used as an important diagnostic and prognostic indicator of this disease

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

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Neuzillet, Yann; Paoletti, Xavier; Ouerhani, Slah; Mongiat-Artus, Pierre; Soliman, Hany; de The, Hugues; Sibony, Mathilde; Denoux, Yves; Molinie, Vincent; Herault, Aurélie; Lepage, May-Linda; Maille, Pascale; Renou, Audrey; Vordos, Dimitri; Abbou, Claude-Clément; Bakkar, Ashraf; Asselain, Bernard; Kourda, Nadia; El Gaaied, Amel; Leroy, Karen; Laplanche, Agnès; Benhamou, Simone; Lebret, Thierry; Allory, Yves; Radvanyi, François

2012-01-01

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12) and OR = 0.99 [0.37-2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.

A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer. A prospective study

International Nuclear Information System (INIS)

Miyanaga, Naoto; Akaza, Hideyuki; Okumura, Toshiyuki

2000-01-01

A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. lntra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function. (author)

Outcome of urinary bladder recurrence after partial cystectomy for en bloc urinary bladder adherent colorectal cancer resection.

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Luo, Hao Lun; Tsai, Kai Lung; Lin, Shung Eing; Chiang, Po Hui

2013-05-01

Around 10 % of colorectal cancers are locally advanced at diagnosis. There are higher incidences for sigmoid and rectal cancer adhered to urinary bladder (UB) rather than other segments of colon cancer. Surgeons often performed partial cystectomy as possible for preservation of patient's life quality. This study investigates prognostic factors in patients who underwent bladder preservation en bloc resection for UB adherent colorectal cancer. From 2000 to 2011, 123 patients with clinically UB involvement colorectal cancer underwent primary colorectal cancer with urinary bladder resection. Seventeen patients were excluded because of the concurrent distant metastasis at diagnosis and another 22 patients were excluded because of total cystectomy with uretero-ileal urinary diversion. Finally, 84 patients with clinical stage IIIC (T4bN0M0, according to AJCC 7th edition) that underwent en bloc colorectal cancer resection with partial cystectomy were enrolled into this study for further analysis. Preoperative colovesical fistula and positive CT result were significantly more in the urinary bladder invasion group (p = 0.043 and 0.010, respectively). Pathological UB invasion is an independent predictor of intravesical recurrence (p = 0.04; HR, 10.71; 95 % CI = 1.12∼102.94) and distant metastasis (p = 0.016; HR, 4.85; 95 % CI = 1.34 ∼ 17.53) in multivariate analysis. For bladder preservation en bloc resection of urinary bladder adherent colorectal cancer, the pathological urinary bladder invasion is significantly associated with more urinary bladder recurrence and distant metastasis. This result helps surgeons make decisions at surgical planning and establish follow-up protocol.

Organ preservation in invasive bladder cancer: Brachytherapy, an alternative to cystectomy and combined modality treatment?

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Pos, Floris; Horenblas, Simon; Dom, Paul; Moonen, Luc; Bartelink, Harry

2005-01-01

Purpose: To evaluate our long-term results of bladder preservation with brachytherapy in the treatment of bladder cancer. Methods and materials: Between 1987 and 2000, 108 patients with T1-G3 and T2-T3a stages of bladder cancer were treated with a transurethral resection (TUR) and a course of external beam radiotherapy (30 Gy in 15 fractions) followed by brachytherapy (40 Gy). All tumors were solitary lesions with a diameter ≤5 cm. Median follow-up was 54 months (range, 1-178 months). Results: The 5-year and 10-year overall survival rates were 62% and 50%, respectively. The 5-year and 10-year disease-specific survival rates were 73% and 67%, respectively. The actuarial local control rate was 73% at 5 and 73% at 10 years, respectively. The 5-year and 10-year disease-specific survival rates for patients with a preserved bladder were 68% and 59%, respectively. Of all long-term surviving patients, 90% preserved their native bladders. The treatment was well tolerated. Acute toxicity was mild. Two patients experienced serious late toxicity: 1 patient developed a persisting vesicocutaneous fistula and the other a stricture of the urethra and ureters. Conclusion: For patients with solitary, organ confined invasive bladder cancer ≤5 cm, bladder preservation with brachytherapy is an excellent alternative to radical cystectomy and combined modality treatment

Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

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Canyilmaz, Emine; Yavuz, Melek Nur; Serdar, Lasif; Uslu, Gonca Hanedan; Zengin, Ahmet Yasar; Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan

2014-01-01

Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy

Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

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Canyilmaz, Emine, E-mail: dremocan@yahoo.com [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey); Yavuz, Melek Nur [Department of Radiation Oncology, Akdeniz University, Antalya (Turkey); Serdar, Lasif [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey); Uslu, Gonca Hanedan; Zengin, Ahmet Yasar [Department of Radiation Oncology, Kanuni Research and Education Hospital, Trabzon (Turkey); Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan [Department of Radiation Oncology, Karadeniz Technical University, Trabzon (Turkey)

2014-11-01

Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

The progress in diagnostic imaging for staging of bladder and prostate cancer. Endorectal magnetic resonance imaging and magnetization transfer contrast

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Arima, Kiminobu; Hayashi, Norio; Yanagawa, Makoto; Kawamura, Juichi; Kobayashi, Shigeki; Takeda, Kan; Sugimura, Yoshiki

1999-01-01

We retrospectively studied the staging accuracy of endorectal magnetic resonance imaging (MRI) in comparison with transrectal ultrasound examination (TRUS) for 71 localized bladder cancers and 19 localized prostate cancers (PC) radically resected. The accuracy of clinical staging for bladder cancer in endorectal MRI and TRUS was 85.9% and 69.2%, respectively. The presence or absence of the continuity of submucosal enhancement on T2-weighted MRI images could be useful for the staging of bladder cancer. The accuracy of the seminal vesicular invasion for prostate cancer in endorectal MRI and TRUS was 95% and 63%, respectively. To determine whether magnetization transfer contrast (MTC) provides additional information in the diagnosis of prostate cancer, the magnetization transfer ratios (MTRs) were calculated in 22 patients with PC, 5 with benign prostatic hyperplasia (BPH) and 4 controls. The mean MTR in the peripheral zone of the normal prostate (8.0%±3.4 [standard deviation]) showed a statistically significant decrease relative to that in the inner zone of the normal prostate (27.4%±3.4, p<0.01), BPH (25.5%±3.7, p<0.01), pre-treatment PC (30.6%±5.9, p<0.01), and PC after hormonal therapy (20.3%±6.3, p<0.01). The mean MTR in pre-treatment PC was significantly higher than that in BPH, or in PC after hormonal therapy (p<0.01). MTC was considered to be useful for conspicuity of prostate cancer lesion. (author)

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

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Conde, Vanessa R. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Oliveira, Pedro F. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP (Portugal); Nunes, Ana R.; Rocha, Cátia S. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Ramalhosa, Elsa; Pereira, José A. [Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança (Portugal); Alves, Marco G., E-mail: alvesmarc@gmail.com [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Silva, Branca M., E-mail: bmcms@ubi.pt [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

2015-07-01

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

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

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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.

Microsatellite instability as prognostic marker in bladder tumors: a clinical significance

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Mittal RD

2005-01-01

Full Text Available Abstract Background Carcinoma of urinary bladder is one of the leading causes of death in India. Successful treatment of bladder cancer depends on the early detection & specific diagnostic approaches. In the present study, microsatellite instability (MSI has been evaluated as a prognostic marker in patients with superficial urinary bladder cancer in lower urinary tract for determining risk of recurrence. Methods A total of 44 patients with bladder tumors diagnosed with Transitional Cell Carcinomas [TCC] from lower urinary tract were selected for the study. Tumors were staged and graded according to AJCC-UICC (1997 classification and patients were followed with cystoscopy as per the protocol. Polymerase chain reaction (PCR was done to amplify microsatellite sequences at mononucleotide BAT – 26, BAT – 40, TGFβ RII, IGFIIR, hMSH3, BAX and dinucleotide D2S123, D9S283, D9S1851 and D18S58 loci in blood (control and tumor DNA. PCR products were separated on 8% denaturing polyacrylamide gel and visualized by autoradiography. Results MSI was observed in 72.7% of tumors at BAT – 26, BAT – 40, D2S123, D9S283, D9S1851 and D18S58 loci. Good association of MSI was seen with tumor stage and grade. MSI – High (instability at > 30% of loci was frequently observed in high stage (40.6% and high grade (59.4% tumors. Of 24 tumors of Ta-T1 stage with different grades, 11 (9/18 high grade and 2/6 low grade tumors recurred in the mean duration of 36 months. MSI positivity was significantly high in patients who had one or more recurrences (p = 0.02 for high grade and 0.04 for low grade tumors. Conclusions MSI may be an independent prognostic marker for assessing risk of recurrence in superficial tumors irrespective of the grade. Further studies on progression would help in stratifying the patients of T1G3 for early cystectomy vs bladder preservation protocol.

Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction

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Ning Liu

2015-01-01

Full Text Available Background: Work in voiding (WIV of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO. Methods: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (P det Q max of ≥40 cmH 2 O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t and WIV per liter of urine voided (WIV/v were also calculated. In men, the relationships between these work capacity parameters and P det Q max and Abrams-Griffiths (AG number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman′s association test. Results: The mean WIV was 1.15 ± 0.78 J and 1.30 ± 0.88 J, mean WIV/t was 22.95 ± 14.45 mW and 23.78 ± 17.02 mW, and mean WIV/v was 5.59 ± 2.32 J/L and 2.83 ± 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with P det Q max (r = 0.845, P = 0.000, AG number (r = 0.814, P = 0.000, and Schafer class (r = 0.726, P = 0.000. Conversely, WIV and WIV/t showed no associations with P det Q max or AG number. In patients with BOO (Schafer class > II, WIV/v correlated positively with increasing BOO grade. Conclusions: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t.

Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages.

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Feng, Huan; Zhang, Wei; Li, Jiajun; Lu, Xiaozhe

2015-01-01

To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (pstage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate.

Stages of Bladder Cancer

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... above the waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste ... to bladder cancer. Being exposed to paints, dyes, metals, or petroleum products in the workplace. Past treatment ...

TUR and postoperative megavolt inrradiation in urinary bladder cancer

International Nuclear Information System (INIS)

Haschek, H.; Kaercher, K.H.; Studler, G.

1984-01-01

100 patients suffering from infiltrating urinary bladder cancer underwent transurethral resection followed by external megavolt irradiation (Betatron) are presented. The value of irradiation and its role in the actual therapeutic concept is discussed. The results of the combined therapy in infiltrative urinary bladder cancer using transurethral resection and megavolt irradiation are demonstrated according to stage (T 2 , T 3 ) and histological grading (G 2 , G 3 ). The 5-years survival rate amounts around 80%, in deep infiltrating bladder cancer about 50%. The morbidity of postoperative megavolt therapy was negligible. The results are superior to megavolt therapy alone and approach the one achieved by radical surgery; in addition the possibility of salvage-cystectomy remains open. (Author)

1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

Science.gov (United States)

Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

2010-01-01

Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.

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Yann Neuzillet

Full Text Available TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001 or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009. However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12 and OR = 0.99 [0.37-2.7] (p = 0.35, respectively. After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4. These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.

Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

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Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei; Tucker, Kai; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David; Keefe, Stephen M. [Department of Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas; Malkowicz, S. Bruce [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2014-03-01

Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, and external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended

Diuretic 18F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique

International Nuclear Information System (INIS)

Nayak, Brusabhanu; Dogra, Prem Nath; Naswa, Niraj; Kumar, Rakesh

2013-01-01

Positron emission tomography/computed tomography (PET/CT) with 18 F-fluorodeoxyglucose (FDG) has been used with limited success in the past in primary diagnosis and locoregional staging of urinary bladder cancer, mainly because of the pharmacokinetics of renal excretion of 18 F-FDG. In the present prospective study, we have evaluated the potential application of diuretic 18 F-FDG PET/CT in improving detection and locoregional staging of urinary bladder tumours. Twenty-five patients suspected of having primary carcinoma of the urinary bladder were evaluated prospectively for diagnosis and staging. All of these 25 patients underwent conventional contrast-enhanced computed tomography (CECT) of the abdomen/pelvis and whole-body diuretic 18 F-FDG PET/CT. In addition, pelvic PET/CT images were obtained using the special technique of forced diuresis using intravenous furosemide (20-40 mg). Of the 25 patients, 10 underwent radical cystectomy and 15 underwent transurethral resection of the bladder tumour (TURBT). Results of CECT and diuretic 18 F-FDG PET/CT were compared considering histopathology as a reference standard. Of the 25 patients, CECT detected a primary tumour in 23 (sensitivity 92 %), while 18 F-FDG PET/CT was positive in 24 patients (sensitivity 96 %). Mean size and maximum standardized uptake value of the bladder tumours were 3.33 cm (range 1.6-6.2) and 5.3 (range 1.3-11.7), respectively. Of the 25 patients, only 10 patients underwent radical cystectomy based on disease status on TURBT. Among those ten patients, nine had locoregional metastases. Among the nine patients who had positive lymph nodes for metastasis on histopathology, CECT and PET/CT scan had a sensitivity of 44 and 78 %, respectively. 18 F-FDG PET/CT was found to be superior to CECT in the detection of the primary tumour and locoregional staging (p 18 F-FDG PET/CT is highly sensitive and specific and plays an important role in improving detection of the primary tumour and locoregional staging of

Cancer of the urinary bladder category T2, T3, (N/sub x/M/sub o/) treated by interstitial radium implant: second report

International Nuclear Information System (INIS)

Werf-Messing, B.; Menon, R.S.; Hop, W.C.J.

1983-01-01

Three-hundred-twenty-eight patients with bladder cancer category T 2 N/sub x/M/sub o/ have been treated by 3 times 3.5 Gy external irradiation followed by a radium implant. Overall 5- and 10-year survival in the T 2 category are 56% adn 37%. In the T 3 category they are 39% adn 13%, respectively. The intercurrent death (i.e. without evidence of bladder malignancy) corrected acuarial survival percentage in the T 2 category is 75% at 5 years and 69% at 10 years. The corresponding percentages in the T 3 category are 62% and 59%. Prognosis is worsened by the following factors: more than 1 diagnostic transurethral resection, a pathological intravenous pyelography, non-papillary structure and poor degree of differentiation of the growth. Prognosis in category T 3 , as compared with category T 2 , is worse because of the prevalence of bad prognosticators in this T 3 category. Therapeutic adaptation to thesse findings might improve prognosis in the future

Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: Initial report

International Nuclear Information System (INIS)

Cervek, J.; Cufer, T.; Kragelj, B.; Zakotnik, B.; Stanonik, M.

1993-01-01

Forty-seven patients with muscle-invasive bladder cancer (T2--T4, Nx, MO) were treated by transurethral resection, followed by 3--4 cycles of combination chemotherapy (methothrexate 30 mg/m2 on days 1, 14; cis-platinum 100 mg/m2 on day 2; vinblastine 3 mg/m2 on days 1, 14; repeated every 21 days), and external beam irradiation (64--66 Gy to the bladder and 40 Gy to the pelvic lymphatics). Complete remission after transurethral resection and chemotherapy was achieved in 24 out of 45 patients (53%). Cystectomy was performed in patients without complete response to transurethral resection and chemotherapy. The therapy was completed as planned in 45/47 patients. After transurethral resection, chemotherapy, and radiation therapy, biopsy proven complete response was achieved in 62% (28/45); Stage T2T3 in 67% (23/24), Stage T4 in 45% (5/11) of patients. Among 19 patients with positive biopsy findings after transurethral resection and chemotherapy, 14 underwent cystectomy. After follow-up of 4--55 months (median 23 months) 75% (34/45) are alive, 68% (31/45) have had their bladders preserved, and 53% (24/45) are free of the primary tumor. The actuarial survival of all 45 patients is 73%. Moderate nausea and vomiting during treatment were common; severe leukopenia and mucositis were observed in five patients. Late side effects such as miction disorders and diarrhea were predominantly mild. Although the observation period has been too short to allow a definitive evaluation of treatment results, the authors feel both from the point of bladder preservation and disease-free survival that the presented treatment approach is successful in a majority of T2T3 patients, whereas a large tumor size (T4) renders this treatment less effective. 17 refs., 4 figs., 4 tabs

Hypofractionated Intensity Modulated Radiation Therapy in Combined Modality Treatment for Bladder Preservation in Elderly Patients With Invasive Bladder Cancer

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Turgeon, Guy-Anne [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.ca [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Sturgeon, Jeremy [Department of Medical Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, Quebec (Canada)

2014-02-01

Purpose/Objective(s): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. Methods and Materials: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. Results: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. Conclusions: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid

The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis

NARCIS (Netherlands)

Kamat, A.M.; Cookson, M.; Witjes, J.A.; Stenzl, A.; Grossman, H.B.

2016-01-01

Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade. Objective: To establish whether blue light

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy.

Science.gov (United States)

Palou-Redorta, J; Solsona, E; Angulo, J; Fernández, J M; Madero, R; Unda, M; Martínez-Piñeiro, J A; Portillo, J; Chantada, V; Moyano, J L

2016-01-01

To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected With Human T-Lymphotropic Virus 1.

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Andrade, Rosana C P; Neto, José A; Andrade, Luciana; Oliveira, Tatiane S; Santos, Dislene N; Oliveira, Cassius J V; Prado, Márcio J; Carvalho, Edgar M

2016-03-01

To evaluate the efficacy of physiotherapy for urinary manifestations in patients with human T-lymphotropic virus 1-associated lower urinary tract dysfunction. Open clinical trial was conducted with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises, and intravaginal or intra-anal electrical stimulation were used. The mean age was 54 ± 12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia, and in the sensation of incomplete emptying (P Physiotherapy was effective in cases of human T-lymphotropic virus 1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, and improving urodynamic parameters and quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

DEFF Research Database (Denmark)

Bitsch, M; Hermann, G G; Andersen, J P

1990-01-01

A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid conta...

Preoperative staging and treatment options in T1 rectal adenocarcinoma

DEFF Research Database (Denmark)

Baatrup, Gunnar; Endreseth, Birger H; Isaksen, Vidar

2009-01-01

. Results. Local treatment of T1 cancers combined with close follow-up, early salvage surgery or later radical resection of local recurrences or with chemo-radiation may lead to fewer severe complications and comparable, or even better, long-term survival. Accurate preoperative staging and careful selection...... of patients for local or non-operative treatment are mandatory. As preoperative staging, at present, is not sufficiently accurate, strategies for completion, salvage or rescue surgery is important, and must be accepted by the patient before local treatment for cure is initiated. Recommendations......Background. Major rectal resection for T1 rectal cancer offers more than 95% cancer specific five-year survival to patients surviving the first 30 days after surgery. A significant further improvement by development of the surgical technique may not be possible. Improvements in the total survival...

Use of thiazolidinediones and risk of bladder cancer

DEFF Research Database (Denmark)

Bazelier, Marloes T; de Vries, Frank; Vestergaard, Peter

2013-01-01

BACKGROUND: Pioglitazone, a drug for the treatment of type 2 diabetes mellitus has been associated with bladder cancer in observational studies. Diabetes mellitus itself has also been linked with bladder cancer. The objective was to estimate the risk of bladder cancer for diabetic patients using...... thialozidinediones (TZDs) compared with patients in other treatment stages of the disease. METHODS: We performed a population-based cohort study (1996-2007) in the Danish National Health Registers. Oral antidiabetic drug users (n=179,056) were matched 1:3 by sex and year of birth to non-users. Hazard ratios (HRs......) of bladder cancer were estimated using Cox proportional hazards models. Time-dependent adjustments were made for age, comorbidity, and drug use. Four different treatment stages were defined: current use of either a biguanide or a sulfonylureum (stage 1), current use of a biguanide and a sulfonylureum...

