Transitional Cell Carcinoma Of The Bladder Research Articles

Low-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Results of a prospective study

ObjectiveTo evaluate the efficacy and safety of low-dose (45mg) intravesical bacille Calmette–Guérin (BCG) therapy in the treatment of patients with non-muscle-invasive bladder cancer (NMIBC), as intravesical BCG is the most acceptable adjuvant therapy for NMI transitional cell carcinoma of the bladder. However, in the standard regimen, undesirable effects are the main cause of treatment discontinuation. Patients and methodsThe present study included 37 men with primary NIMBC. All patients underwent complete TURB and 2weeks later, a 6-week course of 45mg BCG diluted in 50mL isotonic saline was instilled into the bladder and retained for 2h. Patients were evaluated for BCG efficacy (recurrence with or without progression) and safety by documentation of minor and/or major side-effects. ResultsThere were no major or severe side-effects and no treatment discontinuations. Local adverse effects occurred in 20 patients, while systemic effects, in the form of fever, occurred in six patients (16.2%). There was recurrence in 14 patients (37.8%) after 18–34months, with disease progression (muscle invasion) in four (10.8%) after 6–18months. The recurrence index was 0.39/100 patients/month and the mean (range) tumour-free period was 30.97 (7–36) months. ConclusionLow-dose BCG intravesical therapy is an effective adjuvant treatment in NMIBC. However, this needs to be validated in future studies and in comparison with other proposed doses and/or regimens.

Bladder cancer cells re-educate TAMs through lactate shuttling in the microfluidic cancer microenvironment.

In the present study, we aimed to investigate the influence of lactate shuttling on the functional polarization and spatial distribution of transitional cell carcinoma of the bladder (TCCB) cells and macrophages. We designed a microfluidic coculture chip for real-time integrative assays. The effect of lactate shuttling on the re-education of macrophages by TCCB cells was explored by measuring the levels of NO using a total NO assay kit and by evaluating the protein expression of iNOS, p-NFkB-p65, Arg-1 and HIF-1α via cell immunofluorescence and western blotting. Additionally, we examined TCCB cell viability using acridine orange/ethidium bromide (AO/EB) and MitoTracker staining. Moreover, the concentration distributions of lactate and large signaling proteins in the culture chambers were measured using 4',6-diamidino-2-phenylindole (DAPI) and fluorescein isothiocyanate-dextran (FITC-dextran). Furthermore, the recruitment of macrophages and the influence of macrophages on BC metastasis were observed via light microscopy. We confirmed that TCCB cells reprogrammed macrophages into an M2 phenotype. Moreover, lactate inhibited M1 polarization and induced M2 polarization of macrophages, but blockade of cancer cell-macrophage lactate flux significantly inhibited the re-education of macrophages by TCCB cells. In addition, lactate diffused faster and deeper than large signaling proteins in the microfluidic tumor microenvironment. Furthermore, lactate alone induced the migration of macrophages, and M1, but not M2, macrophages reduced the motility of TCCB cells. TCCB cells reprogrammed macrophages into an M2 phenotype in a manner that depended on cancer cell-TAM lactate flux. Furthermore, the lactate shuttle may be a determinant of the density of TAMs in tumor tissue.

An Unordinary Recurrence of Urothelial Bladder Carcinoma in the Colon Presenting as Hematochezia