Radiotherapy of bladder cancer

International Nuclear Information System (INIS)

Ikeda, Yoshiyuki

1978-01-01

Methods of treating bladder cancer include surgery, radiotherapy and chemotherapy, as well as various combinations of these. The author investigated clinically and histopathologically the therapeutic results of preoperative irradiation in cases of bladder cancer. 1. The survival rates (crude survival rates) in forty cases of bladder cancer were 90% after one year, 62.5% after three years and 46% after five years from the treatment. 2. As the result of irradiation, urogram improved in 25%, which was comparatively remarkable in high stage cases. There were no cases of deterioration of urogram findings caused by irradiation. Cystoscopy revealed disappearance or remarkable shrinkage of the tumors in 35% of the total cases and effects of the irradiation was observed not correlated to the stage and grade. 3. With respect to the histopathological changes, the changes became greater as the dosage increased and the higher the stage and grade were the more remarkable tendency was observed. 4. From our clinical observations such as urogram, cystoscopy and histopathologically, we estimated the optimum dosage of preoperative irradiation for bladder cancer is 3000 - 4000 rad. Thus, we concluded that the radiotherapy is effective in reducing both surgical invasion and postoperative recurrence. (author)

Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

Science.gov (United States)

Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

2016-07-01

Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. ©2016 American

Diuretic {sup 18}F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique

Energy Technology Data Exchange (ETDEWEB)

Nayak, Brusabhanu; Dogra, Prem Nath [All India Institute of Medical Sciences, Department of Urology, New Delhi (India); Naswa, Niraj [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Kumar, Rakesh [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); New Delhi (India)

2013-03-15

Positron emission tomography/computed tomography (PET/CT) with {sup 18}F-fluorodeoxyglucose (FDG) has been used with limited success in the past in primary diagnosis and locoregional staging of urinary bladder cancer, mainly because of the pharmacokinetics of renal excretion of {sup 18}F-FDG. In the present prospective study, we have evaluated the potential application of diuretic {sup 18}F-FDG PET/CT in improving detection and locoregional staging of urinary bladder tumours. Twenty-five patients suspected of having primary carcinoma of the urinary bladder were evaluated prospectively for diagnosis and staging. All of these 25 patients underwent conventional contrast-enhanced computed tomography (CECT) of the abdomen/pelvis and whole-body diuretic {sup 18}F-FDG PET/CT. In addition, pelvic PET/CT images were obtained using the special technique of forced diuresis using intravenous furosemide (20-40 mg). Of the 25 patients, 10 underwent radical cystectomy and 15 underwent transurethral resection of the bladder tumour (TURBT). Results of CECT and diuretic {sup 18}F-FDG PET/CT were compared considering histopathology as a reference standard. Of the 25 patients, CECT detected a primary tumour in 23 (sensitivity 92 %), while {sup 18}F-FDG PET/CT was positive in 24 patients (sensitivity 96 %). Mean size and maximum standardized uptake value of the bladder tumours were 3.33 cm (range 1.6-6.2) and 5.3 (range 1.3-11.7), respectively. Of the 25 patients, only 10 patients underwent radical cystectomy based on disease status on TURBT. Among those ten patients, nine had locoregional metastases. Among the nine patients who had positive lymph nodes for metastasis on histopathology, CECT and PET/CT scan had a sensitivity of 44 and 78 %, respectively. {sup 18}F-FDG PET/CT was found to be superior to CECT in the detection of the primary tumour and locoregional staging (p < 0.05). Diuretic {sup 18}F-FDG PET/CT is highly sensitive and specific and plays an important role in improving

Bladder Cancer—Patient Version

Science.gov (United States)

The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Smoking is a major risk factor for bladder cancer. Bladder cancer is often diagnosed at an early stage. Start here to find information on bladder cancer treatment, screening, research, and statistics.

Effects of acute urinary bladder overdistension on bladder response during sacral neurostimulation.

Science.gov (United States)

Bross, S; Schumacher, S; Scheepe, J R; Zendler, S; Braun, P M; Alken, P; Jünemann, K

1999-10-01

Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.

Disulfide high mobility group box-1 causes bladder pain through bladder Toll-like receptor 4.

Science.gov (United States)

Ma, Fei; Kouzoukas, Dimitrios E; Meyer-Siegler, Katherine L; Westlund, Karin N; Hunt, David E; Vera, Pedro L

2017-05-25

Bladder pain is a prominent symptom in several urological conditions (e.g. infection, painful bladder syndrome/interstitial cystitis, cancer). Understanding the mechanism of bladder pain is important, particularly when the pain is not accompanied by bladder pathology. Stimulation of protease activated receptor 4 (PAR4) in the urothelium results in bladder pain through release of urothelial high mobility group box-1 (HMGB1). HGMB1 has two functionally active redox states (disulfide and all-thiol) and it is not known which form elicits bladder pain. Therefore, we investigated whether intravesical administration of specific HMGB1 redox forms caused abdominal mechanical hypersensitivity, micturition changes, and bladder inflammation in female C57BL/6 mice 24 hours post-administration. Moreover, we determined which of the specific HMGB1 receptors, Toll-like receptor 4 (TLR4) or receptor for advanced glycation end products (RAGE), mediate HMGB1-induced changes. Disulfide HMGB1 elicited abdominal mechanical hypersensitivity 24 hours after intravesical (5, 10, 20 μg/150 μl) instillation. In contrast, all-thiol HMGB1 did not produce abdominal mechanical hypersensitivity in any of the doses tested (1, 2, 5, 10, 20 μg/150 μl). Both HMGB1 redox forms caused micturition changes only at the highest dose tested (20 μg/150 μl) while eliciting mild bladder edema and reactive changes at all doses. We subsequently tested whether the effects of intravesical disulfide HMGB1 (10 μg/150 μl; a dose that did not produce inflammation) were prevented by systemic (i.p.) or local (intravesical) administration of either a TLR4 antagonist (TAK-242) or a RAGE antagonist (FPS-ZM1). Systemic administration of either TAK-242 (3 mg/kg) or FPS-ZM1 (10 mg/kg) prevented HMGB1 induced abdominal mechanical hypersensitivity while only intravesical TLR4 antagonist pretreatment (1.5 mg/ml; not RAGE) had this effect. The disulfide form of HMGB1 mediates bladder pain directly (not

Value of dual-phase 18F-FDG PET/CT in preoperative staging of bladder cancer%18F-FDG PET/CT双时相显像在膀胱癌术前分期中的临床价值

Institute of Scientific and Technical Information of China (English)

李洪生; 吴湖炳; 王巧愚; 韩彦江; 王全师

2014-01-01

目的：探讨18F-FDG PET/CT双时相显像在膀胱癌术前分期中的应用价值。方法2003年5月~2012年5月进行18F-FDG PET/CT检查的膀胱癌初诊患者73例，男54例，女19例，年龄58.7（41~80）岁。所有患者18F-FDG PET/CT常规全身显像后，口服40 mg呋塞米并多饮水，多次排尿，服呋塞米后约2 h憋尿充盈膀胱，再进行18F-FDG PET/CT盆腔延迟显像。所有患者于18F-FDG PET/CT检查后1周内进行手术治疗，将PET/CT与手术病理学检查结果进行对比分析，评价18F-FDG PET/CT双时相显像在膀胱癌术前分期中的应用价值。结果18F-FDG PET/CT双时相显像对膀胱癌原发灶的T分期与病理分期符合率为63.0%（46/73），其中pT4期膀胱癌的分期符合率为100%（7/7）；另外检出75.0%（6/8）的淋巴结转移灶，100%（4/4）的远隔器官转移灶和100%（4/4）原发性第二种恶性肿瘤病灶。结论本研究结果表明18F-FDG PET/CT双时相显像在T分期方面，尽管对pTa、pT1、pT2、pT3期膀胱癌的T分期价值不大，但对pT4期膀胱癌的T分期可能有重要的应用价值；在膀胱癌的N分期、M分期及发现第二种原发癌方面也可能有重要的应用价值。%Objective To investigate the clinical value of dual-phase 18F-FDG PET/CT with oral diuretics in preoperative staging of bladder cancer. Methods The imaging data were analyzed of 73 patients with bladder cancer undergoing preoperative dual-phase 18F-FDG PET/CT with oral diuretic between May, 2003 and May, 2012. All the patients underwent whole-body PET/CT scan 60 min after intravenous injection of 270-350 MBq of 18F-FDG. Additional delayed pelvic PET/CT images were acquired after forced diuresis using oral furosemide (40 mg). All the patients underwent subsequent radical cystectomy, and 18F-FDG PET/CT findings were compared with the histopathologic results to evaluate the value of dual-phase 18F-FDG PET/CT in preoperative staging. Results The

Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

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Berrahmoune, Saoussen; Bezdetnaya, Lina; de Witte, Peter; Leroux, Agnès; Dumas, Dominique; Guillemin, François; D'Hallewin, Marie Ange

2009-06-01

The prevalence of bladder cancer is very high, due to its high recurrence rate in superficial bladder cancer (30 to 85%), which is the staging of approximately 80% of the patients at first diagnosis. Risk of recurrence and progression is associated with grade, stage, presence of concomitant carcinoma in situ, size and number of lesions, as well as time to first recurrence. Recurrences can be partly attributed to new occurrences but also to residual tumors after resection. Incomplete tumor removal has been observed in 30 to 50% of TUR's, especially when dealing with T1 or poorly visible malignant or pre-malignant disease1. Fluorescence guided resection with 5 amino levulinic acid (ALA) or its hexyl ester derivative (Hexvix, has now unequivocally been demonstrated to increase detection rate and a growing number of studies indicate this has a positive impact on recurrence and progression ratesImplantation of viable tumor cells, dispersed during resection, is a third factor influencing bladder cancer recurrence. The aim of early intravesical therapy is to interfere with cell viability and thus reduce implantation risks.

A case of bladder leiomyoma with literature review

International Nuclear Information System (INIS)

Zeng Sihui; Chen Zhiguang; Liang Biling

2006-01-01

Objective: Preliminarily analysis of the MRI features of bladder leiomyoma. Methods: The MRI manifestations were analyzed with review of previous released literatures in a case of bladder leiomyoma, which was confirmed by pathology. Results: The lesion manifested homogeneous intermediate signal intensity both on non-enhanced T 1 WI and T 2 WI, and intermediate enhancement on contrast enhanced T 1 WI. There was no pedicle on the tumor and the tumor-bladder junction had an acute angle, indicating its benign nature. Conclusion: Non-epithelial tumor has characteristic signals in non-enhanced MRI, in which the leiomyoma of bladder is the most frequent benign neoplasm encountered. Considering enhanced MRI findings, the morphology and growth pattern of the tumor, accurate diagnosis can be made in some cases of bladder leiomyoma, providing valuable informations for surgical planning. (authors)

Co-expression of HER3 and MUC1 is associated with a favourable prognosis in patients with bladder cancer

DEFF Research Database (Denmark)

Nielsen, Trine O; Borre, Michael; Nexo, Ebba

2015-01-01

OBJECTIVES: To investigate the functional impact of the interaction of MUC1 with the epidermal growth factor receptors HER3 and HER4 in patients with bladder cancer. PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, we examined MUC1 expression in 82 bladder...... the prognostic value of MUC1 (P = 0.488). MUC1 expression had no correlation with survival, tumour stage or grade, or to the prognostic value of HER4. CONCLUSIONS: A high MUC1 expression was associated with a favourable prognosis in patients with bladder cancer when the expression of HER3 was also high....... This suggests an involvement of HER3 in MUC1 function in bladder cancer....

Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience.

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Gerardi, Marianna A; Jereczek-Fossa, Barbara A; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V; De Cobelli, Ottavio; Orecchia, Roberto

2016-01-01

The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis.

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Yang, Shucai; Ma, Jing; Xiao, Jianbing; Lv, Xiaohong; Li, Xinlei; Yang, Huike; Liu, Ying; Feng, Sijia; Zhang, Yafang

2012-08-01

Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose- and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 μmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer. Copyright © 2012 Wiley Periodicals, Inc.

[The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

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Szarvas, Tibor

2009-12-01

Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

Preoperative lymph-node staging of invasive urothelial bladder cancer with 18F-fluorodeoxyglucose positron emission tomography/computed axial tomography and magnetic resonance imaging

DEFF Research Database (Denmark)

Jensen, Thor Knak; Holt, Per; Gerke, Oke

2011-01-01

OBJECTIVE: The treatment and prognosis of bladder cancer are based on the depth of primary tumour invasion and the presence of metastases. A highly accurate preoperative tumour, node, metastasis (TNM) staging is critical to proper patient management and treatment. This study retrospectively...... investigated the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed axial tomography (¹⁸F-FDG PET/CT) and magnetic resonance imaging (MRI) for preoperative N staging of bladder cancer. Material and methods. From June 2006 to January 2008, 48 consecutive patients diagnosed with bladder......) for MRI and ¹⁸F-FDG PET/CT, respectively. The differences in specificity and negative predictive values were not statistically significant. Conclusions. No significant statistical difference between ¹⁸F-FDG PET/CT and MRI for preoperative N staging of urothelial bladder cancer was found in the study...

Invasive bladder cancer: treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation

International Nuclear Information System (INIS)

Shipley, William U.; Zietman, Anthony L.; Kaufman, Donald S.; Althausen, Alex F.; Heney, Niall M.

1997-01-01

Purpose: Combined modality therapy has become the standard oncologic approach to achieve organ preservation in many malignancies. Methods and Materials: Although radical cystectomy has been considered as standard treatment for invasive bladder carcinoma in the United States, good results have been recently reported from several centers using multimodality treatment, particularly in patients with clinical T2 and T3a disease who do not have a ureter obstructed by tumor. Results: The components of the combined treatment are usually transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation therapy. Following an induction course of therapy a histologic response is evaluated by cystoscopy and rebiopsy. Clinical 'complete responders' (tumor site rebiopsy negative and urine cytology with no tumor cells present) continue with a consolidation course of concurrent chemotherapy and radiation. Those patients not achieving a clinical complete response are recommended to have an immediate cystectomy. Individually the local monotherapies of radiation, TURBT, or multidrug chemotherapy each achieve a local control rate of the primary tumor of from 20 to 40%. When these are combined, clinical complete response rates of from 65 to 80% can be achieved. Seventy-five to 85% of the clinical complete responders will remain with bladders free of recurrence of an invasive tumor. Conclusions: Bladder conservation trials using combined modality treatment approaches with selection for organ conservation by response of the tumor to initial treatment report overall 5-year survival rates of approximately 50%, and a 40-45% 5-year survival rate with the bladder intact. These modern multimodality bladder conservation approaches offer survival rates similar to radical cystectomy for patients of similar clinical stage and age. Bladder-conserving therapy should be offered to patients with invasive bladder carcinoma as a realistic alternative to radical

Functional Evaluation of Modified T Pouch as Ileal Neo bladder Ortho topic Reservoir

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Hammouda, H.M.

2004-01-01

We report on the functional results of ortho topic modified T pouch ileal neo bladder, incorporating serous- lined extra mural ileal anti reflux technique for urinary diversion after radical cystectomy. Material and Methods: From September 1998 through November 2001,42 patients of mean age 49 years (range 45-54) having invasive bladder carcinoma underwent radical cystectomy and ortho topic ileal neo bladder urinary diversion, the modified T pouch. Thirty-three patients were males while the remaining 9 were females. The mean follow up was 24 months (range 18-42). Preoperative unior bilateral ureteral dilatation was noted in 13/42 (30.9%) patients). Follow up included clinical examination, laboratory, radiological and uro dynamic investigations. Early postoperative complications were recorded in 3 cases, that were managed conservatively. Day and night continence were achieved in 34/42 (81 %) and 29/42 (69%) patients, night enuresis in 2 (4.8%),while satisfactory day and night continence were noted, respectively. Upper urinary tract (UUT) remained unchanged or improved in all cases. No need for clean intermittent catherization (CIC). No evidence of reflux was detected. Pressure at maximum capacity (average 17 cm H 2 O at 600 ml). Mean flow rate was 17.6 ml/sec (range 15-24). Pelvic cancer recurrence was recorded in 5 patients at mean 24 months, respectively. Modified T pouch has an excellent functional criteria as an ortho topic ileal neo bladder reservoir. It is absolutely indicated in short and/or massively dilated ureter

High expression of HEF1 is associated with poor prognosis in urinary bladder carcinoma

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Zhang Q

2014-07-01

Full Text Available Qi Zhang,1 Hui-Ju Wang,2 Da-Hong Zhang,1 Guo-Qing Ru,3 Xu-Jun He,2 Ying-Yu Ma2 1Department of Urology, 2Key Laboratory of Gastroenterology of Zhejiang Province, 3Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China Abstract: Human enhancer of filamentation 1 (HEF1 is a multidomain scaffolding protein that has been thought to play an important role in the tumor progression of various cancers. HEF1 expression has not previously been reported in urinary bladder carcinoma, and little is known about its prognostic significance. The aim of this study was to evaluate the expression patterns of HEF1 in urinary bladder carcinoma and to investigate its prognostic significance. HEF1 expression was analyzed by immunohistochemistry using tissue microarray. A significant relationship between HEF1 expression and sex, tumor size, number of tumors, invasion depth, lymph node metastasis, and distant metastasis was found, and high expression of HEF1 was associated with worse overall survival when compared to low expression of HEF1. Multivariate analysis showed that HEF1 expression was an independent prognostic factor for overall survival in urinary bladder carcinoma. We investigated HEF1 expression in urinary bladder carcinoma and found that high HEF1 expression was associated with advanced stage, large tumor size, and shortened progression-free survival. Although the biologic function of HEF1 in urinary bladder carcinoma remains unknown, the expression of HEF1 can provide new prognostic information for disease progression. Keywords: human enhancer of filamentation 1, progression-free survival, immunohistochemistry, metastasis, bladder cancer

Hemipelvic irradiation for superficial bladder cancer

International Nuclear Information System (INIS)

Tashiro, Kazuya; Machida, Toyohei; Ooishi, Yukihiko; Ueda, Masataka; Kido, Akira; Wada, Tetsuro; Yoshigoe, Fukuo; Yamashita, Takashi; Mochizuki, Sachio

1985-01-01

In 15 patients with superficial bladder cancer hemipelvic irradiation was performed for prevention of relapse of cancer and decrease in side effects with following results. All patients received TUR-Bt at our department during the six years period from 1978 to 1983. As to stages, one was classified as Ta, 11 as T 1 and 3 as T 2, and pathologic diagnosis was transitional epithelial carcinoma of grade 1 in 1 case, grade 2 in 8 cases and grade 3 in 6 cases. Irradiation was started from the 7 th to 14 th day after TUR-Bt. At first, hemipelvic anterior and posterior field including the field from the affected pelvis to 1 to 2 cm beyond the midline toward the contralateral side and from the aortic bifurcation to the prostatic urethra were irradiated at a dose of 45 Gy. Then, whole bladder field was given an additional rotation irradiation of 20 Gy. The mean observation period was 43 months (ranging from 12 to 79 months) and relapse of cancer was observed in 6 cases out of 15 cases (40%). The site of relapse was in the irradiated site in 2 cases, contralateral site in 3 cases and both side in 1 cases. However, in all of the relapsed cases no aggravation in differential degree or progression in stage was observed. As the side effects, radiation cystitis developed as a delayed damage in 1 case. Thus, although no efficacy for prevention of relapse which we had expected was not seen, this irradiation method effectively inhibited the progression of lesion and development of delayed damage. (author)

Hemipelvic irradiation for superficial bladder cancer

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Tashiro, Kazuya; Machida, Toyohei; Ooishi, Yukihiko; Ueda, Masataka; Kido, Akira; Wada, Tetsuro; Yoshigoe, Fukuo; Yamashita, Takashi; Mochizuki, Sachio

1985-02-01

In 15 patients with superficial bladder cancer hemipelvic irradiation was performed for prevention of relapse of cancer and decrease in side effects with following results. All patients received TUR-Bt at our department during the six years period from 1978 to 1983. As to stages, one was classified as Ta, 11 as T 1 and 3 as T 2, and pathologic diagnosis was transitional epithelial carcinoma of grade 1 in 1 case, grade 2 in 8 cases and grade 3 in 6 cases. Irradiation was started from the 7 th to 14 th day after TUR-Bt. At first, hemipelvic anterior and posterior field including the field from the affected pelvis to 1 to 2 cm beyond the midline toward the contralateral side and from the aortic bifurcation to the prostatic urethra were irradiated at a dose of 45 Gy. Then, whole bladder field was given an additional rotation irradiation of 20 Gy. The mean observation period was 43 months (ranging from 12 to 79 months) and relapse of cancer was observed in 6 cases out of 15 cases (40%). The site of relapse was in the irradiated site in 2 cases, contralateral site in 3 cases and both side in 1 cases. However, in all of the relapsed cases no aggravation in differential degree or progression in stage was observed. As the side effects, radiation cystitis developed as a delayed damage in 1 case. Thus, although no efficacy for prevention of relapse which we had expected was not seen, this irradiation method effectively inhibited the progression of lesion and development of delayed damage. (author).