The conventional route of recurrence and metastasis in primary urothelial cell carcinoma of the bladder is through lymphatics and hematogenous system with regional lymph nodes, lungs, liver, brain and bone being the most commonly involved sites. Invasive urothelial cancers could also spread locoregionally to surrounding organs including female genital tract, prostate and gastrointestinal tract especially colo-rectum. However, recurrence of this cancer inside the colon in the absence of locoregional invasion, and after achieving complete long-term remission is extremely unusual. A review of the literature revealed a single case reported by Yang et al. of an urothelial cancer recurrence in the colon with mixed urothelial/colonic malignant pathology [1]. Herein we report the second case, to our knowledge, of an urothelial cell bladder carcinoma that recurred inside the colon in the form of a mass causing hematochezia, which on pathology and immunohistostaining proved to be primarily of urothelial rather than colonic origin. 67 year old male heavy smoker with stage III (T3a, N0, M0) transitional cell carcinoma of the bladder had undergone radical cystectomy, neo-bladder reconstruction and adjuvant chemotherapy following initial diagnosis. He poved repetitively to have no evidence of disease until he presented 4 years later with intermittent hematochezia and anemia. Colonoscopy revealed a fungating, ulcerated mass in the sigmoid colon suggestive of a primary colon cancer (fig 1). Pathology disclosed high grade/poorly differentiated carcinoma invading the colonic mucosa that surprisingly favored an urothelial origin. Upon further immunostaining, final diagnosis of a metastatic high-grade urothelial carcinoma was confirmed by positive cytokeratin (CK) 7 stain (specific for urothelial cells) and negative villin and CDX2 stains that are both specific for gastrointestinal differentiation (fig 2). CT scan of abdomen and pelvis, and PET scan did not reveal any other sites of cancer recurrence. Patient received a tailored chemotherapy and responded appropriately.Figure 1Figure 2This case illustrates a rare kind of recurrence of urothelial cancer in the form of a colonic mass resembling primary colon cancer. This unordinary way of recurrence could pose a clinico-pathological diagnostic challenge in distinguishing this disease treated basically with chemotherapy, from a primary colon cancer managed primarily by surgical resection. Immunohistochemical stains are essential for an accurate diagnosis. Heightened awareness is of utmost importance in such patients with history of urothelial cancer in order to appropriately tailor further treatment strategies that differ between primary and secondary colonic tumors.

Impact of preoperative hemoglobin and CRP levels on cancer-specific survival in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: results of a single-center study

Different blood parameters have shown to be associated with patient's oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS). Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23%) underwent surgery with a median age of 70years (35-97). Median follow-up time was 24months (max. 108). Outcome was analyzed using Kaplan-Meier method, log-rank test, and Cox regression models. Median CRP level was 0.5mg/dl (0.1-28.3), and median Hb level was 13.4g/dl (6.7-17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70months; p<0.001). Patients with preoperative Hb level below the median had significantly worse outcome than those with Hb level above the median (median CSS 25 vs. 78months; p<0.001). In multivariate analysis, CRP and Hb levels were independent prognostic parameters regarding CSS/OS (CRP p=0.016/p=0.004; Hb p=0.006/p=0.004, respectively). In our single-center study, preoperative CRP and Hb levels were found to be independent prognostic factors, indicating impaired outcome in patients undergoing RC for TCC. These findings could be used for individual risk stratification and optimization of therapeutic strategies.

Effectiveness, toxicity, and economic evaluation of vinflunine for the treatment of patients with transitional cell carcinoma in the Spanish outpatient setting.

The aim of this study was to evaluate the effectiveness and toxicity profile of the vinflunine chemotherapy regimen and to examine the cost-effectiveness relation in a real-world sample of patients with transitional cell carcinoma of the bladder. This is a multicenter, observational, retrospective cohort study. To assess the effectiveness and safety of vinflunine treatment, progression-free survival, overall survival, and adverse events were registered. An economic evaluation was performed and cost-effectiveness ratios were calculated. A total of 37 patients were included in the study, with a mean age of 67 (SD=9) years. The median progression-free survival was 2.61 months (95% confidence interval 1.79-4.23) and the median overall survival was 5.72 months (95% confidence interval 3.34-10.35). An objective response was achieved in eight (22%) patients. Statistically significant differences were found between patients treated with vinflunine as a second-line therapy and those treated with vinflunine as a third-line therapy (P=0.036). The most commonly reported analytical adverse event was anemia (n=34; 92%), and the most severe was neutropenia (n=19; 51%), with nine patients developing grade 4 neutropenia (9/19; 47%). The total cost of vinflunine treatment was &OV0556;553 873, with a median of &OV0556;8524 (interquartile range, &OV0556;9220) per patient. The median-based cost-effectiveness ratio was &OV0556;44 789 (&OV0556;31 706-58 022) per progression-free year gained and &OV0556;22 750 (&OV0556;14 526-34 085) per life-year gained. The data from this study fill an important need for information on the relative value of this treatment in terms of cost-effectiveness and might help achieve an optimal quality healthcare system.