Radiation therapy outcomes in muscle invasive urinary bladder cancer: A single institution experience.

Science.gov (United States)

Tiwana, M S; Ni, L H; Saini, S; Verma, S K; Doddamani, D; Jain, N; Biswas, M; Gupta, Meenu; Gupta, Madhur; Saini, M; Chauhan, N

2016-01-01

To audit the survival outcomes and loco-regional control in muscle invasive urinary bladder cancer patients treated with external beam radiation therapy (RT). From November 2008 through December 2011, 50 consecutively diagnosed muscle invasive urinary bladder carcinoma (T2-4a N0-2, M0) patients were included in this retrospective study. All these patients received external beam RT to a median dose of 60 Gy (range 30-66 Gy), and were not suitable for radical surgery due to patients' preference or medical comorbidities. A stepwise procedure using proportional hazard regression was used to identify prognostic factors with respect to survival. Completion trans-urethral resection of bladder tumor was done in 38 (76%) patients of the cohort and 47 (94%) had transitional cell carcinoma on histopathology. Clinical stage T2 was diagnosed in 40 (80%) patients. The median follow-up for the entire cohort was 14 ± 8.9 months (range 1-36 months). In conclusion, 24 patients (48%) were free of disease, 5 patients (10%) had residual disease, and 13 patients (26%) had died of disease. Two-year and 3 year overall survival of intact bladder for the entire cohort was 58% and 43.6%, respectively. Cox regression modeling strongly suggested clinical stage (P = 0.01) and RT dose (P = 0.001) as being predictors for overall survival. RT shows reliable outcomes and excellent compliance in this advanced disease. Prescribing a higher RT dose could potentially correlate to better intact bladder control rates while maintaining good quality of life in selected patients.

Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

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Tatjana I Djukic

Full Text Available OBJECTIVE: To examine the association of six glutathione transferase (GST gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357 with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006. CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

International Nuclear Information System (INIS)

Bradley, A.J.; MacDonald, L.; Whiteside, S.; Johnson, R.J.; Ramani, V.A.C.

2015-01-01

Aims: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. Materials and methods: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7 th edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. Results: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2–5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. Conclusion: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88

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.

Null mutation for Macrophage Migration Inhibitory Factor (MIF is associated with less aggressive bladder cancer in mice

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Tsimikas John

2007-07-01

Full Text Available Abstract Background Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT and MIF knockout (KO mice given N-butyl-N-(4-hydroxybutyl-nitrosamine (BBN, a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression. Methods 5-month old male C57Bl/6 MIF WT and KO mice were treated with and without BBN. Animals were sacrificed at intervals up to 23 weeks of treatment. Bladder tumor stage and grade were evaluated by H&E. Immunohistochemical (IHC analysis was performed for MIF and platelet/endothelial cell adhesion molecule 1 (PECAM-1, a measure of vascularization. MIF mRNA was analyzed by quantitative real-time polymerase chain reaction. Results Poorly differentiated carcinoma developed in all BBN treated mice by week 20. MIF WT animals developed T2 disease, while KO animals developed only T1 disease. MIF IHC revealed predominantly urothelial cytoplasmic staining in the WT control animals and a shift toward nuclear staining in WT BBN treated animals. MIF mRNA levels were 3-fold higher in BBN treated animals relative to controls when invasive cancer was present. PECAM-1 staining revealed significantly more stromal vessels in the tumors in WT animals when compared to KOs. Conclusion Muscle invasive bladder cancer with increased stromal vascularity was associated with increased MIF mRNA levels and nuclear redistribution. Consistently lower stage tumors were seen in MIF KO compared to WT mice. These data suggest that MIF may play a role in the progression to invasive bladder cancer.

Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

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Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

2013-08-01

Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

[Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism].

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Zhang, Shao-nan; Yong, Qun; Wu, Xin-li; Liu, Xiao-ping

2014-11-01

To investigate the synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and the down-regulating effect of curcumin on the Keapl-Nrf2 pathway, a well recognized anti-drug pathway in almost drugged tumor cells. T24 cells were cultured and treated with increasing concentrations of curcumin(5 ,10 and 20 µmol/mL) combined with cisplatin(30 µg/mL) for 24 hours. The inhibitory effects on T24 cells were tested with MTI colorimetric assay. Nuclear Nrf2 and Keapl , cytoplasmic Keapl and two typical phase II enzymes (GSTP1 and NQOl) were checked with Western blotting. The proliferation of T24 cells was significantly inhibited by different concentrations of curcumin combined with cisplatin. After the treatment with different concentrations of curcumin, Nuclear Nrf2 was decreased but Keapl was increased, and GSTP1 and NQO1 were decreased. Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells is observed in this research. The Keapl-Nrf2 pathway in T24 cells is down-regulated by curcumin. The expression of typical phase I enzymes (GSTP1 and NQO1) mediated by Nrf2 are decreased by curcumin. The sensitivity of tumor cells to chemotherapeutic drugs is then enhanced. These may be the mechanism of synergism effect of curcumin combined with cisplatin.

Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer.

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Abdul-Maksoud, Rehab S; Shalaby, Sally M; Elsayed, Walid S H; Elkady, Saad

2016-10-15

Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (Pbladder cancer reached 97.5% and 92.5%, respectively. Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

Urinary bladder cancer: role of MR imaging.

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Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

2012-01-01

Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. © RSNA, 2012.

Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

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Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

2011-02-01

Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

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Pos, Floris J.; Koedooder, Kees; Hulshof, Maarten C.C.M.; Tienhoven, Geertjan van; Gonzalez Gonzalez, Dionisio

2003-01-01

Purpose: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. Methods and Materials: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. Results: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. Conclusion: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy

Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

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Pos, Floris J; Koedooder, Kees; Hulshof, Maarten C.C.M.; Tienhoven, Geertjan van; Gonzalez Gonzalez, Dionisio

2003-03-01

Purpose: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. Methods and Materials: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. Results: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. Conclusion: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy.

p63 expression defines a lethal subset of muscle-invasive bladder cancers.

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Woonyoung Choi

Full Text Available p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear.We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT in human bladder cancer cell lines (n = 15 and primary tumors (n = 101. We correlated tumor marker expression with stage, disease-specific (DSS, and overall survival (OS. Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1 bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2-T4 tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001. However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007.Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the "epithelial" marker p63 in muscle-invasive tumors is associated with a worse outcome.

High resolution MR imaging of bladder cancer: new criteria for determining depth of wall invasion

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Suh, Chang Hae; Kressel, Herbert Y

1993-01-01

To establish new criteria to determine the depth of bladder cancer as well as to obtain the findings of each stage of bladder cancer we reviewed high resolution MR images of 18 bladder cancer patients including seven cases (26%) with superficial bladder wall invasion. All MR scans were done before biopsy or surgery. Multiple layers of the bladder wall (inner black, middle white, outer black) were demonstrated in 11 cases out of a total 18 cases. Thickening of the middle layer caused by tumor infiltration or edema of lamina propria was seen in 8 of 12 patients with stage T2 or greater, and was suggestive of superficial muscle invasion when multiple layers were demonstrated. Disruption of outer layer (as well as inner layer) and external protrusion of tumor itself were indicative of perivesical invasion. When multiple layers were not demonstrated, the depth of tumor invasion could not be judged. High resolution MR imaging can depict submucosal invasion, muscle invasion, and perivesical invasion secondary to bladder cancer

Orthotopic neo- bladder in women.

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Schettini, Manlio

2010-12-01

Radical cystectomy is the most effective treatment madality for high grade urinary bladder carcinoma and orthotopic reconstruction is the better urinary diversion modality also in women. From 2002 to 2007 we performed 14 radical cystectomies followed by orthotopic reconstruction in women aged between 47 and 68 years (mean age 56) affected by urinary bladder carcinoma. Our reconstructive technique requires the preparation of two strips of the recti muscles fascia, the sectioning of the bladder neck and, when the uterus is present, hysteroannessiectomy and cystectomy en block leaving intact the lateral and inferior vaginal walls. The pelvic floor is stabilized by a colposacropexis with a prosthesis and placing an omental flap over the prosthesis. The orthotopic reconstruction is achieved via a neobladder according to the Padovana technique. The ureters are anastomized to the neobladder and splinted with single J stents. The pathological examination demonstrated in all patients the presence of a high grade carcinoma (G3): more specifically 4 patients had a full thickness intramural infiltration (T2), 2 patients had involvment of the perivescical fat (T3) ad 8 patients were in T1 stage. Lymphnodes were negative for tumour (NO). In 8 patients blood transfusions were necessary to treat post surgical anemia. No significant intra-, peri- or post operative complications were noted. The mean follow-up was 45 months: a patient died for diffuse metastatic disease after 11 months. The remaining patients are still alive and report normal lifestyle: 10 with normal micturition and 4 with urinary retention treated with intermittent self-catetherization. Two patients report nocturnal incontinence treated with hourly micturition and one pad. The five patients who had normal preoperative sexual intercourse resumed a normal sexual activity. The possibility to orthotopically recontruct the female urinary bladder has been established long time after the introduction of orthotopic

Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment.

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Jahnson, Staffan; Hosseini Aliabad, Abolfazl; Holmäng, Sten; Jancke, Georg; Liedberg, Fredrik; Ljungberg, Börje; Malmström, Per-Uno; Rosell, Johan

2016-01-01

The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

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Panebianco, Valeria; Barchetti, Giovanni; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Catalano, Carlo; De Berardinis, Ettore; Leonardo, Constantino; Simone, Giuseppe; Gallucci, Michele; National Cancer Insitute, Rome; Catto, James

2017-01-01

Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. (orig.)

An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

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Panebianco, Valeria; Barchetti, Giovanni; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Catalano, Carlo [Sapienza Univ. Rome (Italy). Dept. of Radiological Sciences, Oncology and Pathology; De Berardinis, Ettore; Leonardo, Constantino [Sapienza Univ. Rome (Italy). Dept. of Gynaecological-Obstetric and Urological Sciences; Simone, Giuseppe; Gallucci, Michele [' ' Regina Elena' ' National Cancer Insitute, Rome (Italy). Dept. of Urology; Catto, James [Sheffield Univ. (United Kingdom). Aademic Urology Unit

2017-09-15

Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. (orig.)

Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis

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Xie LG

2015-12-01

Full Text Available Linguo Xie,1,2,* Yan Sun,2,* Tao Chen,1,2,* Dawei Tian,1,2 Yujuan Li,3 Yu Zhang,1,2 Na Ding,2 Zhonghua Shen,1,2 Hao Xu,1,2 Xuewu Nian,4 Nan Sha,1,2 Ruifa Han,1,2 Hailong Hu,1,2 Changli Wu1,2 Objective: Human murine double minute 2 protein (MDM2 is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05. In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881, and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05. The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05, and no association was observed in total populations and Asians (P>0.05. Conclusion: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

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Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

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Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

2014-09-15

The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

Bladder cancer and schistosomiasis

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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.

Effects and Mechanisms of Checkpoint Inhibitors (CTLA-4, PD-1 and PD-L1 Inhibitors as New Immunotherapeutic Agents for Bladder Cancer

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Serdar Çelik

2018-04-01

Full Text Available Since intravesical Bacillus Calmette-Guerin (BCG began to be used for bladder cancer, our understanding of the importance of immune mechanisms in bladder cancer has steadily grown. With developments in immunotherapy in recent years, the use of new immunotherapeutic agents for bladder cancer, especially chemotherapy-resistant invasive and metastatic cancers, has opened the way for research in this area. Of these new therapeutic agents, this article reviews studies published on PubMed or listed on the ClinicalTrials.gov website as of December 2017 regarding the effects and mechanisms of action of checkpoint inhibitors [cytotoxic t-lymphocyte associated protein-4, programmed cell death 1 receptor (PD-1 and PD-1 ligand inhibitors] on bladder cancer. Because checkpoint inhibitors were first used for chemotherapy-resistant bladder cancer after identification of positive expression in tumor cells and especially in tumor-infiltrating mononuclear cells, significant objective response rates and survival advantages have been reported. Research continues regarding the use of these agents as first- and second-line treatment for metastatic disease in combination with chemotherapy; their efficacy in neoadjuvant, adjuvant, and bladder-preserving approaches to muscle-invasive bladder cancer (MIBC disease, and their use in non-muscle-invasize bladder cancer (NMIBC, especially BCG-refractory disease. Depending on the results of these ongoing studies, immunotherapy may direct the treatment of bladder cancer in the future.

High-Grade Hydronephrosis Predicts Poor Outcomes After Radical Cystectomy in Patients with Bladder Cancer

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Kim, Dong Suk; Cho, Kang Su; Lee, Young Hoon; Cho, Nam Hoon; Oh, Young Taek

2010-01-01

We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy. PMID:20191034

Can re-cTURBT be useful in pT1HG disease as a risk indicator of recurrence and progression? A single centre experience

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Roberto Giulianelli

2017-12-01

Full Text Available Introduction: Understaging after initial transurethral resection is common in patients with high-risk non muscle infiltrating bladder cancer (NMIBC and can delay accurate diagnosis and definitive treatment. The rate of upstaging from T1 to T2 disease after repeated transurethral resection ranges from 0 to 28%, although the rate of upstaging may be even higher up to 49% when muscularis propria is absent in the first specimen. A restaging classic transurethral resection of bladder tumour (re-cTURBT is the better predictor of early stage progression. According to some reports, the rate of positivity for tumor in re-cTURBT performed within eight weeks after initial cTURBT was as high as 18-77%, and in about 40% of the patients a change in tumor stage was reported. We aimed to investigate, in high risk group, the presence of residual tumor following white light classical transurethral resection of bladder tumor (WLre-cTURBT and the different recurrence and progression rate between patients with persistent or negative (pT0 oncological disease after WLre-cTURBT. Materials and methods: A cohort of 285 patients presenting with primitive bladder cancer underwent to WLcTURBT from January 2011 to December 2015; out of them 92 (32.28% were T1HG. In according to EAU guidelines 2011, after 4-6 weeks all HG bladder cancer patients underwent a WL recTURBT . All patients were submitted to a subsequent followup including cystoscopy every 3 months with multiple biopsies, randomly and in the previous zone of resection; urinary citology on 3 specimens and kidney/bladder ultrasound every 6 months. The average follow-up was 48 months. Results: Following WLre-cTURBT we observed a persistent disease in 18 (15.2% patients: 14 (77.7% with a HG-NMIBC and 4 (22.2% with a high grade (HG muscle invasive bladder cancer (pT2HG. After follow up of all 92 patients according to the guidelines EAU, we observed recurrence in 36/92 (39.1% and progression in 14/92 (15.2%. Of 14 NMIBC

Alternating chemo-radiotherapy in bladder cancer: a conservative approach

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Orsatti, Marco; Curotto, Antonio; Canobbio, Luciano; Guarneri, Domenico; Scarpati, Daniele; Venturini, Marco; Franzone, Paola; Giudici, Stefania; Martorana, Giuseppe; Boccardo, Francesco; Giuliani, Luciano; Vitale, Vito

1995-01-01

Purpose: The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. Methods and Materials: Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). Results: A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. Conclusion: Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy

Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

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Anderson, Beverley

2018-05-10

Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

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Yoshizawa, Tsuyoshi; Hayashi, Yukio; Yoshida, Akira; Yoshida, Shohei; Ito, Yoshihiko; Yamaguchi, Kenya; Yamada, Shizuo; Takahashi, Satoru

2018-03-01

To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P 2 X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P 2 X receptor were measured by a radioreceptor assay using [N-methyl- 3 H] scopolamine methyl chloride ([ 3 H]NMS) and α,β-methylene-ATP (2,8- 3 H) tetrasodium salt ([ 3 H]α,β-MeATP). In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [ 3 H]NMS and [ 3 H]α,β-MeATP was concurrently increased in the bladder from diabetic rats. Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P 2 X receptors in STZ-induced diabetic rats.

Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

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Yao Jorge L

2008-04-01

Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

Treatment Options by Stage (Bladder Cancer)

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... above the waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste ... to bladder cancer. Being exposed to paints, dyes, metals, or petroleum products in the workplace. Past treatment ...

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

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Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

2018-01-01

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

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Lea Weber

2018-05-01

Full Text Available Olfactory receptors (ORs are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

Glutathione S-transferase M1 and T1 null genotype frequency ...

Indian Academy of Sciences (India)

PREM CHANDRA SUTHAR

2018-03-24

Mar 24, 2018 ... A comparative analysis with different tribal as well as world population has also been ...... (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus .... from the Spanish Bladder Cancer Study and meta-analyses.

Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.

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Hata, Shuko; Ise, Kazue; Azmahani, Abdullah; Konosu-Fukaya, Sachiko; McNamara, Keely May; Fujishima, Fumiyoshi; Shimada, Keiji; Mitsuzuka, Koji; Arai, Yoichi; Sasano, Hironobu; Nakamura, Yasuhiro

2017-12-01

Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

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Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

2012-01-01

The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

Imaging of urinary bladder tumors

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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

Evaluation of transforming growth factor-β1 suppress Pokemon/epithelial-mesenchymal transition expression in human bladder cancer cells.

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Li, Wei; Kidiyoor, Amritha; Hu, Yangyang; Guo, Changcheng; Liu, Min; Yao, Xudong; Zhang, Yuanyuan; Peng, Bo; Zheng, Junhua

2015-02-01

Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells and the relationship with POK erythroid myeloid ontogenic factor (Pokemon). TGF-β1 and its receptors mediate several tumorigenic cascades that regulate cell proliferation, migration, and survival of bladder cancer cells. Bladder cancer cells T24 were treated with different levels of TGF-β1. Levels of Pokemon, E-cadherin, Snail, MMP2, MMP9, Twist, VEGF, and β-catenin messenger RNA (mRNA) and protein were examined by real-time quantitative fluorescent PCR and Western blot analysis, respectively. The effects of TGF-β1 on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay, proliferation of T24 was evaluated with reference to growth curves with MTT assay, and cell invasive ability was investigated by Transwell assay. Data show that Pokemon was inhibited by TGF-β1 treatment; the gene and protein of E-cadherin and β-catenin expression level showed decreased markedly after TGF-β1 treatment (P Pokemon, β-catenin, and E-cadherin. The high expression of TGF-β1 leads to an increase in the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Related mechanism is worthy of further investigation.

Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

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Tessmann, Josiane Weber; Buss, Julieti; Begnini, Karine Rech; Berneira, Lucas Moraes; Paula, Favero Reisdorfer; de Pereira, Claudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2017-10-01

Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction

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Sun-Ouck Kim

2013-12-01

Full Text Available Purpose This study was designed to investigate the effect of detrusor overactivity induced by partial bladder outlet obstruction (BOO on the expression of aquaporin 1 (AQP1 and caveolin 1 (CAV1 in the rat urinary bladder, and to determine the role of these molecules in detrusor overactivity. Methods Female Sprague-Dawley rats were divided into control (n=30 and experimental (n=30 groups. The BOO group underwent partial BOO, and the control group underwent a sham operation. After 4 weeks, an urodynamic study was performed to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP1 and CAV1 were determined by western blot and immunofluorescence experiments in the rat urinary bladder. Results In cystometrograms, the contraction interval was significantly lower in the BOO group (2.9±1.5 minutes than in the control group (6.7±1.0 minutes (P<0.05. Conversely, the average contraction pressure was significantly higher in the BOO group (21.2±3.3 mmHg than in the control group (13.0±2.5 mmHg (P<0.05. AQP1 and CAV1 were coexpressed in the capillaries, arterioles, and venules of the suburothelial layer. AQP1 and CAV1 protein expression was significantly increased in the BOO rats compared to the control rats (P<0.05. Conclusions Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP1 and CAV1, which were coexpressed in the suburothelial microvasculature. This finding suggests that AQP1 and CAV1 might be closely related to bladder signal activity and may have a functional role in BOO-associated detrusor overactivity.

Expression of Bmi-1 is a prognostic marker in bladder cancer

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Xu Li-Hua

2009-02-01

Full Text Available Abstract Background The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer. Methods We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis. Results Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P P P P P > 0.5. In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P P P > 0.05. Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P P Conclusion Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons.

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Dang, Khoa; Bielefeldt, Klaus; Gebhart, G F

2013-07-01

Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6-S2) or thoracolumbar (TL, T13-L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis.

Downregulation of glutathione S-transferase M1 protein in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced mouse bladder carcinogenesis

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Chuang, Jing-Jing [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China); Dai, Yuan-Chang [Department of Pathology, Chiayi Christian Hospital, Chiayi, Taiwan (China); Lin, Yung-Lun; Chen, Yang-Yi; Lin, Wei-Han [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China); Chan, Hong-Lin [Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan (China); Liu, Yi-Wen, E-mail: ywlss@mail.ncyu.edu.tw [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China)

2014-09-15

Bladder cancer is highly recurrent following specific transurethral resection and intravesical chemotherapy, which has prompted continuing efforts to develop novel therapeutic agents and early-stage diagnostic tools. Specific changes in protein expression can provide a diagnostic marker. In our present study, we investigated changes in protein expression during urothelial carcinogenesis. The carcinogen BBN was used to induce mouse bladder tumor formation. Mouse bladder mucosa proteins were collected and analyzed by 2D electrophoresis from 6 to 20 weeks after commencing continuous BBN treatment. By histological examination, the connective layer of the submucosa showed gradual thickening and the number of submucosal capillaries gradually increased after BBN treatment. At 12-weeks after the start of BBN treatment, the urothelia became moderately dysplastic and tumors arose after 20-weeks of treatment. These induced bladder lesions included carcinoma in situ and connective tissue invasive cancer. In protein 2D analysis, the sequentially downregulated proteins from 6 to 20 weeks included GSTM1, L-lactate dehydrogenase B chain, keratin 8, keratin 18 and major urinary proteins 2 and 11/8. In contrast, the sequentially upregulated proteins identified were GSTO1, keratin 15 and myosin light polypeptide 6. Western blotting confirmed that GSTM1 and NQO-1 were decreased, while GSTO1 and Sp1 were increased, after BBN treatment. In human bladder cancer cells, 5-aza-2′-deoxycytidine increased the GSTM1 mRNA and protein expression. These data suggest that the downregulation of GSTM1 in the urothelia is a biomarker of bladder carcinogenesis and that this may be mediated by DNA CpG methylation. - Highlights: • GSTM1 and NQO-1 proteins decreased in the mouse bladder mucosa after BBN treatment. • BBN induced GSTO1 and Sp1 protein expression in the mouse bladder mucosa. • 5-Aza-2′-deoxycytidine increased GSTM1 mRNA and protein in human bladder cancer cell. • GSTM1

The long term effect and outcome of preoperative chemotherapy combined with radiation therapy for bladder cancer

International Nuclear Information System (INIS)

Nasu, Takahito; Nakane, Hiroshi; Kamata, Seiji; Mitsui, Hiroshi; Hayashida, Shigeaki; Shinohara, Youichi.

1996-01-01

The object of this study is to evaluate the efficacy of preoperative chemotherapy combined with radiation therapy for bladder cancer. A total of 44 patients with bladder cancer were treated by preoperative chemotherapy combined with radiation therapy between October, 1981 and December, 1986. Clinical stages included 4 patients in Ta, 25 in T1, 11 in T2, and 4 in T3. Each patient was treated twice with 15 gray of radiation to the small pelvic cavity and a chemotherapy combination of adriamycin, cis-platinum, tegaful, and peplomycin. The average observation time after the therapy was 83 month, with the maximum being 146 months. Complete remission was included in 5 patients, partial remission in 27, and no change in 12. Thus, the overall effective rate was 72.8%. Operations, selected by the results of the preoperative therapy, included transurethral resection on 28 patients, transurethral fulguration on 2, partial cystectomy on 4, resection of tumor on 4, and total cystectomy on 3. Operations were not performed on 2 patients and not allowed on 1 patient. The outcome during the long-term follow-up included cancer related deaths in 4 patients, and death resulting from other disorders in 9. The 5-year survival rates for superficial and invasive bladder cancer were 92.4%, and 83.9%, respectively. The 10-year survival rates for superficial and invasive bladder cancer were also 92.4% and 83.9%, respectively. The 3-year and 5-year non-recurrence rates for superficial bladder cancer were 75.8%, and 66.9% respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year non-recurrence rates for invasive bladder cancer were both 73.8%. During the follow-up between 9 and 11 years, 3 upper tract tumor were diagnosed (2 ureteral cancer, and 1 renal pelvic cancer). We concluded that preoperative chemotherapy combined with radiation therapy may be effective for the treatment of bladder cancer. (author)

Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

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Zieger, Karsten; Wiuf, Carsten; Jensen, Klaus Møller-Ernst; Ørntoft, Torben Falck; Dyrskjøt, Lars

2009-01-01

Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at 'high risk' of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression. To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with 'high-risk' non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical) resections and full prospective clinical follow-up (> 5 years). We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip ® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes) in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays). Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a 'high-risk' tumor). However, about 25% of the 'high-risk' tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Chromosomal instability (CI) was associated with 'high risk' tumors

Applications of Nanotechnology in Bladder Cancer Therapy

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Jong-Wei Hsu

2012-01-01

Full Text Available Effective therapies can prevent superficial bladder cancer from developing into muscle-invasive stage or more severe stages which require radical cystectomy and negatively affect life quality. In terms of therapeutic approaches against superficial bladder cancer, intravesical (regional therapy has several advantages over oral (systemic therapy. Though urologists can directly deliver drugs to bladder lesions by intravesical instillation after transurethral resection, the efficacy of conventional drug delivery is usually low due to the bladder permeability barrier and bladder periodical discharge. Nanoparticles have been well developed as pharmaceutical carriers. By their versatile properties, nanoparticles can greatly improve the interactions between urothelium and drugs and also enhance the penetration of drugs into urothelium with lesions, which dramatically improves therapeutic efficacy. In this review, we discuss the advances of nanotechnology in bladder cancer therapy by different types of nanoparticles with different encapsulating materials.

The outcome of a multi-centre feasibility study of online adaptive radiotherapy for muscle-invasive bladder cancer TROG 10.01 BOLART

International Nuclear Information System (INIS)

Foroudi, Farshad; Pham, Daniel; Rolfo, Aldo; Bressel, Mathias; Tang, Colin I.; Tan, Alex; Turner, Sandra; Hruby, George; Williams, Stephen; Hayne, Dickon; Lehman, Margot; Skala, Marketa; Jose, Chakiath C.; Gogna, Kumar; Kron, Tomas

2014-01-01

Purpose: To assess whether online adaptive radiotherapy for bladder cancer is feasible across multiple Radiation Oncology departments using different imaging, delivery and recording technology. Materials and methods: A multi-centre feasibility study of online adaptive radiotherapy, using a choice of three “plan of the day”, was conducted at 12 departments. Patients with muscle-invasive bladder cancer were included. Departments were activated if part of the pilot study or after a site-credentialing visit. There was real time review of the first two cases from each department. Results: 54 patients were recruited, with 50 proceeding to radiotherapy. There were 43 males and 7 females with a mean age of 78 years. The tumour stages treated included T1 (1 patient), T2 (35), T3 (10) and T4 (4). One patient died of an unrelated cause during radiotherapy. The three adaptive plans were created before the 10th fraction in all cases. In 8 (16%) of the patients, a conventional plan using a ‘standard’ CTV to PTV margin of 1.5 cm was used for one or more fractions where the pre-treatment bladder CTV was larger than any of the three adaptive plans. The bladder CTV extended beyond the PTV on post treatment imaging in 9 (18%) of the 49 patients. Conclusions: From a technical perspective an online adaptive radiotherapy technique can be instituted in a multi-centre setting. However, without further bladder filling control or imaging, a CTV to PTV margin of 7 mm is insufficient

Detrusor Arreflexia as an End Stage of Neurogenic Bladder in HAM/TSP?

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Matheus Tannus

2011-01-01

Full Text Available The HTLV-1 virus is a known agent involved in the development of HAM/TSP. Past studies have typically observed patients with autonomic dysfunction consisting of detrusor overactivity and detrusor-sphincter dyssynergia, with the occasional observation of underactive detrusor or detrusor arreflexia. However, studies have not yet evaluated the progression of neurogenic bladder over time. In this paper, we describe a HAM/TSP patient with the initial development of overactive detrusor, and subsequent development of detrusor arreflexia. Given a paucity of studies characterizing the effects of HTLV-1 on the autonomic nervous system, particularly aspects controlling continence, this patient's clinical course may represent one type of end point for patients with HAM/TSP and neurogenic bladder. Further cohort or case-series studies, with particular emphasis on the progression of neurogenic bladder, are needed to evaluate the significance of this described case in relation to typical disease progression patterns.

Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (presentation)

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The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously ...

Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (article)

Science.gov (United States)

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously ...

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

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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.

Impact of the Ki-67 labeling index and p53 expression status on disease-free survival in pT1 urothelial carcinoma of the bladder.

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Vetterlein, Malte W; Roschinski, Julia; Gild, Philipp; Marks, Phillip; Soave, Armin; Doh, Ousman; Isbarn, Hendrik; Höppner, Wolfgang; Wagner, Walter; Shariat, Shahrokh F; Brausi, Maurizio; Büscheck, Franziska; Sauter, Guido; Fisch, Margit; Rink, Michael

2017-12-01

The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer. Patients from four Northern German institutions with a primary diagnosis of pT1 bladder cancer between 2009 and 2016 and complete data regarding p53 or Ki-67 expression status were included for final analyses. Baseline patient characteristics (age, gender, age-adjusted Charlson comorbidity index) and tumor characteristics [diagnostic sequence, tumor focality, concomitant carcinoma in situ, 1973 World Health Organization (WHO) grading, lymphovascular invasion, adjuvant instillation therapy] were abstracted by retrospective chart review. Immunohistochemistry for detection of p53 and Ki-67 expression was performed according to standardized protocols. Microscopic analyses were performed by central pathologic review. First, we compared patients with positive vs. negative p53 expression and Ki-67 labeling index [>40% vs. ≤40%; cutoffs based on best discriminative ability in univariable Cox regression analysis with disease-free survival (DFS) as endpoint] with regard to baseline and tumor characteristics. Second, we evaluated the effect of biomarker positivity on DFS by plotting univariable Kaplan-Meier curves and performing uni- and multivariable Cox regression analyses. Of 102 patients with complete information on p53 status, 44 (43.1%) were p53 positive, and they more often harbored concomitant carcinoma in situ (50.0% vs. 27.6%; P=0.032) and 1973 WHO grade 3 (97.7% vs. 69.0%; P=0.001) compared to their p53 negative counterparts. Of 79

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.

Radiotherapy treatment results of bladder cancer: study of 458 patients

International Nuclear Information System (INIS)

Vara Santos, J.; Torre Tomas, A. de la; Romero Fernandez, J.; Regueiro Otero, C.; Clavo Varas, B.; Magallan Sebastian, R.; Valcarcel Sancho, F.; Polo Tolosana, E.; Aragon de la Cruz, G.

1994-01-01

Between 1964 to 1990, 458 patients diagnosed of bladder cancer have been treated with radical radiotherapy in our department. The 5-years and 10-years actuarial survival rates were 37% and 27% respectively. The 5-years and 10-years actuarial local control rates, evaluated in 404 patients, were 41% and 38%. In regard to survival, T stage (p=0.013), advanced intravesical extension or multicentrity (p>0.0001), and squamous differentiation (p<0.0001), reached statistical significance as adverse prognostic factors. In 248 patients, with invasive transitional carcinoma, radical radiotherapy alone was used. In this group of patients, T stage (p=0.006) and advanced intravesical extension or multicentrity (p=0.0002) were adverse prognostic factors for survival. Our results suggest that radical radiotherapy must be considered and alternative to surgery in management of bladder cancer. On the basis of prognostic factors evidenced in this series a subgroup of patients with low probability of survival when treated with exclusive radiotherapy are defined. This patients must be included in clinical research protocols. (Author) 44 refs

Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer

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Fujimoto, Kiyohide; Chihara, Yoshitomo; Kondo, Hideaki; Hirao, Yoshihiko

2006-01-01

We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year non-recurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88)%, respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers. (author)

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.

A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients

DEFF Research Database (Denmark)

Thøgersen, Helle-Merete Vissing; Sørensen, B S; Poulsen, S S

2001-01-01

Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and two receptors of which a subset correlate to tumor stage and survival...... of the EGF family, especially EPI, may be potential bladder tumor markers....

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis.

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Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-04-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments.

[Intradiverticular bladder tumours: review of the Cancer Committee of the French Association of Urology].

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Neuzillet, Y; Comperat, E; Rouprêt, M; Larre, S; Roy, C; Quintens, H; Houede, N; Pignot, G; Wallerand, H; Soulie, M; Pfister, C

2012-07-01

Cancer Committee of the French Association of Urology (CCAFU) conducted a review of the epidemiology, diagnosis and treatment of intradiverticular bladder tumours (TVID) and proposed therapeutic management. A bibliographic research in French and English using Medline(®) with the keywords "tumor", "bladder" and "diverticulum" was performed. TVID are more frequently of stage T ≥ 3a and with non urothelial histology than classical bladder tumors. At diagnosis, the risk of underestimation of the extent and multifocality of the tumor was described. Their prognosis, that was more pejorative than conventional tumors, should impelled to limit the indications of conservative treatment. The evidence levels of analyzed publications were low, with C level according to Sackett score. the specificities of the TVID have lead the CCAFU to propose specific therapeutic guidelines, based on poor evidence level. Ta-T1 low grade TVID can be treated by transurethral resection alone or followed by BCG therapy in cases of associated carcinoma in situ. High-grade TVID, unifocal and without associated carcinoma in situ, can be treated by diverticulectomy associated with pelvic lymphadenectomy. High grade TVID, multiple or associated with carcinoma in situ, warranted total cystectomy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors

International Nuclear Information System (INIS)

Rey, Javier del; Prat, Esther; Ponsa, Immaculada; Lloreta, Josep; Gelabert, Antoni; Algaba, Ferran; Camps, Jordi; Miró, Rosa

2010-01-01

Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001)

Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports.

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Imaoka, Yuki; Kuranishi, Fumito; Miyazaki, Tsubasa; Yasuda, Hiroko; Ohno, Tadao

2017-09-11

The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.

Full-thickness endometriosis of the bladder

DEFF Research Database (Denmark)

Kjer, Jens Jørgen; Kristensen, Jens; Hartwell, Dorthe

2014-01-01

referral centres in Denmark for surgical treatment of stage III and IV endometriosis. POPULATION: Thirty-one women with deep infiltrating bladder endometriosis. METHODS: All women presenting in the Department of Obstetrics and Gynaecology with deep infiltrating bladder endometriosis between March 2002...... and March 2011. We included only patients with symptomatic full-thickness bladder detrusor endometriosis and mucosal involvement. All patients had had bladder symptoms for two to seven years. MAIN OUTCOME MEASURES: Symptoms after surgery and recurrence rate. RESULTS: The main preoperative symptom...

The value of computed tomography in the management of bladder cancer

International Nuclear Information System (INIS)

Karrer, P.; Zingg, E.; Vock, P.; Fischedick, A.; Haertel, M.; Fuchs, W.A.; Bern Univ.

1980-01-01

In 77 patients suffering from bladder cancer histopathological staging and CT-staging are compared. The invasion of bladder and lymph nodes by the tumor is confirmed by histological examination. The CT-results correspond with the pathological findings in 78% for the primary tumor and in 89% for the glands. CT is valuable help to establish the extent and staging of bladder tumors. (orig.) [de

Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers.

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Shiels, Meredith S; Gibson, Todd; Sampson, Joshua; Albanes, Demetrius; Andreotti, Gabriella; Beane Freeman, Laura; Berrington de Gonzalez, Amy; Caporaso, Neil; Curtis, Rochelle E; Elena, Joanne; Freedman, Neal D; Robien, Kim; Black, Amanda; Morton, Lindsay M

2014-12-10

Data on smoking and second cancer risk among cancer survivors are limited. We assessed associations between smoking before first cancer diagnosis and risk of second primary smoking-associated cancers among survivors of lung (stage I), bladder, kidney, and head/neck cancers. Data were pooled from 2,552 patients with stage I lung cancer, 6,386 with bladder cancer, 3,179 with kidney cancer, and 2,967 with head/neck cancer from five cohort studies. We assessed the association between prediagnostic smoking and second smoking-associated cancer risk with proportional hazards regression, and compared these estimates to those for first smoking-associated cancers in all cohort participants. Compared with never smoking, current smoking of ≥ 20 cigarettes per day was associated with increased second smoking-associated cancer risk among survivors of stage I lung (hazard ratio [HR] = 3.26; 95% CI, 0.92 to 11.6), bladder (HR = 3.67; 95% CI, 2.25 to 5.99), head/neck (HR = 4.45; 95% CI, 2.56 to 7.73), and kidney cancers (HR = 5.33; 95% CI, 2.55 to 11.1). These estimates were similar to those for first smoking-associated cancer among all cohort participants (HR = 5.41; 95% CI, 5.23 to 5.61). The 5-year cumulative incidence of second smoking-associated cancers ranged from 3% to 8% in this group of cancer survivors. Understanding risk factors for second cancers among cancer survivors is crucial. Our data indicate that cigarette smoking before first cancer diagnosis increases second cancer risk among cancer survivors, and elevated cancer risk in these survivors is likely due to increased smoking prevalence. The high 5-year cumulative risks of smoking-associated cancers among current smoking survivors of stage I lung, bladder, kidney, and head/neck cancers highlight the importance of smoking cessation in patients with cancer. © 2014 by American Society of Clinical Oncology.

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192

International Nuclear Information System (INIS)

Wijnmaalen, Arendjan; Helle, Peter A.; Koper, Peter C.M.; Jansen, Peter P.; Hanssens, Patrick E.J.; Boeken Kruger, Cornelis G.G.; Putten, Wim L.J. van

1996-01-01

Purpose: In our center interstitial radiation has played an important role in the treatment of bladder cancer patients for over 40 years. Radium needles, that were initially used, were replaced by caesium needles in 1983, whereas the afterloading iridium wire technique was adopted in 1989. Patients with solitary tumors (T1, T2 and T3) with a surface diameter of < 5 cm are considered for interstitial radiation. In this study we report on the results of the afterloading iridium wire technique in patients with muscle invasive bladder cancer. Materials and Methods: From May 1989 to September 1993 interstitial radiation using iridium wires was part of the treatment in 46 patients with muscle invasive bladder cancer (37 T2, 9 T3). The mean age was 67 years. After transurethral resection of all visible tumor (if possible), in most cases 40 Gy (20 x 2.0 Gy, midplane dose) external beam radiation was delivered to the true pelvis, followed by 30 Gy interstitial radiation using iridium-192 wires covering the tumor area in the bladder. Results: After a median follow-up of 26 months, bladder relapses occurred in 7 patients. In 5 of them the tumor relapsed in the initial area, in 1 patient elsewhere in the bladder and in 1 patient tumor recurred in and outside the initial site. Recurrence was superficial (T1) in 4 patients. A relapse in the urethra was found once. Metastases developed in 13 patients, in 8 without bladder relapse. During the observation period 17 patients died, 13 due to bladder cancer. The actuarial bladder relapse-free survival at 4 years was 74% and 82% for T2 and T3 tumors, respectively. The actuarial distant metastases-free survival was 65% for both categories. No serious toxicity was recorded. Conclusion: In a selected group of patients with muscle invasive bladder cancer transurethral resection in combination with external beam and interstitial radiation provides an excellent opportunity to preserve the bladder with a high chance of success. Development of

Endorectal magnetic resonance imaging of the prostate and bladder

International Nuclear Information System (INIS)

Sugimura, Yoshiki; Hayashi, Norio; Yamashita, Atsushi; Kinbara, Hiroyuki; Arima, Kiminobu; Tochigi, Hiromi; Kawamura, Juichi

1994-01-01

Endorectal magnetic resonance imaging (MRI) using an endorectal surface coil has been evaluated basically and clinically. This new modality obtained increased resolution magnetic resonance images of the pathologic conditions of the prostate and bladder. Compared with images obtained with a body coil, the surface coil images clearly demonstrate prostatic intraglandular zonal anatomy. The clear images of prostatic capsule and neurovascular bundle seen on the surface coil may contribute to the local staging of prostate cancer. The staging diagnosis of bladder tumor located in the bladder neck will be the best candidate for endorectal MRI. Enhancement with gadolinium may improve the ability to differentiate superficial from deep bladder-wall tumors. We concluded that endorectal MRI is safely performed and is extremely useful for the local staging of prostate cancer and bladder neck tumor. Further studies will be required to evaluate the clinical significance of this new modality. (author)

Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells.