Abstract 550: Evaluation of NQO1 as a potential diagnostic marker for bladder cancer

Abstract The present method for detection of bladder cancer involves ultrasonography followed by cystoscopy. This process is time intensive, requires skilled personnel and is unpleasant for the patient as a result of its invasive nature. This results in patient drop-out and patients that have recovered from bladder cancer are lost to follow-up due to the necessity for hospital visits for monitoring. We have used a novel test in order to monitor NAD(P)H quinone oxidoreductase 1 (NQO1) activity in cells recovered from routine urine samples since expression of NQO1 has previously been reported to be increased in several tumour types including transitional cell carcinoma of the bladder. Informed consent and urine samples were obtained from 73 bladder cancer patients and 42 age-matched bladder cancer-negative outpatients at the University Hospital of Wales, Cardiff. Live exfoliated cells were collected from the urine and assessed for their ability to metabolise an NQO1-specific substrate into a highly fluorescent product. Fluorescence intensity was then measured in a simple, inexpensive instrument. Results were checked against clinical correlates, bladder cancer stage, age, medication, and smoking status. Initial tests in cell lines showed excellent correlation with NQO1 levels detected by other methods. We found that in patient samples, while cell numbers in urine and expression of NQO1 per cell were not in themselves significant, NQO1 per ml of urine was highly significantly increased in bladder cancer patients (p = 0.009). Further, NQO1 was higher in patients that had high grade tumours as described in the WHO 2004 guidelines (p = 0.003). The sensitive fluorescence-based method to detect NQO1 activity in exfoliated urothelial cells shows exceptional promise in the development of rapid, non-invasive bladder cancer diagnostics. The method will be used on larger numbers of samples in order to be able to verify these initial findings. Note: This abstract was not presented at the meeting. Citation Format: Simone Cuff, Ruth Lewis, Mohammed Jaffar, Richard Knox, Ian Weeks. Evaluation of NQO1 as a potential diagnostic marker for bladder cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 550. doi:10.1158/1538-7445.AM2015-550

The prognostic significance of p53, p63 and her2 expression in non-muscle-invasive bladder cancer in relation to treatment with bacille Calmette–Guerin

ObjectiveTo investigate whether the immunohistochemical expression of p53, p63 and her2/neu is correlated with the prognosis of tumour recurrence and progression in patients with non-muscle invasive (NMI) bladder cancer. Patients and methodsIn all, 88 patients diagnosed with NMI transitional cell carcinoma of the bladder in a Urology Department from May 2009 to April 2014 were included in the study. Paraffin-embedded specimens were obtained by transurethral resection of the bladder tumours. Sections on haematoxylin and eosin-stained slides were examined histologically and tumour grade was classified according to the World Health Organisation system (2004) Mostofi classification. The sections were evaluated using p63, p53 and her2/neu immunohistochemical staining before and after immunotherapy with bacille Calmette–Guerin (BCG), and patients were followed up for 36months in the Urology Department. ResultsFor tumour grade there was a significant relationship with the overexpression of p53 (P=0.010), her2 (P=0.025) and negativity of p63 (P=0.025). There was no significant relationship between p53 or her2/neu overexpression and tumour stage. However, there was a significant correlation (P=0.005) between p63 negativity and tumour stage. There was a significant relationship between p53 (P=0.01), her2/neu (P=0.025) overexpression and p63 negativity (P=0.005) and tumour recurrence and progression. ConclusionPatients with transitional cell carcinoma who are selected for BCG treatment should preferably be positively immunoreactive for p63, but negative for both p53 and her2/neu. These patients were less susceptible to recurrence and/or progression after BCG adjuvant therapy. Further studies are needed to investigate the relationship between these three markers and treatment with anti-her2/neu therapies.

Human epidermal growth factor receptor 2/neu overexpression in urothelial carcinoma of the bladder and its prognostic significance: Is it worth hype?