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Li, Yangle; Zhao, Xiaokun; Tang, Huiting; Zhong, Zhaohui; Zhang, Lei; Xu, Ran; Li, Songchao; Wang, Yi

2012-01-01

It was the aim of this study to explore the effects of 3-(5'-hydroxymethyl-2'-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1α (HIF-1α). BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1α and HIF-1α-mediated genes was detected by Western blotting. RT-PCR was used to detect HIF-1α mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1α protein expression was detected by Western blotting. Hypoxic T24 cells expressed a higher level of HIF-1α, vascular endothelial growth factor, matrix metalloproteinases-2, B-cell lymphoma/leukemia-2 protein and HIF-1α mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1-downregulated HIF-1α expression was reversed by PD98059 and SB203580, respectively. YC-1 inhibits HIF-1α and HIF-1α-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1α. Copyright © 2011 S. Karger AG, Basel.

Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

International Nuclear Information System (INIS)

Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk; Lee, Nam-Ho; Kim, Se-Jae

2011-01-01

Highlights: → Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. → Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. → Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. → Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPARγ, C/EBPα, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

Clinical–Pathologic Stage Discrepancy in Bladder Cancer Patients Treated With Radical Cystectomy: Results From the National Cancer Data Base

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Gray, Phillip J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Lin, Chun Chieh; Jemal, Ahmedin [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Fedewa, Stacey A. [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Kibel, Adam S. [Division of Urology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Rosenberg, Jonathan E. [Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kamat, Ashish M. [Division of Surgery, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Virgo, Katherine S. [Department of Health Policy and Management, Emory University, Atlanta, Georgia (United States); Blute, Michael L. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A., E-mail: jefstathiou@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-04-01

Purpose: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database. Methods and Materials: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical–pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models. Results: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute–designated cancer center (HR 0.90, P=.042). Conclusions: Clinical–pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.

1 The effectiveness of ultrasound in the diagnosis of bladder ...

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evaluating patients presenting with haematuria or suspected to have bladder tumours. It is cheap, ... world, transitional cell carcinoma (TCC) is the commonest, while in developing countries squamous cell ..... Fenlon, H., Bell, T., Ahari, H. & Hussain, S. (1997) Virtual cystoscopy: early clinical experience. Radiology 250 ...

Expression of Vitamin D Receptor (VDR Positively Correlates with Survival of Urothelial Bladder Cancer Patients

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Wojciech Jóźwicki

2015-10-01

Full Text Available Vitamin D3 shows tumoristatic and anticancer effects by acting through the vitamin D receptor (VDR, while hydroxylation of 25-hydroxyvitamin D3 at position 1α by CYP27B1 is an essential step in its activation. The expression of both the VDR and CYP27B1 has been found in many normal and cancer tissues, but there is a lack of information about its expression in human bladder cancers. The aim of the present research was to examine whether the expression of the VDR and CYP27B1 in bladder cancer was related to the prognostic markers and disease outcome. We analyzed VDR and CYP27B1 in samples of tumor and normal tissues obtained from 71 urinary bladder cancer patients. The highest VDR immunostaining was found in normal epithelium and was significantly lower in bladder cancer cells (p < 0.001 with Mann–Whitney U test. VDR expression was lowest in more advanced (pT2b–pT4 (p = 0.005 with Mann–Whitney U test and metastasizing cancers (p < 0.05 and p = 0.004 with Mann–Whitney U test for nuclear and cytoplasmic VDR immunostaining, respectively. The lack of cytoplasmic and nuclear VDR was also related to shorter overall survival (for cytoplasmic VDR immunolocalization 13.3 vs. 55.3 months of survival, HR = 1.92, p = 0.04 and for nuclear VDR immunostaining 13.5 vs. 55.3 months of survival, HR = 2.47, p = 0.002 with Mantel-Cox test. In cases with the lack of high cytoplasmic VDR staining the non-classic differentiations (NDs was observed in higher percentage of tumor area. CYP27B1 expression was lower in cancer cells than in normal epithelial cells (p = 0.03 with Mann–Whitney U test, but its expression did not correlate with tumor stage (pT, metastasizing, grade, mitotic activity or overall survival. In conclusion, expression of the VDR and CYP27B1 are deregulated in urothelial bladder cancers. Although our results showing a relationship between the decreased VDR expression and prognostic markers and survival time indicate potential usefulness of

Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells.

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Liu, Qian; Liu, Hui; Cheng, Hepeng; Li, Yang; Li, Xiaodong; Zhu, Chaoyang

2017-01-01

Bladder cancer is a common serious disease around the world. Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the development and progression of various cancers, including bladder cancer. The aim of this study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1) on proliferation and apoptosis in bladder cancer cell lines and the underlying mechanism. The levels of TUG1 were detected by quantitative real time polymerase chain reaction (qRT-PCR) in bladder cancer tissues and cells. The mRNA and protein levels of zinc finger E-box binding homeobox 2 (ZEB2) were measured by qRT-PCR and Western blot analysis, respectively. The functional targets of TUG1 were predicted by online softwares and confirmed by luciferase reporter assay. The effects of TUG1 on cell proliferation and apoptosis were examined by MTT and apoptosis assay, respectively. The expression levels of β-catenin, cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis. The levels of TUG1 and ZEB2 were significantly increased in bladder cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2 overexpression reversed the effects of TUG1 knockdown on cell proliferation and apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142 could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the Wnt/β-catenin pathway by regulating ZEB2 expression in bladder cancer cells. Downregulation of TUG1 expression inhibited proliferation and induced apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through the inactivation of Wnt/β-catenin pathway.

Antibody conjugate radioimmunotherapy of superficial bladder cancer

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Perkins, Alan; Hopper, Melanie; Murray, Andrea; Frier, Malcolm; Bishop, Mike

2002-01-01

The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C 595 (gG3) which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radio immuno conjugates of the C 595 antibody have been produced with high radiolabelling efficiency and immuno reactivity using Tc-99 m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun. (author)

The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy

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Chung, Woong Ki; Oh, Bong Ryoul; Ahn, Sung Ja; Nah, Byung Sik; Kwon, Dong Deuk; Park, Kwang Sung; Ryu, Soo Bang; Park, Yang Il

2002-01-01

This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Twenty eight patient with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were performed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uniformed in 3. Radiation therapy was performed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was performed on the prognostic factors affecting the survival rate. The survival rate was 76%, 46%, 33%, 33% at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, T-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uni- and multivariate analysis. In univariate analysis, the T-stage (ρ 0.078) and radiation dose (ρ = 0.051) were marginally significant, and the treatment response (ρ = 0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. The

The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy

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Chung, Woong Ki; Oh, Bong Ryoul; Ahn, Sung Ja; Nah, Byung Sik; Kwon, Dong Deuk; Park, Kwang Sung; Ryu, Soo Bang; Park, Yang Il [Chonnam National University Medical School, Chonnam National University Hospital, Kwangju (Korea, Republic of)

2002-06-15

This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Twenty eight patient with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were performed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uniformed in 3. Radiation therapy was performed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was performed on the prognostic factors affecting the survival rate. The survival rate was 76%, 46%, 33%, 33% at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, T-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uni- and multivariate analysis. In univariate analysis, the T-stage ({rho} 0.078) and radiation dose ({rho} = 0.051) were marginally significant, and the treatment response ({rho} = 0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival

Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

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Shipley, William U.; Zietman, Anthony L.

1996-01-01

In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.

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Jiang, Huijuan; Hu, Xigang; Zhang, Hongzhi; Li, Wenbo

2017-04-04

Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo. The levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing. LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.

[Retrospective analysis of 47 cases with hilar cholangiocarcinoma using T-staging system].

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Peng, Cheng-hong; Zhao, Zhi-ming; Peng, Shu-you; Liu, Ying-bin; Wu, Yü-lian; Fang, He-qing; Jiang, Xian-chuan

2005-01-01

To evaluate the clinical value of T-staging system for hilar cholangiocarcinoma which was adopted in memorial Sloan-Kettering cancer center of New York. The image data of these 47 patients were analyzed retrospectively from December 1997 to December 2002 whose data were according with our demand, and they were staged into three-stage according to the criteria of the T-staging system. The difference of respectability, ratio of tumor-free resection margin and actuarial survival rate were analyzed for different T-staging. And the coincident ratio of three different kinds of imaging methods was also analyzed. Twenty patients had T(1) tumors, twenty three had T(2) tumors and four had T(3) tumors. The resectability of the three stage was 60%, 39% and 0% respectively, and the difference was significant (P = 0.013). The likelihood of achieving tumor-free margin decreased progressively with increasing T stage (P = 0.018). The cumulative 1-year survival rates of T(1), T(2) and T(3) patients were 60%, 39% and 0% respectively, and the cumulative 3-year survival rate was 35%, 9% and 0% respectively, the survival of different stage patients differed markedly (P = 0.0103). The coincident ratio of combined using MRCP and color Doppler-ultrasonography was higher than that of combined using MRCP and B-ultrasonography or combined using CT/SCT and color Doppler-ultrasonography (P = 0.007). The T-staging system has a better value for preoperative assessment, and can be used to judge resectability and survival of hilar cholangiocarcinoma. It will be helpful to use MRCP and color Doppler-Ultrasonography combined to verdict the coverage of the tumor and the T-staging preoperatively.

Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation

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Davis Carole A

2007-03-01

Full Text Available Abstract Background In general, inflammation plays a role in most bladder pathologies and represents a defense reaction to injury that often times is two edged. In particular, bladder neurogenic inflammation involves the participation of mast cells and sensory nerves. Increased mast cell numbers and tryptase release represent one of the prevalent etiologic theories for interstitial cystitis and other urinary bladder inflammatory conditions. The activity of mast cell-derived tryptase as well as thrombin is significantly increased during inflammation. Those enzymes activate specific G-protein coupled proteinase-activated receptors (PARs. Four PARs have been cloned so far, and not only are all four receptors highly expressed in different cell types of the mouse urinary bladder, but their expression is altered during experimental bladder inflammation. We hypothesize that PARs may link mast cell-derived proteases to bladder inflammation and, therefore, play a fundamental role in the pathogenesis of cystitis. Results Here, we demonstrate that in addition to the mouse urinary bladder, all four PA receptors are also expressed in the J82 human urothelial cell line. Intravesical administration of PAR-activating peptides in mice leads to an inflammatory reaction characterized by edema and granulocyte infiltration. Moreover, the inflammatory response to intravesical instillation of known pro-inflammatory stimuli such as E. coli lipopolysaccharide (LPS, substance P, and antigen was strongly attenuated by PAR1-, and to a lesser extent, by PAR2-deficiency. Conclusion Our results reveal an overriding participation of PAR1 in bladder inflammation, provide a working model for the involvement of downstream signaling, and evoke testable hypotheses regarding the role of PARs in bladder inflammation. It remains to be determined whether or not mechanisms targeting PAR1 gene silencing or PAR1 blockade will ameliorate the clinical manifestations of cystitis.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

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Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Academic Radiation Oncology Department, Centre Oscar Lambret, Lille (France); Barney, Brandon [Mayo Clinic, Rochester, Minnesota (United States); Sundar, Santhanam [Department of Oncology, Nottingham University Hospitals National Health Service Trust, Nottingham (United Kingdom); Poortmans, Philip [Department of Radiation Oncology, Radboud university medical center, Nijmegen (Netherlands); Villa, Salvador [Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona (Spain); Nasrallah, Haitam [Division of Oncology, Rambam Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ghadjar, Pirus [Department of Radiation Oncology, Bern University Hospital, Bern (Switzerland); Lassen-Ramshad, Yasmin [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Senkus, Elżbieta [Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk (Poland); Oar, Andrew [Genesis Cancer Care, Southport (Australia); Roelandts, Martine [Institut Jules Bordet, Brussels (Belgium); Amichetti, Maurizio [Provincial Agency for Proton Therapy, Trento (Italy); Vees, Hansjoerg [Department of Radiation Oncology, Hopital de Sion, Sion (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

2015-07-15

Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.

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Pasquier, David; Barney, Brandon; Sundar, Santhanam; Poortmans, Philip; Villa, Salvador; Nasrallah, Haitam; Boujelbene, Noureddine; Ghadjar, Pirus; Lassen-Ramshad, Yasmin; Senkus, Elżbieta; Oar, Andrew; Roelandts, Martine; Amichetti, Maurizio; Vees, Hansjoerg; Zilli, Thomas; Ozsahin, Mahmut

2015-07-15

Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this

Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model.

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de Moura, Nelci Antunes; Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; Barbisan, Luís Fernando

2010-02-01

The potential promoting effect of Diuron was investigated in a mouse model of mammary and urinary bladder carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Four-week old female Swiss mice were allocated to five groups: Groups G1-G3 received DMBA (5 x 1.5 mg/mouse) and BBN (8 x 7.5 mg/mouse) and G4 and G5 groups received only vehicles during the first 6 weeks. At week 7, G1 and G5 groups received basal diet and G2, G3 and G4 groups were fed a diet containing Diuron at 1,250, 2,500 and 2,500 ppm, respectively, during 13 weeks. At week 20, the animals were euthanized and the gross tumors were registered. Mammary glands and urinary bladder were processed for histopathological analysis. Samples from non-tumor areas were evaluated for cell proliferation by 5-bromodeoxyuridine labeling index (BrdU-LI%) and apoptosis. Dietary treatment with Diuron at 1,250 and 2,500 ppm significantly increased BrdU-LI% (P Diuron 2,500 ppm (G3). In contrast, in the mammary gland, Diuron feeding for 13 weeks did not significantly alter cell proliferation and apoptosis indexes or the incidence of hyperplastic lesions or neoplasms in the DMBA/BBN-initiated groups. These findings suggest that Diuron is a promoting agent to the urinary bladder but not to the mammary gland in female Swiss mice submitted to a medium-term two-stage carcinogenesis bioassay.

Outcome of urinary bladder cancer after combined therapies.

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Anghel, R M; Gales, L N; Trifanescu, O G

2016-01-01

Rationale: Urinary bladder cancer is the fourth most common cancer in men and the eighth in women, being an important public health issue. Methods: : Medical files of 155 patients (132M/ 23F) with urinary bladder cancer treated between 2006 and 2012 were retrospectively analyzed. The median age at diagnosis was 65 years (range: 19-85 years). Disease free survival (DFS) for patients with complete tumor resection receiving adjuvant treatment and progression free survival (PFS) for patients with post-operative residual disease was estimated. Results: The distribution of the stage disease was: 50 patients (32.2%) stage II, 47 (30.3%) stage III, 58 (37.4%) stage IV. Radical cystectomy was performed in 56 patients (36.1%), while 99 patients (63.9%) underwent repeated transurethral resection of the urinary bladder tumor (TURBT). Postoperative treatment included multimodal therapy in 47 patients (30.3%) (chemotherapy and external beam radiation), external beam radiation alone in 57 patients (36.8%) and chemotherapy alone (methotrexate, vinblastine, doxorubicin, and cisplatin-MVAC or gemcitabine+platinum) in 51 patients (32.9%). After a median follow-up of 31 months (range: 3-79 months), 51 patients (32.9%) presented local recurrence, 32 patients (21%) distant recurrence (metastases), 10 patients (6.4%) both local and distant recurrence, and 62 patients (40%) were free of disease. The median duration until progression was 27 months. Discussion: Despite the combined therapy approaches, urinary bladder carcinoma remains an aggressive disease, with a high relapse rate. Earlier diagnosis, aggressive radical surgery in intention to cure (cystectomy), and adjuvant multimodal treatment (radiotherapy and chemotherapy) are needed for survival improvement.

[miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

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Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2017-10-01

Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

Does phosphorylation of cofilin affect the progression of human bladder cancer?

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Chung, Hong; Kim, Hong Sup; Kim, Bokyung; Jung, Seung-Hyo; Won, Kyung-Jong; Jiang, Xiaowen; Lee, Chang-Kwon; Lim, So Dug; Yang, Sang-Kuk; Song, Ki Hak

2013-01-01

We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer

Comparison of Coregistration Accuracy of Pelvic Structures Between Sequential and Simultaneous Imaging During Hybrid PET/MRI in Patients with Bladder Cancer.

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Rosenkrantz, Andrew B; Balar, Arjun V; Huang, William C; Jackson, Kimberly; Friedman, Kent P

2015-08-01

The aim of this study was to compare coregistration of the bladder wall, bladder masses, and pelvic lymph nodes between sequential and simultaneous PET and MRI acquisitions obtained during hybrid (18)F-FDG PET/MRI performed using a diuresis protocol in bladder cancer patients. Six bladder cancer patients underwent (18)F-FDG hybrid PET/MRI, including IV Lasix administration and oral hydration, before imaging to achieve bladder clearance. Axial T2-weighted imaging (T2WI) was obtained approximately 40 minutes before PET ("sequential") and concurrently with PET ("simultaneous"). Three-dimensional spatial coordinates of the bladder wall, bladder masses, and pelvic lymph nodes were recorded for PET and T2WI. Distances between these locations on PET and T2WI sequences were computed and used to compare in-plane (x-y plane) and through-plane (z-axis) misregistration relative to PET between T2WI acquisitions. The bladder increased in volume between T2WI acquisitions (sequential, 176 [139] mL; simultaneous, 255 [146] mL). Four patients exhibited a bladder mass, all with increased activity (SUV, 9.5-38.4). Seven pelvic lymph nodes in 4 patients showed increased activity (SUV, 2.2-9.9). The bladder wall exhibited substantially less misregistration relative to PET for simultaneous, compared with sequential, acquisitions in in-plane (2.8 [3.1] mm vs 7.4 [9.1] mm) and through-plane (1.7 [2.2] mm vs 5.7 [9.6] mm) dimensions. Bladder masses exhibited slightly decreased misregistration for simultaneous, compared with sequential, acquisitions in in-plane (2.2 [1.4] mm vs 2.6 [1.9] mm) and through-plane (0.0 [0.0] mm vs 0.3 [0.8] mm) dimensions. FDG-avid lymph nodes exhibited slightly decreased in-plane misregistration (1.1 [0.8] mm vs 2.5 [0.6] mm), although identical through-plane misregistration (4.0 [1.9] mm vs 4.0 [2.8] mm). Using hybrid PET/MRI, simultaneous imaging substantially improved bladder wall coregistration and slightly improved coregistration of bladder masses and

Fatores de risco em carcinomas de células transicionais da bexiga: risk factors Transitional cell carcinoma of the bladder

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Ricardo Brianezi Tiraboschi

2002-01-01

Full Text Available OBJETIVO: Investigar alguns dados epidemiológicos do câncer vesical bem como fatores de risco. MÉTODOS: Foram selecionados 125 pacientes atendidos no período 1980-2002, com idade média de 63,6±11,3 anos, sendo 97 (77,6% homens e 28 (22,4% mulheres. As proporções de tumores G1, G2 e G3 foram: 48%, 35,2% e 16,8%. As proporções dos estádios da lesão primária foram: pTa-1 - 85 ( 68% e pT2-4 - 40 ( 32%. Entre os pacientes com tumores superficiais houve recidiva em 41 (48,2%. RESULTADOS: O grau da lesão primária mostrou relação com o estádio T (pOBJECTIVE: To analyse some epidemiological data of patients with transitional cell carcinoma of the bladder (TCC and the predictive value of conventional risk factors. METHODS: From 1980 to 2002, 125 patients were treated at our hospital and selected retrospectively for this study. The series mean age was 63,6±11,3 years, being 77.6% males and 22.4% females. The proportions of G!, G2 and G3 TCC were: 48%, 35.2% and 16.8%. The T stage was: pTa-1 - 85 (68% and pT2-4 - 40 (32%. Superficial tumors were treated by TUR alone or plus BCG (>G1, and the invasives ones by radical cystectomy. The vesical reccurence rate of superficial TCC was 48.2%. RESULTS: TCC grade showed a positive association with T stage (p<0.0001 and patient survival (p<0.0001, but not with local bladder reccurence of superficial tumors (p=0.72. The T stage also showed a strong correlation with patient survival (p<0.0001. CONCLUSION: The TCC is more common in male than in female with mean age of 63.2 years. The tumor grading and staging exhibited as strong predictive value for disease progression and patient survival.

SU-E-J-103: Propagation of Rectum and Bladder Contours for Tandem and Ring (T&R) HDR Treatment Using Deformable Image Registration

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Yuan, Y; Chao, M; Sheu, R; Dumane, V; Gupta, V; Lo, Y [Mount Sinai Medical Center, New York, NY (United States)

2015-06-15

Purpose: To investigate the feasibility of using DIR to propagate the manually contoured rectum and bladder from the 1st insertion to the new CT images on subsequent insertions and evaluate the segmentation performance. Methods: Ten cervical cancer patients, who were treated by T&R brachytherapy in 3–4 insertions, were retrospectively collected. In each insertion, rectum and bladder were manually delineated on the planning CT by a physicist and verified by a radiation oncologist. Using VelocityAI (Velocity Medical Solutions, Atlanta, GA), a rigid registration was firstly employed to match the bony structures between the first insertion and each of the following insertions, then a multi-pass B-spine DIR was carried out to further map the sub volume that encompasses rectum and bladder. The resultant deformation fields propagated contours, and dice similarity coefficient (DSC) was used to quantitatively evaluate the agreement between the propagated contours and the manually-delineated organs. For the 3rd insertion, we also evaluated if the segmentation performance could be improved by propagating the contours from the most recent insertion, i.e., the 2nd insertion. Results: On average, the contour propagation took about 1 minute. The average and standard deviation of DSC over all insertions and patients was 0.67±0.10 (range: 0.44–0.81) for rectum, and 0.78±0.07 (range: 0.63–0.87) for bladder. For the 3rd insertion, propagating contours from the 2nd insertion could improve the segmentation performance in terms of DSC from 0.63±0.10 to 0.72±0.08 for rectum, and from 0.77±0.07 to 0.79±0.06 for bladder. A Wilcoxon signed rank test indicated that the improvement was statistically significant for rectum (p = 0.004). Conclusion: The preliminary results demonstrate that deformable image registration could efficiently and accurately propagate rectum and bladder contours between CT images in different T&R brachytherapy fractions. We are incorporating the propagated

[A comparison between 3.0 T MRI and histopathology for preoperative T staging of potentially resectable esophageal cancer].

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Wang, Z Q; Zhang, F G; Guo, J; Zhang, H K; Qin, J J; Zhao, Y; Ding, Z D; Zhang, Z X; Zhang, J B; Yuan, J H; Li, H L; Qu, J R

2017-03-21

Objective: To explore the value of 3.0 T MRI using multiple sequences (star VIBE+ BLADE) in evaluating the preoperative T staging for potentially resectable esophageal cancer (EC). Methods: Between April 2015 and March 2016, a total of 66 consecutive patients with endoscopically proven resectable EC underwent 3.0T MRI in the Affiliated Cancer Hospital of Zhengzhou University.Two independent readers were assigned a T staging on MRI according to the 7th edition of UICC-AJCC TNM Classification, the results of preoperative T staging were compared and analyzed with post-operative pathologic confirmation. Results: The MRI T staging of two readers were highly consistent with histopathological findings, and the sensitivity, specificity and accuracy of preoperative T staging MR imaging were also very high. Conclusion: 3.0 T MRI using multiple sequences is with high accuracy for patients of potentially resectable EC in T staging. The staging accuracy of T1, T2 and T3 is better than that of T4a. 3.0T MRI using multiple sequences could be used as a noninvasive imaging method for pre-operative T staging of EC.

Adenocarcinoma of the urinary bladder, mesonephroid type: a rare case

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Mahmoud Abbas

2013-02-01

Full Text Available Primary adenocarcinoma of the urinary bladder is a rare disease. It occurs in 0.5-2% of all bladder cancers and is discussed as the malignant counterpart of nephrogenic adenomas. We report a 46-year-old white female presented with gross hematuria for clinical examination. Histopathology revealed pT2, Pn1, L1, G2 adenocarcinoma of the bladder and carcinoma in situ according to the TNM classification. Computed tomography scan diagnostic was unremarkable. Patients with adenocarcinoma of the urinary bladder should be treated vigorously and without time delay. Only 7 cases of adenocarcinoma in the urinary bladder (mesonephroid have been described until now. We present a case of clear cell adenocarcinoma of the urinary bladder, mesonephroid type that early diagnosed and till now 3 months after the cystectomy without symptoms and without complications.

Bladder Cancer Treatment (PDQ®)—Patient Version

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Treatment of bladder cancer depends on the stage of the cancer. Treatment options include different types of surgery (transurethral resection, radical and partial cystectomy, and urinary diversion), radiation therapy, chemotherapy, and immunotherapy. Learn more about how bladder cancer is treated.

18 F-fluorodeoxyglucose positron emission tomography-computed tomography for preoperative lymph node staging in patients undergoing radical cystectomy for bladder cancer: a prospective study.

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Hitier-Berthault, Maryam; Ansquer, Catherine; Branchereau, Julien; Renaudin, Karine; Bodere, Françoise; Bouchot, Olivier; Rigaud, Jérôme

2013-08-01

The objective of our study was to analyze the diagnostic performance of (18) F-fluorodeoxyglucose positron emission tomography-computed tomography for lymph node staging in patients with bladder cancer before radical cystectomy and to compare it with that of computed tomography. A total of 52 patients operated on between 2005 and 2010 were prospectively included in this prospective, mono-institutional, open, non-randomized pilot study. Patients who had received neoadjuvant chemotherapy or radiotherapy were excluded. (18) F-fluorodeoxyglucose positron emission tomography-computed tomography in addition to computed tomography was carried out for lymph node staging of bladder cancer before radical cystectomy. Lymph node dissection during radical cystectomy was carried out. Findings from (18) F-fluorodeoxyglucose positron emission tomography-computed tomography and computed tomography were compared with the results of definitive histological examination of the lymph node dissection. The diagnostic performance of the two imaging modalities was assessed and compared. The mean number of lymph nodes removed during lymph node dissection was 16.5 ± 10.9. Lymph node metastasis was confirmed on histological examination in 22 cases (42.3%). This had been suspected in five cases (9.6%) on computed tomography and in 12 cases (23.1%) on (18) F-fluorodeoxyglucose positron emission tomography-computed tomography. Sensitivity, specificity, positive predictive value, negative predictive value, relative risk and accuracy were 9.1%, 90%, 40%, 57.4%, 0.91 and 55.7%, respectively, for computed tomography, and 36.4%, 86.7%, 66.7%, 65%, 2.72, 65.4%, respectively, for (18) F-fluorodeoxyglucose positron emission tomography-computed tomography. (18) F-fluorodeoxyglucose positron emission tomography-computed tomography is more reliable than computed tomography for preoperative lymph node staging in patients with invasive bladder carcinoma undergoing radical cystectomy. © 2012 The Japanese

Analysis of the prognostic factors for low rectal cancer with the pT1-2NxM0 stage after abdominoperineal resection.

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Zhang, Xing-mao; Ma, Chao; Sun, Da-yong; Wang, Zheng; Zhou, Zhi-xiang

2015-01-01

This study was designed to explore the factors influencing local recurrence and survival for low rectal cancer with pT1-2NxM0 stage after an abdominoperineal resection (APR). Data of 429 patients confirmed to have pT1-2NxM0 after APR were reviewed. The recurrence rate in patients with intraoperative perforation, less than 12 lymph nodes (LNs) harvested, T2 staging, and positive circumferential resection margin (CRM) was 25.1, 19.9, 9.5, and 26.1% compared with 6.9, 7.0, 0, and 5.8% in patients with no perforation, 12 or more LNs harvested, T1, and negative CRM. The 5-year survival rate in patients with age of at least 70, perforation, less than 12 LNs harvested, T2, and positive CRM was 71.1, 60.8, 58.8, 69.9, and 46.0%, but 73.4, 73.5, 73.8, 89.4, and 75.0% in patients with age less than 70, no perforation, 12 or more LNs harvested, T1, and negative CRM. Meanwhile, patients with N0, N1, and N2 had a survival rate of 90.7, 69.9, and 63.9%. Multivariate analysis showed that perforation (PCRM status (P=0.002) were associated with local recurrence, whereas age of the patients (P=0.023), N staging (PCRM status (P=0.004) were associated with survival. APR was affected by patients' age, operation performer, perforation, number of LNs harvested, T staging, N staging, differentiation, and CRM status. Perforation, number of LNs harvested, T staging, differentiation, and CRM status were independent factors for recurrence; meanwhile, age of the patients, N staging, differentiation, and CRM status were independent factors influencing survival.

Genetic instability in urinary bladder cancer: An evolving hallmark.

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Wadhwa, N; Mathew, B B; Jatawa, S K; Tiwari, A

2013-01-01

Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA) mismatch repair (MMR) system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

Genetic instability in urinary bladder cancer: An evolving hallmark

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N Wadhwa

2013-01-01

Full Text Available Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA mismatch repair (MMR system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

Rectal bladder-type: ileum-sigma-rectum pouch

International Nuclear Information System (INIS)

Krajka, K.; Mikszewicz, A.; Stachurski, L.; Perkowski, D.

1994-01-01

The paper presents a method of creating rectal bladder by using the proximal part of rectum, the distal part of sigma and a 40 cm long segment of detubularized ileum. Ureters were attached to the proximal end of ileal segment by Wallace-I technique. Initially the retrograde pyelonephritis was to be prevented by intussuscepting a 4 cm long part of the uretero-ilea anastomosis and by positioning isoperistaltically a 15-16 cm long part of the ileal segment. Because of the insufficiency of such a mechanism, in 4 latest cases the intussuscepted segment was increased to 8 cm. 8 patients suffering from stage T3a and T3b invasive carcinoma of the bladder were treated by this procedure. The ureteral stens were led out via the rectal tube. They were removed days after the operation. The whole post-operative period was uneventful. The patients were under close follow-up from 5 to 22 months. Three of them died due to a progression of the disease. All the patients had 3-4 watery stools a day and one at night. Check-ups performed three and six months after the operation revealed a proper out flow of contrast medium from kidneys and a reduction in the dilatation of ureters. In one case the kidney that failed to function before the procedure, restored its secretion afterwards. The contrast medium reached colon descendens only when more than 350 ml of it were infused into the rectal bladder. (author)

1,25D3 differentially suppresses bladder cancer cell migration and invasion through the induction of miR-101-3p.

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Ma, Yingyu; Luo, Wei; Bunch, Brittany L; Pratt, Rachel N; Trump, Donald L; Johnson, Candace S

2017-09-01

Metastasis is the major cause of bladder cancer death. 1,25D 3 , the active metabolite of vitamin D, has shown anti-metastasis activity in several cancer model systems. However, the role of 1,25D 3 in migration and invasion in bladder cancer is unknown. To investigate whether 1,25D 3 affects migration and invasion, four human bladder cell lines with different reported invasiveness were selected: low-invasive T24 and 253J cells and highly invasive 253J-BV and TCCSUP cells. All of the four bladder cancer cells express endogenous and inducible vitamin D receptor (VDR) as examined by immunoblot analysis. 1,25D 3 had no effect on the proliferation of bladder cancer cells as assessed by MTT assay. In contrast, 1,25D 3 suppressed migration and invasion in the more invasive 253J-BV and TCCSUP cells, but not in the low-invasive 253J and T24 cells using "wound" healing, chemotactic migration and Matrigel-based invasion assays. 1,25D 3 promoted the expression of miR-101-3p and miR-126-3p in 253J-BV cells as examined by qRT-PCR. miR-101-3p inhibitor partially abrogated and pre-miR-101-3p further suppressed the inhibition of 1,25D 3 on migration and invasion in 253J-BV cells. Further, 1,25D 3 enhanced VDR recruitment to the promoter region of miR-101-3p using ChIP-qPCR assay. 1,25D 3 enhanced the promoter activity of miR-101-3p as evaluated by luciferase reporter assay. Taken together, 1,25D 3 suppresses bladder cancer cell migration and invasion in two invasive/migration competent lines but not in two less invasive/motile lines, which is partially through the induction of miR-101-3p expression at the transcriptional level.

The Contrasting Role of the Mediator Subunit MED30 in the Progression of Bladder Cancer.

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Syring, Isabella; Weiten, Richard; Müller, Tim; Schmidt, Doris; Steiner, Susanne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg

2017-12-01

The Mediator complex is a key regulator of gene transcription, and several studies have demonstrated altered expression of particular subunits in diverse human diseases, especially cancer. To date, nothing is known about the role of MED30 in bladder cancer. We, therefore, performed an RNA expression and survival analysis of the subunit MED30 in 537 samples of bladder cancer by using the database cBioPortal. To validate these data on the protein level, we practiced immunohistochemical staining against MED30 on a tissue microarray containing 210 samples of all tumour stages and performed survival analyses. For functional analysis, the siRNA-mediated knockdown of MED30 was performed in the cell lines T24 and TCCSUP followed by proliferation, migration, and invasion assays. On the mRNA and protein levels, higher expression of MED30 is associated with better patient survival. In accordance with this, advanced T- and N-stages showed lower expression of MED30. In contrast, knockdown of MED30 led to reduction of the tumour parameters proliferation, migration, and invasion in the BCa cell lines. MED30 appears to be integrated in the progression of the urothelial tumour in the bladder. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis

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Lucio Dell’Atti

2015-03-01

Full Text Available Objectives: We retrospectively reviewed data of patients with incidental prostate cancer (PCa who underwent radical cystoprostatectomy (RCP for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Material and Methods: Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. Results: 11 out of 64 patients (17.2% who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3% were diagnosed as significant PCa, while 8 cases (72.7% were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79. During the follow-up, biochemical recurrence occurred in 1 patient (9%. Concernig the cancer specific survival there was no statistical significance (P = 0.326 between the clinically significant and clinical insignificant cancer group. Conclusions: In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

MR staging of pelvic endometriosis. Role of fat-suppression T1-weighted images

International Nuclear Information System (INIS)

Oishi-Tanaka, Yumiko; Itai, Yuji; Anno, Izumi; Matsumoto, Kunihiko; Ebihara, Reiko; Nishida, Masato

1996-01-01

We examined whether MR can determine the stage of endometriosis according to the scoring system established and revised by the American Fertility Society (r-AFS), a system which is widely used by gynecologists. We also studied the utility of fat suppression T 1 -weighted images in improving accuracy. Seventeen patients with endometriosis examined by conventional MR were included in this study. All the patients had surgically proved stage III or IV disease. We determined the stage by MR using the following criteria according to the r-AFS system: adnexal masses without normal ovarian tissue were considered deep ovarian lesions, while those with normal tissue were considered superficial. A lack of fat between the lesion and surrounding structures was considered a dense adhesion, and hyperintense spots were considered peritoneal implants. The MR scores of patients with and without fat suppression were correlated with the surgical scores. MR staging corresponded to surgical staging in 15 of the 17 patients. In eight patients, peritoneal implants of less than 1.5 cm were depicted only by fat-suppression images. However, these lesions did not change the score significantly. MR imaging could determine the stage in advanced endometriosis. Fat-suppression could highlight smaller implants. These tiny lesions had little clinical meaning in these advanced cases; however, the clinical value of this technique should be evaluated in milder disease. (author)

Deformation of stages of exchange tower 12T1 - a case study (Paper No. 2.9)

International Nuclear Information System (INIS)

Gulati, B.S.

1992-01-01

Heavy Water Plant at Baroda is based on monothermal hydrogen ammonia exchange process. Exchange tower-12 T1 is the biggest vessel in the plant and has 12 exchange stages and a cable stage. During the annual shut-down in April-May 1991, tower was opened for maintenance when the 12th stage was lifted, frosting/icing was observed on its outer shell with some reported ammonia smell. This paper describes the incident, deformation of stages of exchange tower, possible causes of dent formation and also elaborates the remedial measures taken. (author). 6 figs

Discoidin domain receptor 1 activity drives an aggressive phenotype in bladder cancer

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Xie, Xin; Rui, Wenbin; He, Wei; Shao, Yuan; Sun, Fukang; Zhou, Wenlong; Wu, Yuxuan; Zhu, Yu

2017-01-01

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase which utilizes collagen as a ligand to regulate the interaction between cancer cells and tumor stroma. However, the clinical relevance of DDR1 expression in bladder cancer as well as its molecular regulation have not been previously investigated. Here, we assessed the role of DDR1 in bladder cancer. The DDR1 levels in bladder cancer specimens were examined by Western blot, compared to the paired adhesive normal controls. The eff...

Magnetic resonance for T-staging of nasopharyngeal carcinoma. The most informative pair of sequences

International Nuclear Information System (INIS)

Lau, Kam Y.; Kan, Wai K.; Sze, Wai M.

2004-01-01

The objective of this study was to evaluate the most informative pair of sequences in magnetic resonance (MR) for T-staging of nasopharyngeal carcinoma (NPC). The MR images of 134 patients with newly diagnosed NRC, from 1996 to 2002, were retrospectively reviewed. All the patients were scanned using 1.5 Tesla MR systems. The images of the nasopharynx were reviewed by two qualified radiologists to determine the positive findings and the T-stage by Union Internationale Contre le Cancer (UICC) (6th edition) System, using each sequence separately. The T-stage derived from a single MR sequence was then compared with the T-stage based on the five selected sequences to assess the number and percentage of patients who were being understaged. Therefore, the overall percentage accuracy of each single sequence could be determined. A pair of sequences providing information to achieve almost 100% diagnostic accuracy was then derived. The overall percentage accuracy of five individual sequences of the nasopharynx is as follows: contrast-enhanced (CE) fat suppression (FS) axial T1 (94.8%), CE FS coronal T1 (88.1%), FS axial T2 (85.8%), non-contrast enhanced (NE) axial T1 (78.4%) and NE coronal T1 (77.6%). CE FS axial T1 has the best accuracy. All the structures that are missed in CE FS axial T1 which lead to apparent understaging, are appreciated in NE axial T1-weighted images. Individual sequences supplement each other in the NPC staging. CE FS axial T1 is the most informative individual sequence. Combination of CE FS axial T1 and NE axial T1 of the nasopharynx provides sufficient information to achieve almost 100% diagnostic accuracy in T-staging; therefore, both should be included in the MR-staging protocol. (author)

CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

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

2015-11-01

The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker. © 2014 Wiley Periodicals, Inc.

Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells

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Liu Q

2017-05-01

Full Text Available Qian Liu,* Hui Liu,* Hepeng Cheng, Yang Li, Xiaodong Li, Chaoyang Zhu Department of Urology Surgery, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China *These authors contributed equally to this work Background: Bladder cancer is a common serious disease around the world. Long noncoding RNAs (lncRNAs have been demonstrated to participate in the development and progression of various cancers, including bladder cancer. The aim of this study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1 on proliferation and apoptosis in bladder cancer cell lines and the underlying mechanism.Methods: The levels of TUG1 were detected by quantitative real time polymerase chain reaction (qRT-PCR in bladder cancer tissues and cells. The mRNA and protein levels of zinc finger E-box binding homeobox 2 (ZEB2 were measured by qRT-PCR and Western blot analysis, respectively. The functional targets of TUG1 were predicted by online softwares and confirmed by luciferase reporter assay. The effects of TUG1 on cell proliferation and apoptosis were examined by MTT and apoptosis assay, respectively. The expression levels of β-catenin, cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis.Results: The levels of TUG1 and ZEB2 were significantly increased in bladder cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2 overexpression reversed the effects of TUG1 knockdown on cell proliferation and apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142 could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the Wnt/β-catenin pathway by regulating ZEB2 expression in bladder cancer cells.Conclusion: Downregulation of TUG1 expression inhibited proliferation and induced apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through the inactivation of Wnt

Loss of SHP-1 tyrosine phosphatase expression correlates with the advanced stages of cutaneous T-cell lymphoma

DEFF Research Database (Denmark)

Witkiewicz, Agnieszka; Raghunath, Puthiyaveettil; Wasik, Agnieszka

2007-01-01

Cutaneous T-cell lymphoma (CTCL) comprises distinct and often progressive stages of skin involvement by patches, plaques, and tumors. We have previously demonstrated that CTCL-derived malignant T-cell lines display loss of a tumor suppressor SHP-1 tyrosine phosphatase because of epigenetic...