Aims:In urothelial tumors of the urinary bladder, human epidermal growth factor receptor 2 (HER-2)/neu expression has been reported over 10 years, but there is no clear correlation between prognosis and recurrence rate. The present study evaluates prognostic implication of HER-2/neu expression.Subjects and Methods:In this study, 100 formalin-fixed paraffin-embedded specimens of primary transitional cell carcinoma of the bladder were processed. HER-2/neu monoclonal antibody immunohistochemistry staining procedure used for the study.Results:A total of 70 (70%) patients were positive for overexpression of HER-2/neu. HER-2/neu was positive in patients with 42 (70%) superficial tumor, 28 (70%) muscle invasive tumor, 41 (75.9%) high-grade tumor, 29 (63%) low grade tumor, 31 (68.9%) recurrent tumor, and 6 (66.6%) had positive lymph nodes.Conclusions:Human epidermal growth factor receptor 2/neu over expression was not correlated with the tumor stage, lymphnode metastasis or recurrence of the disease. HER-2/neu overexpression was statistically insignificantly correlated with the differentiation grade (P < 0.161) as compared to previous studies. Future studies on HER-2 expression with chemo-sensitivity and efficacy of HER-2-targeted therapies in urothelial carcinomas is needed.

Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test

Targeted cancer therapies offer great clinical promise, but treatment resistance is common, and basic research aimed at overcoming this challenge is limited by reduced genomic and biologic complexity in artificially induced rodent tumors compared with their human counterparts. Animal models that more faithfully recapitulate genotype-specific human pathology could improve the predictive value of these investigations. Here, a newly identified animal model for oncogenic BRAF-driven cancers is described. With 20,000 new cases in the United States each year, canine invasive transitional cell carcinoma of the bladder (InvTCC) is a common, naturally occurring malignancy that shares significant histologic, biologic, and clinical phenotypes with human muscle invasive bladder cancer. In order to identify somatic drivers of canine InvTCC, the complete transcriptome for multiple tumors was determined by RNAseq. All tumors harbored a somatic mutation that is homologous to the human BRAF(V600E) mutation, and an identical mutation was present in 87% of 62 additional canine InvTCC tumors. The mutation was also detectable in the urine sediments of all dogs tested with mutation-positive tumors. Functional experiments suggest that, like human tumors, canine activating BRAF mutations potently stimulate the MAPK pathway. Cell lines with the mutation have elevated levels of phosphorylated MEK, compared with a line with wild-type BRAF. This effect can be diminished through application of the BRAF(V600E) inhibitor vemurafenib. These findings set the stage for canine InvTCC as a powerful system to evaluate BRAF-targeted therapies, as well as therapies designed to overcome resistance, which could enhance treatment of both human and canine cancers This study demonstrates the activating BRAF mutation (V600E), which is found in multiple human cancers, is a driver of canine InvTCC, and highlights a urine-based test for quick diagnosis.

Highlights of This Issue

Studies have shown that nitric oxide (NO) has both protumor and antitumor growth properties. Rabender and colleagues demonstrate that NO synthase (NOS) in tumor cells is uncoupled and instead of generating NO it synthesizes superoxide and peroxynitrite. Furthermore, recoupling NOS with the BH4 precursor, sepiapterin, is cytotoxic to tumor cells. These findings shed light on the conflicting results of NO signaling and reveal a critical switching mechanism for tumor progression. Synthetic BH4 is used to treat some phenylketonuria patients and diseases associated with endothelial dysfunction, suggesting a testable approach for correcting an abnormality of tumor metabolism and controlling tumor growth.Oral squamous cell carcinoma (OSCC) is a widespread form of cancer with poor survival rates. Progress in treatment strategies has been limited, and thus understanding dysregulated signals contributing to OSCC is required. Hiemer and colleagues show that the transcriptional regulators YAP and TAZ, downstream effectors of the Hippo pathway, drive protumorigenic signals in OSCC in vitro and in vivo. Further, comparing the YAP/TAZ-regulated gene expression changes with those identified in OSCC tissues by The Cancer Genome Atlas (TCGA) demonstrated a significant contribution of nuclear YAP/TAZ activity to OSCC onset and progression. This study reveals novel insight into the dysregulated signals contributing to this poorly understood cancer.Canine invasive transitional cell carcinoma of the bladder (InvTCC) is a common, naturally occurring malignancy that shares histologic, biologic, and clinical characteristics with human invasive bladder cancers. Decker and colleagues observed that a large majority of tested canine InvTCC tumors are driven by a canonical activating BRAF (V600E) mutation. Administration of vemurafenib, a clinical-grade BRAF inhibitor, demonstrably reduced growth of canine bladder cancer cell lines, highlighting both the clinical and translational potential of this animal model for studies of human BRAF-dependent tumors. Finally, a urine-based diagnostic test was developed, based on the BRAF mutation, which is highly effective in dogs.MicroRNA-21 (miR-21) is upregulated in many human malignancies and often correlates with poor clinical outcomes. Wagenaar and colleagues detected significant overexpression of miR-21 in two large independent cohorts of patients with hepatocellular carcinoma (HCC) and in HCC cell lines. Using potent anti–miR-21 compounds and genetic tools, they determined that miR-21 inhibition results in profound deregulation of multiple prosurvival pathways and leads to the suppression of HCC growth in vitro and in vivo. These results establish a critical role for miR-21 in maintaining tumorigenic phenotype in HCC and suggest that miR-21 represents an important target for pharmacologic inhibition in liver cancer.

Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population‐based study

Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry. Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population. There were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis. This is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.

Selective organ preservation with neo-adjuvant chemotherapy for the treatment of muscle invasive transitional cell carcinoma of the bladder.

Background:Radiotherapy for muscle invasive bladder cancer (MIBC) aims to offer organ preservation without oncological compromise. Neo-adjuvant chemotherapy provides survival advantage; response may guide patient selection for bladder preservation and identify those most likely to have favourable result with radiotherapy.Methods:Ninety-four successive patients with T2-T4aN0M0 bladder cancer treated between January 2000 and June 2011 were analysed at the Royal Marsden Hospital. Patients received platinum-based chemotherapy following transurethral resection of bladder tumour; repeat cystoscopy (±biopsy) was performed to guide subsequent management. Responders were treated with radiotherapy. Poor responders were recommended radical cystectomy. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method; univariate and multivariate analyses were performed using the Cox proportional hazard regression model.Results:Response assessment was performed in 89 patients. Seventy-eight (88%) demonstrated response; 53 (60%) achieved complete response (CR); 74 responders had radiotherapy; 4 opted for cystectomy. Eleven (12%) demonstrated poor response, 10 received cystectomy. Median survival for CR was 90 months (95% CI 64.7, 115.9) compared with 16 months (95% CI 5.4, 27.4; P<0.001) poor responders. On multivariate analysis, only response was associated with significantly improved PFS, OS and DSS. After a median follow-up of 39 months (range 4–127 months), 14 patients (16%) required salvage cystectomy (8 for non-muscle invasive disease, 5 for invasive recurrence, 1 for radiotherapy related toxicity). In all, 82% had an intact bladder at last follow-up after radiotherapy; 67% had an intact bladder at last follow-up or death. Our study is limited by its retrospective nature.Conclusions:Response to neo-adjuvant chemotherapy is a favourable prognostic indicator and can be used to select patients for radiotherapy allowing bladder preservation in >80% of the selected patients.

A Case of High-grade Transitional Cell Carcinoma of the Bladder in a Pediatric Patient With Turner Syndrome

Transitional cell carcinoma is a rare entity in children, especially in the first decade of life. The majority of these tumors are of low grade and noninvasive. We report an interesting case of a high-grade superficial transitional cell carcinoma in a 3-year-old girl with Turner syndrome.

Editorial Comment

The report by Byler et al 1 Byler T.K. Reeder J. Nsouli I. Incidental computed tomographic bladder wall abnormalities: harbinger or herring?. Urol. 2015; 85: 288-291 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar on the incidence of transitional cell carcinoma of the bladder in patients with incidental radiologic finding of bladder wall thickening on computerized tomography (CT) scan in the absence of hematuria and gross or microscopic or positive urine cytology is significant and timely. The results are sobering. More than 15% of these patients have bladder cancer, and nearly 9% have high-grade or muscle invasive cancer. Worth noting that in none of the study patients with radiologic finding of focal thickening in the bladder (n = 15) had any type of bladder cancer. On the other hand, patients with diffuse thickening of the bladder wall or intraluminal mass had 31.5% (6 of 19) incidence of bladder cancer, and of these, 15.7% (3 of 19) were high-grade or muscle-invasive cancers. Incidental Computed Tomographic Bladder Wall Abnormalities: Harbinger or Herring?UrologyVol. 85Issue 2PreviewTo evaluate the outcomes of incidental radiographically identified bladder wall abnormalities in the absence of other urologic indications for evaluation. Full-Text PDF ReplyUrologyVol. 85Issue 2PreviewWe appreciate the interest and the comments regarding our work. With widespread use of imaging, incidental findings and evaluation of these findings has become more common in numerous disciplines. This series seeks to give evidence to the workup involved for incidental thickened bladder wall after exclusion of established “high-risk” patients. These high-risk patients include those with hematuria, bladder cancer, or previous radiation. Our survey of patients yielded unexpected results. Our initial thoughts were that the elimination of cystoscopy from this evaluation could save time, morbidity, and money. Full-Text PDF

Transurethral Resection of the Bladder Tumour as a Treatment Method in Children with Transitional Cell Carcinoma of the Bladder--Analysis of Our Material and Literature Review.