[A case of sigmoid colon cancer invading urinary bladder treated with preoperative mFOLFOX6 and urinary bladder conserving surgery].

Science.gov (United States)

Nishino, Takeshi; Katayama, Kazuhisa; Takahashi, Yuji; Tanaka, Takashi

2012-02-01

A 69-year-old man visited our hospital because of melena and anemia. Colonoscopy revealed a type 3 tumor at sigmoid colon, and by abdominal CT, we detected a sigmoid colon cancer invading the urinary bladder with a single liver metastasis. The patient required sigmoidectomy with partial hepatectomy and total urinary bladder resection. Preoperative chemotherapy with mFOLFOX6 was initiated as a part of multidisciplinary therapy. After the 6th course was completed, CT revealed a reduction in the primary tumor's size and the disappearance of liver metastasis. After the 8th course was completed, we performed urinary bladder conserving sigmoidectomy. The pathological diagnosis of the surgical specimen was tub1, pSS, ly0, v0, pN0, and pStage II. Down-sizing chemotherapy might improve the quality of life(QOL)of colon cancer patients with extensive invasion of the urinary bladder.

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

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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.

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

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Nobuhiro Kushida

2015-01-01

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

Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

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Freilich, Jessica M.; Spiess, Philippe E.; Biagioli, Matthew C.; Fernandez, Daniel C.; Shi, Ellen J.; Hunt, Dylan C.; Gupta, Shilpa; Wilder, Richard B., E-mail: richard.wilder@moffitt.org [Moffitt Cancer Center, Tampa, FL (United States)

2014-03-15

Purpose: To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT) for bladder cancer; Materials and Methods: Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost) on computed tomography scans with versus without Lipiodol. Results: Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT) scan for staging. There was no toxicity attributable to Lipiodol: Conclusions: Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost. (author)

Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

Directory of Open Access Journals (Sweden)

Jessica M. Freilich

2014-04-01

Full Text Available Purpose To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT for bladder cancer.Materials and Methods Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT and image-guided radiation therapy (IGRT to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost on computed tomography scans with versus without Lipiodol.Results Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06. In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT scan for staging. There was no toxicity attributable to Lipiodol.Conclusions Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost.

CYP1B1 gene polymorphisms correlate with an increased risk of urinary bladder cancer in India.

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

2016-04-01

The urinary bladder is the target of several toxic compounds, which makes the bladder more prone to cancer. Cytochrome P450 1B1 enzyme is present in tumor tissues and metabolizes the polyaromatic carcinogens and activates several procarcinogens that cause DNA damage. We examined the functional single-nucleotide polymorphisms in the CYP1B1 gene to study their association with the urinary bladder cancer. We recruited 234 cases of pure urothelial and 258 bladder cancer-free control samples from the individuals visiting the clinic for various investigations. We genotyped 4 CYP1B1 single-nucleotide polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype data were analyzed by the Chi-square test. Haplotypes were constructed to evaluate the joint effect of the 4 polymorphisms. Overall, 3 polymorphisms-rs10012, rs150799650, and rs1056827 (odds ratio [OR] = 2.34, CI: 1.59-3.45, Pbladder cancer. Haplotype analysis suggested GTTC, GTTG, and ATGC to be the risk factors for bladder cancer. Overall, 3 polymorphisms, rs10012, rs1056827, and rs150799650 in the CYP1B1 gene correlate with urinary bladder cancer significantly in the Indo-European population of Uttar Pradesh, India. Further investigations in other populations are advised. Copyright © 2016 Elsevier Inc. All rights reserved.

Intrafraction Bladder Motion in Radiation Therapy Estimated From Pretreatment and Posttreatment Volumetric Imaging

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Foroudi, Farshad, E-mail: farshad.foroudi@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Pham, Daniel [Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Bressel, Mathias [Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Gill, Suki [Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Kron, Tomas [Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)

2013-05-01

Purpose: The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Methods and Materials: Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatment and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. Results: The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Conclusion: Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between

Radiation therapy for early stage (T1 - T2) sarcomatoid carcinoma of true vocal cords: outcomes and patterns of failure

International Nuclear Information System (INIS)

Ballo, Matthew T.; Garden, Adam S.; El-Naggar, Adel K.; Morrison, William H.; Ang, K. Kian

1997-01-01

Objectives/hypothesis: Sarcomatoid carcinoma of head and neck mucosal sites is a rare malignancy surrounded with much controversy. One factor consistently reported yet not well supported throughout the literature is their relative radioresistance and a general belief that surgery is the treatment of choice. Our objective was to determine if patients treated with radiation for early glottic carcinoma with this histologic diagnosis had worse outcomes than typical squamous cell carcinoma of similar stage. Materials and Methods: Twenty-eight cases of early stage sarcomatoid carcinoma of the larynx treated with definitive doses of megavoltage irradiation between 1969 and 1995 at the University of Texas M.D. Anderson Cancer Center form the cohort for this analysis. All pathologic material was reviewed to confirm the diagnosis. Follow-up ranged from 1.5 - 24 years (median, 10 years). Results: Twenty-one patients were staged T1 and 7 patients had stage T2 disease. Sixteen tumors had the more typical polypoid morphology of sarcomatoid carcinoma. All patients were treated with small laryngeal fields, median size 20 cm2, and to a median dose of 65 Gy. Four patients (14%) had local disease recurrence. All 4 patients had salvage total laryngectomies and remained free of local disease. Only one patient manifested regional and distant disease. The 10-year actuarial survival rate was 63%. Conclusions: Patients with early staged sarcomatoid carcinoma of the glottis treated with radiation had similar control rates to irradiated patients with similar volume disease with the more typical squamous cell carcinoma. We do not believe that the histologic diagnosis of sarcomatoid carcinoma by itself should influence the decision to not treat a patient with early staged glottic disease with irradiation

Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis

DEFF Research Database (Denmark)

Ødum, Niels; Morling, Niels; Platz, P

1987-01-01

The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 pati...

Benefits and adverse effects of post-operative radiation therapy after radical cystectomy for patients with advanced bladder cancer

International Nuclear Information System (INIS)

Yabusaki, Noboru; Komatsu, Hideki; Tanabe, Nobuaki; Tago, Kiichiro; Ueno, Akira

1995-01-01

The benefits and adverse effects of post-operative irradiation for advanced bladder cancer patients were investigated. Ten patients with pT3b, pT4 or pN+ bladder cancer who underwent radical cystectomy at Yamanashi Medical University Hospital during 7 years and 3 months from October 1983 to December 1991 received adjuvant chemotherapy and radiotherapy (Group 1). During the same period, six patients with recurrent tumor after radical cystectomy were treated by radiotherapy (Group II). Stages of the primary tumors were PT2 in 1, pT3a in 2, pT3b in 6 and pT4 in 7 cases. In addition, 10 of 16 patients (63%) had positive nodes. During the follow-up period, seven patients died of cancer, and one died of other cause. As a result eight patients (5 in Group I, 3 in Group II) are alive. The cumulative 5-year survival rate is 50%. However, nine of the 16 patients (56%) suffered from the small bowel obstruction as an adverse effect of irradiation. Six patients required resection of the small bowel or bypass surgery. Radiation after radical cystectomy seemed to be effective for the local control of the tumor, but the adverse effect to the digestive system was very severe and common. (author)

Factors related to recurrence of bladder transitional cell carcinoma after transurethral resection of bladder tumor (TUR-BT)

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Nam, Ki Dong; Koo, Bong Sik; Yoon, Seong Kuk; Park, Byung Ho; Nam, Kyung Jin; Choi, Jong Cheol; Lee, Ki Nam; Lee, Young Il; Chung, Duck Hwan

1998-01-01

The purpose of this study is to evaluate factors related to the recurrence of TCC (transitional cell carcinoma) in the urinary bladder after transurethal resection of bladder tumor (TUR-BT). We retrospectively reviewed 54 patients in whom TCC (transitional cell carcinoma) after TUR-BT had been confirmed. Recurrence was evaluated by US, CT, cystoscopy and urine smear during the follow-up period of 6 months. The multiplicity, shape, size, and calcification of TCC, as revealed by radiologic studies, were evaluated retrospectively before TUR-BT. After TUR-BT, the histologic grade and pathologic stage of TCC were evaluated. Radiologically, multiple and/or sessile type TCC had a higher recurrence rate than the single and/or pedunculated type. Pathologically, when the grade and stage of bladder tumor were higher, recurrent rates were higher. (author). 17 refs., 3 tabs., 3 figs

Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

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Jonathan A Ewald

Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-injured Rat Bladders.

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Imamura, Tetsuya; Shimamura, Mitsuru; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Silwal Gautam, Sudha; Ishizuka, Osamu

2018-05-08

The ability to repair damaged urinary bladders through the application of bone marrow-derived cells is in the earliest stages of development. We investigated the application of bone marrow-derived cells to repair radiation-injured bladders. We used a three-dimensional (3D) bioprinting robot system to biofabricate bone marrow-derived cell structures. We then determined if the biofabricated structures could restore the tissues and functions of radiation-injured bladders. The bladders of female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2-Gy once a week for 5 weeks. Adherent and proliferating bone marrow-derived cells harvested from the femurs of male 17-week-old green fluorescence protein-transfected Tg-SD rats were cultured in collagen-coated flasks. Bone marrow-derived cell spheroids were formed in 96-well plates. Three layers of spheroids were assembled by the bioprinter onto a 9x9 microneedle array. The assembled spheroids were perfusion cultured for 7 days, and then the microneedle array was removed. Two weeks after the last radiation treatment, the biofabricated structures were transplanted into an incision on the anterior wall of the bladders (n=10). Control rats received the same surgery but without the biofabricated structures (sham-structure, n=12). At 2 and 4 weeks after surgery, the sham-structure control bladder tissues exhibited disorganized smooth muscle layers, decreased nerve cells, and significant fibrosis with increased presence of fibrosis-marker P4HB-positive cells and hypoxia-marker HIF1α-positive cells. The transplanted structures survived within the recipient tissues, and blood vessels extended within them from the recipient tissues. The bone marrow-derived cells in the structures differentiated into smooth muscle cells and formed smooth muscle clusters. The recipient tissues near the transplanted structures had distinct smooth muscle layers and reconstructed nerve cells, and only minimal fibrosis with decreased presence of P4

Decrease of CD4+ T lymphocytes in patients with H1N1 in early stage and its clinical significances

International Nuclear Information System (INIS)

Zuo Lingyun; Zhao Wei; Zhao Hong; Yu Haiying; Sun Weiwei

2010-01-01

Objective: To observe the change of CD4 + T Lymphocytes in patients with H1N1 at early stage and figure out its clinical significances on the progress and therapeutic selection of H1N1. Methods: The absolute counts of T lymphocyte subset from the peripheral blood samples of 48 H1N1 patients in first ten days' duration were detected by flow cytometry, and the serial chest CT examinations were performed. Results: In all 48 clinical cases, 28 cases were in normal range of CD4 + lymphocyte absolute count, whose pulmonary lesions were limited and illness condition stayed in the stability, they didn't need steroid. In the other 20 cases with low level of CD4 + , 4 cases' illness presented the progressive development and needed to be treated with steroid and 16 cases with lightly decreased CD4 + level which had a stable condition without treatment with steroid. The result of Pearson correlation analysis showed that there were negative correlations between absolute count of CD4 + cells and pulmonary lesions (r=-0.299, P + cell absolute count of H1N1 patients at early stage indicates the worse condition of pulmonary lesions. The patients with remarkable decrease of CD4 + lymphocytes are in need of treatment with steroid. (authors)

Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

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Kauffman, Eric C; Robinson, Brian D; Downes, Martin J; Powell, Leagh G; Lee, Ming Ming; Scherr, Douglas S; Gudas, Lorraine J; Mongan, Nigel P

2011-12-01

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. Copyright © 2011 Wiley Periodicals, Inc.

PLK-1 Silencing in Bladder Cancer by siRNA Delivered With Exosomes.

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Greco, Kristin A; Franzen, Carrie A; Foreman, Kimberly E; Flanigan, Robert C; Kuo, Paul C; Gupta, Gopal N

2016-05-01

To use exosomes as a vector to deliver small interfering ribonucleic acid (siRNA) to silence the polo-like kinase 1 (PLK-1) gene in bladder cancer cells. Exosomes were isolated from both human embryonic kidney 293 (HEK293) cell and mesenchymal stem cell (MSC) conditioned media. Fluorescently labeled exosomes were co-cultured with bladder cancer and normal epithelial cells and uptake was quantified by image cytometry. PLK-1 siRNA and negative control siRNA were loaded into HEK293 and MSC exosomes using electroporation. An invasive bladder cancer cell line (UMUC3) was co-cultured with the electroporated exosomes. Quantitative reverse transcriptase polymerase chain reaction was performed. Protein analysis was performed by Western blot. Annexin V staining and MTT assays were used to investigate effects on apoptosis and viability. Bladder cancer cell lines internalize an increased percentage of HEK293 exosomes when compared to normal bladder epithelial cells. Treatment of UMUC3 cells with exosomes electroporated with PLK-1 siRNA achieved successful knockdown of PLK-1 mRNA and protein when compared to cells treated with negative control exosomes. HEK293 and MSC exosomes were effectively used as a delivery vector to transport PLK-1 siRNA to bladder cancer cells in vitro, resulting in selective gene silencing of PLK-1. The use of exosomes as a delivery vector for potential intravesical therapy is attractive. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimation of bladder wall location in ultrasound images.

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Topper, A K; Jernigan, M E

1991-05-01

A method of automatically estimating the location of the bladder wall in ultrasound images is proposed. Obtaining this estimate is intended to be the first stage in the development of an automatic bladder volume calculation system. The first step in the bladder wall estimation scheme involves globally processing the images using standard image processing techniques to highlight the bladder wall. Separate processing sequences are required to highlight the anterior bladder wall and the posterior bladder wall. The sequence to highlight the anterior bladder wall involves Gaussian smoothing and second differencing followed by zero-crossing detection. Median filtering followed by thresholding and gradient detection is used to highlight as much of the rest of the bladder wall as was visible in the original images. Then a 'bladder wall follower'--a line follower with rules based on the characteristics of ultrasound imaging and the anatomy involved--is applied to the processed images to estimate the bladder wall location by following the portions of the bladder wall which are highlighted and filling in the missing segments. The results achieved using this scheme are presented.

Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

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Jose Abraão Carneiro Neto

2018-03-01

Full Text Available Aim: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL. Methods: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS and King's Health Questionnaire. Results: The mean (SD of the age was 52 + 14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12–15 before therapy and decreased to 1.0 (0–12 on day 30 and to 03 (0–14 on day 90 (p < 0.0001. There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. Conclusion: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder. Keywords: Overactive bladder, Onabotulinum toxin, HTLV-1

Glucocorticoid receptor beta increases migration of human bladder cancer cells.

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McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

2016-05-10

Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

Adaptive radiotherapy for invasive bladder cancer: A feasibility study

International Nuclear Information System (INIS)

Pos, Floris J.; Hulshof, Maarten; Lebesque, Joos; Lotz, Heidi; Tienhoven, Geertjan van; Moonen, Luc; Remeijer, Peter

2006-01-01

Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV CONV ). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV ART ). The GTV ART was expanded with a 1 cm margin for the construction of a PTV ART . Starting in the third week, patients were treated to PTV ART . Repeat CT scans were used to evaluate treatment accuracy. Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV ART . On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV ART with PTV CONV (p < 0.0001). Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes

Adaptive radiotherapy for invasive bladder cancer: A feasibility study

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Pos, Floris J [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Hulshof, Maarten [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Lebesque, Joos [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Lotz, Heidi [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Tienhoven, Geertjan van [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Moonen, Luc [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Remeijer, Peter [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

2006-03-01

Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV{sub CONV}). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV{sub ART}). The GTV{sub ART} was expanded with a 1 cm margin for the construction of a PTV{sub ART}. Starting in the third week, patients were treated to PTV{sub ART}. Repeat CT scans were used to evaluate treatment accuracy. Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV{sub ART}. On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV{sub ART} with PTV{sub CONV} (p < 0.0001). Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes.

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.

Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review.

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Cho, Min Hyun; Kim, Sung Han; Park, Weon Seo; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

2016-10-20

Sarcomatoid urothelial carcinoma (SUC) is a rare malignant neoplasm of the urinary bladder comprising 0.2-0.6 % of all histological bladder tumor subtypes. It presents as a high-stage malignancy and exhibits aggressive biological behavior, regardless of the treatment employed. It is defined as histologically indistinguishable from sarcoma and as a high-grade biphasic neoplasm with malignant epithelial and mesenchymal components. The mean age of patients presenting with SUC is 66 years, and the male-to-female ratio is 3:1. In addition, gross hematuria is usually present. The prognosis of SUC is poorer than that of typical urothelial carcinoma because of uncertainty concerning the optimal treatment regimen. We report the case of a 77-year-old woman with SUC containing a chondrosarcoma component who, 12 years previously, had undergone a nephroureterectomy for pT3N0M0 ureter cancer of the contralateral upper urinary tract. From the 4th year of follow-up after nephroureterectomy, multiple recurrent bladder tumors staged as Ta transitional cell carcinoma developed, and six transurethral resections of the bladder (TURB) with multiple intravesical instillations were performed without any evidence of metastases and upper tract recurrences. In 2015, a right partial distal ureterectomy and an additional TURB were performed due to a papillary mass at the right contralateral ureterovesical junction of the bladder, which was confirmed as a high-grade pT1 transitional cell carcinoma. After a further 2 years of follow-up, total pelvic exenteration with an ileal conduit diversion was performed to remove the mass, which was a pT4N0M0 tumor composed of carcinomatous and sarcomatous elements compatible with a sarcomatoid carcinoma including grade 3 transitional cell carcinoma and chondrosarcoma. Immunohistochemical examination showed that tumor cells were positive for vimentin and p63 and negative for NSE and Cd56 markers. In the first postoperative month, a metastatic lung nodule

Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression

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Jiang, Huijuan; Hu, Xigang; Zhang, Hongzhi; Li, Wenbo

2017-01-01

Background Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. Methods Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder canc...

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

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Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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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)

NMR imaging of bladder tumors in males. Preliminary clinical experience

International Nuclear Information System (INIS)

Sigal, R.; Rein, A.J.J.T.; Atlan, H.; Lanir, A.; Kedar, S.; Segal, S.

1985-01-01

Nuclear magnetic resonance (NMR) of the normal and pathologic bladder was performed in 10 male subjects: 5 normal volunteers, 4 with bladder primary carcinoma, 1 with bladder metastasis. All scanning was done using a superconductive magnet operating at 0.5 T. Spin echo was used as pulse sequence. The diagnosis was confirmed in all cases by NMR imaging. The ability of the technique to provide images in axial, sagital and coronal planes allowed a precise assessment of the morphology and the size of the tumors. The lack of hazards and the quality of images may promote NMR imaging to a prominent role in the diagnosis of human bladder cancer [fr

Bladder cancer: epidemiology, staging and grading, and diagnosis.

NARCIS (Netherlands)

Kirkali, Z.; Chan, T.; Manoharan, M.; Algaba, F.; Busch, C.; Cheng, L.; Kiemeney, L.A.L.M.; Kriegmair, M.; Montironi, R.; Murphy, W.M.; Sesterhenn, I.A.; Tachibana, M.; Weider, J.

2005-01-01

Bladder cancer is a heterogeneous disease with a variable natural history. At one end of the spectrum, low-grade Ta tumors have a low progression rate and require initial endoscopic treatment and surveillance but rarely present a threat to the patient. At the other extreme, high-grade tumors have a

Liver fibrosis detection and staging: a comparative study of T1ρ MR imaging and 2D real-time shear-wave elastography.