Bladder cancer occurs mainly in adults. In children, younger than 10 years in particular, it is very rare. The aim of the study is to retrospectively evaluate the efficacy of transurethral resection of the bladder tumour (TUR-BT) of transitional cell carcinoma (TCC) of the bladder in children. Transurethral resection of the bladder tumour was performed in 7boys aged 4to 17 years (median 12.1years). In all cases laboratory tests, ultrasound, and cystoscopic tumour biopsy were carried out prior to the resection. Doxorubicin was additionally instilled intravesically as one dose in two patients. The Foley catheter was left in the bladder for 1to 4days (median 1.85 days). The follow-up period ranged from 10 months to 10 years (median 4years). Papillary urothelial neoplasm of low malignant potential (PUNLMP) was diagnosed in 5patients and urothelial papilloma in 2. Local recurrence was observed in one case two years after the resection. In all other cases complete remission was achieved. Transitional cell carcinoma of the bladder in children is usually benign and endoscopic treatment (TUR-BT) seems to be the treatment of choice. To determine afollow-up schedule amore substantial group of children with bladder cancer should be analysed.

Choroidal metastases from transitional cell carcinoma of the bladder

Secondary metastasis tumors are the most common form of the adult intraocular neoplasm. It has an incidence of 9.3% among all fatal cases of cancer and 4% in patients dying of all types of cancer. We report a rare metastatic spread to the choroid from bladder carcinoma which is unusual primary site in a 64-year-old male. This case describes metastatic spread to the choroids from bladder carcinoma that is a very unusual primary site.

Feasibility of organ preservation in muscle-invasive transitional cell carcinoma bladder: A single institutional approach

Background: Trimodality treatment initial transurethral resection of the bladder tumor [TURBT] followed by concurrent chemotherapy and radiation and organ preservation have been gradually replacing the radical cystectomy in muscle-invasive transitional cell carcinoma (TCC) of bladder. Aims: The aims of this study is to determine the clinical effectiveness, safety and protocol completion rate of trimodality treatment in muscle-invasive TCC of the bladder. Settings and Design: Prospective randomized and open-labeled study. Subjects and Methods: Patients with TCC of bladder, American Joint Committee on Cancer tumor node metastasis (TNM) Bladder Cancer Staging (2002) T2-3, N0, M0. Were underwent TURBT followed by three cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin regimen. The patients were then randomized to receive either concurrent cisplatin 75 mg/m 2 in week 1 and 4 (arm-A) or no cisplatin (arm-B) along with external beam radiation therapy (EBRT) 45 Gy, in 25 fractions over 5 weeks. 4 weeks after completion of the initial phase of treatment, all patients were re-evaluated with TURBT. Those with complete remission (CR) received additional 15 Gy of EBRT in 8 fractions, while patients with residual disease were recommended for immediate radical cystectomy. All the patients of arm-B received boost dose of 15 Gy of EBRT. Statistical Analysis Used: The major statistical endpoints of this study were the CR rate at 8 weeks post-concurrent chemoradiotherapy (CCRT) and only radiotherapy. Statistical significance was accepted at the P Results: 8 weeks after completion of treatment 13/16 (81%) patients were in CR in CCRT arm (arm-A) compare to 6/15 (40%) patients receiving radiation only (arm-B). Conclusions: Patients, after TURBT receiving CCRT, had a better chance of organ preservation (81%) than those receiving radiation only.

Abstract IA19: Canine cancer genetics: What dogs can tell us about ourselves

Abstract The 165 domestic US dogs breeds display tremendous morphologic variation, making them an appealing model for the identification of genetic regulators of vertebrate shape and development and disease susceptibility. We have genotyped over 1000 dogs representing 85 domestic breeds to generate a reference dataset on over 60,000 informative SNPs per dog. This, combined with morphometric data has allowed us to map and sequence loci that control various features of breed-specific traits related to shape and size. In addition to helping us understand the genetics of morphologic variation, the underlying loci have also helped us understand the genetics of growth regulation. We now have a clearer sense of how variation is created in body size, leg length, head shape and other features that define various breeds of dog because of such studies. The domestic dog is also a robust model for studying the genetics of disease susceptibility as some breeds harbor an elevated risk, particularly for types of cancer, in spite of a relatively simple genetic architecture that is common to all dogs. One example of breed-specific disease propensity is squamous cell carcinoma of the digit (SCCoD), a locally aggressive cancer that frequently causes lytic bone lesions and multiple toe recurrence. SCCoD is uncommon in most dog breeds, but occurs in Schnauzers, Briards, and Standard Poodles, who are at about a 10-fold increased risk. Another cancer of interest to humans and dogs is transitional cell carcinoma of the bladder, which we observe at increased risk in Scottish Terriers (22 fold increased risk), West Highland White Terriers and Shelties. A final example is histiocytic carcinoma, which is common to Flat Coated Retrievers and Bernese Mountain dogs. Advances in genomic technologies, together with valued clinical collaborations, have allowed us to undertake studies aimed at understanding the genetic susceptibility of each. Key to advancing these studies has been the availability of dense SNP chips and the ever-increasing amount of data on a variety of dog breeds. We will report on our progress on each. Citation Format: Elaine A. Ostrander. Canine cancer genetics: What dogs can tell us about ourselves. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr IA19.

13 Whole exome sequence analysis of canine transitional cell carcinoma of the bladder

associated drug-response relationships. One specimen was tested in vitro and in vivo using a matched, patient-derived xenograft model. Results: NGS for the 11 tumor panel found ~30% of cases with EGFR amplification, p16, and/or PTEN deletion. Novel potentially actionable targets included a TRIM54-FGFR3 fusion, STAG2 mutation, MDM2 amplification, KIF11 and KIF15 mutation, and BRAF amplification. GBM150 is derived from a recurrent tumor and harbors the TRIM54-FGFR3 fusion, and this line is the first to be analyzed for chemovulnerability. In a Cyquant proliferation assay, GBM150 were relatively resistant to TMZ (IC50 300 uM) but significantly more sensitive to pan-FGFR1−3 inhibitors as compared to GBM108: ponatinib IC50 0.3 uM vs. 1.2 uM; AZD4547 IC50 3 uM vs. >10 uM. Similarly, in a flank tumor regrowth study, established GBM150 tumors were randomized to therapy with placebo, temozolomide, ponatinib or AZD4547. While TMZ-treated tumors were marginally smaller than placebo treated tumors (mean tumor volume 1312±208 vs. 992±183mm3, 97 days after therapy initiation), both ponatinib or AZD4547 resulted in sustained tumor stasis with a mean tumor volume of 240±35 and 199±40mm3, respectively, at the same time-point. Conclusions: These results support the concept that NGS can be used to individualize treatment of GBM and highlight how corresponding patient derived xenograft models can be used to validate the accuracy of potential therapeutic predictions.

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

Small cell carcinoma of the urinary bladder (SCBC) is a type of rare malignant tumor of the urinary tract. As it does not have specific symptoms and its epidemiological features are similar to transitional cell carcinoma of the bladder, it is often misdiagnosed. SCBC is highly aggressive, metastasizes very early and has a poor prognosis, and consequently, it has become a focus for urological surgeons and oncologists. An 82-year-old male visited the Department of Urinary Surgery, in the Affiliated Hospital of Guangdong Medical College (Zhanjiang, China), due to gross hematuria that had persisted for one week. Abdominal computed tomography showed a neoplasm of ~6×6×7 cm on the anterior wall of the bladder. The initial diagnosis was of uroepithelial cell carcinoma of the bladder and surgery was performed to remove the tumor. However, the subsequent pathological examination suggested that the tumor was an SCBC. Small cell carcinoma is a highly malignant disease, with a high mortality rate, and it rarely occurs in the bladder. Upon review of a large number of studies, SCBC was not found to present with specific symptoms, making the early diagnosis of the disease difficult, however, commonly occurring symptoms included dysuria, painless gross hematuria and urinary tract obstruction.