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Li, Ruo-Kun; Ren, Xin-Pin; Yan, Fu-Hua; Qiang, Jin-Wei; Lin, Hui-Min; Tao Wang; Zhao, Hong-Fei; Chen, Wei-Bo

2017-12-02

To compare the results of T1ρ MR imaging and 2D real-time shear-wave elastography (SWE) for liver fibrosis detection and staging. Twenty-nine rabbit models of CCl 4 -induced liver fibrosis were established and six untreated rabbits served as controls. T1ρ MR imaging and 2D real-time SWE examination were performed at 2, 4, 6, 8, 10, and 12 weeks. T1ρ values and liver stiffness (LS) values were measured. Fibrosis was staged according to the METAVIR scoring system. Correlation test was performed among T1ρ values, LS values, and fibrosis stage. Receiver operating characteristic (ROC) analysis was performed for assessing diagnostic performance of T1ρ and SWE in detection of no fibrosis (F0), substantial fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4). There was moderate positive correlation between fibrosis stage and T1ρ values (r = 0.566; 95% CI 0.291-0.754; P < 0.0001), and LS value (r = 0.726; 95% CI 0.521-0.851; P = 0.003). T1ρ values showed moderate positive correlations with LS values [r = 0.693; 95% confidence interval (CI) 0.472-0.832; P < 0.0001]. Areas Under ROC (AUROCs) were 0.861 (95% CI 0.705-0.953) for SWE and 0.856 (95% CI 0.698-0.950) for T1ρ (P = 0.940), 0.906 (95% CI 0.762-0.978) for SWE and 0.849 (95% CI 0.691-0.946) for T1ρ (P = 0.414), 0.870 (95% CI 0.716-0.958) for SWE and 0.799 (95% CI 0.632-0.913) for T1ρ (P = 0.422), and 0.846 (95% CI 0.687-0.944) for SWE and 0.692 (95% CI 0.517-0.835) for T1ρ (P = 0.137), when diagnosing liver fibrosis with ≥ F1, ≥ F2, ≥ F3, and F4, respectively. There was moderate positive correlation between inflammatory activity and T1ρ values (r = 0.520; 95% CI 0.158-0.807; P = 0.013). T1ρ imaging has potential for liver fibrosis detection and staging with good diagnostic capability similar to that of ultrasonography elastography.

Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells.

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Kang, Minyong; Lee, Kyoung-Hwa; Lee, Hye Sun; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

2017-02-04

Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8) assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI) was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA) remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating a novel

Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells

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Minyong Kang

2017-02-01

Full Text Available Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1, chloroquine (CQ and 3-methyladenine (3-MA were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8 assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating

Chemoradiotherapy for muscle invading bladder carcinoma. final report of a single institutional organ-sparing program

International Nuclear Information System (INIS)

Arias, Fernando; Dominguez, Miguel A.; Martinez, Enrique; Illarramendi, Jose J.; Miquelez, Santiago; Pascual, Ignacio; Marcos, Marta

2000-01-01

Purpose: Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with muscle invading bladder cancer. We began a prospective study in 1988 to determine the possibilities of conservative treatment and aiming to improve the results obtained by cystectomy alone in invasive bladder cancer. A combination of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC), followed by radiotherapy and concomitant cisplatin was used. Methods: Fifty patients with good performance status and with stages T2 to T4 operable untreated invasive bladder cancer were entered in the study. Treatment protocol was as follows: (i) cytoreductive transurethral resection; (ii) two cycles of M-VAC chemotherapy; (iii) radiotherapy, 45 Gy on pelvic volume and, at the same time, 20 mg/m 2 cisplatin on days 1 to 5. Cystoscopic evaluation: if there was a complete response, radiotherapy was completed up to 65 Gy; if there was not a complete response, a cystectomy was performed. Median follow-up of the series was 73 months (18-180 m). Results: Tumor response was as follows: 34 complete responses (68%), 9 partial responses (18%), and 7 nonresponses (14%) were observed. The 5-year overall survival and local control were 48% and 47%, respectively. For the complete responder patient, 5-year survival and local control were 65% and 70%, respectively. Severe toxicity was uncommon. The most frequent were leucopenia and cystitis. No treatment-related deaths occurred with either treatment protocol. Conclusions: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial would be required to produce definitive results

Hematuria screening test for urinary bladder mucosal infiltration in cervical cancer.

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Chuttiangtum, Ayuth; Udomthavornsuk, Banchong; Chumworathayi, Bandit

2012-01-01

To determine the diagnostic performance of hematuria as a screening test for urinary bladder infiltration in cervical cancer patients with a prospective study design. Newly diagnosed cervical cancer patients at Srinagarind hospital from 14 June 2011 to 30 April 2012 were enrolled in this study. We collected midstream urine samples for urinalysis from every patient before routine cystoscopic exam for clinical staging. The presence of 3 or more red blood cells (RBCs) per high power field was defined as positive for hematuria. A two-by-two table was used to determine the diagnostic performance of hematuria to detect urinary bladder mucosal infiltration using cystoscopy and biopsy as the gold standard. A total of 130 were patients included, 54 of which (41.5%) had hematuria. Of these, four patients (3.08%) had pathological report from cystoscopic biopsy confirmed metastatic squamous cell carcinoma. The sensitivity, specificity, PPV, NPV, and accuracy of hematuria as a screening test to detect urinary bladder mucosal infiltration of cervical cancer were 100%, 60.3%, 7.4%, 100%, and 61.5%, respectively. There was no single case of urinary bladder mucosal infiltration in patients initially staged less than stage III. Hematuria can be used as a screening test to detect urinary bladder mucosal infiltration of cervical cancer. This can reduce the number of cervical cancer patients who really need to undergo cystoscopy as a staging procedure to less than half and to less than 20% if stage III or more were included without missing a single case of urinary bladder mucosal infiltration.

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.

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

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John D. Terrell

2011-12-01

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

MR staging of pelvic endometriosis. Role of fat-suppression T{sub 1}-weighted images

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Oishi-Tanaka, Yumiko; Itai, Yuji; Anno, Izumi; Matsumoto, Kunihiko; Ebihara, Reiko; Nishida, Masato [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

1996-05-01

We examined whether MR can determine the stage of endometriosis according to the scoring system established and revised by the American Fertility Society (r-AFS), a system which is widely used by gynecologists. We also studied the utility of fat suppression T{sub 1}-weighted images in improving accuracy. Seventeen patients with endometriosis examined by conventional MR were included in this study. All the patients had surgically proved stage III or IV disease. We determined the stage by MR using the following criteria according to the r-AFS system: adnexal masses without normal ovarian tissue were considered deep ovarian lesions, while those with normal tissue were considered superficial. A lack of fat between the lesion and surrounding structures was considered a dense adhesion, and hyperintense spots were considered peritoneal implants. The MR scores of patients with and without fat suppression were correlated with the surgical scores. MR staging corresponded to surgical staging in 15 of the 17 patients. In eight patients, peritoneal implants of less than 1.5 cm were depicted only by fat-suppression images. However, these lesions did not change the score significantly. MR imaging could determine the stage in advanced endometriosis. Fat-suppression could highlight smaller implants. These tiny lesions had little clinical meaning in these advanced cases; however, the clinical value of this technique should be evaluated in milder disease. (author)

Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

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Li, Cheng-Wei; Chen, Bor-Sen

2016-01-01

Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

Non-Hodgkin's lymphoma presenting as a primary bladder tumor: a case report

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Molinos-Castro Sonia

2010-04-01

Full Text Available Abstract Introduction Primary lymphoma of the bladder represents 0.2% of all bladder malignancies. Secondary involvement of the bladder by malignant lymphoma occurs in 10% to 50% of cases. Most lymphomas of the bladder are non-Hodgkin's lymphomas of the B-cell type, with preponderance among women. The impact of positron emission tomography (PET on tumor staging has recently become very important due to its use in the study of diagnosis extension and individual therapy design. Case presentation We report the case of a 79-year-old Caucasian man with intermittent haematuria as the presenting symptom of non-Hodgkin's lymphoma of the bladder. He was first diagnosed with primary lymphoma of the bladder using the current staging method, but a positron emission tomography study subsequently revealed that he instead had a secondary involvement of the bladder. Conclusion The staging of non-Hodgkin's lymphomas, which is useful in order to plan accurate therapy, has been changing since the introduction of positron emission tomography scanning. Primary lymphomas of the bladder, although very rare, may be even more uncommon when this imaging technique is used to assess the extension of the disease. Although the interpretation of this technique has some limitations that should be taken into account, the extensive use of positron emission tomography should nonetheless help improve the diagnosis of this disease.

Patient Characteristics, Treatment Patterns and Prognostic Factors in Squamous Cell Bladder Cancer.

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Zahoor, Haris; Elson, Paul; Stephenson, Andrew; Haber, Georges-Pascal; Kaouk, Jihad; Fergany, Amr; Lee, Byron; Koshkin, Vadim; Ornstein, Moshe; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian; Grivas, Petros

2018-04-01

Squamous cell carcinoma (SCC) is an uncommon histologic subtype of bladder cancer with limited data on treatment patterns, outcomes, and prognostic factors. "Real world" information might inform decision-making, prognostic estimates, and clinical trial designs. A retrospective review of patients with tissue-confirmed bladder SCC treated at Cleveland Clinic from 2007 to 2016 was performed. Data on patient characteristics, treatment patterns, and clinical follow-up were extracted. Univariate analysis was used to identify predictors of overall survival (OS), recurrence-free survival (RFS) and time to recurrence. Of 58 identified patients, 42 had complete data available. Median age at diagnosis was 67 years (range, 37-90). Hematuria was the most common (71%) presenting symptom; 32 patients had pure SCC and 10 predominant/extensive squamous differentiation without major differences noted in clinicopathologic variables or outcomes among those 2 groups. Overall, 35 patients underwent cystectomy with 5 receiving neoadjuvant and 1 adjuvant chemotherapy, whereas 3 had chemotherapy for recurrent disease. Of patients with cystectomy, most had locally advanced disease (75% pT3/4, 35% pN+). Overall, 10 patients progressed and 14 died; median OS was not reached. The 2-year estimated OS, RFS, and cumulative incidence of recurrence were 61% ± 9%, 50% ± 9%, and 32% ± 9%, respectively. Hydronephrosis, older age (70 years or older), lymphovascular invasion, nodal metastases, and advanced T stage were associated with 1 or more poor outcomes. In patients with resectable bladder SCC, radical cystectomy remains the main treatment modality. The role of perioperative chemotherapy remains unclear. The identified prognostic factors might be helpful for prognostication, treatment discussion, and trial eligibility/stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

Results of the conservative treatment associating radiotherapy and concomitant chemotherapy in the bladder filtering cancers

International Nuclear Information System (INIS)

Salem, N.; Bladou, F.; Gravis, G.; Karsenty, G.; Tallet, A.; Lopez, L.; Alzieu, C.; Serment, G.

2004-01-01

Full text of publication follows: purpose: to describe outcome of patients with muscle-invasive bladder carcinoma treated with multimodality therapy in our institution from 1993 to 2002. Patients and methods: the charts of sixty patients with T2-4, N0-1, M0 treated with TURBT followed by a chemo-radiotherapy combination were retrospectively reviewed: 22 received neo-adjuvant chemotherapy (CMV/MVAC) followed by concomitant chemo-radiotherapy (weakly cisplatin/carbo-platin or a cisplatin and 5-fluorouracil association) and the other 38 concomitant chemo-radiotherapy alone. Radiotherapy delivered a median dose of 45 Gy to the pelvis and 65 Gy to the bladder in a mono-fractionated or twice a day fractionation scheme. Follow-up evaluations included cystoscopy with biopsies at regular intervals. Salvage cystectomy was recommended in case of local persistent tumor or bladder relapse. Results: median follow-up was 48.5 months (10-126 months). 82% (18/22) of the patients receiving neo-adjuvant chemotherapy had 2 or more cycles and 85% (51/60) got the concomitant chemotherapy as planned. Radiotherapy was completed in 56 patients. Twenty-eight patients relapsed either locally (14 did not achieve local complete response after chemo-radiation and 6 had true local relapse during follow-up) or at distant sites. Actuarial 5-year disease-specific survival and freedom from local and distant relapse rate are respectively 54% and 42%. Actuarial local control rate with intact bladder was 56% at 5-year. When separated according to stage and grade, patients with T2/3 grade 2 tumors had significantly better chance of remaining relapse-free than the others (p = 0.045). Salvage cystectomy (n = 11) for isolated local failure in this population achieved limited results. Conclusion: our experience shows that a significant number of patients will achieve long survival with their bladder intact after multimodality therapy. (authors)

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease.

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Iacovelli, Elisa; Gilio, Francesca; Meco, Giuseppe; Fattapposta, Francesco; Vanacore, Nicola; Brusa, Livia; Giacomelli, Elena; Gabriele, Maria; Rubino, Alfonso; Locuratolo, Nicoletta; Iani, Cesare; Pichiorri, Floriana; Colosimo, Carlo; Carbone, Antonio; Palleschi, Giovanni; Inghilleri, Maurizio

2010-07-15

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

The UBCTM test may be useful for diagnosis of recurred urinary bladder cancer

International Nuclear Information System (INIS)

Kang, Do Young; Jung, Se Il; Hwang, Joon Seong; Gil, Myung Cheol; Yoon, Jin Han; Kim, Duk Kyu

2001-01-01

Previously we reported the usefulness of UBC TM test compared to urinary cytology for diagnosis of transitional cell carcinoma (TCC) of the bladder in patients with hematuria. Now we evaluated the usefulness of the UBC TM test for diagnosis of recurred urinary bladder cancer. 146 patients with hematuria were included in our study. UNC TM test (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. 33 patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC concentration was greater than 12 μ g/L. We compared UBC TM level with previous value 6 months later in patients whom diagnosed with TCC. UBC levels were significantly different between group A (95.9±166.4 μ g/L) and group B (19.2±85.6 μ g/L) (p TM test and 100% (97/97) in cytology. UBC TM test was significantly more sensitive in stage Ta. T 1 tumors (80 vs 20 %, p TM test showed tendency to be more sensitive as the stage and grade was higher (80% in Ta, 83.3% in T1 and 100% in T2, 80% in Grade I, 85.7% in Grade II and 100% in Grade III). We follow-up UBC TM test in 5 patients after 6 months. UBC TM levels and recurrence were correlated in 4 patient (80%). Follow-up levels of UBC TM were increased in two recurred patients and normalized in non-recurred patients. One patient showed increased level of UBC TM test but clinically no evidence of recurrence. Although Also our patients were small, UBC TM test may be useful method for detecting the recurrence of TCC and further follow-up is necessary

Segmentation of urinary bladder in CT Urography (CTU) using CLASS

Science.gov (United States)

Hadjiiski, Lubomir; Chan, Heang-Ping; Law, Yuen; Cohan, Richard H.; Caoili, Elaine M.; Cho, Hyun-Chong; Zhou, Chuan; Wei, Jun

2012-03-01

We are developing a computerized system for bladder segmentation on CTU, as a critical component for computer aided diagnosis of bladder cancer. A challenge for bladder segmentation is the presence of regions without contrast (NC) and filled with IV contrast (C). We are developing a Conjoint Level set Analysis and Segmentation System (CLASS) specifically for this application. CLASS performs a series of image processing tasks: preprocessing, initial segmentation, and 3D and 2D level set segmentation and post-processing, designed according to the characteristics of the bladder in CTU. The NC and the C regions of the bladder were segmented separately in CLASS. The final contour is obtained in the post-processing stage by the union of the NC and C contours. Seventy bladders (31 containing lesions, 24 containing wall thickening, and 15 normal) were segmented. The performance of CLASS was assessed by rating the quality of the contours on a 5-point scale (1= "very poor", 3= "fair", 5 = "excellent"). For the 53 partially contrast-filled bladders, the average quality ratings for the 53 NC and 53 C regions were 4.0+/-0.7 and 4.0+/-1.0, respectively. 46 NC and 41 C regions were given quality ratings of 4 or above. Only 2 NC and 5 C regions had ratings under 3. The average quality ratings for the remaining 12 completely no contrast (NC) and 5 completely contrast-filled (C) bladder contours were 3.3+/-1.0 and 3.4+/-0.5, respectively. After combining the NC and C contours for each of the 70 bladders, 46 had quality ratings of 4 or above. Only 4 had ratings under 3. The average quality rating was 3.8+/-0.7. The results demonstrate the potential of CLASS for automated segmentation of the bladder.

Comparison of the efficacy and feasibility of laser enucleation of bladder tumor versus transurethral resection of bladder tumor: a meta-analysis.

Science.gov (United States)

Yang, Huan; Wang, Ning; Han, Shanfu; Male, Musa; Zhao, Chenming; Yao, Daqiang; Chen, Zhiqiang

2017-12-01

The transurethral resection of bladder tumor (TURBT) remains the most widely used method in the surgical treatment of the non-muscle invasive bladder tumor (NMIBT). Despite its popularity, the laser technique has been widely used in urology as an alternative, via the application of transurethral laser enucleation of bladder tumor. The aim of the present study was to compare the efficacy and feasibility between transurethral laser enucleation and transurethral resection of bladder tumor. A systematic search of the following databases was conducted: PubMed, Wed of Science, Cochrane Library, EMBASE, Google scholar, and Medline. The search included studies up to the 1st of January 2017. The outcomes of interest that were used in order to assess the two techniques included operation time, catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, 24-month-recurrence rate, and the postoperative adjuvant intravesical chemotherapy. A total of 13 trials with 2012 participants were included, of which 975 and 1037 underwent transurethral laser enucleation and transurethral resection of bladder tumor, respectively. No significant difference was noted in the operation time between the two groups, although significant differences were reported for the variables catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, and 24-month-recurrence rate. In the mitomycin and epirubicin subgroups, no significant differences were observed in the laser enucleation and TURBT methods with regard to the 24-month-recurrence rate. The laser enucleation was superior to TURBT with regard to the parameters obturator nerve reflex, bladder perforation, catheterization time, hospitalization time, and 24-month-recurrence rate. Moreover, laser enucleation can offer a more accurate result of the tumor's pathological stage and grade.

Baicalein and U0126 suppress bladder cancer proliferation via ...

African Journals Online (AJOL)

RT-PCR) and western blot. Results: Baicalein and U0126 suppressed bladder cancer cell T24 proliferation by blocking cell cycle in G0~G1 phase. TUNEL and Annexin V/PI detection showed both baicalein and U0126 induced T24 cell ...

Analysis of prognostic factors in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

Directory of Open Access Journals (Sweden)

Antunes Alberto A.

2006-01-01

Full Text Available OBJECTIVE: To analyze the results of the treatment of transitional cell carcinoma (TCC of the bladder with radical cystectomy and determine which prognostic factors can be utilized as disease-free survival and cancer-specific survival independent variables. MATERIALS AND METHODS: Medical records of 113 patients submitted to radical cystectomy and bilateral iliac lymphadenectomy between 1993 and 2005 were reviewed. The risk factors analyzed were age, sex, pathological stage, tumor grade, presence of carcinoma in situ and the presence of lymph nodes involvement. RESULTS: After a mean follow-up of 31.7 ? 28.5 months, 46 patients (40.7% presented recurrence and 24 patients (21.2% died due to cancer. Only pathological stage and the lymph nodes involvement became independent variables for recurrence and survival. Patients with T4 stage presented 9.6 times the risk of recurrence of the disease when compared with stage T0 patients (p = 0.010 and the patients with lymph node involvement presented 2.5 times the risk of recurrence (p = 0.047 and 3.1 times the risk of death (p = 0.022 when compared to patients without lymph nodes involvement. CONCLUSIONS: Pathological stage and the involvement of lymph nodes represented more important prognostic variables, and in the presence of advanced stage tumors (T3/T4 and involvement of lymph nodes, the institution of adjuvant treatment should be considered.

Radiation dose response in patients with favorable localized prostate cancer (Stage T1-T2, biopsy Gleason ≤6, and pretreatment prostate-specific antigen ≤10)

International Nuclear Information System (INIS)

Kupelian, Patrick A.; Buchsbaum, Jeffrey C.; Reddy, Chandana A.; Klein, Eric A.